Sample records for cd45 side population

  1. Quantitative gene expression profiling of CD45+ and CD45- skeletal muscle-derived side population cells

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    Ditte Caroline Andersen, Ditte Caroline; Kristiansen, Gitte Qvist; Jensen, Line;


    transcripts associated with endothelial cells, Notch signaling and myogenic precursors. By comparing the mRNA signatures of mSPs with those of adipose tissue-derived SP populations, a common endothelial component seemed to reside in both muscle and fat-derived SPCD45(-) entities. However, each SP subset...... a satellite cell subpopulation) remain in the mSPCD45(-) fraction, and we show that these cells express high levels of many of the known myogenic precursor/stem cell related markers, including Pax7 and Myf5.......The skeletal muscle-derived side population (mSP) which highly excludes Hoechst 33342 is composed of CD45(+) and CD45(-) subpopulations; yet, rareness of mSP cells in general has complicated extensive quantitative analysis of gene expression profiles in primarily isolated mSP cells. Here, we...

  2. Quantitative gene expression profiling of CD45(+) and CD45(-) skeletal muscle-derived side population cells

    DEFF Research Database (Denmark)

    Andersen, Ditte Caroline; Kristiansen, Gitte Qvistgaard; Jensen, Line;


    transcripts associated with endothelial cells, Notch signaling and myogenic precursors. By comparing the mRNA signatures of mSPs with those of adipose tissue-derived SP populations, a common endothelial component seemed to reside in both muscle and fat-derived SPCD45(-) entities. However, each SP subset...... a satellite cell subpopulation) remain in the mSPCD45(-) fraction, and we show that these cells express high levels of many of the known myogenic precursor/stem cell related markers, including Pax7 and Myf5. © 2011 International Society for Advancement of Cytometry.......The skeletal muscle-derived side population (mSP) which highly excludes Hoechst 33342 is composed of CD45(+) and CD45(-) subpopulations; yet, rareness of mSP cells in general has complicated extensive quantitative analysis of gene expression profiles in primarily isolated mSP cells. Here, we...

  3. CD27(-)CD45(+) γδ T cells can be divided into two populations, CD27(-)CD45(int) and CD27(-)CD45(hi) with little proliferation potential. (United States)

    Odaira, Kosuke; Kimura, Shin-Nosuke; Fujieda, Nao; Kobayashi, Yukari; Kambara, Kaori; Takahashi, Takuya; Izumi, Takamichi; Matsushita, Hirokazu; Kakimi, Kazuhiro


    In addition to the majority of T cells which carry the αβ T cell receptor (TCR) for antigen, a distinct subset of about 1-5% of human peripheral blood T cells expressing the γδ TCR contributes to immune responses to infection, tissue damage and cancer. T cells with the Vδ2(+) TCR, usually paired with Vγ9, constitute the majority of these γδ T cells. Analogous to αβ T cells, they can be sorted into naive (CD27(+)CD45RA(+)), central memory (CD27(+)CD45RA(-)), effector memory (CD27(-)CD45RA(-)), and terminally-differentiated effector memory (CD27(-)CD45RA(+)) phenotypes. Here, we found that CD27(-)CD45RA(+) γδ T cells can be further divided into two populations based on the level of expression of CD45RA: CD27(-)CD45RA(int) and CD27(-)CD45RA(hi). Those with the CD27(-)CD45RA(hi) phenotype lack extensive proliferative capacity, while those with the CD27(-)CD45RA(int) phenotype can be easily expanded by culture with zoledronate and IL-2. These CD27(-)CD45RA(hi) potentially exhausted γδ T cells were found predominantly in cancer patients but also in healthy subjects. We conclude that γδ T cells can be divided into at least 5 subsets enabling discrimination of γδ T cells with poor proliferative capacity. It was one of our goals to predict the feasibility of γδ T cell expansion to sufficient amounts for adoptive immunotherapy without the necessity for conducting small-scale culture tests. Fulfilling the ≥1.5% criterion for γδ T cells with phenotypes other than CD27(-)CD45RA(hi), may help avoid small-scale culture testing and shorten the preparation period for adoptive γδ T cells by 10 days, which may be beneficial for patients with advanced cancer.

  4. CD45{sup low}c-Kit{sup high} cells have hematopoietic properties in the mouse aorta-gonad-mesonephros region

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    Nobuhisa, Ikuo, E-mail: [Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510 (Japan); Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics/Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, 860-0811 (Japan); Yamasaki, Shoutarou [Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics/Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, 860-0811 (Japan); Ramadan, Ahmed [Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510 (Japan); Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics/Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, 860-0811 (Japan); Taga, Tetsuya, E-mail: [Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510 (Japan); Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics/Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, 860-0811 (Japan)


