WorldWideScience

Sample records for cancer subset enriched

  1. Characterization of a naturally occurring breast cancer subset enriched in EMT and stem cell characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Hennessy, Bryan T.; Gonzalez-Angulo, Ana-Maria; Stemke-Hale, Katherine; Gilcrease, Michael Z.; Krishnamurthy, Savitri; Lee, Ju-Seog; Fridlyand, Jane; Sahin, Aysegul; Agarwal, Roshan; Joy, Corwin; Liu, Wenbin; Stivers, David; Baggerly, Keith; Carey, Mark; Lluch, Ana; Monteagudo, Carlos; He, Xiaping; Weigman, Victor; Fan, Cheng; Palazzo, Juan; Hortobagyi, Gabriel N.; Nolden, Laura K.; Wang, Nicholas J.; Valero, Vicente; Gray, Joe W.; Perou, Charles M.; Mills, Gordon B.

    2009-05-19

    Metaplastic breast cancers (MBC) are aggressive, chemoresistant tumors characterized by lineage plasticity. To advance understanding of their pathogenesis and relatedness to other breast cancer subtypes, 28 MBCs were compared with common breast cancers using comparative genomic hybridization, transcriptional profiling, and reverse-phase protein arrays and by sequencing for common breast cancer mutations. MBCs showed unique DNA copy number aberrations compared with common breast cancers. PIK3CA mutations were detected in 9 of 19 MBCs (47.4%) versus 80 of 232 hormone receptor-positive cancers (34.5%; P = 0.32), 17 of 75 HER-2-positive samples (22.7%; P = 0.04), 20 of 240 basal-like cancers (8.3%; P < 0.0001), and 0 of 14 claudin-low tumors (P = 0.004). Of 7 phosphatidylinositol 3-kinase/AKT pathway phosphorylation sites, 6 were more highly phosphorylated in MBCs than in other breast tumor subtypes. The majority of MBCs displayed mRNA profiles different from those of the most common, including basal-like cancers. By transcriptional profiling, MBCs and the recently identified claudin-low breast cancer subset constitute related receptor-negative subgroups characterized by low expression of GATA3-regulated genes and of genes responsible for cell-cell adhesion with enrichment for markers linked to stem cell function and epithelial-to-mesenchymal transition (EMT). In contrast to other breast cancers, claudin-low tumors and most MBCs showed a significant similarity to a 'tumorigenic' signature defined using CD44{sup +}/CD24{sup -} breast tumor-initiating stem cell-like cells. MBCs and claudin-low tumors are thus enriched in EMT and stem cell-like features, and may arise from an earlier, more chemoresistant breast epithelial precursor than basal-like or luminal cancers. PIK3CA mutations, EMT, and stem cell-like characteristics likely contribute to the poor outcomes of MBC and suggest novel therapeutic targets.

  2. Bulk enrichment of transplantable hemopoietic stem cell subsets from lipopolysaccharide-stimulated murine spleen.

    Science.gov (United States)

    Ploemacher, R E; Brons, R H; Leenen, P J

    1987-02-01

    Counterflow centrifugal elutriation (CCE) in combination with density flotation centrifugation and fluorescence-activated cell sorting on wheat-germ agglutinin-FITC(WGA)-binding cells within the light-scatter "blast window" were used consecutively to enrich pluripotent hemopoietic stem cells (HSC) in bulk from lipopolysaccharide-stimulated mouse spleen. The medium-to-strong WGA + ve fraction contained 3.10(6) cells isolated from 3-4 X 10(9) spleen cells, with an average of 126% day-12 CFU-S and 65% day-8 CFU-S as calculated on the basis of their seeding fraction, suggesting that virtually all cells represented in vivo macroscopic colony formers. In view of the large differences reported elsewhere between stem cell subsets differing in reconstitutive capacity and secondary stem cell generation ability, we also studied various isolated cell fractions with respect to spleen colony formation, radioprotective ability, and spleen- and marrow- repopulating ability. Day-8 and day-12 CFU-S copurified when isolated by CCE. Cells from a fraction with high affinity for WGA were most highly enriched for their radioprotective ability (RPA) and their ability to repopulate the cellularity of the spleen and femur of irradiated recipients. This fraction contained virtually pure day-12 CFU-S. However, the ability to generate secondary day-12 CFU-S and CFU-GM in irradiated organs was enriched most in the medium WGA + ve cell fraction. MRA and SRA, according to the latter criteria, could therefore be partly separated from day-12 CFU-S and RPA on the basis of affinity for WGA. The data strongly suggest that at least part of all day-12 CFU-S have a high potential to proliferate and differentiate into mature progeny, but a relatively low self-renewal ability, and may therefore not be representative of the genuine stem cell. PMID:2880746

  3. CLINICAL VALUE OF DETECTING T LYMPHOCYTE SUBSET AND NK CELL ACTIVITY IN PATIENTS WITH COLORECTAL CANCER

    Institute of Scientific and Technical Information of China (English)

    刘长安; 管增伟; 孙武; 邵玉霞; 李卓; 贾廷珍

    2001-01-01

    Objective To study on the expression and clinical significance of T lymphocyte subset and NK cell activity (NKA) in patients with colorectal cancer. Methods Fifty-seven cancer patients and 33 healthy controls were enrolled in this study. T lymphocyte subset was measured by SAP technique and NKA by LDH release assay based on K562 cells, which served as target cells.

  4. Highly efficient and selective enrichment of peptide subsets combining fluorous chemistry with reversed-phase chromatography

    OpenAIRE

    Ying, Wantao; Perlman, David H.; Li, Lei(Beijing Institute of Petrochemical Technology, Beijing, 102617, People's Republic of China); Théberge, Roger; Costello, Catherine E; McComb, Mark E.

    2009-01-01

    The selective capture of target peptides poses a great challenge to modern chemists and biologists, especially when enriching them from proteome samples possessing extremes in concentration dynamic range and sequence diversity. While approaches based on traditional techniques such as biotin-avidin pairing offer versatile tools to design strategies for selective enrichment, problems are still encountered due to sample loss or poor selectivity of enrichment. Here we show that the recently intro...

  5. EWS and FUS bind a subset of transcribed genes encoding proteins enriched in RNA regulatory functions

    DEFF Research Database (Denmark)

    Luo, Yonglun; Friis, Jenny Blechingberg; Fernandes, Ana Miguel;

    2015-01-01

    IP-seq). Our results show that FUS and EWS bind to a subset of actively transcribed genes, that binding often is downstream the poly(A)-signal, and that binding overlaps with RNA polymerase II. Functional examinations of selected target genes identified that FUS and EWS can regulate gene expression...... at different levels. Gene Ontology analyses showed that FUS and EWS target genes preferentially encode proteins involved in regulatory processes at the RNA level. Conclusions The presented results yield new insights into gene interactions of EWS and FUS and have identified a set of FUS and EWS target genes...

  6. Differential Aspartate Usage Identifies a Subset of Cancer Cells Particularly Dependent on OGDH

    Directory of Open Access Journals (Sweden)

    Eric L. Allen

    2016-10-01

    Full Text Available Although aberrant metabolism in tumors has been well described, the identification of cancer subsets with particular metabolic vulnerabilities has remained challenging. Here, we conducted an siRNA screen focusing on enzymes involved in the tricarboxylic acid (TCA cycle and uncovered a striking range of cancer cell dependencies on OGDH, the E1 subunit of the alpha-ketoglutarate dehydrogenase complex. Using an integrative metabolomics approach, we identified differential aspartate utilization, via the malate-aspartate shuttle, as a predictor of whether OGDH is required for proliferation in 3D culture assays and for the growth of xenograft tumors. These findings highlight an anaplerotic role of aspartate and, more broadly, suggest that differential nutrient utilization patterns can identify subsets of cancers with distinct metabolic dependencies for potential pharmacological intervention.

  7. Circulating Lymphocyte Subsets 
in Patients with Lung Cancer and Their Prognostic Value

    Directory of Open Access Journals (Sweden)

    Jun LUO

    2011-08-01

    Full Text Available Background and objective Lung cancer is one of the most common malignancies. The aim of this study is to investigate the relationship between the change of lymphocyte subsets in the peripheral blood of lung cancer patients and the survival rate. Methods Flow cytometry was used to measure the percentages of lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+, CD19+, CD25+, CD44+, and NK cells in peripheral blood obtained from 221 patients with primary lung cancer without any treatment and from 96 healthy blood donors as the control group. The result was combined with clinical and follow-up data and statistical analysis was conducted. Results The levels of CD3+ and CD8+ in the patient group are significantly lower compared with the control group, whereas the levels of CD4+/CD8+, CD19+, CD25+, CD44+, and NK cells are significantly higher (P<0.05. CD8+ is significantly higher in the small cell lung cancer (SCLC group compared with the non-small cell lung cancer (NSCLC group. However, CD4+ and CD4+/CD8+ are lower in SCLC (P<0.05. There were no significant differences in different stages and differentiation (P>0.05 in the NSCLC group. The level of CD3+ was significantly higher compared with the pre-chemotherapy group, but NK cell, CD19+, and CD44+ were distinctly lower in the post-chemotherapy group (P<0.05. More survival opportunities will be obtained for patients with no increase in CD44+ after chemotherapy (P=0.021, but the other three indices have no obvious influence on survival. Conclusion Widespread changes of lymphocyte occur in the peripheral blood of patients with lung cancer. There is a significant correlation between the change of CD44+ and the prognosis after chemotherapy.

  8. Methylation of PTCH1a gene in a subset of gastric cancers

    Institute of Scientific and Technical Information of China (English)

    Peng Du; Hai-Rong Ye; Jun Gao; Wei Chen; Zhong-Chuan Wang; Hong-Hua Jiang; Ji Xu; Ji-We Zhang; Jian-Cheng Zhang; Long Cui

    2009-01-01

    AIM: To establish if PTCH1a transcriptional regulation region (TRR) is methylated in gastric cancer and its influence in gastric tumorigenesis. METHODS: The CpG islands in PTCH1a TRR were analyzed by Methyl Primer Express v1.0 software. The region from -643 to -355 bp (the transcription initiation site of PTCH1a was designated as 0) that contained 19 CpG sites was chosen for bisulfitesequencing PCR (BSP) and methylation-specific PCR (MSP) detection. The gastric cancer cell line AGS was treated with 5-aza-2'-deoxycytidine (5-Aza-dC; 1 μmol/L) for 3 d. Alterations in PTCH1a TRR methylation in treated AGS cells was measured through BSP clone sequences, and their PTCH1 expression was measured by quantitative RT-PCR. The cell cycle and apoptosis were observed with flow cytometry through propidium iodide (PI) staining or annexin V/PI double staining. The prevalence of PTCH1a TRR methylation was investigated in 170 gastric cancer tissue samples and the adjacent normal tissues by MSP. The correlation of PTCH1a TRR methylation with PTCH1 expression or with patients' clinical features was analyzed. RESULTS: Methylation of PTCH1a TRR was observed in AGS cells and a subset of gastric cancer tissues (32%, 55/170), while no methylation amplification products were observed in any normal tissues by MSP. The methylation of PTCH1a TRR was correlated negatively with PTCH1 expression (Spearman's r = -0.380, P = 0.000). However, methylation of PTCH1a TRR was not related to the gastric cancer patients' clinical features, such as sex, age of onset, clinical stage, lymph node metastasis or histological grade. The methylation of PTCH1a TRR in AGS cells was almost converted to non-methylation after 5-Aza-dC treatment, which increased PTCH1 expression (5.3 ± 2.5 times; n = 3) and apoptosis rate (3.0 ± 0.26 times; P < 0.05; n = 3). CONCLUSION: Methylation of PTCH1a TRR is present in a subset of gastric cancers and correlated negatively with PTCH1 expression. This may be an early event in

  9. Androgen receptors and serum testosterone levels identify different subsets of postmenopausal breast cancers

    Directory of Open Access Journals (Sweden)

    Secreto Giorgio

    2012-12-01

    Full Text Available Abstract Background Androgen receptors (AR are frequently expressed in breast cancers, but their implication in cancer growth is still controversial. In the present study, we further investigated the role of the androgen/AR pathway in breast cancer development. Methods AR expression was evaluated by immunochemistry in a cohort of 528 postmenopausal breast cancer patients previously examined for the association of serum testosterone levels with patient and tumor characteristics. AR expression was classified according to the percentage of stained cells: AR-absent (0% and AR-poorly (1%-30%, AR-moderately (>30%-60%, and AR-highly (>60% positive. Results Statistical analysis was performed in 451 patients who experienced natural menopause. AR-high expression was significantly related with low histologic grade and estrogen receptor (ER- and progesterone receptor (PR-positive status (P trendP=0.022, although a trend across the AR expression categories was not present. When women defined by ER status were analyzed separately, regression analysis in the ER-positive group showed a significant association of high testosterone levels with AR-highly-positive expression (OR 1.86; 95% CI, 1.10-3.16, but the association was essentially due to patients greater than or equal to 65 years (OR 2.42; 95% CI, 1.22-4.82. In ER-positive group, elevated testosterone levels appeared also associated with AR-absent expression, although the small number of patients in this category limited the appearance of significant effects (OR 1.92; 95% CI, 0.73–5.02: the association was present in both age groups ( Conclusions The findings in the present study confirm that testosterone levels are a marker of hormone-dependent breast cancer and suggest that the contemporary evaluation of ER status, AR expression, and circulating testosterone levels may identify different subsets of cancers whose growth may be influenced by androgens.

  10. MicroRNA-125b expands hematopoietic stem cells and enriches for the lymphoid-balanced and lymphoid-biased subsets.

    Science.gov (United States)

    Ooi, A G Lisa; Sahoo, Debashis; Adorno, Maddalena; Wang, Yulei; Weissman, Irving L; Park, Christopher Y

    2010-12-14

    MicroRNAs profoundly impact hematopoietic cells by regulating progenitor cell-fate decisions, as well as mature immune effector function. However to date, microRNAs that regulate hematopoietic stem cell (HSC) function have been less well characterized. Here we show that microRNA-125b (miR-125b) is highly expressed in HSCs and its expression decreases in committed progenitors. Overexpression of miR-125b in mouse HSC enhances their function, demonstrated through serial transplantation of highly purified HSC, and enriches for the previously described Slamf1(lo)CD34(-) lymphoid-balanced and the Slamf1(neg)CD34(-) lymphoid-biased cell subsets within the multipotent HSC (CD34-KLS) fraction. Mature peripheral blood cells derived from the miR-125b-overexpressing HSC are skewed toward the lymphoid lineage. Consistent with this observation, miR-125b overexpression significantly increases the number of early B-progenitor cells within the spleen and induces the expansion and enrichment of the lymphoid-balanced and lymphoid-biased HSC subset via an antiapoptotic mechanism, reducing the mRNA expression levels of two proapoptotic targets, Bmf and KLF13. The antiapoptotic effect of miR-125b is more pronounced in the lymphoid-biased HSC subset because of their intrinsic higher baseline levels of apoptosis. These effects of miR-125b are associated with the development of lymphoproliferative disease, marked by expansion of CD8(+) T lymphocytes. Taken together, these data reveal that miR-125b regulates HSC survival and can promote lymphoid-fate decisions at the level of the HSC by preferentially expanding lymphoid-balanced and lymphoid-biased HSC.

  11. Upregulation of Glycans Containing 3’ Fucose in a Subset of Pancreatic Cancers Uncovered Using Fusion-Tagged Lectins

    OpenAIRE

    Singh, Sudhir; Pal, Kuntal; Yadav, Jessica; Tang, Huiyuan; Partyka, Katie; Kletter, Doron; Hsueh, Peter; Ensink, Elliot; Birendra, KC; Hostetter, Galen; Xu, H. Eric; Bern, Marshall; Smith, David F; Anand S Mehta; Brand, Randall

    2015-01-01

    The fucose post-translational modification is frequently increased in pancreatic cancer, thus forming the basis for promising biomarkers, but a subset of pancreatic cancer patients does not elevate the known fucose-containing biomarkers. We hypothesized that such patients elevate glycan motifs with fucose in linkages and contexts different from the known fucose-containing biomarkers. We used a database of glycan array data to identify the lectins CCL2 to detect glycan motifs with fucose in a ...

  12. Involvement of NRF2 Signaling in Doxorubicin Resistance of Cancer Stem Cell-Enriched Colonospheres.

    Science.gov (United States)

    Ryoo, In-Geun; Kim, Geon; Choi, Bo-Hyun; Lee, Sang-Hwan; Kwak, Mi-Kyoung

    2016-09-01

    Cancer stem cells (CSCs) are a subset of tumor cells, which are characterized by resistance against chemotherapy and environmental stress, and are known to cause tumor relapse after therapy. A number of molecular mechanisms underlie the chemoresistance of CSCs, including high expression levels of drug efflux transporters. We investigated the role of the antioxidant transcription factor NF-E2-related factor 2 (NRF2) in chemoresistance development, using a CSC-enriched colonosphere system. HCT116 colonospheres were more resistant to doxorubicin-induced cell death and expressed higher levels of drug efflux transporters such as P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) compared to HCT116 monolayers. Notably, levels of NRF2 and expression of its target genes were substantially elevated in colonospheres, and these increases were linked to doxorubicin resistance. When NRF2 expression was silenced in colonospheres, Pgp and BCRP expression was downregulated, and doxorubicin resistance was diminished. Collectively, these results indicate that NRF2 activation contributes to chemoresistance acquisition in CSC-enriched colonospheres through the upregulation of drug efflux transporters. PMID:27582554

  13. Changes in percentage of lymphocyte subsets after 131I treatment in patients with differentiated thyroid cancer

    Institute of Scientific and Technical Information of China (English)

    LUO Quan-Yong; CHEN Li-Bo; YU Yong-Li; LU Han-Kui; ZHU Rui-Sen

    2005-01-01

    To monitor the extent and the duration of lymphocyte subset changes in patients with thyroid carcinoma undergoing therapeutic 131I administration, the percentage of lymphocyte subsets were serially analyzed before and after 131I treatment. In patients who received 1850 MBq of 131I for ablation of thyroid remnants, only for NK cells and B cells showed a significant reduction. In patients received 3700 MBq of 131I for treatment of local lymph node metastases, NK cells, B cells and CD4+ were found decreased. In patients received 7400 MBq of 131I for treatment of distant metastases, NK cells, B cells and CD4+ and CD8+ were all affected. However, there is no significant reduction compared to the baseline in the percentage of all lymphocyte subsets three months after 131I treatment. The results show that the sensitivity of lymphocytes to 131I internal radiation depends upon lymphocyte phenotype and 131I activity. The immunosuppression effects are temporary and reversible.

  14. Enrichment of prostate cancer stem cells from primary prostate cancer cultures of biopsy samples

    OpenAIRE

    Wang, Shunqi; Huang, Shengsong; Zhao, Xin; Zhang, Qimin; Wu, Min; Sun, Feng; Han, Gang; Wu, Denglong

    2013-01-01

    This study was to enrich prostate cancer stem cells (PrCSC) from primary prostate cancer cultures (PPrCC). Primary prostate cancer cells were amplified in keratinocyte serum-free medium with epidermal growth factor (EGF) and bovine pituitary extract (BPE), supplemented with leukemia inhibitory factor (LIF), stem cell factor (SCF) and cholera toxin. After amplification, cells were transferred into ultra-low attachment dishes with serum-free DMEM/F12 medium, supplemented with EGF, basic fibrobl...

  15. Gamma-secretase inhibition combined with platinum compounds enhances cell death in a large subset of colorectal cancer cells

    Directory of Open Access Journals (Sweden)

    Feller Stephan M

    2008-10-01

    Full Text Available Abstract Background Notch signalling is essential for the development and maintenance of the colonic epithelium. Its inhibition induces a differentiation phenotype in vivo and reduces adenomas in APCmin mice. Whether Notch signals are also required in colorectal cancer (CRC has remained elusive. Therefore, 64 CRC cell lines were analysed for the occurrence of proteolytically processed, active Notch. Results 63 CRC lines contained a fragment with approximately the size of the Notch1 intracellular domain (NICD, which is required for signalling. Subsequent analyses with an antibody that specifically recognises the free Val1744 residue generated by γ-secretase-mediated cleavage of Notch1 showed that a subset of CRC cells lacks this specific Val1744-NICD. Surprisingly, inhibition of Val1744-NICD signalling with different γ-secretase inhibitors (GSI did not lead to substantial effects on CRC cell line growth or survival. However, transient activation of Erk upon GSI treatment was detected. Since cisplatin relies on Erk activation for bioactivity in some cells, platinum compounds were tested together with GSI and enhanced cell killing in a subset of Val1744-NICD-positive CRC cell lines was detected. Erk inhibition ablated this combination effect. Conclusion We conclude that γ-secretase inhibition results in activation of the MAP kinases Erk1/2 and, when used in conjunction, enhances cell death induced by platinum compounds in a large subset of colorectal cancer cell lines. Furthermore the activation of Erk appears to be of particular importance in mediating the enhanced effect seen, as its inhibition abrogates the observed phenomenon. These findings do not only highlight the importance of signalling pathway crosstalk but they may also suggest a new avenue of combination therapy for some colorectal cancers.

  16. ENRICH Forum: Ethical aNd Regulatory Issues in Cancer ResearcH

    Science.gov (United States)

    ENRICH Forum: Ethical aNd Regulatory Issues in Cancer ResearcH, designed to stimulate dialogue on ethical and regulatory issues in cancer research and promote awareness of developing policies and best practices.

  17. Cell surface galectin-3 defines a subset of chemoresistant gastrointestinal tumor-initiating cancer cells with heightened stem cell characteristics.

    Science.gov (United States)

    Ilmer, Matthias; Mazurek, Nachman; Byrd, James C; Ramirez, Karen; Hafley, Margarete; Alt, Eckhard; Vykoukal, Jody; Bresalier, Robert S

    2016-01-01

    Recurrence of gastrointestinal adenocarcinomas after surgery and chemotherapy may be attributed, in part, to the presence of a small population of tumor-initiating cancer stem cells (CSC). The expression of galectin-3 (Gal3), a multifunctional oncolectin, has been associated with biological behaviors associated with CSC. We examined the ability of Gal3 to characterize the CSC phenotype, and to identify a clinically important gastrointestinal cancer CSC population. Human colorectal and pancreatic cancer cell lines were sorted to identify subpopulations expressing commonly used CSC markers, and Gal3-positive CSC subpopulations. The association of Gal3 with the stem cell properties and alterations of these phenotypes by manipulation of Gal3 expression was examined. Gastrointestinal cancer cell lines contain both Gal3-positive and Gal3-negative subpopulations. Gal3-positive CSCs are characterized by high ALDH activity, enhanced self-renewal ability in vitro (sphere formation) and tumor forming ability in vivo, and resistance to chemotherapeutic agents and death-receptor-mediated apoptosis compared to Gal3-negative CSCs. Silencing Gal3 modifies this behavior. Cell surface Gal3 expression identifies a subset of CSCs in gastrointestinal cancers with high levels of stem cell characteristics, including chemoresistance. This may provide a platform for developing treatment strategies that target CSC. PMID:27512958

  18. Embryonic mammary signature subsets are activated in Brca1-/- and basal-like breast cancers

    OpenAIRE

    Zvelebil, Marketa; Oliemuller, Erik; Gao, Qiong; Wansbury, Olivia; Mackay, Alan; Kendrick, Howard; Matthew J Smalley; Reis-Filho, Jorge S.; Howard, Beatrice A

    2013-01-01

    Introduction Cancer is often suggested to result from development gone awry. Links between normal embryonic development and cancer biology have been postulated, but no defined genetic basis has been established. We recently published the first transcriptomic analysis of embryonic mammary cell populations. Embryonic mammary epithelial cells are an immature progenitor cell population, lacking differentiation markers, which is reflected in their very distinct genetic profiles when compared with ...

  19. Patient subsets with T1-T2, node-negative breast cancer at high locoregional recurrence risk after mastectomy

    International Nuclear Information System (INIS)

    Purpose: To identify patient subsets with T1-T2N0 breast cancer at high risk of locoregional recurrence (LRR) who may warrant consideration for postmastectomy radiotherapy. Methods and Materials: Data were analyzed for 1505 women referred between 1989 and 1999 with pathologic T1-T2N0M0 breast cancer treated with mastectomy with clear margins and no adjuvant radiotherapy. Logistic regression analysis was performed to identify statistically significant factors associated with LRR. Recursive partitioning was used to develop a classification tree model for LRR given the prognostic variables. Results: The median follow-up was 7.0 years. The 10-year Kaplan-Meier LRR rate was 7.8%. On logistic regression analysis, the statistically significant factors predicting LRR were histologic grade (p <0.0001), lymphovascular invasion (LVI) (p <0.0001), T stage (p = 0.05), and systemic therapy use (p = 0.01). In the recursive partitioning model, the first split in the classification tree was histologic grade. For 972 patients without high-grade histologic features, the 10-year Kaplan-Meier LRR rate was 5.5%. For 533 patients with Grade 3 disease (LRR rate 12.1%), the concomitant presence of LVI was associated with a LRR rate of 21.2% (n = 126). In patients with Grade 3 disease without LVI, T2 tumors conferred a LRR rate of 13.4% (n = 194), which increased to 23.2% for patients who did not receive systemic therapy (n = 63). Conclusion: Women with pT1-T2N0 breast cancer experienced a LRR risk of approximately 20% in the presence of Grade 3 disease with LVI or Grade 3 disease, T2 tumors, and no systemic therapy. These subsets of node-negative patients warrant consideration of for postmastectomy radiotherapy

  20. Upregulation of glycans containing 3' fucose in a subset of pancreatic cancers uncovered using fusion-tagged lectins.

    Science.gov (United States)

    Singh, Sudhir; Pal, Kuntal; Yadav, Jessica; Tang, Huiyuan; Partyka, Katie; Kletter, Doron; Hsueh, Peter; Ensink, Elliot; Kc, Birendra; Hostetter, Galen; Xu, H Eric; Bern, Marshall; Smith, David F; Mehta, Anand S; Brand, Randall; Melcher, Karsten; Haab, Brian B

    2015-06-01

    The fucose post-translational modification is frequently increased in pancreatic cancer, thus forming the basis for promising biomarkers, but a subset of pancreatic cancer patients does not elevate the known fucose-containing biomarkers. We hypothesized that such patients elevate glycan motifs with fucose in linkages and contexts different from the known fucose-containing biomarkers. We used a database of glycan array data to identify the lectins CCL2 to detect glycan motifs with fucose in a 3' linkage; CGL2 for motifs with fucose in a 2' linkage; and RSL for fucose in all linkages. We used several practical methods to test the lectins and determine the optimal mode of detection, and we then tested whether the lectins detected glycans in pancreatic cancer patients who did not elevate the sialyl-Lewis A glycan, which is upregulated in ∼75% of pancreatic adenocarcinomas. Patients who did not upregulate sialyl-Lewis A, which contains fucose in a 4' linkage, tended to upregulate fucose in a 3' linkage, as detected by CCL2, but they did not upregulate total fucose or fucose in a 2' linkage. CCL2 binding was high in cancerous epithelia from pancreatic tumors, including areas negative for sialyl-Lewis A and a related motif containing 3' fucose, sialyl-Lewis X. Thus, glycans containing 3' fucose may complement sialyl-Lewis A to contribute to improved detection of pancreatic cancer. Furthermore, the use of panels of recombinant lectins may uncover details about glycosylation that could be important for characterizing and detecting cancer.

  1. A Vulnerability of a Subset of Colon Cancers with Potential Clinical Utility

    NARCIS (Netherlands)

    Vecchione, Loredana; Gambino, Valentina; Raaijmakers, Jonne; Schlicker, Andreas; Fumagalli, Arianna; Russo, Mariangela; Villanueva, Alberto; Beerling, Evelyne; Bartolini, Alice; Mollevi, David G; El-Murr, Nizar; Chiron, Marielle; Calvet, Loreley; Nicolazzi, Céline; Combeau, Cécile; Henry, Christophe; Simon, Iris M; Tian, Sun; In 't Veld, Sjors; D'ario, Giovanni; Mainardi, Sara; Beijersbergen, Roderick L; Lieftink, Cor; Linn, Sabine; Rumpf-Kienzl, Cornelia; Delorenzi, Mauro; Wessels, Lodewyk; Salazar, Ramon; Di Nicolantonio, Federica; Bardelli, Alberto; van Rheenen, Jacco; Medema, René H; Tejpar, Sabine; Bernards, René

    2016-01-01

    BRAF(V600E) mutant colon cancers (CCs) have a characteristic gene expression signature that is also found in some tumors lacking this mutation. Collectively, they are referred to as "BRAF-like" tumors and represent some 20% of CCs. We used a shRNA-based genetic screen focused on genes upregulated in

  2. Epidemiology of doublet/multiplet mutations in lung cancers: evidence that a subset arises by chronocoordinate events.

    Directory of Open Access Journals (Sweden)

    Zhenbin Chen

    Full Text Available BACKGROUND: Evidence strongly suggests that spontaneous doublet mutations in normal mouse tissues generally arise from chronocoordinate events. These chronocoordinate mutations sometimes reflect "mutation showers", which are multiple chronocoordinate mutations spanning many kilobases. However, little is known about mutagenesis of doublet and multiplet mutations (domuplets in human cancer. Lung cancer accounts for about 25% of all cancer deaths. Herein, we analyze the epidemiology of domuplets in the EGFR and TP53 genes in lung cancer. The EGFR gene is an oncogene in which doublets are generally driver plus driver mutations, while the TP53 gene is a tumor suppressor gene with a more typical situation in which doublets derive from a driver and passenger mutation. METHODOLOGY/PRINCIPAL FINDINGS: EGFR mutations identified by sequencing were collected from 66 published papers and our updated EGFR mutation database (www.egfr.org. TP53 mutations were collected from IARC version 12 (www-p53.iarc.fr. For EGFR and TP53 doublets, no clearly significant differences in race, ethnicity, gender and smoking status were observed. Doublets in the EGFR and TP53 genes in human lung cancer are elevated about eight- and three-fold, respectively, relative to spontaneous doublets in mouse (6% and 2.3% versus 0.7%. CONCLUSIONS/SIGNIFICANCE: Although no one characteristic is definitive, the aggregate properties of doublet and multiplet mutations in lung cancer are consistent with a subset derived from chronocoordinate events in the EGFR gene: i the eight frameshift doublets (present in 0.5% of all patients with EGFR mutations are clustered and produce a net in-frame change; ii about 32% of doublets are very closely spaced (< or =30 nt; and iii multiplets contain two or more closely spaced mutations. TP53 mutations in lung cancer are very closely spaced (< or =30 nt in 33% of doublets, and multiplets generally contain two or more very closely spaced mutations. Work in

  3. Enrichment and Function Research of Large Cell Lung Cancer Stem Cell-like Cells

    OpenAIRE

    Wenke YUE; JIAO, FENG; Liu, Bin; Jiacong YOU; Zhou, Qinghua

    2011-01-01

    Background and objective There are no universal method to recognize and screen for lung cancer stem cell markers and indicators. Commonly used methods are flow Cytometry and learning from other cancer stem cell sorting tags to sort lung cancer stem cells. But this method has low specificity screening, the workload is huge. In this study, Serum-free suspension culture was used to enrich lung cancer stem cells, and explore method for lung cancer stem cell screening. Methods Human large lung can...

  4. Effect of Yunpi Huoxue soup combined chemotherapy on T lymphocyte subsets and nutritional status in patients with advanced gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Yi-Jiao Huang; Pei Xiang; Wei-Min Zhu

    2016-01-01

    Objective:To observe the effect of Yunpi Huoxue soup combined with chemotherapy on T lymphocyte subsets and nutritional status in patients with advanced gastric cancer.Methods:A total of 94 cases patients with advanced gastric cancer were randomly divided into the treatment group (49 cases) and the control group (45 cases) according to the results of the draw. The control group was given chemotherapy, the treatment group was given Yunpi Huoxue soup on the basis of the control group. Treated for 6 weeks, observed the changes of T cell subsets (CD3, CD4, CD8 and CD4/CD8) and nutrition indexes: total protein (TP), albumin (ALB), prealbumin (PA) and transferrin (TRF) in the two groups.Results:After treatment, CD3, CD4, CD8 and CD4/CD8 in the treatment group were (57.38±4.03), (31.63±4.26), (30.82±3.52) and (1.16±0.20 ) respectively, there were no significant differences compared with before treatment; After treatment, the levels of CD3, CD4, CD8 and CD4/CD8 in the control group were significantly lower than those before treatment, and the differences were statistically significant; After treatment, the levels of CD3, CD4, CD8 and CD4/CD8 in the treatment group were significant higher than those in the control group after treatment, and the differences were statistically significant. After treatment, TP, ALB, PA and TRF in the treatment group were(54.22±5.93) g/L, (32.47±4.97) g/L, (2.52±0.43) g/L and (1.66±0.40) g/L respectively, there were no significant differences compared with before treatment; After treatment, the levels of TP, ALB, PA and TRF in the control group were significantly lower than those before treatment; After treatment, the levels of TP, ALB, PA and TRF in the treatment group were significant higher than those in the control group after treatment, and the differences were statistically significant.Conclusion:When chemotherapy for patients with advanced gastric cancer, Yunpi Huoxue soup is helpful to maintain the immune function and

  5. Xmrk, kras and myc transgenic zebrafish liver cancer models share molecular signatures with subsets of human hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Weiling Zheng

    Full Text Available Previously three oncogene transgenic zebrafish lines with inducible expression of xmrk, kras or Myc in the liver have been generated and these transgenic lines develop oncogene-addicted liver tumors upon chemical induction. In the current study, comparative transcriptomic approaches were used to examine the correlation of the three induced transgenic liver cancers with human liver cancers. RNA profiles from the three zebrafish tumors indicated relatively small overlaps of significantly deregulated genes and biological pathways. Nevertheless, the three transgenic tumor signatures all showed significant correlation with advanced or very advanced human hepatocellular carcinoma (HCC. Interestingly, molecular signature from each oncogene-induced zebrafish liver tumor correlated with only a small subset of human HCC samples (24-29% and there were conserved up-regulated pathways between the zebrafish and correlated human HCC subgroup. The three zebrafish liver cancer models together represented nearly half (47.2% of human HCCs while some human HCCs showed significant correlation with more than one signature defined from the three oncogene-addicted zebrafish tumors. In contrast, commonly deregulated genes (21 up and 16 down in the three zebrafish tumor models generally showed accordant deregulation in the majority of human HCCs, suggesting that these genes might be more consistently deregulated in a broad range of human HCCs with different molecular mechanisms and thus serve as common diagnosis markers and therapeutic targets. Thus, these transgenic zebrafish models with well-defined oncogene-induced tumors are valuable tools for molecular classification of human HCCs and for understanding of molecular drivers in hepatocarcinogenesis in each human HCC subgroup.

  6. Effect of rosemary polyphenols on human colon cancer cells: transcriptomic profiling and functional enrichment analysis

    OpenAIRE

    Valdés, Alberto; García-Cañas, Virginia; Rocamora-Reverte, Lourdes; Gómez-Martínez, Ángeles; Ferragut, José Antonio; Cifuentes, Alejandro

    2012-01-01

    In this work, the effect of rosemary extracts rich on polyphenols obtained using pressurized fluids was investigated on the gene expression of human SW480 and HT29 colon cancer cells. The application of transcriptomic profiling and functional enrichment analysis was done via two computational approaches, Ingenuity Pathway Analysis and Gene Set Enrichment Analysis. These two approaches were used for functional enrichment analysis as a previous step for a reliable interpretation of the data obt...

  7. The Role of Biomaterials on Cancer Stem Cell Enrichment and Behavior

    Science.gov (United States)

    Ordikhani, Faride; Kim, Yonghyun; Zustiak, Silviya P.

    2015-11-01

    The theory of cancer stem cells (CSCs) and their role in cancer metastasis, tumorigenicity and resistance to therapy is slowly shifting the emphasis on the search for cancer cure: more evidence is surfacing that a successful therapy should be geared against this rare cancer cell population. Unfortunately, CSCs are difficult to culture in vitro which severely limits the progress of CSC research. This review gives a brief overview of CSCs and their microenvironment, with particular focus on studies that used in vitro biomaterial-based models and biomaterial/CSC interfaces for the enrichment of CSCs. Biomaterial properties relevant to CSC behaviors are also addressed. While the discussed research field is still in its infancy, it appears that in vitro cancer models that include a biomaterial can support CSC enrichment and this has proved indispensable to the study of their biology as well as the development of novel cancer therapies.

  8. Eicosapentaenoic Acid Enriched Enteral Nutrition Improves Lean Body Mass in Esophageal, Head and Neck Cancer Patients

    OpenAIRE

    Shieh, Christine

    2015-01-01

    OBJECTIVE: Cachexia is a nutrient deficient condition affecting millions of cancer patients. Cancers of the upper gastrointestinal tract, head and neck are often the most severely affected. Currently, there is no established therapy for cachexia, although several potential anti-cachectic agents are being explored. A meta-analysis was conducted to review the effect of eicosapentaenoic acid (EPA) enriched enteral nutrition on lean body mass (LBM) in esophageal, head and neck cancer patients at ...

  9. ALCHEMIST: Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials

    Science.gov (United States)

    ALCHEMIST represents three integrated, precision medicine trials that are designed to identify people with early-stage lung cancer who have tumors that harbor certain uncommon genetic changes and evaluate whether drug treatments targeted against those mol

  10. Cancer bioinformatics: detection of chromatin states,SNP-containing motifs, and functional enrichment modules

    Institute of Scientific and Technical Information of China (English)

    Xiaobo Zhou

    2013-01-01

    In this editorial preface,I briefly review cancer bioinformatics and introduce the four articles in this special issue highlighting important applications of the field:detection of chromatin states; detection of SNP-containing motifs and association with transcription factor-binding sites; improvements in functional enrichment modules; and gene association studies on aging and cancer.We expect this issue to provide bioinformatics scientists,cancer biologists,and clinical doctors with a better understanding of how cancer bioinformatics can be used to identify candidate biomarkers and targets and to conduct functional analysis.

  11. Cancer bioinformatics: detection of chromatin states, SNP-containing motifs, and functional enrichment modules

    Directory of Open Access Journals (Sweden)

    Xiaobo Zhou

    2013-04-01

    Full Text Available In this editorial preface, I briefly review cancer bioinformatics and introduce the four articles in this special issue highlighting important applications of the field: detection of chromatin states; detection of SNP-containing motifs and association with transcription factor-binding sites; improvements in functional enrichment modules; and gene association studies on aging and cancer. We expect this issue to provide bioinformatics scientists, cancer biologists, and clinical doctors with a better understanding of how cancer bioinformatics can be used to identify candidate biomarkers and targets and to conduct functional analysis.

  12. Identification and characterization of a tumor infiltrating CD56(+)/CD16 (-) NK cell subset with specificity for pancreatic and prostate cancer cell lines.

    Science.gov (United States)

    Frankel, Timothy L; Burns, William; Riley, John; Morgan, Richard A; Davis, Jeremy L; Hanada, Kenichi; Quezado, Martha; Rosenberg, Steven A; Royal, Richard E

    2010-12-01

    In a recent clinical trial, a patient exhibited regression of several pancreatic cancer metastases following the administration of the immune modulator Ipilimumab (anti-CTLA-4 antibody). We sought to characterize the immune cells responsible for this regression. Tumor infiltrating lymphocytes (TIL-2742) and an autologous tumor line (TC-2742) were expanded from a regressing metastatic lesion excised from this patient. Natural killer (NK) cells predominated in the TIL (92% CD56(+)) with few T cells (12% CD3(+)). A majority (88%) of the NK cells were CD56(bright)CD16(-). TIL-2742 secreted IFN-γ and GM-CSF following co-culture with TC-2742 and major histocompatibility complex mismatched pancreatic tumor lines. After sorting TIL-2742, the purified CD56(+)CD16(-)CD3(-) subset showed reactivity similar to TIL-2742 while the CD56(-)CD16(-)CD3(+) cells exhibited no tumor recognition. In co-culture assays, TIL-2742 and the NK subset expressed high reactivity to several pancreatic and prostate cancer cell lines and could lyse the autologous tumor as well as pancreas and prostate cancer lines. Reactivity was partially abrogated by blockade of TRAIL. We thus identified a unique subset of NK cells (CD56(bright)CD16(dim)) isolated from a regressing metastatic pancreatic cancer in a patient responding to Ipilimumab. This represents the first report of CD56(+)CD16(-) NK cells with apparent specificity for pancreatic and prostate cancer cell lines and associated with tumor regression following the treatment with an immune modulating agent. PMID:20734041

  13. CXCR3 expression defines a novel subset of innate CD8+ T cells that enhance immunity against bacterial infection and cancer upon stimulation with IL-15.

    Science.gov (United States)

    Oghumu, Steve; Terrazas, Cesar A; Varikuti, Sanjay; Kimble, Jennifer; Vadia, Stephen; Yu, Lianbo; Seveau, Stephanie; Satoskar, Abhay R

    2015-03-01

    Innate CD8(+) T cells are a heterogeneous population with developmental pathways distinct from conventional CD8(+) T cells. However, their biology, classification, and functions remain incompletely understood. We recently demonstrated the existence of a novel population of chemokine (C-X-C motif) receptor 3 (CXCR3)-positive innate CD8(+) T cells. Here, we investigated the functional properties of this subset and identified effector molecules and pathways which mediate their function. Adoptive transfer of IL-15 activated CXCR3(+) innate CD8(+) T cells conferred increased protection against Listeria monocytogenes infection in susceptible IFN-γ(-/-) mice compared with similarly activated CXCR3(-) subset. This was associated with enhanced proliferation and IFN-γ production in CXCR3(+) cells. Further, CXCR3(+) innate cells showed enhanced cytotoxicity against a tumor cell line in vitro. In depth analysis of the CXCR3(+) subset showed increased gene expression of Ccl5, Klrc1, CtsW, GP49a, IL-2Rβ, Atp5e, and Ly6c but reduced IFN-γR2 and Art2b. Ingenuity pathway analysis revealed an up-regulation of genes associated with T-cell activation, proliferation, cytotoxicity, and translational initiation in CXCR3(+) populations. Our results demonstrate that CXCR3 expression in innate CD8(+) T cells defines a subset with enhanced cytotoxic potential and protective antibacterial immune functions. Immunotherapeutic approaches against infectious disease and cancer could utilize CXCR3(+) innate CD8(+) T-cell populations as novel clinical intervention strategies. PMID:25466888

  14. Enriched transcription factor signatures in triple negative breast cancer indicates possible targeted therapies with existing drugs

    Directory of Open Access Journals (Sweden)

    Scooter Willis

    2015-06-01

    Conclusion: With the increasing number of large sample size breast cancer cohorts, an exploratory analysis of genes that are consistently enriched in TN sharing common promoter motifs allows for the identification of possible therapeutic targets with extensive validation in patient derived data sets.

  15. Enrichment and Function Research of Large Cell Lung Cancer Stem Cell-like Cells

    Directory of Open Access Journals (Sweden)

    Wenke YUE

    2011-06-01

    Full Text Available Background and objective There are no universal method to recognize and screen for lung cancer stem cell markers and indicators. Commonly used methods are flow Cytometry and learning from other cancer stem cell sorting tags to sort lung cancer stem cells. But this method has low specificity screening, the workload is huge. In this study, Serum-free suspension culture was used to enrich lung cancer stem cells, and explore method for lung cancer stem cell screening. Methods Human large lung cancer cell line-L9981 was cultured in serum-free and growth factors added medium, and spheres were obtained. Then the morphological differences of sphere cells and adherent L9981 cells cultured in serum-containing mediums are observed. Cell proliferation was analyzed by Vi-cell viability analyzer; invasion ability was tested by transwell assay; and in vivo tumorigenicity of the two groups of cells was studied in nude mouse. Results Compared with adherent L9981 cells cultured in serum-containing mediums, cells cultured in serum-free medium display sphere appearance. Doubling time of adherent cells and sphere cells are (56.05±1.95 h and (33.00±1.44 h respectively; Spheroid cells had higher invasion and tumorigenicity ability, 5 times and 20 times respectively, than adherent cells. Conclusion Suspension cultured L9981 in Serum-free medium could form spheroid populations. Cells in spheres had higher ability of invasion and Tumorigenicity than adherent L9981 cells. These results indicated spheroid L9981 cells contained enriched lung cancer stem cells, and Serum-free suspension culture can be a candidate method for enriching lung cancer stem cell.

  16. The RNA binding protein HuR differentially regulates unique subsets of mRNAs in estrogen receptor negative and estrogen receptor positive breast cancer

    International Nuclear Information System (INIS)

    The discordance between steady-state levels of mRNAs and protein has been attributed to posttranscriptional control mechanisms affecting mRNA stability and translation. Traditional methods of genome wide microarray analysis, profiling steady-state levels of mRNA, may miss important mRNA targets owing to significant posttranscriptional gene regulation by RNA binding proteins (RBPs). The ribonomic approach, utilizing RNA immunoprecipitation hybridized to microarray (RIP-Chip), provides global identification of putative endogenous mRNA targets of different RBPs. HuR is an RBP that binds to the AU-rich elements (ARE) of labile mRNAs, such as proto-oncogenes, facilitating their translation into protein. HuR has been shown to play a role in cancer progression and elevated levels of cytoplasmic HuR directly correlate with increased invasiveness and poor prognosis for many cancers, including those of the breast. HuR has been described to control genes in several of the acquired capabilities of cancer and has been hypothesized to be a tumor-maintenance gene, allowing for cancers to proliferate once they are established. We used HuR RIP-Chip as a comprehensive and systematic method to survey breast cancer target genes in both MCF-7 (estrogen receptor positive, ER+) and MDA-MB-231 (estrogen receptor negative, ER-) breast cancer cell lines. We identified unique subsets of HuR-associated mRNAs found individually or in both cell types. Two novel HuR targets, CD9 and CALM2 mRNAs, were identified and validated by quantitative RT-PCR and biotin pull-down analysis. This is the first report of a side-by-side genome-wide comparison of HuR-associated targets in wild type ER+ and ER- breast cancer. We found distinct, differentially expressed subsets of cancer related genes in ER+ and ER- breast cancer cell lines, and noted that the differential regulation of two cancer-related genes by HuR was contingent upon the cellular environment

  17. Enrichment of breast cancer stem cells using a keratinocyte serum-free medium

    Institute of Scientific and Technical Information of China (English)

    LIU Zhen-zhen; CHEN Ping; LU Zhen-duo; CUI Shu-de; DONG Zi-ming

    2011-01-01

    Background Keratinocyte serum-free medium (K-SFM) is a defined medium used to support the growth of primary keratinocytes and embryonic stem cell. The aim of this research was to optimize enrichment of breast cancer stem cells (CSCs) using K-SFM.Methods A K-SFM was used to enrich CSCs from two breast cancer cell lines and a primary culture of breast cancer.RPMI-1640 supplemented with 10% fetal calf serum (FCS) was used as a control. CSCs were identified with flow cytometry using CD44+/CD24-as molecular markers. The expression of a variety of CSC markers (Oct-4, ABCG2, Nanog,N-cadherin, and E-cadherin) was analyzed with real-time PCR.Results Much higher percentage of CSCs was achieved with K-SFM: 17.3% for MCF-7 cells, 17.4% for SKBR-3, and 20.0% for primary breast cancer culture. Less than 1% CSC was achieved using RPMI-1640 supplemented with 10% FCS. In comparison to the CSCs obtained with RPMI-1640, CSCs in the K-SFM expressed higher levels of Oct-4,ABCG2, Nanog and N-cadherin, and lower level of E-cadherin.Conclusion K-SFM is an optimal culture medium to maintain and to enrich breast CSCs.

  18. T- Lymphocyte Subset (CD4 /CD8) Ratios of Breast Cancer Patients in Basra-Iraq and Baku-Azerbaijan.

    Science.gov (United States)

    Nasr Ghalib, Noori; Nasrullayeva, G M; Qaziyev, A Y; Al-Ali Jawad, K H

    2016-01-01

    Breast cancer is the most common cancer among the population as a whole and among females, yet it is highly curable if diagnosed at an early stage. Different methods are used to diagnose breast cancer. One of these methods features immunological tests using flow cytometry to determine T-lymphocyte (CD4/CD8) ratios in peripheral blood. One hundred patients with breast cancer (50 from Basra, Iraq, and 50 from Baku, Azerbaijan) confirmed to have breast cancer by histopathology were studied. Blood samples were collected from all patients before initiation of treatment and were used for analysis. The mean age of women from Basra was 51.2 ± 10.7 years and that of women from Baku was slightly higher at 54.8 ± 12.2 . The mean CD4/CD8 ratio in Basra was 1.4 and in Baku was 1.8 with P value < 0.05. The percentage of Basra patients who have CD4/CD8 value less than 1 was 50%, while the percentage for Baku patients was 24 % (p < 0.05). While the CD4/CD8 T-lymphocyte ratio might be useful for early diagnosis in patients with breast cancer parallel with other confirmed tests factors involved in explaining variation between countries such as that observed here need to be taken into account. PMID:27165253

  19. Dietary, lifestyle and clinicopathological factors associated with BRAF and K-ras mutations arising in distinct subsets of colorectal cancers in the EPIC Norfolk study

    Directory of Open Access Journals (Sweden)

    McTaggart Alison

    2010-03-01

    Full Text Available Abstract Background BRAF and K-ras proto-oncogenes encode components of the ERK signalling pathway and are frequently mutated in colorectal cancer. This study investigates the associations between BRAF and K-ras mutations and clinicopathological, lifestyle and dietary factors in colorectal cancers. Methods 186 adenocarcinomas and 16 adenomas from the EPIC Norfolk study were tested for BRAF and K-ras mutations. Diet and lifestyle data were collected prospectively using seven day food diaries. Results BRAF V600E mutation was found in 15.6% of colorectal cancers but at higher frequencies in cancers with proximal location, poor differentiation and microsatellite instability (MSI (all p K-ras mutation (mostly in codons 12 and 13 was found in 22.0% of colorectal cancers but at higher frequencies in cancers of more advanced Dukes' stage (p = 0.001, microsatellite stable (MSS status (p = 0.002 and in individuals with lower blood high-density lipoprotein concentrations (p = 0.04. Analysis of dietary factors demonstrated no link between BRAF mutation and any specific dietary constituent, however, K-ras mutation was found at higher frequencies in individuals with higher white meat consumption (p K-ras were observed at higher frequencies in individuals consuming lower amounts of fruit (p = 0.02. Conclusion These data support the model of BRAF and K-ras mutations arising in distinct colorectal cancer subsets associated with different clinicopathological and dietary factors, acting as mutually exclusive mechanisms of activation of the same signalling pathway.

  20. Enriched environment housing enhances the sensitivity of mouse pancreatic cancer to chemotherapeutic agents.

    Science.gov (United States)

    Wu, Yufeng; Gan, Yu; Yuan, Hui; Wang, Qing; Fan, Yingchao; Li, Guohua; Zhang, Jian; Yao, Ming; Gu, Jianren; Tu, Hong

    2016-04-29

    Living in an enriched housing environment is an established model of eustress and has been consistently shown to reduce the growth of transplanted tumors, including pancreatic cancer. Here, we further investigate the influence of an enriched environment (EE) on the efficacy of chemotherapy in pancreatic cancer. Male C57BL/6 mice were housed in EE or standard environment (SE) conditions and transplanted with syngeneic Panc02 pancreatic cancer cells. Tumor-bearing mice were treated with 5-fluorouracil (5-FU) or gemcitabine (GEM) to examine their sensitivities to chemotherapy. The results showed that both 5-FU and GEM exerted the dose dependent inhibition of tumor growth. The tumor inhibition rates of low-dose 5-FU and GEM were improved from 17.7% and 23.6% to 46.3% and 49.9% by EE housing. Importantly, tumor cells isolated from the pancreatic cancer xenografts of EE mice had significantly enhanced sensitivities to both 5-FU and GEM (IC50 for 5-FU: 2.8 μM versus 27.3 μM; IC50 for GEM: 0.8 μM versus 5.0 μM). Furthermore, using microarray analyses, we identified the "ATP-binding cassette (ABC) transporter" that was overrepresented among EE-induced down-regulated genes in pancreatic cancer. Particularly, the tumoral expression of ABC transporter A8b (ABCA8b) was confirmed to be significantly decreased by EE. Over-expression of ABCA8b in mouse pancreatic cancer cells led to a marked decrease in the sensitivity to chemotherapeutic drugs both in vitro and in vivo. In conclusion, our data indicate that benign stressful stimulation can synergistically boost the efficiency of chemotherapeutics in pancreatic cancer, which suggests a novel strategy for adjuvant cancer therapy.

  1. Selenium enrichment of broccoli sprout extract increases chemosensitivity and apoptosis of LNCaP prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Suzuki Kazuhiro

    2009-11-01

    Full Text Available Abstract Background Broccoli is a Brassica vegetable that is believed to possess chemopreventive properties. Selenium also shows promise as an anticancer agent. Thus, selenium enrichment of broccoli has the potential to enhance the anticancer properties of broccoli sprouts. Method Selenium-enriched broccoli sprouts were prepared using a sodium selenite solution. Their anticancer properties were evaluated in human prostate cancer cell lines and compared with those of a control broccoli sprout extract. Results Selenium-enriched broccoli sprouts were superior to normal broccoli sprouts in inhibiting cell proliferation, decreasing prostate-specific antigen secretion, and inducing apoptosis of prostate cancer cells. Furthermore, selenium-enriched broccoli sprouts but, not normal broccoli sprouts, induced a downregulation of the survival Akt/mTOR pathway. Conclusion Our results suggest that selenium-enriched broccoli sprouts could potentially be used as an alternative selenium source for prostate cancer prevention and therapy.

  2. The effect of TACE combined with tumor interstitial therapy on immune globulin, complement and T lymphocyte subsets in patients with liver cancer

    Institute of Scientific and Technical Information of China (English)

    Bu-Tian Li; Sheng-Ping Zhang

    2016-01-01

    Objective:To explore the effect of TACE combined with interstitial therapy on immune globulin, complement and T lymphocyte subsets in patients with liver cancer.Methods:A total of 95 patients with liver cancer from March 2013 to April 2015 in the hospital were selected, and they were randomly divided into group A (n = 47) and group B (n=48), patients in group A were given simple TACE treatment, while patients in group B underwent TACE + tumor interstitial therapy (percutaneous liver tumor injection of lipiodol chemotherapy). Immune globulin, complement and T lymphocyte subsets in peripheral blood preoperative 1w and postoperative 4w were observed.Results: After treatment, the lipiodol deposition rate, local control rate and tumor reduction rate of group B were significantly higher than that in group A, which had statistically significant difference between the two groups. Compared with that before treatment, CD3+, CD4+, CD4+/CD8+ were significantly increased, CD8+ was significantly decreased after treatment. There were significantly differences in CD3+, CD4+, CD4+/CD8+, CD8+ between the two groups after treatment. The immune globulin and complement levels increased in group A after treatment, but had no significant difference. Immunoglobulin and complement levels increased significantly in group B, there were significantly differences in immunoglobulin and complement levels in the two groups after treatment.Conclusions:The results showed that single TACE treatment in patients with liver cancer could enhance immune function, which had little effect on the humoral immunity. TACE combined with interstitial therapy could improve patients' cellular immunity and humoral immunity, which was benefit for prognosis.

  3. Effect of different anesthesia and analgesia methods on theT lymphocyte subsets, cytokines and stress hormone level in patients with breast cancer surgery

    Institute of Scientific and Technical Information of China (English)

    Yan Ma; Xi-Qiang He; Geng Wang

    2015-01-01

    Objective: To explore the effect of different anesthesia and analgesia methods on the T lymphocyte subsets, cytokines and the levels of the stress hormone in patients with breast cancer surgery.Methods: 86 cases of breast cancer were divided into two groups by random digits table, control group of 43 cases with total intravenous anesthesia, and the observation group of 43 cases with total intravenous anesthesia combined with epidural anesthesia and postoperative underwent analgesia. The T lymphocyte subsets, cytokines and the levels of the stress hormone were detected before and after operation and compared. Results:CD3+, CD4+ and CD4+/CD8+ of the two groups at T1 or T2 were significantly lower than those at T0, and those in the observation group were significantly lower than the control group, and the difference between the two groups has statistical significance. IL-6, CRP and TNF-α levels of the two groups at T1, T2 or T3 were significantly higher than those at T0, and those in the observation group were significantly lower than the control group, and the difference between the two groups has statistical significance. Each index of two groups at T4 were restored to T0, and the differences were no statistically significant. The cortisol levels of two groups at T1 or T2 were significantly increased compared with T0, and the increase in the observation group was less than that of the control group, the difference between the two groups has statistical significance. The cortisol levels of two groups at T4 were restored to T0, and the differences were no statistically significant.Conclusion:Epidural analgesia after the intravenous anesthesia combined with epidural anesthesia for breast cancer cure patients has lighter immunosuppression and stress reaction, has less influence on inflammatory factors, is an ideal anesthesia and analgesia.

  4. Systematic enrichment analysis of gene expression profiling studies identifies consensus pathways implicated in colorectal cancer development

    Directory of Open Access Journals (Sweden)

    Jesús Lascorz

    2011-01-01

    Full Text Available Background: A large number of gene expression profiling (GEP studies on colorectal carcinogenesis have been performed but no reliable gene signature has been identified so far due to the lack of reproducibility in the reported genes. There is growing evidence that functionally related genes, rather than individual genes, contribute to the etiology of complex traits. We used, as a novel approach, pathway enrichment tools to define functionally related genes that are consistently up- or down-regulated in colorectal carcinogenesis. Materials and Methods: We started the analysis with 242 unique annotated genes that had been reported by any of three recent meta-analyses covering GEP studies on genes differentially expressed in carcinoma vs normal mucosa. Most of these genes (218, 91.9% had been reported in at least three GEP studies. These 242 genes were submitted to bioinformatic analysis using a total of nine tools to detect enrichment of Gene Ontology (GO categories or Kyoto Encyclopedia of Genes and Genomes (KEGG pathways. As a final consistency criterion the pathway categories had to be enriched by several tools to be taken into consideration. Results: Our pathway-based enrichment analysis identified the categories of ribosomal protein constituents, extracellular matrix receptor interaction, carbonic anhydrase isozymes, and a general category related to inflammation and cellular response as significantly and consistently overrepresented entities. Conclusions: We triaged the genes covered by the published GEP literature on colorectal carcinogenesis and subjected them to multiple enrichment tools in order to identify the consistently enriched gene categories. These turned out to have known functional relationships to cancer development and thus deserve further investigation.

  5. Alu and LINE-1 hypomethylation is associated with HER2 enriched subtype of breast cancer.

    Science.gov (United States)

    Park, So Yeon; Seo, An Na; Jung, Hae Yoen; Gwak, Jae Moon; Jung, Namhee; Cho, Nam-Yun; Kang, Gyeong Hoon

    2014-01-01

    The changes in DNA methylation status in cancer cells are characterized by hypermethylation of promoter CpG islands and diffuse genomic hypomethylation. Alu and long interspersed nucleotide element-1 (LINE-1) are non-coding genomic repetitive sequences and methylation of these elements can be used as a surrogate marker for genome-wide methylation status. This study was designed to evaluate the changes of Alu and LINE-1 hypomethylation during breast cancer progression from normal to pre-invasive lesions and invasive breast cancer (IBC), and their relationship with characteristics of IBC. We analyzed the methylation status of Alu and LINE-1 in 145 cases of breast samples including normal breast tissue, atypical ductal hyperplasia/flat epithelial atypia (ADH/FEA), ductal carcinoma in situ (DCIS) and IBC, and another set of 129 cases of IBC by pyrosequencing. Alu methylation showed no significant changes during multistep progression of breast cancer, although it tended to decrease during the transition from DCIS to IBC. In contrast, LINE-1 methylation significantly decreased from normal to ADH/FEA, while it was similar in ADH/FEA, DCIS and IBC. In IBC, Alu hypomethylation correlated with negative estrogen receptor (ER) status, and LINE-1 hypomethylation was associated with negative ER status, ERBB2 (HER2) amplification and p53 overexpression. Alu and LINE-1 methylation status was significantly different between breast cancer subtypes, and the HER2 enriched subtype had lowest methylation levels. In survival analyses, low Alu methylation status tended to be associated with poor disease-free survival of the patients. Our findings suggest that LINE-1 hypomethylation is an early event and Alu hypomethylation is probably a late event during breast cancer progression, and prominent hypomethylation of Alu and LINE-1 in HER2 enriched subtype may be related to chromosomal instability of this specific subtype.

  6. Pure Apocrine Carcinomas Represent a Clinicopathologically Distinct Androgen Receptor-Positive Subset of Triple-Negative Breast Cancers.

    Science.gov (United States)

    Mills, Anne M; E Gottlieb, Chelsea; M Wendroth, Scott; M Brenin, Christiana; Atkins, Kristen A

    2016-08-01

    Apocrine carcinomas comprise ∼1% of all breast cancers and are characterized by large cells bearing abundant eosinophilic granular cytoplasm, round nuclei, and prominent nucleoli. They are typically estrogen receptor/progesterone receptor/HER2 negative, making them unresponsive to typical hormonal or HER2-based chemotherapy. However, this subtype of triple-negative breast cancers expresses androgen receptor (AR), a feature not shared by most nonapocrine triple-negative cancers (NA-TNCs). AR therefore represents a potential diagnostic tool and therapeutic target for apocrine breast carcinoma. All pure apocrine carcinomas diagnosed during a 10-year period were reviewed, and clinicopathologic characteristics were compared with a control group of 26 NA-TNC cases. Twenty apocrine carcinomas were identified (∼0.8% of all breast cancers). The mean age at diagnosis was 69.3 years for apocrine carcinomas and 56.7 years for NA-TNC. All apocrine carcinomas and no NA-TNC were AR positive. The proportions of apocrine carcinoma grades varied, with G1 being seen in 15% of patients, G2 in 55%, and G3 in 30%. In contrast, 100% of NA-TNC cases were G3. The majority of apocrine carcinomas presented at low T stage (T1: 70%; T2: 20%; T3: 10%; T4: 0%), whereas NA-TNC cases more often presented at T2 or higher (T1: 46.2%; T2: 30.8%; T3: 11.5%; T4: 11.5%). Thirty percent of apocrine carcinomas and 30.8% of NA-TNCs had nodal metastases at presentation. Apocrine carcinomas had a favorable clinical prognosis, with 80% of patients showing no evidence of disease-related morbidity or mortality (mean follow-up: 45.2 mo). Pure apocrine carcinomas represent a clinicopathologically distinct subgroup of triple-negative breast cancer characterized by AR positivity. When compared with NA-TNC, apocrine carcinomas more often present in older women with lower grade and T stage, a group in which a more conservative treatment regimen is often desired. PMID:27259012

  7. Breast Cancer Stem Cell Culture and Enrichment Using Poly(ε-Caprolactone) Scaffolds.

    Science.gov (United States)

    Palomeras, Sònia; Rabionet, Marc; Ferrer, Inés; Sarrats, Ariadna; Garcia-Romeu, Maria Luisa; Puig, Teresa; Ciurana, Joaquim

    2016-01-01

    The cancer stem cell (CSC) population displays self-renewal capabilities, resistance to conventional therapies, and a tendency to post-treatment recurrence. Increasing knowledge about CSCs' phenotype and functions is needed to investigate new therapeutic strategies against the CSC population. Here, poly(ε-caprolactone) (PCL), a biocompatible polymer free of toxic dye, has been used to fabricate scaffolds, solid structures suitable for 3D cancer cell culture. It has been reported that scaffold cell culture enhances the CSCs population. A RepRap BCN3D+ printer and 3 mm PCL wire were used to fabricate circular scaffolds. PCL design and fabrication parameters were first determined and then optimized considering several measurable variables of the resulting scaffolds. MCF7 breast carcinoma cell line was used to assess scaffolds adequacy for 3D cell culture. To evaluate CSC enrichment, the Mammosphere Forming Index (MFI) was performed in 2D and 3D MCF7 cultures. Results showed that the 60° scaffolds were more suitable for 3D culture than the 45° and 90° ones. Moreover, 3D culture experiments, in adherent and non-adherent conditions, showed a significant increase in MFI compared to 2D cultures (control). Thus, 3D cell culture with PCL scaffolds could be useful to improve cancer cell culture and enrich the CSCs population. PMID:27120585

  8. Breast Cancer Stem Cell Culture and Enrichment Using Poly(ε-Caprolactone Scaffolds

    Directory of Open Access Journals (Sweden)

    Sònia Palomeras

    2016-04-01

    Full Text Available The cancer stem cell (CSC population displays self-renewal capabilities, resistance to conventional therapies, and a tendency to post-treatment recurrence. Increasing knowledge about CSCs’ phenotype and functions is needed to investigate new therapeutic strategies against the CSC population. Here, poly(ε-caprolactone (PCL, a biocompatible polymer free of toxic dye, has been used to fabricate scaffolds, solid structures suitable for 3D cancer cell culture. It has been reported that scaffold cell culture enhances the CSCs population. A RepRap BCN3D+ printer and 3 mm PCL wire were used to fabricate circular scaffolds. PCL design and fabrication parameters were first determined and then optimized considering several measurable variables of the resulting scaffolds. MCF7 breast carcinoma cell line was used to assess scaffolds adequacy for 3D cell culture. To evaluate CSC enrichment, the Mammosphere Forming Index (MFI was performed in 2D and 3D MCF7 cultures. Results showed that the 60° scaffolds were more suitable for 3D culture than the 45° and 90° ones. Moreover, 3D culture experiments, in adherent and non-adherent conditions, showed a significant increase in MFI compared to 2D cultures (control. Thus, 3D cell culture with PCL scaffolds could be useful to improve cancer cell culture and enrich the CSCs population.

  9. The use of targeted and non-targeted advertising to enrich skin cancer screening samples.

    Science.gov (United States)

    Katris, P; Donovan, R J; Gray, B N

    1996-08-01

    The purpose of this study was to determine whether the risk factor profile of persons attending skin cancer screening clinics could be enriched by appropriate advertising prior to the screening events. Eleven screening clinics were held in eight rural and three suburban communities. Matched communities were randomly assigned to either a target or non-target condition. Targeted communities received an advertisement designed to attract high-risk individuals. The advertisement listed a number of risk factors and encouraged readers with one or more of the listed risk factors to attend the screening. Non-targeted communities received a general advertisement requesting individuals who felt they were at risk of skin cancer to attend the clinic. Risk factor profiles of all participants were measured on the factors listed in the targeted advertisement. The risk factor profiles of screenees and the referral rates for skin lesions requiring attention were significantly higher in the targeted communities than in the non-targeted communities. Lesions suspicious of malignant melanoma or Hutchinson's melanotic freckle also were higher, but not statistically significant, in the targeted communities. Population samples attending community-based skin cancer screening clinics can be enriched by appropriate targeted advertising prior to the screening events. This has important implications for determining the potential cost-effectiveness of population screening programmes.

  10. The cancer-testis antigen NY-ESO-1 is highly expressed in myxoid and round cell subset of liposarcomas.

    Science.gov (United States)

    Hemminger, Jessica A; Ewart Toland, Amanda; Scharschmidt, Thomas J; Mayerson, Joel L; Kraybill, William G; Guttridge, Denis C; Iwenofu, O Hans

    2013-02-01

    Liposarcomas are a heterogenous group of fat-derived sarcomas, and surgery with or without chemoradiation therapy remains the main stay of treatment. NY-ESO-1 is a cancer-testis antigen expressed in various cancers where it can induce both cellular and humoral immunity. Immunotherapy has shown promise in clinical trials involving NY-ESO-1-expressing tumors. Gene expression studies have shown upregulation of the gene for NY-ESO-1, CTAG1B, in myxoid and round cell liposarcomas. Herein, we evaluated the expression of NY-ESO-1 among liposarcoma subtypes by quantitative real-time PCR, western blot analysis, and immunohistochemistry. Frozen tissue for quantitative real-time PCR and western blot analysis was obtained for the following liposarcoma subtypes (n=15): myxoid and round cell (n=8); well-differentiated (n=4), and dedifferentiated (n=3). Formalin-fixed paraffin-embedded blocks were obtained for the following liposarcoma subtypes (n=44): myxoid and round cell (n=18); well-differentiated (n=10); dedifferentiated (n=10); and pleomorphic (n=6). Full sections were stained with monoclonal antibody NY-ESO-1, and staining was assessed for intensity (1-3+), percentage of tumor positivity, and location. In all, 7/8 (88%) and 16/18 (89%) myxoid and round cell expressed CTAG1B and NY-ESO-1 by quantitative real-time PCR and immunohistochemistry, respectively. Western blot correlated with mRNA expression levels. By immunohistochemistry, 94% (15/16) of positive cases stained homogenously with 2-3+ intensity. Also, 3/6 (50%) pleomorphic liposarcomas demonstrated a range of staining: 1+ intensity in 50% of cells; 2+ intensity in 5% of cells; and 3+ intensity in 90% of cells. One case of dedifferentiated liposarcoma showed strong, diffuse staining (3+ intensity in 75% of cells). Our study shows that both CTAG1B mRNA and protein are overexpressed with high frequency in myxoid and round cell liposarcoma, enabling the potential use of targeted immunotherapy in the treatment of this

  11. An integrated microfluidic platform for negative selection and enrichment of cancer cells

    Science.gov (United States)

    Luo, Wen-Yi; Tsai, Sung-Chi; Hsieh, Kuangwen; Lee, Gwo-Bin

    2015-08-01

    Circulating tumor cells (CTCs), tumor cells that disseminate from primary tumors to the bloodstream, have recently emerged as promising indicators for cancer diagnosis and prognosis. However, the technical difficulties in isolating and detecting rare CTCs have limited the widespread applicability of this method to date. In this work, a new integrated microfluidic system integrating micromixers and micropumps capable of performing ‘negative selection and enrichment’ of CTCs was developed. By using anti-human CD45 antibodies-coated magnetic beads, leukocytes were effectively removed by applying an external magnetic force, leaving behind an enriched target cell population. The on-chip CTC recovery rate was experimentally found to be 70   ±   5% after a single round of negative selection and enrichment. Meanwhile, CD45 depletion efficiency was 83.99   ±   1.00% and could be improved to 99.84   ±   0.04% after three consecutive rounds of depletion. Notably, on-chip negative selection and enrichment was 58% faster and the repeated depletion could be processed automatically. These promising results suggested the developed microfluidic chip is potentiated for a standardized CTC isolation platform. Preliminary results of the current paper were presented at Micro TAS 2014, San Antonio, Texas, USA, October 26-30, 2014.

  12. Liver cancer stem cells are selectively enriched by low-dose cisplatin

    Directory of Open Access Journals (Sweden)

    H. Zhang

    2014-06-01

    Full Text Available Accumulating evidence has indicated the importance of cancer stem cells in carcinogenesis. The goal of the present study was to determine the effect of low-dose cisplatin on enriched liver cancer stem cells (LCSCs. Human hepatoblastoma HepG2 cells were treated with concentrations of cisplatin ranging from 1 to 5 μg/mL. Cell survival and proliferation were evaluated using a tetrazolium dye (MTT assay. LCSCs were identified using specific markers, namely aldehyde dehydrogenase-1 (ALDH1 and CD133. The percentage of ALDH1+ or CD133+ cells was examined by flow cytometric analysis. The expression of ALDH1 and/or CD133 in HepG2 cells was determined by immunocytochemical analysis. Low-dose cisplatin treatment significantly decreased cell survival in HepG2 cells after 24 or 72 h. However, the percentage of LCSCs in the surviving cells was greatly increased. The percentage of ALDH1+ or CD133+ cells was increased in a time- and dose-dependent manner after treatment with 1-4 μg/mL cisplatin, whereas 5 μg/mL cisplatin exposure slightly reduced the number of positive cells. These findings indicate that low-dose cisplatin treatment may efficiently enrich the LCSC population in HepG2 cells.

  13. Selenium enrichment of broccoli sprout extract increases chemosensitivity and apoptosis of LNCaP prostate cancer cells

    OpenAIRE

    Suzuki Kazuhiro; Ito Kazuto; Suradji Eka W; Yamazaki Chiho; Kobayashi Kenji; Faried Ahmad; Abdulah Rizky; Murakami Masami; Kuwano Hiroyuki; Koyama Hiroshi

    2009-01-01

    Abstract Background Broccoli is a Brassica vegetable that is believed to possess chemopreventive properties. Selenium also shows promise as an anticancer agent. Thus, selenium enrichment of broccoli has the potential to enhance the anticancer properties of broccoli sprouts. Method Selenium-enriched broccoli sprouts were prepared using a sodium selenite solution. Their anticancer properties were evaluated in human prostate cancer cell lines and compared with those of a control broccoli sprout ...

  14. Identification of CD166 as a surface marker for enriching prostate stem/progenitor and cancer initiating cells.

    Directory of Open Access Journals (Sweden)

    Jing Jiao

    Full Text Available New therapies for late stage and castration resistant prostate cancer (CRPC depend on defining unique properties and pathways of cell sub-populations capable of sustaining the net growth of the cancer. One of the best enrichment schemes for isolating the putative stem/progenitor cell from the murine prostate gland is Lin(-;Sca1(+;CD49f(hi (LSC(hi, which results in a more than 10-fold enrichment for in vitro sphere-forming activity. We have shown previously that the LSC(hi subpopulation is both necessary and sufficient for cancer initiation in the Pten-null prostate cancer model. To further improve this enrichment scheme, we searched for cell surface molecules upregulated upon castration of murine prostate and identified CD166 as a candidate gene. CD166 encodes a cell surface molecule that can further enrich sphere-forming activity of WT LSC(hi and Pten null LSC(hi. Importantly, CD166 could enrich sphere-forming ability of benign primary human prostate cells in vitro and induce the formation of tubule-like structures in vivo. CD166 expression is upregulated in human prostate cancers, especially CRPC samples. Although genetic deletion of murine CD166 in the Pten null prostate cancer model does not interfere with sphere formation or block prostate cancer progression and CRPC development, the presence of CD166 on prostate stem/progenitors and castration resistant sub-populations suggest that it is a cell surface molecule with the potential for targeted delivery of human prostate cancer therapeutics.

  15. The Role of Chemokines in Shaping the Balance Between CD4(+) T Cell Subsets and Its Therapeutic Implications in Autoimmune and Cancer Diseases.