    Long-term reconstituting hematopoietic stem cells first arise from the aorta of the aorta-gonad-mesonephros (AGM) region in a mouse embryo. We have previously reported that in cultures of the dispersed AGM region, CD45{sup low}c-Kit{sup +} cells possess the ability to reconstitute multilineage hematopoietic cells, but investigations are needed to show that this is not a cultured artifact and to clarify when and how this population is present. Based on the expression profile of CD45 and c-Kit in freshly dissociated AGM cells from embryonic day 9.5 (E9.5) to E12.5 and aorta cells in the AGM from E13.5 to E15.5, we defined six cell populations (CD45{sup -}c-Kit{sup -}, CD45{sup -}c-Kit{sup low}, CD45{sup -}c-Kit{sup high}, CD45{sup low}c-Kit{sup high}, CD45{sup high}c-Kit{sup high}, and CD45{sup high}c-Kit{sup very} {sup low}). Among these six populations, CD45{sup low}c-Kit{sup high} cells were most able to form hematopoietic cell colonies, but their ability decreased after E11.5 and was undetectable at E13.5 and later. The CD45{sup low}c-Kit{sup high} cells showed multipotency in vitro. We demonstrated further enrichment of hematopoietic activity in the Hoechst dye-effluxing side population among the CD45{sup low}c-Kit{sup high} cells. Here, we determined that CD45{sup low}c-Kit{sup high} cells arise from the lateral plate mesoderm using embryonic stem cell-derived differentiation system. In conclusion, CD45{sup low}c-Kit{sup high} cells are the major hematopoietic cells of mouse AGM.

  5. Reconstruction of endometrium from human endometrial side population cell lines.

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    Irene Cervelló

    Full Text Available Endometrial regeneration is mediated, at least in part, by the existence of a specialized somatic stem cell (SSC population recently identified by several groups using the side population (SP technique. We previously demonstrated that endometrial SP displays genotypic, phenotypic and the functional capability to develop human endometrium after subcutaneous injection in NOD-SCID mice. We have now established seven human endometrial SP (hESP cell lines (ICE 1-7: four from the epithelial and three from the stromal fraction, respectively. SP cell lines were generated under hypoxic conditions based on their cloning efficiency ability, cultured for 12-15 passages (20 weeks and cryopreserved. Cell lines displayed normal 46XX karyotype, intermediate telomerase activity pattern and expressed mRNAs encoding proteins that are considered characteristic of undifferentiated cells (Oct-4, GDF3, DNMT3B, Nanog, GABR3 and those of mesodermal origin (WT1, Cardiac Actin, Enolase, Globin, REN. Phenotype analysis corroborated their epithelial (CD9+ or stromal (vimentin+ cell origin and mesenchymal (CD90+, CD73+ and CD45⁻ attributes. Markers considered characteristic of ectoderm or endoderm were not detected. Cells did not express either estrogen receptor alpha (ERα or progesterone receptor (PR. The hESP cell lines were able to differentiate in vitro into adipocytes and osteocytes, which confirmed their mesenchymal origin. Finally, we demonstrated their ability to generate human endometrium when transplanted beneath the renal capsule of NOD-SCID mice. These findings confirm that SP cells exhibit key features of human endometrial SSC and open up new possibilities for the understanding of gynecological disorders such as endometriosis or Asherman syndrome. Our cell lines can be a valuable model to investigate new targets for endometrium proliferation in endometriosis.

  6. Evaluation of CD45 protein expression and transcript in canine small clear cell/T zone lymphoma.

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    Marzia Cozzi


    Full Text Available Canine small clear cell lymphoma is a peculiar lymphoma entity with T-zone histopathological pattern andindolent clinical course. From an immunophenotypic point of view the main feature is the lack of CD45 staining by flow-cytometry (FC, which accounts for >95% of cases. Underlying mechanisms have never been investigated.Aim of this work was to evaluate CD45 protein and mRNA expression in small clear cell lymphoma.Lymph nodes of 18 cases and 11 controls, with either reactive hyperplasia or CD45-positive high grade T-cell lymphoma, were investigated. FC was performed on lymph node fine needle aspiration and CD45 median fluorescence intensity (MFI was then evaluated on small clear cells and normal residual T-lymphocytes. CD45 surface expression was also evaluated by immunohistochemical reaction on paraffin wax-embedded lymph node sections.Quantitative real-time RT-PCR was performed on cases and controls. Total RNA was isolated from cell suspension in RNA later. The generated CD45cDNA was amplified and ΔΔCt method was used for the relative mRNA quantification.CD45-MFI in neoplastic cells was <1% compared to normal residual T-lymphocytes in the same sample. Cells were also negative for CD45 stain on histopathological preparations. RT-PCR showed a significantly lower amount of CD45 transcript in neoplastic samples compared to controls, likely due to the residual population.Results showed the lack of CD45 surface antigen and the virtually absence of CD45-mRNA in small clear cell lymphoma. We hypothesize a possible genomic/epigenomic aberration; further studies are in progress to investigate the pathogenesis of this aberrancy and the possible linkage to lymphomagenesis.

  7. Non-cultured adipose-derived CD45(-) side population cells are enriched for progenitors that give rise to myofibres in vivo

    DEFF Research Database (Denmark)

    Andersen, Ditte C; Schrøder, Henrik D; Jensen, Charlotte H


    skeletal muscle repair mainly relies on the satellitecell, several reports have shown that vessel-associated cells may adopt a myogenic phenotype when exposed to a muscle environment. In accordance with these findings, we also observed invitro myogenic specification of SPCD45(-) cells when cocultured...... with myoblasts. Furthermore, immediate intramuscular engraftment of non-cultured SPCD45(-) cells gave rise to myofibres andcells lining blood vessels, whereas the SVF only provided donor derived mononuclear cells. We therefore conclude that the SPCD45(-) fraction of adipose-derived SVF is enriched for cells...

  8. CD49d- Treg Cells with High Suppressive Capacity are Remarkably Less Efficient on Activated CD45RA- than on Naive CD45RA+ Teff Cells

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    Britta Kraczyk


    Full Text Available Background: Impairment of regulatory T cells (Tregs in common autoimmune diseases seems likely. However, the extent of Treg deficiency (number, function or differential susceptibility of T effector cells (Teffs to suppression is not completely understood. We hypothesize that even in healthy individuals both cell populations are heterogeneous and differ in their suppressive capability and their susceptibility to suppression. Material and Methods: Lymphocytes were enriched by MACS for CD4+CD25+ Tregs or CD4+CD25- Teffs. After multicolour staining (anti-CD25, anti-CD127, anti-CD49d or anti-CD45RA highly purified Treg and Teff subpopulations were collected by FACS. Functional capacity of Tregs or suppressive susceptibility of Teffs was analyzed in an in vitro assay. Results: When CD4+CD25highCD127-/low CD49d- Tregs were tested on naive CD4+CD127+CD25-CD45RA+ Teffs (93.8 % suppression was almost complete, while the suppressive capacity of CD4+CD25highCD127-/low CD49d+ Tregs was significantly less (71.8 %. Suppressive activity was low when CD4+CD25highCD127-/low CD49d+ Tregs were analyzed on CD4+CD127+CD25-CD45RA- Teffs (48.7%. Conclusion: Although CD49d+ Tregs are functional, the suppressive capacity is significantly lower compared to CD49d- Tregs. CD45RA+ Teffs can be completely suppressed, while CD45RA- Teffs display relative resistance. Phenotypic and functional heterogeneity of Tregs as well as Teffs has to be considered when analyzing deficiencies in immune regulation.

  9. Expression of CD45RB functionally distinguishes intestinal T lymphocytes in inflammatory bowel disease.

    NARCIS (Netherlands)

    Hove, T. ten; The Olle, F.; Berkhout, M.; Bruggeman, J.P.; Vyth-Dreese, F.A.; Slors, J.F.M.; Deventer, S.J.H. van; Velde, A.A. te


    The importance of CD45RB expression on T cells was already shown in mice where CD45RB(high) expression determines pathogenic potential. In this study, we analyzed the expression of CD45RA, CD45RB, and CD45RO on CD4(+) T lymphocytes in the intestinal mucosa and in the circulation of patients with inf

  10. Dynamics of 103K/N and 184M/V HIV-1 drug resistant populations: relative comparison in plasma virus RNA versus CD45RO+T cell proviral DNA

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    Jakobsen, Martin Roelsgaard; Tolstrup, M; Bertelsen, L


    population with linked mutations (103N and 184V) was detected in two patients after more than 2 years of non-NNRTI HAART. CONCLUSION: The ARMS assay is useful for detecting viral quasi-species containing efavirenz and lamivudine resistant mutations in plasma virions and in proviral DNA. Data suggest...

  11. CD45-deficient severe combined immunodeficiency caused by uniparental disomy (United States)

    Roberts, Joseph L.; Buckley, Rebecca H.; Luo, Biao; Pei, Jianming; Lapidus, Alla; Peri, Suraj; Wei, Qiong; Shin, Jinwook; Parrott, Roberta E.; Dunbrack, Roland L.; Testa, Joseph R.; Zhong, Xiao-Ping; Wiest, David L.


    Analysis of the molecular etiologies of SCID has led to important insights into the control of immune cell development. Most cases of SCID result from either X-linked or autosomal recessive inheritance of mutations in a known causative gene. However, in some cases, the molecular etiology remains unclear. To identify the cause of SCID in a patient known to lack the protein-tyrosine phosphatase CD45, we used SNP arrays and whole-exome sequencing. The patient’s mother was heterozygous for an inactivating mutation in CD45 but the paternal alleles exhibited no detectable mutations. The patient exhibited a single CD45 mutation identical to the maternal allele. Patient SNP array analysis revealed no change in copy number but loss of heterozygosity for the entire length of chromosome 1 (Chr1), indicating that disease was caused by uniparental disomy (UPD) with isodisomy of the entire maternal Chr1 bearing the mutant CD45 allele. Nonlymphoid blood cells and other mesoderm- and ectoderm-derived tissues retained UPD of the entire maternal Chr1 in this patient, who had undergone successful bone marrow transplantation. Exome sequencing revealed mutations in seven additional genes bearing nonsynonymous SNPs predicted to have deleterious effects. These findings are unique in representing a reported case of SCID caused by UPD and suggest UPD should be considered in SCID and other recessive disorders, especially when the patient appears homozygous for an abnormal gene found in only one parent. Evaluation for alterations in other genes affected by UPD should also be considered in such cases. PMID:22689986