    Science.gov (United States)

    Karin, Nathan; Wildbaum, Gizi

    2015-01-01

    Chemokines are the key activators of adhesion molecule and also drivers of leukocyte migration to inflammatory sites and are therefore mostly considered as proinflammatory mediators. Many studies, including ours, imply that targeting the function of several key chemokines, but not many others, could effectively suppress inflammatory responses and inflammatory autoimmunity. Along with this, a single chemokine named CXCL10 could be used to induce antitumor immunity, and thereby suppress myeloma. Our working hypothesis is that some chemokines differ from others as aside from being chemoattractants for leukocytes and effective activators of adhesion receptors that possess additional biological properties making them "driver chemokines." We came up with this notion when studying the interlay between CXCR4 and CXCL12 and between CXCR3 and its three ligands: CXCL9, CXCL10, and CXCL11. The current mini-review focuses on these ligands and their biological properties. First, we elaborate the role of cytokines in directing the polarization of effector and regulatory T cell subset and the plasticity of this process. Then, we extend this notion to chemokines while focusing on CXCL 12 and the CXCR3 ligands. Finally, we elaborate the potential clinical implications of these studies for therapy of autoimmunity, graft-versus-host disease, and cancer. PMID:26648938

  16. Repeated observation of immune gene sets enrichment in women with non-small cell lung cancer

    Science.gov (United States)

    Araujo, Jhajaira M.; Prado, Alexandra; Cardenas, Nadezhda K.; Zaharia, Mayer; Dyer, Richard; Doimi, Franco; Bravo, Leny; Pinillos, Luis; Morante, Zaida; Aguilar, Alfredo; Mas, Luis A.; Gomez, Henry L.; Vallejos, Carlos S.; Rolfo, Christian; Pinto, Joseph A.

    2016-01-01

    There are different biological and clinical patterns of lung cancer between genders indicating intrinsic differences leading to increased sensitivity to cigarette smoke-induced DNA damage, mutational patterns of KRAS and better clinical outcomes in women while differences between genders at gene-expression levels was not previously reported. Here we show an enrichment of immune genes in NSCLC in women compared to men. We found in a GSEA analysis (by biological processes annotated from Gene Ontology) of six public datasets a repeated observation of immune gene sets enrichment in women. “Immune system process”, “immune response”, “defense response”, “cellular defense response” and “regulation of immune system process” were the gene sets most over-represented while APOBEC3G, APOBEC3F, LAT, CD1D and CCL5 represented the top-five core genes. Characterization of immune cell composition with the platform CIBERSORT showed no differences between genders; however, there were differences when tumor tissues were compared to normal tissues. Our results suggest different immune responses in NSCLC between genders that could be related with the different clinical outcome. PMID:26958810

  17. Subset Analysis of a Multicenter, Randomized Controlled Trial to Compare Magnifying Chromoendoscopy with Endoscopic Ultrasonography for Stage Diagnosis of Early Stage Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Tomonori Yamada

    Full Text Available Our recent prospective study found equivalent accuracy of magnifying chromoendoscopy (MC and endoscopic ultrasonography (EUS for diagnosing the invasion depth of colorectal cancer (CRC; however, whether these tools show diagnostic differences in categories such as tumor size and morphology remains unclear. Hence, we conducted detailed subset analysis of the prospective data.In this multicenter, prospective, comparative trial, a total of 70 patients with early, flat CRC were enrolled from February 2011 to December 2012, and the results of 66 lesions were finally analyzed. Patients were randomly allocated to primary MC followed by EUS or to primary EUS followed by MC. Diagnoses of invasion depth by each tool were divided into intramucosal to slight submucosal invasion (invasion depth <1000 μm and deep submucosal invasion (invasion depth ≥1000 μm, and then compared with the final pathological diagnosis by an independent pathologist blinded to clinical data. To standardize diagnoses among examiners, this trial was started after achievement of a mean κ value of ≥0.6 which was calculated from the average of κ values between each pair of participating endoscopists.Both MC and EUS showed similar diagnostic outcomes, with no significant differences in prediction of invasion depth in subset analyses according to tumor size, location, and morphology. Lesions that were consistently diagnosed as Tis/T1-SMS or ≥T1-SMD with both tools revealed accuracy of 76-78%. Accuracy was low in borderline lesions with irregular pit pattern in MC and distorted findings of the third layer in EUS (MC, 58.5%; EUS, 50.0%.MC and EUS showed the same limited accuracy for predicting invasion depth in all categories of early CRC. Since the irregular pit pattern in MC, distorted findings to the third layer in EUS and inconsistent diagnosis between both tools were associated with low accuracy, further refinements or even novel methods are still needed for such lesions

  18. Clinical Effects of Shenqi Fuzheng Injection in the Neoadjuvant Chemotherapy for Local Advanced Breast Cancer and the Effects on T-lymphocyte Subsets

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective: To evaluate clinical effects of Shenqi Fuzheng Injection (参芪抉正注射液) in the neoadjuvant chemotherapy for local advanced breast cancer and the effects on T-lymphocyte subsets. Methods: During the period from 2000 to 2005, 126 patients with local advanced breast cancer were treated with the neoadjuvant chemotherapy. They were randomly divided into the following two groups: a control group of 61 cases treated by chemotherapy alone and a study group of 65 cases treated by chemotherapy plus Shenqi Fuzheng Injection. All the cases of both groups were given the CEF (CTX 500 mg/m2, d1, 8; EPI 40 mg/m2, d1, 8; and 5-Fu 500 mg/m2, d1,8) regimen. The clinical effects, the effects on T-lymphocyte subgroup and NK cells, and the toxic side effects were observed. Results: All the patients completed two cycles of the chemotherapy, and the efficacy and the toxic side effects were evaluated. For the primary tumor in the breast, the total effective rate was 69.2% (45/65) in the study group and 49.2% (30/61) in the control group with a statistically significant difference in the intergroup comparison (χ2=5.251, P=0.022, < 0.05). There was no progression of the disease in both the groups, and there were no grade IV toxic side effects in the two groups. The major toxic responses were myelosuppression and gastrointestinal reaction, which were milder in the study group than the control group, and with a shorter recovery course in the former than the latter. Besides, an obvious rise of the T-lymphocyte subgroup and NK cells was found in the study group after the neoadjuvant chemotherapy, with a very significant difference from the controls (P<0.01). Conclusions: Shenqi Fuzheng Injection can improve and regulate immune function of the patients with local advanced breast cancer given the neoadjuvant chemotherapy, and therefore it can enhance the curative effect and reduce the side effect as well.

  19. Integrative Analysis of Gene Expression Data Including an Assessment of Pathway Enrichment for Predicting Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Pingzhao Hu

    2006-01-01

    Full Text Available Background: Microarray technology has been previously used to identify genes that are differentially expressed between tumour and normal samples in a single study, as well as in syntheses involving multiple studies. When integrating results from several Affymetrix microarray datasets, previous studies summarized probeset-level data, which may potentially lead to a loss of information available at the probe-level. In this paper, we present an approach for integrating results across studies while taking probe-level data into account. Additionally, we follow a new direction in the analysis of microarray expression data, namely to focus on the variation of expression phenotypes in predefined gene sets, such as pathways. This targeted approach can be helpful for revealing information that is not easily visible from the changes in the individual genes. Results: We used a recently developed method to integrate Affymetrix expression data across studies. The idea is based on a probe-level based test statistic developed for testing for differentially expressed genes in individual studies. We incorporated this test statistic into a classic random-effects model for integrating data across studies. Subsequently, we used a gene set enrichment test to evaluate the significance of enriched biological pathways in the differentially expressed genes identified from the integrative analysis. We compared statistical and biological significance of the prognostic gene expression signatures and pathways identified in the probe-level model (PLM with those in the probeset-level model (PSLM. Our integrative analysis of Affymetrix microarray data from 110 prostate cancer samples obtained from three studies reveals thousands of genes significantly correlated with tumour cell differentiation. The bioinformatics analysis, mapping these genes to the publicly available KEGG database, reveals evidence that tumour cell differentiation is significantly associated with many

  20. On best subset regression

    OpenAIRE

    Xiong, Shifeng

    2011-01-01

    In this paper we discuss the variable selection method from \\ell0-norm constrained regression, which is equivalent to the problem of finding the best subset of a fixed size. Our study focuses on two aspects, consistency and computation. We prove that the sparse estimator from such a method can retain all of the important variables asymptotically for even exponentially growing dimensionality under regularity conditions. This indicates that the best subset regression method can efficiently shri...

  1. Human bladder cancer stem cells exist in epithelial membrane antigen-subset%人膀胱癌干细胞存在于EMA-细胞亚群

    Institute of Scientific and Technical Information of China (English)

    杨宇明; 畅继武

    2008-01-01

    BACKGROUND:Cancer stem cell (CSC) hypothesis suggests that tumorous clones are maintained by a rare fraction of cells with stem cell proprieties. Several kinds of CSCs of solid tumor have been isolated in recent years. However, there have been fewer studies on the objective existence of bladder cancer stem cells (BCSCs) and on the methods to effectively isolate and identify BCSCs. OBJECTIVE:To investigate possibilities of BCSC existence and of epithelial membrane antigen (EMA) used as a surface marker of BCSC. DESIGN:A control observation experiment. SETTING:Tianjin Institute of Urinary Surgery & Second Hospital of Tianjin Medical University. MATERIALS:This study was performed at the Room for Tumor Immunity of Tianjin Institute of Urinary Surgery (key laboratory for State "211 Project") from March 2006 to July 2007. Nine specimens of human bladder were obtained from patients who received treatment in the Second Hospital of Tianjin Medical University. These specimens corresponded to the diagnostic criteria of low malignant potential papillary urothelial neoplasm and low-grade papillary urothelial carcinoma. Additionally, 40 samples of human low malignant bladder transitional cell carcinomas (BTCC) and 10 samples of normal urothelium that were used for immunohistochemistry were obtained from the patients who received treatment in the Department of Urinary Surgery, Second Hospital of Tianjin Medical University. Written informed consent for the specimen providing was obtained from the patients, and the protocol was approved by the hospital’s Ethics Committee. METHODS:The genes that were differentially expressed between normal urothelium and BTCC were identified through a DNA array assay to preliminarily determine the existence of BTCC. Overpressed stem cell related genes, Bmi-1 and EZH2, were verified by immunohistochemistry. A total of 27 potential surface markers of BCSCs were assayed to determine the location of positive cells. EMA- subsets were obtained through

  2. Impact of fish oil enriched total parenteral nutrition on elderly patients after colorectal cancer surgery

    Institute of Scientific and Technical Information of China (English)

    ZHU Ming-wei; TANG Da-nian; HOU Jing; WEI Jun-min; HUA Bin; SUN Jian-hua; CUI Hong-yuan

    2012-01-01

    Background Polyunsaturated omega-3 fatty acids may beneficially influence healing processes and patient outcomes.The aim of this research was to study the clinical efficacy of fish oil enriched total parenteral nutrition in elderly patients after colorectal cancer surgery.Methods Fifty-seven elderly patients with colorectal cancer were enrolled in this prospective,randomized,double-blind,controlled clinical trial.All patients received isocaloric and isonitrogenous total parenteral nutrition by continuous infusion (20-24 hours per day) for seven days after surgery.The control group (n=28) received 1.2 g/kg soybean oil per day,whereas the treatment group (n=29) received 0.2 g/kg fish oil and 1.0 g/kg soybean oil per day.Blood samples were taken pre-operatively,and at days one and eight after the operation.The plasma levels of CD4,CD8,CD4/CD8,interleukin 6 (IL-6) and tumor necrosis factor a (TNF-a) were measured.Clinical outcomes were then analysed.Results Patient characteristics were comparable between the two groups.At day eight post-surgery,IL-6,TNF-α and CD8 titres were lower in the treatment group when compared to the control group; these results reached statistical significance.In the treatment group,there were fewer infectious complications and incidences of systemic inflammatory response syndrome (SIRS),and shorter lengths of hospital stay were observed.The total cost of medical care was comparable for the two groups.No serious adverse events occurred in either group.Conclusions Fish oil 0.2 g/kg per day administrated to elderly patients after colorectal surgery was safe and may shorten the length of hospital stay and improve clinical outcomes.

  3. Pros and cons of HaloPlex enrichment in cancer predisposition genetic diagnosis

    Directory of Open Access Journals (Sweden)

    Agnès Collet

    2015-12-01

    Full Text Available Panel sequencing is a practical option in genetic diagnosis. Enrichment and library preparation steps are critical in the diagnostic setting. In order to test the value of HaloPlex technology in diagnosis, we designed a custom oncogenetic panel including 62 genes. The procedure was tested on a training set of 71 controls and then blindly validated on 48 consecutive hereditary breast/ovarian cancer (HBOC patients tested negative for BRCA1/2 mutation. Libraries were sequenced on HiSeq2500 and data were analysed with our academic bioinformatics pipeline. Point mutations were detected using Varscan2, median size indels were detected using Pindel and large genomic rearrangements (LGR were detected by DESeq. Proper coverage was obtained. However, highly variable read depth was observed within genes. Excluding pseudogene analysis, all point mutations were detected on the training set. All indels were also detected using Pindel. On the other hand, DESeq allowed LGR detection but with poor specificity, preventing its use in diagnostics. Mutations were detected in 8% of BRCA1/2-negative HBOC cases. HaloPlex technology appears to be an efficient and promising solution for gene panel diagnostics. Data analysis remains a major challenge and geneticists should enhance their bioinformatics knowledge in order to ensure good quality diagnostic results.

  4. Co-expression network analysis identifies Spleen Tyrosine Kinase (SYK) as a candidate oncogenic driver in a subset of small-cell lung cancer

    OpenAIRE

    Udyavar, Akshata R; Hoeksema, Megan D.; Clark, Jonathan E; Zou, Yong; Tang, Zuojian; Li, Zhiguo; Li, Ming; Chen, Heidi; Statnikov, Alexander; Shyr, Yu; Liebler, Daniel C.; Field, John; Eisenberg, Rosana; Estrada, Lourdes; Massion, Pierre P.

    2013-01-01

    Background Oncogenic mechanisms in small-cell lung cancer remain poorly understood leaving this tumor with the worst prognosis among all lung cancers. Unlike other cancer types, sequencing genomic approaches have been of limited success in small-cell lung cancer, i.e., no mutated oncogenes with potential driver characteristics have emerged, as it is the case for activating mutations of epidermal growth factor receptor in non-small-cell lung cancer. Differential gene expression analysis has al...

  5. Stem cell marker aldehyde dehydrogenase 1 (ALDH1)-expressing cells are enriched in triple-negative breast cancer.

    Science.gov (United States)

    Li, Huihui; Ma, Fei; Wang, Haijuan; Lin, Chen; Fan, Ying; Zhang, Xueyan; Qian, Haili; Xu, Binghe

    2013-12-17

    The stem cell marker ALDH1 has been of particular interest to scientists since it has been successfully used as a marker to isolate cancer stem cells from breast cancers. However, little is known, especially in Chinese breast cancer patients, on whether ALDH1 enrichment is prevalent in certain subtypes of breast cancer. In this study, we performed flow cytometry and immunohistochemistry to measure the expression of ALDH1 in 10 breast cancer cell lines and in a set of tissue microarrays consisting of 101 breast cancer tissues from the Chinese population. The 101 breast cancer tissues included 4 cancer subtypes defined on bases of their ER, PR, and HER2 statuses: triple-negative (25 cases), luminal A (33 cases), luminal B (16 cases) and HER2-overexpressing (HER2-OE, 27 cases). We found that ALDH1 was expressed in 25 of the 101 cases of breast cancer tissues. When the analysis was stratified, we found that the expression of ALDH1 varied significantly among the 4 subtypes, with a higher expression in triple-negative breast cancer (TNBC, p=0.003) than in the other 3 subtypes. In a series of breast cancer cell lines, we also confirmed that ALDH1 activity was mainly found in TNBC cell lines compared with non-TNBC ones (15.6% ± 2.45% vs 5.5% ± 2.58%, p=0.026). These data support the concept that the expression of ALDH1 is higher in TNBC than non-TNBC, which may be clinically meaningful for a better understanding of the poor prognosis of TNBC patients.

  6. Germline Heterozygous Variants in SEC23B Are Associated with Cowden Syndrome and Enriched in Apparently Sporadic Thyroid Cancer

    Science.gov (United States)

    Yehia, Lamis; Niazi, Farshad; Ni, Ying; Ngeow, Joanne; Sankunny, Madhav; Liu, Zhigang; Wei, Wei; Mester, Jessica L.; Keri, Ruth A.; Zhang, Bin; Eng, Charis

    2015-01-01

    Cancer-predisposing genes associated with inherited cancer syndromes help explain mechanisms of sporadic carcinogenesis and often inform normal development. Cowden syndrome (CS) is an autosomal-dominant disorder characterized by high lifetime risks of epithelial cancers, such that ∼50% of affected individuals are wild-type for known cancer-predisposing genes. Using whole-exome and Sanger sequencing of a multi-generation CS family affected by thyroid and other cancers, we identified a pathogenic missense heterozygous SEC23B variant (c.1781T>G [p.Val594Gly]) that segregates with the phenotype. We also found germline heterozygous SEC23B variants in 3/96 (3%) unrelated mutation-negative CS probands with thyroid cancer and in The Cancer Genome Atlas (TCGA), representing apparently sporadic cancers. We note that the TCGA thyroid cancer dataset is enriched with unique germline deleterious SEC23B variants associated with a significantly younger age of onset. SEC23B encodes Sec23 homolog B (S. cerevisiae), a component of coat protein complex II (COPII), which transports proteins from the endoplasmic reticulum (ER) to the Golgi apparatus. Interestingly, germline homozygous or compound-heterozygous SEC23B mutations cause an unrelated disorder, congenital dyserythropoietic anemia type II, and SEC23B-deficient mice suffer from secretory organ degeneration due to ER-stress-associated apoptosis. By characterizing the p.Val594Gly variant in a normal thyroid cell line, we show that it is a functional alteration that results in ER-stress-mediated cell-colony formation and survival, growth, and invasion, which reflect aspects of a cancer phenotype. Our findings suggest a different role for SEC23B, whereby germline heterozygous variants associate with cancer predisposition potentially mediated by ER stress “addiction.” PMID:26522472

  7. Optimization of an Enrichment process for Circulating tumor cells from the blood of Head and Neck Cancer patients through depletion of normal cells

    OpenAIRE

    Yang, Liying; Lang, James C.; Balasubramanian, Priya; Jatana, Kris R.; Schuller, David; Agrawal, Amit; Zborowski, Maciej; Chalmers, Jeffrey J.

    2009-01-01

    The optimization of a purely negative depletion, enrichment process for circulating tumor cells, CTC's, in the peripheral blood of Head and Neck cancer patients is presented. The enrichment process uses a red cell lysis step followed by immunomagnetic labeling, and subsequent depletion, of CD45 positive cells. A number of relevant variables are quantified, or attempted to be quantified, which control the performance of the enrichment process. Six different immunomagnetic labeling combinations...

  8. CXCR3 expression defines a novel subset of innate CD8+ T cells that enhance immunity against bacterial infection and cancer upon stimulation with IL-15

    OpenAIRE

    Oghumu, Steve; Terrazas, Cesar A.; Varikuti, Sanjay; Kimble, Jennifer; Vadia, Stephen; Yu, Lianbo; Seveau, Stephanie; Abhay R Satoskar

    2014-01-01

    Innate CD8+ T cells are a heterogeneous population with developmental pathways distinct from conventional CD8+ T cells. However, their biology, classification, and functions remain incompletely understood. We recently demonstrated the existence of a novel population of chemokine (C-X-C motif) receptor 3 (CXCR3)-positive innate CD8+ T cells. Here, we investigated the functional properties of this subset and identified effector molecules and pathways which mediate their function. Adoptive trans...

  9. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

    OpenAIRE

    Wang, Zhaoming; Zhu, Bin; Zhang, Mingfeng; Parikh, Hemang; Jia, Jinping; Chung, Charles C.; Sampson, Joshua N.; Hoskins, Jason W.; Hutchinson, Amy; Burdette, Laurie; Ibrahim, Abdisamad; Hautman, Christopher; Raj, Preethi S.; Abnet, Christian C.; Adjei, Andrew A.

    2014-01-01

    Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based...

  10. DNA-methyltransferase 3B 39179 G > T polymorphism and risk of sporadic colorectal cancer in a subset of Iranian population

    Directory of Open Access Journals (Sweden)

    Abdolreza Daraei

    2011-01-01

    Full Text Available Background: Epigenetic event is a biological regulation that influences the expression of various genes involved in cancer. DNA methylation is established by DNA methyltransferases, particularly DNAmethyltransferase 3B (DNMT3B. It seems to play an oncogenic role in the creation of abnormal methylation during tumorigenesis. The polymorphisms of the DNMT3B gene may influence DNMT3B activity in DNA methylation and increase the susceptibility to several cancers. These genetic polymorphisms have been studied in several cancers in different populations. Methods: In this study, we performed a case-control study with 125 colorectal cancer patients and 135 cancer-free controls to evaluate the association between DNMT3B G39179T polymorphism (rs1569686 in the promoter region and the risk of sporadic colorectal cancer. Up to now, few studies have investigated the role of this gene variant in sporadic colorectal cancer with no familial history. The genotypes of DNMT3B G39179T polymorphism was analyzed by PCR-RFLP. Results: We found that compared with G allele carriers, statistically the DNMT3B TT genotype (%34 was significantly associated with increased risk of colorectal cancer (adjusted OR, 3.993, 95% CI, 1.726-9.238, P = 0.001. Compared with DNMT3B TT genotype, the GT and GG genotypes had lower risk of developing sporadic colorectal cancer (OR = 0.848, 95% CI = 0.436-1.650. Conclusions: Our findings were consistent with that of previously reported case-control studies with colorectal cancer. These results suggest that the DNMT3B G39179T polymorphism influences DNMT3B expression, thus contributing to the genetic susceptibility to colorectal cancer. Further mechanistic studies are needed to unravel the causal molecular mechanisms.

  11. Detection of T-lymphocyte subsets of axillary nodes in patients with breast cancer and its significance%乳腺癌患者腋窝淋巴结T细胞亚群检测及其临床意义

    Institute of Scientific and Technical Information of China (English)

    何伟华; 王长松; 贠田; 原旭涛

    2013-01-01

    It has been known that CD4+ and CD8+ T cells participate in the immune adjust of cancer patients,however the T-lymphocytes subsets in axillary nodes of breast cancer patients and its clinical significance have not been studied.In this paper,T-lymphocyte subsets in axillary nodes of 60 patients with breast cancer and 23 cases of benign diseases were detected by flow cytometry methods and analyzed with clinical pathological characteristics.Results showed that percentages of CD4+ and CD4+/CD8+ cells in patients with breast cancer were significantly lower than those with breast benign disease (P< 0.05),and CD8+ T cells was increased in breast cancer patients compared with benign diseases patients.CD4+ and CD4+CD8+ cells in patients with positive axillary nodes were lower markedly than that of negative axillary nodes patients (P<0.05),however there was no significant difference in percentage of CD8+ cells between these two groups (P> 0.05).Percentage of CD4+,CD8+ and CD4+/CD8+ ratio in axillary nodes related with clinical TNM stage,but not with family history,age,size of tumor,condition of ER,PR and HER-2 (P>0.05) of breast cancer patients.In conclusion,T cell subsets are abnormal in patients with breast cancer.Detection of T lymphocyte subsets in axillary nodes could estimate the prognosis of patients with breast cancer.%目的 分析乳腺癌及乳腺良性病变患者腋窝淋巴结T细胞亚群的变化及其临床病理意义.方法 应用流式细胞术对60例乳腺癌患者及23例乳腺良性病变患者腋窝淋巴结T细胞亚群进行检测,同时结合临床病理特征进行分析.结果 乳腺癌患者腋窝淋巴结CD4+细胞百分比和CD4+/CD8+比值显著低于乳腺良性病变组(P<0.05);CD8+细胞百分比则高于乳腺良性病变组.伴腋窝淋巴结转移者CD4+细胞百分比和CD4+/CD8+比值也显著降低(P<0.05);而CD8+细胞百分比则变化不显著(P>0.05).乳腺癌患者腋窝淋巴结中CD4+细胞百分比、CD8+

  12. Enriched environment inhibits mouse pancreatic cancer growth and down-regulates the expression of mitochondria-related genes in cancer cells.

    Science.gov (United States)

    Li, Guohua; Gan, Yu; Fan, Yingchao; Wu, Yufeng; Lin, Hechun; Song, Yanfang; Cai, Xiaojin; Yu, Xiang; Pan, Weihong; Yao, Ming; Gu, Jianren; Tu, Hong

    2015-01-19

    Psycho-social stress has been suggested to influence the development of cancer, but it remains poorly defined with regard to pancreatic cancer, a lethal malignancy with few effective treatment modalities. In this study, we sought to investigate the impacts of enriched environment (EE) housing, a rodent model of "eustress", on the growth of mouse pancreatic cancer, and to explore the potential underlying mechanisms through gene expression profiling. The EE mice showed significantly reduced tumor weights in both subcutaneous (53%) and orthotopic (41%) models, while each single component of EE (inanimate stimulation, social stimulation or physical exercise) was not profound enough to achieve comparative anti-tumor effects as EE. The integrative transcriptomic and proteomic analysis revealed that in response to EE, a total of 129 genes in the tumors showed differential expression at both the mRNA and protein levels. The differentially expressed genes were mostly localized to the mitochondria and enriched in the citrate cycle and oxidative phosphorylation pathways. Interestingly, nearly all of the mitochondria-related genes were down-regulated by EE. Our data have provided experimental evidence in favor of the application of positive stress or of benign environmental stimulation in pancreatic cancer therapy.

  13. A Walnut-Enriched Diet Reduces the Growth of LNCaP Human Prostate Cancer Xenografts in Nude Mice

    OpenAIRE

    Reiter, Russel J.; Tan, Dun-Xian; Manchester, Lucien C.; Korkmaz, Ahmet; Fuentes-Broto, Lorena; Hardman, W. Elaine; Rosales-Corral, Sergio A; Qi, Wenbo

    2013-01-01

    It was investigated whether a standard mouse diet (AIN-76A) supplemented with walnuts reduced the establishment and growth of LNCaP human prostate cancer cells in nude (nu/nu) mice. The walnut-enriched diet reduced the number of tumors and the growth of the LNCaP xenografts; 3 of 16 (18.7%) of the walnut-fed mice developed tumors; conversely, 14 of 32 mice (44.0%) of the control diet-fed animals developed tumors. Similarly, the xenografts in the walnut-fed animals grew more slowly than those ...

  14. Down-regulation of gut-enriched Krüppel-like factor expression in esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    Nan Wang; Zhi-Hua Liu; Fang Ding; Xiu-Qin Wang; Chuan-Nong Zhou; Min Wu

    2002-01-01

    AIM: Esophageal carcinoma is one of the most common malignant tumors in China. But the molecular mechanisms of esophageal carcinoma remains unclear. Gut-enriched factor which is expressed abandantly in the epithelial cells of the gastrointestinal tract and deregulation of GKLF was linked to several types of cancer. It is of interest to study the expression and role of GKLF in esophageal carcinoma.METHODS: Semi-quantitative RT-PCR was used to compare GKLF expression in esophageal squamous cell carcinoma to normal mucosa of the same patients. The serum deprivation inducibility of GKLF was observed in an esophageal squamous cancer cell line by comparison to the primary culture of human fibroblast. The effect of antisense GKLF transfection on the proliferation and adhesion of esophageal squamous cancer cell line was also observed.RESULTS: The level of GKLF transcript is lower in esophageal squamous cell carcinoma compared to paired normal-appearing mucosa in 14 of 17 of the tumors analyzed.The serum deprivation inducibility of GKLF was greatly decreased in an esophageal squamous cancer cell line compared to the primary culture of human fibroblast.Decreased expression of GKLF in the esophageal cancer cell by antisense GKLF transfection increased its proliferation rate compared with that of vector transfected cell control (P<0.05). Transfection of antisense GKLF decreased its adhesion ability (P<0.05).CONCLUSION: The findings of this study demonstrate the down-regulation of GKLF in esophageal squamous cancer,and suggest that deregulation of GKLF may play a role in initiation and/or progression as well as the metastasis of esophageal squamous cancer.

  15. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

    Science.gov (United States)

    Wang, Zhaoming; Zhu, Bin; Zhang, Mingfeng; Parikh, Hemang; Jia, Jinping; Chung, Charles C.; Sampson, Joshua N.; Hoskins, Jason W.; Hutchinson, Amy; Burdette, Laurie; Ibrahim, Abdisamad; Hautman, Christopher; Raj, Preethi S.; Abnet, Christian C.; Adjei, Andrew A.; Ahlbom, Anders; Albanes, Demetrius; Allen, Naomi E.; Ambrosone, Christine B.; Aldrich, Melinda; Amiano, Pilar; Amos, Christopher; Andersson, Ulrika; Andriole, Gerald; Andrulis, Irene L.; Arici, Cecilia; Arslan, Alan A.; Austin, Melissa A.; Baris, Dalsu; Barkauskas, Donald A.; Bassig, Bryan A.; Beane Freeman, Laura E.; Berg, Christine D.; Berndt, Sonja I.; Bertazzi, Pier Alberto; Biritwum, Richard B.; Black, Amanda; Blot, William; Boeing, Heiner; Boffetta, Paolo; Bolton, Kelly; Boutron-Ruault, Marie-Christine; Bracci, Paige M.; Brennan, Paul; Brinton, Louise A.; Brotzman, Michelle; Bueno-de-Mesquita, H. Bas; Buring, Julie E.; Butler, Mary Ann; Cai, Qiuyin; Cancel-Tassin, Geraldine; Canzian, Federico; Cao, Guangwen; Caporaso, Neil E.; Carrato, Alfredo; Carreon, Tania; Carta, Angela; Chang, Gee-Chen; Chang, I-Shou; Chang-Claude, Jenny; Che, Xu; Chen, Chien-Jen; Chen, Chih-Yi; Chen, Chung-Hsing; Chen, Constance; Chen, Kuan-Yu; Chen, Yuh-Min; Chokkalingam, Anand P.; Chu, Lisa W.; Clavel-Chapelon, Francoise; Colditz, Graham A.; Colt, Joanne S.; Conti, David; Cook, Michael B.; Cortessis, Victoria K.; Crawford, E. David; Cussenot, Olivier; Davis, Faith G.; De Vivo, Immaculata; Deng, Xiang; Ding, Ti; Dinney, Colin P.; Di Stefano, Anna Luisa; Diver, W. Ryan; Duell, Eric J.; Elena, Joanne W.; Fan, Jin-Hu; Feigelson, Heather Spencer; Feychting, Maria; Figueroa, Jonine D.; Flanagan, Adrienne M.; Fraumeni, Joseph F.; Freedman, Neal D.; Fridley, Brooke L.; Fuchs, Charles S.; Gago-Dominguez, Manuela; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M.; Garcia-Closas, Montserrat; Garcia-Closas, Reina; Gastier-Foster, Julie M.; Gaziano, J. Michael; Gerhard, Daniela S.; Giffen, Carol A.; Giles, Graham G.; Gillanders, Elizabeth M.; Giovannucci, Edward L.; Goggins, Michael; Gokgoz, Nalan; Goldstein, Alisa M.; Gonzalez, Carlos; Gorlick, Richard; Greene, Mark H.; Gross, Myron; Grossman, H. Barton; Grubb, Robert; Gu, Jian; Guan, Peng; Haiman, Christopher A.; Hallmans, Goran; Hankinson, Susan E.; Harris, Curtis C.; Hartge, Patricia; Hattinger, Claudia; Hayes, Richard B.; He, Qincheng; Helman, Lee; Henderson, Brian E.; Henriksson, Roger; Hoffman-Bolton, Judith; Hohensee, Chancellor; Holly, Elizabeth A.; Hong, Yun-Chul; Hoover, Robert N.; Hosgood, H. Dean; Hsiao, Chin-Fu; Hsing, Ann W.; Hsiung, Chao Agnes; Hu, Nan; Hu, Wei; Hu, Zhibin; Huang, Ming-Shyan; Hunter, David J.; Inskip, Peter D.; Ito, Hidemi; Jacobs, Eric J.; Jacobs, Kevin B.; Jenab, Mazda; Ji, Bu-Tian; Johansen, Christoffer; Johansson, Mattias; Johnson, Alison; Kaaks, Rudolf; Kamat, Ashish M.; Kamineni, Aruna; Karagas, Margaret; Khanna, Chand; Khaw, Kay-Tee; Kim, Christopher; Kim, In-Sam; Kim, Jin Hee; Kim, Yeul Hong; Kim, Young-Chul; Kim, Young Tae; Kang, Chang Hyun; Jung, Yoo Jin; Kitahara, Cari M.; Klein, Alison P.; Klein, Robert; Kogevinas, Manolis; Koh, Woon-Puay; Kohno, Takashi; Kolonel, Laurence N.; Kooperberg, Charles; Kratz, Christian P.; Krogh, Vittorio; Kunitoh, Hideo; Kurtz, Robert C.; Kurucu, Nilgun; Lan, Qing; Lathrop, Mark; Lau, Ching C.; Lecanda, Fernando; Lee, Kyoung-Mu; Lee, Maxwell P.; Le Marchand, Loic; Lerner, Seth P.; Li, Donghui; Liao, Linda M.; Lim, Wei-Yen; Lin, Dongxin; Lin, Jie; Lindstrom, Sara; Linet, Martha S.; Lissowska, Jolanta; Liu, Jianjun; Ljungberg, Börje; Lloreta, Josep; Lu, Daru; Ma, Jing; Malats, Nuria; Mannisto, Satu; Marina, Neyssa; Mastrangelo, Giuseppe; Matsuo, Keitaro; McGlynn, Katherine A.; McKean-Cowdin, Roberta; McNeill, Lorna H.; McWilliams, Robert R.; Melin, Beatrice S.; Meltzer, Paul S.; Mensah, James E.; Miao, Xiaoping; Michaud, Dominique S.; Mondul, Alison M.; Moore, Lee E.; Muir, Kenneth; Niwa, Shelley; Olson, Sara H.; Orr, Nick; Panico, Salvatore; Park, Jae Yong; Patel, Alpa V.; Patino-Garcia, Ana; Pavanello, Sofia; Peeters, Petra H. M.; Peplonska, Beata; Peters, Ulrike; Petersen, Gloria M.; Picci, Piero; Pike, Malcolm C.; Porru, Stefano; Prescott, Jennifer; Pu, Xia; Purdue, Mark P.; Qiao, You-Lin; Rajaraman, Preetha; Riboli, Elio; Risch, Harvey A.; Rodabough, Rebecca J.; Rothman, Nathaniel; Ruder, Avima M.; Ryu, Jeong-Seon; Sanson, Marc; Schned, Alan; Schumacher, Fredrick R.; Schwartz, Ann G.; Schwartz, Kendra L.; Schwenn, Molly; Scotlandi, Katia; Seow, Adeline; Serra, Consol; Serra, Massimo; Sesso, Howard D.; Severi, Gianluca; Shen, Hongbing; Shen, Min; Shete, Sanjay; Shiraishi, Kouya; Shu, Xiao-Ou; Siddiq, Afshan; Sierrasesumaga, Luis; Sierri, Sabina; Loon Sihoe, Alan Dart; Silverman, Debra T.; Simon, Matthias; Southey, Melissa C.; Spector, Logan; Spitz, Margaret; Stampfer, Meir; Stattin, Par; Stern, Mariana C.; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael Z.; Stram, Daniel O.; Strom, Sara S.; Su, Wu-Chou; Sund, Malin; Sung, Sook Whan; Swerdlow, Anthony; Tan, Wen; Tanaka, Hideo; Tang, Wei; Tang, Ze-Zhang; Tardon, Adonina; Tay, Evelyn; Taylor, Philip R.; Tettey, Yao; Thomas, David M.; Tirabosco, Roberto; Tjonneland, Anne; Tobias, Geoffrey S.; Toro, Jorge R.; Travis, Ruth C.; Trichopoulos, Dimitrios; Troisi, Rebecca; Truelove, Ann; Tsai, Ying-Huang; Tucker, Margaret A.; Tumino, Rosario; Van Den Berg, David; Van Den Eeden, Stephen K.; Vermeulen, Roel; Vineis, Paolo; Visvanathan, Kala; Vogel, Ulla; Wang, Chaoyu; Wang, Chengfeng; Wang, Junwen; Wang, Sophia S.; Weiderpass, Elisabete; Weinstein, Stephanie J.; Wentzensen, Nicolas; Wheeler, William; White, Emily; Wiencke, John K.; Wolk, Alicja; Wolpin, Brian M.; Wong, Maria Pik; Wrensch, Margaret; Wu, Chen; Wu, Tangchun; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S.; Xiang, Yong-Bing; Xu, Jun; Yang, Hannah P.; Yang, Pan-Chyr; Yatabe, Yasushi; Ye, Yuanqing; Yeboah, Edward D.; Yin, Zhihua; Ying, Chen; Yu, Chong-Jen; Yu, Kai; Yuan, Jian-Min; Zanetti, Krista A.; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Zhou, Baosen; Mirabello, Lisa; Savage, Sharon A.; Kraft, Peter; Chanock, Stephen J.; Yeager, Meredith; Landi, Maria Terese; Shi, Jianxin; Chatterjee, Nilanjan; Amundadottir, Laufey T.

    2014-01-01

    Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10−39; Region 3: rs2853677, P = 3.30 × 10−36 and PConditional = 2.36 × 10−8; Region 4: rs2736098, P = 3.87 × 10−12 and PConditional = 5.19 × 10−6, Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10−6; and Region 6: rs10069690, P = 7.49 × 10−15 and PConditional = 5.35 × 10−7) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10−18 and PConditional = 7.06 × 10−16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci. PMID:25027329

  16. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.

    Science.gov (United States)

    Wang, Zhaoming; Zhu, Bin; Zhang, Mingfeng; Parikh, Hemang; Jia, Jinping; Chung, Charles C; Sampson, Joshua N; Hoskins, Jason W; Hutchinson, Amy; Burdette, Laurie; Ibrahim, Abdisamad; Hautman, Christopher; Raj, Preethi S; Abnet, Christian C; Adjei, Andrew A; Ahlbom, Anders; Albanes, Demetrius; Allen, Naomi E; Ambrosone, Christine B; Aldrich, Melinda; Amiano, Pilar; Amos, Christopher; Andersson, Ulrika; Andriole, Gerald; Andrulis, Irene L; Arici, Cecilia; Arslan, Alan A; Austin, Melissa A; Baris, Dalsu; Barkauskas, Donald A; Bassig, Bryan A; Beane Freeman, Laura E; Berg, Christine D; Berndt, Sonja I; Bertazzi, Pier Alberto; Biritwum, Richard B; Black, Amanda; Blot, William; Boeing, Heiner; Boffetta, Paolo; Bolton, Kelly; Boutron-Ruault, Marie-Christine; Bracci, Paige M; Brennan, Paul; Brinton, Louise A; Brotzman, Michelle; Bueno-de-Mesquita, H Bas; Buring, Julie E; Butler, Mary Ann; Cai, Qiuyin; Cancel-Tassin, Geraldine; Canzian, Federico; Cao, Guangwen; Caporaso, Neil E; Carrato, Alfredo; Carreon, Tania; Carta, Angela; Chang, Gee-Chen; Chang, I-Shou; Chang-Claude, Jenny; Che, Xu; Chen, Chien-Jen; Chen, Chih-Yi; Chen, Chung-Hsing; Chen, Constance; Chen, Kuan-Yu; Chen, Yuh-Min; Chokkalingam, Anand P; Chu, Lisa W; Clavel-Chapelon, Francoise; Colditz, Graham A; Colt, Joanne S; Conti, David; Cook, Michael B; Cortessis, Victoria K; Crawford, E David; Cussenot, Olivier; Davis, Faith G; De Vivo, Immaculata; Deng, Xiang; Ding, Ti; Dinney, Colin P; Di Stefano, Anna Luisa; Diver, W Ryan; Duell, Eric J; Elena, Joanne W; Fan, Jin-Hu; Feigelson, Heather Spencer; Feychting, Maria; Figueroa, Jonine D; Flanagan, Adrienne M; Fraumeni, Joseph F; Freedman, Neal D; Fridley, Brooke L; Fuchs, Charles S; Gago-Dominguez, Manuela; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M; Garcia-Closas, Montserrat; Garcia-Closas, Reina; Gastier-Foster, Julie M; Gaziano, J Michael; Gerhard, Daniela S; Giffen, Carol A; Giles, Graham G; Gillanders, Elizabeth M; Giovannucci, Edward L; Goggins, Michael; Gokgoz, Nalan; Goldstein, Alisa M; Gonzalez, Carlos; Gorlick, Richard; Greene, Mark H; Gross, Myron; Grossman, H Barton; Grubb, Robert; Gu, Jian; Guan, Peng; Haiman, Christopher A; Hallmans, Goran; Hankinson, Susan E; Harris, Curtis C; Hartge, Patricia; Hattinger, Claudia; Hayes, Richard B; He, Qincheng; Helman, Lee; Henderson, Brian E; Henriksson, Roger; Hoffman-Bolton, Judith; Hohensee, Chancellor; Holly, Elizabeth A; Hong, Yun-Chul; Hoover, Robert N; Hosgood, H Dean; Hsiao, Chin-Fu; Hsing, Ann W; Hsiung, Chao Agnes; Hu, Nan; Hu, Wei; Hu, Zhibin; Huang, Ming-Shyan; Hunter, David J; Inskip, Peter D; Ito, Hidemi; Jacobs, Eric J; Jacobs, Kevin B; Jenab, Mazda; Ji, Bu-Tian; Johansen, Christoffer; Johansson, Mattias; Johnson, Alison; Kaaks, Rudolf; Kamat, Ashish M; Kamineni, Aruna; Karagas, Margaret; Khanna, Chand; Khaw, Kay-Tee; Kim, Christopher; Kim, In-Sam; Kim, Jin Hee; Kim, Yeul Hong; Kim, Young-Chul; Kim, Young Tae; Kang, Chang Hyun; Jung, Yoo Jin; Kitahara, Cari M; Klein, Alison P; Klein, Robert; Kogevinas, Manolis; Koh, Woon-Puay; Kohno, Takashi; Kolonel, Laurence N; Kooperberg, Charles; Kratz, Christian P; Krogh, Vittorio; Kunitoh, Hideo; Kurtz, Robert C; Kurucu, Nilgun; Lan, Qing; Lathrop, Mark; Lau, Ching C; Lecanda, Fernando; Lee, Kyoung-Mu; Lee, Maxwell P; Le Marchand, Loic; Lerner, Seth P; Li, Donghui; Liao, Linda M; Lim, Wei-Yen; Lin, Dongxin; Lin, Jie; Lindstrom, Sara; Linet, Martha S; Lissowska, Jolanta; Liu, Jianjun; Ljungberg, Börje; Lloreta, Josep; Lu, Daru; Ma, Jing; Malats, Nuria; Mannisto, Satu; Marina, Neyssa; Mastrangelo, Giuseppe; Matsuo, Keitaro; McGlynn, Katherine A; McKean-Cowdin, Roberta; McNeill, Lorna H; McWilliams, Robert R; Melin, Beatrice S; Meltzer, Paul S; Mensah, James E; Miao, Xiaoping; Michaud, Dominique S; Mondul, Alison M; Moore, Lee E; Muir, Kenneth; Niwa, Shelley; Olson, Sara H; Orr, Nick; Panico, Salvatore; Park, Jae Yong; Patel, Alpa V; Patino-Garcia, Ana; Pavanello, Sofia; Peeters, Petra H M; Peplonska, Beata; Peters, Ulrike; Petersen, Gloria M; Picci, Piero; Pike, Malcolm C; Porru, Stefano; Prescott, Jennifer; Pu, Xia; Purdue, Mark P; Qiao, You-Lin; Rajaraman, Preetha; Riboli, Elio; Risch, Harvey A; Rodabough, Rebecca J; Rothman, Nathaniel; Ruder, Avima M; Ryu, Jeong-Seon; Sanson, Marc; Schned, Alan; Schumacher, Fredrick R; Schwartz, Ann G; Schwartz, Kendra L; Schwenn, Molly; Scotlandi, Katia; Seow, Adeline; Serra, Consol; Serra, Massimo; Sesso, Howard D; Severi, Gianluca; Shen, Hongbing; Shen, Min; Shete, Sanjay; Shiraishi, Kouya; Shu, Xiao-Ou; Siddiq, Afshan; Sierrasesumaga, Luis; Sierri, Sabina; Loon Sihoe, Alan Dart

    2014-12-15

    Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci. PMID:25027329

  17. Prediction based on mean subset

    DEFF Research Database (Denmark)

    Øjelund, Henrik; Brown, P. J.; Madsen, Henrik;

    2002-01-01

    Shrinkage methods have traditionally been applied in prediction problems. In this article we develop a shrinkage method (mean subset) that forms an average of regression coefficients from individual subsets of the explanatory variables. A Bayesian approach is taken to derive an expression of how...... the coefficient vectors from each subset should be weighted. It is not computationally feasible to calculate the mean subset coefficient vector for larger problems, and thus we suggest an algorithm to find an approximation to the mean subset coefficient vector. In a comprehensive Monte Carlo simulation study......, it is found that the proposed mean subset method has superior prediction performance than prediction based on the best subset method, and in some settings also better than the ridge regression and lasso methods. The conclusions drawn from the Monte Carlo study is corroborated in an example in which prediction...

  18. A subset of cancer cell lines is acutely sensitive to the Chk1 inhibitor MK-8776 as monotherapy due to CDK2 activation in S phase.

    Science.gov (United States)

    Sakurikar, Nandini; Thompson, Ruth; Montano, Ryan; Eastman, Alan

    2016-01-12

    DNA damage activates Checkpoint kinase 1 (Chk1) to halt cell cycle progression thereby preventing further DNA replication and mitosis until the damage has been repaired. Consequently, Chk1 inhibitors have emerged as promising anticancer therapeutics in combination with DNA damaging drugs, but their single agent activity also provides a novel approach that may be particularly effective in a subset of patients. From analysis of a large panel of cell lines, we demonstrate that 15% are very sensitive to the Chk1 inhibitor MK-8776. Upon inhibition of Chk1, sensitive cells rapidly accumulate DNA double-strand breaks in S phase in a CDK2- and cyclin A-dependent manner. In contrast, resistant cells can continue to grow for at least 7 days despite continued inhibition of Chk1. Resistance can be circumvented by inhibiting Wee1 kinase and thereby directly activating CDK2. Hence, sensitivity to Chk1 inhibition is regulated upstream of CDK2 and correlates with accumulation of CDC25A. We conclude that cells poorly tolerate CDK2 activity in S phase and that a major function of Chk1 is to ensure it remains inactive. Indeed, inhibitors of CDK1 and CDK2 arrest cells in G1 or G2, respectively, but do not prevent progression through S phase demonstrating that neither kinase is required for S phase progression. Inappropriate activation of CDK2 in S phase underlies the sensitivity of a subset of cell lines to Chk1 inhibitors, and this may provide a novel therapeutic opportunity for appropriately stratified patients. PMID:26595527

  19. Exome Enrichment and SOLiD Sequencing of Formalin Fixed Paraffin Embedded (FFPE) Prostate Cancer Tissue

    OpenAIRE

    Saskia Biskup; Detlef Boehm; Diana Boehm; Falko Fend; Martin Braun; Mario Deng; Roopika Menon; Sven Perner

    2012-01-01

    Next generation sequencing (NGS) technologies have revolutionized cancer research allowing the comprehensive study of cancer using high throughput deep sequencing methodologies. These methods detect genomic alterations, nucleotide substitutions, insertions, deletions and copy number alterations. SOLiD (Sequencing by Oligonucleotide Ligation and Detection, Life Technologies) is a promising technology generating billions of 50 bp sequencing reads. This robust technique, successfully applied in ...

  20. Enrichment of breast cancer stem-like cells by growth on electrospun polycaprolactone-chitosan nanofiber scaffolds

    Directory of Open Access Journals (Sweden)

    Sims-Mourtada J

    2014-02-01

    Full Text Available Jennifer Sims-Mourtada,1 Rohina A Niamat,2 Shani Samuel,2 Chris Eskridge,2 Eric B Kmiec1,2 1Center for Translational Cancer Research, Helen F Graham Cancer Center and Research Institute, Christiana Care Health Services, Inc, Newark, 2Department of Chemistry, Delaware State University, Dover, DE, USA Abstract: A small population of highly tumorigenic breast cancer cells has recently been identified. These cells, known as breast-cancer stem-like cells (BCSC, express markers similar to mammary stem cells, and are highly resistant to chemotherapy. Currently, study of BCSC is hampered by the inability to propagate these cells in tissue culture without inducing differentiation. Recently, it was reported that proliferation and differentiation can be modified by culturing cells on electrospun nanofibers. Here, we sought to characterize the chemoresistance and stem-like properties of breast cancer cell lines grown on nanofiber scaffolds. Cells cultured on three-dimensional templates of electrospun poly(ε-caprolactone-chitosan nanofibers showed increases in mammary stem cell markers and in sphere-forming ability compared with cells cultured on polystyrene culture dishes. There was no increase in proliferation of stem cell populations, indicating that culture on nanofibers may inhibit differentiation of BCSC. The increase in stemness was accompanied by increases in resistance to docetaxel and doxorubicin. These data indicate that BCSC populations are enriched in cells cultured on electrospun poly(ε-caprolactone-chitosan nanofibers, scaffolds that may provide a useful system to study BCSC and their response to anticancer drug treatment. Keywords: breast cancer, mammary stem cells, chemoresistance, nanofibers, three-dimensional culture

  1. Enrichment of osteosarcoma stem cells by chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Qing-Lian Tang; Yi Liang; Xian-Biao Xie; Jun-Qiang Yin; Chang-Ye Zou; Zhi-Qiang Zhao; Jing-Nan Shen; Jin Wang

    2011-01-01

    Osteosamoma is the most common primary malignant bone cancer in children and adolescents. Emerging evidence has suggested that the capability of a tumor to grow is driven by a small subset of cells within a tumor, termed cancer stem cells (CSCs). Although several methods have been explored to identify or enrich CSCs in osteosarcoma, these methods sometimes seem impractical, and chemotherapy enrichment for CSCs in osteosarcoma is rarely investigated. In the present study, we found that short exposure to chemotherapy could change the morphology of osteosarcoma cells and increase sarcosphere formation in vitro, as well as increase tumor formation in vivo. Furthermore, methotrexate (MTX)-resistant U2OS/MTX300 osteosarcoma cells were larger in size and grew much more tightly than parental U2OS cells. More importantly, U2OS/MTX300 cells possessed a higher potential to generate sarcospheres in serum-free conditions compared to parental U2OS cells. Also, U2OS/MTX300 cells exhibited the side population (SP) phenotype and expressed CSC surface markers CD117 and Stro-1. Notably, U2OS/ MTX300 cells showed a substantially higher tumorigenicity in nude mice relative to U2OS cells. Therefore, we conclude that chemotherapy enrichment is a feasible and practical way to enrich osteosamoma stem cells.

  2. Down—regulation of gut—enriched Kruppel—like factor expression in esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    fangDing; Xiu-QinWang; Chuan-NongZhou; MinWu; NanWang; Zhi-HuaLiu

    2002-01-01

    AIM:Esophageal carcinoma is one of the most common malignant tumors in Chian.But the molecular mechanisms of esophageal cracinoma remains unclear.Gut-enriched Kruppel-like factor(GKLF)is a newly identified transcription factor which is expressed abandantly in the epithelial cells of the gastrointestinal tract and deregulation of GKLF was linked to several types of cancet.It is of interest to study the expression and role of GKLF in esophageal crcinoma.

  3. Systematic enrichment analysis of gene expression profiling studies identifies consensus pathways implicated in colorectal cancer development

    OpenAIRE

    Jesús Lascorz; Kari Hemminki; Asta Försti

    2011-01-01

    Background: A large number of gene expression profiling (GEP) studies on colorectal carcinogenesis have been performed but no reliable gene signature has been identified so far due to the lack of reproducibility in the reported genes. There is growing evidence that functionally related genes, rather than individual genes, contribute to the etiology of complex traits. We used, as a novel approach, pathway enrichment tools to define functionally related genes that are consistently up- or down-r...

  4. Increased CD4 and CD8-positive T cell infiltrate signifies good prognosis in a subset of triple-negative breast cancer.

    Science.gov (United States)

    Matsumoto, Hirofumi; Thike, Aye Aye; Li, Huihua; Yeong, Joe; Koo, Si-Lin; Dent, Rebecca Alexandra; Tan, Puay Hoon; Iqbal, Jabed

    2016-04-01

    Tumour-infiltrating lymphocytes (TILs) signify immune response to tumour in a variety of cancers including breast cancer. However, earlier studies examining the clinical significance of TILs in breast cancers have generated mixed results. There are only a few that address the relationship between TILs and clinical outcomes in triple-negative breast cancers (TNBC). The aim of this study is to evaluate the clinical significance of TILs that express CD4 + and CD8 + , in TNBC. Immunohistochemical staining of CD4 and CD8 was performed on tissue microarrays of 164 cases of TNBC. TILs were counted separately as intratumoral when within the cancer cell nests (iTILs) and as stromal when within cancer stroma (sTILs). High CD8 + iTILs and sTILs, and CD4 + iTILs correlated with histologic grade. On Kaplan-Meier analysis, a significantly better survival rate was observed in high CD8 + iTIL (disease-free survival, DFS: P = 0.004, overall survival, OS: P = 0.02) and both high CD4 + iTILs (DFS: P = 0.025, OS: P = 0.023) and sTILs (DFS: P = 0.01, OS: P = 0.002). In multivariate analysis, CD8 + iTILs (DFS: P = 0.0095), CD4 + sTILs (DFS: P = 0.0084; OS: P = 0.0118), and CD4 (high) CD8 (high) CD8 iTILs (DFS: P = 0.0121; OS: P = 0.0329) and sTILs (DFS: P = 0.0295) showed significantly better survival outcomes. These results suggest that high levels of both CD8 + iTILs and CD4 + sTILs as well as CD4 (high) CD8 (high) iTILs and sTILs are independent prognostic factors in TNBC. PMID:26960711

  5. Increased CD4 and CD8-positive T cell infiltrate signifies good prognosis in a subset of triple-negative breast cancer.

    Science.gov (United States)

    Matsumoto, Hirofumi; Thike, Aye Aye; Li, Huihua; Yeong, Joe; Koo, Si-Lin; Dent, Rebecca Alexandra; Tan, Puay Hoon; Iqbal, Jabed

    2016-04-01

    Tumour-infiltrating lymphocytes (TILs) signify immune response to tumour in a variety of cancers including breast cancer. However, earlier studies examining the clinical significance of TILs in breast cancers have generated mixed results. There are only a few that address the relationship between TILs and clinical outcomes in triple-negative breast cancers (TNBC). The aim of this study is to evaluate the clinical significance of TILs that express CD4 + and CD8 + , in TNBC. Immunohistochemical staining of CD4 and CD8 was performed on tissue microarrays of 164 cases of TNBC. TILs were counted separately as intratumoral when within the cancer cell nests (iTILs) and as stromal when within cancer stroma (sTILs). High CD8 + iTILs and sTILs, and CD4 + iTILs correlated with histologic grade. On Kaplan-Meier analysis, a significantly better survival rate was observed in high CD8 + iTIL (disease-free survival, DFS: P = 0.004, overall survival, OS: P = 0.02) and both high CD4 + iTILs (DFS: P = 0.025, OS: P = 0.023) and sTILs (DFS: P = 0.01, OS: P = 0.002). In multivariate analysis, CD8 + iTILs (DFS: P = 0.0095), CD4 + sTILs (DFS: P = 0.0084; OS: P = 0.0118), and CD4 (high) CD8 (high) CD8 iTILs (DFS: P = 0.0121; OS: P = 0.0329) and sTILs (DFS: P = 0.0295) showed significantly better survival outcomes. These results suggest that high levels of both CD8 + iTILs and CD4 + sTILs as well as CD4 (high) CD8 (high) iTILs and sTILs are independent prognostic factors in TNBC.

  6. Enrichment of prostate cancer cells from blood cells with a hybrid dielectrophoresis and immunocapture microfluidic system

    OpenAIRE

    Huang, Chao; Liu, He; Bander, Neil H.; Kirby, Brian J.

    2013-01-01

    The isolation of circulating tumor cells (CTCs) from cancer patient blood is a technical challenge that is often addressed by microfluidic approaches. Two of the most prominent techniques for rare cancer cell separation, immunocapture and dielectrophoresis (DEP), are currently limited by a performance tradeoff between high efficiency and high purity. The development of a platform capable of these two performance criteria can potentially be facilitated by incorporating both DEP and immunocaptu...

  7. Exome Enrichment and SOLiD Sequencing of Formalin Fixed Paraffin Embedded (FFPE Prostate Cancer Tissue

    Directory of Open Access Journals (Sweden)

    Saskia Biskup

    2012-07-01

    Full Text Available Next generation sequencing (NGS technologies have revolutionized cancer research allowing the comprehensive study of cancer using high throughput deep sequencing methodologies. These methods detect genomic alterations, nucleotide substitutions, insertions, deletions and copy number alterations. SOLiD (Sequencing by Oligonucleotide Ligation and Detection, Life Technologies is a promising technology generating billions of 50 bp sequencing reads. This robust technique, successfully applied in gene identification, might be helpful in detecting novel genes associated with cancer initiation and progression using formalin fixed paraffin embedded (FFPE tissue. This study’s aim was to compare the validity of whole exome sequencing of fresh-frozen vs. FFPE tumor tissue by normalization to normal prostatic FFPE tissue, obtained from the same patient. One primary fresh-frozen sample, corresponding FFPE prostate cancer sample and matched adjacent normal prostatic tissue was subjected to exome sequencing. The sequenced reads were mapped and compared. Our study was the first to show comparable exome sequencing results between FFPE and corresponding fresh-frozen cancer tissues using SOLiD sequencing. A prior study has been conducted comparing the validity of sequencing of FFPE vs. fresh frozen samples using other NGS platforms. Our validation further proves that FFPE material is a reliable source of material for whole exome sequencing.

  8. Identification of Distinct Breast Cancer Stem Cell Populations Based on Single-Cell Analyses of Functionally Enriched Stem and Progenitor Pools

    OpenAIRE

    Nina Akrap; Daniel Andersson; Eva Bom; Pernilla Gregersson; Anders Ståhlberg; Göran Landberg

    2016-01-01

    Summary The identification of breast cancer cell subpopulations featuring truly malignant stem cell qualities is a challenge due to the complexity of the disease and lack of general markers. By combining extensive single-cell gene expression profiling with three functional strategies for cancer stem cell enrichment including anchorage-independent culture, hypoxia, and analyses of low-proliferative, label-retaining cells derived from mammospheres, we identified distinct stem cell clusters in b...

  9. Exosomes enriched in stemness/metastatic-related mRNAS promote oncogenic potential in breast cancer.

    Science.gov (United States)

    Rodríguez, Marta; Silva, Javier; Herrera, Alberto; Herrera, Mercedes; Peña, Cristina; Martín, Paloma; Gil-Calderón, Beatriz; Larriba, María Jesús; Coronado, M Josés; Soldevilla, Beatriz; Turrión, Víctor S; Provencio, Mariano; Sánchez, Antonio; Bonilla, Félix; García-Barberán, Vanesa

    2015-12-01

    Cancer cells efficiently transfer exosome contents (essentially mRNAs and microRNAs) to other cell types, modifying immune responses, cell growth, angiogenesis and metastasis. Here we analyzed the exosomes release by breast tumor cells with different capacities of stemness/metastasis based on CXCR4 expression, and evaluated their capacity to generate oncogenic features in recipient cells. Breast cancer cells overexpressing CXCR4 showed an increase in stemness-related markers, and in proliferation, migration and invasion capacities. Furthermore, recipient cells treated with exosomes from CXCR4-cells showed increased in the same abilities. Moreover, inoculation of CXCR4-cell-derived exosomes in immunocompromised mice stimulated primary tumor growth and metastatic potential. Comparison of nucleic acids contained into exosomes isolated from patients revealed a "stemness and metastatic" signature in exosomes of patients with worse prognosis. Finally, our data supported the view that cancer cells with stem-like properties show concomitant metastatic behavior, and their exosomes stimulate tumor progression and metastasis. Exosomes-derived nucleic acids from plasma of breast cancer patients are suitable markers in the prognosis of such patients.

  10. The expression of TRMT2A, a novel cell cycle regulated protein, identifies a subset of breast cancer patients with HER2 over-expression that are at an increased risk of recurrence

    Directory of Open Access Journals (Sweden)

    Tubbs Raymond

    2010-03-01

    Full Text Available Abstract Background Over-expression of HER2 in a subset of breast cancers (HER2+ is associated with high histological grade and aggressive clinical course. Despite these distinctive features, the differences in response of HER2+ patients to both adjuvant cytotoxic chemotherapy and targeted therapy (e.g. trastuzumab suggests that unrecognized biologic and clinical diversity is confounding treatment strategies. Furthermore, the small but established risk of cardiac morbidity with trastuzumab therapy compels efforts towards the identification of biomarkers that might help stratify patients. Methods A single institution tissue array cohort assembled at the Clearview Cancer Institute of Huntsville (CCIH was screened by immunohistochemistry staining using a large number of novel and commercially available antibodies to identify those with a univariate association with clinical outcome in HER2+ patients. Staining with antibody directed at TRMT2A was found to be strongly associated with outcome in HER2+ patients. This association with outcome was tested in two independent validation cohorts; an existing staining dataset derived from tissue assembled at the Cleveland Clinic Foundation (CCF, and in a new retrospective study performed by staining archived paraffin blocks available at the Roswell Park Cancer Institute (RPCI. Results TRMT2A staining showed a strong correlation with likelihood of recurrence at five years in 67 HER2+ patients from the CCIH discovery cohort (HR 7.0; 95% CI 2.4 to 20.1, p HER2+ patients from the CCF cohort (HR 3.6; 95% CI 1.3 to 10.2, p Conclusions Studies from three independent single institution cohorts support TRMT2A protein expression as a biomarker of increased risk of recurrence in HER2+ breast cancer patients. These results suggest that TRMT2A expression should be further studied in the clinical trial setting to explore its predictive power for response to adjuvant cytotoxic chemotherapy in combination with HER2 targeted

  11. Exercise and nutrition routine improving cancer health (ENRICH: The protocol for a randomized efficacy trial of a nutrition and physical activity program for adult cancer survivors and carers

    Directory of Open Access Journals (Sweden)

    Boyes Allison

    2011-04-01

    Full Text Available Abstract Background The Exercise and Nutrition Routine Improving Cancer Health (ENRICH study is investigating a novel lifestyle intervention aimed at improving the health behaviors of adult cancer survivors and their carers. The main purpose of the study is to determine the efficacy of lifestyle education and skill development delivered via group-based sessions on the physical activity and dietary behaviors of participants. This article describes the intervention development, study design, and participant recruitment. Methods/Design ENRICH is a randomized controlled trial, conducted in Australia, with two arms: an intervention group participating in six, two-hour face-to-face sessions held over eight weeks, and a wait-list control group. Intervention sessions are co-facilitated by an exercise physiologist and dietician. Content includes healthy eating education, and a home-based walking (utilizing a pedometer and resistance training program (utilizing elastic tubing resistance devices. The program was developed with reference to social cognitive theory and chronic disease self-management models. The study population consists of cancer survivors (post active-treatment and their carers recruited through community-based advertising and referral from health professionals. The primary outcome is seven-days of sealed pedometry. Secondary outcomes include: self-reported physical activity levels, dietary intake, sedentary behavior, waist circumference, body mass index, quality of life, and perceived social support. The outcomes will be measured at baseline (one week prior to attending the program, eight-weeks (at completion of intervention sessions, and 20-weeks. The intervention group will also be invited to complete 12-month follow-up data collection. Process evaluation data will be obtained from participants by questionnaire and attendance records. Discussion No trials are yet available that have evaluated the efficacy of group-based lifestyle

  12. Effect of paclitaxel liposome combined with nedaplatin on serum HE4, CA125, CA19-9, AFP, CEA and T lymphocyte subsets in patients with advanced ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Su-Yu Zhu; Jie Tan; Chen-Lu Zhang; Qun-Ying Wu; Xue-Xin Xie; Hua-Fang Yin

    2016-01-01

    Objective:To study the effect of paclitaxel liposome combined with nedaplatin on serum HE4, CA125, CA19-9, AFP, CEA and T lymphocyte subsets in patients with advanced ovarian cancer.Methods:A total of 80 patients with advanced ovarian cancer in our hospital from December 2012 to December 2015 were enrolled in this study. The subjects were divided into control group (n=40) and experiment group (n=40) randomly. The control group were treated with paclitaxel and cisplatin, the experiment group were treated with paclitaxel liposome combined with nedaplatin. 21 days for a period of treatment and the two groups were treated for 3 periods. The serum HE4, CA125, CA19-9, AFP, CEA levels and peripheral blood CD3+, CD4+, CD8+ and NK cells of the two groups before and after treatment were compared. Results:There were no significantly differences of the serum HE4, CA125, CA19-9, AFP, CEA level and peripheral blood CD3+, CD4+, CD8+ and NK cells of the two groups before treatment (P>0.05). The serum HE4, CA125, CA19-9, AFP and CEA level of the two groups after treatment were significantly lower than before treatment (P<0.05), and that of experiment were significantly lower than control group (P<0.05). The peripheral blood CD3+, CD4+, CD8+and NK cells of the two groups after treatment were significantly lower than before treatment (P<0.05), and that of experiment were significantly higher than control group (P<0.05). Conclusions:Paclitaxel liposome combined with nedaplatin can significantly reduce the serum HE4, CA125, CA19-9, AFP and CEA levels, improve peripheral blood CD3+, CD4+, CD8+ and NK levels of patients with advanced ovarian cancer, and it was worthy clinical application.

  13. Method for Recovery and Immunoaffinity Enrichment of Membrane Proteins Illustrated with Metastatic Ovarian Cancer Tissues

    Directory of Open Access Journals (Sweden)

    Luke V. Schneider

    2012-01-01

    Full Text Available Integral membrane proteins play key biological roles in cell signaling, transport, and pathogen invasion. However, quantitative clinical assays for this critical class of proteins remain elusive and are generally limited to serum-soluble extracellular fragments. Furthermore, classic proteomic approaches to membrane protein analysis typically involve proteolytic digestion of the soluble pieces, resulting in separation of intra- and extracellular segments and significant informational loss. In this paper, we describe the development of a new method for the quantitative extraction of intact integral membrane proteins (including GPCRs from solid metastatic ovarian tumors using pressure cycling technology in combination with a new (ProteoSolve-TD buffer system. This new extraction buffer is compatible with immunoaffinity methods (e.g., ELISA and immunoaffinity chromatography, as well as conventional proteomic techniques (e.g., 2D gels, western blots. We demonstrate near quantitative recovery of membrane proteins EDG2, EDG4, FASLG, KDR, and LAMP-3 by western blots. We have also adapted commercial ELISAs for serum-soluble membrane protein fragments (e.g., sVEGFR2 to measure the tissue titers of their transmembrane progenitors. Finally, we demonstrate the compatibility of the new buffers with immunoaffinity enrichment/mass spectrometric characterization of tissue proteins.

  14. Bacteria-human somatic cell lateral gene transfer is enriched in cancer samples.

    Directory of Open Access Journals (Sweden)

    David R Riley

    Full Text Available There are 10× more bacterial cells in our bodies from the microbiome than human cells. Viral DNA is known to integrate in the human genome, but the integration of bacterial DNA has not been described. Using publicly available sequence data from the human genome project, the 1000 Genomes Project, and The Cancer Genome Atlas (TCGA, we examined bacterial DNA integration into the human somatic genome. Here we present evidence that bacterial DNA integrates into the human somatic genome through an RNA intermediate, and that such integrations are detected more frequently in (a tumors than normal samples, (b RNA than DNA samples, and (c the mitochondrial genome than the nuclear genome. Hundreds of thousands of paired reads support random integration of Acinetobacter-like DNA in the human mitochondrial genome in acute myeloid leukemia samples. Numerous read pairs across multiple stomach adenocarcinoma samples support specific integration of Pseudomonas-like DNA in the 5'-UTR and 3'-UTR of four proto-oncogenes that are up-regulated in their transcription, consistent with conversion to an oncogene. These data support our hypothesis that bacterial integrations occur in the human somatic genome and may play a role in carcinogenesis. We anticipate that the application of our approach to additional cancer genome projects will lead to the more frequent detection of bacterial DNA integrations in tumors that are in close proximity to the human microbiome.

  15. Anti-CD20 antibody promotes cancer escape via enrichment of tumor-evoked regulatory B cells expressing low levels of CD20 and CD137L.

    Science.gov (United States)

    Bodogai, Monica; Lee Chang, Catalina; Wejksza, Katarzyna; Lai, Jinping; Merino, Maria; Wersto, Robert P; Gress, Ronald E; Chan, Andrew C; Hesdorffer, Charles; Biragyn, Arya

    2013-04-01

    The possible therapeutic benefits of B-cell depletion in combating tumoral immune escape have been debated. In support of this concept, metastasis of highly aggressive 4T1 breast cancer cells in mice can be abrogated by inactivation of tumor-evoked regulatory B cells (tBreg). Here, we report the unexpected finding that B-cell depletion by CD20 antibody will greatly enhance cancer progression and metastasis. Both murine and human tBregs express low levels of CD20 and, as such, anti-CD20 mostly enriches for these cells. In the 4T1 model of murine breast cancer, this effect of enriching for tBregs suggests that B-cell depletion by anti-CD20 may not be beneficial at all in some cancers. In contrast, we show that in vivo-targeted stimulation of B cells with CXCL13-coupled CpG oligonucleotides (CpG-ODN) can block cancer metastasis by inhibiting CD20(Low) tBregs. Mechanistic investigations suggested that CpG-ODN upregulates low surface levels of 4-1BBL on tBregs to elicit granzyme B-expressing cytolytic CD8(+) T cells, offering some explanative power for the effect. These findings underscore the immunotherapeutic importance of tBreg inactivation as a strategy to enhance cancer therapy by targeting both the regulatory and activating arms of the immune system in vivo. PMID:23365136

  16. Identification of Distinct Breast Cancer Stem Cell Populations Based on Single-Cell Analyses of Functionally Enriched Stem and Progenitor Pools

    Directory of Open Access Journals (Sweden)

    Nina Akrap

    2016-01-01

    Full Text Available The identification of breast cancer cell subpopulations featuring truly malignant stem cell qualities is a challenge due to the complexity of the disease and lack of general markers. By combining extensive single-cell gene expression profiling with three functional strategies for cancer stem cell enrichment including anchorage-independent culture, hypoxia, and analyses of low-proliferative, label-retaining cells derived from mammospheres, we identified distinct stem cell clusters in breast cancer. Estrogen receptor (ERα+ tumors featured a clear hierarchical organization with switch-like and gradual transitions between different clusters, illustrating how breast cancer cells transfer between discrete differentiation states in a sequential manner. ERα− breast cancer showed less prominent clustering but shared a quiescent cancer stem cell pool with ERα+ cancer. The cellular organization model was supported by single-cell data from primary tumors. The findings allow us to understand the organization of breast cancers at the single-cell level, thereby permitting better identification and targeting of cancer stem cells.

  17. Anti-protozoal and anti-bacterial antibiotics that inhibit protein synthesis kill cancer subtypes enriched for stem cell-like properties.

    Science.gov (United States)

    Cuyàs, Elisabet; Martin-Castillo, Begoña; Corominas-Faja, Bruna; Massaguer, Anna; Bosch-Barrera, Joaquim; Menendez, Javier A

    2015-01-01

    Key players in translational regulation such as ribosomes might represent powerful, but hitherto largely unexplored, targets to eliminate drug-refractory cancer stem cells (CSCs). A recent study by the Lisanti group has documented how puromycin, an old antibiotic derived from Streptomyces alboniger that inhibits ribosomal protein translation, can efficiently suppress CSC states in tumorspheres and monolayer cultures. We have used a closely related approach based on Biolog Phenotype Microarrays (PM), which contain tens of lyophilized antimicrobial drugs, to assess the chemosensitivity profiles of breast cancer cell lines enriched for stem cell-like properties. Antibiotics directly targeting active sites of the ribosome including emetine, puromycin and cycloheximide, inhibitors of ribosome biogenesis such as dactinomycin, ribotoxic stress agents such as daunorubicin, and indirect inhibitors of protein synthesis such as acriflavine, had the largest cytotoxic impact against claudin-low and basal-like breast cancer cells. Thus, biologically aggressive, treatment-resistant breast cancer subtypes enriched for stem cell-like properties exhibit exacerbated chemosensitivities to anti-protozoal and anti-bacterial antibiotics targeting protein synthesis. These results suggest that old/existing microbicides might be repurposed not only as new cancer therapeutics, but also might provide the tools and molecular understanding needed to develop second-generation inhibitors of ribosomal translation to eradicate CSC traits in tumor tissues.