  12. Muscle side population cells from dystrophic or injured muscle adopt a fibro-adipogenic fate.

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    Christopher M Penton

    Full Text Available Muscle side population (SP cells are rare multipotent stem cells that can participate in myogenesis and muscle regeneration upon transplantation. While they have been primarily studied for the development of cell-based therapies for Duchenne muscular dystrophy, little is known regarding their non-muscle lineage choices or whether the dystrophic muscle environment affects their ability to repair muscle. Unfortunately, the study of muscle SP cells has been challenged by their low abundance and the absence of specific SP cell markers. To address these issues, we developed culture conditions for the propagation and spontaneous multi-lineage differentiation of muscle SP cells. Using this approach, we show that SP cells from wild type muscle robustly differentiate into satellite cells and form myotubes without requiring co-culture with myogenic cells. Furthermore, this myogenic activity is associated with SP cells negative for immune (CD45 and vascular (CD31 markers but positive for Pax7, Sca1, and the mesenchymal progenitor marker PDGFRα. Additionally, our studies revealed that SP cells isolated from dystrophic or cardiotoxin-injured muscle fail to undergo myogenesis. Instead, these SP cells rapidly expand giving rise to fibroblast and adipocyte progenitors (FAPs and to their differentiated progeny, fibroblasts and adipocytes. Our findings indicate that muscle damage affects the lineage choices of muscle SP cells, promoting their differentiation along fibro-adipogenic lineages while inhibiting myogenesis. These results have implications for a possible role of muscle SP cells in fibrosis and fat deposition in muscular dystrophy. In addition, our studies provide a useful in vitro system to analyze SP cell biology in both normal and pathological conditions.

  13. Identification of multipotent mesenchymal stromal cells in the reactive stroma of a prostate cancer xenograft by side population analysis

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    Santamaria-Martinez, Albert [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat de Barcelona, Barcelona (Spain); Barquinero, Jordi [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain); Banc de Sang i Teixits, Barcelona (Spain); Barbosa-Desongles, Anna; Hurtado, Antoni; Pinos, Tomas [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain); Seoane, Joan [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain); Medical Oncology program, Vall d' Hebron Institute of Oncology, Barcelona (Spain); Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona (Spain); Poupon, Marie-France [Institut Curie, Paris (France); Morote, Joan [Universitat Autonoma de Barcelona, Barcelona (Spain); Servei d' Urologia. Hospital Vall d' Hebron, Barcelona (Spain); Reventos, Jaume [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain); Munell, Francina, E-mail: [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain)


    Cancer stem cells are a distinct cellular population that is believed to be responsible for tumor initiation and maintenance. Recent data suggest that solid tumors also contain another type of stem cells, the mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs), which contribute to the formation of tumor-associated stroma. The Hoechst 33342 efflux assay has proved useful to identify a rare cellular fraction, named Side Population (SP), enriched in cells with stem-like properties. Using this assay, we identified SP cells in a prostate cancer xenograft containing human prostate cancer cells and mouse stromal cells. The SP isolation, subculture and sequential sorting allowed the generation of single-cell-derived clones of murine origin that were recognized as MSC by their morphology, plastic adherence, proliferative potential, adipogenic and osteogenic differentiation ability and immunophenotype (CD45{sup -}, CD81{sup +} and Sca-1{sup +}). We also demonstrated that SP clonal cells secrete transforming growth factor {beta}1 (TGF-{beta}1) and that their inhibition reduces proliferation and accelerates differentiation. These results reveal the existence of SP cells in the stroma of a cancer xenograft, and provide evidence supporting their MSC nature and the role of TGF-{beta}1 in maintaining their proliferation and undifferentiated status. Our data also reveal the usefulness of the SP assay to identify and isolate MSC cells from carcinomas.

  14. Immunohistochemical Analysis of Scarring Trachoma Indicates Infiltration by Natural Killer and Undefined CD45 Negative Cells.

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    Victor H Hu


    Full Text Available The phenotype and function of immune cells infiltrating the conjunctiva in scarring trachoma have yet to be fully characterized. We assessed tissue morphology and immunophenotype of cellular infiltrates found in trachomatous scarring compared to control participants.Clinical assessments and conjunctival biopsy samples were obtained from 34 individuals with trachomatous scarring undergoing trichiasis surgery and 33 control subjects undergoing cataract or retinal detachment surgery. Biopsy samples were fixed in buffered formalin and embedded in paraffin wax. Hematoxylin and eosin (H&E staining was performed for assessment of the inflammatory cell infiltrate. Immunohistochemical staining of single markers on individual sections was performed to identify cells expressing CD3 (T-cells, CD4 (helper T-cells, CD8 (suppressor/cytotoxic T-cells and Natural Killer, NK, cells, NCR1 (NK cells, CD20 (B-cells, CD45 (nucleated hematopoietic cells, CD56 (NK and T-cells, CD68 (macrophages/monocytes and CD83 (mature dendritic cells. The degree of scarring was assessed histologically using cross-polarized light to visualize collagen fibres.Scarring, regardless of clinical inflammation, was associated with increased inflammatory cell infiltrates on H&E and CD45 staining. Scarring was also associated with increased CD8+ and CD56+ cells, but not CD3+ cells, suggestive of a NK cell infiltrate. This was supported by the presence of NCR1+ cells. There was some increase in CD20+ cells, but no evidence for increased CD4+, CD68+ or CD83+ cells. Numerous CD45 negative cells were also seen in the population of infiltrating inflammatory cells in scarred conjunctiva. Disorganization of the normal collagen architecture was strongly associated with clinical scarring.These data point to the infiltration of immune cells with a phenotype suggestive of NK cells in conjunctival trachomatous scarring. A large proportion of CD45 negative inflammatory cells were also present. Future work

  15. 小儿传染性单核细胞增多症患者外周血CD45RO+、CD45RA+T淋巴细胞亚群表达的研究%Study on the Expression of CD45RO+ and CD45RA+T Lymphocytes in Peripheral Blood of Children Patients with Infectious Mononucleosis

    Institute of Scientific and Technical Information of China (English)

    陈正平; 王志琴


    Objective To study the changes of CD45RO+ and CD45RA+T lymphocytess in peripheral blood in children with infectious mononucleosis. Method The expression of CD45RO+ and CD45RA+T lymphocytess in peripheral blood of children patients and controls was detected by flow cytometry. Results Compared with the control, the expression of CD4+CD45RO+ T lymphocytess in children with infectious mononucleosis in acute stage obviously increased (P < 0.05), but the expression of CD4+CD45RA+ T lymphocytes was lower (P < 0.05 ). The expression of CD4+CD45RO+ T lymphocytes in children in recovery stage was siginificantly lower than those in acute stage (P < 0.05) , but was still higher than those in control (P < 0.05). The expression of CD4+CD45RA+ T lymphocytes in children in convalescence stage was siginificantly higher than those in acute stage (P< 0.05), but was still lower than those in control (P< 0.05). Conclusion CD4+CD45RO+ and CD4+CD45RA+T lymphocytes play an important role in cell immunity in children with infectious mononucleosis. The decrease of CD45RA+Th cell is one of the important reason to immune function overbalance.%目的 探讨传染性单核细胞增多症(IM)患儿CD4T辅助淋巴细胞CD4CD45RO和CD4CD45RAT淋巴细胞亚群的变化.方法 用流式细胞术检测了30例活动期IM、急性期及恢复期患者CD4T辅助细胞CD45RO、CD45RA的表达率,并与对照组进行了比较.结果 IM患者急性期与对照组相比CD4CD45RO明显增高(PCD45RA明显对低于对照组(PCD45RO与急性期比较明显降低(PCD45RA与急性期相比明显升高(PCD45RO和CD4CD45RAT淋巴细胞在IM患者的细胞免疫中起重要作用,CD45RAT辅助细胞减少是导致机体免疫功能失去平衡的重要原因.

  16. Prevalence of left-sided melanomas in an Irish population.

    LENUS (Irish Health Repository)

    de Blacam, C


    BACKGROUND: A predominance of melanomas on the left side of the body has recently been described. No associations between tumour laterality and gender, age or anatomical site have been identified. AIM: The aim of this study was to investigate the prevalence of left-sided melanomas in an Irish population and to examine potential associations with various patient and tumour characteristics. METHODS: A retrospective chart review of patients with cutaneous melanoma who were treated over a 10-year period was carried out. Lateral distribution of melanoma on either side of the body was compared using χ(2) analysis and evaluated by gender, age group, anatomic location, histologic subtype and Breslow depth. RESULTS: More melanomas occurred on the left side (57%, P = 0.015), and this finding was particularly significant in females. For both genders combined, there were no statistically significant differences in laterality by age group, anatomic location, type of melanoma and Breslow depth. There were significantly more superficial spreading melanomas on the left side in both men and women. CONCLUSIONS: This study demonstrates a predominance of left-sided melanomas in Irish patients. While a number of demographic and molecular associations have been proposed, further research is required to fully explain this phenomenon.

  17. Prevalence of left-sided melanomas in an Irish population.

    LENUS (Irish Health Repository)

    de Blacam, C


    BACKGROUND: A predominance of melanomas on the left side of the body has recently been described. No associations between tumour laterality and gender, age or anatomical site have been identified. AIM: The aim of this study was to investigate the prevalence of left-sided melanomas in an Irish population and to examine potential associations with various patient and tumour characteristics. METHODS: A retrospective chart review of patients with cutaneous melanoma who were treated over a 10-year period was carried out. Lateral distribution of melanoma on either side of the body was compared using chi(2) analysis and evaluated by gender, age group, anatomic location, histologic subtype and Breslow depth. RESULTS: More melanomas occurred on the left side (57%, P = 0.015), and this finding was particularly significant in females. For both genders combined, there were no statistically significant differences in laterality by age group, anatomic location, type of melanoma and Breslow depth. There were significantly more superficial spreading melanomas on the left side in both men and women. CONCLUSIONS: This study demonstrates a predominance of left-sided melanomas in Irish patients. While a number of demographic and molecular associations have been proposed, further research is required to fully explain this phenomenon.