  18. Anti-protozoal and anti-bacterial antibiotics that inhibit protein synthesis kill cancer subtypes enriched for stem cell-like properties

    Science.gov (United States)

    Cuyàs, Elisabet; Martin-Castillo, Begoña; Corominas-Faja, Bruna; Massaguer, Anna; Bosch-Barrera, Joaquim; Menendez, Javier A

    2015-01-01

    Key players in translational regulation such as ribosomes might represent powerful, but hitherto largely unexplored, targets to eliminate drug-refractory cancer stem cells (CSCs). A recent study by the Lisanti group has documented how puromycin, an old antibiotic derived from Streptomyces alboniger that inhibits ribosomal protein translation, can efficiently suppress CSC states in tumorspheres and monolayer cultures. We have used a closely related approach based on Biolog Phenotype Microarrays (PM), which contain tens of lyophilized antimicrobial drugs, to assess the chemosensitivity profiles of breast cancer cell lines enriched for stem cell-like properties. Antibiotics directly targeting active sites of the ribosome including emetine, puromycin and cycloheximide, inhibitors of ribosome biogenesis such as dactinomycin, ribotoxic stress agents such as daunorubicin, and indirect inhibitors of protein synthesis such as acriflavine, had the largest cytotoxic impact against claudin-low and basal-like breast cancer cells. Thus, biologically aggressive, treatment-resistant breast cancer subtypes enriched for stem cell-like properties exhibit exacerbated chemosensitivities to anti-protozoal and anti-bacterial antibiotics targeting protein synthesis. These results suggest that old/existing microbicides might be repurposed not only as new cancer therapeutics, but also might provide the tools and molecular understanding needed to develop second-generation inhibitors of ribosomal translation to eradicate CSC traits in tumor tissues. PMID:25970790

  19. Stearidonic acid-enriched flax oil reduces the growth of human breast cancer in vitro and in vivo.

    Science.gov (United States)

    Subedi, K; Yu, H-M; Newell, M; Weselake, R J; Meesapyodsuk, D; Qiu, X; Shah, S; Field, C J

    2015-01-01

    The 20 and 22 carbon n-3 long-chain polyunsaturated fatty acids (LCPUFA) inhibit the growth of tumors in vitro and in animal models, but less is known about the 18 carbon n-3, stearidonic acid (SDA). This study aimed to establish and determine a mechanism for the anti-cancer activity of SDA-enriched oil (SO). SO (26 % of lipid) was produced by genetically engineering flax and used to treat human tumorigenic (MDA-MB-231, MCF-7) and non-tumorigenic (MCF-12A) breast cells. Nu/nu mice bearing MDA-MB-231 tumor were fed SO (SDA, 4 % of fat). Cell/tumor growth, phospholipid (PL) composition, apoptosis, CD95, and pro-apoptotic molecules were determined in SO-treated cells/tumors. Compared to a control lipid mixture, SO reduced (p < 0.05) the number of tumorigenic, but not MCF-12A cells, and resulted in higher concentration of most of the n-3 fatty acids in PL of all cells (p < 0.05). However, docosapentaenoic acid increased only in tumorigenic cells (p < 0.05). SO diet decreased tumor growth and resulted in more n-3 LCPUFA, including DPA and less arachidonic acid (AA) levels in major tumor PL (p < 0.05). Treatment of MDA-MB-231 cells/tumors with SO resulted in more apoptotic cells (in tumors) and in vivo and in vitro, more CD95+ positive cells and a higher expression of apoptotic molecules caspase-10, Bad, or Bid (p < 0.05). Supplementing SO alters total PL and PL classes by increasing membrane content of n-3 LCPUFA and lowering AA (in vivo), which is associated with increased CD95-mediated apoptosis, thereby suggesting a possible mechanism for reduce tumor survival. PMID:25417173

  20. Metabolic response to feeding in weight-losing pancreatic cancer patients and its modulation by a fish-oil-enriched nutritional supplement.

    Science.gov (United States)

    Barber, M D; McMillan, D C; Preston, T; Ross, J A; Fearon, K C

    2000-04-01

    Weight-losing patients with advanced cancer often fail to gain weight with conventional nutritional support. This suboptimal response might be explained, in part, by an increased metabolic response to feeding. It has been suggested that eicosapentaenoic acid (EPA) can modify beneficially the metabolic response to cancer. The aim of the present study was to examine the metabolic response to feeding in cancer and the effects of an EPA-enriched oral food supplement on this response. A total of 16 weight-losing, non-diabetic patients with unresectable pancreatic adenocarcinoma and six healthy, weight-stable controls were studied by indirect calorimetry in the fasting and fed states. Body composition was estimated by bioimpedence analysis. Cancer patients were then given a fish-oil-enriched nutritional supplement providing 2 g of EPA and 2550 kJ daily, and underwent repeat metabolic study after 3 weeks of such supplementation. At baseline, resting energy expenditure whether expressed per kg body weight, lean body mass or body cell mass was significantly greater in the cancer patients compared with controls. Fat oxidation was significantly higher in the fasting state in cancer patients [median 1.26 g.kg(-1).min(-1) (interquartile range 0.95-1.38)] than in controls [0.76 g.kg(-1). min(-1) (0.62-0.92); Pfeeding period, changes in insulin and glucose concentrations in cancer patients suggested relative glucose intolerance. In response to oral meal feeding, the percentage change in the area under the curve of energy expenditure was significantly lower in the cancer patients [median 7.9% (interquartile range 3.4-9.0)] than in controls [12.6% (9.9-15.1); Ppatients had increased and the energy expenditure in response to feeding had risen significantly [9.6% (6. 3-12.4)], such that it was no different from baseline healthy control values. Similarly, fasting fat oxidation fell to 1.02 g. kg(-1).min(-1) (0.8-1.18), again no longer significantly different from baseline healthy

  1. Selenium Nanoparticle-Enriched Lactobacillus Brevis Causes More Efficient Immune Responses In Vivo And Reduces The Liver Metastasis In Metastatic Form Of Mouse Breast Cancer

    Directory of Open Access Journals (Sweden)

    Mohammad Esfandyar

    2013-04-01

    Full Text Available Background and the purpose of the study:Selenium enriched Lactobacillus has been reported as an immunostimulatory agent which can be used to increase the life span of cancer bearing animals. Lactic acid bacteria can reduce selenium ions to elemental selenium nanoparticles (SeNPs and deposit them in intracellular spaces. In this strategy two known immunostimulators, lactic acid bacteria (LAB and SeNPs, are concomitantly administered for enhancing of immune responses in cancer bearing mice.Methods:Forty five female inbred BALB/c mice were divided into three groups of tests and control, each containing 15 mice. Test mice were orally administered with SeNP-enriched Lactobacillus brevis or Lactobacillus brevis alone for 3 weeks before tumor induction. After that the administration was followed in three cycles of seven days on/three days off. Control group received phosphate buffer saline (PBS at same condition. During the study the tumor growth was monitored using caliper method. At the end of study the spleen cell culture was carried out for both NK cytotoxicity assay and cytokines measurement. Delayed type hypersensitivity (DTH responses were also assayed after 72h of tumor antigen recall. Serum lactate dehydrogenase (LDH and alkaline phosphatase (ALP levels were measured, the livers of mice were removed and prepared for histopathological analysis.Results:High level of IFN-γ and IL-17 besides the significant raised in NK cytotoxicity and DTH responses were observed in SeNP-enriched L. brevis administered mice and the extended life span and decrease in the tumor metastasis to liver were also recorded in this group compared to the control mice or L.brevis alone administered mice.Conclusion:Our results suggested that the better prognosis could be achieved by oral administration of SeNP-enriched L. brevis in highly metastatic breast cancer mice model.

  2. Enrichment of the Cancer Stem Phenotype in Sphere Cultures of Prostate Cancer Cell Lines Occurs through Activation of Developmental Pathways Mediated by the Transcriptional Regulator ΔNp63α.

    Directory of Open Access Journals (Sweden)

    Roberto Portillo-Lara

    Full Text Available Cancer stem cells (CSC drive prostate cancer tumor survival and metastasis. Nevertheless, the development of specific therapies against CSCs is hindered by the scarcity of these cells in prostate tissues. Suspension culture systems have been reported to enrich CSCs in primary cultures and cell lines. However, the molecular mechanisms underlying this phenomenon have not been fully explored.We describe a prostasphere assay for the enrichment of CD133+ CSCs in four commercial PCa cell lines: 22Rv1, DU145, LNCaP, and PC3. Overexpression of CD133, as determined by flow cytometric analysis, correlated with an increased clonogenic, chemoresistant, and invasive potential in vitro. This phenotype is concordant to that of CSCs in vivo. Gene expression profiling was then carried out using the Cancer Reference panel and the nCounter system from NanoString Technologies. This analysis revealed several upregulated transcripts that can be further explored as potential diagnostic markers or therapeutic targets. Furthermore, functional annotation analysis suggests that ΔNp63α modulates the activation of developmental pathways responsible for the increased stem identity of cells growing in suspension cultures.We conclude that profiling the genetic mechanisms involved in CSC enrichment will help us to better understand the molecular pathways that underlie CSC pathophysiology. This platform can be readily adapted to enrich and assay actual patient samples, in order to design patient-specific therapies that are aimed particularly against CSCs.

  3. Circulating tumour cells: the evolving concept and the inadequacy of their enrichment by EpCAM-based methodology for basic and clinical cancer research.

    Science.gov (United States)

    Grover, P K; Cummins, A G; Price, T J; Roberts-Thomson, I C; Hardingham, J E

    2014-08-01

    Increasing evidence suggests that circulating tumour cells (CTCs) are responsible for metastatic relapse and this has fuelled interest in their detection and quantification. Although numerous methods have been developed for the enrichment and detection of CTCs, none has yet reached the 'gold' standard. Since epithelial cell adhesion molecule (EpCAM)-based enrichment of CTCs offers several advantages, it is one of the most commonly used and has been adapted for high-throughput technology. However, emerging evidence suggests that CTCs are highly heterogeneous: they consist of epithelial tumour cells, epithelial-to-mesenchymal transition (EMT) cells, hybrid (epithelial/EMT(+)) tumour cells, irreversible EMT(+) tumour cells, and circulating tumour stem cells (CTSCs). The EpCAM-based approach does not detect CTCs expressing low levels of EpCAM and non-epithelial phenotypes such as CTSCs and those that have undergone EMT and no longer express EpCAM. Thus, the approach may lead to underestimation of the significance of CTCs, in general, and CTSCs and EMT(+) tumour cells, in particular, in cancer dissemination. Here, we provide a critical review of research literature on the evolving concept of CTCs and the inadequacy of their enrichment by EpCAM-based technology for basic and clinical cancer research. The review also outlines future perspectives in the field.

  4. Mitosis Phase Enrichment with Identification of Mitotic Centromere-Associated Kinesin As a Therapeutic Target in Castration-Resistant Prostate Cancer

    Science.gov (United States)

    Sircar, Kanishka; Huang, Heng; Hu, Limei; Liu, Yuexin; Dhillon, Jasreman; Cogdell, David; Aprikian, Armen; Efstathiou, Eleni; Navone, Nora; Troncoso, Patricia; Zhang, Wei

    2012-01-01

    The recently described transcriptomic switch to a mitosis program in castration-resistant prostate cancer (CRPC) suggests that mitotic proteins may be rationally targeted at this lethal stage of the disease. In this study, we showed upregulation of the mitosis-phase at the protein level in our cohort of 51 clinical CRPC cases and found centrosomal aberrations to also occur preferentially in CRPC compared with untreated, high Gleason–grade hormone-sensitive prostate cancer (P<0.0001). Expression profiling of chemotherapy-resistant CRPC samples (n = 25) was performed, and the results were compared with data from primary chemotherapy-naïve CRPC (n = 10) and hormone-sensitive prostate cancer cases (n = 108). Our results showed enrichment of mitosis-phase genes and pathways, with progression to both castration-resistant and chemotherapy-resistant disease. The mitotic centromere-associated kinesin (MCAK) was identified as a novel mitosis-phase target in prostate cancer that was overexpressed in multiple CRPC gene-expression datasets. We found concordant gene expression of MCAK between our parent and murine CRPC xenograft pairs and increased MCAK protein expression with clinical progression of prostate cancer to a castration-resistant disease stage. Knockdown of MCAK arrested the growth of prostate cancer cells suggesting its utility as a potential therapeutic target. PMID:22363599

  5. Mitosis phase enrichment with identification of mitotic centromere-associated kinesin as a therapeutic target in castration-resistant prostate cancer.

    Directory of Open Access Journals (Sweden)

    Kanishka Sircar

    Full Text Available The recently described transcriptomic switch to a mitosis program in castration-resistant prostate cancer (CRPC suggests that mitotic proteins may be rationally targeted at this lethal stage of the disease. In this study, we showed upregulation of the mitosis-phase at the protein level in our cohort of 51 clinical CRPC cases and found centrosomal aberrations to also occur preferentially in CRPC compared with untreated, high Gleason-grade hormone-sensitive prostate cancer (P<0.0001. Expression profiling of chemotherapy-resistant CRPC samples (n = 25 was performed, and the results were compared with data from primary chemotherapy-naïve CRPC (n = 10 and hormone-sensitive prostate cancer cases (n = 108. Our results showed enrichment of mitosis-phase genes and pathways, with progression to both castration-resistant and chemotherapy-resistant disease. The mitotic centromere-associated kinesin (MCAK was identified as a novel mitosis-phase target in prostate cancer that was overexpressed in multiple CRPC gene-expression datasets. We found concordant gene expression of MCAK between our parent and murine CRPC xenograft pairs and increased MCAK protein expression with clinical progression of prostate cancer to a castration-resistant disease stage. Knockdown of MCAK arrested the growth of prostate cancer cells suggesting its utility as a potential therapeutic target.

  6. Domino: Extracting, Comparing, and Manipulating Subsets across Multiple Tabular Datasets

    Science.gov (United States)

    Gratzl, Samuel; Gehlenborg, Nils; Lex, Alexander; Pfister, Hanspeter; Streit, Marc

    2016-01-01

    Answering questions about complex issues often requires analysts to take into account information contained in multiple interconnected datasets. A common strategy in analyzing and visualizing large and heterogeneous data is dividing it into meaningful subsets. Interesting subsets can then be selected and the associated data and the relationships between the subsets visualized. However, neither the extraction and manipulation nor the comparison of subsets is well supported by state-of-the-art techniques. In this paper we present Domino, a novel multiform visualization technique for effectively representing subsets and the relationships between them. By providing comprehensive tools to arrange, combine, and extract subsets, Domino allows users to create both common visualization techniques and advanced visualizations tailored to specific use cases. In addition to the novel technique, we present an implementation that enables analysts to manage the wide range of options that our approach offers. Innovative interactive features such as placeholders and live previews support rapid creation of complex analysis setups. We introduce the technique and the implementation using a simple example and demonstrate scalability and effectiveness in a use case from the field of cancer genomics. PMID:26356916

  7. THE FEATURE SUBSET SELECTION ALGORITHM

    Institute of Scientific and Technical Information of China (English)

    Liu Yongguo; Li Xueming; Wu Zhongfu

    2003-01-01

    The motivation of data mining is how to extract effective information from huge data in very large database. However, some redundant and irrelevant attributes, which result in low performance and high computing complexity, are included in the very large database in general.So, Feature Subset Selection (FSS) becomes one important issue in the field of data mining. In this letter, an FSS model based on the filter approach is built, which uses the simulated annealing genetic algorithm. Experimental results show that convergence and stability of this algorithm are adequately achieved.

  8. eEF1A1 binds and enriches protoporphyrin IX in cancer cells in 5-aminolevulinic acid based photodynamic therapy

    Science.gov (United States)

    Fan, Zhichao; Cui, Xiaojun; Wei, Dan; Liu, Wei; Li, Buhong; He, Hao; Ye, Huamao; Zhu, Naishuo; Wei, Xunbin

    2016-05-01

    Photodynamic therapy (PDT) with protoporphyrin IX (PpIX), which is endogenously derived from 5-aminolevulinic acid (5-ALA) or its derivatives, is a promising modality for the treatment of both pre-malignant and malignant lesions. However, the mechanisms of how ALA-induced PpIX selectively accumulated in the tumors are not fully elucidated. Here we discovered that eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) interacted with PpIX (with an affinity constant of 2.96 × 106 M‑1). Microscopy imaging showed that ALA-induced PpIX was co-localized with eEF1A1 in cancer cells. eEF1A1 was found to enrich ALA-induced PpIX in cells by competitively blocking the downstream bioavailability of PpIX. Taken together, our study discovered eEF1A1 as a novel photosensitizer binding protein, which may play an essential role in the enrichment of ALA-induced PpIX in cancer cells during PDT. These suggested eEF1A1 as a molecular marker to predict the selectivity and efficiency of 5-ALA based PDT in cancer therapy.

  9. Integrative ChIP-seq/microarray analysis identifies a CTNNB1 target signature enriched in intestinal stem cells and colon cancer.

    Directory of Open Access Journals (Sweden)

    Kazuhide Watanabe

    Full Text Available BACKGROUND: Deregulation of canonical Wnt/CTNNB1 (beta-catenin pathway is one of the earliest events in the pathogenesis of colon cancer. Mutations in APC or CTNNB1 are highly frequent in colon cancer and cause aberrant stabilization of CTNNB1, which activates the transcription of Wnt target genes by binding to chromatin via the TCF/LEF transcription factors. Here we report an integrative analysis of genome-wide chromatin occupancy of CTNNB1 by chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq and gene expression profiling by microarray analysis upon RNAi-mediated knockdown of CTNNB1 in colon cancer cells. RESULTS: We observed 3629 CTNNB1 binding peaks across the genome and a significant correlation between CTNNB1 binding and knockdown-induced gene expression change. Our integrative analysis led to the discovery of a direct Wnt target signature composed of 162 genes. Gene ontology analysis of this signature revealed a significant enrichment of Wnt pathway genes, suggesting multiple feedback regulations of the pathway. We provide evidence that this gene signature partially overlaps with the Lgr5+ intestinal stem cell signature, and is significantly enriched in normal intestinal stem cells as well as in clinical colorectal cancer samples. Interestingly, while the expression of the CTNNB1 target gene set does not correlate with survival, elevated expression of negative feedback regulators within the signature predicts better prognosis. CONCLUSION: Our data provide a genome-wide view of chromatin occupancy and gene regulation of Wnt/CTNNB1 signaling in colon cancer cells.

  10. Enrichment of breast cancer stem-like cells by growth on electrospun polycaprolactone-chitosan nanofiber scaffolds

    OpenAIRE

    Sims-Mourtada J; Niamat RA; Samuel S; Eskridge C; Kmiec EB

    2014-01-01

    Jennifer Sims-Mourtada,1 Rohina A Niamat,2 Shani Samuel,2 Chris Eskridge,2 Eric B Kmiec1,2 1Center for Translational Cancer Research, Helen F Graham Cancer Center and Research Institute, Christiana Care Health Services, Inc, Newark, 2Department of Chemistry, Delaware State University, Dover, DE, USA Abstract: A small population of highly tumorigenic breast cancer cells has recently been identified. These cells, known as breast-cancer stem-like cells (BCSC), express markers similar to mammary...

  11. The Low Chamber Pancreatic Cancer Cells Had Stem-Like Characteristics in Modified Transwell System: Is It a Novel Method to Identify and Enrich Cancer Stem-Like Cells?

    Directory of Open Access Journals (Sweden)

    Dongqing Wang

    2014-01-01

    Full Text Available Cancer stem cells (CSCs or cancer-initiating cells (CICs play an important role in tumor initiation, progression, metastasis, chemoresistance, and recurrence. It is important to construct an effective method to identify and isolate CSCs for biotherapy of cancer. During the past years, many researchers had paid more attention to it; however, this method was still on seeking. Therefore, compared to the former methods that were used to isolate the cancer stem cell, in the present study, we tried to use modified transwell system to isolate and enrich CSCs from human pancreatic cancer cell lines (Panc-1. Our results clearly showed that the lower chamber cells in modified transwell system were easily forming spheres; furthermore, these spheres expressed high levels of stem cell markers (CD133/CD44/CD24/Oct-4/ESA and exhibited chemoresistance, underwent epithelial-to-mesenchymal transition (EMT, and possessed the properties of self-renewal in vitro and tumorigenicity in vivo. Therefore, we speculated that modified transwell assay system, as a rapid and effective method, can be used to isolate and enrich CSCs.

  12. Evaluation of phosphopeptide enrichment strategies for quantitative TMT analysis of complex network dynamics in cancer-associated cell signalling

    Directory of Open Access Journals (Sweden)

    Benedetta Lombardi

    2015-03-01

    Full Text Available Defining alterations in signalling pathways in normal and malignant cells is becoming a major field in proteomics. A number of different approaches have been established to isolate, identify and quantify phosphorylated proteins and peptides. In the current report, a comparison between SCX prefractionation versus an antibody based approach, both coupled to TiO2 enrichment and applied to TMT labelled cellular lysates, is described. The antibody strategy was more complete for enriching phosphopeptides and allowed the identification of a large set of proteins known to be phosphorylated (715 protein groups with a minimum number of not previously known phosphorylated proteins (2.

  13. Mining Representative Subset Based on Fuzzy Clustering

    Institute of Scientific and Technical Information of China (English)

    ZHOU Hongfang; FENG Boqin; L(U) Lintao

    2007-01-01

    Two new concepts-fuzzy mutuality and average fuzzy entropy are presented. Then based on these concepts, a new algorithm-RSMA (representative subset mining algorithm) is proposed, which can abstract representative subset from massive data.To accelerate the speed of producing representative subset, an improved algorithm-ARSMA(accelerated representative subset mining algorithm) is advanced, which adopt combining putting forward with backward strategies. In this way, the performance of the algorithm is improved. Finally we make experiments on real datasets and evaluate the representative subset. The experiment shows that ARSMA algorithm is more excellent than RandomPick algorithm either on effectiveness or efficiency.

  14. Is Job Enrichment Really Enriching?

    OpenAIRE

    Robert D. Mohr; Cindy Zoghi

    2006-01-01

    This study uses a survey of Canadian workers with rich, matched data on job characteristics to examine whether “enriched” job design, with features like quality circles, feedback, suggestion programs, and task teams, affects job satisfaction. We identify two competing hypotheses on the relationship between enriched jobs and job satisfaction. The “motivation hypothesis,” implies that enrichment will generally increase satisfaction and the “intensification hypothesis,” implies that enrichment m...

  15. Inhibitory effects of polyphenol-enriched extract from Ziyang tea against human breast cancer MCF-7 cells through reactive oxygen species-dependent mitochondria molecular mechanism

    Directory of Open Access Journals (Sweden)

    Wenfeng Li

    2016-07-01

    Full Text Available A polyphenol-enriched extract from selenium-enriched Ziyang green tea (ZTP was selected to evaluate its antitumor effects against human breast cancer MCF-7 cells. In ZTP, (−-epigallocatechin gallate (28.2% was identified as the major catechin, followed by (−-epigallocatechin (5.7% and (−-epicatechin gallate (12.6%. ZTP was shown to inhibit MCF-7 cell proliferation (half maximal inhibitory concentration, IC50 = 172.2 μg/mL by blocking cell-cycle progression at the G0/G1 phase and inducing apoptotic death. Western blotting assay indicated that ZTP induced cell-cycle arrest by upregulation of p53 and reduced the expression of CDK2 in MCF-7 cells. ZTP-caused cell apoptosis was associated with an increase in Bax/Bcl-2 ratio, and activation of caspase-3 and -9. MCF-7 cells treated with ZTP also showed an overproduction of reactive oxygen species, suggesting that reactive oxygen species played an important role in the induction of apoptosis in MCF-7 cells. This is the first report showing that ZTP is a potential novel dietary agent for cancer chemoprevention or chemotherapy.

  16. Uranium enrichment

    International Nuclear Information System (INIS)

    GAO was asked to address several questions concerning a number of proposed uranium enrichment bills introduced during the 100th Congress. The bill would have restructured the Department of Energy's uranium enrichment program as a government corporation to allow it to compete more effectively in the domestic and international markets. Some of GAO's findings discussed are: uranium market experts believe and existing market models show that the proposed DOE purchase of a $750 million of uranium from domestic producers may not significantly increase production because of large producer-held inventories; excess uranium enrichment production capacity exists throughout the world; therefore, foreign producers are expected to compete heavily in the United States throughout the 1990s as utilities' contracts with DOE expire; and according to a 1988 agreement between DOE's Offices of Nuclear Energy and Defense Programs, enrichment decommissioning costs, estimated to total $3.6 billion for planning purposes, will be shared by the commercial enrichment program and the government

  17. Uranium enrichment

    International Nuclear Information System (INIS)

    Canada is the world's largest producer and exporter of uranium, most of which is enriched elsewhere for use as fuel in LWRs. The feasibility of a Canadian uranium-enrichment enterprise is therefore a perennial question. Recent developments in uranium-enrichment technology, and their likely impacts on separative work supply and demand, suggest an opportunity window for Canadian entry into this international market. The Canadian opportunity results from three particular impacts of the new technologies: 1) the bulk of the world's uranium-enrichment capacity is in gaseous diffusion plants which, because of their large requirements for electricity (more than 2000 kW·h per SWU), are vulnerable to competition from the new processes; 2) the decline in enrichment costs increases the economic incentive for the use of slightly-enriched uranium (SEU) fuel in CANDU reactors, thus creating a potential Canadian market; and 3) the new processes allow economic operation on a much smaller scale, which drastically reduces the investment required for market entry and is comparable with the potential Canadian SEU requirement. The opportunity is not open-ended. By the end of the century the enrichment supply industry will have adapted to the new processes and long-term customer/supplier relationships will have been established. In order to seize the opportunity, Canada must become a credible supplier during this century

  18. Human NK Cell Subset Functions Are Differentially Affected by Adipokines

    OpenAIRE

    Huebner, Lena; Engeli, Stefan; Christiane D Wrann; Goudeva, Lilia; Laue, Tobias; Kielstein, Heike

    2013-01-01

    Background: Obesity is a risk factor for various types of infectious diseases and cancer. The increase in adipose tissue causes alterations in both adipogenesis and the production of adipocyte-secreted proteins (adipokines). Since natural killer (NK) cells are the host’s primary defense against virus-infected and tumor cells, we investigated how adipocyte-conditioned medium (ACM) affects functions of two distinct human NK cell subsets. Methods: Isolated human peripheral blood mononuclear cell...

  19. Investigation of Human Cancers for Retrovirus by Low-Stringency Target Enrichment and High-Throughput Sequencing

    DEFF Research Database (Denmark)

    Vinner, Lasse; Mourier, Tobias; Friis-Nielsen, Jens;

    2015-01-01

    Although nearly one fifth of all human cancers have an infectious aetiology, the causes for the majority of cancers remain unexplained. Despite the enormous data output from high-throughput shotgun sequencing, viral DNA in a clinical sample typically constitutes a proportion of host DNA that is too......-stringency in-solution hybridization method enables detection of discovery of hitherto unknown viral sequences by high-throughput sequencing. The sensitivity was sufficient to detect retroviral...

  20. Enrichment of Breast Cancer Stem Cells by Serum-free Shaking Suspension Culture%无血清摇动悬浮培养富集乳腺癌干细胞

    Institute of Scientific and Technical Information of China (English)

    闫文星; 陈玉丙; 张红梅; 国春龙; 王铁君

    2011-01-01

    Objective To investigate the characteristics of division of breast cancer MCF-7 cells under various conditions so as to develop a rapid and effective method for enrichment of breast cancer stem cells. Methods MCF-7 cells were subjected to static culture in complete medium (group A), shaking culture in complete medium (group B), static culture with cytokine (group C) and shaking culture with cytokine (group D) respectively, for 12, 24 and 36 h, then observed for division under inverted phase contrast microscope, based on which clone formation rate was calculated, and determined for the percentage of CD44+/CD24"/low lymphocyte subsets. Results In groups B and C, rod-like divisions were observed in both about 30% of cells 12 h, and in about 50% and about 60% of cells respectively 24 h, while large cell clones were formed 36 h after culture. However, in group D, rod-like division was observed in about 50% of cells 12 h, and in about 80% of cells 24 h when several cell clones appeared, while the number of cell clones decreased 36 h after culture. The percentage of CD44+/CD24"/km lymphocyte subsets 12 h after culture in group D (8. 05%) was 8 times of those in group B (0. 99%) and 2. 1 times of those in group C (3. 80%). However, the percentage 24 h after culture in group D (15. 24%) was 3 times of those in group B (4. 83%) and 6 times of those in group C (2. 30%). The percentage in group D decreased to 9. 68% 36 h after culture, which was about 9 times of those in groups B (0. 95%) and C (1. 03%). Conclusion The mitotic division of MCF-7 cells was accelerated in shaking culture with cytokine, while the percentage of CD44+/CD24'/low lymphocyte subsets increased rapidly, and stem cell pool increased significantly, indicating serum-free shaking suspension culture a rapid and effective method for enrichment of breast cancer stem cells.%目的 探讨不同培养条件下乳腺癌MCF-7细胞的分裂特点,建立快速、有效的乳腺癌干细胞富集方法.方法 将MCF-7

  1. Almost Chebyshev set with respect to bounded subsets

    Institute of Scientific and Technical Information of China (English)

    李冲; 王兴华

    1997-01-01

    The uniqueness and existence of restricted Chebyshev center with respect to arbitrary subset are investigated. The concept of almost Chebyshev sets with respect to bounded subsets is introduced. It is proved that each closed subset in a reflexive locally uniformly convex (uniformly convex, respectively) Banach space is an almost Chebyshev subset with respect to compact convex subsets (bounded convex subsets and bounded subsets, respectively).

  2. Long non-coding RNAs harboring miRNA seed regions are enriched in prostate cancer exosomes

    OpenAIRE

    Alireza Ahadi; Samuel Brennan; Kennedy, Paul J.; Gyorgy Hutvagner; Nham Tran

    2016-01-01

    Long non-coding RNAs (lncRNAs) form the largest transcript class in the human transcriptome. These lncRNA are expressed not only in the cells, but they are also present in the cell-derived extracellular vesicles such as exosomes. The function of these lncRNAs in cancer biology is not entirely clear, but they appear to be modulators of gene expression. In this study, we characterize the expression of lncRNAs in several prostate cancer exosomes and their parental cell lines. We show that certai...

  3. Comprehensive Proteomic Study of the Antiproliferative Activity of a Polyphenol-Enriched Rosemary Extract on Colon Cancer Cells Using Nanoliquid Chromatography-Orbitrap MS/MS.

    Science.gov (United States)

    Valdés, Alberto; Artemenko, Konstantin A; Bergquist, Jonas; García-Cañas, Virginia; Cifuentes, Alejandro

    2016-06-01

    In this work, a proteomics strategy based on nanoliquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) using an Orbitrap high-resolution mass spectrometer together with stable isotope dimethyl labeling (DML) is applied to quantitatively examine relative changes in the protein fraction of HT-29 human colon cancer cells treated with different concentrations of a polyphenol-enriched rosemary extract over the time. The major objective of this study was to gain insights into the antiproliferative mechanisms induced by rosemary polyphenols. Using this methodology, 1909 and 698 proteins were identified and quantified in cell extracts. The polyphenol-enriched rosemary extract treatment changed the expression of several proteins in a time- and concentration-dependent manner. Most of the altered proteins are implicated in the activation of Nrf2 transcription factor and the unfolded protein response. In conclusion, rosemary polyphenols induced proteomic changes that were related to the attenuation of aggresome formation and activation of autophagy to alleviate cellular stress. PMID:27103343

  4. Development of a Synchronous Subset of AADL

    DEFF Research Database (Denmark)

    Filali, Mamoun; Lawall, Julia

    2010-01-01

    We study the definition and the mapping of an AADL subset: the so called synchronous subset. We show that the data port protocol used for delayed and immediate connections between periodic threads can be interpreted in a  synchronous way. In this paper, we formalize this interpretation and study...

  5. Digital Image Correlation with Dynamic Subset Selection

    Science.gov (United States)

    Hassan, Ghulam Mubashar; MacNish, Cara; Dyskin, Arcady; Shufrin, Igor

    2016-09-01

    The quality of the surface pattern and selection of subset size play a critical role in achieving high accuracy in Digital Image Correlation (DIC). The subset size in DIC is normally selected by testing different subset sizes across the entire image, which is a laborious procedure. This also leads to the problem that the worst region of the surface pattern influences the performance of DIC across the entire image. In order to avoid these limitations, a Dynamic Subset Selection (DSS) algorithm is proposed in this paper to optimize the subset size for each point in an image before optimizing the correlation parameters. The proposed DSS algorithm uses the local pattern around the point of interest to calculate a parameter called the Intensity Variation Ratio (Λ), which is used to optimize the subset size. The performance of the DSS algorithm is analyzed using numerically generated images and is compared with the results of traditional DIC. Images obtained from laboratory experiments are also used to demonstrate the utility of the DSS algorithm. Results illustrate that the DSS algorithm provides a better alternative to subset size "guessing" and finds an appropriate subset size for each point of interest according to the local pattern.

  6. Molecular Pathways: Targeting DNA Repair Pathway Defects Enriched in Metastasis.

    Science.gov (United States)

    Corcoran, Niall M; Clarkson, Michael J; Stuchbery, Ryan; Hovens, Christopher M

    2016-07-01

    The maintenance of a pristine genome, free from errors, is necessary to prevent cellular transformation and degeneration. When errors in DNA are detected, DNA damage repair (DDR) genes and their regulators are activated to effect repair. When these DDR pathways are themselves mutated or aberrantly downregulated, cancer and neurodegenerative disorders can ensue. Multiple lines of evidence now indicate, however, that defects in key regulators of DNA repair pathways are highly enriched in human metastasis specimens and hence may be a key step in the acquisition of metastasis and the ability of localized disease to disseminate. Some of the key regulators of checkpoints in the DNA damage response are the TP53 protein and the PARP enzyme family. Targeting of these pathways, especially through PARP inhibition, is now being exploited therapeutically to effect significant clinical responses in subsets of individuals, particularly in patients with ovarian cancer or prostate cancer, including cancers with a marked metastatic burden. Targeting DNA repair-deficient tumors with drugs that take advantage of the fundamental differences between normal repair-proficient cells and repair-deficient tumors offers new avenues for treating advanced disease in the future. Clin Cancer Res; 22(13); 3132-7. ©2016 AACR. PMID:27169997

  7. In vitro antiproliferative/cytotoxic activity on cancer cell lines of a cardanol and a cardol enriched from Thai Apis mellifera propolis

    Directory of Open Access Journals (Sweden)

    Teerasripreecha Dungporn

    2012-03-01

    Full Text Available Abstract Background Propolis is a complex resinous honeybee product. It is reported to display diverse bioactivities, such as antimicrobial, anti-inflammatory and anti-tumor properties, which are mainly due to phenolic compounds, and especially flavonoids. The diversity of bioactive compounds depends on the geography and climate, since these factors affect the floral diversity. Here, Apis mellifera propolis from Nan province, Thailand, was evaluated for potential anti-cancer activity. Methods Propolis was sequentially extracted with methanol, dichloromethane and hexane and the cytotoxic activity of each crude extract was assayed for antiproliferative/cytotoxic activity in vitro against five human cell lines derived from duet carcinoma (BT474, undifferentiated lung (Chaco, liver hepatoblastoma (Hep-G2, gastric carcinoma (KATO-III and colon adenocarcinoma (SW620 cancers. The human foreskin fibroblast cell line (Hs27 was used as a non-transformed control. Those crude extracts that displayed antiproliferative/cytotoxic activity were then further fractionated by column chromatography using TLC-pattern and MTT-cytotoxicity bioassay guided selection of the fractions. The chemical structure of each enriched bioactive compound was analyzed by nuclear magnetic resonance and mass spectroscopy. Results The crude hexane and dichloromethane extracts of propolis displayed antiproliferative/cytotoxic activities with IC50 values across the five cancer cell lines ranging from 41.3 to 52.4 μg/ml and from 43.8 to 53.5 μg/ml, respectively. Two main bioactive components were isolated, one cardanol and one cardol, with broadly similar in vitro antiproliferation/cytotoxicity IC50 values across the five cancer cell lines and the control Hs27 cell line, ranging from 10.8 to 29.3 μg/ml for the cardanol and . Conclusion This is the first report that Thai A. mellifera propolis contains at least two potentially new compounds (a cardanol and a cardol with potential anti-cancer

  8. 乳腺癌转移相关通路的基因集富集分析%Gene set enrichment analysis of breast cancer metastasis related pathways

    Institute of Scientific and Technical Information of China (English)

    余海浪; 刘安玲; 周珏宇; 孟伟; 郑文岭; 马文丽

    2013-01-01

    Objective To investigate pathways involved in metastasis of breast cancer by use of gene expression data sets. Methods Three gene expression profiling datasets related to the breast cancer metastasis ( accession number GSE2034, GSE2603 and GSE12276 respectively) were downloaded from gene expression omnibus ( GEO) , which were used in this study. Breast cancer samples were separated into two groups; primary tumors and metastatic tumors. Expression value of samples was obtained after raw profile data were normalized and quality control by RMAExpress software. Breast cancer metastasis related pathways were analyzed by the GSEA pathway enrichment tool. Results A total of 20 biological pathways associated with breast cancer metastasis were identified, of which 17 upregulated and 3 downregulated, mainly including cell cycle and proliferation, cell adhesion, cell migration, angiogenesis, immune system and so on. Conclusions In addition the improvement of tumor cell viability and proliferation, breast cancer metastasis is also associated with the increasement of tumor cell migration and movement and the damage of immune system.%目的 探讨与乳腺癌转移相关的生物信号通路及因素.方法 以乳腺癌转移相关的3组基因芯片表达谱数据为研究材料,登录号分别为GSE2034、GSE2603以及GSE12276.将乳腺癌样本分为原发癌和转移癌两组,原始数据经RMAExpress软件进行质量检验和标准化,采用GSEA通路富集工具对乳腺癌转移相关通路进行分析.结果 有20条生物信号通路与乳腺癌的转移有着密切关系,其中基因集上调的有17个,下调的有3个,主要涉及细胞周期与增殖、代谢途径、血管生成、迁移、免疫系统等信号通路.结论 乳腺癌转移除与肿瘤细胞的活力和增殖能力提高有关外,还与肿瘤细胞的迁移和运动能力进一步增强及机体免疫系统损害有关.

  9. Enrichment of lung cancer stem cells and expression of related markers%肺癌干细胞富集及相关标志物的表达

    Institute of Scientific and Technical Information of China (English)

    陈平; 王键

    2015-01-01

    背景:肺癌干细胞与肺癌的治疗和预后等紧密相关,通过对其表面标志物和致瘤性的研究,可以为临床诊治提供更多的参考依据。目的:探讨肺癌球体干细胞的富集方法及其致瘤性。方法:使用含有表皮细胞生长因子、胰岛素样生长因子1以及碱性成纤维细胞生长因子的无血清培养基对肺癌细胞进行诱导,采用免疫荧光检测诱导后细胞相关标志物的表达。小鼠皮下移植诱导后肺球体细胞,以了解其致瘤性。结果与结论:经无血清悬浮培养和诱导,肺癌细胞形成细胞球体,免疫荧光检测显示80%以上的球体细胞呈SP-C、CCSP以及OCT4染色阳性。小鼠皮下移植球体细胞后可形成肿瘤。结果表明,无血清悬浮培养肺癌细胞可增殖形成细胞球体,该细胞球体中肺癌干细胞高度富集并具有致瘤性。%BACKGROUND:Lung cancer stem cel s are tightly related to the treatment and prognosis of lung cancer. We can provide more references for clinical diagnosis and treatment of lung cancer through the study on the tumorigenicity and surface markers of lung cancer stem cel s. OBJECTIVE:To explore the enrichment methods for lung cancer stem cel s and cel ular tumorigenicity. METHODS:Lung cancer stem cel s were induced in serum-free culture medium containing epidermal growth factor, insulin-like growth factor 1, and basic fibroblast growth factor. Then, the expressions of related surface markers were detected using immunofluorescence method. After that, mice were implanted subcutaneous with lung cancer stem cel spheres to understand the tumorigenicity of lung cancer stem cel s. RESULTS AND CONCLUSION:Lung cancer stem cel s under serum-free induction and culture were changed to sphere-forming cel s, and the immunofluorescence detection showed that over 80%of sphere-forming cel s were positive for CCSP, SP-C and OCT4. After transplantation of sphere-forming cel s, the mice showed a

  10. A Subpopulation of Circulating Endothelial Cells Express CD109 and is Enriched in the Blood of Cancer Patients

    OpenAIRE

    Patrizia Mancuso; Angelica Calleri; Giuliana Gregato; Valentina Labanca; Jessica Quarna; Pierluigi Antoniotti; Lucia Cuppini; Gaetano Finocchiaro; Marica Eoli; Vittorio Rosti; Francesco Bertolini

    2014-01-01

    Background The endothelium is not a homogeneous organ. Endothelial cell heterogeneity has been described at the level of cell morphology, function, gene expression, and antigen composition. As a consequence of the genetic, transcriptome and surrounding environment diversity, endothelial cells from different vascular beds have differentiated functions and phenotype. Detection of circulating endothelial cells (CECs) by flow cytometry is an approach widely used in cancer patients, and their numb...

  11. Doxorubicin-enriched, ALDHbr mouse breast cancer stem cells are treatable to oncolytic herpes simplex virus type 1

    Directory of Open Access Journals (Sweden)

    Zhuang Xiufen

    2012-11-01

    Full Text Available Abstract Background The primary objective of this study was to test whether oncolytic herpes simplex virus type 1 (HSV1 could eradicate chemoresistant cancer stem cells (CSCs. Methods The fluorescent aldefluor reagent-based technique was used to identify and isolate ALDHbr cells as CSCs from the 4T1 murine breast cancer cell line. The presence of ALDHbr 4T1 cells was also examined in 4T1 breast cancer transplanted in immune-competent syngeneic mice. Results Compared with ALDHlo cells, ALDHbr cells had a markedly higher ability to form tumor spheres in vitro and a higher tumorigenic potential in vivo. ALDHbr cells also exhibited increased doxorubicin resistance in vitro, which correlated with a selective increase in the percentage of ALDHbr cells after doxorubicin treatment and an increased expression of P-glycoprotein (P-gp, a known chemoresistance factor. In contrast, oncolytic HSV1 was able to kill ALDHbr cells in vitro and even more markedly in vivo. Furthermore, in in vivo studies, systemic administration of doxorubicin followed by intratumoral injection of oncolytic HSV1 resulted in much more significant suppression of tumor growth with increased median survival period compared with each treatment given alone (p+ T lymphocytes were induced by oncolytic HSV1, no significant specific T cell response against CSCs was detected in vivo. Conclusions These results suggested that the use of oncolytic HSV1 following doxorubicin treatment may help eradicate residual chemoresistant CSCs in vivo.

  12. Job Enrichment

    Science.gov (United States)

    Sanders, Rick

    1970-01-01

    Job enrichment means giving people more decision-making power, more responsibility, more grasp of the totality of the job, and a sense of their own importance in the company. This article presents evidence of the successful working of this approach (Donnelly Mirrors), and the lack of success with an opposing approach (General Motors). (NL)

  13. Screening Key Genes Associated with the Development and Progression of Non-small Cell Lung Cancer Based on Gene-enrichment Analysis and Meta-analysis

    Directory of Open Access Journals (Sweden)

    Wenwu HE

    2012-07-01

    Full Text Available Background and objective Non-small cell lung cancer (NSCLC is one of the most common malignant tumors; however, its causes are still not completely understood. This study was designed to screen the key genes and pathways related to NSCLC occurrence and development and to establish the scientific foundation for the genetic mechanisms and targeted therapy of NSCLC. Methods Both gene set-enrichment analysis (GSEA and meta-analysis (meta were used to screen the critical pathways and genes that might be corretacted with the development and progression of lung cancer at the transcription level. Results Using the GSEA and meta methods, focal adhesion and regulation of actin cytoskeleton were determined to be the more prominent overlapping significant pathways. In the focal adhesion pathway, 31 genes were statistically significant (P<0.05, whereas in the regulation of actin cytoskeleton pathway, 32 genes were statistically significant (P<0.05. Conclusion The focal adhesion and the regulation of actin cytoskeleton pathways might play important roles in the occurrence and development of NSCLC. Further studies are needed to determine the biological function for the positiue genes.

  14. A subpopulation of circulating endothelial cells express CD109 and is enriched in the blood of cancer patients.

    Directory of Open Access Journals (Sweden)

    Patrizia Mancuso

    Full Text Available The endothelium is not a homogeneous organ. Endothelial cell heterogeneity has been described at the level of cell morphology, function, gene expression, and antigen composition. As a consequence of the genetic, transcriptome and surrounding environment diversity, endothelial cells from different vascular beds have differentiated functions and phenotype. Detection of circulating endothelial cells (CECs by flow cytometry is an approach widely used in cancer patients, and their number, viability and kinetic is a promising tool to stratify patient receiving anti-angiogenic treatment.Currently CECs are identified as positive for a nuclear binding antigen (DNA+, negative for the pan leukocyte marker CD45, and positive for CD31 and CD146. Following an approach recently validated in our laboratory, we investigated the expression of CD109 on CECs from the peripheral blood of healthy subject and cancer patients. The endothelial nature of these cells was validated by RT-PCR for the presence of m-RNA level of CDH5 (Ve-Cadherin and CLDN5 (Claudin5, two endothelial specific transcripts. Before treatment, significantly higher levels of CD109+ CECs and viable CD109+CECs were found in breast cancer patients and glioblastoma patients compared to healthy controls, and their number significantly decreased after treatment. Higher levels of endothelial specific transcripts expressed in developing endothelial cells CLEC14a, TMEM204, ARHGEF15, GPR116, were observed in sorted CD109+CECs when compared to sorted CD146+CECs, suggesting that these genes can play an important role not only during embryogenesis but also in adult angiogenesis. Interestingly, mRNA levels of TEM8 (identified as Antrax Toxin Receptor1, Antrax1 were expressed in CD109+CECs+ but not in CD146+CECs.Taken together our results suggest that CD109 represent a rare population of circulating tumor endothelial cells, that play a potentially useful prognostic role in patients with glioblastoma. The role of

  15. Subset Selection by Local Convex Approximation

    DEFF Research Database (Denmark)

    Øjelund, Henrik; Sadegh, Payman; Madsen, Henrik;

    1999-01-01

    This paper concerns selection of the optimal subset of variables in a lenear regression setting. The posed problem is combinatiorial and the globally best subset can only be found in exponential time. We define a cost function for the subset selection problem by adding the penalty term to the usual...... least squares criterion. We propose an optimization technique for the posed probelm based on a modified version of the Newton-Raphson iterations, combined with a backward elimination type algorithm. THe Newton-Raphson modification concerns iterative approximations to the non-convex cost function...... of the subset selection problem so as to guarantee positive definiteness of the Hessian term, hence avoiding numerical instability. The backward Elemination type algorithm attempts to improve the results upon termination of the modified Newton-Raphson search by sing the current solution as an initial guess...

  16. Subsets of configurations and canonical partition functions

    DEFF Research Database (Denmark)

    Bloch, J.; Bruckmann, F.; Kieburg, M.;

    2013-01-01

    We explain the physical nature of the subset solution to the sign problem in chiral random matrix theory: the subset sum over configurations is shown to project out the canonical determinant with zero quark charge from a given configuration. As the grand canonical chiral random matrix partition f...... function is independent of the chemical potential, the zero-quark-charge sector provides the full result. © 2013 American Physical Society....

  17. Efficient enrichment of hepatic cancer stem-like cells from a primary rat HCC model via a density gradient centrifugation-centered method.

    Directory of Open Access Journals (Sweden)

    Wei-hui Liu

    Full Text Available BACKGROUND: Because few definitive markers are available for hepatic cancer stem cells (HCSCs, based on physical rather than immunochemical properties, we applied a novel method to enrich HCSCs. METHODOLOGY: After hepatic tumor cells (HTCs were first isolated from diethylinitrosamine-induced F344 rat HCC model using percoll discontinuous gradient centrifugation (PDGC and purified via differential trypsinization and differential attachment (DTDA, they were separated into four fractions using percoll continuous gradient centrifugation (PCGC and sequentially designated as fractions I-IV (FI-IV. Morphological characteristics, mRNA and protein levels of stem cell markers, proliferative abilities, induced differentiation, in vitro migratory capacities, in vitro chemo-resistant capacities, and in vivo malignant capacities were determined for the cells of each fraction. FINDINGS: As the density of cells increased, 22.18%, 11.62%, 4.73% and 61.47% of primary cultured HTCs were segregated in FI-FIV, respectively. The cells from FIII (density between 1.041 and 1.062 g/ml displayed a higher nuclear-cytoplasmic ratio and fewer organelles and expressed higher levels of stem cell markers (AFP, EpCAM and CD133 than cells from other fractions (P<0.01. Additionally, in vitro, the cells from FIII showed a greater capacity to self-renew, differentiate into mature HTCs, transit across membranes, close scratches, and carry resistance to chemotherapy than did cells from any other fraction; in vivo, injection of only 1×10(4 cells from FIII could generate tumors not only in subcutaneous tissue but also in the livers of nude mice. CONCLUSIONS: Through our novel method, HCSC-like cells were successfully enriched in FIII. This study will greatly contribute to two important areas of biological interest: CSC isolation and HCC therapy.

  18. Uranium enrichment

    International Nuclear Information System (INIS)

    This paper reports that in 1990 the Department of Energy began a two-year project to illustrate the technical and economic feasibility of a new uranium enrichment technology-the atomic vapor laser isotope separation (AVLIS) process. GAO believes that completing the AVLIS demonstration project will provide valuable information about the technical viability and cost of building an AVLIS plant and will keep future plant construction options open. However, Congress should be aware that DOE still needs to adequately demonstrate AVLIS with full-scale equipment and develop convincing cost projects. Program activities, such as the plant-licensing process, that must be completed before a plant is built, could take many years. Further, an updated and expanded uranium enrichment analysis will be needed before any decision is made about building an AVLIS plant. GAO, which has long supported legislation that would restructure DOE's uranium enrichment program as a government corporation, encourages DOE's goal of transferring AVLIS to the corporation. This could reduce the government's financial risk and help ensure that the decision to build an AVLIS plant is based on commercial concerns. DOE, however, has no alternative plans should the government corporation not be formed. Further, by curtailing a planned public access program, which would have given private firms an opportunity to learn about the technology during the demonstration project, DOE may limit its ability to transfer AVLIS to the private sector

  19. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

    DEFF Research Database (Denmark)

    Wang, Zhaoming; Zhu, Bin; Zhang, Mingfeng;

    2014-01-01

    Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may pl...

  20. IRAK1 is a therapeutic target that drives breast cancer metastasis and resistance to paclitaxel

    DEFF Research Database (Denmark)

    Wee, Zhen Ning; Yatim, Siti Maryam J M; Kohlbauer, Vera K;

    2015-01-01

    Metastatic tumour recurrence due to failed treatments remains a major challenge of breast cancer clinical management. Here we report that interleukin-1 receptor-associated kinase 1 (IRAK1) is overexpressed in a subset of breast cancers, in particular triple-negative breast cancer (TNBC), where it...... and pharmacologic inhibition of IRAK1. Importantly, paclitaxel treatment induces strong IRAK1 phosphorylation, an increase in inflammatory cytokine expression, enrichment of cancer stem cells and acquired resistance to paclitaxel treatment. Pharmacologic inhibition of IRAK1 is able to reverse...

  1. Magnetic Enrichment of Dendritic Cell Vaccine in Lymph Node with Fluorescent-Magnetic Nanoparticles Enhanced Cancer Immunotherapy

    Science.gov (United States)

    Jin, Honglin; Qian, Yuan; Dai, Yanfeng; Qiao, Sha; Huang, Chuan; Lu, Lisen; Luo, Qingming; Chen, Jing; Zhang, Zhihong

    2016-01-01

    Dendritic cell (DC) migration to the lymph node is a key component of DC-based immunotherapy. However, the DC homing rate to the lymphoid tissues is poor, thus hindering the DC-mediated activation of antigen-specific T cells. Here, we developed a system using fluorescent magnetic nanoparticles (α-AP-fmNPs; loaded with antigen peptide, iron oxide nanoparticles, and indocyanine green) in combination with magnetic pull force (MPF) to successfully manipulate DC migration in vitro and in vivo. α-AP-fmNPs endowed DCs with MPF-responsiveness, antigen presentation, and simultaneous optical and magnetic resonance imaging detectability. We showed for the first time that α-AP-fmNP-loaded DCs were sensitive to MPF, and their migration efficiency could be dramatically improved both in vitro and in vivo through MPF treatment. Due to the enhanced migration of DCs, MPF treatment significantly augmented antitumor efficacy of the nanoparticle-loaded DCs. Therefore, we have developed a biocompatible approach with which to improve the homing efficiency of DCs and subsequent anti-tumor efficacy, and track their migration by multi-modality imaging, with great potential applications for DC-based cancer immunotherapy.

  2. Alterations in p53-specific T cells and other lymphocyte subsets in breast cancer patients during vaccination with p53-peptide loaded dendritic cells and low-dose interleukin-2

    DEFF Research Database (Denmark)

    Svane, Inge Marie; Pedersen, Anders E; Nikolajsen, Kirsten;

    2008-01-01

    We have previously established a cancer vaccine using autologous DCs, generated by in vitro stimulation with IL-4 and GM-CSF, and pulsed with six HLA-A*0201 binding wild-type p53 derived peptides. This vaccine was used in combination with low-dose interleukin-2 in a recently published clinical...... Phase II trial where 26 HLA-A2+ patients with progressive late-stage metastatic breast cancer (BC) were included. Almost 1/3rd of the patients obtained stable disease or minor regression during treatment with a positive correlation to tumour over-expression of p53. In the present study, we performed...... a comprehensive analysis of the effector stage of the p53-specific CD8+ T cells by the use of Dextramer Technology and multicolour FACS. Pre- and post-treatment blood samples from eight BC patients were analysed. Independent of clinical outcome p53-specific T cells were phenotypic distinctly antigen experienced...

  3. Therapeutic implications of an enriched cancer stem-like cell population in a human osteosarcoma cell line

    International Nuclear Information System (INIS)

    Osteosarcoma is a bone-forming tumor of mesenchymal origin that presents a clinical pattern that is consistent with the cancer stem cell model. Cells with stem-like properties (CSCs) have been identified in several tumors and hypothesized as the responsible for the relative resistance to therapy and tumor relapses. In this study, we aimed to identify and characterize CSCs populations in a human osteosarcoma cell line and to explore their role in the responsiveness to conventional therapies. CSCs were isolated from the human MNNG/HOS cell line using the sphere formation assay and characterized in terms of self-renewal, mesenchymal stem cell properties, expression of pluripotency markers and ABC transporters, metabolic activity and tumorigenicity. Cell's sensitivity to conventional chemotherapeutic agents and to irradiation was analyzed and related with cell cycle-induced alterations and apoptosis. The isolated CSCs were found to possess self-renewal and multipotential differentiation capabilities, express markers of pluripotent embryonic stem cells Oct4 and Nanog and the ABC transporters P-glycoprotein and BCRP, exhibit low metabolic activity and induce tumors in athymic mice. Compared with parental MNNG/HOS cells, CSCs were relatively more resistant to both chemotherapy and irradiation. None of the treatments have induced significant cell-cycle alterations and apoptosis in CSCs. MNNG/HOS osteosarcoma cells contain a stem-like cell population relatively resistant to conventional chemotherapeutic agents and irradiation. This resistant phenotype appears to be related with some stem features, namely the high expression of the drug efflux transporters P-glycoprotein and BCRP and their quiescent nature, which may provide a biological basis for resistance to therapy and recurrence commonly observed in osteosarcoma

  4. Therapeutic implications of an enriched cancer stem-like cell population in a human osteosarcoma cell line

    Directory of Open Access Journals (Sweden)

    Martins-Neves Sara R

    2012-04-01

    Full Text Available Abstract Background Osteosarcoma is a bone-forming tumor of mesenchymal origin that presents a clinical pattern that is consistent with the cancer stem cell model. Cells with stem-like properties (CSCs have been identified in several tumors and hypothesized as the responsible for the relative resistance to therapy and tumor relapses. In this study, we aimed to identify and characterize CSCs populations in a human osteosarcoma cell line and to explore their role in the responsiveness to conventional therapies. Methods CSCs were isolated from the human MNNG/HOS cell line using the sphere formation assay and characterized in terms of self-renewal, mesenchymal stem cell properties, expression of pluripotency markers and ABC transporters, metabolic activity and tumorigenicity. Cell's sensitivity to conventional chemotherapeutic agents and to irradiation was analyzed and related with cell cycle-induced alterations and apoptosis. Results The isolated CSCs were found to possess self-renewal and multipotential differentiation capabilities, express markers of pluripotent embryonic stem cells Oct4 and Nanog and the ABC transporters P-glycoprotein and BCRP, exhibit low metabolic activity and induce tumors in athymic mice. Compared with parental MNNG/HOS cells, CSCs were relatively more resistant to both chemotherapy and irradiation. None of the treatments have induced significant cell-cycle alterations and apoptosis in CSCs. Conclusions MNNG/HOS osteosarcoma cells contain a stem-like cell population relatively resistant to conventional chemotherapeutic agents and irradiation. This resistant phenotype appears to be related with some stem features, namely the high expression of the drug efflux transporters P-glycoprotein and BCRP and their quiescent nature, which may provide a biological basis for resistance to therapy and recurrence commonly observed in osteosarcoma.

  5. Variable and subset selection in PLS regression

    DEFF Research Database (Denmark)

    Høskuldsson, Agnar

    2001-01-01

    The purpose of this paper is to present some useful methods for introductory analysis of variables and subsets in relation to PLS regression. We present here methods that are efficient in finding the appropriate variables or subset to use in the PLS regression. The general conclusion...... is that variable selection is important for successful analysis of chemometric data. An important aspect of the results presented is that lack of variable selection can spoil the PLS regression, and that cross-validation measures using a test set can show larger variation, when we use different subsets of X, than...... obtained by different methods. We also present an approach to orthogonal scatter correction. The procedures and comparisons are applied to industrial data. (C) 2001 Elsevier Science B.V. All rights reserved....

  6. Subset specification of central serotonergic neurons

    Directory of Open Access Journals (Sweden)

    Marten P Smidt

    2013-10-01

    Full Text Available The last decade the serotonin (5-hydroxytryptamine; 5-HT system has received enormous attention due to its role in regulation of behavior, exemplified by the discovery that increased 5-HT tone in the central nervous system is able to alleviate affective disorders. Here, we review the developmental processes, with a special emphasis on subset specification, leading to the formation of the 5-HT system in the brain. Molecular classification of 5-HT neuronal groups leads to the definition of two independent rostral groups positioned in rhombomere 1 and 2/3 and a caudal group in rhombomere 5-8. In addition, more disperse refinement of these subsets is present as shown by the selective expression of the 5-HT1A autoreceptor, indicating functional diversity between 5-HT subsets. The functional significance of the molecular coding differences is not well known and the molecular basis of described specific connectivity patterns remain to be elucidated. Recent developments in genetic lineage tracing models will provide these data and form a major step-up towards the full understanding of the importance of developmental programming and function of 5-HT neuronal subsets.

  7. Ordered subsets algorithms for transmission tomography.

    Science.gov (United States)

    Erdogan, H; Fessler, J A

    1999-11-01

    The ordered subsets EM (OSEM) algorithm has enjoyed considerable interest for emission image reconstruction due to its acceleration of the original EM algorithm and ease of programming. The transmission EM reconstruction algorithm converges very slowly and is not used in practice. In this paper, we introduce a simultaneous update algorithm called separable paraboloidal surrogates (SPS) that converges much faster than the transmission EM algorithm. Furthermore, unlike the 'convex algorithm' for transmission tomography, the proposed algorithm is monotonic even with nonzero background counts. We demonstrate that the ordered subsets principle can also be applied to the new SPS algorithm for transmission tomography to accelerate 'convergence', albeit with similar sacrifice of global convergence properties as for OSEM. We implemented and evaluated this ordered subsets transmission (OSTR) algorithm. The results indicate that the OSTR algorithm speeds up the increase in the objective function by roughly the number of subsets in the early iterates when compared to the ordinary SPS algorithm. We compute mean square errors and segmentation errors for different methods and show that OSTR is superior to OSEM applied to the logarithm of the transmission data. However, penalized-likelihood reconstructions yield the best quality images among all other methods tested. PMID:10588288

  8. Product-free subsets of profinite groups

    CERN Document Server

    Bardestani, Mohammad

    2012-01-01

    Gowers in his paper on quasirandom groups studies a question of Babai and Sos asking whether there exists a constant $c > 0$ such that every finite group $G$ has a product-free subset of size at least $c|G|$. Answering the question negatively, he proves that for sufficiently large prime $p$, the group $\\mathrm{PSL}_2(\\mathbb{F}_p)$ has no product-free subset of size $cn^{8/9}$, where $n$ is the order of $\\mathrm{PSL}_2(\\mathbb{F}_p)$. We will consider the problem for compact groups and in particular for profinite groups $\\SL_k(\\ZZ_p)$ obtain lower and upper exponential bounds for the supremal measure of the product-free sets. The proof involves establishing a lower bound for the dimension of non-trivial representations of the finite groups $\\SL_k(\\Z{p^n})$.

  9. Fluorouracil Selectively Enriches Stem-like Leukemic Cells in a Leukemic Cell Line

    Directory of Open Access Journals (Sweden)

    Ling Zhang, Song Yang, Yu-Juan He, Hui-Yuan Shao, Li Wang, Hui Chen, Yu-Jie Gao, Feng-Xian Qing, Xian-Chun Chen, Liu-Yang Zhao, Shi Tan

    2010-01-01

    Full Text Available Recent studies have reported that cancer stem cells (CSCs could be isolated from solid cancer cell lines, in which the purity of CSCs was higher than that from tumor tissues. Separation of CSCs from leukemic cell lines was rarely reported. In this study, CD34+CD38- stem-like cell subsets in human KG-1a leukemic cell line were enriched by cytotoxic agent 5-fluorouracil (5-FU. After 4 days incubation of KG-1a cell line with 5-FU (50 μg/ml, the CD34+CD38- subpopulation of cell lines was enriched more than 10 times. The enriched cells had proliferate potential in vitro, low level of RNA transcription and Hoechst 33342 dye efflux ability, accompanied by high expression of ATP-binding cassette transporter protein ABCG2. Our findings suggest that treatment with 5-FU offers an easy method to isolate leukemic stem-like subpopulation. It can facilitate studies of leukemic stem cell biology and the development of new therapeutic strategies.

  10. Competitive Market Structures: A Subset Selection Analysis

    OpenAIRE

    P. K. Kannan; Sanchez, Susan M.

    1994-01-01

    Market structure models are used to identify submarkets or to test for the presence of submarkets where within-group competition is much stronger than across group competition. The implicit assumption in such models is that the brands in a submarket compete on the basis of their shared product features. However, if significant variety-seeking effect exist in the market, such an assumption may not be valid. We present a model based on a subset selection procedure for analyzing competitive mark...

  11. Th Subset Balance in Lupus Nephritis

    OpenAIRE

    Katsuhisa Miyake; Mitsuteru Akahoshi; Hitoshi Nakashima

    2011-01-01

    Lupus nephritis, which has various histological patterns and variable clinical outcomes, is one of the most important complications of systemic lupus nephritis (SLE). This pathogenetic mechanism in each histologically different type of lupus nephritis (LN) remains unclear. Although SLE is suggested to be a Th2-driven disease, elevation of both Th1 and Th2 cytokines occurs in both humans and mice, suggesting that SLE is a complex disease driven by different lymphocyte subsets with high heterog...

  12. Median Selection Subset Aggregation for Parallel Inference

    OpenAIRE

    Wang, Xiangyu; Peng, Peichao; Dunson, David

    2014-01-01

    For massive data sets, efficient computation commonly relies on distributed algorithms that store and process subsets of the data on different machines, minimizing communication costs. Our focus is on regression and classification problems involving many features. A variety of distributed algorithms have been proposed in this context, but challenges arise in defining an algorithm with low communication, theoretical guarantees and excellent practical performance in general settings. We propose...

  13. Human NK cell subset functions are differentially affected by adipokines.

    Directory of Open Access Journals (Sweden)

    Lena Huebner

    Full Text Available BACKGROUND: Obesity is a risk factor for various types of infectious diseases and cancer. The increase in adipose tissue causes alterations in both adipogenesis and the production of adipocyte-secreted proteins (adipokines. Since natural killer (NK cells are the host's primary defense against virus-infected and tumor cells, we investigated how adipocyte-conditioned medium (ACM affects functions of two distinct human NK cell subsets. METHODS: Isolated human peripheral blood mononuclear cells (PBMCs were cultured with various concentrations of human and murine ACM harvested on two different days during adipogenesis and analyzed by fluorescent-activated cell sorting (FACS. RESULTS: FACS analyses showed that the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, granzyme A (GzmA and interferon (IFN-γ in NK cells was regulated in a subset-specific manner. ACM treatment altered IFN-γ expression in CD56(dim NK cells. The production of GzmA in CD56(bright NK cells was differentially affected by the distinct adipokine compositions harvested at different states of adipogenesis. Comparison of the treatment with either human or murine ACM revealed that adipokine-induced effects on NK cell expression of the leptin receptor (Ob-R, TRAIL and IFN-γ were species-specific. CONCLUSION: Considering the growing prevalence of obesity and the various disorders related to it, the present study provides further insights into the roles human NK cell subsets play in the obesity-associated state of chronic low-grade inflammation.

  14. Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors

    Science.gov (United States)

    Sutton, Lesley-Ann; Young, Emma; Baliakas, Panagiotis; Hadzidimitriou, Anastasia; Moysiadis, Theodoros; Plevova, Karla; Rossi, Davide; Kminkova, Jana; Stalika, Evangelia; Pedersen, Lone Bredo; Malcikova, Jitka; Agathangelidis, Andreas; Davis, Zadie; Mansouri, Larry; Scarfò, Lydia; Boudjoghra, Myriam; Navarro, Alba; Muggen, Alice F.; Yan, Xiao-Jie; Nguyen-Khac, Florence; Larrayoz, Marta; Panagiotidis, Panagiotis; Chiorazzi, Nicholas; Niemann, Carsten Utoft; Belessi, Chrysoula; Campo, Elias; Strefford, Jonathan C.; Langerak, Anton W.; Oscier, David; Gaidano, Gianluca; Pospisilova, Sarka; Davi, Frederic; Ghia, Paolo; Stamatopoulos, Kostas; Rosenquist, Richard

    2016-01-01

    We report on markedly different frequencies of genetic lesions within subsets of chronic lymphocytic leukemia patients carrying mutated or unmutated stereotyped B-cell receptor immunoglobulins in the largest cohort (n=565) studied for this purpose. By combining data on recurrent gene mutations (BIRC3, MYD88, NOTCH1, SF3B1 and TP53) and cytogenetic aberrations, we reveal a subset-biased acquisition of gene mutations. More specifically, the frequency of NOTCH1 mutations was found to be enriched in subsets expressing unmutated immunoglobulin genes, i.e. #1, #6, #8 and #59 (22–34%), often in association with trisomy 12, and was significantly different (Pimmunoglobulin genes). Interestingly, subsets harboring a high frequency of NOTCH1 mutations were found to carry few (if any) SF3B1 mutations. This starkly contrasts with subsets #2 and #3 where, despite their immunogenetic differences, SF3B1 mutations occurred in 45% and 46% of cases, respectively. In addition, mutations within TP53, whilst enriched in subset #1 (16%), were rare in subsets #2 and #8 (both 2%), despite all being clinically aggressive. All subsets were negative for MYD88 mutations, whereas BIRC3 mutations were infrequent. Collectively, this striking bias and skewed distribution of mutations and cytogenetic aberrations within specific chronic lymphocytic leukemia subsets implies that the mechanisms underlying clinical aggressiveness are not uniform, but rather support the existence of distinct genetic pathways of clonal evolution governed by a particular stereotyped B-cell receptor selecting a certain molecular lesion(s). PMID:27198719

  15. CXCR6 marks a novel subset of T-bet(lo)Eomes(hi) natural killer cells residing in human liver.

    Science.gov (United States)

    Stegmann, Kerstin A; Robertson, Francis; Hansi, Navjyot; Gill, Upkar; Pallant, Celeste; Christophides, Theodoros; Pallett, Laura J; Peppa, Dimitra; Dunn, Claire; Fusai, Giuseppe; Male, Victoria; Davidson, Brian R; Kennedy, Patrick; Maini, Mala K

    2016-05-23

    Natural killer cells (NK) are highly enriched in the human liver, where they can regulate immunity and immunopathology. We probed them for a liver-resident subset, distinct from conventional bone-marrow-derived NK. CXCR6+ NK were strikingly enriched in healthy and diseased liver compared to blood (p hi)Eomes(lo)(CXCR6-) and T-bet(lo)Eomes(hi)(CXCR6+); the latter was virtually absent in the periphery. The small circulating CXCR6+ subset was predominantly T-bet(hi)Eomes(lo), suggesting its lineage was closer to CXCR6- peripheral than CXCR6+ liver NK. These data reveal a large subset of human liver-resident T-bet(lo)Eomes(hi) NK, distinguished by their surface expression of CXCR6, adapted for hepatic tolerance and inducible anti-viral immunity.

  16. Sampling to estimate arbitrary subset sums

    OpenAIRE

    Duffield, Nick; Lund, Carsten; Thorup, Mikkel

    2005-01-01

    Starting with a set of weighted items, we want to create a generic sample of a certain size that we can later use to estimate the total weight of arbitrary subsets. For this purpose, we propose priority sampling which tested on Internet data performed better than previous methods by orders of magnitude. Priority sampling is simple to define and implement: we consider a steam of items i=0,...,n-1 with weights w_i. For each item i, we generate a random number r_i in (0,1) and create a priority ...

  17. 基因修饰树突状细胞诱导前列腺癌患者外周血T细胞亚群重排的研究%Gene-transducted dendritic cells induce T lymphocyte subsets repopulation in peripheral blood of patients with prostate cancer

    Institute of Scientific and Technical Information of China (English)

    宋浩杰; 涂小玉; 严晓; 尤长宣; 罗荣城; 吕成伟

    2011-01-01

    Objective To investigate the characteristics of rAAV/PSA-transducted dendritic cells (DCs) to induce T lymphocyte subsets repopulation in peripheral blood of patients with prostate cancer, and its clinical significance. Methods 30 patients with prostate cancer were included in this study. Peripheral blood mononuclear cells ( PBMC, the DC precursor cells and lymphocytes) were isolated from prostate cancer patients by density gradient centrifugation and infected with rAAV/PSA virus. Maturation of the DC precursor was induced by series of cytokine. On day 6, the DCs were collected and mixed with T cells to induce cytotoxic T lymphocytes (CTL). The proportion of T lymphocyte subsets and regulatory T cells (CD4+ CD25+ FoxP3+ Treg) in peripheral blood were analyzed by flow cytometry before and after mixed culture. Results The DCs transducted with PSA gene stimulated high proliferation of T cell populations. After mixed culture for 6 days, the percentage of CD8+, CD8+ CD69+, CD8+CD28+T cells, the CD8+:CD4+ ratio were significantly increased (P0.05). Conclusion The rAAV/PSA loading of DCs can effectively activate the CD8+antigen-specific CTL, decrease immunosuppressive T cell and improve the cellular immunological function in patients. These findings may provide a potent immune therapeutic strategy for prostate cancer patients.%目的 探讨以腺相关病毒(AAV)为载体,前列腺特异性抗原(PSA)基因转染树突状细胞(DC)诱导前列腺癌患者外周血T细胞亚群变化特点及临床意义.方法 抽取30例前列腺癌患者外周血,采用密度梯度离心法分离外周血单个核细胞,以rAAV/PSA感染DC前体细胞,采用系列细胞因子诱导DC前体细胞成熟.第6天收集成熟DC并与T细胞按比例混合培养,诱导细胞毒性T淋巴细胞(CTL).分别于DC与T细胞混合培养前后应用流式细胞术分析外周血T细胞亚群及调节性T细胞( CD4+CD25+ FoxP3+ Treg)的表达水平.结果 PSA基因转染DC刺激T淋巴细胞爆发

  18. Human breast cancer stem cell markers CD44 and CD24: enriching for cells with functional properties in mice or in man?

    OpenAIRE

    Fillmore, Christine; Kuperwasser, Charlotte

    2007-01-01

    Identification of breast cancer stem cells as the cells within breast tumors that have the ability to give rise to cells that make up the bulk of the tumor mass has shifted the focus of cancer research. However, there is still much debate concerning the unique nature of the markers that distinguish cancer stem cells in the breast. As such, understanding whether CD44+/CD24- breast cancer cells are merely more successful in overcoming an engraftment incompatibility that exists when injecting hu...

  19. Maximal Symmetric Difference-Free Families of Subsets of $[n]$

    OpenAIRE

    Buck, Travis G.; Godbole, Anant P.

    2010-01-01

    Union-free families of subsets of $[n]=\\{1,... n\\}$ have been studied in \\cite{FF}. In this paper, we provide a complete characterization of maximal {\\it symmetric difference}-free families of subsets of $[n]$.

  20. Flavonol-enriched fraction from Vaccinium macrocarpon fruit inhibits matrix metalloproteinase-2, matrix metalloproteinase-9 and urokinase-type plasminogen activator expression in human prostate cancer cells in vitro

    Directory of Open Access Journals (Sweden)

    James MacPhee

    2014-11-01

    Full Text Available Background: Prostate cancer, amongst other cancer types has a genetic and environmental component, which can contribute to prostate cancer development and progression. Vaccinum macrocarpon (American cranberry is a botanical that contains several phytochemicals which have been suggested to play a role in preventing cardiovascular disease, cancer, and urinary tract infections as well as in the maintenance of oral health. Context and purpose of this study: This investigation evaluated the effects of a flavonolenriched fraction (FL from the American cranberry (Vaccinium macrocarpon containing quercetin and myricetin glycosides on matrix metalloproteinase (MMP and urokinase-type plasminogen activator (uPA activities and their associated regulatory proteins in DU145 human prostate cancer cells in vitro. Results: A flavonol-enriched fraction (FL was prepared from Vaccinium macrocarpon berries and the effect of this fraction on prostate cancer cell behaviour was assessed using biochemical and molecular approaches including cytotoxicity assays and Western blot analysis to determine protein expression. Cranberry FL decreased cellular viability of DU145 cells at a concentration of 25 ug/ml by 20% after 6 hours of treatment. Further investigations determined that associated with this cytotoxicity, cranberry FL decreases matrix metalloproteinase (MMP ( specifically MMP-2 and MMP-9 activity and urokinase plasminogen activator (uPA activity through effects on specific temporal MMP regulators and uPA regulators and by affecting either the phosphorylation status and/or expression of specific MAP kinase, PI-3 kinase, NF-kB and AP-1 pathway associated proteins. Conclusion: This study demonstrates, for the first time, the ability of Vaccinium macrocarpon flavonols to modulate cellular pathways associated with migration, invasion, and proliferation, suggesting that cranberry (Vaccinium macrocarpon is a viable candidate for further research as a natural product that

  1. Th Subset Balance in Lupus Nephritis

    Directory of Open Access Journals (Sweden)

    Katsuhisa Miyake

    2011-01-01

    Full Text Available Lupus nephritis, which has various histological patterns and variable clinical outcomes, is one of the most important complications of systemic lupus nephritis (SLE. This pathogenetic mechanism in each histologically different type of lupus nephritis (LN remains unclear. Although SLE is suggested to be a Th2-driven disease, elevation of both Th1 and Th2 cytokines occurs in both humans and mice, suggesting that SLE is a complex disease driven by different lymphocyte subsets with high heterogeneity of clinical manifestations and organ involvement. Recent findings in LN elucidate an essential role for the Th1, IL-17 producing T cells and Th17 cells in the development of diffuse proliferative lupus nephritis (DPLN, and Th2 cytokine in that of membranous lupus nephritis (MLN. These data support the hypothesis that individual Th1/Th2 balance is one of the critical determinants for histopathology of LN.

  2. Isolation of Human Skin Dendritic Cell Subsets.

    Science.gov (United States)

    Gunawan, Merry; Jardine, Laura; Haniffa, Muzlifah

    2016-01-01

    Dendritic cells (DCs) are specialized leukocytes with antigen-processing and antigen-presenting functions. DCs can be divided into distinct subsets by anatomical location, phenotype and function. In human, the two most accessible tissues to study leukocytes are peripheral blood and skin. DCs are rare in human peripheral blood (Nestle et al., J Immunol 151:6535-6545, 1993). These factors led to the extensive use of skin DCs as the "prototype" migratory DCs in human studies. In this chapter, we detail the protocols to isolate DCs and resident macrophages from human skin. We also provide a multiparameter flow cytometry gating strategy to identify human skin DCs and to distinguish them from macrophages. PMID:27142012

  3. Sensor Placement for Modal Parameter Subset Estimation

    DEFF Research Database (Denmark)

    Ulriksen, Martin Dalgaard; Bernal, Dionisio; Damkilde, Lars

    2016-01-01

    The present paper proposes an approach for deciding on sensor placements in the context of modal parameter estimation from vibration measurements. The approach is based on placing sensors, of which the amount is determined a priori, such that the minimum Fisher information that the frequency...... responses carry on the selected modal parameter subset is, in some sense, maximized. The approach is validated in the context of a simple 10-DOF mass-spring-damper system by computing the variance of a set of identified modal parameters in a Monte Carlo setting for a set of sensor configurations, whose......). It is shown that the widely used Effective Independence (EI) method, which uses the modal amplitudes as surrogates for the parameters of interest, provides sensor configurations yielding theoretical lower bound variances whose maxima are up to 30 % larger than those obtained by use of the max-min approach....

  4. Lymphocytes subsets in children with febrile convulsions.

    Science.gov (United States)

    Tuncer, Oğuz; Karaman, Sait; Caksen, Hüseyin; Oner, Ahmet Faik; Odabas, Dursun; Yilmaz, Cahide; Atas, Bülent

    2007-07-01

    In this study, lymphocytes subsets including blood CD3, CD4, CD8, CD16, CD19, and CD56 values were analyzed in children with febrile convulsion (FC) to determine whether there was the association of lymphocytes subsets in the pathogenesis of FC. The study includes 48 children with FC, and 55 healthy age matched control subjects, followed in Yüzüncü Yil University, Faculty of Medicine, Department of Pediatrics between October 2003 and June 2004. Blood CD3, CD4, CD8, CD16, CD19, and CD56 values were examined in the study and control groups. The analyses were performed in the Hematology Laboratory, Yüzüncü Yil University Faculty of Medicine, with flow cytometer device (Coulter Epics XL2, Flow Cytometer). A total of 48 children [17 girls (35.5%) and 31 boys (64.5%)], aged 6 months to 60 months (mean 22.20 +/- 13.75 months) with FC and 55 healthy children [28 girls (51%) and 27 boys (49%)], aged 6 months to 60 months (mean 28.87 +/- 17.04 months) were included in the study. When compared with the control group, the study found significantly decreased blood CD3 and CD4 values in the study group (p .05). When comparing the children with and without positive family history for FC, the study did not find any difference for all CD values between the groups (p >.05). Similarly, there was not significant difference in CD values between the children with simple and complex FC (p >.05). The findings suggested that decreased blood CD3 and CD4 values might be responsible for the infections connected with FC or that they might be related to the pathogenesis of FC in some children.

  5. Molecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes.

    Directory of Open Access Journals (Sweden)

    Jenny-Maria Jönsson

    Full Text Available OBJECTIVE: Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities with the well-established intrinsic molecular subtypes of breast cancer. METHODS: Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published gene profiles for the ovarian and breast cancer subtypes. Correlations to gene expression modules representing key biological breast cancer features were also sought. Validation was performed using an independent, publicly available dataset. RESULTS: 5,944 genes were significantly differentially expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal-like breast cancer subtype were found. The benign and borderline serous tumors together were significantly correlated to the normal-like breast cancer subtype and the ovarian cancer signature derived from borderline tumors. The borderline tumors in the study dataset, in addition, also correlated significantly to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged. CONCLUSIONS: These data link the transcriptional profiles of serous ovarian cancer to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and

  6. Hierarchical modeling for rare event detection and cell subset alignment across flow cytometry samples.

    Directory of Open Access Journals (Sweden)

    Andrew Cron

    Full Text Available Flow cytometry is the prototypical assay for multi-parameter single cell analysis, and is essential in vaccine and biomarker research for the enumeration of antigen-specific lymphocytes that are often found in extremely low frequencies (0.1% or less. Standard analysis of flow cytometry data relies on visual identification of cell subsets by experts, a process that is subjective and often difficult to reproduce. An alternative and more objective approach is the use of statistical models to identify cell subsets of interest in an automated fashion. Two specific challenges for automated analysis are to detect extremely low frequency event subsets without biasing the estimate by pre-processing enrichment, and the ability to align cell subsets across multiple data samples for comparative analysis. In this manuscript, we develop hierarchical modeling extensions to the Dirichlet Process Gaussian Mixture Model (DPGMM approach we have previously described for cell subset identification, and show that the hierarchical DPGMM (HDPGMM naturally generates an aligned data model that captures both commonalities and variations across multiple samples. HDPGMM also increases the sensitivity to extremely low frequency events by sharing information across multiple samples analyzed simultaneously. We validate the accuracy and reproducibility of HDPGMM estimates of antigen-specific T cells on clinically relevant reference peripheral blood mononuclear cell (PBMC samples with known frequencies of antigen-specific T cells. These cell samples take advantage of retrovirally TCR-transduced T cells spiked into autologous PBMC samples to give a defined number of antigen-specific T cells detectable by HLA-peptide multimer binding. We provide open source software that can take advantage of both multiple processors and GPU-acceleration to perform the numerically-demanding computations. We show that hierarchical modeling is a useful probabilistic approach that can provide a

  7. Hierarchical modeling for rare event detection and cell subset alignment across flow cytometry samples.

    Science.gov (United States)

    Cron, Andrew; Gouttefangeas, Cécile; Frelinger, Jacob; Lin, Lin; Singh, Satwinder K; Britten, Cedrik M; Welters, Marij J P; van der Burg, Sjoerd H; West, Mike; Chan, Cliburn

    2013-01-01

    Flow cytometry is the prototypical assay for multi-parameter single cell analysis, and is essential in vaccine and biomarker research for the enumeration of antigen-specific lymphocytes that are often found in extremely low frequencies (0.1% or less). Standard analysis of flow cytometry data relies on visual identification of cell subsets by experts, a process that is subjective and often difficult to reproduce. An alternative and more objective approach is the use of statistical models to identify cell subsets of interest in an automated fashion. Two specific challenges for automated analysis are to detect extremely low frequency event subsets without biasing the estimate by pre-processing enrichment, and the ability to align cell subsets across multiple data samples for comparative analysis. In this manuscript, we develop hierarchical modeling extensions to the Dirichlet Process Gaussian Mixture Model (DPGMM) approach we have previously described for cell subset identification, and show that the hierarchical DPGMM (HDPGMM) naturally generates an aligned data model that captures both commonalities and variations across multiple samples. HDPGMM also increases the sensitivity to extremely low frequency events by sharing information across multiple samples analyzed simultaneously. We validate the accuracy and reproducibility of HDPGMM estimates of antigen-specific T cells on clinically relevant reference peripheral blood mononuclear cell (PBMC) samples with known frequencies of antigen-specific T cells. These cell samples take advantage of retrovirally TCR-transduced T cells spiked into autologous PBMC samples to give a defined number of antigen-specific T cells detectable by HLA-peptide multimer binding. We provide open source software that can take advantage of both multiple processors and GPU-acceleration to perform the numerically-demanding computations. We show that hierarchical modeling is a useful probabilistic approach that can provide a consistent labeling

  8. CD133 is a temporary marker of cancer stem cells in small cell lung cancer, but not in non-small cell lung cancer.

    Science.gov (United States)

    Cui, Fei; Wang, Jian; Chen, Duan; Chen, Yi-Jiang

    2011-03-01

    Lung cancer is the most common cause of cancer-related death worldwide. Current investigations in the field of cancer research have intensively focused on the 'cancer stem cell' or 'tumor-initiating cell'. While CD133 was initially considered as a stem cell marker only in the hematopoietic system and the nervous system, the membrane antigen also identifies tumorigenic cells in certain solid tumors. In this study, we investigated the human lung cancer cell lines A549, H157, H226, Calu-1, H292 and H446. The results of real-time PCR analysis after chemotherapy drug selection and the fluorescence-activated cell sorting analysis showed that CD133 only functioned as a marker in the small cell lung cancer line H446. The sorted CD133+ subset presented stem cell-like features, including self-renewal, differentiation, proliferation and tumorigenic capacity in subsequent assays. Furthermore, a proportion of the CD133+ cells had a tendency to remain stable, which may explain the controversies arising from previous studies. Therefore, the CD133+ subset should provide an enriched source of tumor-initiating cells among H446 cells. Moreover, the antigen could be used as an investigative marker of the tumorigenic process and an effective treatment for small cell lung cancer. PMID:21174061

  9. 新辅助化疗对局部晚期非小细胞肺癌肿瘤标记物和淋巴细胞亚群的影响%Effect of neoadjuvant chemotherapy on locally advanced non-small cell lung cancer tumor markers and lymphocyte subsets

    Institute of Scientific and Technical Information of China (English)

    王纯; 卢宏达

    2014-01-01

    目的:观察新辅助化疗对不同病理类型的局部晚期非小细胞肺癌(NSCLC )肿瘤标记物、淋巴细胞亚群的影响。方法选取该院新辅助化疗的局部晚期NSCLC患者为研究对象,共计40例,选取20例体检的健康人群为对照组,比较不同病理类型的NSCLC肿瘤标记物癌胚抗原(CEA)、糖类蛋白-125(CA-125)、细胞角蛋白19可溶性片段(CYFRA21-1)的水平以及淋巴细胞亚群CD3+、CD4+、CD8+比例。分析不同疗效的NSCLC患者肿瘤标记物水平及淋巴细胞亚群的差异。结果(1)腺癌、鳞癌患者CEA、CA-125和CYFRA21-1水平均显著高于健康人群(P<0.05);鳞癌患者CEA升高水平低于腺癌,而鳞癌CA-125和CYFRA21-1升高水平高于腺癌(P<0.05);相对于健康人群,腺癌、鳞癌患者CD3+、CD4+、CD4+/CD8+均显著降低,而CD8+升高(P<0.05);但鳞癌、腺癌患者CD3+、CD4+、CD8+、CD4+/CD8+差异无统计学意义(P>0.05)。(2)经2个周期化疗后,缓解和部分缓解共18例,稳定和进展共22例。新辅助化疗有效的鳞癌患者血清CA-125和CYFRA21-1水平显著降低(P<0.05),新辅助化疗有效的腺癌患者血清CEA 和 CYFRA21-1水平显著降低(P<0.05)。新辅助化疗有效鳞癌、腺癌患者CD3+、CD4+、CD4+/CD8+升高,CD8+降低。结论不同病理类型的晚期NSCLC患者血清肿瘤标记物表达水平具有一定的差异,血清标记物与淋巴细胞亚群的变化均可作为评价新辅助化疗疗效的指标。%Objective To observe and analyze the effect of neoadjuvant chemotherapy on locally advanced non-small cell lung cancer tumor markers and lymphocyte subsets of different pathological type .Methods A total number of 40 NSCLC patients which received neoadjuvant chemotherapy and 20 normal people were selected in our study .To compare the differences of CEA ,CA-125 , CYFRA21-1 and

  10. Beyond Job Enrichment to Employment Enrichment

    Science.gov (United States)

    Werther, William B., Jr.

    1975-01-01

    Employment enrichment views the total work environment confronting employees as a system consisting of two overlapping areas: worker-job and worker-organization subsystems. Job enrichment has improved the worker-job subsystem. The focus of this article is on methods of improving the worker-organization relationship. (Author/JB)

  11. 高强度聚焦超声对前列腺癌小鼠的疗效及T细胞亚群的影响%Therapeutic Effects of High Intensity Focused Ultrasound on Mice with Prostate Cancer and Its Influence on Systemic T Cell Subsets in Mice

    Institute of Scientific and Technical Information of China (English)

    武睿毅; 王国民; 徐叶青

    2012-01-01

    目的 探讨高强度聚焦超声(high intensity focused ultrasound,HIFU)对前列腺癌荷瘤小鼠的疗效及T细胞亚群的影响.方法 RM-1细胞接种于C57BL6小鼠建立小鼠前列腺癌皮下移植瘤模型,随机分为肿瘤对照组、HIFU组、放疗组和HIFU联合放疗组.观察治疗后各组的肿瘤生长曲线,计算肿瘤体积倍增时间(DT).2周后,通过流式细胞仪检测正常小鼠和荷瘤小鼠外周血CD3+、CD3+CD4+、CD3+ CD8+细胞占白细胞总数的百分比.结果 与肿瘤对照组相比,HIFU组、放疗组肿瘤生长延缓,DT显著延长.HIFU组小鼠的CD3+(%)、CD4+(%)显著高于肿瘤对照组,而放疗组与肿瘤对照组差异无统计学意义.HIFU联合放疗组的DT较HIFU组显著延长,小鼠的CD3+(%)、CD4+(%)显著高于HIFU组,且CD4+(%)显著高于正常小鼠.结论 HIFU治疗前列腺癌不仅能局部抑制肿瘤生长,而且能通过对T细胞亚群的影响提高机体的细胞免疫水平.HIFU联合放疗能进一步提高疗效.%Objective To explore therapeutic effects of high intensity focused ultrasound( HIFU) on prostate cancer and influence on systemic T cell subsets in mice. Methods Subcutaneous prostate carcinoma model was established by vaccinating RM-1 cells to C57BL6 mice. Model mice were randomly divided into control group, radiotherapy group, HIFU group,and HIFU combined with radiotherapy group. We calculated the growing curve of tumor and the tumor doubling time(DT). Two weeks later,CD3 + , CD3 + CD4+ and CD3+ /CD8+ ratio within the total white blood cell were observed by flow cytometric analysis in diffferent groups. Results Comparing with control group, both HIFU and radiotherapy groups had slower tumor's growth and significantly longer the DT. CD3+ (%) and CD4+ (%) in HIFU group were higher than those in control group, and there was no significant difference between radiotherapy group and control group. The DT of HIFU combined with radiotherapy group was significantly

  12. Sorting through subsets: Which T cell populations mediate highly effective adoptive immunotherapy?

    Science.gov (United States)

    Klebanoff, Christopher A.; Gattinoni, Luca; Restifo, Nicholas P.

    2012-01-01

    CD8+ T cells have been described as being naïve (TN) or one of four antigen-experienced subtypes representing a continuum of differentiation and maturation: stem cell memory (TSCM), central memory (TCM), effector memory (TEM), and terminally differentiated effector T cells (TEFF). In mice, adoptive cell transfer (ACT) of less differentiated TN, TSCM and TCM subsets have consistently demonstrated superior in vivo expansion, persistence, and antitumor capacities relative to the more differentiated TEM and TEFF cells. Retrospective analyses from human ACT trials have confirmed that transfer of less differentiated T cell subsets is highly correlated with objective clinical responses. These findings, combined with the recent ability to convey de novo antigen reactivity with high efficiency through genetic engineering of exogenous T cell or chimeric antigen receptors, now challenge the field with three important questions: 1) how should less differentiated T cell subsets be isolated for human clinical trials?; 2) what is the best means of expanding T cells ex vivo in such a way as to not corrupt the beneficial traits of the younger subsets?; and 3) is it necessary to physically separate younger subsets from their more differentiated counterparts? Answering these questions will allow for the rational development of the next generation of highly effective and potentially curative T cell therapies for the treatment of cancer. PMID:23090074

  13. A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1.

    OpenAIRE

    Pillay, J.; Kamp, V.M.; van Hoffen, E; Visser, T.; Tak, T; Lammers, J. W.; Ulfman, L.H.; Leenen, L.P.H.; Pickkers, P; Koenderman, L

    2012-01-01

    Suppression of immune responses is necessary to limit damage to host tissue during inflammation, but it can be detrimental in specific immune responses, such as sepsis and antitumor immunity. Recently, immature myeloid cells have been implicated in the suppression of immune responses in mouse models of cancer, infectious disease, bone marrow transplantation, and autoimmune disease. Here, we report the identification of a subset of mature human neutrophils (CD11cbright/CD62Ldim/CD11bbright/CD1...

  14. Lymphocyte subsets and response to PHA among atomic bomb survivors

    International Nuclear Information System (INIS)

    In an effort to elucidate the effect of radiation exposure on immune competence in man, the number of lymphocytes, lymphocyte subsets, and the percentage of phytohemagglutinin (PHA)-induced transformation of lymphocytes were determined in 66 cancer patients, 25 of whom were exposed to atomic radiation at ≤ 2,000 m from ground zero and 41 others were not exposed. The number of lymphocytes was decreased with increasing age at exposure. The percentage of OKT3-positive cells tended to be lower in exposed patients who were in their twenties at the time of exposure than the non-exposed patients. Among patients in their teens and twenties at the time of exposure, there was a tendency toward decreased percentage of OKT4-positive cells (T4) and increased percentage of OKT8-positive cells (T8). The T4/T8 ratio was reduced. Patients who were in their first decade of life at the time of exposure tended to have decreased OKIa 1-positive cells, and increased Leulla-positive cells. Patients exposed in their twenties and thirties had slightly decreased percentage of PHA-induced transformation of lymphocytes. (Namekawa, K.)

  15. T-lymphocyte subsets in recurrent aphthous ulceration

    DEFF Research Database (Denmark)

    Pedersen, A; Klausen, B; Hougen, H P;

    1989-01-01

    Peripheral T-lymphocyte subsets: T-helper (OKT4) and T-suppressor (OKT8) cells were studied quantitatively in 20 patients with recurrent aphthous ulceration (RAU) in ulcerative, as well as inactive, stages of the disease. The figures were compared with T-lymphocyte subsets from matched control...

  16. Uranium enrichment. Principles

    International Nuclear Information System (INIS)

    Uranium enrichment industry is a more than 60 years old history and has developed without practically no cost, efficiency or profit constraints. However, remarkable improvements have been accomplished since the Second World War and have led to the development of various competing processes which reflect the diversity of uranium compositions and of uranium needs. Content: 1 - general considerations: uranium isotopes, problem of uranium enrichment, first realizations (USA, Russia, Europe, Asia, other countries), present day situation, future needs and market evolution; 2 - principles of isotopic separation: processes classification (high or low enrichment), low elementary enrichment processes, equilibrium time, cascade star-up and monitoring, multi-isotopes case, uranium reprocessing; 3 - enrichment and proliferation. (J.S.)

  17. Role of plasmacytoid dendritic cell subsets in allergic asthma

    OpenAIRE

    Maazi, Hadi; Lam, Jonathan; Lombardi, Vincent; Akbari, Omid

    2013-01-01

    Plasmacytoid dendritic cells (pDCs) are major type-I interferon producing cells that play important roles in antiviral immunity and tolerance induction. These cells share a common DC progenitor with conventional DCs and Fms-like tyrosine kinase-3 ligand is essential for their development. Several subsets of pDCs have been identified to date including CCR9+, CD9+ and CD2+ pDCs. Recently, three subsets of pDCs were described namely, CD8α−β−, CD8α+β− and CD8α+β+ subsets. Interestingly, CD8α+β− a...

  18. 人大细胞肺癌干细胞样细胞的富集及其功能研究%Enrichment and Function Research of Large Cell Lung Cancer Stem Cell-like Cells

    Institute of Scientific and Technical Information of China (English)

    月文科; 焦锋; 刘彬; 尤嘉琮; 周清华

    2011-01-01

    Background and objective There are no universal method to recognize and screen for lung cancer stem cell markers and indicators.Commonly used methods are flow Cytometry and learning from other cancer stem cell sorting tags to sort lung cancer stem cells.But this method has low specificity screening, the workload is huge.In this study, Serum-free suspension culture was used to enrich lung cancer stem cells, and explore method for lung cancer stem cell screening.Methods Human large lung cancer cell line-L9981 was cultured in serum-free and growth factors added medium, and spheres were obtained.Then the morphological differences of sphere cells and adherent L9981 cells cultured in serum-containing mediums are observed.Cell proliferation was analyzed by Vi-cell viability analyzer; invasion ability was tested by transwell assay; and in vivo tumorigenicity of the two groups of cells was studied in nude mouse.Results Compared with adherent L9981 cells cultured in serum-containing mediums, cells cultured in serum-free medium display sphere appearance.Doubling time of adherent cells and sphere cells are (56.05±1.95) h and (33.00±1.44) h respectively; Spheroid cells had higher invasion and tumorigenicity ability, 5 times and 20 times respectively, than adherent cells.Conclusion Suspension cultured L9981 in Serum-free medium could form spheroid populations.Cells in spheres had higher ability of invasion and Tumorigenicity than adherent L9981 cells.These results indicated spheroid L9981 cells contained enriched lung cancer stem cells, and Serum-free suspension culture can be a candidate method for enriching lung cancer stem cell.%背景与目的 目前国内外还没有确切的、得到公认的肺癌干细胞的筛选标记分子、指标和方法,常用方法 为通过流式细胞技术,借鉴其他肿瘤干细胞分选标记来分选肺癌干细胞,但其筛选特异性低、工作量巨大.本研究采用无血清悬浮培养法富集肺癌干细胞,对

  19. A novel HMM-based method for detecting enriched transcription factor binding sites reveals RUNX3 as a potential target in pancreatic cancer biology.

    Directory of Open Access Journals (Sweden)

    Liron Levkovitz

    Full Text Available BACKGROUND: Pancreatic adenocarcinoma (PAC is one of the most intractable malignancies. In order to search for potential new therapeutic targets, we relied on computational methods aimed at identifying transcription factor binding sites (TFBSs over-represented in the promoter regions of genes differentially expressed in PAC. Though many computational methods have been implemented to accomplish this, none has gained overall acceptance or produced proven novel targets in PAC. To this end we have developed DEMON, a novel method for motif detection. METHODOLOGY: DEMON relies on a hidden Markov model to score the appearance of sequence motifs, taking into account all potential sites in a promoter of potentially varying binding affinities. We demonstrate DEMON's accuracy on simulated and real data sets. Applying DEMON to PAC-related data sets identifies the RUNX family as highly enriched in PAC-related genes. Using a novel experimental paradigm to distinguish between normal and PAC cells, we find that RUNX3 mRNA (but not RUNX1 or RUNX2 mRNAs exhibits time-dependent increases in normal but not in PAC cells. These increases are accompanied by changes in mRNA levels of putative RUNX gene targets. CONCLUSIONS: The integrated application of DEMON and a novel differentiation system led to the identification of a single family member, RUNX3, which together with four of its putative targets showed a robust response to a differentiation stimulus in healthy cells, whereas this regulatory mechanism was absent in PAC cells, emphasizing RUNX3 as a promising target for further studies.

  20. Random sum-free subsets of abelian groups

    CERN Document Server

    Balogh, József; Samotij, Wojciech

    2011-01-01

    We characterize the structure of maximum-size sum-free subsets of a random subset of an abelian group $G$. In particular, we determine the threshold $p_c \\approx \\sqrt{\\log n / n}$ above which, with high probability as $|G| \\to \\infty$, each such subset is contained in a maximum-size sum-free subset of $G$, whenever $q$ divides $|G|$ for some (fixed) prime $q$ with $q \\equiv 2 \\pmod 3$. Moreover, in the special case $G = \\ZZ_{2n}$, we determine a sharp threshold for the above property. The proof uses recent 'transference' theorems of Conlon and Gowers, together with stability theorems for sum-free sets of abelian groups.

  1. TRIGA low enrichment fuel

    International Nuclear Information System (INIS)

    Sixty TRIGA reactors have been sold and the earliest of these are now passing twenty years of operation. All of these reactors use the uranium-zirconium hydride fuel (UZrH) which provides certain unique advantages arising out of its large prompt negative temperature coefficient, very low fission product release, and high temperature capability. Eleven of these Sixty reactors are conversions from plate fuel to TRIGA fuel which were made as a result of these advantages. With only a few exceptions, TRIGA reactors have always used low-enriched-uranium (LEU) fuel with an enrichment of 19.9%. The exceptions have either been converted from the standard low-enriched fuel to the 70% enriched FLIP fuel in order to achieve extended lifetime, or are higher powered reactors which were designed for long life using 93%-enriched uranium during the time when the use and export of highly enriched uranium (HEU) was not restricted. The advent of international policies focusing attention on nonproliferation and safeguards made the HEU fuels obsolete. General Atomic immediately undertook a development effort (nearly two years ago) in order to be in a position to comply with these policies for all future export sales and also to provide a low-enriched alternative to fully enriched plate-type fuels. This important work was subsequently partially supported by the U.S. Department of Energy. The laboratory and production tests have shown that higher uranium densities can be achieved to compensate for reducing the enrichment to 20%, and that the fuels maintain the characteristics of the very thoroughly proven standard TRIGA fuels. In May of 1978, General Atomic announced that these fuels were available for TRIGA reactors and for plate-type reactors with power levels up to 15 MW with GA's standard commercial warranty

  2. TRIGA low enrichment fuel

    International Nuclear Information System (INIS)

    Sixty TRIGA reactors have been sold and the earliest of these are now passing twenty years of operation. All of these reactors use the uranium zirconium hydride fuel (UZrH) which provides certain unique advantages arising out of its large prompt negative temperature coefficient, very low fission product release, and high temperature capability. Eleven of these Sixty reactors are conversions from plate fuel to TRIGA fuel which were made as a result of these advantages. With only a few exceptions, TRIGA reactors have always used low-enriched uranium (LEU) fuel with an enrichment of 19.9%. The exceptions have either been converted from the standard low-enriched fuel to the 70% enriched FLIP fuel in order to achieve extended lifetime, or are higher powered reactors which were designed for long life using 93%-enriched uranium during the time when the use and export of highly enriched uranium (HEU) was not restricted. The advent of international policies focusing attention on nonproliferation and safeguards made the HEU fuels obsolete. General Atomic immediately undertook a development effort (nearly two years ago) in order to be in a position to comply with these policies for all future export sales and also to provide a low-enriched alternative to fully enriched plate-type fuels. This important work was subsequently partially supported by the U.S. Department of Energy. The laboratory and production tests have shown that higher uranium densities can be achieved to compensate for reducing the enrichment to 20%, and that the fuels maintain the characteristics of the very thoroughly proven standard TRIGA fuels. In May of 1978, General Atomic announced that these fuels were available for TRIGA reactors and for plate-type reactors with power levels up to 15 MW with General Atomic's standard commercial warranty

  3. Stream sampling for variance-optimal estimation of subset sums

    OpenAIRE

    Cohen, Edith; Duffield, Nick; Kaplan, Haim; Lund, Carsten; Thorup, Mikkel

    2008-01-01

    From a high volume stream of weighted items, we want to maintain a generic sample of a certain limited size $k$ that we can later use to estimate the total weight of arbitrary subsets. This is the classic context of on-line reservoir sampling, thinking of the generic sample as a reservoir. We present an efficient reservoir sampling scheme, $\\varoptk$, that dominates all previous schemes in terms of estimation quality. $\\varoptk$ provides {\\em variance optimal unbiased estimation of subset sum...

  4. Sterile inflammation - do innate lymphoid cell subsets play a role?

    OpenAIRE

    Walsh, Patrick

    2012-01-01

    PUBLISHED The recent identification of several novel innate lymphoid cell (iLC) subsets has increased our understanding of the mechanisms which link the innate and adaptive immune systems. While the contribution of these subsets toward the pathogenesis of human disease remains largely to be determined, it seems likely that they will play a particularly important role in sterile inflammatory settings where the innate response is seen as a critical mediator of inflammation. Several recent st...

  5. Ineffective oesophageal motility: Manometric subsets exhibit different symptom profiles

    Institute of Scientific and Technical Information of China (English)

    Horst Gunter Haack; Ross David Hansen; Allison Malcolm; John Edward Kellow

    2008-01-01

    AIM: To compare the demographic and clinical features of different manometric subsets of ineffective oesophageal motility (IOM; defined as ≥30% wet swallows with distal contractile amplitude <30 mmHg), and to determine whether the prevalence of gastro-oesophageal reflux differs between IOM subsets.METHODS: Clinical characteristics of manometric subsets were determined in 100 IOM patients (73 female, median age 58 years) and compared to those of 100 age-and gender-matched patient controls with oesophageal symptoms, but normal manometry. Supine oesophageal manometry was performed with an eight-channel DentSleeve water-perfused catheter, and an ambulatory pH study assessed gastrooesophageal reflux.RESULTS: Patients in the IOM subset featuring a majority of low-amplitude simultaneous contractions (LASC) experienced less heartburn (prevalence 26%), but more dysphagia (57%) than those in the IOM subset featuring low-amplitude propagated contractions (LAP; heartburn 70%, dysphagia 24%; both P≤0.01). LASC patients also experienced less heartburn and more dysphagia than patient controls (heartburn 68%, dysphagia 11%; both P<0.001). The prevalence of heartburn and dysphagia in IOM patients featuring a majority of non-transmitted sequences (NT) was 54% (P=0.04 vs LASC) and 36% (P<0.01 vs controls), respectively. No differences in age and gender distribution, chest pain prevalence, acid exposure time (AET) and symptom/reflux association existed between IOM subsets, or between subsets and controls.CONCLUSION: IOM patients with LASC exhibit a different symptom profile to those with LAP, but do not differ in gastro-oesophageal reflux prevalence. These findings raise the possibility of different pathophysiological mechanisms in IOM subsets, which warrants further investigation.

  6. Origin of CD8+ Effector and Memory T Cell Subsets

    Institute of Scientific and Technical Information of China (English)

    Christian Stemberger; Michael Neuenhahn; Veit R.Buchholz; Dirk H.Busch

    2007-01-01

    It is well accepted that CD8+ T cells play a pivotal role in providing protection against infection with intracellular pathogens and some tumors. In many cases protective immunity is maintained for long periods of time (immunological memory). Over the past years, it has become evident that in order to fulfill these multiple tasks,distinct subsets of effector and memory T cells have to be generated. Until today, however, little is known about the underlying mechanisms of subset differentiation and the timing of lineage fate decisions. In this context, it is of special importance to determine at which level of clonal expansion functional and phenotypical heterogeneity is achieved. Different models for T cell subset diversification have been proposed; these differ mainly in the time point during priming and clonal expansion (prior, during, or beyond the first cell division) when differentiation programs are induced. Recently developed single-cell adoptive transfer technology has allowed us to demonstrate that individual precursor cell still bears the full plasticity to develop into a plethora different T cell subsets. This observation targets the shaping of T cell subset differentiation towards factors that are still operative beyond the first cell division. These findings have important implications for vaccine development, as the modulation of differentiation patterns towards distinct subsets could become a powerful strategy to enhance the efficacy and quality of vaccines.

  7. Stem cell-like gene expression in ovarian cancer predicts type II subtype and prognosis.

    Directory of Open Access Journals (Sweden)

    Matthew Schwede

    Full Text Available Although ovarian cancer is often initially chemotherapy-sensitive, the vast majority of tumors eventually relapse and patients die of increasingly aggressive disease. Cancer stem cells are believed to have properties that allow them to survive therapy and may drive recurrent tumor growth. Cancer stem cells or cancer-initiating cells are a rare cell population and difficult to isolate experimentally. Genes that are expressed by stem cells may characterize a subset of less differentiated tumors and aid in prognostic classification of ovarian cancer. The purpose of this study was the genomic identification and characterization of a subtype of ovarian cancer that has stem cell-like gene expression. Using human and mouse gene signatures of embryonic, adult, or cancer stem cells, we performed an unsupervised bipartition class discovery on expression profiles from 145 serous ovarian tumors to identify a stem-like and more differentiated subgroup. Subtypes were reproducible and were further characterized in four independent, heterogeneous ovarian cancer datasets. We identified a stem-like subtype characterized by a 51-gene signature, which is significantly enriched in tumors with properties of Type II ovarian cancer; high grade, serous tumors, and poor survival. Conversely, the differentiated tumors share properties with Type I, including lower grade and mixed histological subtypes. The stem cell-like signature was prognostic within high-stage serous ovarian cancer, classifying a small subset of high-stage tumors with better prognosis, in the differentiated subtype. In multivariate models that adjusted for common clinical factors (including grade, stage, age, the subtype classification was still a significant predictor of relapse. The prognostic stem-like gene signature yields new insights into prognostic differences in ovarian cancer, provides a genomic context for defining Type I/II subtypes, and potential gene targets which following further

  8. A computational approach to identifying gene-microRNA modules in cancer.

    Science.gov (United States)

    Jin, Daeyong; Lee, Hyunju

    2015-01-01

    MicroRNAs (miRNAs) play key roles in the initiation and progression of various cancers by regulating genes. Regulatory interactions between genes and miRNAs are complex, as multiple miRNAs can regulate multiple genes. In addtion, these interactions vary from patient to patient and even among patients with the same cancer type, as cancer development is a heterogeneous process. These relationships are more complicated because transcription factors and other regulatory molecules can also regulate miRNAs and genes. Hence, it is important to identify the complex relationships between genes and miRNAs in cancer. In this study, we propose a computational approach to constructing modules that represent these relationships by integrating the expression data of genes and miRNAs with gene-gene interaction data. First, we used a biclustering algorithm to construct modules consisting of a subset of genes and a subset of samples to incorporate the heterogeneity of cancer cells. Second, we combined gene-gene interactions to include genes that play important roles in cancer-related pathways. Then, we selected miRNAs that are closely associated with genes in the modules based on a Gaussian Bayesian network and Bayesian Information Criteria. When we applied our approach to ovarian cancer and glioblastoma (GBM) data sets, 33 and 54 modules were constructed, respectively. In these modules, 91% and 94% of ovarian cancer and GBM modules, respectively, were explained either by direct regulation between genes and miRNAs or by indirect relationships via transcription factors. In addition, 48.4% and 74.0% of modules from ovarian cancer and GBM, respectively, were enriched with cancer-related pathways, and 51.7% and 71.7% of miRNAs in modules were ovarian cancer-related miRNAs and GBM-related miRNAs, respectively. Finally, we extensively analyzed significant modules and showed that most genes in these modules were related to ovarian cancer and GBM. PMID:25611546

  9. A computational approach to identifying gene-microRNA modules in cancer.

    Directory of Open Access Journals (Sweden)

    Daeyong Jin

    2015-01-01

    Full Text Available MicroRNAs (miRNAs play key roles in the initiation and progression of various cancers by regulating genes. Regulatory interactions between genes and miRNAs are complex, as multiple miRNAs can regulate multiple genes. In addtion, these interactions vary from patient to patient and even among patients with the same cancer type, as cancer development is a heterogeneous process. These relationships are more complicated because transcription factors and other regulatory molecules can also regulate miRNAs and genes. Hence, it is important to identify the complex relationships between genes and miRNAs in cancer. In this study, we propose a computational approach to constructing modules that represent these relationships by integrating the expression data of genes and miRNAs with gene-gene interaction data. First, we used a biclustering algorithm to construct modules consisting of a subset of genes and a subset of samples to incorporate the heterogeneity of cancer cells. Second, we combined gene-gene interactions to include genes that play important roles in cancer-related pathways. Then, we selected miRNAs that are closely associated with genes in the modules based on a Gaussian Bayesian network and Bayesian Information Criteria. When we applied our approach to ovarian cancer and glioblastoma (GBM data sets, 33 and 54 modules were constructed, respectively. In these modules, 91% and 94% of ovarian cancer and GBM modules, respectively, were explained either by direct regulation between genes and miRNAs or by indirect relationships via transcription factors. In addition, 48.4% and 74.0% of modules from ovarian cancer and GBM, respectively, were enriched with cancer-related pathways, and 51.7% and 71.7% of miRNAs in modules were ovarian cancer-related miRNAs and GBM-related miRNAs, respectively. Finally, we extensively analyzed significant modules and showed that most genes in these modules were related to ovarian cancer and GBM.

  10. Enhancing OPeNDAP for Multi-Source Subset Selection

    Science.gov (United States)

    Fulker, D. W.

    2012-12-01

    For nearly two decades, web services built on OPeNDAP methods have increased the practicality of accessing scientific data from multiple, disparate sources. Data accessible via the Data Access Protocol (DAP) now include public holdings at NOAA, NASA, and many other organizations whose disciplinary foci are diverse. Central to the DAP's utility is its domain-neutral data model, which includes simple mechanisms for retrieving user-specified subsets of the source data. Though DAP allows whole-dataset retrievals in principle, network limitations and other constraints often make subsetting essential. DAP subsetting is particularly efficient where data are organized as multidimensional arrays, common for many kinds of satellite imagery and model outputs. The current version (DAP2) lets users define which array elements are returned by specifying their indices, skipping some (decimation) and/or limiting their ranges. This permits, e.g., rapid selection of a 2-D slice from a dataset organized as a 4-D hypercube, whose axes might correspond to three dimensions of space and one of time. Despite its power, DAP2 subsetting has significant limitations in cases where the subset of interest is not nicely defined by lines or hyperplanes that parallel the axes of the source array. Though DAP2 servers can allow specification of subset boundaries by coordinate values, rather than indices, the resulting subsets nonetheless must take the form of subarrays whose shapes are tightly linked to those of the source arrays. Ways to overcome these limitations are being considered in a project dubbed OPULS (OPeNDAP-Unidata Linked Servers), funded by NOAA. Project goals include DAP4 (the DAP2 successor) and a new, experimental form of subsetting. The latter addresses the case where the source data and the desired subset are irregular meshes (AKA UGRIDS or unstructured grids), whose shapes are defined polygonally. Though the experiment is a special case, where client and server both are aware of

  11. CXCR6 marks a novel subset of T-bet(lo)Eomes(hi) natural killer cells residing in human liver.

    Science.gov (United States)

    Stegmann, Kerstin A; Robertson, Francis; Hansi, Navjyot; Gill, Upkar; Pallant, Celeste; Christophides, Theodoros; Pallett, Laura J; Peppa, Dimitra; Dunn, Claire; Fusai, Giuseppe; Male, Victoria; Davidson, Brian R; Kennedy, Patrick; Maini, Mala K

    2016-01-01

    Natural killer cells (NK) are highly enriched in the human liver, where they can regulate immunity and immunopathology. We probed them for a liver-resident subset, distinct from conventional bone-marrow-derived NK. CXCR6+ NK were strikingly enriched in healthy and diseased liver compared to blood (p bright)CD16-CD57-), and expressed the tissue-residency marker CD69. CXCR6+ NK produced fewer cytotoxic mediators and pro-inflammatory cytokines than the non-liver-specific CXCR6- fraction. Instead CXCR6+ NK could upregulate TRAIL, a key death ligand in hepatitis pathogenesis. CXCR6 demarcated liver NK into two transcriptionally distinct populations: T-bet(hi)Eomes(lo)(CXCR6-) and T-bet(lo)Eomes(hi)(CXCR6+); the latter was virtually absent in the periphery. The small circulating CXCR6+ subset was predominantly T-bet(hi)Eomes(lo), suggesting its lineage was closer to CXCR6- peripheral than CXCR6+ liver NK. These data reveal a large subset of human liver-resident T-bet(lo)Eomes(hi) NK, distinguished by their surface expression of CXCR6, adapted for hepatic tolerance and inducible anti-viral immunity. PMID:27210614

  12. Unique Eomes+ NK cell subsets are present in uterus and decidua during early pregnancy

    Directory of Open Access Journals (Sweden)

    Elisa eMontaldo

    2016-01-01

    Full Text Available Decidual and uterine Natural Killer (NK cells have been shown to contribute to the successful pregnancy both in humans and mice. NK cells represent cytotoxic group 1 innate lymphoid cells (ILCs and are distinct from the recently described helper ILC1. Here we show that both in humans and mice the majority of group 1 ILC in endometrium/uterus and decidua express Eomesodermin (Eomes, thus suggesting that they are developmentally related to conventional NK cells. However, they differed from peripheral NK cells. In humans Eomes+ decidual NK cells expressed CD49a and other markers of tissue residency including CD103, integrin β7, CD9, and CD69. The expression of CD103 allows the identification of different subsets of IFNγ-producing Eomes+ NK cells. We show that TGFβ can sustain/induce CD103 and CD9 expression in decidual NK cells and decidual CD34-derived NK cells, indicating that the decidual microenvironment can instruct the phenotype of Eomes+ NK cells.In murine decidua and uterus, Eomes+ cells included CD49a-CD49b+ conventional NK cells and CD49a+ cells. Notably, Eomes+CD49a+cells were absent in spleen and liver. Decidual and uterine Eomes+CD49a+ cells could be dissected in two peculiar cell subsets according to CD49b expression. CD49a-CD49b+ cells are enriched in mature CD11bhighCD27low cells, while CD49a+CD49b- and CD49a+CD49b+ cells contain higher percentages of immature CD11blowCD27high cells, both in uterus and decidua. Moreover, Eomes+CD49a+CD49b- cells decrease during gestation, thus suggesting that this peculiar subset may be required in early pregnancy rather than on later phases. Conversely, a minor Eomes-CD49a+ ILC1 population present in decidua and uterus increases during pregnancy. CD49b-Eomes+/- cells produce mainly TNF, while CD49a-CD49b+ conventional NK cells and CD49a+CD49b+ cells produce both IFNγ and TNF. Thus, human and murine decidua contains unique subsets of group 1 ILCs, including Eomes+ and Eomes- cells, with peculiar

  13. Variance optimal sampling based estimation of subset sums

    CERN Document Server

    Cohen, Edith; Kaplan, Haim; Lund, Carsten; Thorup, Mikkel

    2008-01-01

    From a high volume stream of weighted items, we want to maintain a generic sample of a certain limited size $k$ that we can later use to estimate the total weight of arbitrary subsets. This is the classic context of on-line reservoir sampling, thinking of the generic sample as a reservoir. We present a reservoir sampling scheme providing variance optimal estimation of subset sums. More precisely, if we have seen $n$ items of the stream, then for any subset size $m$, our scheme based on $k$ samples minimizes the average variance over all subsets of size $m$. In fact, the optimality is against any off-line sampling scheme tailored for the concrete set of items seen: no off-line scheme based on $k$ samples can perform better than our on-line scheme when it comes to average variance over any subset size. Our scheme has no positive covariances between any pair of item estimates. Also, our scheme can handle each new item of the stream in $O(\\log k)$ time, which is optimal even on the word RAM.

  14. Chemokine-mediated distribution of dendritic cell subsets in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Meyer Werner

    2010-10-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC represents one of the most immunoresponsive cancers. Antigen-specific vaccination with dendritic cells (DCs in patients with metastatic RCC has been shown to induce cytotoxic T-cell responses associated with objective clinical responses. Thus, clinical trials utilizing DCs for immunotherapy of advanced RCCs appear to be promising; however, detailed analyses concerning the distribution and function of DC subsets in RCCs are lacking. Methods We characterized the distribution of the different immature and mature myeloid DC subsets in RCC tumour tissue and the corresponding normal kidney tissues. In further analyses, the expression of various chemokines and chemokine receptors controlling the migration of DC subsets was investigated. Results The highest numbers of immature CD1a+ DCs were found within RCC tumour tissue. In contrast, the accumulation of mature CD83+/DC-LAMP+ DCs were restricted to the invasive margin of the RCCs. The mature DCs formed clusters with proliferating T-cells. Furthermore, a close association was observed between MIP-3α-producing tumour cells and immature CCR6+ DC recruitment to the tumour bed. Conversely, MIP-3β and SLC expression was only detected at the tumour border, where CCR7-expressing T-cells and mature DCs formed clusters. Conclusion Increased numbers of immature DCs were observed within the tumour tissue of RCCs, whereas mature DCs were found in increased numbers at the tumour margin. Our results strongly implicate that the distribution of DC subsets is controlled by local lymphoid chemokine expression. Thus, increased expression of MIP-3α favours recruitment of immature DCs to the tumour bed, whereas de novo local expression of SLC and MIP-3β induces accumulation of mature DCs at the tumour margin forming clusters with proliferating T-cells reflecting a local anti-tumour immune response.

  15. Enrichment: Dealing with overcapacity

    International Nuclear Information System (INIS)

    Today's surplus of enrichment capacity will continue until at least the end of this century. This will challenge the ingenuity of the separative work unit (SWU) suppliers as they attempt to keep market share and remain profitable in a very competitive marketplace. The utilities will be faced with attractive choices, but making the best choice will require careful analysis and increased attention to market factors. Current demand projections will probably prove too high to the extent that more reactors are canceled or delayed. The DOE has the vast majority of the unused capacity, so it will feel the most immediate impact of this large surplus in productive capacity. The DOE has responded to these market challenges by planning another reorganization of its enriching operations. Without a major agreement among the governments affected by the current surplus in enrichment capacity, the future will see lower prices, more competitive terms, and the gradual substitution of centrifuge or laser enrichment for the gaseous diffusion plants. The competition that is forcing the gaseous diffusion prices down to marginal cost will provide the long-term price basis for the enrichment industry

  16. Optimal Orderings of k-subsets for Star Identification

    CERN Document Server

    Mueller, Joerg H; Simões, Luís F; Izzo, Dario

    2016-01-01

    Finding the optimal ordering of k-subsets with respect to an objective function is known to be an extremely challenging problem. In this paper we introduce a new objective for this task, rooted in the problem of star identification on spacecrafts: subsets of detected spikes are to be generated in an ordering that minimizes time to detection of a valid star constellation. We carry out an extensive analysis of the combinatorial optimization problem, and propose multiple algorithmic solutions, offering different quality-complexity trade-offs. Three main approaches are investigated: exhaustive search (branch and prune), goal-driven (greedy scene elimination, minimally intersecting subsets), and stateless algorithms which implicitly seek to satisfy the problem's goals (pattern shifting, base unrank). In practical terms, these last algorithms are found to provide satisfactory approximations to the ideal performance levels, at small computational costs.

  17. Cancer

    Science.gov (United States)

    ... Blood tests (which look for chemicals such as tumor markers) Bone marrow biopsy (for lymphoma or leukemia) Chest ... the case with skin cancers , as well as cancers of the lung, breast, and colon. If the tumor has spread ...

  18. Cancer

    Science.gov (United States)

    Cancer begins in your cells, which are the building blocks of your body. Normally, your body forms ... be benign or malignant. Benign tumors aren't cancer while malignant ones are. Cells from malignant tumors ...

  19. Investigating evolutionary conservation of dendritic cell subset identity and functions

    Directory of Open Access Journals (Sweden)

    Thien-Phong eVu Manh

    2015-06-01

    Full Text Available Dendritic cells (DC were initially defined as mononuclear phagocytes with a dendritic morphology and an exquisite efficiency for naïve T cell activation. DC encompass several subsets initially identified by their expression of specific cell surface molecules and later shown to excel in distinct functions and to develop under the instruction of different transcription factors or cytokines. Very few cell surface molecules are expressed in a specific manner on any immune cell type. Hence, to identify cell types, the sole use of a small number of cell surface markers in classical flow cytometry can be deceiving. Moreover, the markers currently used to define mononuclear phagocyte subsets vary depending on the tissue and animal species studied and even between laboratories. This has led to confusion in the definition of DC subset identity and in their attribution of specific functions. There is a strong need to identify a rigorous and consensus way to define mononuclear phagocyte subsets, with precise guidelines potentially applicable throughout tissues and species. We will discuss the advantages, drawbacks and complementarities of different methodologies: cell surface phenotyping, ontogeny, functional characterization and molecular profiling. We will advocate that gene expression profiling is a very rigorous, largely unbiased and accessible method to define the identity of mononuclear phagocyte subsets, which strengthens and refines surface phenotyping. It is uniquely powerful to yield new, experimentally testable, hypotheses on the ontogeny or functions of mononuclear phagocyte subsets, their molecular regulation and their evolutionary conservation. We propose defining cell populations based on a combination of cell surface phenotyping, expression analysis of hallmark genes and robust functional assays, in order to reach a consensus and integrate faster the huge but scattered knowledge accumulated by different laboratories on different cell types

  20. Oxygen enrichment incineration

    International Nuclear Information System (INIS)

    Oxygen enriched combustion technology has recently been used in waste incineration. To apply the oxygen enrichment on alpha-bearing waste incineration, which is being developed, a state-of-an-art review has been performed. The use of oxygen or oxygen-enriched air instead of air in incineration would result in increase of combustion efficiency and capacity, and reduction of off-gas product. Especially, the off-gas could be reduced below a quarter, which might reduce off-gas treatment facilities, and also increase an efficiency of off-gas treatment. However, the use of oxygen might also lead to local overheating and high nitrogen oxides (NOx) formation. To overcome these problems, an application of low NOx oxy-fuel burner and recycling of a part of off-gas to combustion chamber have been suggested

  1. Oxygen enrichment incineration

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeong Guk; Yang, Hee Chul; Park, Geun Il; Kim, Joon Hyung

    2000-10-01

    Oxygen enriched combustion technology has recently been used in waste incineration. To apply the oxygen enrichment on alpha-bearing waste incineration, which is being developed, a state-of-an-art review has been performed. The use of oxygen or oxygen-enriched air instead of air in incineration would result in increase of combustion efficiency and capacity, and reduction of off-gas product. Especially, the off-gas could be reduced below a quarter, which might reduce off-gas treatment facilities, and also increase an efficiency of off-gas treatment. However, the use of oxygen might also lead to local overheating and high nitrogen oxides (NOx) formation. To overcome these problems, an application of low NOx oxy-fuel burner and recycling of a part of off-gas to combustion chamber have been suggested.

  2. Laser and gas centrifuge enrichment

    Energy Technology Data Exchange (ETDEWEB)

    Heinonen, Olli [Senior Fellow, Belfer Center for Science and International Affairs, Harvard Kennedy School, Cambridge, Massachusetts (United States)

    2014-05-09

    Principles of uranium isotope enrichment using various laser and gas centrifuge techniques are briefly discussed. Examples on production of high enriched uranium are given. Concerns regarding the possibility of using low end technologies to produce weapons grade uranium are explained. Based on current assessments commercial enrichment services are able to cover the global needs of enriched uranium in the foreseeable future.

  3. Laser and gas centrifuge enrichment

    Science.gov (United States)

    Heinonen, Olli

    2014-05-01

    Principles of uranium isotope enrichment using various laser and gas centrifuge techniques are briefly discussed. Examples on production of high enriched uranium are given. Concerns regarding the possibility of using low end technologies to produce weapons grade uranium are explained. Based on current assessments commercial enrichment services are able to cover the global needs of enriched uranium in the foreseeable future.

  4. Segal Enriched Categories I

    CERN Document Server

    Bacard, Hugo V

    2010-01-01

    We develop a theory of enriched categories over a (higher) category M equipped with a class W of morphisms called homotopy equivalences. We call them Segal M_W -categories. Our motivation was to generalize the notion of "up-to-homotopy monoids" in a monoidal category M, introduced by Leinster. The formalism adopted generalizes the classical Segal categories and extends the theory of enriched category over a bicategory. In particular we have a linear version of Segal categories which did not exist so far. Our goal in this paper is to present the theory and provide some examples. Applications are reserved for the future.

  5. Advanced uranium enrichment processes

    International Nuclear Information System (INIS)

    Three advanced Uranium enrichment processes are dealt with in the report: AVLIS (Atomic Vapour LASER Isotope Separation), MLIS (Molecular LASER Isotope Separation) and PSP (Plasma Separation Process). The description of the physical and technical features of the processes constitutes a major part of the report. If further presents comparisons with existing industrially used enrichment technologies, gives information on actual development programmes and budgets and ends with a chapter on perspectives and conclusions. An extensive bibliography of the relevant open literature is added to the different subjects discussed. The report was drawn up by the nuclear research Centre (CEA) Saclay on behalf of the Commission of the European Communities

  6. Enriching Number Knowledge

    Science.gov (United States)

    Mack, Nancy K.

    2011-01-01

    Exploring number systems of other cultures can be an enjoyable learning experience that enriches students' knowledge of numbers and number systems in important ways. It helps students deepen mental computation fluency, knowledge of place value, and equivalent representations for numbers. This article describes how the author designed her…

  7. Designing job enrichment projects.

    Science.gov (United States)

    Clakeley, G L

    1988-01-01

    This paper describes a management strategy for a job satisfaction program utilized in a large occupational therapy department. The goal of the program is to retain satisfied, productive employees and reduce attrition of therapists and assistants. The use of job enrichment projects for occupational therapy assistants will be presented with brief descriptions of two projects. PMID:23944880

  8. Job Enrichment in Extension.

    Science.gov (United States)

    Fourman, Louis S.; Jones, Jo

    1997-01-01

    Interviews with 10 participants in Ohio State University's job enrichment program for midcareer extension agents found that 5 returned to their same jobs after the experience but only 2 felt challenged/renewed. Part-time participation while working made it difficult to balance responsibilities. More information and a structured orientation were…

  9. Enriching the Catalog

    Science.gov (United States)

    Tennant, Roy

    2004-01-01

    After decades of costly and time-consuming effort, nearly all libraries have completed the retrospective conversion of their card catalogs to electronic form. However, bibliographic systems still are really not much more than card catalogs on wheels. Enriched content that Amazon.com takes for granted--such as digitized tables of contents, cover…

  10. Methodology for content enrichment

    NARCIS (Netherlands)

    Nederbragt, H.; Heerlien, M.

    2010-01-01

    The STERNA project mainly focuses on enrichment of existing content of content holding organisations in the natural history domain. Therefore, developing a methodology on how to best integrate one’s content into the STERNA information space is an essential part of the project. This document is the o

  11. Effects of a Simulated Tennis Match on Lymphocyte Subset Measurements

    Science.gov (United States)

    Schafer, Mark; Kell, Holly; Navalta, James; Tibana, Ramires; Lyons, Scott; Arnett, Scott

    2014-01-01

    Tennis is an activity requiring both endurance and anaerobic components, which could have immunosuppressive effects postexercise. Purpose: The purpose of this investigation was to determine the effect of a simulated tennis match on apoptotic and migratory markers on lymphocyte subsets. Method: Male high school (n = 5) and college (n = 3) tennis…

  12. T-lymphocyte subsets, thymic size and breastfeeding in infancy

    DEFF Research Database (Denmark)

    Jeppesen, Dorthe Lisbeth; Hasselbalch, Helle; Lisse, Ida M;

    2004-01-01

    We followed the changes in concentration of T-lymphocyte subsets (CD4+ and CD8+ cells) in peripheral blood and thymus size during infancy. Previous studies have found increased thymus size in breastfed infants. The present study analyzed the association between breastfeeding and the number of CD4...

  13. Modelling subset multivariate ARCH model via the AIC principle

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    In this paper we consider the problem of identifying a parsimonious subset multivariate ARCH model based on the AIC principle. The proposed approach can reduce the number of parameters in the final ARCH specification and allows for non-constant correlations between the components. Some simulation results illustrate the viability of the proposed procedure.

  14. A SOAP Web Service for accessing MODIS land product subsets

    Energy Technology Data Exchange (ETDEWEB)

    SanthanaVannan, Suresh K [ORNL; Cook, Robert B [ORNL; Pan, Jerry Yun [ORNL; Wilson, Bruce E [ORNL

    2011-01-01

    Remote sensing data from satellites have provided valuable information on the state of the earth for several decades. Since March 2000, the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor on board NASA s Terra and Aqua satellites have been providing estimates of several land parameters useful in understanding earth system processes at global, continental, and regional scales. However, the HDF-EOS file format, specialized software needed to process the HDF-EOS files, data volume, and the high spatial and temporal resolution of MODIS data make it difficult for users wanting to extract small but valuable amounts of information from the MODIS record. To overcome this usability issue, the NASA-funded Distributed Active Archive Center (DAAC) for Biogeochemical Dynamics at Oak Ridge National Laboratory (ORNL) developed a Web service that provides subsets of MODIS land products using Simple Object Access Protocol (SOAP). The ORNL DAAC MODIS subsetting Web service is a unique way of serving satellite data that exploits a fairly established and popular Internet protocol to allow users access to massive amounts of remote sensing data. The Web service provides MODIS land product subsets up to 201 x 201 km in a non-proprietary comma delimited text file format. Users can programmatically query the Web service to extract MODIS land parameters for real time data integration into models, decision support tools or connect to workflow software. Information regarding the MODIS SOAP subsetting Web service is available on the World Wide Web (WWW) at http://daac.ornl.gov/modiswebservice.

  15. Clustering, Seriation, and Subset Extraction of Confusion Data

    Science.gov (United States)

    Brusco, Michael J.; Steinley, Douglas

    2006-01-01

    The study of confusion data is a well established practice in psychology. Although many types of analytical approaches for confusion data are available, among the most common methods are the extraction of 1 or more subsets of stimuli, the partitioning of the complete stimulus set into distinct groups, and the ordering of the stimulus set. Although…

  16. Combinatorial Identities Via Phi Functions and Relatively Prime Subsets

    CERN Document Server

    Bachraoui, Mohamed El

    2010-01-01

    Let $n$ be a positive integer and let $A$ be nonempty finite set of positive integers. We say that $A$ is relatively prime if $\\gcd(A) =1$ and that $A$ is relatively prime to $n$ if $\\gcd(A,n)=1$. In this work we count the number of nonempty subsets of $A$ which are relatively prime and the number of nonempty subsets of $A$ which are relatively prime to $n$. Related formulas are also obtained for the number of such subsets having some fixed cardinality. This extends previous work for the cases where $A$ is an interval or a set in arithmetic progression. Applications include: a) An exact formula is obtained for the number of elements of $A$ which are co-prime to $n$; note that this number is $\\phi(n)$ if $A=[1,n]$. b) Algebraic characterizations are found for a nonempty finite set of positive integers to have elements which are all pairwise co-prime and consequently a formula is given for the number of nonempty subsets of $A$ whose elements are pairwise co-prime. c) We provide combinatorial formulas involving ...

  17. Discovering cancer genes by integrating network and functional properties

    Directory of Open Access Journals (Sweden)

    Davis David P

    2009-09-01

    Full Text Available Abstract Background Identification of novel cancer-causing genes is one of the main goals in cancer research. The rapid accumulation of genome-wide protein-protein interaction (PPI data in humans has provided a new basis for studying the topological features of cancer genes in cellular networks. It is important to integrate multiple genomic data sources, including PPI networks, protein domains and Gene Ontology (GO annotations, to facilitate the identification of cancer genes. Methods Topological features of the PPI network, as well as protein domain compositions, enrichment of gene ontology categories, sequence and evolutionary conservation features were extracted and compared between cancer genes and other genes. The predictive power of various classifiers for identification of cancer genes was evaluated by cross validation. Experimental validation of a subset of the prediction results was conducted using siRNA knockdown and viability assays in human colon cancer cell line DLD-1. Results Cross validation demonstrated advantageous performance of classifiers based on support vector machines (SVMs with the inclusion of the topological features from the PPI network, protein domain compositions and GO annotations. We then applied the trained SVM classifier to human genes to prioritize putative cancer genes. siRNA knock-down of several SVM predicted cancer genes displayed greatly reduced cell viability in human colon cancer cell line DLD-1. Conclusion Topological features of PPI networks, protein domain compositions and GO annotations are good predictors of cancer genes. The SVM classifier integrates multiple features and as such is useful for prioritizing candidate cancer genes for experimental validations.

  18. [Cancer].

    Science.gov (United States)

    de la Peña-López, Roberto; Remolina-Bonilla, Yuly Andrea

    2016-09-01

    Cancer is a group of diseases which represents a significant public health problem in Mexico and worldwide. In Mexico neoplasms are the second leading cause of death. An increased morbidity and mortality are expected in the next decades. Several preventable risk factors for cancer development have been identified, the most relevant including tobacco use, which accounts for 30% of the cancer cases; and obesity, associated to another 30%. These factors, in turn, are related to sedentarism, alcohol abuse and imbalanced diets. Some agents are well knokn to cause cancer such as ionizing radiation, viruses such as the papilloma virus (HPV) and hepatitis virus (B and C), and more recently environmental pollution exposure and red meat consumption have been pointed out as carcinogens by the International Agency for Research in Cancer (IARC). The scientific evidence currently available is insufficient to consider milk either as a risk factor or protective factor against different types of cancer. PMID:27603890

  19. IL-10 conditioning of human skin affects the distribution of migratory dendritic cell subsets and functional T cell differentiation.

    Directory of Open Access Journals (Sweden)

    Jelle J Lindenberg

    Full Text Available In cancer patients pervasive systemic suppression of Dendritic Cell (DC differentiation and maturation can hinder vaccination efficacy. In this study we have extensively characterized migratory DC subsets from human skin and studied how their migration and T cell-stimulatory abilities were affected by conditioning of the dermal microenvironment through cancer-related suppressive cytokines. To assess effects in the context of a complex tissue structure, we made use of a near-physiological skin explant model. By 4-color flow cytometry, we identified migrated Langerhans Cells (LC and five dermis-derived DC populations in differential states of maturation. From a panel of known tumor-associated suppressive cytokines, IL-10 showed a unique ability to induce predominant migration of an immature CD14(+CD141(+DC-SIGN(+ DC subset with low levels of co-stimulatory molecules, up-regulated expression of the co-inhibitory molecule PD-L1 and the M2-associated macrophage marker CD163. A similarly immature subset composition was observed for DC migrating from explants taken from skin overlying breast tumors. Whereas predominant migration of mature CD1a(+ subsets was associated with release of IL-12p70, efficient Th cell expansion with a Th1 profile, and expansion of functional MART-1-specific CD8(+ T cells, migration of immature CD14(+ DDC was accompanied by increased release of IL-10, poor expansion of CD4(+ and CD8(+ T cells, and skewing of Th responses to favor coordinated FoxP3 and IL-10 expression and regulatory T cell differentiation and outgrowth. Thus, high levels of IL-10 impact the composition of skin-emigrated DC subsets and appear to favor migration of M2-like immature DC with functional qualities conducive to T cell tolerance.

  20. Genome-wide Analysis Identifies Novel Loci Associated with Ovarian Cancer Outcomes

    DEFF Research Database (Denmark)

    Johnatty, Sharon E; Tyrer, Jonathan P; Kar, Siddhartha;

    2015-01-01

    PURPOSE: Chemotherapy resistance remains a major challenge in the treatment of ovarian cancer. We hypothesize that germline polymorphisms might be associated with clinical outcome. EXPERIMENTAL DESIGN: We analyzed approximately 2.8 million genotyped and imputed SNPs from the iCOGS experiment...... at standard doses. We evaluated the top SNPs in 4,434 EOC patients, including patients from The Cancer Genome Atlas. In addition, we conducted pathway analysis of all intragenic SNPs and tested their association with PFS and OS using gene set enrichment analysis. RESULTS: Five SNPs were significantly...... for progression-free survival (PFS) and overall survival (OS) in 2,901 European epithelial ovarian cancer (EOC) patients who underwent first-line treatment of cytoreductive surgery and chemotherapy regardless of regimen, and in a subset of 1,098 patients treated with ≥ 4 cycles of paclitaxel and carboplatin...

  1. A reassessment of IgM memory subsets in humans

    Science.gov (United States)

    Bagnara, Davide; Squillario, Margherita; Kipling, David; Mora, Thierry; Walczak, Aleksandra M.; Da Silva, Lucie; Weller, Sandra; Dunn-Walters, Deborah K.; Weill, Jean-Claude; Reynaud, Claude-Agnès

    2015-01-01

    From paired blood and spleen samples from three adult donors we performed high-throughput V-h sequencing of human B-cell subsets defined by IgD and CD27 expression: IgD+CD27+ (“MZ”), IgD−CD27+(“memory”, including IgM (“IgM-only”), IgG and IgA) and IgD−CD27− cells (“double-negative”, including IgM, IgG and IgA). 91,294 unique sequences clustered in 42,670 clones, revealing major clonal expansions in each of these subsets. Among these clones, we further analyzed those shared sequences from different subsets or tissues for Vh-gene mutation, H-CDR3-length, and Vh/Jh usage, comparing these different characteristics with all sequences from their subset of origin, for which these parameters constitute a distinct signature. The IgM-only repertoire profile differed notably from that of MZ B cells by a higher mutation frequency, and lower Vh4 and higher Jh6 gene usage. Strikingly, IgM sequences from clones shared between the MZ and the memory IgG/IgA compartments showed a mutation and repertoire profile of IgM-only and not of MZ B cells. Similarly, all IgM clonal relationships (between MZ, IgM-only, and double-negative compartments) involved sequences with the characteristics of IgM-only B cells. Finally, clonal relationships between tissues suggested distinct recirculation characteristics between MZ and switched B cells. The “IgM-only” subset (including cells with its repertoire signature but higher IgD or lower CD27 expression levels) thus appear as the only subset showing precursor-product relationships with CD27+ switched memory B cells, indicating that they represent germinal center-derived IgM memory B cells, and that IgM memory and MZ B cells constitute two distinct entities. PMID:26355154

  2. Implementing Modifed Burg Algorithms in Multivariate Subset Autoregressive Modeling

    Directory of Open Access Journals (Sweden)

    A. Alexandre Trindade

    2003-02-01

    Full Text Available The large number of parameters in subset vector autoregressive models often leads one to procure fast, simple, and efficient alternatives or precursors to maximum likelihood estimation. We present the solution of the multivariate subset Yule-Walker equations as one such alternative. In recent work, Brockwell, Dahlhaus, and Trindade (2002, show that the Yule-Walker estimators can actually be obtained as a special case of a general recursive Burg-type algorithm. We illustrate the structure of this Algorithm, and discuss its implementation in a high-level programming language. Applications of the Algorithm in univariate and bivariate modeling are showcased in examples. Univariate and bivariate versions of the Algorithm written in Fortran 90 are included in the appendix, and their use illustrated.

  3. Auditing Complex Concepts in Overlapping Subsets of SNOMED

    Science.gov (United States)

    Wang, Yue; Wei, Duo; Xu, Junchuan; Elhanan, Gai; Perl, Yehoshua; Halper, Michael; Chen, Yan; Spackman, Kent A.; Hripcsak, George

    2008-01-01

    Limited resources and the sheer volume of concepts make auditing a large terminology, such as SNOMED CT, a daunting task. It is essential to devise techniques that can aid an auditor by automatically identifying concepts that deserve attention. A methodology for this purpose based on a previously introduced abstraction network (called the p-area taxonomy) for a SNOMED CT hierarchy is presented. The methodology algorithmically gathers concepts appearing in certain overlapping subsets, defined exclusively with respect to the p-area taxonomy, for review. The results of applying the methodology to SNOMED’s Specimen hierarchy are presented. These results are compared against a control sample composed of concepts residing in subsets without the overlaps. With the use of the double bootstrap, the concept group produced by our methodology is shown to yield a statistically significant higher proportion of error discoveries. PMID:18998838

  4. Enrichment marketplace - today (and tomorrow)

    International Nuclear Information System (INIS)

    The technologies and capacities of the four primary sources of enrichment services, the United States Department of Energy, Eurodif, Techsnabexport of the Soviet Union, and Urenco, were given. Forecasts of future capacities and prices of enriched uranium were also included

  5. The separator of a subset of a semigroup

    OpenAIRE

    Nagy, Attila

    2015-01-01

    In this paper we introduce a new notion by the help of the idealizer. This new notion is the separator of a subset of a semigroup. We investigate the properties of the separator in an arbitrary semigroup and characterize the unitary subsemigroups and the prime ideals by the help of their separator. The last section of this paper treats the separator of a free subsemigroup of a free semigroup.

  6. Differentiable structure of ω-subsets of symplectic groups

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In this paper, we study the differentiable structure of theω-subset of Sp(2n), which is formed by all matrices in Sp(2n) possessing ω as an eigenvalue, for ω on the unit circle in the complex plane. Based on this result the ω-index theory parametrized by all ω on the unit circle for arbitrary symplectic paths is defined.

  7. Genetic Diversity in A Core Subset of Wild Barley Germplasm

    OpenAIRE

    Fu, Yong-Bi; Horbach, Carolee

    2012-01-01

    Wild barley [Hordeum vulgare ssp. spontaneum (C. Koch) Thell.] is a part of the primary gene pool with valuable sources of beneficial genes for barley improvement. This study attempted to develop a core subset of 269 accessions representing 16 countries from the Plant Gene Resources of Canada (PGRC) collection of 3,782 accessions, and to characterize them using barley simple sequence repeat (SSR) markers. Twenty-five informative primer pairs were applied to screen all samples and 359 alleles ...

  8. Genetic Diversity in A Core Subset of Wild Barley Germplasm

    OpenAIRE

    Yong-Bi Fu; Carolee Horbach

    2012-01-01

    Wild barley [Hordeum vulgare ssp. spontaneum (C. Koch) Thell.] is a part of the primary gene pool with valuable sources of beneficial genes for barley improvement. This study attempted to develop a core subset of 269 accessions representing 16 countries from the Plant Gene Resources of Canada (PGRC) collection of 3,782 accessions, and to characterize them using barley simple sequence repeat (SSR) markers. Twenty-five informative p...

  9. Ordered subsets convex algorithm for 3D terahertz transmission tomography

    OpenAIRE

    Recur, Benoît; Balacey, Hugo; Bou Sleiman, Joyce; Perraud, Jean-Baptiste; Guillet, Jean-Paul; Kingston, Andrew; Mounaix, Patrick

    2014-01-01

    International audience We investigate in this paper a new reconstruction method in order to perform 3D Terahertz (THz) tomography using a continuous wave acquisition setup in transmission mode. This method is based on the Maximum Likelihood for TRansmission tomography (ML-TR) first developed for X-ray imaging. We optimize the Ordered Subsets Convex (OSC) implementation of the ML-TR by including the Gaussian propagation model of THz waves and take into account the intensity distributions of...

  10. T Helper Cell Subsets in Clinical Manifestations of Psoriasis

    Directory of Open Access Journals (Sweden)

    Marco Diani

    2016-01-01

    Full Text Available Psoriasis is a chronic inflammatory skin disease, which is associated with systemic inflammation and comorbidities, such as psoriatic arthritis and cardiovascular diseases. The autoimmune nature of psoriasis has been established only recently, conferring a central role to epidermal CD8 T cells recognizing self-epitopes in the initial phase of the disease. Different subsets of helper cells have also been reported as key players in the psoriasis pathogenesis. Here, we reviewed the knowledge on the role of each subset in the psoriatic cascade and in the different clinical manifestations of the disease. We will discuss the role of Th1 and Th17 cells in the initiation and in the amplification phase of cutaneous inflammation. Moreover, we will discuss the recently proposed role of tissue resident Th22 cells in disease memory in sites of recurrent psoriasis and the possible involvement of Th9 cells. Finally, we will discuss the hypothesis of a link between T helper cell subsets recirculating from the skin and the systemic manifestations of psoriasis.

  11. T Helper Cell Subsets in Clinical Manifestations of Psoriasis

    Science.gov (United States)

    Diani, Marco; Altomare, Gianfranco

    2016-01-01

    Psoriasis is a chronic inflammatory skin disease, which is associated with systemic inflammation and comorbidities, such as psoriatic arthritis and cardiovascular diseases. The autoimmune nature of psoriasis has been established only recently, conferring a central role to epidermal CD8 T cells recognizing self-epitopes in the initial phase of the disease. Different subsets of helper cells have also been reported as key players in the psoriasis pathogenesis. Here, we reviewed the knowledge on the role of each subset in the psoriatic cascade and in the different clinical manifestations of the disease. We will discuss the role of Th1 and Th17 cells in the initiation and in the amplification phase of cutaneous inflammation. Moreover, we will discuss the recently proposed role of tissue resident Th22 cells in disease memory in sites of recurrent psoriasis and the possible involvement of Th9 cells. Finally, we will discuss the hypothesis of a link between T helper cell subsets recirculating from the skin and the systemic manifestations of psoriasis. PMID:27595115

  12. Preparation of Internal Quality Control Material for Lymphocyte Subset Analysis.

    Science.gov (United States)

    Roh, Eun Youn; Shin, Sue; Yoon, Jong Hyun; Oh, Sohee; Park, Kyoung Un; Lee, Nuri; Song, Eun Young

    2016-07-01

    Lymphocyte subset analysis is widely used in clinical laboratories, and more than two levels of daily QC materials are required for reliable results. Commercially available, expensive QC materials have short shelf lives and may not be suitable in resource-poor settings. We compared different methods for preparing homemade QC material, including fixation with 1%, 2%, or 4% paraformaldehyde (PFA); freezing with 10% dimethylsulfoxide (DMSO), 0.1% bovine serum albumin-phosphate buffered saline, or after ethanolic dehydration; and using cryopreservation temperatures of -20°C, -80°C, or -196°C. We found an optimal experimental condition, which is 'fixation with 4% PFA, freezing with 10% DMSO, and storage at 80°C'. To evaluate long-term stability of QC materials prepared in this optimal condition, two levels of QC materials (QM1 and QM2) were thawed after 30, 33, 35, 37, 60, 62, 64, and 67 days of cryopreservation. Lymphocyte subset was analyzed with BD Multitest IMK kit (BD Biosciences, USA). QM1 and QM2 were stable after 1-2 months of cryopreservation (CV materials for lymphocyte subset analysis in resource-poor settings.