  18. Natural antisense RNAs are involved in the regulation of CD45 expression in autoimmune diseases. (United States)

    Rong, J; Yin, J; Su, Z


    CD45 is a transmembrane protein tyrosine phosphatase that is specifically expressed in hematopoietic cells and can initiate signal transduction via the dephosphorylation of tyrosine. Alternatively spliced transcript variants of this gene encode distinct isoforms, which indicate different functional states of CD45. Among these variants, CD45RO, which contains neither exon 4, 5, or 6, is over-expressed in lymphocytes in autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and type I diabetes. The CD45 RO serves as a marker of the immune response activity and lymphocyte development. Previous studies have indicated that exon splicing is generally correlated with local hypermethylated DNA and acetylated histone modification, while autoimmune diseases are commonly associated with global hypomethylation and histone deacetylation in lymphocytes. Thus, the question arises of how exons 4, 5, and 6 of CD45RO are excluded under the status of global DNA hypomethylation and histone deacetylation in these autoimmune diseases. On the basis of the analyses of the context sequence of CD45 and its natural antisense RNA in GenBank, we proposed that the long noncoding RNA encoded by the natural antisense gene of CD45 contributes to the expressional regulation of the CD45RO splicing variant via recruitment of DNA methyltransferase and histone modification modulators specific to the sense gene CD45; thus, it is associated with the over-expression of CD45RO and the functional regulation of lymphocytes in the pathogenic development of autoimmune diseases.

  19. Malignant T cells exhibit CD45 resistant Stat3 activation and proliferation in cutaneous

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    Krejsgaard, Thorbjørn Frej; Helvad, Rikke; Ralfkiaer, Elisabeth;


    CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in T and B cells via its effect on Src kinases. It has recently been shown that CD45 can also dephosphorylate Janus kinases (Jaks) and thereby regulate Signal transducer and activator of transcr......-mediated inhibition of proliferation. In conclusion, our data suggest that CD45 dysregulation might play a role in the aberrant proliferation and Jak3/Stat3 activation in CTCL....

  20. CD45 immunoaffinity depletion of vesicles from Jurkat T cells demonstrates that exosomes contain CD45: no evidence for a distinct exosome/HIV-1 budding pathway

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    Ott David E


    Full Text Available Abstract The presence of relatively high levels of cellular protein contamination in density-purified virion preparations is a confounding factor in biochemical analyses of HIV and SIV produced from hematopoietic cells. A major source of this contamination is from vesicles, either microvesicles or exosomes, that have similar physical properties as virions. Thus, these particles can not be removed by size or density fractionation. Although virions and vesicles have similar cellular protein compositions, CD45 is excluded from HIV-1 yet is present in vesicles produced from hematopoietic cells. By exploiting this finding, we have developed a CD45 immunoaffinity depletion procedure that removes vesicles from HIV-1 preparations. While this approach has been successfully applied to virion preparations from several different cell types, some groups have concluded that "exosomes" from certain T cell lines, specifically Jurkat, do not contain CD45. If this interpretation is correct, then these vesicles could not be removed by CD45 immunoaffinity depletion. Here we show that dense vesicles produced by Jurkat and SupT1/CCR5 cells contain CD45 and are efficiently removed from preparations by CD45-immunoaffinity depletion. Also, contaminating cellular proteins were removed from virion preparations produced by these lines. Previously, the absence of CD45 from both "exosomes" and virions has been used to support the so called Trojan exosome hypothesis, namely that HIV-1 is simply an exosome containing viral material. The presence of CD45 on vesicles, including exosomes, and its absence on virions argues against a specialized budding pathway that is shared by both exosomes and HIV-1.

  1. Biodistribution of Yttrium-90-Labeled Anti-CD45 Antibody in a Nonhuman Primate Model

    Energy Technology Data Exchange (ETDEWEB)

    Nemecek, Eneida; Hamlin, Donald K.; Fisher, Darrell R.; Krohn, Kenneth A.; Pagel, John M.; Applebaum, F. R.; Press, Oliver W.; Matthews, Dana C.