  13. Chemoresistance of CD133+ cancer stem cells in laryngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    YANG Jing-pu; LIU Yan; ZHONG Wei; YU Dan; WEN Lian-ji; JIN Chun-shun

    2011-01-01

    Background Mounting evidence suggests that tumors are histologically heterogeneous and are maintained by a small population of tumor cells termed cancer stem cells. CD133 has been identified as a candidate marker of cancer stem cells in laryngeal carcinoma. This study aimed to analyze the chemoresistance of CD133+ cancer stem cells.Methods The response of Hep-2 cells to different chemotherapeutic agents was investigated and the expression of CD133 was studied. Fluorescence-activated cell sorting analysis was used to identify CD133,and the CD133+ subset of cells was separated and analyzed in colony formation assays,cell invasion assays,chemotherapy resistance studies,and analyzed for the expression of the drug resistance gene ABCG2.Results About 1%-2% of Hep-2 cells were CD133+ cells,and the CD133+ proportion was enriched by chemotherapy.CD133+ cancer stem cells exhibited higher potential for clonogenicity and invasion,and were more resistant to chemotherapy. This resistance was correlated with higher expression of ABCG2.Conclusions This study suggested that CD133+ cancer stem cells are more resistant to chemotherapy. The expression of ABCG2 could be partially responsible for this. Targeting this small population of CD133+ cancer stem cells could be a strategy to develop more effective treatments for laryngeal carcinoma.

  14. Expression of CD11c Is Associated with Unconventional Activated T Cell Subsets with High Migratory Potential

    Science.gov (United States)

    Cantero, Jon; Tarrats, Antoni; Fernández, Marco Antonio; Sumoy, Lauro; Rodolosse, Annie; McSorley, Stephen J.

    2016-01-01

    CD11c is an α integrin classically employed to define myeloid dendritic cells. Although there is little information about CD11c expression on human T cells, mouse models have shown an association of CD11c expression with functionally relevant T cell subsets. In the context of genital tract infection, we have previously observed increased expression of CD11c in circulating T cells from mice and women. Microarray analyses of activated effector T cells expressing CD11c derived from naïve mice demonstrated enrichment for natural killer (NK) associated genes. Here we find that murine CD11c+ T cells analyzed by flow cytometry display markers associated with non-conventional T cell subsets, including γδ T cells and invariant natural killer T (iNKT) cells. However, in women, only γδ T cells and CD8+ T cells were enriched within the CD11c fraction of blood and cervical tissue. These CD11c+ cells were highly activated and had greater interferon (IFN)-γ secretory capacity than CD11c- T cells. Furthermore, circulating CD11c+ T cells were associated with the expression of multiple adhesion molecules in women, suggesting that these cells have high tissue homing potential. These data suggest that CD11c expression distinguishes a population of circulating T cells during bacterial infection with innate capacity and mucosal homing potential. PMID:27119555

  15. Characterization of a chromosome-specific chimpanzee alpha satellite subset: Evolutionary relationship to subsets on human chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Warburton, P.E.; Gosden, J.; Lawson, D. [Western General Hospital, Edinburgh (United Kingdom)] [and others

    1996-04-15

    Alpha satellite DNA is a tandemly repeated DNA family found at the centromeres of all primate chromosomes examined. The fundamental repeat units of alpha satellite DNA are diverged 169- to 172-bp monomers, often found to be organized in chromosome-specific higher-order repeat units. The chromosomes of human (Homo sapiens (HSA)), chimpanzee (Pan troglodytes (PTR) and Pan paniscus), and gorilla (Gorilla gorilla) share a remarkable similarity and synteny. It is of interest to ask if alpha satellite arrays at centromeres of homologous chromosomes between these species are closely related (evolving in an orthologous manner) or if the evolutionary processes that homogenize and spread these arrays within and between chromosomes result in nonorthologous evolution of arrays. By using PCR primers specific for human chromosome 17-specific alpha satellite DNA, we have amplified, cloned, and characterized a chromosome-specific subset from the PTR chimpanzee genome. Hybridization both on Southern blots and in situ as well as sequence analysis show that this subset is most closely related, as expected, to sequences on HSA 17. However, in situ hybridization reveals that this subset is not found on the homologous chromosome in chimpanzee (PTR 19), but instead on PTR 12, which is homologous to HSA 2p. 40 refs., 3 figs.

  16. A short and valid measure of work-family enrichment.

    Science.gov (United States)

    Kacmar, K Michele; Crawford, Wayne S; Carlson, Dawn S; Ferguson, Merideth; Whitten, Dwayne

    2014-01-01

    The stream of research concerning work-family enrichment has generated a significant body of research because it plays an important role in occupational health (Masuda, McNall, Allen, & Nicklin, 2012). work-family enrichment has been defined as "the extent to which experiences in one role improve the quality of life in the other role" (Greenhaus & Powell, 2006, p. 73). Within work-family enrichment, there are two directions: work to family and family to work. Carlson, Kacmar, Wayne, and Grzywacz (2006) developed an 18-item scale to measure this construct. Although the scale has been shown to be both reliable and valid, it also requires work-family researchers to include a proportionally large number of items to capture this construct in a study. The goal of the current study was to isolate a subset of the items in this measure that produces results similar to the full version thereby providing a more streamlined scale for researchers. Using a five-sample study that follows the scale reduction procedures offered by Stanton, Sinar, Balzer, and Smith (2002), we provide evidence that scales containing only three items for each direction of enrichment produce results equivalent to the full scale with respect to reliability and discriminant, convergent, and predictive validity. Reducing the original scale by two thirds, without losing explanatory power, allows scholars to measure enrichment in the work and family domains more efficiently, which should help minimize survey time, lower refusal rates, and generate less missing data.

  17. Uranium enrichment by gas centrifuge

    International Nuclear Information System (INIS)

    After recalling the physical principles and the techniques of centrifuge enrichment the report describes the centrifuge enrichment programmes of the various countries concerned and compares this technology with other enrichment technologies like gaseous diffusion, laser, aerodynamic devices and chemical processes. The centrifuge enrichment process is said to be able to replace with advantage the existing enrichment facilities in the short and medium term. Future prospects of the process are also described, like recycled uranium enrichment and economic improvements; research and development needs to achieve the economic prospects are also indicated. Finally the report takes note of the positive aspect of centrifuge enrichment as far as safeguards and nuclear safety are concerned. 27 figs, 113 refs

  18. Influenza a virus induces an immediate cytotoxic activity in all major subsets of peripheral blood mononuclear cells.

    Directory of Open Access Journals (Sweden)

    Sanda Sturlan

    Full Text Available BACKGROUND: A replication defective influenza A vaccine virus (delNS1 virus was developed. Its attenuation is due to potent stimulation of the innate immune system by the virus. Since the innate immune system can also target cancer cells, we reasoned that delNS1 virus induced immune-stimulation should also lead to the induction of innate cytotoxic effects towards cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: Peripheral blood mononuclear cells (PBMCs, isolated CD56+, CD3+, CD14+ and CD19+ subsets and different combinations of the above subsets were stimulated by delNS1, wild type (wt virus or heat inactivated virus and co-cultured with tumor cell lines in the presence or absence of antibodies against the interferon system. Stimulation of PBMCs by the delNS1 virus effectively induced cytotoxicity against different cancer cell lines. Surprisingly, virus induced cytotoxicity was exerted by all major subtypes of PBMCs including CD56+, CD3+, CD14+ and CD19+ cells. Virus induced cytotoxicity in CD3+, CD14+ and CD19+ cells was dependent on virus replication, whereas virus induced cytotoxicity in CD56+ cells was only dependent on the binding of the virus. Virus induced cytotoxicity of isolated cell cultures of CD14+, CD19+ or CD56+ cells could be partially blocked by antibodies against type I and type II (IFN interferon. In contrast, virus induced cytotoxicity in the complete PBMC preparation could not be inhibited by blocking type I or type II IFN, indicating a redundant system of activation in whole blood. CONCLUSIONS/SIGNIFICANCE: Our data suggest that apart from their well known specialized functions all main subsets of peripheral blood cells also initially exert a cytotoxic effect upon virus stimulation. This closely links the innate immune system to the adaptive immune response and renders delNS1 virus a potential therapeutic tool for viro-immunotherapy of cancer.

  19. Flavonol-enriched fraction from Vaccinium macrocarpon fruit inhibits matrix metalloproteinase-2, matrix metalloproteinase-9 and urokinase-type plasminogen activator expression in human prostate cancer cells in vitro

    OpenAIRE

    James MacPhee; Colin R. Stetson; Benjamin W. Elwood; Kunal Patel; Jason McCallum; Catherine Neto; Robert A. R. Hurta

    2014-01-01

    Background: Prostate cancer, amongst other cancer types has a genetic and environmental component, which can contribute to prostate cancer development and progression. Vaccinum macrocarpon (American cranberry) is a botanical that contains several phytochemicals which have been suggested to play a role in preventing cardiovascular disease, cancer, and urinary tract infections as well as in the maintenance of oral health. Context and purpose of this study: This investigation evaluated th...

  20. T lymphocyte subset imbalances in patients contribute to ankylosing spondylitis.

    Science.gov (United States)

    Wang, Chenggong; Liao, Qiande; Hu, Yihe; Zhong, DA

    2015-01-01

    Ankylosing spondylitis is a chronic inflammatory rheumatic disease, which is characterized by inflammation of the spine and the sacroiliac joints. To date, the disease etiology remains unclear. In the present study, the correlation of T lymphocyte subset changes with the progression of ankylosing spondylitis was investigated. A total of 55 patients with ankylosing spondylitis (22 severe and 23 mild cases) and 20 healthy individuals were selected. Firstly, the punctured cells in the lesions and the serum were collected, and the lymphocytes and the peripheral blood mononuclear cells were prepared. Secondly, quantitative PCR, ELISA and flow cytometry analyses were carried out to detect the levels of a series of immunoglobulins, complements, helper T cells, cytotoxic T cells, regulatory cells and cytokines. The expression levels of α-globulin, γ-globulin, immunoglobulin (Ig)G, IgA, IgM, serum complement C3, and complement C4 were found to be significantly increased in ankylosing spondylitis patients. In addition, the percentage of Th1 and Th17 cells was found to be significantly higher in the ankylosing spondylitis groups (mild and severe) compared with the healthy individuals. As a result, the Th1/Th2 and Th17/Treg ratios were significantly higher in patients with ankylosing spondylitis. In addition, T lymphocyte subset ratio imbalances contributed to an increased expression of immune mediators, including interferon (IFN)-γ and interleukin (IL)-17A. The mRNA and protein expression levels of IFN-γ and IL-17A were found to be higher in the ankylosing spondylitis groups compared with the control group. The present study provided further evidence on the function and underlying mechanism of T lymphocyte subsets, which may be useful in the diagnosis and treatment of ankylosing spondylitis.

  1. Cytokine profile and lymphocyte subsets in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    C.O. Francisco

    2016-01-01

    Full Text Available Type 2 diabetes mellitus (T2D is a metabolic disease with inflammation as an important pathogenic background. However, the pattern of immune cell subsets and the cytokine profile associated with development of T2D are unclear. The objective of this study was to evaluate different components of the immune system in T2D patients' peripheral blood by quantifying the frequency of lymphocyte subsets and intracellular pro- and anti-inflammatory cytokine production by T cells. Clinical data and blood samples were collected from 22 men (51.6±6.3 years old with T2D and 20 nonsmoking men (49.4±7.6 years old who were matched for age and sex as control subjects. Glycated hemoglobin, high-sensitivity C-reactive protein concentrations, and the lipid profile were measured by a commercially available automated system. Frequencies of lymphocyte subsets in peripheral blood and intracellular production of interleukin (IL-4, IL-10, IL-17, tumor necrosis factor-α, and interferon-γ cytokines by CD3+ T cells were assessed by flow cytometry. No differences were observed in the frequency of CD19+ B cells, CD3+CD8+ and CD3+CD4+ T cells, CD16+56+ NK cells, and CD4+CD25+Foxp3+ T regulatory cells in patients with T2D compared with controls. The numbers of IL-10- and IL-17-producing CD3+ T cells were significantly higher in patients with T2D than in controls (P<0.05. The frequency of interferon-γ-producing CD3+ T cells was positively correlated with body mass index (r=0.59; P=0.01. In conclusion, this study shows increased numbers of circulating IL-10- and IL-17-producing CD3+ T cells in patients with T2D, suggesting that these cytokines are involved in the immune pathology of this disease.

  2. Dysregulation of microRNA expression drives aberrant DNA hypermethylation in basal-like breast cancer.

    Science.gov (United States)

    Sandhu, Rupninder; Rivenbark, Ashley G; Mackler, Randi M; Livasy, Chad A; Coleman, William B

    2014-02-01

    Basal-like breast cancers frequently express aberrant DNA hypermethylation associated with concurrent silencing of specific genes secondary to DNMT3b overexpression and DNMT hyperactivity. DNMT3b is known to be post-transcriptionally regulated by microRNAs. The objective of the current study was to determine the role of microRNA dysregulation in the molecular mechanism governing DNMT3b overexpression in primary breast cancers that express aberrant DNA hypermethylation. The expression of microRNAs (miRs) that regulate (miR-29a, miR-29b, miR-29c, miR-148a and miR-148b) or are predicted to regulate DNMT3b (miR‑26a, miR-26b, miR-203 and miR-222) were evaluated among 70 primary breast cancers (36 luminal A-like, 13 luminal B-like, 5 HER2‑enriched, 16 basal-like) and 18 normal mammoplasty tissues. Significantly reduced expression of miR-29c distinguished basal-like breast cancers from other breast cancer molecular subtypes. The expression of aberrant DNA hypermethylation was determined in a subset of 33 breast cancers (6 luminal A-like, 6 luminal B-like, 5 HER2-enriched and 16 basal-like) through examination of methylation‑sensitive biomarker gene expression (CEACAM6, CDH1, CST6, ESR1, GNA11, MUC1, MYB, TFF3 and SCNN1A), 11/33 (33%) cancers exhibited aberrant DNA hypermethylation including 9/16 (56%) basal-like cancers, but only 2/17 (12%) non-basal-like cancers (luminal A-like, n=1; HER2-enriched, n=1). Breast cancers with aberrant DNA hypermethylation express diminished levels of miR-29a, miR-29b, miR-26a, miR-26b, miR-148a and miR-148b compared to cancers lacking aberrant DNA hypermethylation. A total of 7/9 (78%) basal-like breast cancers with aberrant DNA hypermethylation exhibit diminished levels of ≥6 regulatory miRs. The results show that i) reduced expression of miR-29c is characteristic of basal-like breast cancers, ii) miR and methylation-sensitive gene expression patterns identify two subsets of basal-like breast cancers, and iii) the subset of basal

  3. Transcriptome Analysis Identifies the Dysregulation of Ultraviolet Target Genes in Human Skin Cancers

    Science.gov (United States)

    Shen, Yao; Kim, Arianna L.; Du, Rong; Liu, Liang

    2016-01-01

    Exposure to ultraviolet radiation (UVR) is a major risk factor for both melanoma and non-melanoma skin cancers. In addition to its mutagenic effect, UVR can also induce substantial transcriptional instability in skin cells affecting thousands of genes, including many cancer genes, suggesting that transcriptional instability may be another important etiological factor in skin photocarcinogenesis. In this study, we performed detailed transcriptomic profiling studies to characterize the kinetic changes in global gene expression in human keratinocytes exposed to different UVR conditions. We identified a subset of UV-responsive genes as UV signature genes (UVSGs) based on 1) conserved UV-responsiveness of this subset of genes among different keratinocyte lines; and 2) UV-induced persistent changes in their mRNA levels long after exposure. Interestingly, 11 of the UVSGs were shown to be critical to skin cancer cell proliferation and survival. Through computational Gene Set Enrichment Analysis, we demonstrated that a significant portion of the UVSGs were dysregulated in human skin squamous cell carcinomas, but not in other human malignancies. This highlights the potential and specificity of the UVSGs in clinical diagnosis of UV damage and stratification of skin cancer risk. PMID:27643989

  4. Transcriptome Analysis Identifies the Dysregulation of Ultraviolet Target Genes in Human Skin Cancers.

    Science.gov (United States)

    Shen, Yao; Kim, Arianna L; Du, Rong; Liu, Liang

    2016-01-01

    Exposure to ultraviolet radiation (UVR) is a major risk factor for both melanoma and non-melanoma skin cancers. In addition to its mutagenic effect, UVR can also induce substantial transcriptional instability in skin cells affecting thousands of genes, including many cancer genes, suggesting that transcriptional instability may be another important etiological factor in skin photocarcinogenesis. In this study, we performed detailed transcriptomic profiling studies to characterize the kinetic changes in global gene expression in human keratinocytes exposed to different UVR conditions. We identified a subset of UV-responsive genes as UV signature genes (UVSGs) based on 1) conserved UV-responsiveness of this subset of genes among different keratinocyte lines; and 2) UV-induced persistent changes in their mRNA levels long after exposure. Interestingly, 11 of the UVSGs were shown to be critical to skin cancer cell proliferation and survival. Through computational Gene Set Enrichment Analysis, we demonstrated that a significant portion of the UVSGs were dysregulated in human skin squamous cell carcinomas, but not in other human malignancies. This highlights the potential and specificity of the UVSGs in clinical diagnosis of UV damage and stratification of skin cancer risk. PMID:27643989

  5. Radioiodine-induced changes in lymphocyte subsets in patients with differentiated thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Tofani, A.; Sciuto, R.; Cioffi, R.P.; Pasqualoni, R.; Rea, S.; Festa, A.; Maini, C.L. [Department of Nuclear Medicine, Regina Elena Cancer Institute, Rome (Italy); Gandolfo, G.M.; Arista, M.C. [Department of Clinical Pathology, Regina Elena Cancer Institute, Rome (Italy)

    1999-08-01

    This study evaluated changes in lymphocyte subsets in patients with thyroid carcinoma who received iodine-131 for diagnostic and therapeutic purposes. Twenty thyroid cancer patients were entered in the study after total thyroidectomy: ten patients (group A) underwent whole-body scintigraphy with 185 MBq of {sup 131}I and the other ten (group B) received 3700 MBq of {sup 131}I therapy. All patients were in a hypothyroid state at the time of administration of {sup 131}I and started l-thyroxine 150 {mu}g/day 3 days after {sup 131}I administration. Free and bound triiodothyronine and thyroxine, thyroid-stimulating hormone, thyroglobulin, thyroglobulin antibodies, thyroid peroxidase/microsomal antibodies, white blood cell, lymphocyte counts and lymphocyte subsets were serially determined at baseline and at days 2, 7, 15, 30 and 60 after {sup 131}I administration. Twenty healthy age- and sex-matched individuals were used as a reference population for lymphocyte subset values. In group A only a reduction in NK cells at days 7 (P=0.043) and 15 (P=0.037) was observed. In group B, patients showed a delayed reduction in the total lymphocyte count at days 15, 30 and 60 (P=0.008, 0.004 and 0.018, respectively), and a decrease in B cells throughout the study (at days 7, 15, 30 and 60: P=0.006, 0.0017, 0.0017 and 0.0017 respectively). A transient decrease in NK cells was observed at days 15 (P=0.025) and 30 (P=0.008). Among T cells, the helper phenotype (CD4+) was mainly affected, resulting in a reduction in the CD4+/CD8+ ratio at day 60 (P=0.046). Comparing the two groups, the numbers of B lymphocytes at day 30 (P=0.023) and NK cells at days 2 (P=0.037) and 30 (P=0.023) were significantly lower in group B. Neither group showed any clinical sign of immunosuppression during the follow-up period. In patients with thyroid cancer the sensitivity of lymphocytes to the effects of {sup 131}I administered for diagnostic or therapeutic purposes depends upon lymphocyte phenotype and {sup

  6. Soluble Groups with a Condition on Infinite Subsets

    Institute of Scientific and Technical Information of China (English)

    Nadir Trabelsi

    2002-01-01

    We prove that a finitely generated soluble group G is nilpotent-by-finite (respectively, finite-by-nilpotent) if every infinite subset of G contains two elements x,y generating a nilpotent-by-finite (respectively, finite-by-nilpotent)group.Moreover,for a positive integer k,if we suppose is (nipotent of class k)-by-finite (respectively, finite-by-(nilpotent of class k)), then there is an integer c =c(k) such that G is (nilpotent of class c)-by-finite (respectively, finiteby-(nilpotent of class c)).

  7. CD163 positive subsets of blood dendritic cells

    DEFF Research Database (Denmark)

    Maniecki, Maciej Bogdan; Møller, Holger Jon; Moestrup, Søren Kragh;

    2006-01-01

    expression in dendritic cells (DCs) was investigated using multicolor flow cytometry in peripheral blood from 31 healthy donors and 15 HIV-1 patients in addition to umbilical cord blood from 5 newborn infants. Total RNA was isolated from MACS purified DCs and CD163 mRNA was determined with real-time reverse...... transcriptase polymerase chain reaction. The effect of glucocorticoid and phorbol ester stimulation on monocyte and dendritic cell CD163 and CD91 expression was investigated in cell culture of mononuclear cells using multicolor flow cytometry. We identified two CD163+ subsets in human blood with dendritic cell...

  8. A novel cell subset:Interferon-producing killer dendritic cells

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Recent reports introduce a novel cell subset of DCs with antigenic phenotypes shared by both NK cells and B cells, but without surface markers of pDCs and T cells, appearing to be a chimera of NK cells and DCs, namely interferon-producing killer dendritic cells(IKDCs).IKDCs not only secret type I and type II interferons to recognize and kill tumor cells effectively, but also express MHC-II molecules to present antigens.Thus, IKDCs are considered as important immunosurveilance cells for tumors, providing a link between innate and adaptive immunity.

  9. Optimum unambiguous discrimination between subsets of non-orthogonal states

    CERN Document Server

    Sun, Y; Hillery, M; Sun, Yuqing; Bergou, Janos; Hillery, Mark

    2001-01-01

    Unambiguous discrimination among non-orthogonal but linearly independent quantum states is possible with a certain probability of success. Here we consider a variant of that problem; rather than discriminating among all of the different states, we shall discriminate between two subsets of them. In particular, for the case of 3 states, we find the optimal strategy to distinguish one from the other two. This procedure has a higher probability of success than distinguishing all 3 states. We show how to construct generalized interferometers that provide an implementation of the optimal strategy.

  10. A novel cell subset: Interferon-producing killer dendritic cells

    Institute of Scientific and Technical Information of China (English)

    WANG JiongKun; XING FeiYue

    2008-01-01

    Recent reports introduce a novel cell subset of DCs with antigenic phenotypes shared by both NK cells and B cells, but without surface markers of pDCs and T cells, appearing to be a chimera of NK cells and DCs, namely interferon-producing killer dendritic cells (IKDCs). IKDCs not only secret type Ⅰ and type Ⅱ interferons to recognize and kill tumor cells effectively, but also express MHC-Ⅱ molecules to present antigens. Thus, IKDCs are considered as important immunosurveilance cells for tumors, providing a link between innate and adaptive immunity.

  11. Estimation of Discriminative Feature Subset Using Community Modularity

    Science.gov (United States)

    Zhao, Guodong; Liu, Sanming

    2016-04-01

    Feature selection (FS) is an important preprocessing step in machine learning and data mining. In this paper, a new feature subset evaluation method is proposed by constructing a sample graph (SG) in different k-features and applying community modularity to select highly informative features as a group. However, these features may not be relevant as an individual. Furthermore, relevant in-dependency rather than irrelevant redundancy among the selected features is effectively measured with the community modularity Q value of the sample graph in the k-features. An efficient FS method called k-features sample graph feature selection is presented. A key property of this approach is that the discriminative cues of a feature subset with the maximum relevant in-dependency among features can be accurately determined. This community modularity-based method is then verified with the theory of k-means cluster. Compared with other state-of-the-art methods, the proposed approach is more effective, as verified by the results of several experiments.

  12. Monocyte Subsets in Schistosomiasis Patients with Periportal Fibrosis

    Directory of Open Access Journals (Sweden)

    Jamille Souza Fernandes

    2014-01-01

    Full Text Available A major issue with Schistosoma mansoni infection is the development of periportal fibrosis, which is predominantly caused by the host immune response to egg antigens. Experimental studies have pointed to the participation of monocytes in the pathogenesis of liver fibrosis. The aim of this study was to characterize the subsets of monocytes in individuals with different degrees of periportal fibrosis secondary to schistosomiasis. Monocytes were classified into classical (CD14++CD16−, intermediate (CD14++CD16+, and nonclassical (CD14+CD16++. The expressions of monocyte markers and cytokines were assessed using flow cytometry. The frequency of classical monocytes was higher than the other subsets. The expression of HLA-DR, IL-6, TNF-α, and TGF-β was higher in monocytes from individuals with moderate to severe fibrosis as compared to other groups. Although no differences were observed in receptors expression (IL-4R and IL-10R between groups of patients, the expression of IL-12 was lower in monocytes from individuals with moderate to severe fibrosis, suggesting a protective role of this cytokine in the development of fibrosis. Our data support the hypothesis that the three different monocyte populations participate in the immunopathogenesis of periportal fibrosis, since they express high levels of proinflammatory and profibrotic cytokines and low levels of regulatory markers.

  13. Peripheral blood and milk leukocytes subsets of lactating Sarda ewes

    Directory of Open Access Journals (Sweden)

    Piero Bonelli

    2013-05-01

    Full Text Available Leukocytes subpopulations in blood and milk of lactating Sarda ewes were investigated. Animals characterized by a SSC level <500×103cells/mL and a negative bacteriological examination were sampled in early, mid and late lactation. Milk differential cell count evidenced that macrophage represented the main population (42.8%±3.5 followed by lymphocytes (40.2%±3.4 and neutrophils (8,6%±2.1. Flow cytometry analysis showed that lymphocytes subsets in milk were quite different from blood. High CD8+ and low CD4+ lymphocytes percentages determined a CD4/CD8 ratio inversion in milk compared to blood (0.3%±0.03 vs 1.8%±0.08. CD8+ decreased while, conversely, CD4+ increased in late lactation. γδ T cells were more represented in milk (12.6%±1.3 than in blood (6.8%±0.3 and their proportions appeared similar throughout lactation in both compartments. IL-2 receptor was mainly expressed in milk on T cytotoxic lymphocytes. Data obtained in uninfected mammary glands could allow an early discrimination between physiological and pathological changes occurring in ewe milk. Further phenotypical and functional studies on milk leukocytes subsets might help to understand defense mechanisms of the ovine mammary gland against IMI.

  14. Fast Edge Detection Based on the Combination of Fuzzy Subsets

    Institute of Scientific and Technical Information of China (English)

    TuChengyuan; ZengYanjun; PeiWei; XieJian

    2005-01-01

    A fast edge detection method basing on the combination of fuzzy subsets is developed, in which the detection of an edge as a classification problem will be considered, partitioning the image into two portions: the edge portion and the non-edge portion. The latter one, as the main constituent of an image, consists of the object and its background. Removing the non-edge portion from an image, the remainder is nothing but the edge of this image. As far as the fuzziness of the edge of an image is concerned, some fuzzy operations can be made. In this paper, the gray level histogram is partitioned into several sub-regions, and some operations are performed with the associated fuzzy subsets corresponding to those sub-edges in the sub-regions on the gray-level-square-difference histogrmn, and the edge of this image is finally obtained. Practical examples in this paper illustrate that, the described method is simple and effective to achieve an ideal edge image.

  15. Mast cell subsets and neuropeptides in leprosy reactions

    Directory of Open Access Journals (Sweden)

    Antunes Sérgio Luiz Gomes

    2003-01-01

    Full Text Available The immunohistochemical identification of neuropeptides (calcitonin gene-related peptide, vasoactive intestinal polypeptide, substance P, alpha-melanocyte stimulating hormone and gamma-melanocyte stimulating hormone quantification of mast cells and their subsets (tryptase/chymase-immunoreactive mast cells = TCMC and tryptase-immunoreactive mast cells = TMC were determined in biopsies of six patients with leprosy reactions (three patients with type I reaction and three with type II. Biopsies were compared with those taken from the same body site in the remission stage of the same patient. We found a relative increase of TMC in the inflammatory infiltrate of the reactional biopsies compared to the post-reactional biopsy. Also, the total number of mast cells and the TMC/TCMC ratio in the inflammatory infiltrate was significantly higher than in the intervening dermis of the biopsies of both periods. No significant difference was found regarding neuroptide expression in the reactional and post-reactional biopsies. The relative increase of TMC in the reactional infiltrates could implicate this mast cell subset in the reported increase of the immune response in leprosy reactions.

  16. Aldehyde dehydrogenase 1a3 defines a subset of failing pancreatic β cells in diabetic mice.

    Science.gov (United States)

    Kim-Muller, Ja Young; Fan, Jason; Kim, Young Jung R; Lee, Seung-Ah; Ishida, Emi; Blaner, William S; Accili, Domenico

    2016-01-01

    Insulin-producing β cells become dedifferentiated during diabetes progression. An impaired ability to select substrates for oxidative phosphorylation, or metabolic inflexibility, initiates progression from β-cell dysfunction to β-cell dedifferentiation. The identification of pathways involved in dedifferentiation may provide clues to its reversal. Here we isolate and functionally characterize failing β cells from various experimental models of diabetes and report a striking enrichment in the expression of aldehyde dehydrogenase 1 isoform A3 (ALDH(+)) as β cells become dedifferentiated. Flow-sorted ALDH(+) islet cells demonstrate impaired glucose-induced insulin secretion, are depleted of Foxo1 and MafA, and include a Neurogenin3-positive subset. RNA sequencing analysis demonstrates that ALDH(+) cells are characterized by: (i) impaired oxidative phosphorylation and mitochondrial complex I, IV and V; (ii) activated RICTOR; and (iii) progenitor cell markers. We propose that impaired mitochondrial function marks the progression from metabolic inflexibility to dedifferentiation in the natural history of β-cell failure. PMID:27572106

  17. 凸模糊子集的再定义%Convex Fuzzy Subsets Redefined

    Institute of Scientific and Technical Information of China (English)

    鞠红梅; 袁学海; 陈图云

    2001-01-01

    Definition of convex subsets based on t-norm is introduced. The properties of homomorphic image of this kind of convex subsets are discussed. Tm-convex fuzzy subsets generated by convex subset and Tm-convex fuzzy subsets generated by functions are studied. It is proved that each T∧-convex fuzzy subset is a Tm-convex fuzzy subset generated by convex subset.%给出基于t-范上的凸模糊子集的定义,讨论这种凸模糊子集的同态像性质,重点研究Tm-凸模糊子集的生成性,证明每一个T∧-凸模糊子集为凸子集生成的Tm-凸模糊子集。

  18. mIL-2R, T cell subsets & hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Chao-Pin Li; Ke-Xia Wang; Jian Wang; Bo-Rong Pan

    2002-01-01

    AIM: To study the levels of membrane interleukin-2 receptor(mIL-2R ) and T cell subsets in peripheral bloodmononuclear cells (PBMC) from patients with hepatitis Cand their role in the pathogenesis of hepatitis C.METHODS: The levels of mlL-2R and T cells subsets in PBMCWere detected by biotin- streptstividin (BSA) technique beforeand after stimulation with PHA in 203 patients with hepatitis Cwith HCV-RNA( + ), anti-HCV( + ), anti-HCV(-).RESULTS: The total expressive levels of mlL-2R before andafter stimulation with PHA(0.03 ± 0.01, 0.03 ± 0.02, 0.04 ± 0.02, 0.36±0.03), and Tcell subsets in PBMC (0.62±0.06,0.37 ± 0.05, 0.35 ± 0.07) were all lower in patients withhepatitis C than those in normal controls (0.66 ± 0.07, 0.41± 0.06, 0.31 ± 0.05, P < 0.01 ). Among the patients, thelevels of mlL-2R were lower in silence than those in situationof PHA inducting (P< 0.01). However, the levels of mlL-2Rwere similar in acute hepatitis C to that in chronic hepatitis C(P>0.05). The levels of CD3+, CD4+, CD4 +/CD8+ Were lov erand CD8 + was higher in patients with acute and chronichepatitis C with anti-HCV( + ) than those in normal controls (0.62±0.06, 0.37±0.05, 0.35±0.07, 1.18±0.30, 0.61±0.07, 0.37±0.05, 1.39±0.33, 0.31±0.05, P<0.05-P<0.01).CONCLUSION: The cellular immunity is obviously changed inpatients with hepatitis C. The levels of mlL-2R end activationof T cells am closely associated with chronicity of hepatitis C.

  19. Changes in T lymphocyte subsets after severe traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Yulu Miao; Mingxia Zhang; Yulin Nie; Wan Zhao; Bin Huang; Zhengming Jiang; Shaoxiong Yu; Zhibin Huang; Hongjin Fu

    2007-01-01

    BACKGROUND: Besides local changes of cranial parenchymal cells, hemorrhage, etc., severe traumatic brain injuries also cause the changes of total body fluid and various functions, and the changes of lymphocytes and T lymphocyte subsets should be paid more attention to.OBJECTIVE: To reveal the changing laws of T lymphocyte subsets after severe traumatic brain injury, and compare with mild to moderate brain injury.DESIGN: A comparative observation.SETTINGS: Department of Neurosurgery, Longgang District Buji People's Hospital of Shenzhen City;Central Laboratory of Shenzhen Hospital of Prevention and Cure for Chronic Disease.PARTICIPANTS: All the subjects were selected from the Department of Neurosurgery, Longgang District Buji People's Hospital of Shenzhen City from August 2002 to August 2005. Thirty patients with severe brain injury, whose Glasgow coma score (GCS) was ≤ 8 points, were taken as the experimental group, including 21 males and 9 females, aging 16 - 62 years. Meanwhile, 30 patients with mild traumatic brain injury were taken as the control group (GCS ranged 14 - 15 points), including 18 males and 12 females, aging 15 - 58 years. All the subjects were in admission at 6 hours after injury, without disease of major organs before injury.Informed consents were obtained from all the patients or their relatives.conditions of pulmonaryinfections were observed at 4 days after injury. The differences of measurement data were compared with the t test.MAIN OUTCOME MEASURES: Changes of T lymphocytes subsets at 1 - 14 days after severe and mild or moderate traumatic injury.RESULTS: Finally, 28 and 25 patients with mild to moderate traumatic brain injury, whereas 25 and 21 patients with severe traumatic brain injury were analyzed at 7 and 14 days respectively, and the missed ones CD3, CD4, CD8, CD4/CD8 began to decrease, whereas CD8 increased in the experimental group, which were very significantly different from those in the control group (t =2.77 - 3.26, P < 0

  20. Supervised Feature Subset Selection based on Modified Fuzzy Relative Information Measure for classifier Cart

    OpenAIRE

    K.SAROJINI,; Dr. K.THANGAVEL; D.DEVAKUMARI

    2010-01-01

    Feature subset selection is an essential task in data mining. This paper presents a new method for dealing with supervised feature subset selection based on Modified Fuzzy Relative Information Measure (MFRIM). First, Discretization algorithm is applied to discretize numeric features to construct the membership functions of each fuzzy sets of a feature. Then the proposed MFRIM is applied to select the feature subset focusing on boundary samples. The proposed method can select feature subset wi...

  1. A community study of T lymphocyte subsets and malaria parasitaemia

    DEFF Research Database (Denmark)

    Lisse, I M; Aaby, P; Whittle, H;

    1994-01-01

    In a community survey of 312 children aged 3-6 years in urban Guinea-Bissau, we examined Plasmodium falciparum parasitaemia and T cell subsets. 183 children (59%) had parasites in their blood, 13 had fever > or = 37.5 degrees C, and 9 (3%) had fever and a parasite density > 5000/microL (clinical....... Children with parasitaemia but without fever had a significantly lower percentage of CD4 cells than children without parasites (P = 0.031), but did not differ in any other haematological index. Controlling for other factors, the CD4 cell percentage was inversely correlated with the density of malaria...... malaria). Compared with children with no parasitaemia or asymptomatic parasitaemia, children with acute malaria had lymphopenia and significantly lower total CD4 and CD8 cell counts, but there was no significant difference in white blood cell count percentages of CD4 and CD8 cells, or the CD4/CD8 ratio...

  2. On curves contained in convex subsets of the plane

    CERN Document Server

    Coppersmith, Don; Ravsky, Alex

    2012-01-01

    If K' and K are convex bodies of the plane such that K' is a subset of K then the perimeter of K' is not greater than the perimeter of K. We obtain the following generalization of this fact. Let K be a convex compact body of the plane with the perimeter p and the diameter d and r>1 be an integer. Let s be the smallest number such that for any curve of length greater than s contained in K there is a straight line intersecting the curve at least in r+1 different points. Then s=rp/2 if r is even and s=(r-1)p/2+d if r is odd.

  3. Seronegative necrolytic acral erythema: A distinct clinical subset?

    Directory of Open Access Journals (Sweden)

    Panda S

    2010-01-01

    Full Text Available A patient was referred to us with asymptomatic, erythematous, nonitchy, scaly lesions present bilaterally on the dorsa of his feet and toes since the last 2 months. Both the legs had pitting edema as well. There were hyperkeratosis, focal parakeratosis, acanthosis and scattered spongiosis in the epidermis, and proliferation of capillaries with perivascular infiltration of lymphomononuclear cells in the dermis. There was no serological evidence of hepatitis C virus. Laboratory investigations revealed hypoalbuminemia and low-normal serum zinc. On clinicopathological correlation, we made a diagnosis of necrolytic acral erythema (NAE. The lesions responded dramatically to oral zinc sulfate and topical clobetasol propionate within 3 weeks with disappearance of edema and scaling and only a minimal residual erythema. This is the first reported case of NAE from Eastern India. NAE with negative serology for hepatitis C may be viewed as a distinct subset of the condition that had been originally described.

  4. REST represses a subset of the pancreatic endocrine differentiation program

    DEFF Research Database (Denmark)

    Martin, David; Kim, Yung-Hae; Sever, Dror;

    2015-01-01

    To contribute to devise successful beta-cell differentiation strategies for the cure of Type 1 diabetes we sought to uncover barriers that restrict endocrine fate acquisition by studying the role of the transcriptional repressor REST in the developing pancreas. Rest expression is prevented...... in neurons and in endocrine cells, which is necessary for their normal function. During development, REST represses a subset of genes in the neuronal differentiation program and Rest is down-regulated as neurons differentiate. Here, we investigate the role of REST in the differentiation of pancreatic...... endocrine cells, which are molecularly close to neurons. We show that Rest is widely expressed in pancreas progenitors and that it is down-regulated in differentiated endocrine cells. Sustained expression of REST in Pdx1(+) progenitors impairs the differentiation of endocrine-committed Neurog3...

  5. T-lymphocyte subsets, thymic size and breastfeeding in infancy

    DEFF Research Database (Denmark)

    Jeppesen, Dorthe Lisbeth; Hasselbalch, Helle; Lisse, Ida M;

    2004-01-01

    We followed the changes in concentration of T-lymphocyte subsets (CD4+ and CD8+ cells) in peripheral blood and thymus size during infancy. Previous studies have found increased thymus size in breastfed infants. The present study analyzed the association between breastfeeding and the number of CD4......+ and CD8+ cells. Two different populations of infants between birth and 1 year of age were examined. Study Group I: infants with a variable duration of breastfeeding. Study Group II: long-term breastfed infants. In both groups a correlation was found between CD8+ cells and the thymic index at 10 months...... from 8 to 10 months of age; and a positive correlation between the number of breastfeedings per day at 8 months of age, and an increase in CD4+ cells from 8 to 10 months of age (p <0.01). In conclusion, a correlation was found between thymus size and CD8+ cells. Breastfeeding might have both a current...

  6. 5-azacytidine induces anoikis, inhibits mammosphere formation and reduces metalloproteinase 9 activity in MCF-7 human breast cancer cells.

    Science.gov (United States)

    Chang, Hsueh-Wei; Wang, Hui-Chun; Chen, Chiau-Yi; Hung, Ting-Wei; Hou, Ming-Feng; Yuan, Shyng-Shiou F; Huang, Chih-Jen; Tseng, Chao-Neng

    2014-01-01

    Cancer stem cells are a subset of cancer cells that initiate the growth of tumors. Low levels of cancer stem cells also exist in established cancer cell lines, and can be enriched in serum-free tumorsphere cultures. Since cancer stem cells have been reported to be resilient to common chemotherapeutic drugs in comparison to regular cancer cells, screening for compounds selectively targeting cancer stem cells may provide an effective therapeutic strategy. We found that 5-azacytidine (5-AzaC) selectively induced anoikis of MCF-7 in suspension cultures with an EC₅₀ of 8.014 µM, and effectively inhibited tumorsphere formation, as well as the migration and matrix metalloproteinases-9 (MMP-9) activity of MCF-7 cells. Furthermore, 5-AzaC and radiation collaboratively inhibited MCF-7 tumorsphere formation at clinically relevant radiation doses. Investigating the underlying mechanism may provide insight into signaling pathways crucial for cancer stem cell survival and pave the way to novel potential therapeutic targets. PMID:24633350

  7. 5-Azacytidine Induces Anoikis, Inhibits Mammosphere Formation and Reduces Metalloproteinase 9 Activity in MCF-7 Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Hsueh-Wei Chang

    2014-03-01

    Full Text Available Cancer stem cells are a subset of cancer cells that initiate the growth of tumors. Low levels of cancer stem cells also exist in established cancer cell lines, and can be enriched in serum-free tumorsphere cultures. Since cancer stem cells have been reported to be resilient to common chemotherapeutic drugs in comparison to regular cancer cells, screening for compounds selectively targeting cancer stem cells may provide an effective therapeutic strategy. We found that 5-azacytidine (5-AzaC selectively induced anoikis of MCF-7 in suspension cultures with an EC50 of 8.014 µM, and effectively inhibited tumorsphere formation, as well as the migration and matrix metalloproteinases-9 (MMP-9 activity of MCF-7 cells. Furthermore, 5-AzaC and radiation collaboratively inhibited MCF-7 tumorsphere formation at clinically relevant radiation doses. Investigating the underlying mechanism may provide insight into signaling pathways crucial for cancer stem cell survival and pave the way to novel potential therapeutic targets.

  8. Distinct Oral Neutrophil Subsets Define Health and Periodontal Disease States.

    Science.gov (United States)

    Fine, N; Hassanpour, S; Borenstein, A; Sima, C; Oveisi, M; Scholey, J; Cherney, D; Glogauer, M

    2016-07-01

    Neutrophils exit the vasculature and swarm to sites of inflammation and infection. However, these cells are abundant in the healthy, inflammation-free human oral environment, suggesting a unique immune surveillance role within the periodontium. We hypothesize that neutrophils in the healthy oral cavity occur in an intermediary parainflammatory state that allows them to interact with and contain the oral microflora without eliciting a marked inflammatory response. Based on a high-throughput screen of neutrophil CD (cluster of differentiation) marker expression and a thorough literature review, we developed multicolor flow cytometry panels to determine the surface marker signatures of oral neutrophil subsets in periodontal health and disease. We define here 3 distinct neutrophil subsets: resting/naive circulatory neutrophils, parainflammatory neutrophils found in the healthy oral cavity, and proinflammatory neutrophils found in the oral cavity during chronic periodontal disease. Furthermore, parainflammatory neutrophils manifest as 2 distinct subpopulations-based on size, granularity, and expression of specific CD markers-and exhibit intermediate levels of activation as compared with the proinflammatory oral neutrophils. These intermediately activated parainflammatory populations occur in equal proportions in the healthy oral cavity, with a shift to one highly activated proinflammatory neutrophil population in chronic periodontal disease. This work is the first to identify and characterize oral parainflammatory neutrophils that interact with commensal biofilms without inducing an inflammatory response, thereby demonstrating that not all neutrophils trafficking through periodontal tissues are fully activated. In addition to establishing possible diagnostic and treatment monitoring biomarkers, this oral neutrophil phenotype model builds on existing literature suggesting that the healthy periodontium may be in a parainflammatory state. PMID:27270666

  9. Tachykinins stimulate a subset of mouse taste cells.

    Directory of Open Access Journals (Sweden)

    Jeff Grant

    Full Text Available The tachykinins substance P (SP and neurokinin A (NKA are present in nociceptive sensory fibers expressing transient receptor potential cation channel, subfamily V, member 1 (TRPV1. These fibers are found extensively in and around the taste buds of several species. Tachykinins are released from nociceptive fibers by irritants such as capsaicin, the active compound found in chili peppers commonly associated with the sensation of spiciness. Using real-time Ca(2+-imaging on isolated taste cells, it was observed that SP induces Ca(2+ -responses in a subset of taste cells at concentrations in the low nanomolar range. These responses were reversibly inhibited by blocking the SP receptor NK-1R. NKA also induced Ca(2+-responses in a subset of taste cells, but only at concentrations in the high nanomolar range. These responses were only partially inhibited by blocking the NKA receptor NK-2R, and were also inhibited by blocking NK-1R indicating that NKA is only active in taste cells at concentrations that activate both receptors. In addition, it was determined that tachykinin signaling in taste cells requires Ca(2+-release from endoplasmic reticulum stores. RT-PCR analysis further confirmed that mouse taste buds express NK-1R and NK-2R. Using Ca(2+-imaging and single cell RT-PCR, it was determined that the majority of tachykinin-responsive taste cells were Type I (Glial-like and umami-responsive Type II (Receptor cells. Importantly, stimulating NK-1R had an additive effect on Ca(2+ responses evoked by umami stimuli in Type II (Receptor cells. This data indicates that tachykinin release from nociceptive sensory fibers in and around taste buds may enhance umami and other taste modalities, providing a possible mechanism for the increased palatability of spicy foods.

  10. Earthquake forecast enrichment scores

    Directory of Open Access Journals (Sweden)

    Christine Smyth

    2012-03-01

    Full Text Available The Collaboratory for the Study of Earthquake Predictability (CSEP is a global project aimed at testing earthquake forecast models in a fair environment. Various metrics are currently used to evaluate the submitted forecasts. However, the CSEP still lacks easily understandable metrics with which to rank the universal performance of the forecast models. In this research, we modify a well-known and respected metric from another statistical field, bioinformatics, to make it suitable for evaluating earthquake forecasts, such as those submitted to the CSEP initiative. The metric, originally called a gene-set enrichment score, is based on a Kolmogorov-Smirnov statistic. Our modified metric assesses if, over a certain time period, the forecast values at locations where earthquakes have occurred are significantly increased compared to the values for all locations where earthquakes did not occur. Permutation testing allows for a significance value to be placed upon the score. Unlike the metrics currently employed by the CSEP, the score places no assumption on the distribution of earthquake occurrence nor requires an arbitrary reference forecast. In this research, we apply the modified metric to simulated data and real forecast data to show it is a powerful and robust technique, capable of ranking competing earthquake forecasts.

  11. CANCER

    Directory of Open Access Journals (Sweden)

    N. Kavoussi

    1973-09-01

    Full Text Available There are many carcinogenetic elements in industry and it is for this reason that study and research concerning the effect of these materials is carried out on a national and international level. The establishment and growth of cancer are affected by different factors in two main areas:-1 The nature of the human or animal including sex, age, point and method of entry, fat metabolism, place of agglomeration of carcinogenetic material, amount of material absorbed by the body and the immunity of the body.2 The different nature of the carcinogenetic material e.g. physical, chemical quality, degree of solvency in fat and purity of impurity of the element. As the development of cancer is dependent upon so many factors, it is extremely difficult to determine whether a causative element is principle or contributory. Some materials are not carcinogenetic when they are pure but become so when they combine with other elements. All of this creates an industrial health problem in that it is almost impossible to plan an adequate prevention and safety program. The body through its system of immunity protects itself against small amounts of carcinogens but when this amount increases and reaches a certain level the body is not longer able to defend itself. ILO advises an effective protection campaign against cancer based on the Well –equipped laboratories, Well-educated personnel, the establishment of industrial hygiene within factories, the regular control of safety systems, and the implementation of industrial health principles and research programs.

  12. Tumor initiating but differentiated luminal-like breast cancer cells are highly invasive in the absence of basal-like activity

    DEFF Research Database (Denmark)

    Kim, Jiyoung; Villadsen, René; Sørlie, Therese;

    2012-01-01

    The majority of human breast cancers exhibit luminal epithelial differentiation. However, most aggressive behavior, including invasion and purported cancer stem cell activity, are considered characteristics of basal-like cells. We asked the following questions: Must luminal-like breast cancer cells...... become basal-like to initiate tumors or to invade? Could luminally differentiated cells within a basally initiated hierarchy also be tumorigenic? To answer these questions, we used rare and mutually exclusive lineage markers to isolate subsets of luminal-like and basal-like cells from human breast tumors....... We enriched for populations with or without prominent basal-like traits from individual tumors or single cell cloning from cell lines and recovered cells with a luminal-like phenotype. Tumor cells with basal-like traits mimicked phenotypic and functional behavior associated with stem cells assessed...

  13. Ovarian cancer: emerging concept on cancer stem cells

    OpenAIRE

    Ponnusamy Moorthy P; Batra Surinder K

    2008-01-01

    Abstract Emerging evidence suggests that the capacity of a tumor to grow and propagate is dependent on a small subset of cells within a tumor, termed cancer stem cells. In fact, cancer cells, like stem cells, can proliferate indefinitely through a dysregulated cellular self-renewal capacity. Cancer stem cells may originate due to the distribution into self-renewal and differentiation pathways occurring in multi-potential stem cells, tissue-specific stem cells, progenitor cells and cancer cell...

  14. Hydrogen-enriched fuels

    Energy Technology Data Exchange (ETDEWEB)

    Roser, R. [NRG Technologies, Inc., Reno, NV (United States)

    1998-08-01

    NRG Technologies, Inc. is attempting to develop hardware and infrastructure that will allow mixtures of hydrogen and conventional fuels to become viable alternatives to conventional fuels alone. This commercialization can be successful if the authors are able to achieve exhaust emission levels of less than 0.03 g/kw-hr NOx and CO; and 0.15 g/kw-hr NMHC at full engine power without the use of exhaust catalysts. The major barriers to achieving these goals are that the lean burn regimes required to meet exhaust emissions goals reduce engine output substantially and tend to exhibit higher-than-normal total hydrocarbon emissions. Also, hydrogen addition to conventional fuels increases fuel cost, and reduces both vehicle range and engine output power. Maintaining low emissions during transient driving cycles has not been demonstrated. A three year test plan has been developed to perform the investigations into the issues described above. During this initial year of funding research has progressed in the following areas: (a) a cost effective single-cylinder research platform was constructed; (b) exhaust gas speciation was performed to characterize the nature of hydrocarbon emissions from hydrogen-enriched natural gas fuels; (c) three H{sub 2}/CH{sub 4} fuel compositions were analyzed using spark timing and equivalence ratio sweeping procedures and finally; (d) a full size pick-up truck platform was converted to run on HCNG fuels. The testing performed in year one of the three year plan represents a baseline from which to assess options for overcoming the stated barriers to success.

  15. Ultraconservation identifies a small subset of extremely constrained developmental enhancers

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.; Visel, Axel; Prabhakar, Shyam; Akiyama, Jennifer A.; Shoukry, Malak; Lewis, Keith D.; Holt, Amy; Plajzer-Frick, Ingrid; Afzal, Veena; Rubin, Edward M.; Pennacchio, Len A.

    2007-10-01

    While experimental studies have suggested that non-coding ultraconserved DNA elements are central nodes in the regulatory circuitry that specifies mammalian embryonic development, the possible functional relevance of their>200bp of perfect sequence conservation between human-mouse-rat remains obscure 1,2. Here we have compared the in vivo enhancer activity of a genome-wide set of 231 non-exonic sequences with ultraconserved cores to that of 206 sequences that are under equivalently severe human-rodent constraint (ultra-like), but lack perfect sequence conservation. In transgenic mouse assays, 50percent of the ultraconserved and 50percent of the ultra-like conserved elements reproducibly functioned as tissue-specific enhancers at embryonic day 11.5. In this in vivo assay, we observed that ultraconserved enhancers and constrained non-ultraconserved enhancers targeted expression to a similar spectrum of tissues with a particular enrichment in the developing central nervous system. A human genome-wide comparative screen uncovered ~;;2,600 non-coding elements that evolved under ultra-like human-rodent constraint and are similarly enriched near transcriptional regulators and developmental genes as the much smaller number of ultraconserved elements. These data indicate that ultraconserved elements possessing absolute human-rodent sequence conservation are not distinct from other non-coding elements that are under comparable purifying selection in mammals and suggest they are principal constituents of the cis-regulatory framework of mammalian development.

  16. A Short Note on Disjointness Conditions for Triples of Group Subsets Satisfying the Triple Product Property

    CERN Document Server

    Murthy, Sandeep

    2009-01-01

    We deduce some elementary pairwise disjointness and semi-disjointness conditions on triples of subsets in arbitrary groups satisfying the so-called triple product property (TPP) as originally defined by H. Cohn and C. Umans in 2003. This property TPP for a triple of group subsets, called a TPP triple, allows the group to "realize" matrix multiplication of dimensions the sizes of the subsets, with the subsets acting as indexing sets for input matrices which are embedded into the regular algebra of the group. We derive nine different disjointness casetypes for an arbitrary TPP triple, and classify these into four different disjointness classes based on an integer measure of the degree of pairwise disjointness among the subsets. Finally, we derive lower and upper bounds for the sum of sizes of the subsets forming a TPP triple, which is the additive equivalent of the multiplicative bounds originally derived by Cohn and Umans for the product of sizes of subsets forming a TPP triple.

  17. 术前热疗联合灌注化疗对非小细胞肺癌患者T淋巴细胞亚群及血清P53抗体水平的影响%Effects of preoperative infusion chemotherapy combined with hyperthermia on T lymphocyte subsets and serum P53 antibody level of non-small cell lung cancer patients

    Institute of Scientific and Technical Information of China (English)

    祝淮阳; 熊瑜

    2012-01-01

    目的:评估术前热疗联合灌注化疗对非小细胞肺癌患者免疫功能的影响.方法:选取中晚期非小细胞肺癌患者68例,31例(A组)术前给予单纯顺铂和丝裂霉素动脉灌注化疗;余37例(B组)灌注化疗前1 h和注药24 h后,用体外高频热疗机热疗1次.2组分别于灌注化疗前、术前1 天、术后第10天采集静脉血,应用间接免疫荧光法测定T淋巴细胞亚群;分别于灌注化疗前,术前1天,术后第10、30、60和90天抽取清晨空腹静脉血,应用ELISA法检测P53抗体水平.结果:A组术前CD3、CD4水平较灌注化疗前降低,CD8、CD4/CD8轻微升高;术后CD3、CD4及CD4/CD8水平升高,CD8降低.B组术前CD3、CD4水平较灌注化疗前明显增高,CD8降低,CD4/CD8升高;术后上述指标变化趋势未发生改变(P均<0.001).2组术后血清P53抗体水平均逐渐降低,B组较A组降低明显(F组间=52.735,F时间=9.297,F交互=4.219,P<0.001).结论:术前热疗联合灌注化疗可以改善晚期非小细胞肺癌患者的免疫力.%Aim:To study the effect of preoperalive infusion chemoltherapy combined with hyperlhermia on the immunnily of non-small cell lung cancer( NSCLC ) patients. Methods:A total of 68 patients with intermediate and advanced NSCLC were divided into ttwo groups. Croup A( n =31 ) was treated with inlervenlional arterial infusion chemotherapy alone. Group B( n = 37 ) was treated with transcatheter arterial infusion chemotherapy combined with hyperlhermia. The levels of the subsets of the peripheral blood T lymphocytes( CD3,CD4,CD8 )and the P53 antibody were delected by indirect immunofluorescence lech-nique and ELISA,respectively. Results:The CD3 and CD4 levels before operation were significantly lower than those before infusion chemotherapy in group A, CDS and CD4/CD8 were higher; but CD3, CD4 level and CD4/CD8 increased, and CD8 level decreased after operation. As to group li,CD3,CD4 and CD4/CD8 levels before operation were significantly higher than

  18. A Subset of Protective γ9δ2 T Cells Is Activated by Novel Mycobacterial Glycolipid Components.

    Science.gov (United States)

    Xia, Mei; Hesser, Danny C; De, Prithwiraj; Sakala, Isaac G; Spencer, Charles T; Kirkwood, Jay S; Abate, Getahun; Chatterjee, Delphi; Dobos, Karen M; Hoft, Daniel F

    2016-09-01

    γ9δ2 T cells provide a natural bridge between innate and adaptive immunity, rapidly and potently respond to pathogen infection in mucosal tissues, and are prominently induced by both tuberculosis (TB) infection and bacillus Calmette Guérin (BCG) vaccination. Mycobacterium-expanded γ9δ2 T cells represent only a subset of the phosphoantigen {isopentenyl pyrophosphate [IPP] and (E)-4-hydroxy-3-methyl-but-2-enylpyrophosphate [HMBPP]}-responsive γ9δ2 T cells, expressing an oligoclonal set of T cell receptor (TCR) sequences which more efficiently recognize and inhibit intracellular Mycobacterium tuberculosis infection. Based on this premise, we have been searching for M. tuberculosis antigens specifically capable of inducing a unique subset of mycobacterium-protective γ9δ2 T cells. Our screening strategy includes the identification of M. tuberculosis fractions that expand γ9δ2 T cells with biological functions capable of inhibiting intracellular mycobacterial replication. Chemical treatments of M. tuberculosis whole-cell lysates (MtbWL) ruled out protein, nucleic acid, and nonpolar lipids as the M. tuberculosis antigens inducing protective γ9δ2 T cells. Mild acid hydrolysis, which transforms complex carbohydrate to monomeric residues, abrogated the specific activity of M. tuberculosis whole-cell lysates, suggesting that a polysaccharide was required for biological activity. Extraction of MtbWL with chloroform-methanol-water (10:10:3) resulted in a polar lipid fraction with highly enriched specific activity; this activity was further enriched by silica gel chromatography. A combination of mass spectrometry and nuclear magnetic resonance analysis of bioactive fractions indicated that 6-O-methylglucose-containing lipopolysaccharides (mGLP) are predominant components present in this active fraction. These results have important implications for the development of new immunotherapeutic approaches for prevention and treatment of TB. PMID:27297390

  19. Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Aaron Topol

    2016-05-01

    Full Text Available Converging evidence indicates that microRNAs (miRNAs may contribute to disease risk for schizophrenia (SZ. We show that microRNA-9 (miR-9 is abundantly expressed in control neural progenitor cells (NPCs but also significantly downregulated in a subset of SZ NPCs. We observed a strong correlation between miR-9 expression and miR-9 regulatory activity in NPCs as well as between miR-9 levels/activity, neural migration, and diagnosis. Overexpression of miR-9 was sufficient to ameliorate a previously reported neural migration deficit in SZ NPCs, whereas knockdown partially phenocopied aberrant migration in control NPCs. Unexpectedly, proteomic- and RNA sequencing (RNA-seq-based analysis revealed that these effects were mediated primarily by small changes in expression of indirect miR-9 targets rather than large changes in direct miR-9 targets; these indirect targets are enriched for migration-associated genes. Together, these data indicate that aberrant levels and activity of miR-9 may be one of the many factors that contribute to SZ risk, at least in a subset of patients.

  20. Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells.

    Science.gov (United States)

    Topol, Aaron; Zhu, Shijia; Hartley, Brigham J; English, Jane; Hauberg, Mads E; Tran, Ngoc; Rittenhouse, Chelsea Ann; Simone, Anthony; Ruderfer, Douglas M; Johnson, Jessica; Readhead, Ben; Hadas, Yoav; Gochman, Peter A; Wang, Ying-Chih; Shah, Hardik; Cagney, Gerard; Rapoport, Judith; Gage, Fred H; Dudley, Joel T; Sklar, Pamela; Mattheisen, Manuel; Cotter, David; Fang, Gang; Brennand, Kristen J

    2016-05-01

    Converging evidence indicates that microRNAs (miRNAs) may contribute to disease risk for schizophrenia (SZ). We show that microRNA-9 (miR-9) is abundantly expressed in control neural progenitor cells (NPCs) but also significantly downregulated in a subset of SZ NPCs. We observed a strong correlation between miR-9 expression and miR-9 regulatory activity in NPCs as well as between miR-9 levels/activity, neural migration, and diagnosis. Overexpression of miR-9 was sufficient to ameliorate a previously reported neural migration deficit in SZ NPCs, whereas knockdown partially phenocopied aberrant migration in control NPCs. Unexpectedly, proteomic- and RNA sequencing (RNA-seq)-based analysis revealed that these effects were mediated primarily by small changes in expression of indirect miR-9 targets rather than large changes in direct miR-9 targets; these indirect targets are enriched for migration-associated genes. Together, these data indicate that aberrant levels and activity of miR-9 may be one of the many factors that contribute to SZ risk, at least in a subset of patients.

  1. High enrichment to low enrichment core's conversion. Technical securities

    International Nuclear Information System (INIS)

    This work presents the fulfillment of the technical securities subscribed by INVAP S.E. for the conversion of a high enriched uranium core. The reactor (of 5 thermal Mw), built in the 50's and 60's, is of the 'swimming pool' type, with light water and fuel elements of the curve plates MTR type, enriched at 93.15 %. These are neutronic and thermohydraulic securities. (Author)

  2. Research on the enrichment of CD44+CD24-cancer stem cells in breast cancer multi-drug resistant cell lines MCF-7/PTX%MCF-7/PTX多药耐药细胞株中CD44+CD24-乳腺癌干细胞富集的研究

    Institute of Scientific and Technical Information of China (English)

    韩娜娜; 孙长岗; 庄静; 杨静

    2013-01-01

    Objective To establish human breast cancer multi-drug resistant cell lines MCF-7/PTX in order to study the enrichment of CD+44CD-24 breast cancer cells. Methods We established the multidrug resistant cell line MCF-7/PTX by method of intermittently induction with high dose of PTX. The resistance and cross-resistance of MCF-7 and MCF-7/PTX on PTX were identified by MTT method. The proportion of CD+44CD-24 cells was detected by method of flow cytometry. Results The resistance indices of MCF-7/PTX on paclitaxel, doxorubicin, docetaxel, epirubicin, vincristine, methotrexate, cis-platin were 53, 45.72, 38.30,41.26, 23.75, 17.62 and 35. 80, respectively. The proportion of CD+44CD-24 cells in MCF-7 and MCF-7/PTX were 8.60% , 73. 20% , respectively. Conclusion The MCF-7/PTX cell line established in this study was a kind of multi-drug resistant cell line. The CD+44CD-24 cells in MCF-7/PTX were enriched.%目的 建立人乳腺癌紫杉醇(PTX)多药耐药细胞株MCF-7/PTX,观察MCF-7、MCF-7/PTX细胞株中CD44+CD24-乳腺癌干细胞的富集情况.方法 以MCF-7为亲本细胞,以PTX为诱导药物,高浓度间歇诱导法建立多药耐药细胞株MCF-7/PTX;MTT法检测MCF-7、MCF-7/PTX对PTX等多种化疗药物的耐药性及交叉耐药性;流式细胞术检测细胞株CD44+CD24-乳腺癌干细胞的含量.结果 ①MCF-7/PTX对PTX、阿霉素、多西紫杉醇、表阿霉素、长春新碱、甲氨蝶呤、顺铂的耐药指数分别为53.00、45.72、38.30、41.26、23.75、17.62、35.80.②MCF-7、MCF-7/PTX细胞株中CD44+CD24-细胞的比例分别为8.60%、73.20%,P<0.01.结论 本实验所建立的MCF-7/PTX为多药耐药细胞株;MCF-7/PTX存在着CD44+CD24-乳腺癌干细胞的富集.

  3. Application of subset simulation in reliability estimation of underground pipelines

    International Nuclear Information System (INIS)

    This paper presents a computational framework for implementing an advanced Monte Carlo simulation method, called Subset Simulation (SS) for time-dependent reliability prediction of underground flexible pipelines. The SS can provide better resolution for low failure probability level of rare failure events which are commonly encountered in pipeline engineering applications. Random samples of statistical variables are generated efficiently and used for computing probabilistic reliability model. It gains its efficiency by expressing a small probability event as a product of a sequence of intermediate events with larger conditional probabilities. The efficiency of SS has been demonstrated by numerical studies and attention in this work is devoted to scrutinise the robustness of the SS application in pipe reliability assessment and compared with direct Monte Carlo simulation (MCS) method. Reliability of a buried flexible steel pipe with time-dependent failure modes, namely, corrosion induced deflection, buckling, wall thrust and bending stress has been assessed in this study. The analysis indicates that corrosion induced excessive deflection is the most critical failure event whereas buckling is the least susceptible during the whole service life of the pipe. The study also shows that SS is robust method to estimate the reliability of buried pipelines and it is more efficient than MCS, especially in small failure probability prediction

  4. Alteration of peripheral blood lymphocyte subsets in acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Miroslawa Pietruczuk; Milena I Dabrowska; Urszula Wereszczynska-Siemiatkowska; Andrzej Dabrowski

    2006-01-01

    AIM: To evaluate peripheral blood lymphocyte subsets in patients with acute pancreatitis (AP).METHODS: Twenty patients with mild AP (M-AP) and 15 with severe AP (S-AP) were included in our study. Peripheral blood lymphocytes were examined at d 1-3, 5,10 and 30 by means of flow cytometry.RESULTS: A significant depletion of circulating lymphocytes was found in AP. In the early AP, the magnitude of depletion was similar for T- and B- lymphocytes. In the late course of S-AP, B-lymphocytes were much more depleted than T-lymphocytes. At d 10, strong shift in the CD7+/CD19+ ratio implicating predominance of Tover B-lymphocytes in S-AP was found. Among T-lymphocytes, the significant depletion of the CD4+ population was observed in M-AP and S-AP, while CD8+ cells were in the normal range. Lymphocytes were found to strongly express activation markers: CD69, CD25, CD28,CD38 and CD122. Serum interleukin-2 (IL-2), IL-4, IL-5,IL-10, interferon-γ (IFN-γ) and tumor necrosis factor-α(TNF-α) levels were significantly increased in both forms of AP. The magnitude of elevation of cytokines known to be produced by Th2 was much higher than cytokines produced by Th1 cells.CONCLUSION: AP in humans is characterized by significant reduction of peripheral blood T- and B-lymphocytes.

  5. Optimal Features Subset Selection and Classification for Iris Recognition

    Directory of Open Access Journals (Sweden)

    Prabir Bhattacharya

    2008-06-01

    Full Text Available The selection of the optimal features subset and the classification have become an important issue in the field of iris recognition. We propose a feature selection scheme based on the multiobjectives genetic algorithm (MOGA to improve the recognition accuracy and asymmetrical support vector machine for the classification of iris patterns. We also suggest a segmentation scheme based on the collarette area localization. The deterministic feature sequence is extracted from the iris images using the 1D log-Gabor wavelet technique, and the extracted feature sequence is used to train the support vector machine (SVM. The MOGA is applied to optimize the features sequence and to increase the overall performance based on the matching accuracy of the SVM. The parameters of SVM are optimized to improve the overall generalization performance, and the traditional SVM is modified to an asymmetrical SVM to treat the false accept and false reject cases differently and to handle the unbalanced data of a specific class with respect to the other classes. Our experimental results indicate that the performance of SVM as a classifier is better than the performance of the classifiers based on the feedforward neural network, the k-nearest neighbor, and the Hamming and the Mahalanobis distances. The proposed technique is computationally effective with recognition rates of 99.81% and 96.43% on CASIA and ICE datasets, respectively.

  6. Optimal Features Subset Selection and Classification for Iris Recognition

    Directory of Open Access Journals (Sweden)

    Roy Kaushik

    2008-01-01

    Full Text Available Abstract The selection of the optimal features subset and the classification have become an important issue in the field of iris recognition. We propose a feature selection scheme based on the multiobjectives genetic algorithm (MOGA to improve the recognition accuracy and asymmetrical support vector machine for the classification of iris patterns. We also suggest a segmentation scheme based on the collarette area localization. The deterministic feature sequence is extracted from the iris images using the 1D log-Gabor wavelet technique, and the extracted feature sequence is used to train the support vector machine (SVM. The MOGA is applied to optimize the features sequence and to increase the overall performance based on the matching accuracy of the SVM. The parameters of SVM are optimized to improve the overall generalization performance, and the traditional SVM is modified to an asymmetrical SVM to treat the false accept and false reject cases differently and to handle the unbalanced data of a specific class with respect to the other classes. Our experimental results indicate that the performance of SVM as a classifier is better than the performance of the classifiers based on the feedforward neural network, the k-nearest neighbor, and the Hamming and the Mahalanobis distances. The proposed technique is computationally effective with recognition rates of 99.81% and 96.43% on CASIA and ICE datasets, respectively.

  7. Zone diagrams in compact subsets of uniformly convex normed spaces

    CERN Document Server

    Kopecká, Eva; Reich, Simeon

    2010-01-01

    A zone diagram is a relatively new concept which has emerged in computational geometry and is related to Voronoi diagrams. Formally, it is a fixed point of a certain mapping, and neither its uniqueness nor its existence are obvious in advance. It has been studied by several authors, starting with T. Asano, J. Matousek and T. Tokuyama, who considered the Euclidean plane with singleton sites, and proved the existence and uniqueness of zone diagrams there. In the present paper we prove the existence of zone diagrams with respect to finitely many pairwise disjoint compact sites contained in a compact and convex subset of a uniformly convex normed space. The proof is based on the Schauder fixed point theorem, the Curtis-Schori theorem regarding the Hilbert cube, and on recent results concerning the characterization of Voronoi cells as a collection of line segments and their geometric stability with respect to small changes of the corresponding sites. Along the way we obtain the continuity of the Dom mapping as wel...

  8. Leukocyte subsets and neutrophil function after short-term spaceflight

    Science.gov (United States)

    Stowe, R. P.; Sams, C. F.; Mehta, S. K.; Kaur, I.; Jones, M. L.; Feeback, D. L.; Pierson, D. L.

    1999-01-01

    Changes in leukocyte subpopulations and function after spaceflight have been observed but the mechanisms underlying these changes are not well defined. This study investigated the effects of short-term spaceflight (8-15 days) on circulating leukocyte subsets, stress hormones, immunoglobulin levels, and neutrophil function. At landing, a 1.5-fold increase in neutrophils was observed compared with preflight values; lymphocytes were slightly decreased, whereas the results were variable for monocytes. No significant changes were observed in plasma levels of immunoglobulins, cortisol, or adrenocorticotropic hormone. In contrast, urinary epinephrine, norepinephrine, and cortisol were significantly elevated at landing. Band neutrophils were observed in 9 of 16 astronauts. Neutrophil chemotactic assays showed a 10-fold decrease in the optimal dose response after landing. Neutrophil adhesion to endothelial cells was increased both before and after spaceflight. At landing, the expression of MAC-1 was significantly decreased while L-selectin was significantly increased. These functional alterations may be of clinical significance on long-duration space missions.

  9. Bayesian Subset Modeling for High-Dimensional Generalized Linear Models

    KAUST Repository

    Liang, Faming

    2013-06-01

    This article presents a new prior setting for high-dimensional generalized linear models, which leads to a Bayesian subset regression (BSR) with the maximum a posteriori model approximately equivalent to the minimum extended Bayesian information criterion model. The consistency of the resulting posterior is established under mild conditions. Further, a variable screening procedure is proposed based on the marginal inclusion probability, which shares the same properties of sure screening and consistency with the existing sure independence screening (SIS) and iterative sure independence screening (ISIS) procedures. However, since the proposed procedure makes use of joint information from all predictors, it generally outperforms SIS and ISIS in real applications. This article also makes extensive comparisons of BSR with the popular penalized likelihood methods, including Lasso, elastic net, SIS, and ISIS. The numerical results indicate that BSR can generally outperform the penalized likelihood methods. The models selected by BSR tend to be sparser and, more importantly, of higher prediction ability. In addition, the performance of the penalized likelihood methods tends to deteriorate as the number of predictors increases, while this is not significant for BSR. Supplementary materials for this article are available online. © 2013 American Statistical Association.

  10. Regulatory T cells subsets in filarial infection and their function

    Directory of Open Access Journals (Sweden)

    Simon eMetenou

    2013-09-01

    Full Text Available Filarial infections in humans are chronic infections that cause significant morbidity. The chronic nature of these infections with continuous antigen release is associated with a parasite-specific T cell hypo-responsiveness that may over time also affect the immune responses to bystander antigens. Previous studies have shown the filarial parasite antigen-specific T cells hypo-responsiveness is mediated by regulatory cytokines -- IL-10 and TGF-β in particular. Recent studies have suggested that the modulated/regulated T cell responses associated with patent filarial infection may reflect an expansion of regulatory T cells (Tregs that include both Tregs induced in peripheral circulation or pTregs and the thymus-derived Tregs or tTregs. Although much is known about the phenotype of these regulatory populations, the mechanisms underlying their expansion and their mode of action in filarial and other infections remain unclear. Nevertheless there are data to suggest that while many of these regulatory cells are activated in an antigen-specific manner the ensuing effectors of this activation are relatively non-specific and may affect a broad range of immune cells. This review will focus on the subsets and function of regulatory T cells in filarial infection.

  11. Characterization of HPV and host genome interactions in primary head and neck cancers

    Science.gov (United States)

    Parfenov, Michael; Pedamallu, Chandra Sekhar; Gehlenborg, Nils; Freeman, Samuel S.; Danilova, Ludmila; Bristow, Christopher A.; Lee, Semin; Hadjipanayis, Angela G.; Ivanova, Elena V.; Wilkerson, Matthew D.; Protopopov, Alexei; Yang, Lixing; Seth, Sahil; Song, Xingzhi; Tang, Jiabin; Ren, Xiaojia; Zhang, Jianhua; Pantazi, Angeliki; Santoso, Netty; Xu, Andrew W.; Mahadeshwar, Harshad; Wheeler, David A.; Haddad, Robert I.; Jung, Joonil; Ojesina, Akinyemi I.; Issaeva, Natalia; Yarbrough, Wendell G.; Hayes, D. Neil; Grandis, Jennifer R.; El-Naggar, Adel K.; Meyerson, Matthew; Park, Peter J.; Chin, Lynda; Seidman, J. G.; Hammerman, Peter S.; Kucherlapati, Raju; Ally, Adrian; Balasundaram, Miruna; Birol, Inanc; Bowlby, Reanne; Butterfield, Yaron S.N.; Carlsen, Rebecca; Cheng, Dean; Chu, Andy; Dhalla, Noreen; Guin, Ranabir; Holt, Robert A.; Jones, Steven J.M.; Lee, Darlene; Li, Haiyan I.; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Robertson, A. Gordon; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Wong, Tina; Protopopov, Alexei; Santoso, Netty; Lee, Semin; Parfenov, Michael; Zhang, Jianhua; Mahadeshwar, Harshad S.; Tang, Jiabin; Ren, Xiaojia; Seth, Sahil; Haseley, Psalm; Zeng, Dong; Yang, Lixing; Xu, Andrew W.; Song, Xingzhi; Pantazi, Angeliki; Bristow, Christopher; Hadjipanayis, Angela; Seidman, Jonathan; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Akbani, Rehan; Casasent, Tod; Liu, Wenbin; Lu, Yiling; Mills, Gordon; Motter, Thomas; Weinstein, John; Diao, Lixia; Wang, Jing; Fan, You Hong; Liu, Jinze; Wang, Kai; Auman, J. Todd; Balu, Saianand; Bodenheimer, Tom; Buda, Elizabeth; Hayes, D. Neil; Hoadley, Katherine A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Corbin D.; Kimes, Patrick K.; Marron, J.S.; Meng, Shaowu; Mieczkowski, Piotr A.; Mose, Lisle E.; Parker, Joel S.; Perou, Charles M.; Prins, Jan F.; Roach, Jeffrey; Shi, Yan; Simons, Janae V.; Singh, Darshan; Soloway, Mathew G.; Tan, Donghui; Veluvolu, Umadevi; Walter, Vonn; Waring, Scot; Wilkerson, Matthew D.; Wu, Junyuan; Zhao, Ni; Cherniack, Andrew D.; Hammerman, Peter S.; Tward, Aaron D.; Pedamallu, Chandra Sekhar; Saksena, Gordon; Jung, Joonil; Ojesina, Akinyemi I.; Carter, Scott L.; Zack, Travis I.; Schumacher, Steven E.; Beroukhim, Rameen; Freeman, Samuel S.; Meyerson, Matthew; Cho, Juok; Chin, Lynda; Getz, Gad; Noble, Michael S.; DiCara, Daniel; Zhang, Hailei; Heiman, David I.; Gehlenborg, Nils; Voet, Doug; Lin, Pei; Frazer, Scott; Stojanov, Petar; Liu, Yingchun; Zou, Lihua; Kim, Jaegil; Lawrence, Michael S.; Sougnez, Carrie; Lichtenstein, Lee; Cibulskis, Kristian; Lander, Eric; Gabriel, Stacey B.; Muzny, Donna; Doddapaneni, HarshaVardhan; Kovar, Christie; Reid, Jeff; Morton, Donna; Han, Yi; Hale, Walker; Chao, Hsu; Chang, Kyle; Drummond, Jennifer A.; Gibbs, Richard A.; Kakkar, Nipun; Wheeler, David; Xi, Liu; Ciriello, Giovanni; Ladanyi, Marc; Lee, William; Ramirez, Ricardo; Sander, Chris; Shen, Ronglai; Sinha, Rileen; Weinhold, Nils; Taylor, Barry S.; Aksoy, B. Arman; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Jacobsen, Anders; Reva, Boris; Schultz, Nikolaus; Sumer, S. Onur; Sun, Yichao; Chan, Timothy; Morris, Luc; Stuart, Joshua; Benz, Stephen; Ng, Sam; Benz, Christopher; Yau, Christina; Baylin, Stephen B.; Cope, Leslie; Danilova, Ludmila; Herman, James G.; Bootwalla, Moiz; Maglinte, Dennis T.; Laird, Peter W.; Triche, Timothy; Weisenberger, Daniel J.; Van Den Berg, David J.; Agrawal, Nishant; Bishop, Justin; Boutros, Paul C.; Bruce, Jeff P; Byers, Lauren Averett; Califano, Joseph; Carey, Thomas E.; Chen, Zhong; Cheng, Hui; Chiosea, Simion I.; Cohen, Ezra; Diergaarde, Brenda; Egloff, Ann Marie; El-Naggar, Adel K.; Ferris, Robert L.; Frederick, Mitchell J.; Grandis, Jennifer R.; Guo, Yan; Haddad, Robert I.; Hammerman, Peter S.; Harris, Thomas; Hayes, D. Neil; Hui, Angela BY; Lee, J. Jack; Lippman, Scott M.; Liu, Fei-Fei; McHugh, Jonathan B.; Myers, Jeff; Ng, Patrick Kwok Shing; Perez-Ordonez, Bayardo; Pickering, Curtis R.; Prystowsky, Michael; Romkes, Marjorie; Saleh, Anthony D.; Sartor, Maureen A.; Seethala, Raja; Seiwert, Tanguy Y.; Si, Han; Tward, Aaron D.; Van Waes, Carter; Waggott, Daryl M.; Wiznerowicz, Maciej; Yarbrough, Wendell; Zhang, Jiexin; Zuo, Zhixiang; Burnett, Ken; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Penny, Robert; Shelton, Candance; Shelton, Troy; Sherman, Mark; Yena, Peggy; Black, Aaron D.; Bowen, Jay; Frick, Jessica; Gastier-Foster, Julie M.; Harper, Hollie A.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Wise, Lisa; Zmuda, Erik; Baboud, Julien; Jensen, Mark A.; Kahn, Ari B.; Pihl, Todd D.; Pot, David A.; Srinivasan, Deepak; Walton, Jessica S.; Wan, Yunhu; Burton, Robert; Davidsen, Tanja; Demchok, John A.; Eley, Greg; Ferguson, Martin L.; Shaw, Kenna R. Mills; Ozenberger, Bradley A.; Sheth, Margi; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean Claude; Saller, Charles; Tarvin, Katherine; Chen, Chu; Bollag, Roni; Weinberger, Paul; Golusiński, Wojciech; Golusiński, Paweł; Ibbs, Matthiew; Korski, Konstanty; Mackiewicz, Andrzej; Suchorska, Wiktoria; Szybiak, Bartosz; Wiznerowicz, Maciej; Burnett, Ken; Curley, Erin; Gardner, Johanna; Mallery, David; Penny, Robert; Shelton, Troy; Yena, Peggy; Beard, Christina; Mitchell, Colleen; Sandusky, George; Agrawal, Nishant; Ahn, Julie; Bishop, Justin; Califano, Joseph; Khan, Zubair; Bruce, Jeff P; Hui, Angela BY; Irish, Jonathan; Liu, Fei-Fei; Perez-Ordonez, Bayardo; Waldron, John; Boutros, Paul C.; Waggott, Daryl M.; Myers, Jeff; Lippman, Scott M.; Egea, Sophie; Gomez-Fernandez, Carmen; Herbert, Lynn; Bradford, Carol R.; Carey, Thomas E.; Chepeha, Douglas B.; Haddad, Andrea S.; Jones, Tamara R.; Komarck, Christine M.; Malakh, Mayya; McHugh, Jonathan B.; Moyer, Jeffrey S.; Nguyen, Ariane; Peterson, Lisa A.; Prince, Mark E.; Rozek, Laura S.; Sartor, Maureen A.; Taylor, Evan G.; Walline, Heather M.; Wolf, Gregory T.; Boice, Lori; Chera, Bhishamjit S.; Funkhouser, William K.; Gulley, Margaret L.; Hackman, Trevor G.; Hayes, D. Neil; Hayward, Michele C.; Huang, Mei; Rathmell, W. Kimryn; Salazar, Ashley H.; Shockley, William W.; Shores, Carol G.; Thorne, Leigh; Weissler, Mark C.; Wrenn, Sylvia; Zanation, Adam M.; Chiosea, Simion I.; Diergaarde, Brenda; Egloff, Ann Marie; Ferris, Robert L.; Romkes, Marjorie; Seethala, Raja; Brown, Brandee T.; Guo, Yan; Pham, Michelle; Yarbrough, Wendell G.

    2014-01-01

    Previous studies have established that a subset of head and neck tumors contains human papillomavirus (HPV) sequences and that HPV-driven head and neck cancers display distinct biological and clinical features. HPV is known to drive cancer by the actions of the E6 and E7 oncoproteins, but the molecular architecture of HPV infection and its interaction with the host genome in head and neck cancers have not been comprehensively described. We profiled a cohort of 279 head and neck cancers with next generation RNA and DNA sequencing and show that 35 (12.5%) tumors displayed evidence of high-risk HPV types 16, 33, or 35. Twenty-five cases had integration of the viral genome into one or more locations in the human genome with statistical enrichment for genic regions. Integrations had a marked impact on the human genome and were associated with alterations in DNA copy number, mRNA transcript abundance and splicing, and both inter- and intrachromosomal rearrangements. Many of these events involved genes with documented roles in cancer. Cancers with integrated vs. nonintegrated HPV displayed different patterns of DNA methylation and both human and viral gene expressions. Together, these data provide insight into the mechanisms by which HPV interacts with the human genome beyond expression of viral oncoproteins and suggest that specific integration events are an integral component of viral oncogenesis. PMID:25313082

  12. Replication error deficient and proficient colorectal cancer gene expression differences caused by 3'UTR polyT sequence deletions

    DEFF Research Database (Denmark)

    Wilding, Jennifer L; McGowan, Simon; Liu, Ying;

    2010-01-01

    Replication error deficient (RER+) colorectal cancers are a distinct subset of colorectal cancers, characterized by inactivation of the DNA mismatch repair system. These cancers are typically pseudodiploid, accumulate mutations in repetitive sequences as a result of their mismatch repair deficiency...

  13. Identification of 2R-ohnologue gene families displaying the same mutation-load skew in multiple cancers.

    Science.gov (United States)

    Tinti, Michele; Dissanayake, Kumara; Synowsky, Silvia; Albergante, Luca; MacKintosh, Carol

    2014-01-01

    The complexity of signalling pathways was boosted at the origin of the vertebrates, when two rounds of whole genome duplication (2R-WGD) occurred. Those genes and proteins that have survived from the 2R-WGD-termed 2R-ohnologues-belong to families of two to four members, and are enriched in signalling components relevant to cancer. Here, we find that while only approximately 30% of human transcript-coding genes are 2R-ohnologues, they carry 42-60% of the gene mutations in 30 different cancer types. Across a subset of cancer datasets, including melanoma, breast, lung adenocarcinoma, liver and medulloblastoma, we identified 673 2R-ohnologue families in which one gene carries mutations at multiple positions, while sister genes in the same family are relatively mutation free. Strikingly, in 315 of the 322 2R-ohnologue families displaying such a skew in multiple cancers, the same gene carries the heaviest mutation load in each cancer, and usually the second-ranked gene is also the same in each cancer. Our findings inspire the hypothesis that in certain cancers, heterogeneous combinations of genetic changes impair parts of the 2R-WGD signalling networks and force information flow through a limited set of oncogenic pathways in which specific non-mutated 2R-ohnologues serve as effectors. The non-mutated 2R-ohnologues are therefore potential therapeutic targets. These include proteins linked to growth factor signalling, neurotransmission and ion channels.

  14. Survival and signaling changes in antigen presenting cell subsets after radiation

    Science.gov (United States)

    Parker, Jennifer Janell

    Radiation therapy is a widely used cancer treatment that has the potential to influence anti-tumor immune responses. Both myeloablative and non-myeloablative radiation are often used as part of preparatory regimens for hematopoetic stem cell transplantation, in combination with other chemotherapy or immuno-modulatory (e.g. Anti-thymocyte globulin (ATG)) therapies for both cytotoxic and immune modulatory purposes. However, the mechanisms responsible for the effect of radiation on antigen presenting cell (APC) responsiveness and radioresistance are poorly understood. The first studies described in this thesis were designed to identify and characterize early radiation-induced signaling changes in antigen presenting cells and to determine the effects of these signaling changes on APC receptor expression and function. The NFkappaB pathway in antigen presenting cells was chosen for study because it is activated by radiation in a wide range of other cell types and plays a vital role in the maintenance and regulation of the immune system. The effects of therapeutically relevant doses radiation (2 and 20 Gy) were compared at various timepoints in the human monocytic cell line (U937) using phospho-flow cytometry staining methods and cytometric analysis. These studies demonstrated that radiation-induced changes in the phosphorylation state of NFkappaB family members that were p53 independent. However, these changes were dependent upon activation of ATM in response to single or double-stranded breaks in DNA, as shown in experiments using an inhibitor of ATM and ATM siRNA knockdown U937 cells. In addition, studies examining the effect of radiation on co-stimulatory receptors with and without inhibition of the NFkappaB pathway via phospho-flow cytometry revealed that radiation-induced phosphorylation of NEMO promoted the activation and functional maturation of U937 cells. Furthermore, functional studies using both phospho-flow cytometry and/or mixed lymphocyte reactions to

  15. Meadow enriched ACP process algebras

    OpenAIRE

    J.A. Bergstra; Middelburg, C.A.

    2009-01-01

    We introduce the notion of an ACP process algebra. The models of the axiom system ACP are the origin of this notion. ACP process algebras have to do with processes in which no data are involved. We also introduce the notion of a meadow enriched ACP process algebra, which is a simple generalization of the notion of an ACP process algebra to processes in which data are involved. In meadow enriched ACP process algebras, the mathematical structure for data is a meadow.

  16. Phenotypic and functional distinctions between the TH2+ and JRA+ T cell subsets in man.

    Science.gov (United States)

    Reinherz, E L; Strelkauskas, A J; O'Brien, C; Schlossman, S F

    1979-07-01

    Prior work has demonstrated the existence of distinct human peripheral blood T cell subsets by utilizing heterologous as well as autoimmune antisera. In the present study, the relationship between the TH2+ and JRA+ T cell subsets was examined. T cells were purified with Sephadex G-200 anti-F(ab)2' affinity chromatography and E-rosetting technique, and subsequently fractionated into TH2+ and TH2- subsets by utilizing indirect immunofluorescence on FACS. Approximately 40 to 45% of the TH2- subset was shown to be JRA+, whereas less than 5% of the TH2+ subset was JRA+. In reciprocal studies, T cells were fractionated into JRA+ and JRA- subsets and reacted with heterologous antisera with anti-TH2+ specificity and indirect immunofluorescence. FACS analysis demonstrated that the JRA+ population contained no TH2+ T cells. In contrast, the JRA- population contained TH2+ T cells and accounted for the entire TH2+ subset found in the unfractionated T cell population. Functional studies showed that the TH2+ subset, and not the JRA+ subset, contain the effector population for cell-mediated lympholysis. It is concluded that the TH2+ and JRA+ T cell subsets define distinct and different T cell populations in man.

  17. Differential expression of HLA-DR antigens in subsets of human CFU-GM.

    Science.gov (United States)

    Griffin, J D; Sabbath, K D; Herrmann, F; Larcom, P; Nichols, K; Kornacki, M; Levine, H; Cannistra, S A

    1985-10-01

    Expression of HLA-DR surface antigens by granulocyte/monocyte colony-forming cells (CFU-GM) may be important in the regulation of proliferation of these cells. Using immunological techniques to enrich for progenitor cells, we investigated the expression of HLA-DR in subsets of CFU-GM. "Early" (day 14) CFU-GM express higher levels of HLA-DR than do "late" (day 7) CFU-GM. Among late CFU-GM, cells destined to form monocyte (alpha-naphthyl acetate esterase-positive) colonies express higher levels of HLA-DR than do CFU-GM destined to form granulocyte (chloroacetate esterase-positive) colonies. Because high-level expression of DR antigen was a marker for monocyte differentiation, we examined several lymphokines for their effects on both DR expression and in vitro commitment to monocyte differentiation by myeloid precursor cells. DR antigen density could be increased by more than twofold over 48 hours upon exposure to gamma-interferon (gamma-IFN), whereas colony-stimulating factors had no effect. This was associated with a dose-dependent inhibition of total CFU-GM number, and a relative, but not absolute, increase in the ratio of monocyte colonies to granulocyte colonies. Similarly, in day 7 suspension cultures of purified myeloid precursor cells, gamma-IFN inhibited cell proliferation and increased the ratio of monocytes to granulocytes. Thus, despite the induction of high levels of HLA-DR antigen on precursor cells (a marker of monocyte commitment), the dominant in vitro effect of gamma-IFN was inhibition of granulocyte differentiation.

  18. A taxonomy of epithelial human cancer and their metastases

    Directory of Open Access Journals (Sweden)

    De Moor Bart

    2009-12-01

    Full Text Available Abstract Background Microarray technology has allowed to molecularly characterize many different cancer sites. This technology has the potential to individualize therapy and to discover new drug targets. However, due to technological differences and issues in standardized sample collection no study has evaluated the molecular profile of epithelial human cancer in a large number of samples and tissues. Additionally, it has not yet been extensively investigated whether metastases resemble their tissue of origin or tissue of destination. Methods We studied the expression profiles of a series of 1566 primary and 178 metastases by unsupervised hierarchical clustering. The clustering profile was subsequently investigated and correlated with clinico-pathological data. Statistical enrichment of clinico-pathological annotations of groups of samples was investigated using Fisher exact test. Gene set enrichment analysis (GSEA and DAVID functional enrichment analysis were used to investigate the molecular pathways. Kaplan-Meier survival analysis and log-rank tests were used to investigate prognostic significance of gene signatures. Results Large clusters corresponding to breast, gastrointestinal, ovarian and kidney primary tissues emerged from the data. Chromophobe renal cell carcinoma clustered together with follicular differentiated thyroid carcinoma, which supports recent morphological descriptions of thyroid follicular carcinoma-like tumors in the kidney and suggests that they represent a subtype of chromophobe carcinoma. We also found an expression signature identifying primary tumors of squamous cell histology in multiple tissues. Next, a subset of ovarian tumors enriched with endometrioid histology clustered together with endometrium tumors, confirming that they share their etiopathogenesis, which strongly differs from serous ovarian tumors. In addition, the clustering of colon and breast tumors correlated with clinico-pathological characteristics

  19. Comparative genomics analysis of mononuclear phagocyte subsets confirms homology between lymphoid tissue-resident and dermal XCR1(+) DCs in mouse and human and distinguishes them from Langerhans cells.

    Science.gov (United States)

    Carpentier, Sabrina; Vu Manh, Thien-Phong; Chelbi, Rabie; Henri, Sandrine; Malissen, Bernard; Haniffa, Muzlifah; Ginhoux, Florent; Dalod, Marc

    2016-05-01

    Dendritic cells (DC) are mononuclear phagocytes which exhibit a branching (dendritic) morphology and excel at naïve T cell activation. DC encompass several subsets initially identified by their expression of cell surface molecules and later shown to possess distinct functions. DC subset differentiation is orchestrated by transcription factors, growth factors and cytokines. Identifying DC subsets is challenging as very few cell surface molecules are uniquely expressed on any one of these cell populations. There is no standard consensus to identify mononuclear phagocyte subsets; varying antigens are employed depending on the tissue and animal species studied and between laboratories. This has led to confusion in how to accurately define and classify DCs across tissues and between species. Here we report a comparative genomics strategy that enables universal definition of DC and other mononuclear phagocyte subsets across species. We performed a meta-analysis of several public datasets of human and mouse mononuclear phagocyte subsets isolated from blood, spleen, skin or cutaneous lymph nodes, including by using a novel and user friendly software, BubbleGUM, which generates and integrates gene signatures for high throughput gene set enrichment analysis. This analysis demonstrates the equivalence between human and mouse skin XCR1(+) DCs, and between mouse and human Langerhans cells.

  20. Lung-resident eosinophils represent a distinct regulatory eosinophil subset.

    Science.gov (United States)

    Mesnil, Claire; Raulier, Stéfanie; Paulissen, Geneviève; Xiao, Xue; Birrell, Mark A; Pirottin, Dimitri; Janss, Thibaut; Starkl, Philipp; Ramery, Eve; Henket, Monique; Schleich, Florence N; Radermecker, Marc; Thielemans, Kris; Gillet, Laurent; Thiry, Marc; Belvisi, Maria G; Louis, Renaud; Desmet, Christophe; Marichal, Thomas; Bureau, Fabrice

    2016-09-01

    Increases in eosinophil numbers are associated with infection and allergic diseases, including asthma, but there is also evidence that eosinophils contribute to homeostatic immune processes. In mice, the normal lung contains resident eosinophils (rEos), but their function has not been characterized. Here, we have reported that steady-state pulmonary rEos are IL-5-independent parenchymal Siglec-FintCD62L+CD101lo cells with a ring-shaped nucleus. During house dust mite-induced airway allergy, rEos features remained unchanged, and rEos were accompanied by recruited inflammatory eosinophils (iEos), which were defined as IL-5-dependent peribronchial Siglec-FhiCD62L-CD101hi cells with a segmented nucleus. Gene expression analyses revealed a more regulatory profile for rEos than for iEos, and correspondingly, mice lacking lung rEos showed an increase in Th2 cell responses to inhaled allergens. Such elevation of Th2 responses was linked to the ability of rEos, but not iEos, to inhibit the maturation, and therefore the pro-Th2 function, of allergen-loaded DCs. Finally, we determined that the parenchymal rEos found in nonasthmatic human lungs (Siglec-8+CD62L+IL-3Rlo cells) were phenotypically distinct from the iEos isolated from the sputa of eosinophilic asthmatic patients (Siglec-8+CD62LloIL-3Rhi cells), suggesting that our findings in mice are relevant to humans. In conclusion, our data define lung rEos as a distinct eosinophil subset with key homeostatic functions. PMID:27548519

  1. Genetic Diversity in A Core Subset of Wild Barley Germplasm

    Directory of Open Access Journals (Sweden)

    Yong-Bi Fu

    2012-06-01

    Full Text Available Wild barley [Hordeum vulgare ssp. spontaneum (C. Koch Thell.] is a part of the primary gene pool with valuable sources of beneficial genes for barley improvement. This study attempted to develop a core subset of 269 accessions representing 16 countries from the Plant Gene Resources of Canada (PGRC collection of 3,782 accessions, and to characterize them using barley simple sequence repeat (SSR markers. Twenty-five informative primer pairs were applied to screen all samples and 359 alleles were detected over seven barley chromosomes. Analyses of the SSR data showed the effectiveness of the stratified sampling applied in capturing country-wise SSR variation. The frequencies of polymorphic alleles ranged from 0.004 to 0.708 and averaged 0.072. More than 24% or 7% SSR variation resided among accessions of 16 countries or two regions, respectively. Accessions from Israel and Jordan were genetically most diverse, while accessions from Lebanon and Greece were most differentiated. Four and five optimal clusters of accessions were obtained using STRUCTURE and BAPS programs and partitioned 16.3% and 20.3% SSR variations, respectively. The five optimal clusters varied in size from 15 to 104 and two clusters had only country-specific accessions. A genetic separation was detected between the accessions east and west of the Zagros Mountains only at the country, not the individual, level. These SSR patterns enhance our understanding of the wild barley gene pool, and are significant for conserving wild barley germplasm and exploring new sources of useful genes for barley improvement.

  2. Molecular subsets in the gene expression signatures of scleroderma skin.

    Directory of Open Access Journals (Sweden)

    Ausra Milano

    Full Text Available BACKGROUND: Scleroderma is a clinically heterogeneous disease with a complex phenotype. The disease is characterized by vascular dysfunction, tissue fibrosis, internal organ dysfunction, and immune dysfunction resulting in autoantibody production. METHODOLOGY AND FINDINGS: We analyzed the genome-wide patterns of gene expression with DNA microarrays in skin biopsies from distinct scleroderma subsets including 17 patients with systemic sclerosis (SSc with diffuse scleroderma (dSSc, 7 patients with SSc with limited scleroderma (lSSc, 3 patients with morphea, and 6 healthy controls. 61 skin biopsies were analyzed in a total of 75 microarray hybridizations. Analysis by hierarchical clustering demonstrates nearly identical patterns of gene expression in 17 out of 22 of the forearm and back skin pairs of SSc patients. Using this property of the gene expression, we selected a set of 'intrinsic' genes and analyzed the inherent data-driven groupings. Distinct patterns of gene expression separate patients with dSSc from those with lSSc and both are easily distinguished from normal controls. Our data show three distinct patient groups among the patients with dSSc and two groups among patients with lSSc. Each group can be distinguished by unique gene expression signatures indicative of proliferating cells, immune infiltrates and a fibrotic program. The intrinsic groups are statistically significant (p<0.001 and each has been mapped to clinical covariates of modified Rodnan skin score, interstitial lung disease, gastrointestinal involvement, digital ulcers, Raynaud's phenomenon and disease duration. We report a 177-gene signature that is associated with severity of skin disease in dSSc. CONCLUSIONS AND SIGNIFICANCE: Genome-wide gene expression profiling of skin biopsies demonstrates that the heterogeneity in scleroderma can be measured quantitatively with DNA microarrays. The diversity in gene expression demonstrates multiple distinct gene expression programs

  3. Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma.

    Science.gov (United States)

    Ceccarelli, Michele; Barthel, Floris P; Malta, Tathiane M; Sabedot, Thais S; Salama, Sofie R; Murray, Bradley A; Morozova, Olena; Newton, Yulia; Radenbaugh, Amie; Pagnotta, Stefano M; Anjum, Samreen; Wang, Jiguang; Manyam, Ganiraju; Zoppoli, Pietro; Ling, Shiyun; Rao, Arjun A; Grifford, Mia; Cherniack, Andrew D; Zhang, Hailei; Poisson, Laila; Carlotti, Carlos Gilberto; Tirapelli, Daniela Pretti da Cunha; Rao, Arvind; Mikkelsen, Tom; Lau, Ching C; Yung, W K Alfred; Rabadan, Raul; Huse, Jason; Brat, Daniel J; Lehman, Norman L; Barnholtz-Sloan, Jill S; Zheng, Siyuan; Hess, Kenneth; Rao, Ganesh; Meyerson, Matthew; Beroukhim, Rameen; Cooper, Lee; Akbani, Rehan; Wrensch, Margaret; Haussler, David; Aldape, Kenneth D; Laird, Peter W; Gutmann, David H; Noushmehr, Houtan; Iavarone, Antonio; Verhaak, Roel G W

    2016-01-28

    Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes. PMID:26824661

  4. Supervised Feature Subset Selection based on Modified Fuzzy Relative Information Measure for classifier Cart

    Directory of Open Access Journals (Sweden)

    K.SAROJINI,

    2010-06-01

    Full Text Available Feature subset selection is an essential task in data mining. This paper presents a new method for dealing with supervised feature subset selection based on Modified Fuzzy Relative Information Measure (MFRIM. First, Discretization algorithm is applied to discretize numeric features to construct the membership functions of each fuzzy sets of a feature. Then the proposed MFRIM is applied to select the feature subset focusing on boundary samples. The proposed method can select feature subset with minimum number of features, which are relevant to get higher average classification accuracy for datasets. The experimental results with UCI datasets show that the proposed algorithm is effective and efficient in selecting subset with minimum number of features getting higher average classification accuracy than the consistency based feature subset selection method.

  5. Brefeldin A Reduces Anchorage-Independent Survival, Cancer Stem Cell Potential and Migration of MDA-MB-231 Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Chao-Neng Tseng

    2014-10-01

    Full Text Available Cancer stem cells (CSCs are a subset of cancer cells in tumors or established cancer cell lines that can initiate and sustain the growth of tumors in vivo. Cancer stem cells can be enriched in serum-free, suspended cultures that allow the formation of tumorspheres over several days to weeks. Brefeldin A (BFA is a mycotoxin that induces endoplasmic reticulum (ER stress in eukaryotic cells. We found that BFA, at sub-microgram per milliliter concentrations, preferentially induced cell death in MDA-MB-231 suspension cultures (EC50: 0.016 µg/mL compared to adhesion cultures. BFA also effectively inhibited clonogenic activity and the migration and matrix metalloproteinases-9 (MMP-9 activity of MDA-MB-231 cells. Western blotting analysis indicated that the effects of BFA may be mediated by the down-regulation of breast CSC marker CD44 and anti-apoptotic proteins Bcl-2 and Mcl-1, as well as the reversal of epithelial-mesenchymal transition. Furthermore, BFA also displayed selective cytotoxicity toward suspended MDA-MB-468 cells, and suppressed tumorsphere formation in T47D and MDA-MB-453 cells, suggesting that BFA may be effective against breast cancer cells of various phenotypes.

  6. An Architecture for End-User TV Content Enrichment

    Directory of Open Access Journals (Sweden)

    A.J. Jansen

    2007-01-01

    Full Text Available This paper proposes an extension to the television-watching paradigm that permits an end-user to enrich broadcast content. Examples of this enriched content are: virtual edits that allow the order of presentation within the content to be changed or that allow the content to be subsetted; conditional text, graphic or video objects that can be placed to appear within content and triggered by viewer interaction; additional navigation links that can be added to structure how other users view the base content object. The enriched content can be viewed directly within the context of the TV viewing experience. It may also be shared with other users within a distributed peer group. Our architecture is based on a model that allows the original content to remain unaltered, and which respects DRM restrictions on content reuse. The fundamental approach we use is to define an intermediate content enhancement layer that is based on the W3C′s SMIL language. Using a pen-based enhancement interface, end-users can manipulate content that is saved in a home PDR setting. This paper describes our architecture and it provides several examples of how our system handles content enhancement. We also describe a reference implementation for creating and viewing enhancements.

  7. Hereditary colorectal cancer diagnostics

    DEFF Research Database (Denmark)

    Klarskov, Louise; Holck, Susanne; Bernstein, Inge;

    2012-01-01

    BackgroundThe hereditary non-polyposis colorectal cancer (HNPCC) subset of tumours can broadly be divided into tumours caused by an underlying mismatch-repair gene mutation, referred to as Lynch syndrome, and those that develop in families with similar patterns of heredity but without disease......-predisposing germline mismatch repair mutations, referred to as familial colorectal cancer type X (FCCTX). Recognition of HNPCC-associated colorectal cancers is central since surveillance programmes effectively reduce morbidity and mortality. The characteristic morphological features linked to Lynch syndrome can aid...... in the identification of this subset, whereas the possibility to use morphological features as an indicator of FCCTX is uncertain.Objective and methodsTo perform a detailed morphological evaluation of HNPCC-associated colorectal cancers and demonstrate significant differences between tumours associated with FCCTX...

  8. Uranium enrichment: technology, economics, capacity

    International Nuclear Information System (INIS)

    Large-scale enrichment of uranium has now been carried out for 40 years. While the gaseous diffusion process was the original choice of several countries and continues today to provide the major component of the world production of separative work, the last two decades have witnessed the development of a number of alternative processes for enrichment. These processes, which are being studied and deployed around the world, offer a wide range of technical and economic characteristics which will be useful in assuring adequate capacity to meet projected reactor fuel market needs through the rest of this century at competitive prices. With present uncertainties in future enriched uranium needs, it is apparent that flexibility in the deployment and operation of any enrichment process will be one of the prime considerations for the future. More economical production of separative work not only can have a beneficial impact on reactor fuel costs, but also tends to conserve natural uranium resources. This paper reviews the world scene in the enrichment component of the fuel cycle, including existing or planned commercial-scale facilities and announced R and D efforts on various processes

  9. Enrichment of light hydrocarbon mixture

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Dali (Los Alamos, NM); Devlin, David (Santa Fe, NM); Barbero, Robert S. (Santa Cruz, NM); Carrera, Martin E. (Naperville, IL); Colling, Craig W. (Warrenville, IL)

    2011-11-29

    Light hydrocarbon enrichment is accomplished using a vertically oriented distillation column having a plurality of vertically oriented, nonselective micro/mesoporous hollow fibers. Vapor having, for example, both propylene and propane is sent upward through the distillation column in between the hollow fibers. Vapor exits neat the top of the column and is condensed to form a liquid phase that is directed back downward through the lumen of the hollow fibers. As vapor continues to ascend and liquid continues to countercurrently descend, the liquid at the bottom of the column becomes enriched in a higher boiling point, light hydrocarbon (propane, for example) and the vapor at the top becomes enriched in a lower boiling point light hydrocarbon (propylene, for example). The hollow fiber becomes wetted with liquid during the process.

  10. A Systematic Approach to Marital Enrichment.

    Science.gov (United States)

    Dinkmeyer, Don; Carlson, Jon

    1986-01-01

    Presents a systematic approach to enriching marital relationships. The history and current status of marital enrichment is reviewed. An Adlerian approach to marital enrichment is described. Applications of the program in enrichment groups, marriage therapy and couple groups are included. (Author)

  11. Advances in uranium enrichment processes

    International Nuclear Information System (INIS)

    Advances in gas centrifuges and development of the atomic vapour laser isotope separation process promise substantial reductions in the cost of enriched uranium. The resulting reduction in LWR fuel costs could seriously erode the economic advantage of CANDU, and in combination with LWR design improvements, shortened construction times and increased operational reliability could allow the LWR to overtake CANDU. CANDU's traditional advantages of neutron economy and high reliability may no longer be sufficient - this is the challenge. The responses include: combining neutron economy and dollar economy by optimizing CANDU for slightly enriched uranium fuel; developing cost-reducing improvements in design, manufacture and construction; and reducing the cost of heavy water. Technology is a renewable resource which must be continually applied to a product for it to remain competitive in the decades to come. Such innovation is a prerequisite to Canada increasing her share of the international market for nuclear power stations. The higher burn-up achievable with enriched fuel in CANDU can reduce the fuel cycle costs by 20 to 40 percent for a likely range of costs for yellowcake and separative work. Alternatively, some of the benefits of a higher fissile content can take the form of a cheaper reactor core containing fewer fuel channels and less heavy water, and needing only a single fuelling machine. An opportunity that is linked to this need to introduce an enriched uranium fuel cycle into CANDU is to build an enrichment business in Canada. This could offer greater value added to our uranium exports, security of supply for enriched CANDUs, technological growth in Canada and new employment opportunities. AECL has a study in progress to define this opportunity

  12. Uranium enrichment. 1980 annual report

    International Nuclear Information System (INIS)

    This report contains data and related information on the production of enriched uranium at the gaseous diffusion plants and an update on the construction and project control center for the gas centrifuge plant. Power usage at the gaseous diffusion plants is illustrated. The report contains several glossy color pictures of the plants and processes described. In addition to gaseous diffusion and the centrifuge process, three advanced isotope separation process are now being developed. The business operation of the enrichment plants is described; charts on revenue, balance sheets, and income statements are included

  13. Comprehensive annotation of bidirectional promoters identifies co-regulation among breast and ovarian cancer genes.

    Directory of Open Access Journals (Sweden)

    Mary Q Yang

    2007-04-01

    Full Text Available A "bidirectional gene pair" comprises two adjacent genes whose transcription start sites are neighboring and directed away from each other. The intervening regulatory region is called a "bidirectional promoter." These promoters are often associated with genes that function in DNA repair, with the potential to participate in the development of cancer. No connection between these gene pairs and cancer has been previously investigated. Using the database of spliced-expressed sequence tags (ESTs, we identified the most complete collection of human transcripts under the control of bidirectional promoters. A rigorous screen of the spliced EST data identified new bidirectional promoters, many of which functioned as alternative promoters or regulated novel transcripts. Additionally, we show a highly significant enrichment of bidirectional promoters in genes implicated in somatic cancer, including a substantial number of genes implicated in breast and ovarian cancers. The repeated use of this promoter structure in the human genome suggests it could regulate co-expression patterns among groups of genes. Using microarray expression data from 79 human tissues, we verify regulatory networks among genes controlled by bidirectional promoters. Subsets of these promoters contain similar combinations of transcription factor binding sites, including evolutionarily conserved ETS factor binding sites in ERBB2, FANCD2, and BRCA2. Interpreting the regulation of genes involved in co-expression networks, especially those involved in cancer, will be an important step toward defining molecular events that may contribute to disease.

  14. Cancer Basics

    Science.gov (United States)

    ... Cancer? Breast Cancer Colon/Rectum Cancer Lung Cancer Prostate Cancer Skin Cancer Show All Cancer Types News and Features Cancer Glossary ACS Bookstore Cancer Information Cancer Basics Cancer Prevention & Detection Signs & Symptoms of Cancer Treatments & Side Effects ...

  15. In vitro antiproliferative/cytotoxic activity on cancer cell lines of a cardanol and a cardol enriched from Thai Apis mellifera propolis

    OpenAIRE

    Teerasripreecha Dungporn; Phuwapraisirisan Preecha; Puthong Songchan; Kimura Kiyoshi; Okuyama Masayuki; Mori Haruhide; Kimura Atsuo; Chanchao Chanpen

    2012-01-01

    Abstract Background Propolis is a complex resinous honeybee product. It is reported to display diverse bioactivities, such as antimicrobial, anti-inflammatory and anti-tumor properties, which are mainly due to phenolic compounds, and especially flavonoids. The diversity of bioactive compounds depends on the geography and climate, since these factors affect the floral diversity. Here, Apis mellifera propolis from Nan province, Thailand, was evaluated for potential anti-cancer activity. Methods...

  16. Meadow enriched ACP process algebras

    NARCIS (Netherlands)

    J.A. Bergstra; C.A. Middelburg

    2009-01-01

    We introduce the notion of an ACP process algebra. The models of the axiom system ACP are the origin of this notion. ACP process algebras have to do with processes in which no data are involved. We also introduce the notion of a meadow enriched ACP process algebra, which is a simple generalization o

  17. Environmental Development Plan: uranium enrichment

    International Nuclear Information System (INIS)

    This Environmental Development Plan identifies and examines the environmental, health, safety, and socioeconomic concerns and corresponding requirements associated with the DOE research, development, demonstration, and operation of the Uranium Enrichment program, including the gaseous diffusion process, the centrifuge process, centrifuge rotor fabrication, and related research and development activities

  18. Pediatric cancer epigenome and the influence of folate

    OpenAIRE

    Yiu, Teresa T; Li, Wei

    2015-01-01

    Despite improvement in clinical treatment of childhood cancer, it remains the leading cause of disease-related mortality in children with survivors often suffering from treatment-related toxicity and premature death. Because childhood cancer is vastly different from cancer in adults, a thorough understanding of the underlying molecular mechanisms specific to childhood cancer is essential. Although childhood cancer contains much fewer mutations, a subset of cancer subtypes has a higher frequen...

  19. Job enrichment in job design.

    Science.gov (United States)

    Bobeng, B J

    1977-03-01

    For optimal operation in labor-intensive industries, such as foodservice, not only scientific management principles but also behavioral aspects (the people) must be considered in designing job content. Three psychologic states--work that is meaningful, responsibility for outcomes, and knowledge of outcomes--are critical in motivating people. These, in turn encompass the core dimensions of skill variety, task identity, task significance, autonomy, and feedback. Job enrichment and job enlargement--related but not identical means of expanding job content--when combined, offer the likelihood of redesigned jobs in the core dimensions. Effective implementation of a job enrichment program hinges on diagnosing problems in the work system, actual changes in the work, and systematic evaluation of the changes. The importance of the contribution of the behavioral sciences to management cannot be neglected.

  20. T-lymphocyte subsets in West African children: impact of age, sex, and season

    DEFF Research Database (Denmark)

    Lisse, I M; Aaby, P; Whittle, H;

    1997-01-01

    determinants of T-lymphocyte subset levels. METHODS: A total of 803 healthy West African children younger than 6 years were included in the three community studies of T-lymphocyte subsets among twins and singletons, after measles infection and after measles immunization. We used the immunoalkaline phosphatase...... method to determine T-lymphocyte subsets. RESULTS: We found differences by age, sex, and season, whereas there were no significant differences by birth order, twinning, or ethnic group. The CD4+ percentage declined from birth to age 2 years, at which time it started to increase to higher levels at age 4...

  1. Feature subset selection based on mahalanobis distance: a statistical rough set method

    Institute of Scientific and Technical Information of China (English)

    Sun Liang; Han Chongzhao

    2008-01-01

    In order to select effective feature subsets for pattern classification, a novel statistics rough set method is presented based on generalized attribute reduction. Unlike classical reduction approaches, the objects in universe of discourse are signs of training sample sets and values of attributes are taken as statistical parameters. The binary relation and discernibility matrix for the reduction are induced by distance function. Furthermore, based on the monotony of the distance function defined by Mahalanobis distance, the effective feature subsets are obtained as generalized attribute reducts. Experiment result shows that the classification performance can be improved by using the selected feature subsets.

  2. Boron Enrichment in Martian Clay

    OpenAIRE

    James D Stephenson; Lydia J Hallis; Kazuhide Nagashima; Freeland, Stephen J.

    2013-01-01

    We have detected a concentration of boron in martian clay far in excess of that in any previously reported extra-terrestrial object. This enrichment indicates that the chemistry necessary for the formation of ribose, a key component of RNA, could have existed on Mars since the formation of early clay deposits, contemporary to the emergence of life on Earth. Given the greater similarity of Earth and Mars early in their geological history, and the extensive disruption of Earth's earliest minera...

  3. Enrichment of lanthanides in aragonite

    Institute of Scientific and Technical Information of China (English)

    瞿成利; 路波; 刘刚

    2009-01-01

    Using the constant addition technique,the coprecipitation of lanthanum,gadolinium,and lutetium with aragonite in seawater was experimentally investigated at 25 ℃.Their concentrations in aragonite overgrowths were determined by inductive coupled plasma mass spectrometer.All these lanthanides were strongly enriched in aragonite overgrowths.The amount of lanthanum,gadolinium,and lutetium incorporated into aragonite accounted for 57%-99%,50%-89%,and 40%-91% of their initial total amount,respectively.With the in...

  4. Environmental signatures of enrichment facilities

    International Nuclear Information System (INIS)

    Environmental sampling is a potentially useful tool that could be used for the detection of undeclared enrichment facilities. However, this would be likely to require the use of sophisticated and expensive analytical techniques to evaluate 235U/238U ratios. It would be, therefore, unlikely to be an inexpensive approach to detect proliferation. The probability of detecting an enrichment operation will depend on the type of facility. A gaseous diffusion operation will be relatively difficult to detect in relation to an EMIS facility and a gaseous centrifuge plant will be more difficult still. Releases from an enrichment operation are likely to be restricted to atmospheric discharges. Aquatic discharges would be relatively easy to contain and it would be unwise to devise a sampling strategy based on the measurement of these. The detection of atmospheric discharges is likely to be dependent on meteorological conditions, in particular stability. Stable atmospheric conditions are the most favourable for detecting releases at significant distances from the plant. Given stable conditions, detection of an EMIS facility might be possible at a distance of several 10s of km

  5. Enrichment and aggression in primates.

    Science.gov (United States)

    Honess, P E; Marin, C M

    2006-01-01

    There is considerable evidence that primates housed under impoverished conditions develop behavioural abnormalities, including, in the most extreme example, self-harming behaviour. This has implications for all contexts in which primates are maintained in captivity from laboratories to zoos since by compromising the animals' psychological well-being and allowing them to develop behavioural abnormalities their value as appropriate educational and research models is diminished. This review examines the extensive body of literature documenting attempts to improve living conditions with a view to correcting behavioural abnormalities and housing primates in such a way that they are encouraged to exhibit a more natural range and proportion of behaviours, including less self-directed and social aggression. The results of housing, feeding, physical, sensory and social enrichment efforts are examined with specific focus on their effect on aggressive behaviour and variation in their use and efficacy. It is concluded that while inappropriate or poorly distributed enrichment may encourage aggressive competition, enrichment that is species, sex, age and background appropriate can dramatically reduce aggression, can eliminate abnormal behaviour and substantially improve the welfare of primates maintained in captivity.

  6. Job Enrichment and the Mentally Retarded Worker.

    Science.gov (United States)

    Morris, Jerry L.; And Others

    1981-01-01

    The effect of job enrichment on the production rate of 14 mentally retarded adult workers was evaluated. Job enrichment led to increases in standard rates of production for high IQ Ss and lower rates for low IQ Ss. (Author)

  7. Uranium enrichment (a strategy analysis overview)

    International Nuclear Information System (INIS)

    An analysis of available information on enrichment technology, separative work supply and demand, and SWU cost is presented. Estimates of present and future enrichment costs are provided for use in strategy analyses of alternate nuclear fuel cycles and systems. (auth)

  8. Identifying cancer genes from cancer mutation profiles by cancer functions

    Institute of Scientific and Technical Information of China (English)

    LI YanHui; GUO Zheng; PENG ChunFang; LIU Qing; MA WenCai; WANG Jing; YAO Chen; ZHANG Min; ZHU Jing

    2008-01-01

    It is of great importance to identify new cancer genes from the data of large scale genome screenings of gene mutations in cancers. Considering the alternations of some essential functions are indispensable for oncogenesis, we define them as cancer functions and select, as their approximations, a group of detailed functions in GO (Gene Ontology) highly enriched with known cancer genes. To evaluate the efficiency of using cancer functions as features to identify cancer genes, we define, in the screened genes, the known protein kinase cancer genes as gold standard positives and the other kinase genes as gold standard negatives. The results show that cancer associated functions are more efficient in identifying cancer genes than the selection pressure feature. Furthermore, combining cancer functions with the number of non-silent mutations can generate more reliable positive predictions. Finally, with precision 0.42, we suggest a list of 46 kinase genes as candidate cancer genes which are annotated to cancer functions and carry at least 3 non-silent mutations.

  9. Canine Mammary Cancer Stem Cells are Radio- and Chemo-Resistant and Exhibit an Epithelial-Mesenchymal Transition Phenotype

    International Nuclear Information System (INIS)

    Canine mammary carcinoma is the most common cancer among female dogs and is often fatal due to the development of distant metastases. In humans, solid tumors are made up of heterogeneous cell populations, which perform different roles in the tumor economy. A small subset of tumor cells can hold or acquire stem cell characteristics, enabling them to drive tumor growth, recurrence and metastasis. In veterinary medicine, the molecular drivers of canine mammary carcinoma are as yet undefined. Here we report that putative cancer stem cells (CSCs) can be isolated form a canine mammary carcinoma cell line, REM134. We show that these cells have an increased ability to form tumorspheres, a characteristic of stem cells, and that they express embryonic stem cell markers associated with pluripotency. Moreover, canine CSCs are relatively resistant to the cytotoxic effects of common chemotherapeutic drugs and ionizing radiation, indicating that failure of clinical therapy to eradicate canine mammary cancer may be due to the survival of CSCs. The epithelial to mesenchymal transition (EMT) has been associated with cancer invasion, metastasis, and the acquisition of stem cell characteristics. Our results show that canine CSCs predominantly express mesenchymal markers and are more invasive than parental cells, indicating that these cells have a mesenchymal phenotype. Furthermore, we show that canine mammary cancer cells can be induced to undergo EMT by TGFβ and that these cells have an increased ability to form tumorspheres. Our findings indicate that EMT induction can enrich for cells with CSC properties, and provide further insight into canine CSC biology

  10. Enriched uranium sales: effect on supply industry

    International Nuclear Information System (INIS)

    The subject is covered in sections: introduction (combined effect of low-enriched uranium (LEU) inventory sales and utility services enrichment contract terms); enrichment market overview; enrichment market dynamics; the reaction of the US Department of Energy; elimination of artificial demand; draw down of inventories; purchase and sale of LEU inventories; tails assay option; unfulfilled requirements for U3O8; conclusions. (U.K.)

  11. NEAT: an efficient network enrichment analysis test

    OpenAIRE

    Signorelli, Mirko; Vinciotti, Veronica; Wit, Ernst C

    2016-01-01

    Background Network enrichment analysis is a powerful method, which allows to integrate gene enrichment analysis with the information on relationships between genes that is provided by gene networks. Existing tests for network enrichment analysis deal only with undirected networks, they can be computationally slow and are based on normality assumptions. Results We propose NEAT, a test for network enrichment analysis. The test is based on the hypergeometric distribution, which naturally arises ...

  12. Nfil3 is required for the development of all innate lymphoid cell subsets.

    Science.gov (United States)

    Seillet, Cyril; Rankin, Lucille C; Groom, Joanna R; Mielke, Lisa A; Tellier, Julie; Chopin, Michael; Huntington, Nicholas D; Belz, Gabrielle T; Carotta, Sebastian

    2014-08-25

    Innate lymphoid cell (ILC) populations protect against infection and are essential for lymphoid tissue formation and tissue remodeling after damage. Nfil3 is implicated in the function of adaptive immune lineages and NK cell development, but it is not yet known if Nfil3 regulates other innate lymphoid lineages. Here, we identify that Nfil3 is essential for the development of Peyer's patches and ILC2 and ILC3 subsets. Loss of Nfil3 selectively reduced Peyer's patch formation and was accompanied by impaired recruitment and distribution of lymphocytes within the patches. ILC subsets exhibited high Nfil3 expression and genetic deletion of Nfil3 severely compromised the development of all subsets. Subsequently, Nfil3(-/-) mice were highly susceptible to disease when challenged with inflammatory or infectious agents. Thus, we demonstrate that Nfil3 is a key regulator of the development of ILC subsets essential for immune protection in the lung and gut.

  13. mIL-2R, T cell subsets and hepatitis C

    OpenAIRE

    Li, Chao-Pin; Wang, Ke-Xia; Wang, Jian; Pan, Bo-Rong

    2002-01-01

    AIM: To study the levels of membrane interleukin-2 receptor (mIL-2R) and T cell subsets in peripheral blood mononuclear cells (PBMC) from patients with hepatitis C and their role in the pathogenesis of hepatitis C.

  14. NK ACTIVITY OF LYMPHOCYTE SUBSETS AND THE EFFECTS OF LOW DOSE RADIATION

    Institute of Scientific and Technical Information of China (English)

    Su Liaoyuan; Tian Hailin; Xu Yingdong; Geng Yongzhi

    1998-01-01

    Objective: To determine the NK activity of lymphocyte subsets and the effects of low dose radiation.Methods: Lymphocyte subsets were separated by monoclonal antibodies. The NK activity of each subset on tumor cells was detected by radioactive release method.Results: The results showed that besides NK cells, CD4,CD8 and B cells alone can kill tumor cells. But the cellkilling activity of NK cells appeared to be strongest.There was synergistic effect between CD4 and NK cells.The activity of mixed lymphocytes was more than that of only one subset. The effect of low dose radiation (LDR)on NK activity of panlymphocytes or NK cells was different. Conclusion: This paper demonstrated that NK activity of mononuclear cells was called "NK activity of lymphocytes", but it is not true. Only when NK cells were separated by monoclonal antibodies, its killer activity can be called "activity of NK cells".

  15. Differential control of Helios+/− Treg development by monocyte subsets through disparate inflammatory cytokines

    OpenAIRE

    Zhong, Hui; Yazdanbakhsh, Karina

    2013-01-01

    Control of Helios+/− Treg subset development is mediated through distinct cytokines and monocyte subpopulations.CD16+ monocytes inhibit Helios+ Treg proliferation through IL-12, whereas CD16− monocytes suppress Helios− Treg development through TNF-α.

  16. Tailored immune responses: novel effector helper T cell subsets in protective immunity.

    Directory of Open Access Journals (Sweden)

    Ervin E Kara

    2014-02-01

    Full Text Available Differentiation of naïve CD4⁺ cells into functionally distinct effector helper T cell subsets, characterised by distinct "cytokine signatures," is a cardinal strategy employed by the mammalian immune system to efficiently deal with the rapidly evolving array of pathogenic microorganisms encountered by the host. Since the T(H1/T(H2 paradigm was first described by Mosmann and Coffman, research in the field of helper T cell biology has grown exponentially with seven functionally unique subsets having now been described. In this review, recent insights into the molecular mechanisms that govern differentiation and function of effector helper T cell subsets will be discussed in the context of microbial infections, with a focus on how these different helper T cell subsets orchestrate immune responses tailored to combat the nature of the pathogenic threat encountered.

  17. Tailored immune responses: novel effector helper T cell subsets in protective immunity.

    Science.gov (United States)

    Kara, Ervin E; Comerford, Iain; Fenix, Kevin A; Bastow, Cameron R; Gregor, Carly E; McKenzie, Duncan R; McColl, Shaun R

    2014-02-01

    Differentiation of naïve CD4⁺ cells into functionally distinct effector helper T cell subsets, characterised by distinct "cytokine signatures," is a cardinal strategy employed by the mammalian immune system to efficiently deal with the rapidly evolving array of pathogenic microorganisms encountered by the host. Since the T(H)1/T(H)2 paradigm was first described by Mosmann and Coffman, research in the field of helper T cell biology has grown exponentially with seven functionally unique subsets having now been described. In this review, recent insights into the molecular mechanisms that govern differentiation and function of effector helper T cell subsets will be discussed in the context of microbial infections, with a focus on how these different helper T cell subsets orchestrate immune responses tailored to combat the nature of the pathogenic threat encountered.

  18. Enriching Music and Language Arts Experiences

    Science.gov (United States)

    Flohr, John W.

    2006-01-01

    The article focuses on enriching music and language arts experiences of students. Music can enrich literature and language arts, poetry, theater arts, transitions, science, and math, as well as help meet special learner needs. A well-understood example of enrichment is the alphabet song. A music or classroom teacher using the alphabet song helps…

  19. How Did the IGM Become Enriched?

    CERN Document Server

    Aguirre, A; Aguirre, Anthony; Schaye, Joop

    2006-01-01

    The enrichment of the intergalactic medium with heavy elements is a process that lies at the nexus of poorly-understood aspects of physical cosmology. We review current understanding of the processes that may remove metals from galaxies, the basic predictions of these models, the key observational constraints on enrichment, and how intergalactic enrichment may be used to test cosmological simulations.

  20. Perspectives on Job Enrichment and Productivity.

    Science.gov (United States)

    Suojanen, Waino W., Ed.; And Others

    The book of reading focuses on the state of job enrichment in the United States today, as well as some of its international implications. Featured in the book are 20 selected working papers analyzing the development and use of job enrichment in various types of organizations, union response to job enrichment, and its outlook for the future. The…

  1. Interval-valued fuzzy ideals generated by an interval-valued fuzzy subset in ordered semigroups

    OpenAIRE

    M. Shabir; Israr, Ali Khan

    2008-01-01

    In this paper, we de ne the concept of interval-valued fuzzy left (right, two sided, interior, bi-) ideal in ordered semigroups. We show that the interval- valued fuzzy subset J is an interval-valued fuzzy left (right, two sided, interior, bi-) ideal generated by an interval-valued fuzzy subset A i J and J + are fuzzy left (right, two sided, interior, bi-) ideals generated by A and A + respectively Peer Reviewed

  2. TCR repertoire and Foxp3 expression define functionally distinct subsets of CD4+ Treg cells1

    OpenAIRE

    Kuczma, Michal; Pawlikowska, Iwona; Kopij, Magdalena; Podolsky, Robert; Rempala, Grzegorz A.; Kraj, Piotr

    2009-01-01

    Despite extensive research efforts to characterize peripheral regulatory T cells (Treg) expressing transcription factor Foxp3, their subset complexity, phenotypic characteristics, TCR repertoire and antigen specificities remain ambiguous. Here, we identify and define two subsets of peripheral Treg cells differing in Foxp3 expression level and TCR repertoires. Treg cells expressing a high level of Foxp3 and TCRs not utilized by naive CD4+ T cells present a stable suppressor phenotype and domin...

  3. Sterile inflammation – do innate lymphoid cell subsets play a role?

    OpenAIRE

    Shane E Russell; Walsh, Patrick T.

    2012-01-01

    The recent identification of several novel innate lymphoid cell (iLC) subsets has increased our understanding of the mechanisms which link the innate and adaptive immune systems. While the contribution of these subsets toward the pathogenesis of human disease remains largely to be determined, it seems likely that they will play a particularly important role in sterile inflammatory settings where the innate response is seen as a critical mediator of inflammation. Several recent studies have hi...

  4. Sterile Inflammation-Do innate lymphoid cell subsets play a role?

    OpenAIRE

    Shane E Russell; Walsh, Patrick T.

    2012-01-01

    The recent identification of several novel innate lymphoid cell subsets (iLCs) has increased our understanding of the mechanisms which link the innate and adaptive immune systems. While the contribution of these subsets towards the pathogenesis of human disease remains largely to be determined, it seems likely that they will play a particularly important role in sterile inflammatory settings where the innate response is seen as a critical mediator of inflammation. Several recent studies have ...

  5. Characterizing a subset of the PPS maintaining the reference hyperplane of the radial projection point

    OpenAIRE

    N Nasrabadi; A Dehnokhalaji; M Soleimani-damaneh

    2014-01-01

    In this paper, we characterize a subset of the production possibility set consisting of production points whose radial projection points lie on the same supporting hyperplane of the production possibility set (PPS). To this end, we consider the CCR and BCC models1 and establish some theoretical results by utilizing linear programming-based techniques. Determining such a subset of the PPS provides a means to perform sensitivity analysis of inefficient units. This allows us to categorize DMUs i...

  6. Changes of monocyte subsets in patients with acute coronary syndrome and correlation with myocardial injury markers

    OpenAIRE

    Zhu, Li; Yin, Yigang; Zhou, Ruifang; Lin, Jie; Li, Jianming; Ye, Jun

    2015-01-01

    Objective: To explore the changes of peripheral blood monocytes subsets in acute coronary syndrome (ACS) and its clinical significance. Methods: A total of 68 ACS patients and 27 healthy subjects (HS) were enrolled. Monocyte subset analysis was performed using flow cytometry: CD14++CD16-(Mon1), CD14++CD16+ (Mon2), and CD14+CD16++ (Mon3). Results: 1. The number of Mon1 and Mon3 were significantly increased in ACS patients compared with HS (P

  7. LAP TGF-Beta Subset of CD4+CD25+CD127− Treg Cells is Increased and Overexpresses LAP TGF-Beta in Lung Adenocarcinoma Patients

    Directory of Open Access Journals (Sweden)

    Lorenzo Islas-Vazquez

    2015-01-01

    Full Text Available Lung cancer is the leading cause of cancer death worldwide. Adenocarcinoma, the most commonly diagnosed histologic type of lung cancer, is associated with smoking. Cigarette smoke promotes inflammation on the airways, which might be mediated by Th17 cells. This inflammatory environment may contribute to tumor development. In contrast, some reports indicate that tumors may induce immunosuppressive Treg cells to dampen immune reactivity, supporting tumor growth and progression. Thus, we aimed to analyze whether chronic inflammation or immunosuppression predominates at the systemic level in lung adenocarcinoma patients, and several cytokines and Th17 and Treg cells were studied. Higher proportions of IL-17-producing CD4+ T-cells were found in smoking control subjects and in lung adenocarcinoma patients compared to nonsmoking control subjects. In addition, lung adenocarcinoma patients increased both plasma concentrations of IL-2, IL-4, IL-6, and IL-10, and proportions of Latency Associated Peptide (LAP TGF-β subset of CD4+CD25+CD127− Treg cells, which overexpressed LAP TGF-β. This knowledge may lead to the development of immunotherapies that could inhibit the suppressor activity mediated by the LAP TGF-β subset of CD4+CD25+CD127− Treg cells to promote reactivity of immune cells against lung adenocarcinoma cells.

  8. Comparison of Human Neonatal and Adult Blood Leukocyte Subset Composition Phenotypes.

    Science.gov (United States)

    Prabhu, Savit B; Rathore, Deepak K; Nair, Deepa; Chaudhary, Anita; Raza, Saimah; Kanodia, Parna; Sopory, Shailaja; George, Anna; Rath, Satyajit; Bal, Vineeta; Tripathi, Reva; Ramji, Siddharth; Batra, Aruna; Aggarwal, Kailash C; Chellani, Harish K; Arya, Sugandha; Agarwal, Nidhi; Mehta, Umesh; Natchu, Uma Chandra Mouli; Wadhwa, Nitya; Bhatnagar, Shinjini

    2016-01-01

    The human peripheral leukocyte subset composition depends on genotype variation and pre-natal and post-natal environmental influence diversity. We quantified this composition in adults and neonates, and compared the median values and dispersal ranges of various subsets in them. We confirmed higher frequencies of monocytes and regulatory T cells (Tregs), similar frequencies of neutrophils, and lower frequencies of CD8 T cells, NKT cells, B1 B cells and gamma-delta T cells in neonatal umbilical cord blood. Unlike previous reports, we found higher frequencies of eosinophils and B cells, higher CD4:CD8 ratios, lower frequencies of T cells and iNKT cells, and similar frequencies of CD4 T cells and NK cells in neonates. We characterized monocyte subsets and dendritic cell (DC) subsets in far greater detail than previously reported, using recently described surface markers and gating strategies and observed that neonates had lower frequencies of patrolling monocytes and lower myeloid dendritic cell (mDC):plasmacytoid DC (pDC) ratios. Our data contribute to South Asian reference values for these parameters. We found that dispersal ranges differ between different leukocyte subsets, suggesting differential determination of variation. Further, some subsets were more dispersed in adults than in neonates suggesting influences of postnatal sources of variation, while some show the opposite pattern suggesting influences of developmental process variation. Together, these data and analyses provide interesting biological possibilities for future exploration. PMID:27610624

  9. Role of distinct CD4(+) T helper subset in pathogenesis of oral lichen planus.

    Science.gov (United States)

    Wang, Hui; Zhang, Dunfang; Han, Qi; Zhao, Xin; Zeng, Xin; Xu, Yi; Sun, Zheng; Chen, Qianming

    2016-07-01

    Oral lichen planus (OLP) is one of the most common chronic inflammatory oral mucosal diseases with T-cell-mediated immune pathogenesis. In subepithelial and lamina propria of OLP local lesions, the presence of CD4(+) T helper (CD4(+) Th) cells appeared as the major lymphocytes. These CD4(+) T lymphocytes can differentiate into distinct Th cell types such as Th1, Th2, Treg, Th17, Th22, Th9, and Tfh within the context of certain cytokines environment. Growing evidence indicated that Th1/Th2 imbalance may greatly participate into the cytokine network of OLP immunopathology. In addition, Th1/Th2 imbalance can be regulated by the Treg subset and also greatly influenced by the emerging novel CD4(+) Th subset Th17. Furthermore, the presence of novel subsets Th22, Th9 and Tfh in OLP patients is yet to be clarified. All these Th subsets and their specific cytokines may play a critical role in determining the character, extent and duration of immune responses in OLP pathogenesis. Therefore, we review the roles of distinct CD4(+) Th subsets and their signature cytokines in determining disease severity and susceptibility of OLP and also reveal the novel therapeutic strategies based on T lymphocytes subsets in OLP treatment. PMID:26693958

  10. Non-suppressive regulatory T cell subset expansion in pulmonary arterial hypertension.

    Science.gov (United States)

    Sada, Yoshiharu; Dohi, Yoshihiro; Uga, Sayuri; Higashi, Akifumi; Kinoshita, Hiroki; Kihara, Yasuki

    2016-08-01

    Regulatory T cells (Tregs) have been reported to play a pivotal role in the vascular remodeling of pulmonary arterial hypertension (PAH). Recent studies have revealed that Tregs are heterogeneous and can be characterized by three phenotypically and functionally different subsets. In this study, we investigated the roles of Treg subsets in the pathogenesis of PAH in eight patients with PAH and 14 healthy controls. Tregs and their subsets in peripheral blood samples were analyzed by flow cytometry. Treg subsets were defined as CD4(+)CD45RA(+)FoxP3(low) resting Tregs (rTregs), CD4(+)CD45RA(-)FoxP3(high) activated Tregs (aTregs), and CD4(+)CD45RA(-)FoxP3(low) non-suppressive Tregs (non-Tregs). The proportion of Tregs among CD4(+) T cells was significantly higher in PAH patients than in controls (6.54 ± 1.10 vs. 3.81 ± 0.28 %, p Tregs was significantly elevated in PAH patients compared with controls (4.06 ± 0.40 vs. 2.79 ± 0.14 %, p Tregs (p Treg subset was expanded and functionally activated in peripheral lymphocytes obtained from IPAH patients. We hypothesize that immunoreactions involving the specific activation of the non-Treg subset might play a role in the vascular remodeling of PAH. PMID:26319442

  11. An evaluation of exact methods for the multiple subset maximum cardinality selection problem.

    Science.gov (United States)

    Brusco, Michael J; Köhn, Hans-Friedrich; Steinley, Douglas

    2016-05-01

    The maximum cardinality subset selection problem requires finding the largest possible subset from a set of objects, such that one or more conditions are satisfied. An important extension of this problem is to extract multiple subsets, where the addition of one more object to a larger subset would always be preferred to increases in the size of one or more smaller subsets. We refer to this as the multiple subset maximum cardinality selection problem (MSMCSP). A recently published branch-and-bound algorithm solves the MSMCSP as a partitioning problem. Unfortunately, the computational requirement associated with the algorithm is often enormous, thus rendering the method infeasible from a practical standpoint. In this paper, we present an alternative approach that successively solves a series of binary integer linear programs to obtain a globally optimal solution to the MSMCSP. Computational comparisons of the methods using published similarity data for 45 food items reveal that the proposed sequential method is computationally far more efficient than the branch-and-bound approach. PMID:27027582

  12. Comparison of the quantities and subset distributions of natural killer cells among different races

    Institute of Scientific and Technical Information of China (English)

    FENG Yan-meng; ZHANG Rui-jun; ZHU Hong; PENG Hong; ZHOU Xiao-ping; HONG Kun-xue; LIU Jian-li; CHEN Jian-ping; SHAO Yi-ming

    2010-01-01

    Background Natural killer (NK) cells play critical roles in host immune defense, while the quantities and subset distributions may vary among different races. To address the difference, we compared these variables among Chinese Han, the Caucasians and the Blacks. The study may provide critical background information for both basic research and clinical investigation.Methods Blood samples collected from populations of different races were tested within 12 hours after collection and subsets of NK cells were characterized using flow cytometry.Results The absolute NK count in the Chinese Han was significantly higher than that in the Caucasian. The Han and Caucasian groups showed higher percentages of cytotoxic subset compared to that of the Black group. The percentage of cytokine-producing subset of Chinese Han group was lower than that of Caucasian and Black groups. Black group had a higher percentage of function-unknown NK subset than that of the Hah and Caucasian groups.Conclusion Our data indicated that NK cell count and the distribution of different subsets varied among different races,which should be taken into consideration in related investigations.

  13. Enriching Orphans’ Potentials through Interpersonal and Intrapersonal Intelligence Enrichment Activities

    Directory of Open Access Journals (Sweden)

    Nurulwahida Hj Azid

    2016-01-01

    Full Text Available Orphans are considered a minority and they should be given a greater emphasis so that they do not feel left out and can build their own lives without a sense of humility. This does not mean that the orphans should be pampered instead they should be given the confidence and motivation to strive for success in later life. Humility among orphans can be associated with interpersonal and intrapersonal intelligences. This study aims to evaluate the impact of problem-solving activity treatment based on the interpersonal and intrapersonal intelligences. 46 students from two orphanages were involved as the treatment group. The research design used was a one-group pretest-posttest design applied through a combination of quantitative and qualitative approaches. Enrichment activities that provided interpersonal and intrapersonal skills as evidenced in this study should be carried out regularly at orphanages. Our study has proven that orphans‟ rights to learn cannot be neglected and „no child left behind „policy needs to be carried through by everybody involved with orphans‟ well-being. Teachers and carers need to be trained to use these enrichment activities at their orphanages to help maximize the orphans‟ potentials.

  14. A functional family-wide screening of SP/KLF proteins identifies a subset of suppressors of KRAS-mediated cell growth.

    Science.gov (United States)

    Fernandez-Zapico, Martin E; Lomberk, Gwen A; Tsuji, Shoichiro; DeMars, Cathrine J; Bardsley, Michael R; Lin, Yi-Hui; Almada, Luciana L; Han, Jing-Jing; Mukhopadhyay, Debabrata; Ordog, Tamas; Buttar, Navtej S; Urrutia, Raul

    2011-04-15

    SP/KLF (Specificity protein/Krüppel-like factor) transcription factors comprise an emerging group of proteins that may behave as tumour suppressors. Incidentally, many cancers that display alterations in certain KLF proteins are also associated with a high incidence of KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue) mutations. Therefore in the present paper we investigate whether SP/KLF proteins suppress KRAS-mediated cell growth, and more importantly, the potential mechanisms underlying these effects. Using a comprehensive family-wide screening of the 24 SP/KLF members, we discovered that SP5, SP8, KLF2, KLF3, KLF4, KLF11, KLF13, KLF14, KLF15 and KLF16 inhibit cellular growth and suppress transformation mediated by oncogenic KRAS. Each protein in this subset of SP/KLF members individually inhibits BrdU (5-bromo-2-deoxyuridine) incorporation in KRAS oncogenic-mutant cancer cells. SP5, KLF3, KLF11, KLF13, KLF14 and KLF16 also increase apoptosis in these cells. Using KLF11 as a representative model for mechanistic studies, we demonstrate that this protein inhibits the ability of cancer cells to form both colonies in soft agar and tumour growth in vivo. Molecular studies demonstrate that these effects of KLF11 are mediated, at least in part, through silencing cyclin A via binding to its promoter and leading to cell-cycle arrest in S-phase. Interestingly, similar to KLF11, KLF14 and KLF16 mechanistically share the ability to modulate the expression of cyclin A. Collectively, the present study stringently defines a distinct subset of SP/KLF proteins that impairs KRAS-mediated cell growth, and that mechanistically some members of this subset accomplish this, at least in part, through regulation of the cyclin A promoter. PMID:21171965

  15. [Cellular immunity changes after total parenteral nutrition enriched with glutamine in patients with sepsis and malnutrition].

    Science.gov (United States)

    Słotwiński, R; Pertkiewicz, M; Lech, G; Szczygieł, B

    2000-06-01

    The influence of glutamine on human immune system is multidirectional but the exact changes still remain unclear. In this study the effect of total parenteral nutrition (TPN) enriched with glutamine on some selected immunological and nutritional parameters was examined in twelve surgical patients with sepsis and malnutrition. The reason for glutamine supplementation was lack of clinical improvement after standard TPN. All patients received TPN enriched with glutamine for 10 days. Phenotypic analysis of peripheral blood mononuclear subsets (CD4, CD8, CD16, CD56, HLA-DR) were measured before, during (on days 2, 4, 6) glutamine administration and two days after (day 12) glutamine withdrawal. Simultaneously some nutritional parameters were assessed. The number and percentage of CD4, CD16, CD56 mononuclear subsets increased significantly on day 2 and stayed on the same level during observation (with exception in CD4 on day 6, 12 and CD56 on day 4). No significant differences in CD8 and HLA-DR number and percentages were observed after TPN enriched with glutamine. BIA examination revealed on days 2 and 12 significant decrease of total body water and significant increase of body cell mass, intracellular water on day 12. It was correlated with significant higher total lymphocytes count and significantly higher total protein, serum albumin, transferrin, cholesterol and CRP concentration. Results demonstrated that TPN supplemented with glutamine improved rapidly some immunological and nutritional parameters in surgical, malnutrition patients with sepsis.

  16. EMIS: Enrichment Management Information System

    International Nuclear Information System (INIS)

    The objective of the effort was the development of a calculational tool which would permit DOE to make realistic projections of the separative work demands of its customers as an aid in planning for the future operation of the enrichment facilities. The calculational methods were to recognize the flexibility in scheduling, etc., available to DOE customers under their enrichment contreacts as well as the ability to pool separative work withdrawn under two or more contracts. It was also to be designed to permit the user to add new customers or delete existing contracts as well as to allow variation of the estimated start-up dates for those reactors currently under construction. The output of the model was to display projections of separative work demand as SWU and in triplet form for several categories of reactors. These included, in addition to the total demand on the enrichment complex, separate totals for domestic and foreign customers, for reactors with Requirements and Adjustable Fixed Commitment contracts and for reactors in operation, under construction and projected new reactors designated by the user. The foundations upon which the system is based are described in this report. This includes a discussion of the available alternatives for customer management of separative work and the assumptions and guidelines established for development of the model. The report also contains a description of the computational procedures used in the model, and a description of the EMIS system itself, which also serves as a users' manual for the code. Finally, samples demonstrating the use of the system and indicating the form of the input and output are included

  17. Enrichment planting without soil treatment

    Energy Technology Data Exchange (ETDEWEB)

    Hagner, Mats

    1998-12-31

    Where enrichment planting had been carried out with either of the two species Picea abies and Pinus contorta, the survival of the planted seedlings was at least as good as after planting in a normal clear cut area treated with soil scarification. This was in spite of the fact that the seedlings were placed shallow in the humus layer without any soil treatment. However, they were sheltered from insects by treatment before planting. Where enrichment planting was carried out with Pinus sylvestris the survival in dense forest was poor, but in open forest the survival was good. The growth of planted seedlings was enhanced by traditional clearing and soil treatment. However, this was for Pinus sylvestris not enough to compensate for the loss of time, 1-2 years, caused by arrangement of soil scarification. The growth of seedlings planted under crown cover was directly related to basal area of retained trees. However, the variation in height growth among individual seedlings was very big, which meant that some seedlings grow well also under a fairly dense forest cover. The pioneer species Pinus sylvestris reacted more strongly to basal area of retained trees than did the shade tolerant species Picea abies. Enrichment planting seems to be a necessary tool for preserving volume productivity, at places where fairly intensive harvest of mature trees has been carried out in stands of ordinary forest type in central Sweden. If double seedlings, with one Picea abies and one Pinus sylvestris, are used, the probability for long term establishment is enhanced 13 refs, 20 figs, 4 tabs

  18. Boron enrichment in martian clay.

    Science.gov (United States)

    Stephenson, James D; Hallis, Lydia J; Nagashima, Kazuhide; Freeland, Stephen J

    2013-01-01

    We have detected a concentration of boron in martian clay far in excess of that in any previously reported extra-terrestrial object. This enrichment indicates that the chemistry necessary for the formation of ribose, a key component of RNA, could have existed on Mars since the formation of early clay deposits, contemporary to the emergence of life on Earth. Given the greater similarity of Earth and Mars early in their geological history, and the extensive disruption of Earth's earliest mineralogy by plate tectonics, we suggest that the conditions for prebiotic ribose synthesis may be better understood by further Mars exploration. PMID:23762242

  19. DOE enrichment plant hums ahead

    International Nuclear Information System (INIS)

    The Department of Energy's $10-billion gas centrifuge uranium enrichment plant, after three years of construction, is rising on schedule near Piketon, Ohio. A detailed conceptual design, smart management, liberal design fees, hungry contractors and cooperative unions are combining to get the job done. One reason for completing the task is that this will be a far more efficient process - 135 MW will be required to operate the centrifuge plant vs more than 2100 MW to produce the same amount of fuel at the mile-square diffusion plant near Portsmouth, Ohio

  20. Boron enrichment in martian clay.

    Directory of Open Access Journals (Sweden)

    James D Stephenson

    Full Text Available We have detected a concentration of boron in martian clay far in excess of that in any previously reported extra-terrestrial object. This enrichment indicates that the chemistry necessary for the formation of ribose, a key component of RNA, could have existed on Mars since the formation of early clay deposits, contemporary to the emergence of life on Earth. Given the greater similarity of Earth and Mars early in their geological history, and the extensive disruption of Earth's earliest mineralogy by plate tectonics, we suggest that the conditions for prebiotic ribose synthesis may be better understood by further Mars exploration.