    Radioimmunotherapy may improve the outcome of hematopoietic cell transplantation for hematologic malignancies by delivering targeted radiation to hematopoietic organs while relatively sparing nontarget organs. We evaluated the organ localization of yttrium-90-labeled anti-CD45 (90Y-anti-CD45) antibody in macaques, a model that had previously predicted iodine-131-labeled anti-CD-45 (131I-anti-CD45) antibody biodistribution in humans. Experimental Design: Twelve Macaca nemestrina primates received anti-CD45 antibody labeled with 1 to 2 mCi of 90Y followed by serial blood sampling and marrow and lymph node biopsies, and necropsy. The content of 90Y per gram of tissue was determined by liquid scintillation spectrometry. Time-activity curves were constructed using average isotope concentrations in each tissue at measured time points to yield the fractional residence time and estimate radiation absorbed doses for each organ per unit of administered activity. The biodistribution of 90Y-anti-CD45 antibody was then compared with that previously obtained with 131I-anti-CD45 antibody in macaques. Results: The spleen received 2,120, marrow 1,060, and lymph nodes 315 cGy/mCi of 90Y injected. The liver and lungs were the nontarget organs receiving the highest radiation absorbed doses (440 and 285 cGy/mCi, respectively). Ytrrium-90-labeled anti-CD45 antibody delivered 2.5- and 3.7-fold more radiation to marrow than to liver and lungs, respectively. The ratios previously observed with 131I-antiCD45 antibody were 2.5-and 2.2-fold more radiation to marrow than to liver and lungs, respectively. Conclusions: This study shows that 90Y-anti-CD45 antibody can deliver relatively selective radiation to hematopoietic tissues, with similar ratios of radiation delivered to target versus nontarget organs, as compared with the 131I immunoconjugate in the same animal model.

  2. Expression of CD45RA and CD45RO in peripheral blood mononuclear cells of mycosis fungoides%蕈样肉芽肿患者外周血单一核细胞CD45RA及CD45RO表达的研究

    Institute of Scientific and Technical Information of China (English)

    许静; 梁再赋; 张士发; 狄正鸿; 郭英军


    目的:探讨蕈样肉芽肿(Mycosis fungoides,MF)患者外周血单个核细胞CD45RA及CD45RO的表达及其与MF发病的关系.方法:应用双荧光抗体标记、流式细胞仪检测15例MF患者外周血单个核细胞CD45RA及CD45RO的表达.结果:(1)MF患者外周血CD3+、CD3+CD8+细胞与正常对照比较差异不显著(P>0.05).(2)MF患者外周血CD4+细胞低于正常对照,差异非常显著(P<0.001).(3)MF患者外周血T细胞CD3+CD4+/CD3+CD8+比值低于正常对照,差异显著(P<0.001).(4)MF患者外周血CD45RA+细胞低于正常对照,差异非常显著(P<0.001),CD45RO+细胞高于正常对照,差异非常显著(P<0.001).(5)MF患者外周血CD45RO+/CD45RA+比值高于正常对照,差异非常显著(P<0.001).(6)MF患者外周血CD4+CD45RA+细胞低于正常对照,差异非常显著(P<0.001).(7)MF患者外周血CD4+CD45RO+细胞及CD8+CD45RO+细胞均高于正常对照,差异非常显著(均P<0.001).(8)MF患者外周血CD4+CD45RO+/CD4+CD45RA+比值及CD8+CD45RO+/CD8+CD45RA+比值均高于正常对照,差异非常显著(P<0.01及P<0.001).结论:MF患者外周血中,不仅存在CD4+亚群失调和CD4+/CD8+比值降低,而且在CD4+和CD8+亚群中也存在CD45RA+、CD45RO+亚群失调和CD45RO+/CD45RA+比值升高,从而导致的机体免疫功能紊乱,可能与MF的发病或病情加剧有关.

  3. Antithyroid Drug Side Effects in the Population and in Pregnancy

    DEFF Research Database (Denmark)

    Andersen, Stine Linding; Olsen, Jørn; Laurberg, Peter


    OBJECTIVE: Methimazole (MMI) and Propylthiouracil (PTU) are both associated with birth defects, and may also rarely be associated with agranulocytosis and liver failure. The frequency of these side effects when antithyroid drugs (ATD) are used in the population in general or in pregnancy remains...... of agranulocytosis (1 in pregnancy) and 10 cases of liver failure (1 in pregnancy). This corresponded to 41/11 cases of agranulocytosis/liver failure per 5 million inhabitants during a 10-year period (agranulocytosis: 0.16% of ATD exposed (MMI: 0.11% vs. PTU: 0.27%, p=0.02); liver failure: 0.03% of ATD exposed (MMI......: 0.03% vs. PTU: 0.05%, p=0.4)). The majority (83%) developed the side effect within 3 months of ATD treatment, and 25% during hyperthyroidism relapse. The use of ATD in pregnancy was associated with birth defects in 3.4% of exposed children (44 cases/5 million inhabitants/10 years), and the frequency...