  1. Uranium enrichment plant risk analysis

    International Nuclear Information System (INIS)

    A method for risk analysis of enrichment facilities is presented and applied to a small scale ultracentrifuge plant. Internal events are identified and the consequences of accidental releases of U F6 are quantified in terms of its toxicological and radiological impact. It is shown that releases in the feed and the cascade areas offers no hazards to the public . Releases of liquefied U F6 in the withdrawal areas, associated with failures in the building isolation systems, may cause undesirable consequences. (author). 11 refs, 4 figs, 3 tabs

  2. HUMAN PAPILLOMAVIRUS INFECTIONS IN LARYNGEAL CANCER

    NARCIS (Netherlands)

    Torrente, Mariela C.; Rodrigo, Juan P.; Haigentz, Missak; Dikkers, Frederik G.; Rinaldo, Alessandra; Takes, Robert P.; Olofsson, Jan; Ferlito, Alfio

    2011-01-01

    Although the association and clinical significance of human papillomavirus (HPV) infections with a subset of head and neck cancers, particularly for oropharyngeal carcinoma, has recently been well documented, the involvement of HPV in laryngeal cancer has been inadequately evaluated. Herein we revie

  3. Circulating TFH subset distribution is strongly affected in lupus patients with an active disease.

    Directory of Open Access Journals (Sweden)

    Carole Le Coz

    Full Text Available Follicular helper T cells (TFH represent a distinct subset of CD4(+ T cells specialized in providing help to B lymphocytes, which may play a central role in autoimmune diseases having a major B cell component such as systemic lupus erythematosus. Recently, TFH subsets that share common phenotypic and functional characteristics with TFH cells from germinal centers, have been described in the peripheral blood from healthy individuals. The aim of this study was to analyze the distribution of such populations in lupus patients. Circulating TFH cell subsets were defined by multicolor flow cytometry as TFH17 (CXCR3(-CCR6(+, TFH1 (CXCR3 (+ CCR6(- or TFH2 (CXCR3(-CCR6(- cells among CXCR5 (+ CD45RA(-CD4(+ T cells in the peripheral blood of 23 SLE patients and 23 sex and age-matched healthy controls. IL-21 receptor expression by B cells was analyzed by flow cytometry and the serum levels of IL-21 and Igs were determined by ELISA tests. We found that the TFH2 cell subset frequency is strongly and significantly increased in lupus patients with an active disease (SLEDAI score>8, while the TFH1 cell subset percentage is greatly decreased. The TFH2 and TFH1 cell subset frequency alteration is associated with the presence of high Ig levels and autoantibodies in patient's sera. Moreover, the TFH2 cell subset enhancement correlates with an increased frequency of double negative memory B cells (CD27(-IgD(-CD19(+ cells expressing the IL-21R. Finally, we found that IgE levels in lupus patients' sera correlate with disease activity and seem to be associated with high TFH2 cell subset frequency. In conclusion, our study describes for the first time the distribution of circulating TFH cell subsets in lupus patients. Interestingly, we found an increased frequency of TFH2 cells, which correlates with disease activity. Our results suggest that this subset might play a key role in lupus pathogenesis.

  4. Cancer outlier detection based on likelihood ratio test

    OpenAIRE

    Hu, Jianhua

    2008-01-01

    Motivation: Microarray experiments can be used to help study the role of chromosomal translocation in cancer development through cancer outlier detection. The aim is to identify genes that are up- or down-regulated in a subset of cancer samples in comparison to normal samples.

  5. CD27 natural killer cell subsets play different roles during the pre-onset stage of experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Gao, Ming; Yang, Yan; Li, Daling; Ming, Bingxia; Chen, Huoying; Sun, Yan; Xiao, Yifan; Lai, Lin; Zou, Huijuan; Xu, Yong; Xiong, Ping; Tan, Zheng; Gong, Feili; Zheng, Fang

    2016-08-01

    NK cells participate in the development of human multiple sclerosis (MS) and mouse experimental autoimmune encephalomyelitis (EAE), but the roles of different NK cell subsets in disease onset remain poorly understood. In this study, murine NK cells were divided into CD27(high) and CD27(low/-) subsets. The CD27(high) subset was decreased and the CD27(low/-) subset was increased in lymphoid organs during the pre-onset stage of EAE. Compared with the counterpart in naïve mice, the CD27(high) subset showed lower expression of Ly49D, Ly49H and NKG2D, and less production of IFN-γ, whereas the CD27(low/-) subset showed similar expression of the above mentioned surface receptors but higher cytotoxic activity in EAE mice. Compared with the CD27(high) subset, the CD27(low/-) subset exhibited increased promotion of DC maturation and no significant inhibition of T cells proliferation and Th17 cells differentiation in vitro Additionally, adoptive transfer of the CD27(low/-) subset, but not the CD27(high) subset, exacerbated the severity of EAE. Collectively, our data suggest the CD27 NK cell subsets play different roles in controlling EAE onset, which provide a new understanding for the regulation of NK cell subsets in early autoimmune disease. PMID:27368310

  6. Comparison of Subset-Based Local and Finite Element-Based Global Digital Image Correlation

    KAUST Repository

    Pan, Bing

    2015-02-12

    Digital image correlation (DIC) techniques require an image matching algorithm to register the same physical points represented in different images. Subset-based local DIC and finite element-based (FE-based) global DIC are the two primary image matching methods that have been extensively investigated and regularly used in the field of experimental mechanics. Due to its straightforward implementation and high efficiency, subset-based local DIC has been used in almost all commercial DIC packages. However, it is argued by some researchers that FE-based global DIC offers better accuracy because of the enforced continuity between element nodes. We propose a detailed performance comparison between these different DIC algorithms both in terms of measurement accuracy and computational efficiency. Then, by measuring displacements of the same calculation points using the same calculation algorithms (e.g., correlation criterion, initial guess estimation, subpixel interpolation, optimization algorithm and convergence conditions) and identical calculation parameters (e.g., subset or element size), the performances of subset-based local DIC and two FE-based global DIC approaches are carefully compared in terms of measurement error and computational efficiency using both numerical tests and real experiments. A detailed examination of the experimental results reveals that, when subset (element) size is not very small and the local deformation within a subset (element) can be well approximated by the shape function used, standard subset-based local DIC approach not only provides better results in measured displacements, but also demonstrates much higher computation efficiency. However, several special merits of FE-based global DIC approaches are indicated.

  7. Evaluación de la eficacia de un suplemento oral en polvo enriquecido con ácido eicosapentaenoico en un grupo de pacientes con cáncer Efficacy evaluation of an oral powder supplement enriched with eicosapentaenoic acid in cancer patients

    Directory of Open Access Journals (Sweden)

    C. Gómez-Candela

    2011-12-01

    Full Text Available Introducción: El efecto beneficioso del ácido eicosapentaenoico en pacientes con cáncer está ampliamente descrito sobre todo en lo que respecta a su rol en la caquexia tumoral. Objetivo: Evaluar la eficacia de la administración de un nuevo suplemento oral en polvo con adición de este componente frente a un suplemento líquido estándar en un grupo de pacientes oncológicos. Pacientes y métodos: 61 adultos mayores de 18 años de ambos sexos con cáncer, fueron aleatorizados en dos grupos para recibir durante un mes 600 kcal extras añadidas a su alimentación; uno a través de un suplemento oral en polvo con 1,5 g de ácido eicosapentaenoico/día (RSI y el otro con un producto líquido estándar (RE. Tanto al inicio como al final del estudio se realizaron las siguientes medidas: valoración global subjetiva generada por el paciente (VGS-gp, parámetros antropométricos (Pliegues, circunferencia del brazo y bioimpedancia, dietéticos (registro alimentario de 72 horas, bioquímicos e inflamatorios (bioquímica básica, citoquinas, prealbúmina y PCR. La calidad de vida fue valorada mediante el cuestionario SF-36. Así mismo se emplearon escalas de percepción sensorial, tolerancia de los productos y motivación y saciedad al comer durante el estudio. Resultados: Finalizaron el estudio 40 pacientes. Tras la intervención ambos grupos mantuvieron sus parámetros antropométricos y aumentaron significativamente la prealbúmina (RSI 16,11 ± 5,66 mg/dl vs 19.81 ± 6.75 mg/dl p Background and objectives: The beneficial effect of eicosapentaenoic acid in cancer patients is widely described especially in relation to its role in tumour cachexia. The aim of the study was to evaluate the efficacy of administration of a new oral powder supplement enriched with eicosapentaenoic acid compared to a standard liquid supplement in cancer patients. Patients and methods: A total of 61 cancer patients, aged more than 18 years, were randomized to receive during

  8. Method for semi-automated microscopy of filtration-enriched circulating tumor cells

    OpenAIRE

    Pailler, Emma; Oulhen, Marianne; Billiot, Fanny; Galland, Alexandre; Auger, Nathalie; Faugeroux, Vincent; Laplace-Builhé, Corinne; Besse, Benjamin; Loriot, Yohann; Ngo-Camus, Maud; Hemanda, Merouan; Colin R. Lindsay; Soria, Jean-Charles; Vielh, Philippe; Farace, Françoise

    2016-01-01

    Background Circulating tumor cell (CTC)-filtration methods capture high numbers of CTCs in non-small-cell lung cancer (NSCLC) and metastatic prostate cancer (mPCa) patients, and hold promise as a non-invasive technique for treatment selection and disease monitoring. However filters have drawbacks that make the automation of microscopy challenging. We report the semi-automated microscopy method we developed to analyze filtration-enriched CTCs from NSCLC and mPCa patients. Methods Spiked cell l...

  9. Screening Key Genes Associated with the Development and Progression of Non-small Cell Lung Cancer Based on Gene-enrichment Analysis and Meta-analysis%基因富集及meta分析筛选非小细胞肺癌发生发展关键基因的研究

    Institute of Scientific and Technical Information of China (English)

    何文武; 冼磊; 王永勇; 胡艳玲; 陈铭伍

    2012-01-01

    Background and objective Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors; however, its causes are still not completely understood. This study was designed to screen the key genes and pathways related to NSCLC occurrence and development and to establish the scientific foundation for the genetic mechanisms and targeted therapy of NSCLC. Methods Both gene set-enrichment analysis (GSEA) and meta-analysis (meta) were used to screen the critical pathways and genes that might be corretacted with the development and progression of lung cancer at the transcription level. Results Using the GSEA and meta methods, focal adhesion and regulation of act in cytoskeleton were determined to be the more prominent overlapping significant pathways. In the focal adhesion pathway, 31 genes were statistically significant (P<0.05), whereas in the regulation of actin cytoskeleton pathway, 32 genes were statistically significant (P<0.05). Conclusion The focal adhesion and the regulation of actin cytoskeleton pathways might play important roles in the occurrence and development of NSCLC. Further studies are needed to determine the biological function for the positiue genes.%背景与目的 非小细胞肺癌(non-small cell lung cancer,NSCLC)是全球最常见的恶性肿瘤之一,其发病遗传机制仍不清楚.本研究旨在筛选影响NSCLC发生发展的关键基因和通路,为NSCLC发病遗传机制及靶向治疗的研究奠定科学基础.方法 运用基因组富集分析(gene set enrichment analysis,GSEA)以及对单套数据集单个基因元分析(meta-analysis,meta)的方法,筛选出在转录水平上影响NSCLC发生发展的关键通路和基因.结果 通过GSEA和meta两种分析方法得出的通路中,重叠性较高的主要为粘着斑通路和细胞骨架肌动蛋白调控通路.在粘着斑通路中31个基因具有统计学意义(P<0.05);细胞骨架肌动蛋白调控通路中32个基因具有统计学意义(P<0.05).结论 粘着

  10. Proteomic profiling of patient-derived glioblastoma xenografts identifies a subset with activated EGFR: implications for drug development.

    Science.gov (United States)

    Brown, Kristine E; Chagoya, Gustavo; Kwatra, Shawn G; Yen, Timothy; Keir, Stephen T; Cooter, Mary; Hoadley, Katherine A; Rasheed, Ahmed; Lipp, Eric S; Mclendon, Roger; Ali-Osman, Francis; Bigner, Darell D; Sampson, John H; Kwatra, Madan M

    2015-06-01

    The development of drugs to inhibit glioblastoma (GBM) growth requires reliable pre-clinical models. To date, proteomic level validation of widely used patient-derived glioblastoma xenografts (PDGX) has not been performed. In the present study, we characterized 20 PDGX models according to subtype classification based on The Cancer Genome Atlas criteria, TP53, PTEN, IDH 1/2, and TERT promoter genetic analysis, EGFR amplification status, and examined their proteomic profiles against those of their parent tumors. The 20 PDGXs belonged to three of four The Cancer Genome Atlas subtypes: eight classical, eight mesenchymal, and four proneural; none neural. Amplification of EGFR gene was observed in 9 of 20 xenografts, and of these, 3 harbored the EGFRvIII mutation. We then performed proteomic profiling of PDGX, analyzing expression/activity of several proteins including EGFR. Levels of EGFR phosphorylated at Y1068 vary considerably between PDGX samples, and this pattern was also seen in primary GBM. Partitioning of 20 PDGX into high (n = 5) and low (n = 15) groups identified a panel of proteins associated with high EGFR activity. Thus, PDGX with high EGFR activity represent an excellent pre-clinical model to develop therapies for a subset of GBM patients whose tumors are characterized by high EGFR activity. Further, the proteins found to be associated with high EGFR activity can be monitored to assess the effectiveness of targeting EGFR. The development of drugs to inhibit glioblastoma (GBM) growth requires reliable pre-clinical models. We validated proteomic profiles using patient-derived glioblastoma xenografts (PDGX), characterizing 20 PDGX models according to subtype classification based on The Cancer Genome Atlas (TCGA) criteria, TP53, PTEN, IDH 1/2, and TERT promoter genetic analysis, EGFR amplification status, and examined their proteomic profiles against those of their parent tumors. Proteins found to be associated with high EGFR activity represent potential

  11. Effects of Enrichment and Litter Parity on Reproductive Performance and Behavior in BALB/c and 129/Sv Mice.

    Science.gov (United States)

    Whitaker, Julia W; Moy, Sheryl S; Pritchett-Corning, Kathleen R; Fletcher, Craig A

    2016-01-01

    We examined the effect of adding species-appropriate environmental enrichment items to breeding cages of BALB/cAnNCrl and 129S2/SvPasCrl mice. The 3 enrichment conditions were: 1) cotton nesting material; 2) nesting material plus a paper shelter and rolled paper bedding; and 3) an igloo dome with an exercise wheel in addition to the shelter-group enrichments. We measured litter size, litter survival to weaning age, average pup weight at 21 d, and the interlitter interval to evaluate reproductive performance. A random subset of the first- or second-litter offspring from each enrichment condition and strain was assessed in multiple behavioral tests. Enrichment significantly affected anxiety-like behavior and sociability, with the direction of change dependent on strain and sex. Litter parity had greater effects on some reproductive parameters than did the enrichment condition, and this effect was not solely due to a difference between the first compared with subsequent litters. The significant effects of litter parity on the number of pups born and weaned, female pup weight, and interlitter interval were dependent on the enrichment condition in BALB/c but not 129/Sv mice. Offspring from the first or second litter were included in a generational component to investigate whether enrichment effects on reproduction persist in adult offspring after transfer to a different facility for breeding. Natal cage enrichment had no effect on any reproductive parameter in the transferred mice. Overall, additional enrichment beyond nesting material had a beneficial effect on the interlitter interval in BALB/c mice and on the number of pups weaned in 129/Sv mice. PMID:27423144

  12. Label-free haemogram using wavelength modulated Raman spectroscopy for identifying immune-cell subset

    Science.gov (United States)

    Ashok, Praveen C.; Praveen, Bavishna B.; Campbell, Elaine C.; Dholakia, Kishan; Powis, Simon J.

    2014-03-01

    Leucocytes in the blood of mammals form a powerful protective system against a wide range of dangerous pathogens. There are several types of immune cells that has specific role in the whole immune system. The number and type of immune cells alter in the disease state and identifying the type of immune cell provides information about a person's state of health. There are several immune cell subsets that are essentially morphologically identical and require external labeling to enable discrimination. Here we demonstrate the feasibility of using Wavelength Modulated Raman Spectroscopy (WMRS) with suitable machine learning algorithms as a label-free method to distinguish between different closely lying immune cell subset. Principal Component Analysis (PCA) was performed on WMRS data from single cells, obtained using confocal Raman microscopy for feature reduction, followed by Support Vector Machine (SVM) for binary discrimination of various cell subset, which yielded an accuracy >85%. The method was successful in discriminating between untouched and unfixed purified populations of CD4+CD3+ and CD8+CD3+ T lymphocyte subsets, and CD56+CD3- natural killer cells with a high degree of specificity. It was also proved sensitive enough to identify unique Raman signatures that allow clear discrimination between dendritic cell subsets, comprising CD303+CD45+ plasmacytoid and CD1c+CD141+ myeloid dendritic cells. The results of this study clearly show that WMRS is highly sensitive and can distinguish between cell types that are morphologically identical.

  13. Absolute count of T and B lymphocyte subsets is decreased in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Gambichler T

    2010-01-01

    Full Text Available Abstract Background Previous reports on lymphocyte subpopulations in systemic sclerosis (SSc are conflicting. Therefore, we aimed to investigate the lymphocyte subsets in SSc patients who were not on immunosuppressive therapy. Methods Lymphocyte subsets were assessed in the peripheral blood of SSc patients (n = 29 and healthy controls (n = 29 using the four colour flow cytometry method. Correlation studies were also performed in order to assess the relationship between lymphocyte subsets and clinical parameters. Results The absolute count of lymphocytes (P = 0.0042, CD3+ (P = 0.0014, CD4+ (P = 0.0070, CD8+ (P = 0.021, and CD19+ cells (P = 0.024 was significantly decreased in SSc patients when compared to healthy controls. CD4+/CD8+ ratio and the absolute count of CD56+ cells observed in SSc patients did not significantly differ from controls (P = 0.165; P = 0.632, respectively. There was no substantial relationship between the lymphocyte subset levels and clinical features (i.e., SSc subtype, autoantibody profiles, organ involvement, except for a significant inverse correlation of CD19+ cells and the modified Rodnan skin score (r = -0.43, P = 0.020. Conclusion Our data support previous reports indicating that subsets of T lymphocytes as well as B lymphocytes play a role in the pathogenesis of SSc.

  14. Increased Peripheral Proinflammatory T Helper Subsets Contribute to Cardiovascular Complications in Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Ru-xing Zhao

    2014-01-01

    Full Text Available Background. Coronary atherosclerotic heart disease (CHD is one of the major concerns in type 2 diabetes (T2D. The systemic chronic inflammation has been postulated to bridge the increased risk of cardiovascular disease and T2D. We formulated that increased peripheral proinflammatory T helper subsets contributed to the development of cardiovascular complications in diabetic patients. Methods. The frequencies of peripheral total CD4+ T helper cells, proinflammatory Th1, Th17, and Th22 subsets were determined by flow cytometry in diabetic patients with or without CHD (n=42 and 67, resp.. Results. Both peripheral frequencies and total numbers of Th1, Th17, and Th22 cells were further increased in diabetic patients with CHD. Logistic regression and categorical cross-table analysis further confirmed that increased proinflammatory Th subsets, especially Th22, were independent risk factors of cardiovascular complication in diabetes. Elevated Th subsets also correlated with increased CRP levels and the atherogenic index of plasma. Moreover, Th1 frequency and Th22 numbers demonstrated remarkable potential in predicting CHD in diabetes. Conclusions. Increased peripheral proinflammatory T helper subsets act in concert and contribute to the increased prevalence of diabetic cardiovasculopathy. The recently identified Th22 cells might play an independent role in CHD and represent a novel proxy for cardiovascular risks in diabetes.

  15. Effects of Environmental Enrichment on Spatial Memory and Neurochemistry in Middle-Aged Mice

    OpenAIRE

    Frick, Karyn M.; Stearns, Nancy A.; Pan, Jing-Yu; Berger-Sweeney, Joanne

    2003-01-01

    The present study compared the effects of environmental enrichment on spatial memory, glutamic acid decarboxylase (GAD) activity, and synaptophysin levels in middle-aged male and female mice. Prior to testing, a subset of 18-month-old male and female C57BL/6 mice was housed with two to three toys and a running wheel in the home cage for up to 29 d. Adult mice (7 mo) of both sexes and the remaining middle-aged mice were group (social) housed, but not exposed to enrichin...

  16. Novel Therapies for Pediatric Cancers

    OpenAIRE

    Macy, Margaret E.; Sawczyn, Kelly K.; Garrington, Timothy P.; Graham, Douglas K.; Gore, Lia

    2008-01-01

    The current high cure rates for children diagnosed with cancer can in part be attributed to emphasis on large cooperative group clinical trials. The significant improvement in pediatric cancer survival over the last few decades is the result of optimized chemotherapy drug dosing, timing, and intensity; however, further alterations in traditional chemotherapy agents are unlikely to produce substantially better outcomes. Furthermore, there remains a subset of patients who have a very poor progn...

  17. Uranium enrichment and the environment

    International Nuclear Information System (INIS)

    The three gaseous diffusion plants comprise one of the largest industrial complexes in the free world. Since all of the enrichment is done inside a very large plumbing maze, the control of radioactivity does not present a serious problem. Conventional, nonexotic engineering and administrative measures adequately control the minor levels of radioactivity associated with support activities such as equipment decontamination and maintenance. The treatment and control of chemical waste streams to comply with Federal and state regulations has required the commitment of 47 million dollars since 1974. Through 1982, an additional 84 million dollars may be required. The high cost is not a reflection of initially poor conditions but is rather the result of providing large treatment systems to meet very low discharge limits. Examples that will be discussed include airborne particulate removal, recirculating cooling water treatment, and hazardous waste disposal concepts

  18. Topological Features In Cancer Gene Expression Data

    OpenAIRE

    Lockwood, Svetlana; Krishnamoorthy, Bala

    2014-01-01

    We present a new method for exploring cancer gene expression data based on tools from algebraic topology. Our method selects a small relevant subset from tens of thousands of genes while simultaneously identifying nontrivial higher order topological features, i.e., holes, in the data. We first circumvent the problem of high dimensionality by dualizing the data, i.e., by studying genes as points in the sample space. Then we select a small subset of the genes as landmarks to construct topologic...

  19. Selective effects of alpha interferon on human T-lymphocyte subsets during mixed lymphocyte cultures

    DEFF Research Database (Denmark)

    Hokland, M; Hokland, P; Heron, I;

    1983-01-01

    Mixed lymphocyte reaction (MLR) cultures of human lymphocyte subsets with or without the addition of physiological doses of human alpha interferon (IFN-alpha) were compared with respect to surface marker phenotypes and proliferative capacities of the responder cells. A selective depression on the T...... T4 cells and decreased numbers of T4 cells harvested from IFN MLRs (days 5-6 of culture). In contrast, it was shown that the T8 (cytotoxic/suppressor) subset in MLRs was either not affected or slightly stimulated by the addition of IFN. The depression of the T4 cells by IFN was accompanied......4 (inducer) T-cell subset could be demonstrated as a sequence of events: decreased fluorescence intensity of the T4 inducer cells (day 2 of culture), decreased percentages of T4 cells as demonstrated by cell cytofluorometry (days 3-6 of culture), and decreased 3H-thymidine incorporation of purified...

  20. Crossing the Vascular Wall: Common and Unique Mechanisms Exploited by Different Leukocyte Subsets during Extravasation

    Directory of Open Access Journals (Sweden)

    Michael Schnoor

    2015-01-01

    Full Text Available Leukocyte extravasation is one of the essential and first steps during the initiation of inflammation. Therefore, a better understanding of the key molecules that regulate this process may help to develop novel therapeutics for treatment of inflammation-based diseases such as atherosclerosis or rheumatoid arthritis. The endothelial adhesion molecules ICAM-1 and VCAM-1 are known as the central mediators of leukocyte adhesion to and transmigration across the endothelium. Engagement of these molecules by their leukocyte integrin receptors initiates the activation of several signaling pathways within both leukocytes and endothelium. Several of such events have been described to occur during transendothelial migration of all leukocyte subsets, whereas other mechanisms are known only for a single leukocyte subset. Here, we summarize current knowledge on regulatory mechanisms of leukocyte extravasation from a leukocyte and endothelial point of view, respectively. Specifically, we will focus on highlighting common and unique mechanisms that specific leukocyte subsets exploit to succeed in crossing endothelial monolayers.

  1. Digital image correlation involves an inverse problem: A regularization scheme based on subset size constraint

    Science.gov (United States)

    Zhan, Qin; Yuan, Yuan; Fan, Xiangtao; Huang, Jianyong; Xiong, Chunyang; Yuan, Fan

    2016-06-01

    Digital image correlation (DIC) is essentially implicated in a class of inverse problem. Here, a regularization scheme is developed for the subset-based DIC technique to effectively inhibit potential ill-posedness that likely arises in actual deformation calculations and hence enhance numerical stability, accuracy and precision of correlation measurement. With the aid of a parameterized two-dimensional Butterworth window, a regularized subpixel registration strategy is established, in which the amount of speckle information introduced to correlation calculations may be weighted through equivalent subset size constraint. The optimal regularization parameter associated with each individual sampling point is determined in a self-adaptive way by numerically investigating the curve of 2-norm condition number of coefficient matrix versus the corresponding equivalent subset size, based on which the regularized solution can eventually be obtained. Numerical results deriving from both synthetic speckle images and actual experimental images demonstrate the feasibility and effectiveness of the set of newly-proposed regularized DIC algorithms.

  2. The Subset Sum Problem: Reducing Time Complexity of NP-Completeness with Quantum Search

    Directory of Open Access Journals (Sweden)

    Bo Moon

    2012-01-01

    Full Text Available The Subset Sum Problem is a member of the NP-complete class, so no known polynomial time algorithm exists for it. Although there are polynomial time approximations and heuristics, these are not always acceptable, yet exact-solution algorithms are unfeasible for large input. Quantum computation offers new insights for not only the Subset Sum Problem but also the entire NP-complete class; most notably, Grover's quantum algorithm for an unstructured database search can be tailored to identify solutions to problems within mathematics and computer science. This paper discusses the physical and conceptual feasibility of quantum computation and demonstrates the utility of quantum search by analyzing the time complexities of the classical dynamic programming algorithm and Grover's algorithm in solving the Subset Sum Problem, evincing the implications this has on the NP-complete class in general.

  3. Oncofetal Epigenetic Bivalency in Breast Cancer Cells: H3K4 and H3K27 Tri-Methylation as a Biomarker for Phenotypic Plasticity.

    Science.gov (United States)

    Messier, Terri L; Boyd, Joseph R; Gordon, Jonathan A R; Stein, Janet L; Lian, Jane B; Stein, Gary S

    2016-11-01

    Alterations in the epigenetic landscape are fundamental drivers of aberrant gene expression that contribute to cancer progression and pathology. Understanding specific modes of epigenetic regulation can be used to identify novel biomarkers or targets for therapeutic intervention to clinically treat solid tumors and leukemias. The bivalent marking of gene promoters by H3K4me3 and H3K27me3 is a primary mechanism to poise genes for expression in pluripotent embryonic stem cells (ESC). In this study we interrogated three well-established mammary cell lines to model epigenetic programming observed among breast cancer subtypes. Evidence is provided for a distinct bivalent signature, activating and repressive histone marks co-residing at the same gene promoter, in the MCF7 (ESR/PGR+) luminal breast cancer cell line. We identified a subset of genes, enriched for developmental pathways that regulate cellular phenotype and signaling, and partially recapitulate the bivalent character observed in ESC. We validated the biological relevance of this "oncofetal epigenetic" signature using data from ESR/PGR+ tumor samples from breast cancer patients. This signature of oncofetal epigenetic control is an informative biomarker and may provide novel therapeutic targets, selective for both recurring and treatment-resistant cancers. J. Cell. Physiol. 231: 2474-2481, 2016. © 2016 Wiley Periodicals, Inc. PMID:26916849

  4. CD4+ T-cell subsets in inflammatory diseases: beyond the Th1/Th2 paradigm.

    Science.gov (United States)

    Hirahara, Kiyoshi; Nakayama, Toshinori

    2016-04-01

    CD4(+)T cells are crucial for directing appropriate immune responses during host defense and for the pathogenesis of inflammatory diseases. In addition to the classical biphasic model of differentiation of T-helper 1 (Th1) and Th2 cells, unexpected increases in the numbers of CD4(+)T-cell subsets, including Th17, Th9, T follicular-helper (Tfh) and T-regulatory (Treg) cells, have been recognized. In the present review, we focus on how these various T-helper cell subsets contribute to the pathogenesis of immune-mediated inflammatory diseases. In particular, we focus on multiple sclerosis, psoriasis and asthma as typical model diseases in which multiple T-helper cell subsets have recently been suggested to play a role. We will also discuss various unique sub-populations of T-helper cells that have been identified. First, we will introduce the heterogeneous T-helper cell subsets, which are classified by their simultaneous expression of multiple key transcription factors. We will also introduce different kinds of memory-type Th2 cells, which are involved in the pathogenesis of chronic type-2 immune-related diseases. Finally, we will discuss the molecular mechanisms underlying the generation of the plasticity and heterogeneity of T-helper cell subsets. The latest progress in the study of T-helper cell subsets has forced us to reconsider the etiology of immune-mediated inflammatory diseases beyond the model based on the Th1/Th2 balance. To this end, we propose another model--the pathogenic T-helper population disease-induction model--as a possible mechanism for the induction and/or persistence of immune-mediated inflammatory diseases. PMID:26874355

  5. Azacytidine and decitabine induce gene-specific and non-random DNA demethylation in human cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Sabine Hagemann

    Full Text Available The DNA methyltransferase inhibitors azacytidine and decitabine represent archetypal drugs for epigenetic cancer therapy. To characterize the demethylating activity of azacytidine and decitabine we treated colon cancer and leukemic cells with both drugs and used array-based DNA methylation analysis of more than 14,000 gene promoters. Additionally, drug-induced demethylation was compared to methylation patterns of isogenic colon cancer cells lacking both DNA methyltransferase 1 (DNMT1 and DNMT3B. We show that drug-induced demethylation patterns are highly specific, non-random and reproducible, indicating targeted remethylation of specific loci after replication. Correspondingly, we found that CG dinucleotides within CG islands became preferentially remethylated, indicating a role for DNA sequence context. We also identified a subset of genes that were never demethylated by drug treatment, either in colon cancer or in leukemic cell lines. These demethylation-resistant genes were enriched for Polycomb Repressive Complex 2 components in embryonic stem cells and for transcription factor binding motifs not present in demethylated genes. Our results provide detailed insights into the DNA methylation patterns induced by azacytidine and decitabine and suggest the involvement of complex regulatory mechanisms in drug-induced DNA demethylation.

  6. Longterm decrease in the CD57 lymphocyte subset in a patient with chronic Lyme disease.

    Science.gov (United States)

    Stricker, Raphael B; Burrascano, Joseph; Winger, Edward

    2002-01-01

    Lyme disease is a tickborne illness caused by the spirochete Borrelia burgdorferi. In a previous report we described a decrease in the CD57 lymphocyte subset in patients with chronic Lyme disease. We have now identified a patient with chronic relapsing and remitting symptoms of Lyme disease who had decreased levels of CD57 lymphocytes over 10 years. This observation represents the longest duration of an immunologic abnormality ever documented in chronic Lyme disease. The CD57 lymphocyte subset appears to be a useful marker of longterm infection with the Lyme disease spirochete.

  7. Gamma-Ray Bursts Subset and Supernova Remnants Low Radio-Frequency Turnover

    Institute of Scientific and Technical Information of China (English)

    LIU Xiang

    2000-01-01

    Durations of gamma-ray bursts (GRB's) are featured by >2s subset and <2s one, with initial corresponding energy ratio being 20:1. It is found that supernova remants(SNR 's) turnover frequencies peak at 100 and 500 MHz. After assuming that GRB's originate from hypernova and making an analysis on the evolution of GRB's, we find that the initial energy of two GRB subsets leads to a different radio-frequency turnover of their remnant spectra, which accords positively with the turnover-frequency ratio of SNR's.

  8. T cell subsets in human airways prior to and following endobronchial administration of endotoxin

    DEFF Research Database (Denmark)

    Ronit, Andreas; Plovsing, Ronni R; Gaardbo, Julie C;

    2015-01-01

    BACKGROUND AND OBJECTIVES: Bronchial instillation of lipopolysaccharide (LPS) provides a reversible model of lung inflammation that may resemble early stages of acute respiratory distress syndrome (ARDS). We investigated the distributions of T-cell subsets in the human airways and sought to deter......BACKGROUND AND OBJECTIVES: Bronchial instillation of lipopolysaccharide (LPS) provides a reversible model of lung inflammation that may resemble early stages of acute respiratory distress syndrome (ARDS). We investigated the distributions of T-cell subsets in the human airways and sought...

  9. Technical Note: Proximal Ordered Subsets Algorithms for TV Constrained Optimization in CT Image Reconstruction

    CERN Document Server

    Rose, Sean; Sidky, Emil Y; Pan, Xiaochuan

    2016-01-01

    This article is intended to supplement our 2015 paper in Medical Physics titled "Noise properties of CT images reconstructed by use of constrained total-variation, data-discrepancy minimization", in which ordered subsets methods were employed to perform total-variation constrained data-discrepancy minimization for image reconstruction in X-ray computed tomography. Here we provide details regarding implementation of the ordered subsets algorithms and suggestions for selection of algorithm parameters. Detailed pseudo-code is included for every algorithm implemented in the original manuscript.

  10. The behaviour of total leucocytes and lymphocyte subsets in female athletes after physical exercise

    OpenAIRE

    Engelmann, Dirk Torben

    2010-01-01

    The aim of the study was the demonstration of the leucocytes and lymphocyte subsets changes after physical exercise of female athletes, in this case after a triathlon and a marathon. For the first time, the probands were all female athletes with an average age of 29 y and 10 h of weekly workout for the triathlon and an average age of 40.5 y and 6.5 h of weekly workout for the marathon. For the identification of total leucocytes and lymphocyte subsets we analysed the blood with a flow cytomete...

  11. How to create order in large closed subsets of WordNet-type dictionaries

    Directory of Open Access Journals (Sweden)

    Ahti Lohk

    2013-04-01

    Full Text Available This article presents a new two-step method to handle and study large closed subsets of WordNet-type dictionaries with the goal of finding possible structural inconsistencies. The notion of closed subset is explained using a WordNet tree. A novel and very fast method to order large relational systems is described and compared with some other fast methods. All the presented methods have been tested using Estonian1 and Princeton WordNet2 largest closed sets.DOI: http://dx.doi.org/10.5128/ERYa9.10

  12. Environmental enrichment in farm, zoo, companion and experimental animals

    Directory of Open Access Journals (Sweden)

    Vučinić Marijana

    2009-01-01

    Full Text Available The paper deals with environmental enrichment for domestic animals at farms, animals in zoos, experimental animals and pet animals. Also, the paper defines and describes different strategies of environmental enrichment. Environmental enrichment is a simple and effective mean of prevention of boredom, behavioral disorders as well as an effective mean of improving animal welfare in farm, zoo, companion and experimental animals. Different items and materials may be used for environmental enrichment. They need to be evaluated for use by taking into account the following: the species of an animal, its needs, habits and capabilities, the type of an enrichment device, the device's ability to stimulate the animal's interest and the safety of the device. Enrichment programmes should always include two forms of enrichment: behavioral enrichment and environmental enrichment. Enrichment comes in many forms such as structural or physical enrichment, sensory enrichment (auditory and olfactory stimulation, dietary enrichment, manipulatable enrichment and social enrichment.

  13. Functionalized diamond nanopowder for phosphopeptides enrichment from complex biological fluids

    Energy Technology Data Exchange (ETDEWEB)

    Hussain, Dilshad [Division of Analytical Chemistry, Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800 (Pakistan); Najam-ul-Haq, Muhammad, E-mail: najamulhaq@bzu.edu.pk [Division of Analytical Chemistry, Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800 (Pakistan); Institute of Analytical Chemistry and Radiochemistry, Leopold-Franzens University, Innrain 80-82, A-6020 Innsbruck (Austria); Jabeen, Fahmida; Ashiq, Muhammad N.; Athar, Muhammad [Division of Analytical Chemistry, Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800 (Pakistan); Rainer, Matthias; Huck, Christian W.; Bonn, Guenther K. [Institute of Analytical Chemistry and Radiochemistry, Leopold-Franzens University, Innrain 80-82, A-6020 Innsbruck (Austria)

    2013-05-02

    Graphical abstract: -- Highlights: •Derivatization of diamond nanopowder as IMAC and RP. •Characterization with SEM, EDX and FT-IR. •Phosphopeptide enrichment from standard as well as real samples. •Desalting and human serum profiling with reproducible results. •MALDI-MS analysis with database identification. -- Abstract: Diamond is known for its high affinity and biocompatibility towards biomolecules and is used exclusively in separation sciences and life science research. In present study, diamond nanopowder is derivatized as Immobilized Metal Ion Affinity Chromatographic (IMAC) material for the phosphopeptides enrichment and as Reversed Phase (C-18) media for the desalting of complex mixtures and human serum profiling through MALDI-TOF-MS. Functionalized diamond nanopowder is characterized by Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy. Diamond-IMAC is applied to the standard protein (β-casein), spiked human serum, egg yolk and non-fat milk for the phosphopeptides enrichment. Results show the selectivity of synthesized IMAC-diamond immobilized with Fe{sup 3+} and La{sup 3+} ions. To comprehend the elaborated use, diamond-IMAC is also applied to the serum samples from gall bladder carcinoma for the potential biomarkers. Database search is carried out by the Mascot program ( (www.matrixscience.com)) for the assignment of phosphorylation sites. Diamond nanopowder is thus a separation media with multifunctional use and can be applied to cancer protein profiling for the diagnosis and biomarker identification.

  14. Functionalized diamond nanopowder for phosphopeptides enrichment from complex biological fluids

    International Nuclear Information System (INIS)

    Graphical abstract: -- Highlights: •Derivatization of diamond nanopowder as IMAC and RP. •Characterization with SEM, EDX and FT-IR. •Phosphopeptide enrichment from standard as well as real samples. •Desalting and human serum profiling with reproducible results. •MALDI-MS analysis with database identification. -- Abstract: Diamond is known for its high affinity and biocompatibility towards biomolecules and is used exclusively in separation sciences and life science research. In present study, diamond nanopowder is derivatized as Immobilized Metal Ion Affinity Chromatographic (IMAC) material for the phosphopeptides enrichment and as Reversed Phase (C-18) media for the desalting of complex mixtures and human serum profiling through MALDI-TOF-MS. Functionalized diamond nanopowder is characterized by Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy. Diamond-IMAC is applied to the standard protein (β-casein), spiked human serum, egg yolk and non-fat milk for the phosphopeptides enrichment. Results show the selectivity of synthesized IMAC-diamond immobilized with Fe3+ and La3+ ions. To comprehend the elaborated use, diamond-IMAC is also applied to the serum samples from gall bladder carcinoma for the potential biomarkers. Database search is carried out by the Mascot program ( (www.matrixscience.com)) for the assignment of phosphorylation sites. Diamond nanopowder is thus a separation media with multifunctional use and can be applied to cancer protein profiling for the diagnosis and biomarker identification

  15. BIOLOGICAL ACTIVITY OF APPLE JUICE ENRICHED BY HERBAL EXTRACTS

    Directory of Open Access Journals (Sweden)

    Eva Ivanišová

    2015-02-01

    Full Text Available Herbal phytochemicals have recently become an attractive subject for scientists in many different research areas. The aim of this study was to determine antioxidant activity, total polyphenol and flavonoid content of apple juice enriched by water herbal extracts. Secondary was to evaluate sensory characteristic of enriched apple juice. It was found that applications of water herbal extracts to apple juice increase antioxidant activities, and also total polyphenol and flavonoid content with compare to pure apple juice. The highest biological activities were detected in apple juice with addition of lemon balm (14.42 mg TEAC/L; 84.38 mg TEAC/L; 50.88 mg GAE/L; 36.26 μg QE/L, oregano (14.92 mg TEAC/L; 79.97 mg TEAC/L; 50.51 mg GAE/L; 31.02 μg QE/L and salvia (8.40 mg TEAC/L; 30.40 mg TEAC/L; 23.33 mg GAE/L; 27.67 μg QE/L water extract. Sensorial analysis of samples showed, that enriched juices had better properties for evaluators with compared to pure juice. The aim of this study was also to mention the potential use of medicinal herbs in food industry, because plant bioactive compounds can play an important role in preventing cardiovascular diseases, cancers and reduction inflammatory action.

  16. Efficacy of Neoadjuvant Cisplatin in Triple-Negative Breast Cancer

    DEFF Research Database (Denmark)

    Szallasi, Zoltan Imre; Eklund, Aron Charles; Li, Qiyuan;

    2010-01-01

    PURPOSE Cisplatin is a chemotherapeutic agent not used routinely for breast cancer treatment. As a DNA cross-linking agent, cisplatin may be effective treatment for hereditary BRCA1-mutated breast cancers. Because sporadic triple-negative breast cancer (TNBC) and BRCA1-associated breast cancer sh......1 promoter methylation (P = .04), p53 nonsense or frameshift mutations (P = .01), and a gene expression signature of E2F3 activation (P = .03). CONCLUSION Single-agent cisplatin induced response in a subset of patients with TNBC. Decreased BRCA1 expression may identify subsets of TNBCs...

  17. Dorsal horn-enriched genes identified by DNA microarray, in situ hybridization and immunohistochemistry

    Directory of Open Access Journals (Sweden)

    Koblan Kenneth S

    2002-08-01

    Full Text Available Abstract Background Neurons in the dorsal spinal cord play important roles in nociception and pain. These neurons receive input from peripheral sensory neurons and then transmit the signals to the brain, as well as receive and integrate descending control signals from the brain. Many molecules important for pain transmission have been demonstrated to be localized to the dorsal horn of the spinal cord. Further understanding of the molecular interactions and signaling pathways in the dorsal horn neurons will require a better knowledge of the molecular neuroanatomy in the dorsal spinal cord. Results A large scale screening was conducted for genes with enriched expression in the dorsal spinal cord using DNA microarray and quantitative real-time PCR. In addition to genes known to be specifically expressed in the dorsal spinal cord, other neuropeptides, receptors, ion channels, and signaling molecules were also found enriched in the dorsal spinal cord. In situ hybridization and immunohistochemistry revealed the cellular expression of a subset of these genes. The regulation of a subset of the genes was also studied in the spinal nerve ligation (SNL neuropathic pain model. In general, we found that the genes that are enriched in the dorsal spinal cord were not among those found to be up-regulated in the spinal nerve ligation model of neuropathic pain. This study also provides a level of validation of the use of DNA microarrays in conjunction with our novel analysis algorithm (SAFER for the identification of differences in gene expression. Conclusion This study identified molecules that are enriched in the dorsal horn of the spinal cord and provided a molecular neuroanatomy in the spinal cord, which will aid in the understanding of the molecular mechanisms important in nociception and pain.

  18. Integrated exon level expression analysis of driver genes explain their role in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Mohammad Azhar Aziz

    Full Text Available Integrated analysis of genomic and transcriptomic level changes holds promise for a better understanding of colorectal cancer (CRC biology. There is a pertinent need to explain the functional effect of genome level changes by integrating the information at the transcript level. Using high resolution cytogenetics array, we had earlier identified driver genes by 'Genomic Identification of Significant Targets In Cancer (GISTIC' analysis of paired tumour-normal samples from colorectal cancer patients. In this study, we analyze these driver genes at three levels using exon array data--gene, exon and network. Gene level analysis revealed a small subset to experience differential expression. These results were reinforced by carrying out separate differential expression analyses (SAM and LIMMA. ATP8B1 was found to be the novel gene associated with CRC that shows changes at cytogenetic, gene and exon levels. Splice index of 29 exons corresponding to 13 genes was found to be significantly altered in tumour samples. Driver genes were used to construct regulatory networks for tumour and normal groups. There were rearrangements in transcription factor genes suggesting the presence of regulatory switching. The regulatory pattern of AHR gene was found to have the most significant alteration. Our results integrate data with focus on driver genes resulting in highly enriched novel molecules that need further studies to establish their role in CRC.

  19. Anticancer and Antioxidant Activity of Bread Enriched with Broccoli Sprouts

    Directory of Open Access Journals (Sweden)

    Urszula Gawlik-Dziki

    2014-01-01

    Full Text Available This study is focused on antioxidant and anticancer capacity of bread enriched with broccoli sprouts (BS in the light of their potential bioaccessibility and bioavailability. Generally, bread supplementation elevated antioxidant potential of product (both nonenzymatic and enzymatic antioxidant capacities; however, the increase was not correlated with the percent of BS. A replacement up to 2% of BS gives satisfactory overall consumers acceptability and desirable elevation of antioxidant potential. High activity was especially found for extracts obtained after simulated digestion, which allows assuming their protective effect for upper gastrointestinal tract; thus, the anticancer activity against human stomach cancer cells (AGS was evaluated. A prominent cytostatic response paralleled by the inhibition of AGS motility in the presence of potentially mastication-extractable phytochemicals indicates that phenolic compounds of BS retain their biological activity in bread. Importantly, the efficient phenolics concentration was about 12 μM for buffer extract, 13 μM for extracts after digestion in vitro, and 7 μM for extract after absorption in vitro. Our data confirm chemopreventive potential of bread enriched with BS and indicate that BS comprise valuable food supplement for stomach cancer chemoprevention.

  20. Basic uranium-235 enrichment by the Asahi Chemical Enrichment Process (ACEP)

    International Nuclear Information System (INIS)

    The development of Asahi Chemical Enrichment Process (ACEP) led to the establishment of basic process technology permitting attainment of 3% enrichment within several months of operation by the mid-1980s, through advances which brought increased electron-exchange and adsorption-desorption reaction rates, effective uranium adsorption band formation and maintenance, and equilibrium plate height reductions based on the elucidation of mobile-phase dispersion. The theoretical and experimental development of redox agent self-regeneration led to a new 'Super Process' characterized by greater simplicity and efficiency than previously thought possible. A semi-commercial plant with enrichment columns of 1 m in diameter and 3 m in height, constructed at Hyuga City in Miyazaki Prefecture, demonstrated 3% uranium enrichment in April 1988. Through the improvement of enrichment efficiency, overall enrichment costs have been greatly lowered. The advantage of the chemical enrichment process, and its low cost of enrichment, have now been clearly demonstrated. (author)

  1. Potential usefulness of an EPA-enriched nutritional supplement on chemotherapy tolerability in cancer patients without overt malnutrition Uso potencial de un suplemento nutricional enriquecido en EPA en la tolerabilidad a la quimioterapia en pacientes con cáncer sin desnutrición manifiesta

    Directory of Open Access Journals (Sweden)

    Joan Trabal

    2010-10-01

    Full Text Available Objectives: To assess the effect of an intervention with an Eicosapentaenoic Acid-enriched oral nutritional supplement on chemotherapy tolerability in patients with advanced colorectal cancer. Methods: Thirteen patients diagnosed with stage IV colorectal cancer were included. Patients in the experimental group received 2 packs of supplement per day during 12 weeks plus dietary counseling. The control group only received dietary counseling. Patients were assessed for nutritional status, dietary intake, health related quality of life (HRQOL and chemotherapy compliance. Results: Only patients in the supplemented group significantly increased their weight after the intervention. They also had better scores in important domains of HRQOL, compared to controls. Although not statistically significant, the supplemented group did not experience interruptions in their chemotherapy treatment compared to the control group, with more interruptions due to toxicity. Conclusions: The present study, although limited by sample size, points out towards a positive effect of the intervention on chemotherapy tolerability.Objetivos: Valorar el efecto de una intervención con un suplemento nutricional oral enriquecido en Ácido Eicosapentaenoico sobre la tolerabilidad a la quimioterapia en pacientes con cáncer colorrectal avanzado. Métodos: Se incluyeron 13 pacientes diagnosticados con cáncer colorrectal en estadio IV. Los pacientes en el grupo experimental recibieron 2 briks de suplemento al día durante 12 semanas junto a consejo dietético. El grupo control solo recibió consejo dietético. Se valoró el estado nutricional, ingesta dietética, calidad de vida relacionada con la salud (CVRS y el cumplimento de la quimioterapia de los pacientes. Resultados: Solo los pacientes en el grupo suplementado incrementaron su peso significativamente tras la intervención. También obtuvieron mejores puntuaciones en importantes dominios de la CVRS, comparado con los controles

  2. Merging transcriptomics and metabolomics - advances in breast cancer profiling

    Directory of Open Access Journals (Sweden)

    Bathen Tone F

    2010-11-01

    Full Text Available Abstract Background Combining gene expression microarrays and high resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS of the same tissue samples enables comparison of the transcriptional and metabolic profiles of breast cancer. The aim of this study was to explore the potential of combining these two different types of information. Methods Breast cancer tissue from 46 patients was analyzed by HR MAS MRS followed by gene expression microarrays. Two strategies were used to combine the gene expression and metabolic data; first using multivariate analyses to identify different groups based on gene expression and metabolic data; second correlating levels of specific metabolites to transcripts to suggest new hypotheses of connections between metabolite levels and the underlying biological processes. A parallel study was designed to address experimental issues of combining microarrays and HR MAS MRS. Results In the first strategy, using the microarray data and previously reported molecular classification methods, the majority of samples were classified as luminal A. Three subgroups of luminal A tumors were identified based on hierarchical clustering of the HR MAS MR spectra. The samples in one of the subgroups, designated A2, showed significantly lower glucose and higher alanine levels than the other luminal A samples, suggesting a higher glycolytic activity in these tumors. This group was also enriched for genes annotated with Gene Ontology (GO terms related to cell cycle and DNA repair. In the second strategy, the correlations between concentrations of myo-inositol, glycine, taurine, glycerophosphocholine, phosphocholine, choline and creatine and all transcripts in the filtered microarray data were investigated. GO-terms related to the extracellular matrix were enriched among the genes that correlated the most to myo-inositol and taurine, while cell cycle related GO-terms were enriched for the genes that correlated the most

  3. Merging transcriptomics and metabolomics - advances in breast cancer profiling

    International Nuclear Information System (INIS)

    Combining gene expression microarrays and high resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS) of the same tissue samples enables comparison of the transcriptional and metabolic profiles of breast cancer. The aim of this study was to explore the potential of combining these two different types of information. Breast cancer tissue from 46 patients was analyzed by HR MAS MRS followed by gene expression microarrays. Two strategies were used to combine the gene expression and metabolic data; first using multivariate analyses to identify different groups based on gene expression and metabolic data; second correlating levels of specific metabolites to transcripts to suggest new hypotheses of connections between metabolite levels and the underlying biological processes. A parallel study was designed to address experimental issues of combining microarrays and HR MAS MRS. In the first strategy, using the microarray data and previously reported molecular classification methods, the majority of samples were classified as luminal A. Three subgroups of luminal A tumors were identified based on hierarchical clustering of the HR MAS MR spectra. The samples in one of the subgroups, designated A2, showed significantly lower glucose and higher alanine levels than the other luminal A samples, suggesting a higher glycolytic activity in these tumors. This group was also enriched for genes annotated with Gene Ontology (GO) terms related to cell cycle and DNA repair. In the second strategy, the correlations between concentrations of myo-inositol, glycine, taurine, glycerophosphocholine, phosphocholine, choline and creatine and all transcripts in the filtered microarray data were investigated. GO-terms related to the extracellular matrix were enriched among the genes that correlated the most to myo-inositol and taurine, while cell cycle related GO-terms were enriched for the genes that correlated the most to choline. Additionally, a subset of transcripts was

  4. Enriching the hot circumgalactic medium

    CERN Document Server

    Crain, Robert A; Schaye, Joop; Frenk, Carlos S; Theuns, Tom

    2013-01-01

    Models of galaxy formation in a CDM universe predict that massive galaxies are surrounded by a hot, quasi-hydrostatic circumgalactic corona of slowly cooling gas, predominantly accreted from the IGM. This prediction is borne out by the cosmological hydrodynamical simulations of Crain et al., which reproduce scaling relations between the X-ray and optical properties of nearby disc galaxies. Such coronae are metal poor, but observations of the X-ray emitting circumgalactic medium (CGM) of local galaxies typically indicate enrichment to near-solar iron abundance, potentially signalling a shortcoming in galaxy formation models. We show here that, while the hot CGM of galaxies formed in the simulations is metal poor in a mass-weighted sense, its X-ray luminosity-weighted metallicity is often close to solar. This bias arises because the soft X-ray emissivity of a typical 0.1 keV corona is dominated by collisionally-excited metal ions that are synthesised in stars and recycled into the hot CGM. We find that these me...

  5. Student science enrichment training program

    Energy Technology Data Exchange (ETDEWEB)

    Sandhu, S.S.

    1994-08-01

    This is a report on the Student Science Enrichment Training Program, with special emphasis on chemical and computer science fields. The residential summer session was held at the campus of Claflin College, Orangeburg, SC, for six weeks during 1993 summer, to run concomitantly with the college`s summer school. Fifty participants selected for this program, included high school sophomores, juniors and seniors. The students came from rural South Carolina and adjoining states which, presently, have limited science and computer science facilities. The program focused on high ability minority students, with high potential for science engineering and mathematical careers. The major objective was to increase the pool of well qualified college entering minority students who would elect to go into science, engineering and mathematical careers. The Division of Natural Sciences and Mathematics and engineering at Claflin College received major benefits from this program as it helped them to expand the Departments of Chemistry, Engineering, Mathematics and Computer Science as a result of additional enrollment. It also established an expanded pool of well qualified minority science and mathematics graduates, which were recruited by the federal agencies and private corporations, visiting Claflin College Campus. Department of Energy`s relationship with Claflin College increased the public awareness of energy related job opportunities in the public and private sectors.

  6. The performance of tests on endogeneity of subsets of explanatory variables scanned by simulation

    NARCIS (Netherlands)

    J.F. Kiviet; M. Pleus

    2011-01-01

    Tests for classification as endogenous or predetermined of arbitrary subsets of regressors are formulated as significance tests in auxiliary IV regressions and their relationships with various more classic test procedures are examined. Simulation experiments are designed by solving the data generati

  7. Different Subsets of T Cells, Memory, Effector Functions, and CAR-T Immunotherapy

    Directory of Open Access Journals (Sweden)

    Vita Golubovskaya

    2016-03-01

    Full Text Available This review is focused on different subsets of T cells: CD4 and CD8, memory and effector functions, and their role in CAR-T therapy––a cellular adoptive immunotherapy with T cells expressing chimeric antigen receptor. The CAR-T cells recognize tumor antigens and induce cytotoxic activities against tumor cells. Recently, differences in T cell functions and the role of memory and effector T cells were shown to be important in CAR-T cell immunotherapy. The CD4+ subsets (Th1, Th2, Th9, Th17, Th22, Treg, and Tfh and CD8+ memory and effector subsets differ in extra-cellular (CD25, CD45RO, CD45RA, CCR-7, L-Selectin [CD62L], etc.; intracellular markers (FOXP3; epigenetic and genetic programs; and metabolic pathways (catabolic or anabolic; and these differences can be modulated to improve CAR-T therapy. In addition, CD4+ Treg cells suppress the efficacy of CAR-T cell therapy, and different approaches to overcome this suppression are discussed in this review. Thus, next-generation CAR-T immunotherapy can be improved, based on our knowledge of T cell subsets functions, differentiation, proliferation, and signaling pathways to generate more active CAR-T cells against tumors.

  8. Some Observations on the Subset Simulation Related to the Wind Turbine Mechanics

    DEFF Research Database (Denmark)

    Sichani, Mahdi Teimouri; Nielsen, Søren R.K.; Thoft-Christensen, Palle

    2012-01-01

    systems. It is interesting to determine applicability of the Subset Simulation (SS) techniques, as a powerful representative of Variance Reduction Monte Carlo (VRMC) methods, on the wind turbine systems specifically with an active controller. Hence in this paper we apply and discuss these methods...

  9. The acquisition of subset and superset phonotactic knowledge in a second language

    NARCIS (Netherlands)

    M. Trapman; R. Kager

    2009-01-01

    Can second language (L2) learners acquire a grammar that allows a subset of the structures allowed by their native grammar? This question is addressed here with respect to acquisition of phonotactics. On the assumption that the L2 initial state equals the native grammar's final state, learnability t

  10. Mis-parametrization subsets for a penalized least squares model selection

    OpenAIRE

    Guyon, Xavier; Hardouin, Cécile

    2011-01-01

    When identifying a model by a penalized minimum contrast procedure, we give a description of the over and under fitting parametrization subsets for a least squares contrast. This allows to determine an accurate sequence of penalization rates ensuring good identification. We present applications for the identification of the covariance for a general time series, and for the variogram identification of a geostatistical model.

  11. Alterations in lymphocyte subset patterns and co-stimulatory molecules in patients with Alzheimer disease

    Institute of Scientific and Technical Information of China (English)

    XUE Shou-ru; XU Dong-hua; YANG Xin-xin; DONG Wan-li

    2009-01-01

    @@ Alzheimer disease (AD) is characterized by the presence of β-amyloid (Aβ) plaques in the brain.1 More evidence of inflammatory parameters, such as, complement factors, proinflammatory cytokines and lymphocytes has been found to be co-localized with Aβ plaques,1,2 The research in the past decades has demonstrated abnormalities of both the humoral and cellular immune responses, suggesting an association of immunological aberration and AD. The total percentage of lymphocytes was not found to be altered, whereas the alterations of T-cell function, differentiation and subset distribution have still been unresolved.3,4 A significantly decreased function of suppressor as well as helper T-cells and natural killer (NK) cells in AD patients has been observed. Studies on lymphocyte subpopulations showed conflicting results, while other studies could not find alterations in lymphocyte subset distribution. In the present study, we assume the immune system dysregulation depending on a defective immune response which also affects lymphocyte differentiation and subset distribution. We investigated T lymphocyte subset pattems and co-stimulatory molecules, as well as B lymphocytes and NK cells in peripheral blood of AD patients and age matched healthy controls.

  12. Proteome profiling of human neutrophil granule subsets, secretory vesicles, and cell membrane

    DEFF Research Database (Denmark)

    Rørvig, Sara; Østergaard, Ole; Heegaard, Niels Henrik Helweg;

    2013-01-01

    granules, SVs, and plasma membrane has been performed before. Here, we performed subcellular fractionation on freshly isolated human neutrophils by nitrogen cavitation and density centrifugation on a four-layer Percoll gradient. Granule subsets were pooled and subjected to SDS-PAGE, and gel pieces were in...

  13. The Approximation of a Group Stimulus Space by Averaging Responses to Selected Subsets of the Stimuli

    Science.gov (United States)

    Robinson, Earl J.; Lissitz, Robert W.

    1977-01-01

    This paper presents a simple random procedure for selecting subsets of stimulus pairs for presentation to subjects. The resulting set of ratings from the group of subjects allows the construction of a group space through the use of an existing computer program. (Author/JKS)

  14. Different Subsets of T Cells, Memory, Effector Functions, and CAR-T Immunotherapy.

    Science.gov (United States)

    Golubovskaya, Vita; Wu, Lijun

    2016-01-01

    This review is focused on different subsets of T cells: CD4 and CD8, memory and effector functions, and their role in CAR-T therapy--a cellular adoptive immunotherapy with T cells expressing chimeric antigen receptor. The CAR-T cells recognize tumor antigens and induce cytotoxic activities against tumor cells. Recently, differences in T cell functions and the role of memory and effector T cells were shown to be important in CAR-T cell immunotherapy. The CD4⁺ subsets (Th1, Th2, Th9, Th17, Th22, Treg, and Tfh) and CD8⁺ memory and effector subsets differ in extra-cellular (CD25, CD45RO, CD45RA, CCR-7, L-Selectin [CD62L], etc.); intracellular markers (FOXP3); epigenetic and genetic programs; and metabolic pathways (catabolic or anabolic); and these differences can be modulated to improve CAR-T therapy. In addition, CD4⁺ Treg cells suppress the efficacy of CAR-T cell therapy, and different approaches to overcome this suppression are discussed in this review. Thus, next-generation CAR-T immunotherapy can be improved, based on our knowledge of T cell subsets functions, differentiation, proliferation, and signaling pathways to generate more active CAR-T cells against tumors.

  15. Different Subsets of T Cells, Memory, Effector Functions, and CAR-T Immunotherapy

    Science.gov (United States)

    Golubovskaya, Vita; Wu, Lijun

    2016-01-01

    This review is focused on different subsets of T cells: CD4 and CD8, memory and effector functions, and their role in CAR-T therapy––a cellular adoptive immunotherapy with T cells expressing chimeric antigen receptor. The CAR-T cells recognize tumor antigens and induce cytotoxic activities against tumor cells. Recently, differences in T cell functions and the role of memory and effector T cells were shown to be important in CAR-T cell immunotherapy. The CD4+ subsets (Th1, Th2, Th9, Th17, Th22, Treg, and Tfh) and CD8+ memory and effector subsets differ in extra-cellular (CD25, CD45RO, CD45RA, CCR-7, L-Selectin [CD62L], etc.); intracellular markers (FOXP3); epigenetic and genetic programs; and metabolic pathways (catabolic or anabolic); and these differences can be modulated to improve CAR-T therapy. In addition, CD4+ Treg cells suppress the efficacy of CAR-T cell therapy, and different approaches to overcome this suppression are discussed in this review. Thus, next-generation CAR-T immunotherapy can be improved, based on our knowledge of T cell subsets functions, differentiation, proliferation, and signaling pathways to generate more active CAR-T cells against tumors. PMID:26999211

  16. Distinct patterns of novel gene mutations in poor-prognostic stereotyped subsets of chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Strefford, J C; Sutton, L-A; Baliakas, P;

    2013-01-01

    Recent studies have revealed recurrent mutations of the NOTCH1, SF3B1 and BIRC3 genes in chronic lymphocytic leukemia (CLL), especially among aggressive, chemorefractory cases. Nevertheless, it is currently unknown whether their presence may differ in subsets of patients carrying stereotyped B...

  17. Leukocyte Subset Changes in Response to a 164-km Road Cycle Ride in a Hot Environment

    Science.gov (United States)

    LUK, HUI-YING; MCKENZIE, AMY L.; DUPLANTY, ANTHONY A.; BUDNAR, RONALD G.; LEVITT, DANIELLE; FERNANDEZ, ALEX; LEE, ELAINE C.; ARMSTRONG, LAWRENCE E.; VINGREN, JAKOB L.

    2016-01-01

    The purpose of this observational study was to determine the circulating leukocyte subset response to completing the 2013 Hotter’N Hell Hundred recreational 164-km road cycle event in a hot and humid environmental condition. Twenty-eight men and four women were included in this study. Whole blood samples were obtained 1–2 hours before (PRE) and immediately after (POST) the event. Electronic sizing/sorting and cytometry were used to determine complete blood counts (CBC) including neutrophil, monocyte, and lymphocyte subsets. The concentration of circulating total leukocytes (103·μL−1) increased 134% from PRE to POST with the greatest increase in neutrophils (319%, pHHH), a 100 mile recreational cycling race in extreme (hot and humid) environmental conditions, induces a substantial increase in total leukocytes in circulation. The contribution of increases in specific immune cell subsets is not equal, with neutrophils increasing to greater than 4-fold starting values from PRE to POST race. It is likely that exercise in stressful environmental conditions affects the complement of circulating immune cells, although activational state and characterization of specific leukocyte subsets remains unclear. The observed increase in circulating cell sub-populations suggests that the circulating immune surveillance system may be acutely affected by exercise in hot and humid conditions. PMID:27293505

  18. The ICPC coding system in pharmacy : developing a subset, ICPC-Ph

    NARCIS (Netherlands)

    van Mil, JWF; Brenninkmeijer, R; Tromp, TFJ

    1998-01-01

    The ICPC system is a coding system developed for general medical practice, to be able to code the GP-patient encounters and other actions. Some of the codes can be easily used by community pharmacists to code complaints and diseases in pharmaceutical care practice. We developed a subset of the ICPC

  19. Enrichment technology. Dependable vendor of gas centrifuges

    International Nuclear Information System (INIS)

    Enrichment Technology is an innovative, high-tech company that develops, manufactures and installs gas centrifuges for enriching uranium. In addition, Enrichment Technology designs enrichment plants that use gas centrifuge technology. This technology offers the most efficient and cost-effective method for enriching uranium yet: high-performance, safe technology that dominates the market with a global share of 45 percent. A determining factor in Enrichment Technology's success is its mission: supplying its customers with safe, reliable technology. Production of the centrifuges requires versatile know-how and collaboration between different departments as well as interdisciplinary teams at the various sites. More than 2000 operators at 8 sites in 5 countries contribute their individual knowledge and personal skills in order to produce this exceptional technology. The head office is in Beaconsfield near London and the operational headquarters are in Almelo in the Netherlands. There are other sites in Germany (Juelich und Gronau), Great Britain (Capenhurst) as well as project sites in the USA and France. Capenhurst is where experienced engineers design new enrichment plants and organise their construction. Centrifuge components are manufactured in Almelo and Juelich, while the pipework needed to connect up the centrifuges is produced at the site in Gronau. In Juelich, highly qualified scientists in interdisciplinary teams are continuously researching ways of improving the current centrifuges. Communication between specialists in the fields of chemistry, physics and engineering forms the basis for the company's success and the key to extending this leading position in the global enrichment market. (orig.)

  20. 21 CFR 137.350 - Enriched rice.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Enriched rice. 137.350 Section 137.350 Food and... Related Products § 137.350 Enriched rice. (a) The foods for which definitions and standards of identity are prescribed by this section are forms of milled rice (except rice coated with talc and glucose...

  1. Perspectives for the uranium enrichment in Brazil

    International Nuclear Information System (INIS)

    Through an analysis of the electrical energy future in Brazil, the needs for enriched uranium are discussed, and therefore the importance of developing local capability for self-production. A description of the production processes that are well established is given first, then the analysis itself is performed and finally a visualization of the International Market for enriched uranium is shown. (author)

  2. A Component Analysis of Marriage Enrichment.

    Science.gov (United States)

    Buston, Beverley G.; And Others

    Although marriage enrichment programs have been shown to be effective for many couples, a multidimensional approach to assessment is needed in investigating these groups. The components of information and social support in successful marriage enrichment programs were compared in a completely crossed 2 x 2 factorial design with repeated measures.…

  3. Time Series Forecasting by using Seasonal Autoregressive Integrated Moving Average: Subset, Multiplicative or Additive Model

    Directory of Open Access Journals (Sweden)

    Suhartono

    2011-01-01

    Full Text Available Problem statement: Most of Seasonal Autoregressive Integrated Moving Average (SARIMA models that used for forecasting seasonal time series are multiplicative SARIMA models. These models assume that there is a significant parameter as a result of multiplication between nonseasonal and seasonal parameters without testing by certain statistical test. Moreover, most popular statistical software such as MINITAB and SPSS only has facility to fit a multiplicative model. The aim of this research is to propose a new procedure for indentifying the most appropriate order of SARIMA model whether it involves subset, multiplicative or additive order. In particular, the study examined whether a multiplicative parameter existed in the SARIMA model. Approach: Theoretical derivation about Autocorrelation (ACF and Partial Autocorrelation (PACF functions from subset, multiplicative and additive SARIMA model was firstly discussed and then R program was used to create the graphics of these theoretical ACF and PACF. Then, two monthly datasets were used as case studies, i.e. the international airline passenger data and series about the number of tourist arrivals to Bali, Indonesia. The model identification step to determine the order of ARIMA model was done by using MINITAB program and the model estimation step used SAS program to test whether the model consisted of subset, multiplicative or additive order. Results: The theoretical ACF and PACF showed that subset, multiplicative and additive SARIMA models have different patterns, especially at the lag as a result of multiplication between non-seasonal and seasonal lags. Modeling of the airline data yielded a subset SARIMA model as the best model, whereas an additive SARIMA model is the best model for forecasting the number of tourist arrivals to Bali. Conclusion: Both of case studies showed that a multiplicative SARIMA model was not the best model for forecasting these data. The comparison evaluation showed that subset

  4. Enrichment of high ammonia tolerant methanogenic culture

    DEFF Research Database (Denmark)

    Fotidis, Ioannis; Karakashev, Dimitar Borisov; Proietti, Nicolas;

    of the current study was to isolate and identify methanogenic cultures tolerant to high ammonia concentrations. A mixed methanogenic population was stepwise exposed to ammonia concentrations (1 to 9.26 g NH4+-N L-1) during an enrichment process with successive batch cultivations. The methanogenic population...... was derived from a full scale biogas reactor (Hashøj, Denmark), fed with 75% animal manure and 25% food industries organic waste. Basal anaerobic medium was used for the enrichment along with sodium acetate (1 g HAc L-1) as a carbon source. Fluorescence insitu hybridization (FISH) was used to determine...... microbial community composition. The outcome of the enrichment process was a mesophilic aceticlastic methanogenic enriched culture able to withstand high ammonia loads and utilize acetate and form methane stoichiometrically. FISH analysis showed that the methanogens of the enriched culture belonged...

  5. Computer-aided image geometry analysis and subset selection for optimizing texture quality in photorealistic models

    Science.gov (United States)

    Sima, Aleksandra Anna; Bonaventura, Xavier; Feixas, Miquel; Sbert, Mateu; Howell, John Anthony; Viola, Ivan; Buckley, Simon John

    2013-03-01

    Photorealistic 3D models are used for visualization, interpretation and spatial measurement in many disciplines, such as cultural heritage, archaeology and geoscience. Using modern image- and laser-based 3D modelling techniques, it is normal to acquire more data than is finally used for 3D model texturing, as images may be acquired from multiple positions, with large overlap, or with different cameras and lenses. Such redundant image sets require sorting to restrict the number of images, increasing the processing efficiency and realism of models. However, selection of image subsets optimized for texturing purposes is an example of complex spatial analysis. Manual selection may be challenging and time-consuming, especially for models of rugose topography, where the user must account for occlusions and ensure coverage of all relevant model triangles. To address this, this paper presents a framework for computer-aided image geometry analysis and subset selection for optimizing texture quality in photorealistic models. The framework was created to offer algorithms for candidate image subset selection, whilst supporting refinement of subsets in an intuitive and visual manner. Automatic image sorting was implemented using algorithms originating in computer science and information theory, and variants of these were compared using multiple 3D models and covering image sets, collected for geological applications. The image subsets provided by the automatic procedures were compared to manually selected sets and their suitability for 3D model texturing was assessed. Results indicate that the automatic sorting algorithms are a promising alternative to manual methods. An algorithm based on a greedy solution to the weighted set-cover problem provided image sets closest to the quality and size of the manually selected sets. The improved automation and more reliable quality indicators make the photorealistic model creation workflow more accessible for application experts

  6. Improving radar estimates of rainfall using an input subset of artificial neural networks

    Science.gov (United States)

    Yang, Tsun-Hua; Feng, Lei; Chang, Lung-Yao

    2016-04-01

    An input subset including average radar reflectivity (Zave) and its standard deviation (SD) is proposed to improve radar estimates of rainfall based on a radial basis function (RBF) neural network. The RBF derives a relationship from a historical input subset, called a training dataset, consisting of radar measurements such as reflectivity (Z) aloft and associated rainfall observation (R) on the ground. The unknown rainfall rate can then be predicted over the derived relationship with known radar measurements. The selection of the input subset has a significant impact on the prediction performance. This study simplified the selection of input subsets and studied its improvement in rainfall estimation. The proposed subset includes: (1) the Zave of the observed Z within a given distance from the ground observation to represent the intensity of a storm system and (2) the SD of the observed Z to describe the spatial variability. Using three historical rainfall events in 1999 near Darwin, Australia, the performance evaluation is conducted using three approaches: an empirical Z-R relation, RBF with Z, and RBF with Zave and SD. The results showed that the RBF with both Zave and SD achieved better rainfall estimations than the RBF using only Z. Two performance measures were used: (1) the Pearson correlation coefficient improved from 0.15 to 0.58 and (2) the average root-mean-square error decreased from 14.14 mm to 11.43 mm. The proposed model and findings can be used for further applications involving the use of neural networks for radar estimates of rainfall.

  7. The low-enrichment fuel development program

    International Nuclear Information System (INIS)

    In the 1950s and 1960s, low-power research reactors were built around the world utilized MTR-type fuel elements containing 20% enriched uranium. However, the demand for higher specific power created a need for greater uranium-235 concentrations. Early difficulties in increasing uranium content led to the substitution of highly enriched uranium in place of the 20% enriched fuel previously utilized. The highly enriched material also yielded other benefits including longer core residence time, higher specific reactivity, and somewhat lower cost. Highly enriched material then became readily available and was used for high-power reactors as well as in low-power reactors where 20% enriched material would have sufficed. The trend toward higher and higher specific power also led to the development of the dispersion-type fuels which utilized highly enriched uranium at a concentration of about 40 wt%. In the 1970's, however, concerns were raised about the proliferation resistance of fuels and fuel cycles. As a consequence, the U.S. Department of State has recently prohibited the foreign shipment of highly enriched material, except where prior contractual obligation or special merit exists. This will impact on the availability and utilization of highly enriched uranium for research and test reactor fuel. It has also stimulated development programs on fuels with higher uranium content which would allow the use of uranium of lower enrichment. The purpose of this report is to briefly describe the overall fuel development program which is coordinated by Argonne National Laboratory for the Department of Energy, and to indicate the current and potential uranium loadings. Other reports will address the individual fuel-development activities in greater detail

  8. The low-enrichment fuel development program

    International Nuclear Information System (INIS)

    In the 1950s and 1960s, low-power research reactors were built around the world utilized MTR-type fuel elements containing 20% enriched uranium. However, the demand for higher specific power created a need for greater uranium-235 concentrations. Early difficulties in increasing uranium content led to the substitution of highly enriched uranium in place of the 20% enriched fuel previously utilized. The highly enriched material also yielded other benefits including longer core residence time, higher specific reactivity, and somewhat lower cost. Highly enriched material then became readily available and was used for high-power reactors as well as in low-power reactors where 20% enriched material would have sufficed. The trend toward higher and higher specific power also led to the development of the dispersion-type fuels which utilized highly enriched uranium at a concentration of about 40 wt%. In the 1970's, however, concerns were raised about the proliferation resistance of fuels and fuel cycles. As a consequence, the U.S. Department of State has recently prohibited the foreign shipment of highly enriched material, except where prior contractual obligation or special merit exists. This will impact on the availability and utilization of highly enriched uranium for research and test reactor fuel. It has also stimulated development programs on fuels with higher uranium content which would allow the use of uranium of lower enrichment. The purpose of this report is to briefly describe the overall fuel-development program which is coordinated by Argonne National Laboratory for the Department of Energy, and to indicate the current and potential uranium loadings. Other reports will address the individual fuel-development activities in greater detail

  9. Biomarker-driven trial in metastatic pancreas cancer: feasibility in a multicenter study of saracatinib, an oral Src inhibitor, in previously treated pancreatic cancer

    International Nuclear Information System (INIS)

    Src tyrosine kinases are overexpressed in pancreatic cancers, and the oral Src inhibitor saracatinib has shown antitumor activity in preclinical models of pancreas cancer. We performed a CTEP-sponsored Phase II clinical trial of saracatinib in previously treated pancreas cancer patients, with a primary endpoint of 6-month survival. A Simon MinMax two-stage phase II design was used. Saracatinib (175 mg/day) was administered orally continuously in 28-day cycles. In the unselected portion of the study, 18 patients were evaluable. Only two (11%) patients survived for at least 6 months, and three 6-month survivors were required to move to second stage of study as originally designed. The study was amended as a biomarker-driven trial (leucine rich repeat containing protein 19 [LRRC19] > insulin-like growth factor-binding protein 2 [IGFBP2] “top scoring pairs” polymerase chain reaction [PCR] assay, and PIK3CA mutant) based on preclinical data in a human pancreas tumor explant model. In the biomarker study, archival tumor tissue or fresh tumor biopsies were tested. Biomarker-positive patients were eligible for the study. Only one patient was PIK3CA mutant in a 3′ untranslated region (UTR) portion of the gene. This patient was enrolled in the study and failed to meet the 6-month survival endpoint. As the frequency of biomarker-positive patients was very low (<3%), the study was closed. Although we were unable to conclude whether enriching for a subset of second/third line pancreatic cancer patients treated with a Src inhibitor based on a biomarker would improve 6-month survival, we demonstrate that testing pancreatic tumor samples for a biomarker-driven, multicenter study in metastatic pancreas cancer is feasible

  10. Effect of silencing HIF-2α expression on the enrichment of breast cancer stem cell microspheres under hypoxia%沉默HIF-2α表达对低氧下乳腺癌干细胞微球体富集的影响

    Institute of Scientific and Technical Information of China (English)

    屈洪波; 范原铭; 韩明利; 陈鑫; 吴诚义; 汤为学

    2013-01-01

      目的:探讨沉默低氧诱导因子-2α(hypoxia-inducible factor-2α,HIF-2α)表达对低氧下乳腺癌干细胞(breast cancer stem cells,BCSCs)微球体富集的影响.方法:构建HIF-2α RNA干扰慢病毒载体,并转染至MCF-7细胞,RT-PCR和Western blot检测HIF-2α mRNA及蛋白表达;MTT检测MCF-7细胞在不同氧浓度下增殖活性;显微镜下观察低氧下BCSCs微球体形成情况;有限稀释法检测微球体细胞单克隆形成能力;RT-PCR检测微球体细胞干细胞相关标志物ABCG2、CD44及OCT-4 mRNA表达.结果:成功构建了HIF-2α基因siRNA慢病毒表达载体,RT-PCR和Western blot结果显示干扰组细胞HIF-2α mRNA及蛋白表达均明显降低(P<0.05).与未转染组及空载体组比较,低氧下 RNA 干扰组细胞增殖活性及 BCSCs 单克隆形成能力明显降低(P<0.05);RT-PCR结果亦显示RNA干扰组BCSCs相关标志物ABCG2、CD44及OCT-4 mRNA表达显著降低(P<0.05).结论:低氧能够诱导和强化MCF-7细胞乳腺癌癌干细胞样特性,而沉默HIF-2α表达可抑制低氧下BCSCs富集,提示HIF-2α有望成为乳腺癌治疗新的靶点.%Objective: This work aims to explore the effect of silencing hypoxia-inducible factor (HIF)-2α expression on the enrichment of breast cancer stem cell (BCSC) microspheres under hypoxia. Methods: A lentiviral vector of the RNA interference (RNAi) of human HIF-2α gene was constructed and transfected into Michigan Cancer Foundation (MCF)-7 cells. The mRNA and protein expressions of HIF-2α were determined using real time-polymerase chain reaction (RT-PCR) and Western blot, respectively. The proliferation activity of the MCF-7 cells under different oxygen concentrations was measured using the methyl thiazolyl tetrazolium assay. The formation of the BCSC microspheres under hypoxia was observed by a fluorescence microscope. The monoclonal formation ability of the microsphere cells was detected by limiting dilution assay. The mRNA expressions

  11. Deuterium enrichment of interstellar dusts

    Science.gov (United States)

    Das, Ankan; Chakrabarti, Sandip Kumar; Majumdar, Liton; Sahu, Dipen

    2016-07-01

    High abundance of some abundant and simple interstellar species could be explained by considering the chemistry that occurs on interstellar dusts. Because of its simplicity, the rate equation method is widely used to study the surface chemistry. However, because the recombination efficiency for the formation of any surface species is highly dependent on various physical and chemical parameters, the Monte Carlo method is best suited for addressing the randomness of the processes. We carry out Monte-Carlo simulation to study deuterium enrichment of interstellar grain mantle under various physical conditions. Based on the physical properties, various types of clouds are considered. We find that in diffuse cloud regions, very strong radiation fields persists and hardly a few layers of surface species are formed. In translucent cloud regions with a moderate radiation field, significant number of layers would be produced and surface coverage is mainly dominated by photo-dissociation products such as, C, CH_3, CH_2D, OH and OD. In the intermediate dense cloud regions (having number density of total hydrogen nuclei in all forms ˜2 × 10^4 cm^{-3}), water and methanol along with their deuterated derivatives are efficiently formed. For much higher density regions (˜10^6 cm^{-3}), water and methanol productions are suppressed but surface coverage of CO, CO_2, O_2, O_3 are dramatically increased. We find a very high degree of fractionation of water and methanol. Observational results support a high fractionation of methanol but surprisingly water fractionation is found to be low. This is in contradiction with our model results indicating alternative routes for de-fractionation of water.

  12. Italian activities in uranium enrichment

    International Nuclear Information System (INIS)

    The paper describes Italian activities in uranium enrichment, which have mainly developed along the lines of the two classical processes: gaseous diffusion and centrifuges. Research, development and industrial activities play different roles in the two methods, and a special working group, GIAU, was established by CNEN to help co-ordinate this activity. In the field of gaseous diffusion, R and D effort was, from the start of the programme in 1968, mainly devoted to barriers and compressors, with the object of fully understanding the process and of demonstrating that it was capable of overcoming the main problems in this technology. Isotope separation of UF6 was demonstrated in 1974 at experimental plant level. Cost-sharing contracts were signed between CNEN and industries to build prototypes and ''first-of-a-kind'' components; small production lines have been set up to evaluate economics and assess production quality. Eurodif is partially associated with the development of this activity. On the industrial level, AGIP Nucleare and CNEN were among the promoters of the Eurodif venture from the beginning in 1973 and now own 25% of the shares. In the field of ultracentrifugation, work is still devoted mainly to R and D on the machines. The separation process was demonstrated in 1973 at laboratory level with a Zippe type centrifuge. Later activities aimed at developing high-capacity machines; different solutions are under close scrutiny. Carbon fibres and multiplerotor machines have been mechanically tested, and the first reference design of a small cascade plant has been completed. In the field of laser separation, after a complete and critical survey of different processes under development in other countries, experimental research work is now being undertaken, and experiments on basic aspects of the process are in progress. (author)

  13. Detection of infectious organisms in archival prostate cancer tissues

    OpenAIRE

    Yow, Melissa A; Tabrizi, Sepehr N.; Severi, Gianluca; Bolton, Damien M; Pedersen, John; Longano, Anthony; Suzanne M Garland; Southey, Melissa C.; Graham G Giles

    2014-01-01

    Background Seroepidemiological studies have reported associations between exposure to sexually transmitted organisms and prostate cancer risk. This study sought DNA evidence of candidate organisms in archival prostate cancer tissues with the aim of assessing if a subset of these cancers show any association with common genital infections. Methods 221 archival paraffin-embedded tissue blocks representing 128 histopathologically confirmed prostate cancers comprising 52 “aggressive” (Gleason sco...

  14. Fas and Bcl-2 Expression on T Lymphocyte Subsets in the Peripheral Blood of Relapsing Patients with Condyloma Acuminatum

    Institute of Scientific and Technical Information of China (English)

    顾军; 范清源; 高春芳; 代夫; 郑茂荣

    2003-01-01

    Objective: To study the expression of Fas and Bcl-2 proteins on T lymphocyte subsets in the peripheral blood of relapsing patients with condyloma acuminatum(CA) and healthy controls.Methods: Flow cytometry (permeabization and staining procedure with conjugated antibodies) was used.Results: We observed that the expression of Fas protein on CD4+ T lymphocyte subset of CA patients was significantly higher than that of healthy controls( P<0.01 ).Conclusions: Increased expression of Fas proteinon CD4+ T lymphocyte subset may be a cause of de-creased percentage of CD4+ T lymphocyte subset. This induces the increased ratio of CD4+/CD8+.

  15. Separable Bilayer Microfiltration Device for Viable Label-free Enrichment of Circulating Tumour Cells

    Science.gov (United States)

    Zhou, Ming-Da; Hao, Sijie; Williams, Anthony J.; Harouaka, Ramdane A.; Schrand, Brett; Rawal, Siddarth; Ao, Zheng; Brennaman, Randall; Gilboa, Eli; Lu, Bo; Wang, Shuwen; Zhu, Jiyue; Datar, Ram; Cote, Richard; Tai, Yu-Chong; Zheng, Si-Yang

    2014-12-01

    The analysis of circulating tumour cells (CTCs) in cancer patients could provide important information for therapeutic management. Enrichment of viable CTCs could permit performance of functional analyses on CTCs to broaden understanding of metastatic disease. However, this has not been widely accomplished. Addressing this challenge, we present a separable bilayer (SB) microfilter for viable size-based CTC capture. Unlike other single-layer CTC microfilters, the precise gap between the two layers and the architecture of pore alignment result in drastic reduction in mechanical stress on CTCs, capturing them viably. Using multiple cancer cell lines spiked in healthy donor blood, the SB microfilter demonstrated high capture efficiency (78-83%), high retention of cell viability (71-74%), high tumour cell enrichment against leukocytes (1.7-2 × 103), and widespread ability to establish cultures post-capture (100% of cell lines tested). In a metastatic mouse model, SB microfilters successfully enriched viable mouse CTCs from 0.4-0.6 mL whole mouse blood samples and established in vitro cultures for further genetic and functional analysis. Our preliminary studies reflect the efficacy of the SB microfilter device to efficiently and reliably enrich viable CTCs in animal model studies, constituting an exciting technology for new insights in cancer research.

  16. 围手术期免疫增强型全肠外营养对胃肠恶性肿瘤患者术后免疫功能的影响%Effects of Immune-Enriched Total Parenteral Nutrition on Postoperative Immune Function in Patients with Gastrointestinal Cancer

    Institute of Scientific and Technical Information of China (English)

    殷庆章; 洪亮; 殷琛庆; 齐翀; 汤承辉

    2011-01-01

    目的:评价免疫增强型全肠外营养对胃肠恶性肿瘤患者术后免疫功能、营养状况及预后的影响.方法:120例消化道恶性肿瘤手术患者随机分为A组(术前和术后应用免疫增强型全肠外营养组)、B组(术后应用免疫增强型全肠外营养组)和对照组(常规全肠外营养组).于入院时、术后第1天和第6天时分别检测各项免疫、营养及预后指标.结果:与入院时比较,3组免疫和营养指标于术后第1天降低,术后第6天均有所恢复.术后第6天,A、B组中的淋巴细胞总数和IgA、IgM、IgG、CD3、CD4、CD4/CD8值及中性数细胞吞噬率均显著高于C组,A、B组的术后感染性并发症发生率显著低于C组,平均住院时间则显著长于C组(P<0.05),而A组和B组间各项免疫及预后指标无显著差异(P>0.05).研究期间各组白蛋白、前白蛋白和转铁蛋白血清浓度无显著差异(P>0.05).结论:免疫增强型全肠外营养可增强胃肠恶性肿瘤患者术后机体免疫功能并改善预后.%Objective:To study the effect of Immune-enriched total parenteral nutrition (TPN) on the postoperative immune function, nutritional status and prognosis in the patients with gastrointestinal cancer. Methods: A hundred and twenty patients with gastrointestinal cancer were randomly divided into three groups. One group was given TPN supplemented with glutamine and arginine before and after operation( Group A), One group was given TPN supplemented with glutamine and arginine only after operation( Group B), and the other group was given conventional parenteral nutrition after operation as the control group (Group C). The nutrition status, immune function and prognostic indicators were measured on admission day,on the first day and the sixth day after operation respectively. Results: Compared with the admission day, the levels of most humoral and cellular immune parametes declined on the first day, but they resumed on the sixth day after

  17. World enrichment services market 1990-2005

    International Nuclear Information System (INIS)

    Growth in world enrichment capacity, already in oversupply, will lead to a very competitive enrichment services market by the second half of the 1990s. Three of the four primary enrichment suppliers (USDOE, Eurodif, and Urenco) already have the capacity to produce 33 million SWU per year. Explorts from the Soviet Union and the People's Republic of China (PRC) currently make available an additional six million SWU per year, and that figure could rise substantially. With additional supply capability expected from China, the Soviet Union, Louisiana Energy Services (LES) and Isotope Technologies (ITI), and the increased capacity of Urenco, and possibly even AVLIS from DOE, enrichment supply capability could exceed 46 million SWU per year by the year 2000. Yet annual enrichment requirements are only estimated to grow from 23.5 million SWU in 1990, to 28.9 million SWU by 2000. Total unfilled enrichment requirements will rise significantly in the second half of the 1990s, particularly from US utilities, creating sales opportunities for which suppliers will compete aggressively. These factors foretell a very competitive market in which sellers will offer low prices and flexible contracts. The anticipation of such strong competition also raises the question of which enrichment technology will succeed, and puts tremendous pressure on all suppliers to find cost-effective means of production as quickly as possible

  18. Two-stage atlas subset selection in multi-atlas based image segmentation

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Tingting, E-mail: tingtingzhao@mednet.ucla.edu; Ruan, Dan, E-mail: druan@mednet.ucla.edu [The Department of Radiation Oncology, University of California, Los Angeles, California 90095 (United States)

    2015-06-15

    Purpose: Fast growing access to large databases and cloud stored data presents a unique opportunity for multi-atlas based image segmentation and also presents challenges in heterogeneous atlas quality and computation burden. This work aims to develop a novel two-stage method tailored to the special needs in the face of large atlas collection with varied quality, so that high-accuracy segmentation can be achieved with low computational cost. Methods: An atlas subset selection scheme is proposed to substitute a significant portion of the computationally expensive full-fledged registration in the conventional scheme with a low-cost alternative. More specifically, the authors introduce a two-stage atlas subset selection method. In the first stage, an augmented subset is obtained based on a low-cost registration configuration and a preliminary relevance metric; in the second stage, the subset is further narrowed down to a fusion set of desired size, based on full-fledged registration and a refined relevance metric. An inference model is developed to characterize the relationship between the preliminary and refined relevance metrics, and a proper augmented subset size is derived to ensure that the desired atlases survive the preliminary selection with high probability. Results: The performance of the proposed scheme has been assessed with cross validation based on two clinical datasets consisting of manually segmented prostate and brain magnetic resonance images, respectively. The proposed scheme demonstrates comparable end-to-end segmentation performance as the conventional single-stage selection method, but with significant computation reduction. Compared with the alternative computation reduction method, their scheme improves the mean and medium Dice similarity coefficient value from (0.74, 0.78) to (0.83, 0.85) and from (0.82, 0.84) to (0.95, 0.95) for prostate and corpus callosum segmentation, respectively, with statistical significance. Conclusions: The authors

  19. Cancer Statistics: Endometrial Cancer

    Science.gov (United States)

    ... a third party. HPF: Did You Know? Endometrial Cancer Endometrial Cancer - Did you know that endometrial cancer ... mfhs0vbvWi8?rel=0 SEER Stat Fact Sheets: Endometrial Cancer Expand All Collapse All Lifetime risk estimates are ...

  20. The US Enrichment Corp.. Looking towards privatisation

    International Nuclear Information System (INIS)

    The United States Enrichment Corporation (USEC) was launched in 1993 with the intention of bringing private sector disciplines into the US enrichment industry. It is charged with operating as a business enterprise on a profitable and efficient basis, with maximizing the long term value of the Corporation to the Treasury and taxpayer, and with maintaining a reliable and economic source of enriched uranium. Though acting like a commercial business, it remains for the moment in US government ownership. The directors have an obligation, however, to recommend to the government in 1995 if, how and when the Corporation should be privatized. (UK)

  1. Metal enrichment of the CGM through outflows

    Science.gov (United States)

    Christensen, Charlotte

    2016-01-01

    Galactic outflows enrich the circumgalactic medium through the redistribution of metals from the disks of galaxies. We examine the history of this enrichment by analyzing the outflows of twenty high-resolution simulated galaxies spanning two and a half orders of magnitude in halo mass. These simulations match many observed trends, including the mass-metallicity relation. By tracking particles in the simulations, we follow the removal and reaccretion of metals between redshift 3.5 and 0. We also determine the enrichment of the outflowing gas compared to the local interstellar media. Finally we compare the redshift zero metal census to observed values.

  2. Gene expression analysis in human breast cancer associated blood vessels.

    Directory of Open Access Journals (Sweden)

    Dylan T Jones

    Full Text Available Angiogenesis is essential for solid tumour growth, whilst the molecular profiles of tumour blood vessels have been reported to be different between cancer types. Although presently available anti-angiogenic strategies are providing some promise for the treatment of some cancers it is perhaps not surprisingly that, none of the anti-angiogenic agents available work on all tumours. Thus, the discovery of novel anti-angiogenic targets, relevant to individual cancer types, is required. Using Affymetrix microarray analysis of laser-captured, CD31-positive blood vessels we have identified 63 genes that are upregulated significantly (5-72 fold in angiogenic blood vessels associated with human invasive ductal carcinoma (IDC of the breast as compared with blood vessels in normal human breast. We tested the angiogenic capacity of a subset of these genes. Genes were selected based on either their known cellular functions, their enriched expression in endothelial cells and/or their sensitivity to anti-VEGF treatment; all features implicating their involvement in angiogenesis. For example, RRM2, a ribonucleotide reductase involved in DNA synthesis, was upregulated 32-fold in IDC-associated blood vessels; ATF1, a nuclear activating transcription factor involved in cellular growth and survival was upregulated 23-fold in IDC-associated blood vessels and HEX-B, a hexosaminidase involved in the breakdown of GM2 gangliosides, was upregulated 8-fold in IDC-associated blood vessels. Furthermore, in silico analysis confirmed that AFT1 and HEX-B also were enriched in endothelial cells when compared with non-endothelial cells. None of these genes have been reported previously to be involved in neovascularisation. However, our data establish that siRNA depletion of Rrm2, Atf1 or Hex-B had significant anti-angiogenic effects in VEGF-stimulated ex vivo mouse aortic ring assays. Overall, our results provide proof-of-principle that our approach can identify a cohort of

  3. Profile of World Uranium Enrichment Programs - 2007

    Energy Technology Data Exchange (ETDEWEB)

    Laughter, Mark D [ORNL

    2007-11-01

    It is generally agreed that the most difficult step in building a nuclear weapon is acquiring weapons grade fissile material, either plutonium or highly enriched uranium (HEU). Plutonium is produced in a nuclear reactor, while HEU is produced using a uranium enrichment process. Enrichment is also an important step in the civil nuclear fuel cycle, in producing low enriched uranium (LEU) for use in fuel for nuclear reactors. However, the same equipment used to produce LEU for nuclear fuel can also be used to produce HEU for weapons. Safeguards at an enrichment plant are the array of assurances and verification techniques that ensure uranium is only enriched to LEU, no undeclared LEU is produced, and no uranium is enriched to HEU or secretly diverted. There are several techniques for enriching uranium. The two most prevalent are gaseous diffusion, which uses older technology and requires a lot of energy, and gas centrifuge separation, which uses more advanced technology and is more energy efficient. Gaseous diffusion plants (GDPs) provide about 40% of current world enrichment capacity, but are being phased out as newer gas centrifuge enrichment plants (GCEPs) are constructed. Estimates of current and future enrichment capacity are always approximate, due to the constant upgrades, expansions, and shutdowns occurring at enrichment plants, largely determined by economic interests. Currently, the world enrichment capacity is approximately 53 million kg-separative work units (SWU) per year, with 22 million in gaseous diffusion and 31 million in gas centrifuge plants. Another 23 million SWU/year of capacity are under construction or planned for the near future, almost entirely using gas centrifuge separation. Other less-efficient techniques have also been used in the past, including electromagnetic and aerodynamic separations, but these are considered obsolete, at least from a commercial perspective. Laser isotope separation shows promise as a possible enrichment technique

  4. Relay Subset Selection in Wireless Networks Using Partial Decode-and-Forward Transmission

    CERN Document Server

    Lo, Caleb K; Heath, Robert W

    2007-01-01

    This paper considers the problem of selecting a subset of nodes in a two-hop wireless network to act as relays in aiding the communication between the source-destination pair. Optimal relay subset selection with the objective of maximizing the overall throughput is a difficult problem that depends on multiple factors including node locations, queue lengths and power consumption. A partial decode-and-forward strategy is applied in this paper to improve the tractability of the relay selection problem and performance of the overall network. Note that the number of relays selected ultimately determines the performance of the network. This paper benchmarks this performance by determining the net diversity achieved using the relays selected and the partial decode-and-forward strategy. This framework is subsequently used to further transform relay selection into a simpler relay placement problem, and two proximity-based approximation algorithms are developed to determine the appropriate set of relays to be selected ...

  5. Cross-presentation of cell-associated antigens by MHC class I in dendritic cell subsets

    Directory of Open Access Journals (Sweden)

    Enric eGutiérrez-Martínez

    2015-07-01

    Full Text Available Dendritic cells have the unique ability to pick up dead cells carrying antigens in tissue and migrate to the lymph nodes where they can cross-present cell-associated antigens by MHC class I to CD8+ T cells. There is strong in vivo evidence that the mouse XCR1+ dendritic cells subset acts as a key player in this process. The intracellular processes underlying cross-presentation remain controversial and several pathways have been proposed. Indeed, a wide number of studies have addressed the cellular process of cross-presentation in vitro using a variety of sources of antigen and antigen presenting cells. Here we review the in vivo and in vitro evidence supporting the current mechanistic models and disscuss their physiological relevance to the cross-presentation of cell-associated antigens by dendritic cells subsets

  6. Long term impact of high titer Edmonston-Zagreb measles vaccine on T lymphocyte subsets

    DEFF Research Database (Denmark)

    Lisse, I M; Aaby, P; Knudsen, K;

    1994-01-01

    conducted in Guinea-Bissau. To test for possible long term impact on the immune system, an investigation of T cell subsets was conducted among all children still residing in the community at 3 to 5 years of age. No differences were found between recipients of medium titer vaccine and controls. In the second......Several trials of high titer measles vaccine (> 10(4.7) plaque-forming unit) have found female recipients of Edmonston-Zagreb (EZ) vaccine to have lower survival than female recipients of standard measles vaccine. Two trials with medium and high titer EZ vaccine from the age of 4 months were...... unlikely to explain the reduced survival which has been associated with high titer EZ measles vaccination. In the 2 years after the investigation of T cell subsets, there was no increased mortality for recipients of EZ vaccine. Hence it is unlikely that high titer vaccine has an persistent adverse effect...

  7. Interpretation of Fuzzy Attribute Subsets in Generalized One-Sided Concept Lattices

    Directory of Open Access Journals (Sweden)

    Peter Butka

    2013-12-01

    Full Text Available In this paper we describe possible interpretation and reduction of fuzzy attributes in GeneralizedOne-sided Concept Lattices (GOSCL. This type of concept lattices represent generalization ofFormal Concept Analysis (FCA suitable for analysis of datatables with different types of attributes. FCA as well as generalized one-sided concept lattices represent conceptual data miningmethods. With growing number of attributes the interpretation of fuzzy subsets may become unclear, hence another interpretation of this fuzzy attribute subsets can be valuable. The originalityof the presented method is based on the usage of one-sided concept lattices derived from submodels of former object-attribute model by grouping attributes with the same truth value structure.This leads to new method for attribute reduction in GOSCL environment.

  8. Sterile Inflammation-Do innate lymphoid cell subsets play a role?

    Directory of Open Access Journals (Sweden)

    Shane E Russell

    2012-08-01

    Full Text Available The recent identification of several novel innate lymphoid cell subsets (iLCs has increased our understanding of the mechanisms which link the innate and adaptive immune systems. While the contribution of these subsets towards the pathogenesis of human disease remains largely to be determined, it seems likely that they will play a particularly important role in sterile inflammatory settings where the innate response is seen as a critical mediator of inflammation. Several recent studies have highlighted the role of endogenous damage associated molecular patterns such as IL-33, IL-1 and IL-1 in promoting lymphoid cell responses. This review discusses the influence of such endogenous danger signals on novel iLCs such as Lymphoid Tissue-inducer (LTi cells, innate type 2 helper cells and  T cells and explores how these responses may contribute to the development of an inflammatory response in a sterile setting.

  9. OPTIMAL ANTENNA SUBSET SELECTION AND BLIND DETECTION APPROACH APPLIED TO ORTHOGONAL SPACE-TIME BLOCK CODING

    Institute of Scientific and Technical Information of China (English)

    Xu Hongji; Liu Ju; Gu Bo

    2007-01-01

    An approach combining optimal antenna subset selection with blind detection scheme for Orthogonal Space-Time Block Coding (OSTBC) is proposed in this paper. The optimal antenna subset selection is taken into account at transmitter and/or receiver sides, which chooses the optimal antennas to increase the diversity order of OSTBC and improve further its performance. In order to enhance the robustness of the detection used in the conventional OSTBC scheme, a blind detection scheme based on Independent Component Analysis (ICA) is exploited which can directly extract transmitted signals without channel estimation. Performance analysis shows that the proposed approach can achieve the full diversity and the flexibility of system design by using the antenna selection and the ICA based blind detection schemes.

  10. Antenna Subset Selection for Cyclic Prefix Assisted MIMO Wireless Communications over Frequency Selective Channels

    Directory of Open Access Journals (Sweden)

    T. Kaiser

    2008-04-01

    Full Text Available Antenna (subset selection techniques are feasible to reduce the hardware complexity of multiple-input multiple-output (MIMO systems, while keeping the benefits of higher-order MIMO systems. Many studies of antenna selection schemes are based on frequency-flat channel models, which are inconsistent to broadband MIMO systems employing spatial-multiplexing. In broadband MIMO systems aiming to provide high-data-rate links, the employed signal bandwidth is typically larger than the coherence bandwidth of the channel so that the channel will be of frequency selective nature. Within this contribution we provide an overview on joint transmitter- and receiver-side antenna subset selection methods for frequency selective channels and deploy them in MIMO orthogonal frequency division multiplexing (OFDM systems and MIMO single-carrier (SC systems employing frequency domain equalization (FDE.

  11. Ordered-subset analysis of savant skills in autism for 15q11-q13.

    Science.gov (United States)

    Ma, D Q; Jaworski, J; Menold, M M; Donnelly, S; Abramson, R K; Wright, H H; Delong, G R; Gilbert, J R; Pericak-Vance, M A; Cuccaro, Michael L

    2005-05-01

    Autism is a complex disorder characterized by genetic and phenotypic heterogeneity. Analysis of phenotypically homogeneous subtypes has been used to both confirm and narrow potential autism linkage regions such as the chromosomal region 15q11-q13. Increased evidence for linkage in this region had been found in a subgroup of 21 autism families (total families = 94) stratified based on a savant skill factor (SSF) from the Autism Diagnostic Interview, Revised (ADI-R). We examined the savant phenotypic finding in our sample of 91 multiplex autism families. Using two-point parametric analysis in stratification with a cutoff point of a savant skill score of 0.16, our families failed to demonstrate linkage to 15q11-q13. In addition, ordered subset analysis (OSA) using SSF as a covariate also failed to show evidence for linkage. Our findings do not support savant skills as an informative phenotypic subset for linkage in our sample.

  12. Efficient IRIS Recognition through Improvement of Feature Extraction and subset Selection

    CERN Document Server

    Azizi, Amir

    2009-01-01

    The selection of the optimal feature subset and the classification has become an important issue in the field of iris recognition. In this paper we propose several methods for iris feature subset selection and vector creation. The deterministic feature sequence is extracted from the iris image by using the contourlet transform technique. Contourlet transform captures the intrinsic geometrical structures of iris image. It decomposes the iris image into a set of directional sub-bands with texture details captured in different orientations at various scales so for reducing the feature vector dimensions we use the method for extract only significant bit and information from normalized iris images. In this method we ignore fragile bits. And finally we use SVM (Support Vector Machine) classifier for approximating the amount of people identification in our proposed system. Experimental result show that most proposed method reduces processing time and increase the classification accuracy and also the iris feature vec...

  13. Cancer - resources

    Science.gov (United States)

    Resources - cancer ... The following organizations are good resources for information on cancer : American Cancer Society -- www.cancer.org Cancer Care -- www.cancercare.org National Cancer Institute -- www.cancer.gov

  14. Cancer Statistics

    Science.gov (United States)

    ... What Is Cancer? Cancer Statistics Cancer Disparities Cancer Statistics Cancer has a major impact on society in ... success of efforts to control and manage cancer. Statistics at a Glance: The Burden of Cancer in ...

  15. Parameter subset selection for the dynamic calibration of activated sludge models (ASMs): experience versus systems analysis

    DEFF Research Database (Denmark)

    Ruano, MV; Ribes, J; de Pauw, DJW;

    2007-01-01

    to describe nitrogen and phosphorus removal in the Haaren WWTP (The Netherlands). The parameter significance ranking shows that the temperature correction coefficients are among the most influential parameters on the model output. This outcome confronts the previous identifiability studies and the experience......). An appropriate combinations of both approaches is proposed which offers a realistic (doable) and sound approach for parameter subset selection in activated sludge modelling....

  16. Contribution of T Cell Subsets to the Pathophysiology of Pneumocystis-Related Immunorestitution Disease

    OpenAIRE

    Samir P Bhagwat; Gigliotti, Francis; Xu, Haodong; Wright, Terry W.

    2006-01-01

    Immune-mediated lung injury is an important component of Pneumocystis pneumonia (PcP)-related immunorestitution disease (IRD). However, the individual contribution of CD4+ and CD8+ T cells to the pathophysiology of IRD remains undetermined. Therefore, IRD was modeled in severe combined immunodeficient mice, and specific T cell depletion was used to determine how T cell subsets interact to affect the nature and severity of disease. CD4+ cells were more abundant than CD8+ cells during the acute...

  17. Methamphetamine Administration Targets Multiple Immune Subsets and Induces Phenotypic Alterations Suggestive of Immunosuppression

    OpenAIRE

    Robert Harms; Brenda Morsey; Craig W Boyer; Fox, Howard S.; Nora Sarvetnick

    2012-01-01

    Methamphetamine (Meth) is a widely abused stimulant and its users are at increased risk for multiple infectious diseases. To determine the impact of meth on the immune system, we utilized a murine model that simulates the process of meth consumption in a typical addict. Our phenotypic analysis of leukocytes from this dose escalation model revealed that meth affected key immune subsets. Meth administration led to a decrease in abundance of natural killer (NK) cells and the remaining NK cells p...

  18. Defining mononuclear phagocyte subset homology across several distant warm-blooded vertebrates through comparative transcriptomics

    Directory of Open Access Journals (Sweden)

    Thien eVu Manh

    2015-06-01

    Full Text Available Mononuclear phagocytes are organized in a complex system of ontogenically and functionally-distinct subsets, that has been best described in mouse and to some extent in human. Identification of homologous mononuclear phagocyte subsets in other vertebrate species of biomedical, economic and environmental interest is needed to improve our knowledge in physiologic and physio-pathologic processes, and to design intervention strategies against a variety of diseases, including zoonotic infections.We developed a streamlined approach combining refined cell sorting and integrated comparative transcriptomics analyses which revealed conservation of the mononuclear phagocyte organization across human, mouse, sheep, pigs and, in some respect, chicken. This strategy should help democratizing the use of omics analyses for the identification and study of cell types across tissues and species. Moreover we identified conserved gene signatures that enable robust identification and universal definition of these cell types. We identified new evolutionarily conserved gene candidates and gene interaction networks for the molecular regulation of the development or functions of these cell types, as well as conserved surface candidates for refined subset phenotyping throughout species. A phylogenetic analysis revealed that orthologous genes of the conserved signatures exist in teleost fishes and apparently not in Lamprey, indicating conservation of the genetic support for mononuclear phagocyte organization throughout jawed vertebrates but likely not in agnathans. Altogether this work provides molecular clues to the definition and functions of mononuclear phagocyte subsets across vertebrates which shall be useful to rigorously identify these cells and to design universal strategies to manipulate them in many target species towards the goal to reach and maintain global health.

  19. Immunoelectron microscopic study of the distribution of T cell subsets in rheumatoid synovium

    OpenAIRE

    1983-01-01

    The perivascular mononuclear cell collections of the rheumatoid synovium were examined both at the light and electron microscopic level by an immunoperoxidase staining technique using monoclonal antibodies directed against T cell subsets. These accumulations were variable in composition and size, not only in specimens from different patients but in the same specimen. Some areas (lymphocyte-rich areas) contained mainly small lymphocytes in clusters and others (transitional areas) contained bla...

  20. Peripheral T lymphocyte subset imbalances in children with enterovirus 71-induced hand, foot and mouth disease.

    Science.gov (United States)

    Li, Shuxian; Cai, Chunyan; Feng, Jinyan; Li, Xuejing; Wang, Yingshuo; Yang, Jun; Chen, Zhimin

    2014-02-13

    Inflammatory mediators (i.e. cytokines) play a pivotal role in the regulation of pathophysiological processes during EV71-induced hand, foot and mouth disease (HFMD). Different T cell subsets have distinct cytokine secretion profiles, and alteration in the T cell subsets frequency (imbalance) during infection leads to changed cytokine patterns. However, the effects of EV71 infection on T cell subsets were not clear. The objective of this study was to determine whether EV71-induced HFMD can be explained by the emergence of particular T-cell subsets (Th1, Th2, Tc1, Tc2, Th17, Tc17 and Treg cells) and the cytokine they produced (IFN-γ, IL-4, IL-17A and TGF-β1), as well as distinct responses to EV71 infection. We found that when compared to the control group, the percentage of Th1 and Tc1 cells was significantly higher in mild and severe HFMD group. Similar results were found in the Th1/Th2 ratio and IFN-γ levels. On the other hand, the percentage of Th17 cells and IL-17A levels were the highest in severe HFMD cases, and lowest in controls. Similar trend was also found for the Th17/Treg cell ratio. An optimal cutoff value of 2.15% for Th17 cell and 6.72 pg/ml for IL-17A provided a discriminatory value for differentiating the severity of HFMD cases by receiver operating characteristic curve analyses. These findings reveal that the Th1/Th2 and Th17/Treg imbalance exist in HFMD patients, suggesting their involvement in the pathogenesis of EV71 infection, which may have potential value as biomarkers. PMID:24316007

  1. Differences in the composition of the human antibody repertoire by B cell subsets in the blood

    OpenAIRE

    Eva Szymanska eMroczek; Ippolito, Gregory C.; Tobias eRogosch; Kam Hon eHoi; Tracy A Hwangpo; Marsha G Brand; Yingxin eZhuang; Cun Ren eLiu; Schneider, David A; Michael eZemlin; Brown, Elizabeth E.; George eGeorgiou; Schroeder, Harry W.

    2014-01-01

    The vast initial diversity of the antibody repertoire is generated centrally by means of a complex series of V (D) J gene rearrangement events, variation in the site of gene segment joining, and TdT catalyzed N- region addition. Although the diversity is great, close inspection has revealed distinct and unique characteristics in the antibody repertoires expressed by different B cell developmental subsets. In order to illustrate our approach to repertoire analysis, we present an in-depth com...

  2. Differences in the Composition of the Human Antibody Repertoire by B Cell Subsets in the Blood

    OpenAIRE

    Mroczek, Eva Szymanska; Ippolito, Gregory C.; Rogosch, Tobias; Hoi, Kam Hon; Tracy A Hwangpo; Marsha G Brand; Zhuang, Yingxin; Liu, Cun Ren; Schneider, David A; Zemlin, Michael; Brown, Elizabeth E.; Georgiou, George; Schroeder, Harry W.

    2014-01-01

    The vast initial diversity of the antibody repertoire is generated centrally by means of a complex series of V(D)J gene rearrangement events, variation in the site of gene segment joining, and TdT catalyzed N-region addition. Although the diversity is great, close inspection has revealed distinct and unique characteristics in the antibody repertoires expressed by different B cell developmental subsets. In order to illustrate our approach to repertoire analysis, we present an in-depth comparis...

  3. Hypermobility associated with osteoarthritis of the thumb base: a clinical and radiological subset of hand osteoarthritis.

    OpenAIRE

    Jónsson, H; Valtýsdóttir, S T; Kjartansson, O.; Brekkan, A

    1996-01-01

    OBJECTIVES: To study the impact of articular hypermobility on the clinical and radiological features of hand osteoarthritis (OA) and to investigate whether hand osteoarthritis associated with hypermobility should be considered a separate subset of hand OA. METHODS: Fifty consecutive female patients with clinical hand OA and thumb base symptoms were examined for hypermobility according to the Beighton criteria. RESULTS: Thirty one of the 50 patients had hypermobility features (Beighton score >...

  4. An Intrinsic Encoding of a Subset of C and its Application to TLS Network Packet Processing

    OpenAIRE

    Reynald Affeldt; Kazuhiko Sakaguchi

    2014-01-01

    TLS is such a widespread security protocol that errors in its implementation can have disastrous consequences. This responsibility is mostly borne by programmers, caught between specifications with the ambiguities of natural language and error-prone low-level parsing of network packets. We report here on the construction in the Coq proof-assistant of libraries to model, specify, and verify C programs to process TLS packets. We provide in particular an encoding of the core subset of C whose or...

  5. Feature subset selection based on mahalanobis distance: a statistical rough set method

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    In order to select effective feature subsets for pattern classification, a novel statistics rough set method is presented based on generalized attribute reduction. Unlike classical reduction approaches, the objects in universe of discourse are signs of training sample sets and values of attributes are taken as statistical parameters. The binary relation and discernibility matrix for the reduction are induced by distance function. Furthermore, based on the monotony of the distance function defined by Mahalan...

  6. Subset Simulation and its Application to Seismic Risk Based on Dynamic Analysis

    OpenAIRE

    Au, S. K.; Beck, J. L.

    2003-01-01

    A method is presented for efficiently computing small failure probabilities encountered in seismic risk problems involving dynamic analysis. It is based on a procedure recently developed by the writers called Subset Simulation in which the central idea is that a small failure probability can be expressed as a product of larger conditional failure probabilities, thereby turning the problem of simulating a rare failure event into several problems that involve the conditional simulation...

  7. Protein similarity search with subset seeds on a dedicated reconfigurable hardware

    OpenAIRE

    Peterlongo, Pierre; Noé, Laurent; Lavenier, Dominique; Georges, Gilles; Jacques, Julien; Kucherov, Gregory; Giraud, Mathieu

    2007-01-01

    Genome sequencing of numerous species raises the need of complete genome comparison with precise and fast similarity searches. Today, advanced seed-based techniques (spaced seeds, multiple seeds, subset seeds) provide better sensitivity/specificity ratios. We present an implementation of such a seed-based technique onto parallel specialized hardware embedding reconfigurable architecture (FPGA), where the FPGA is tightly connected to large capacity Flash memories. This parallel system allows l...

  8. Testing over-representation of observations in subsets of a DEA technology

    DEFF Research Database (Denmark)

    Asmild, Mette; Hougaard, Jens Leth; Olesen, Ole Bent

    2013-01-01

    This paper proposes a test for whether data are over-represented in a given production zone, i.e. a subset of a production possibility set which has been estimated using the non-parametric Data Envelopment Analysis (DEA) approach. A binomial test is used that relates the number of observations in...... space. Potential applications include tests for whether benchmark units dominate more (or less) observations than expected....

  9. A note on fuzzy PS-ideals in PS-algebra and its level subsets

    Directory of Open Access Journals (Sweden)

    Priya Thirugapillai

    2014-03-01

    Full Text Available In this paper, a new notion, named fuzzification of PS – Algebra, which is a generalization of BCK/BCI/TM/BH/Q/d/KU-algebras, is introduced, along with PS-ideal and we have discussed some of their properties in detail. Keywords: PS-Algebra, PS-ideal, Fuzzy PS-Ideal, Level Subsets, PS-Subalgebra and Fuzzy PS-Subalgebra.

  10. Peripheral Blood Lymphocyte Subsets in Adolescents: a Longitudinal Analysis from the REACH Project

    OpenAIRE

    Bret J. Rudy; Wilson, Craig M.; Durako, Stephen; Moscicki, Anna-Barbara; Muenz, Larry; Douglas, Steven D.

    2002-01-01

    Flow cytometry analysis of lymphocyte subset markers was performed for a group of sexually active, human immunodeficiency virus (HIV)-negative adolescents over a 2-year period to establish normative data. Data were collected in the REACH Project (Reaching for Excellence in Adolescent Care and Health), a multicenter, longitudinal study of HIV-positive and high-risk HIV-negative adolescents. Two- and three-color flow cytometry data were collected every 6 months for these subjects. We determined...

  11. Investigation of Combining Plant Genotypic Values and Molecular Marker Information for Constructing Core Subsets

    Institute of Scientific and Technical Information of China (English)

    Jian-Cheng Wang; Jin Hu; Ning-Ning Liu; Hai-Ming Xu; Sheng Zhang

    2006-01-01

    In the present study, a strategy was proposed for constructing plant core subsets by clusters based on the combination of continuous data for genotypic values and discrete data for molecular marker information. A mixed linear model approach was used to predict genotypic values for eliminating the environment effect.The "mixed genetic distance" was designed to solve the difficult problem of combining continuous and discrete data to construct a core subset by cluster. Four commonly used genetic distances for continuous data (Euclidean distance, standardized Euclidean distance, city block distance, and Mahalanobis distance)were used to assess the validity of the continuous data part of the mixed genetic distance; three commonly used genetic distances for discrete data (cosine distance, correlation distance, and Jaccard distance) were used to assess the validity of the discrete data part of the mixed genetic distance. A rice germplasm group with eight quantitative traits and information for 60 molecular markers was used to evaluate the validity of the new strategy. The results suggest that the validity of both parts of the mixed genetic distance are equal to or higher than the common genetic distance. The core subset constructed on the basis of a combination of data for genotypic values and molecular marker information was more representative than that constructed on the basis of data from genotypic values or molecular marker information alone. Moreover, the strategy of using combined data was able to treat dominant marker information and could combine any other continuous data and discrete data together to perform cluster to construct a plant core subset.

  12. Diagnosing Warm Frontal Cloud Formation in a GCM: A Novel Approach Using Conditional Subsetting

    Science.gov (United States)

    Booth, James F.; Naud, Catherine M.; DelGenio, Anthony D.

    2013-01-01

    This study analyzes characteristics of clouds and vertical motion across extratropical cyclone warm fronts in the NASA Goddard Institute for Space Studies general circulation model. The validity of the modeled clouds is assessed using a combination of satellite observations from CloudSat, Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO), Advanced Microwave Scanning Radiometer for Earth Observing System (AMSR-E), and the NASA Modern-Era Retrospective Analysis for Research and Applications (MERRA) reanalysis. The analysis focuses on developing cyclones, to test the model's ability to generate their initial structure. To begin, the extratropical cyclones and their warm fronts are objectively identified and cyclone-local fields are mapped into a vertical transect centered on the surface warm front. To further isolate specific physics, the cyclones are separated using conditional subsetting based on additional cyclone-local variables, and the differences between the subset means are analyzed. Conditional subsets are created based on 1) the transect clouds and 2) vertical motion; 3) the strength of the temperature gradient along the warm front, as well as the storm-local 4) wind speed and 5) precipitable water (PW). The analysis shows that the model does not generate enough frontal cloud, especially at low altitude. The subsetting results reveal that, compared to the observations, the model exhibits a decoupling between cloud formation at high and low altitudes across warm fronts and a weak sensitivity to moisture. These issues are caused in part by the parameterized convection and assumptions in the stratiform cloud scheme that are valid in the subtropics. On the other hand, the model generates proper covariability of low-altitude vertical motion and cloud at the warm front and a joint dependence of cloudiness on wind and PW.

  13. A Guide to Job Enrichment and Redesign.

    Science.gov (United States)

    Cunningham, J. Barton; Eberle, Ted

    1990-01-01

    Describes job design alternatives--job enrichment, the job characteristics model, Japanese style management, and quality-of-worklife approaches. Focuses on the problems that human resources professionals may encounter when attempting to implement these approaches. (Author/JOW)

  14. Management's Ecstasy and Disparity Over Job Enrichment

    Science.gov (United States)

    King, Albert S.

    1976-01-01

    A case study analyzing job enrichment schemes and manager expectations of increased productivity is presented. It was found that it was the managers' expectations of increased productivity, not the reorganization of work, that led to higher productivity. (EC)

  15. Job Enrichment: How to Avoid the Pitfalls

    Science.gov (United States)

    Tregoe, Benjamin B., Jr.

    1974-01-01

    While many job enrichment programs fail, a program called Analytical Trouble Shooting has been successful in training people to increase their problem-solving capabilities and to communicate readily with persons in other areas and on different levels. (AG)

  16. Status of laser enrichment technology updated

    Science.gov (United States)

    Sakabe, Y.

    1986-08-01

    The principles of uranium enrichment by a laser method, the technology's current status and future prospects, centered on research and development activity at the Japan Atomic Energy Research Institute and the Institute of Physical and Chemical Research are described.

  17. Creating a non-linear total sediment load formula using polynomial best subset regression model

    Science.gov (United States)

    Okcu, Davut; Pektas, Ali Osman; Uyumaz, Ali

    2016-08-01

    The aim of this study is to derive a new total sediment load formula which is more accurate and which has less application constraints than the well-known formulae of the literature. 5 most known stream power concept sediment formulae which are approved by ASCE are used for benchmarking on a wide range of datasets that includes both field and flume (lab) observations. The dimensionless parameters of these widely used formulae are used as inputs in a new regression approach. The new approach is called Polynomial Best subset regression (PBSR) analysis. The aim of the PBRS analysis is fitting and testing all possible combinations of the input variables and selecting the best subset. Whole the input variables with their second and third powers are included in the regression to test the possible relation between the explanatory variables and the dependent variable. While selecting the best subset a multistep approach is used that depends on significance values and also the multicollinearity degrees of inputs. The new formula is compared to others in a holdout dataset and detailed performance investigations are conducted for field and lab datasets within this holdout data. Different goodness of fit statistics are used as they represent different perspectives of the model accuracy. After the detailed comparisons are carried out we figured out the most accurate equation that is also applicable on both flume and river data. Especially, on field dataset the prediction performance of the proposed formula outperformed the benchmark formulations.

  18. PD1-Expressing T Cell Subsets Modify the Rejection Risk in Renal Transplant Patients

    Science.gov (United States)

    Pike, Rebecca; Thomas, Niclas; Workman, Sarita; Ambrose, Lyn; Guzman, David; Sivakumaran, Shivajanani; Johnson, Margaret; Thorburn, Douglas; Harber, Mark; Chain, Benny; Stauss, Hans J.

    2016-01-01

    We tested whether multi-parameter immune phenotyping before or after renal ­transplantation can predict the risk of rejection episodes. Blood samples collected before and weekly for 3 months after transplantation were analyzed by multi-parameter flow cytometry to define 52 T cell and 13 innate lymphocyte subsets in each sample, producing more than 11,000 data points that defined the immune status of the 28 patients included in this study. Principle component analysis suggested that the patients with histologically confirmed rejection episodes segregated from those without rejection. Protein death 1 (PD-1)-expressing subpopulations of regulatory and conventional T cells had the greatest influence on the principal component segregation. We constructed a statistical tool to predict rejection using a support vector machine algorithm. The algorithm correctly identified 7 out of 9 patients with rejection, and 14 out of 17 patients without rejection. The immune profile before transplantation was most accurate in determining the risk of rejection, while changes of immune parameters after transplantation were less accurate in discriminating rejection from non-rejection. The data indicate that pretransplant immune subset analysis has the potential to identify patients at risk of developing rejection episodes, and suggests that the proportion of PD1-expressing T cell subsets may be a key indicator of rejection risk. PMID:27148254

  19. On sets of directions and angles determined by subsets of ${\\Bbb R}^d$

    CERN Document Server

    Iosevich, Alex; Senger, Steven

    2010-01-01

    Given $E \\subset \\mathbb{R}^d$, $d \\ge 2$, define ${\\mathcal D}(E) \\equiv \\left\\{\\frac{x-y}{|x-y|}: x,y \\in E \\right\\} \\subset S^{d-1},$ the set of directions determined by $E$. We prove that if the Hausdorff dimension of $E$ is greater than $d-1$, then $\\sigma({\\mathcal D}(E))>0$, where $\\sigma$ denotes the surface measure on $S^{d-1}$. This result is sharp since the conclusion fails to hold if $E$ is a $(d-1)$-dimensional hyper-plane. This result can be viewed as a continuous analog of a recent result of Pach, Pinchasi, and Sharir (\\cite{PPS04}, \\cite{PPS07}) on angles determined by finite subsets of $\\mathbb{R}^d$. Also define ${\\mathcal A}(E)=\\{\\theta(x,y,z): x,y,z \\in E\\},$ where $\\theta(x,y,z)$ is the angle between $x-y$ and $y-z$. We use the techniques developed to handle the problem of directions and results on distance sets previously obtained by Wolff and Erdogan to prove that if the Hasudorff dimension of $E$ is greater than $\\frac{d-1}{2}+\\frac{1}{3}$, then the Lebesgue measure of ${\\mathcal A}(E)...

  20. Detection of T lymphocyte subsets of children with Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    Lin-Lin Wang; Qing-Wen Shan; Hai-Xing Jiang; Dinh-Binh Tran; Xue Qin; Xiang-Zhi Xie; Dan-Mei Liang

    2005-01-01

    AIM: To study the transformation of T lymphocyte subsets in children with Heliobacter pylori (H pylori) infection. METHODS: The H pylori infection status were determined by a combination of ELISA and Western blot (immunoblot) technique in 98 children and T lymphocyte subsets in peripheral blood were determined by flow cytometrical analysis.RESULTS: There were 75 children positive with H pylori infection and 23 negative in 98 children. Comparing the proportion of peripheral blood T lymphocytic subsets in children with H pylori infection and without H pylori infection, it was found that a higher proportion of CD4 T-cells in infected children (39.02±7.71 vs34.25±10.73,t = 2.246,P<0.05) and higher value of CD4 to CD8 T-cells ratio (1.51±0.52 vs 1.25, t= 2.104,P<0.05) were present, but there were not significant differences in CD3 T-cells and CD8 T-cells (73.11±10.02 vs69.49±17.08, 27.22±6.07vs 28.27±8.67, P>0.05).CONCLUSION: Th1 cell-mediated immune responses may be induced by H pylori infection in children.

  1. Interaction between nitric oxide and subsets of human T lymphocytes with differences in glutathione metabolism

    Science.gov (United States)

    Roozendaal, Ramon; Kauffman, Henk F; Dijkhuis, Anne-Jan; Ommen, Elisabeth T V; Postma, Dirkje S; De Monchy, Jan G R; Vellenga, Edo

    2002-01-01

    Nitric oxide (NO) modulates human T-lymphocyte responses through several mechanisms. In the current study we show that interactions between NO and glutathione (GSH) metabolism are related to the selective persistent inhibition of interferon-γ (IFN-γ) production by NO, which we previously identified. T cells were exposed to NO using the NO-donor compound Spermine-nonoate (Sper) and activated using anti-CD3 plus anti-CD28 monoclonal antibodies. Persistent inhibition of IFN-γ by Sper was prevented by addition of the GSH precursor l-cysteine, which inhibits Sper induced GSH depletion. Subsets of cells were either susceptible (GSHlow) or resistant (GSHhigh) to NO-induced GSH depletion. The GSHlow subset was characterized by enhanced numbers of CD4+ cells, reduced numbers of activated cells as characterized by CD25 and CD69, and reduced numbers of memory (CD45RO+) cells relative to the GSHhigh population. Rather than directly affecting susceptibility to NO, these surface markers reflected different expression patterns. Particularly, the GSHlow subset was further characterized by decreased activity of the GSH synthesis related enzymes multi-drug resistance related protein (MRP)-1 and γ-glutamyltranspeptidase (γ-GT). Blocking γ-GT, using acivicin was shown to exacerbate NO-induced GSH depletion and NO-induced apoptosis. Since NO induced apoptosis selectively affects IFN-γ production these findings implicate GSH metabolism in the modulation and maintenance of the T helper (Th)1/Th2 balance. PMID:12423309

  2. Characterization and Quantification of Innate Lymphoid Cell Subsets in Human Lung.

    Directory of Open Access Journals (Sweden)

    Katrien C De Grove

    Full Text Available Innate lymphoid cells (ILC are a new family of innate immune cells that have emerged as important regulators of tissue homeostasis and inflammation. However, limited data are available concerning the relative abundance and characteristics of ILC in the human lung.The aim of this study was to characterize and enumerate the different ILC subsets in human lung by multi-color flow cytometry.Within the CD45+ Lin- CD127+ pulmonary ILC population, we identified group 1 (ILC1, group 2 (ILC2 and group 3 (ILC3 innate lymphoid cells using specific surface markers (i.e. IL12Rβ2, CRTH2 and CD117 respectively and key transcription factors (i.e. T-bet, GATA-3 and RORγT respectively. Based on the presence of NKp44, ILC3 were further subdivided in natural cytotoxicity receptor (NCR+ and NCR- ILC3. In addition, we demonstrated the production of signature cytokines IFN-γ, IL-5, IL-17A, IL-22 and GM-CSF in the pulmonary ILC population. Interestingly, we observed a tendency to a higher frequency of NCR- ILC3 in lungs of patients with chronic obstructive pulmonary disease (COPD compared with controls.We show that the three main ILC subsets are present in human lung. Importantly, the relative abundance of ILC subsets tended to change in COPD patients in comparison to control individuals.

  3. Towards Qualifiable Code Generation from a Clocked Synchronous Subset of Modelica

    Directory of Open Access Journals (Sweden)

    Bernhard Thiele

    2015-01-01

    Full Text Available So far no qualifiable automatic code generators (ACGs are available for Modelica. Hence, digital control applications can be modeled and simulated in Modelica, but require tedious additional efforts (e.g., manual reprogramming to produce qualifiable target system production code. In order to more fully leverage the potential of a model-based development (MBD process in Modelica, a qualifiable automatic code generator is needed. Typical Modelica code generation is a fairly complex process which imposes a huge development burden to any efforts of tool qualification. This work aims at mapping a Modelica subset for digital control function development to a well-understood synchronous data-flow kernel language. This kernel language allows to resort to established compilation techniques for data-flow languages which are understood enough to be accepted by certification authorities. The mapping is established by providing a translational semantics from the Modelica subset to the synchronous data-flow kernel language. However, this translation turned out to be more intricate than initially expected and has given rise to several interesting issues that require suitable design decisions regarding the mapping and the language subset.

  4. Lymphocyte subsets in human immunodeficiency virus-unexposed Brazilian individuals from birth to adulthood

    Directory of Open Access Journals (Sweden)

    Maria Isabel de Moraes-Pinto

    2014-12-01

    Full Text Available Ethnic origin, genetics, gender and environmental factors have been shown to influence some immunologic indices, so that development of reference values for populations of different backgrounds may be necessary. We have determined the distribution of lymphocyte subsets in healthy Brazilian individuals from birth to adulthood. Lymphocyte subsets were determined using four-colour cytometry in a cross-sectional study of 463 human immunodeficiency virus-unexposed children and adults from birth through 49 years of age. Lymphocyte subsets varied according to age, as previously observed in other studies. However, total CD4+ T cell numbers were lower than what was described in the Pediatric AIDS Clinical Trials Group P1009 (PACTG P1009, which assessed an American population of predominantly African and Hispanic backgrounds until the 12-18 year age range, when values were comparable. Naïve percentages and absolute values of CD8+ T cells, as assessed by CD45RA expression, were also lower than the PACTG P1009 data for all analysed age ranges. CD38 expression on both CD4+ and CD8+ T cells was lower than the PACTG P1009 values, with a widening gap between the two studies at older age ranges. Different patterns of cell differentiation seem to occur in different settings and may have characteristic expression within each population.

  5. Neurohypophysial Receptor Gene Expression by Thymic T Cell Subsets and Thymic T Cell Lymphoma Cell Lines

    Directory of Open Access Journals (Sweden)

    I. Hansenne

    2004-01-01

    transcribed in thymic epithelium, while immature T lymphocytes express functional neurohypophysial receptors. Neurohypophysial receptors belong to the G protein-linked seven-transmembrane receptor superfamily and are encoded by four distinct genes, OTR, V1R, V2R and V3R. The objective of this study was to identify the nature of neurohypophysial receptor in thymic T cell subsets purified by immunomagnetic selection, as well as in murine thymic lymphoma cell lines RL12-NP and BW5147. OTR is transcribed in all thymic T cell subsets and T cell lines, while V3R transcription is restricted to CD4+ CD8+ and CD8+ thymic cells. Neither V1R nor V2R transcripts are detected in any kind of T cells. The OTR protein was identified by immunocytochemistry on thymocytes freshly isolated from C57BL/6 mice. In murine fetal thymic organ cultures, a specific OTR antagonist does not modify the percentage of T cell subsets, but increases late T cell apoptosis further evidencing the involvement of OT/OTR signaling in the control of T cell proliferation and survival. According to these data, OTR and V3R are differentially expressed during T cell ontogeny. Moreover, the restriction of OTR transcription to T cell lines derived from thymic lymphomas may be important in the context of T cell leukemia pathogenesis and treatment.

  6. Memory T cell subsets in tuberculosis: what should we be targeting?

    Science.gov (United States)

    Henao-Tamayo, Marcela; Ordway, Diane J; Orme, Ian M

    2014-09-01

    The purpose of vaccination is to establish a stable population of long lived memory T cells. In the context of tuberculosis, the BCG vaccine has been widely used for well over 60 years, but during that time its weaknesses, particularly its ineffectiveness in adults, has been increasingly recognized. In this commentary we review what is known about memory T cells, both in general and in the context of their role in expressing specific acquired resistance to tuberculosis. Current knowledge indicates that both effector memory and central memory can be generated, depending on the experimental conditions, but both in animal models and in clinical studies it is clear that effector memory T cells are the predominant subset. These issues are of importance, given the concerted effort to make new TB vaccines, not all of which may work in precisely the same manner. At the present time whether a TB vaccine would work better if it targeted one specific T cell subset rather than another is as yet completely unknown, and this is now further complicated by new evidence that suggests other subsets such as IL-17 secreting CD4 T cells and cells with stem cell-like qualities may also play important roles.

  7. Molecular marker differences relate to developmental position and subsets of mesodiencephalic dopaminergic neurons.

    Directory of Open Access Journals (Sweden)

    Simone M Smits

    Full Text Available The development of mesodiencephalic dopaminergic (mdDA neurons located in the substantia nigra compacta (SNc and ventral tegmental area (VTA follow a number of stages marked by distinct events. After preparation of the region by signals that provide induction and patterning, several transcription factors have been identified, which are involved in specifying the neuronal fate of these cells. The specific vulnerability of SNc neurons is thought to root in these specific developmental programs. The present study examines the positions of young postmitotic mdDA neurons to relate developmental position to mdDA subset specific markers. MdDA neurons were mapped relative to the neuromeric domains (prosomeres 1-3 (P1-3, midbrain, and hindbrain as well as the longitudinal subdivisions (floor plate, basal plate, alar plate, as proposed by the prosomeric model. We found that postmitotic mdDA neurons are located mainly in the floorplate domain and very few in slightly more lateral domains. Moreover, mdDA neurons are present along a large proportion of the anterior/posterior axis extending from the midbrain to P3 in the diencephalon. The specific positions relate to some extent to the presence of specific subset markers as Ahd2. In the adult stage more of such subsets specific expressed genes are present and may represent a molecular map defining molecularly distinct groups of mdDA neurons.

  8. Differences in the composition of the human antibody repertoire by B cell subsets in the blood

    Directory of Open Access Journals (Sweden)

    Eva Szymanska eMroczek

    2014-03-01

    Full Text Available The vast initial diversity of the antibody repertoire is generated centrally by means of a complex series of V (D J gene rearrangement events, variation in the site of gene segment joining, and TdT catalyzed N- region addition. Although the diversity is great, close inspection has revealed distinct and unique characteristics in the antibody repertoires expressed by different B cell developmental subsets. In order to illustrate our approach to repertoire analysis, we present an in-depth comparison of V (D J gene usage, hydrophobicity, length, DH reading frame, and amino acid usage between heavy chain repertoires expressed by immature, transitional, mature, memory IgD+, memory IgD-, and plasmacytes isolated from the blood of a single individual. Our results support the view that in both human and mouse the H chain repertoires expressed by individual, developmental B cell subsets appear to differ in sequence content. Sequencing of unsorted B cells from the blood is thus likely to yield an incomplete or compressed view of what is actually happening in the immune response of the individual. Our findings support the view that studies designed to correlate repertoire expression with diseases of immune function will likely require deep sequencing of B cells sorted by subset.

  9. Challenges when developing omega-3 enriched foods

    OpenAIRE

    Jacobsen, Charlotte

    2010-01-01

    Due to the polyunsaturated nature of omega-3 fatty acids, lipid oxidation is a major challenge when developing omega-3 enriched foods. In multiphase food systems, several factors can affect lipid oxidation and efficacy of antioxidants, added to prevent lipid oxidation. This review discusses the influence of important factors such as oil quality, delivery systems for omega-3 fatty acids, processing conditions, composition of the food matrix on lipid oxidation in different omega-3 enriched food...

  10. NRC licensing of uranium enrichment plants

    International Nuclear Information System (INIS)

    The US Nuclear Regulatory Commission (NRC) is preparing a rule making that establishes the licensing requirements for low-enriched uranium enrichment plants. Although implementation of this rule making is timed to correspond with receipt of a license application for the Louisiana Energy Services centrifuge enrichment plant, the rule making is applicable to all uranium enrichment technologies. If ownership of the US gaseous diffusion plants and/or atomic vapor laser isotope separation is transferred to a private or government corporation, these plants also would be licensable under the new rule making. The Safeguards Studies Department was tasked by the NRC to provide technical assistance in support of the rule making and guidance preparation process. The initial and primary effort of this task involved the characterization of the potential safeguards concerns associated with a commercial enrichment plant, and the licensing issues associated with these concerns. The primary safeguards considerations were identified as detection of the loss of special nuclear material, detection of unauthorized production of material of low strategic significance, and detection of production of uranium enriched to >10% 235U. The primary safeguards concerns identified were (1) large absolute limit of error associated with the material balance closing, (2) the inability to shutdown some technologies to perform a cleanout inventory of the process system, and (3) the flexibility of some technologies to produce higher enrichments. Unauthorized production scenarios were identified for some technologies that could prevent conventional material control and accounting programs from detecting the production and removal of 5 kg 235U as highly enriched uranium. Safeguards techniques were identified to mitigate these concerns

  11. Modeling of Transients in an Enrichment Circuit

    International Nuclear Information System (INIS)

    In the present work a mathematical model is presented in order to describe the dynamic behavior inside a closed enrichment loop, the latter representing a single stage of an uranium gaseous diffusion enrichment cascade.The analytical model is turned into a numerical model, and implemented through a computational code.Transients of two species separation were numerically analyzed, including setting times of each magnitude, behavior of each one of them during different transients, and redistribution of concentrations along the closed loop

  12. U.S. forms uranium enrichment corporation

    International Nuclear Information System (INIS)

    After almost 40 years of operation, the federal government is withdrawing from the uranium enrichment business. On July 1, the Department of Energy turned over to a new government-owned entity--the US Enrichment Corp. (USEC)--both the DOE enrichment plants at Paducah, Ky., and Portsmouth, Ohio, and domestic and international marketing of enriched uranium from them. Pushed by the inability of DOE's enrichment operations to meet foreign competition, Congress established USEC under the National Energy Policy Act of 1992, envisioning the new corporation as the first step to full privatization. With gross revenues of $1.5 billion in fiscal 1992, USEC would rank 275th on the Fortune 500 list of top US companies. USEC will lease from DOE the Paducah and Portsmouth facilities, built in the early 1950s, which use the gaseous diffusion process for uranium enrichment. USEC's stock is held by the US Treasury, to which it will pay annual dividends. Martin Marietta Energy Systems, which has operated Paducah since 1984 and Portsmouth since 1986 for DOE, will continue to operate both plants for USEC. Closing one of the two facilities will be studied, especially in light of a 40% world surplus of capacity over demand. USEC also will consider other nuclear-fuel-related ventures. USEC will produce only low-enriched uranium, not weapons-grade material. Indeed, USEC will implement a contract now being completed under which the US will purchase weapons-grade uranium from dismantled Russian nuclear weapons and convert it into low-enriched uranium for power reactor fuel

  13. Identification of a human CD8+ regulatory T cell subset that mediates suppression through the chemokine CC chemokine ligand 4.

    NARCIS (Netherlands)

    Joosten, S.A.; Meijgaarden, K.E. van; Savage, N.D.; Boer, T. de; Triebel, F.; Wal, A. van der; Heer, E. de; Klein, M.R.; Geluk, A.; Ottenhoff, T.H.M.

    2007-01-01

    Regulatory T cells (Treg) comprise multiple subsets and are important in controlling immunity and inflammation. However, the induction and mode of action of the various distinct Treg subsets remain ill defined, particularly in humans. Here, we describe a human CD8+ lymphocyte activation gene-3 (LAG-

  14. RNA Helicase DDX5 Regulates MicroRNA Expression and Contributes to Cytoskeletal Reorganization in Basal Breast Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Daojing; Huang, Jing; Hu, Zhi

    2011-11-15

    RNA helicase DDX5 (also p68) is involved in all aspects of RNA metabolism and serves as a transcriptional co-regulator, but its functional role in breast cancer remains elusive. Here, we report an integrative biology study of DDX5 in breast cancer, encompassing quantitative proteomics, global MicroRNA profiling, and detailed biochemical characterization of cell lines and human tissues. We showed that protein expression of DDX5 increased progressively from the luminal to basal breast cancer cell lines, and correlated positively with that of CD44 in the basal subtypes. Through immunohistochemistry analyses of tissue microarrays containing over 200 invasive human ductal carcinomas, we observed that DDX5 was upregulated in the majority of malignant tissues, and its expression correlated strongly with those of Ki67 and EGFR in the triple-negative tumors. We demonstrated that DDX5 regulated a subset of MicroRNAs including miR-21 and miR-182 in basal breast cancer cells. Knockdown of DDX5 resulted in reorganization of actin cytoskeleton and reduction of cellular proliferation. The effects were accompanied by upregulation of tumor suppressor PDCD4 (a known miR-21 target); as well as upregulation of cofilin and profilin, two key proteins involved in actin polymerization and cytoskeleton maintenance, as a consequence of miR-182 downregulation. Treatment with miR-182 inhibitors resulted in morphologic phenotypes resembling those induced by DDX5 knockdown. Using bioinformatics tools for pathway and network analyses, we confirmed that the network for regulation of actin cytoskeleton was predominantly enriched for the predicted downstream targets of miR-182. Our results reveal a new functional role of DDX5 in breast cancer via the DDX5→miR-182→actin cytoskeleton pathway, and suggest the potential clinical utility of DDX5 and its downstream MicroRNAs in the theranostics of breast cancer.

  15. Oak Ridge National Laboratory's isotope enrichment program

    International Nuclear Information System (INIS)

    The Isotope Enrichment Program (IEP) at Oak Ridge National Laboratory (ORNL) is responsible for the production and distribution of ∼225 enriched stable isotopes from 50 multi-isotopic elements. In addition, ORNL distributes enriched actinide isotopes and provides extensive physical- and chemical-form processing of enriched isotopes to meet customer requirements. For more than 50 yr, ORNL has been a major provider of enriched isotopes and isotope-related services to research, medical, and industrial institutions throughout the world. Consolidation of the Isotope Distribution Office (IDO), the Isotope Research Materials Laboratory (IRML), and the stable isotope inventories in the Isotope Enrichment Facility (IEF) have improved operational efficiencies and customer services. Recent changes in the IEP have included adopting policies for long-term contracts, which offer program stability and pricing advantages for the customer, and prorated service charges, which greatly improve pricing to the small research users. The former U.S. Department of Energy (DOE) Loan Program has been converted to a lease program, which makes large-quantity or very expensive isotopes available for nondestructive research at a nominal cost. Current efforts are being pursued to improve and expand the isotope separation capabilities as well as the extensive chemical- and physical-form processing that now exists. The IEF's quality management system is ISO 9002 registered and accredited in the United States, Canada, and Europe

  16. Carbon dioxide enrichment of greenhouse crops

    Energy Technology Data Exchange (ETDEWEB)

    Enoch, H.Z.; Kimball, B.A.

    1986-01-01

    This volume contains the following on these major topics of physiology, yield and economics: Fixation of Inorganic Carbon in Plant Cells. Effects of CO/sub 2/ Enrichment on Photosynthesis of C/sub 3/ Plants. Effects of CO/sub 2/ Concentration on Photosynthesis and Respiration of C/sub 4/ and CAM Plants. Effects of CO/sub 2/ Concentration on Composition, Anatomy, and Morphology of Plants. Stimulation of Growth and Yield Under Environmental Restraints. Woody Plant Reactions to CO/sub 2/ Enrichment. Influence of the CO/sub 2/ Content of the Ambient Air on Stomatal Conductance and CO/sub 2/ Concentration in Leaves. Influence of Elevated CO/sub 2/ on Crop Yield. Fertilization of Carnations and Some Other Flower Crops. CO/sub 2/ Enrichment for Greenhouse Rose Production. CO/sub 2/ Enrichment of Tomato Crops. CO/sub 2/ Enrichment Duration and Heating Credit as Determined by Climate. Economics of CO/sub 2/ Enrichment in Greenhouses. Units Conversion. Currency Exchange Rates.

  17. 6 Common Cancers - Prostate Cancer

    Science.gov (United States)

    ... PSA tests. Read More "6 Common Cancers" Articles Lung Cancer / Breast Cancer / Prostate Cancer / Colorectal Cancer / Skin Cancer / Gynecologic Cancers Spring 2007 Issue: Volume 2 Number 2 Page 10 MedlinePlus | Subscribe | Magazine Information | Contact Us | Viewers & ...

  18. 6 Common Cancers - Colorectal Cancer

    Science.gov (United States)

    ... certain people. Read More "6 Common Cancers" Articles Lung Cancer / Breast Cancer / Prostate Cancer / Colorectal Cancer / Skin Cancer / Gynecologic Cancers Spring 2007 Issue: Volume 2 Number 2 Page 11 MedlinePlus | Subscribe | Magazine Information | Contact Us | Viewers & ...

  19. Characterization of Plasma Membrane Proteins from Ovarian Cancer Cells Using Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    David L. Springer

    2004-01-01

    Full Text Available To determine how the repertoire of plasma membrane proteins change with disease state, specifically related to cancer, several methods for preparation of plasma membrane proteins were evaluated. Cultured cells derived from stage IV ovarian tumors were grown to 90% confluence and harvested in buffer containing CHAPS detergent. This preparation was centrifuged at low speed to remove insoluble cellular debris resulting in a crude homogenate. Glycosylated proteins in the crude homogenate were selectively enriched using lectin affinity chromatography. The crude homogenate and the lectin purified sample were prepared for mass spectrometric evaluation. The general procedure for protein identification began with trypsin digestion of protein fractions followed by separation by reversed phase liquid chromatography that was coupled directly to a conventional tandem mass spectrometer (i.e. LCQ ion trap. Mass and fragmentation data for the peptides were searched against a human proteome data base using the informatics program SEQUEST. Using this procedure 398 proteins were identified with high confidence, including receptors, membrane-associated ligands, proteases, phosphatases, as well as structural and adhesion proteins. Results indicate that lectin chromatography provides a select subset of proteins and that the number and quality of the identifications improve as does the confidence of the protein identifications for this subset. These results represent the first step in development of methods to separate and successfully identify plasma membrane proteins from advanced ovarian cancer cells. Further characterization of plasma membrane proteins will contribute to our understanding of the mechanisms underlying progression of this deadly disease and may lead to new targeted interventions as well as new biomarkers for diagnosis.

  20. Methionine enkephalin: immunomodulator in normal volunteers, cancer and AIDS patients

    Directory of Open Access Journals (Sweden)

    Nicholas P. Plotnikoff

    1987-01-01

    Full Text Available Clinical studies of the immunological effects of methionine enkephalin in normal volunteers, cancer, and AIDS patients are summarized. The major immunology changes seen were increases in T cell subsets, natural killer activity, as well as mitogen blastogenesis. Clinically, the cancer and ARC patients did not develop infections.