  4. A novel stem cell source for vasculogenesis in ischemia: subfraction of side population cells from dental pulp. (United States)

    Iohara, Koichiro; Zheng, Li; Wake, Hiroaki; Ito, Masataka; Nabekura, Junichi; Wakita, Hideaki; Nakamura, Hiroshi; Into, Takeshi; Matsushita, Kenji; Nakashima, Misako


    Cell therapy with stem cells and endothelial progenitor cells (EPCs) to stimulate vasculogenesis as a potential treatment for ischemic disease is an exciting area of research in regenerative medicine. EPCs are present in bone marrow, peripheral blood, and adipose tissue. Autologous EPCs, however, are obtained by invasive biopsy, a potentially painful procedure. An alternative approach is proposed in this investigation. Permanent and deciduous pulp tissue is easily available from teeth after extraction without ethical issues and has potential for clinical use. We isolated a highly vasculogenic subfraction of side population (SP) cells based on CD31 and CD146, from dental pulp. The CD31(-);CD146(-) SP cells, demonstrating CD34+ and vascular endothelial growth factor-2 (VEGFR2)/Flk1+, were similar to EPCs. These cells were distinct from the hematopoietic lineage as CD11b, CD14, and CD45 mRNA were not expressed. They showed high proliferation and migration activities and multilineage differentiation potential including vasculogenic potential. In models of mouse hind limb ischemia, local transplantation of this subfraction of SP cells resulted in successful engraftment and an increase in the blood flow including high density of capillary formation. The transplanted cells were in proximity of the newly formed vasculature and expressed several proangiogenic factors, such as VEGF-A, G-CSF, GM-CSF, and MMP3. Conditioned medium from this subfraction showed the mitogenic and antiapoptotic activity on human umbilical vein endothelial cells. In conclusion, subfraction of SP cells from dental pulp is a new stem cell source for cell-based therapy to stimulate angiogenesis/vasculogenesis during tissue regeneration.

  5. Does Oxidative Inactivation of CD45 Phosphatase in Rheumatoid Arthritis Underlie Immune Hyporesponsiveness?


    Rider, David A.; Bayley, Rachel; Clay, Elizabeth; Young, Stephen P


    The protein tyrosine phosphatase (PTP) CD45 is critical in regulating the earliest steps in T-cell-receptor signaling but, similar to all PTPs, it is susceptible to oxidative inactivation. Given the widely reported effects of oxidant damage associated with rheumatoid arthritis (RA), we examined whether CD45 phosphatase activity was altered in CD4+ T cells from RA patients and related this to CD4+ T-cell function and redox status. CD45 phosphatase specific activity in T cells from RA periphera...

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  14. Identification of side population cells in chicken embryonic gonads. (United States)

    Bachelard, Elodie; Raucci, Franca; Montillet, Guillaume; Pain, Bertrand


    The side population (SP) phenotype, defined by the ability of a cell to efflux fluorescent dyes such as Hoechst, is common to several stem/progenitor cell types. In avian species, SP phenotype has been identified in pubertal and adult testes, but nothing is known about its expression during prenatal development of a male gonad. In this study, we characterized the Hoechst SP phenotype via the cytofluorimetric analysis of disaggregated testes on different days of chicken embryonic development. Male prenatal gonads contained a fraction of SP cells at each stage analyzed. At least two main SP fractions, named P3 and P4, were identified. The percentage of P3 fraction decreased as development proceeds, whereas P4 cell number was not affected by gonad growth. Functional inhibition of BCRP1 channel membrane using Verapamil and/or Ko143 showed that P3, but not P4 phenotype, was dependent on BCRP1 activity. Molecular analysis of both P3- and P4-sorted fractions revealed a differential RNA expression pattern, indicating that P3 cells mainly contained germinal stem cell markers, whereas P4 was preferentially composed of both Sertoli and Leydig cell progenitor markers. Finally, these findings provided evidence that the SP phenotype is a common feature of both germ and somatic cells detected in chicken developing testis.

  15. Flow Cytometry of the Side Population: Tips & Tricks

    Directory of Open Access Journals (Sweden)

    Irene Sales-Pardo


    Full Text Available Background: The Side Population (SP has become an important hallmark for the definition of the stem cell compartment, especially in the detection of these cells and in their physical isolation by fluorescence-activated cell sorting (FACS. SP cells are CD34neg and were discovered using ultraviolet excitation based on the efflux of Hoechst 33342 (Ho342. Although the method works as originally described, we believe that this method is difficult for most investigators. First, because the ability to discriminate SP cells is based on the differential retention of Ho342 during a functional assay; second, because of the difficulties in setting the right experimental and acquisition conditions; and third, because the analysis of the acquired data requires an extensive expertise on flow cytometry to accurately detect the SP events. Methods: First of all and mainly for the SP application, the laser beam paths were exhaustively checked to ensure the lowest coefficients of variation. Blood suspensions were prepared by erythrocyte lysis with ammonium chloride and hematopoietic cells were labeled with Ho342. Results: The Ho342 concentration and the staining procedure are critical for the optimal resolution of the SP cells. Although UV laser alignment is very important to resolve the dim tail that outlines the SP, the problem with Ho342 excitation is not the Hoechst Blue emission, but rather the Hoechst Red's (because of the weak emission. Conclusions: Each laboratory must establish its own expected ranges based on its instrument and results may vary slightly due to instrument differences such as the narrowness of the band pass filters, laser power, laser emission wavelength, nozzle type, differential of pressure, light collection system (cuvette versus jet-in-air and beam shaping optics.

  16. In multiple myeloma, only a single stage of neoplastic plasma cell differentiation can be identified by VLA-5 and CD45 expression. (United States)

    Rawstron, A C; Barrans, S L; Blythe, D; English, A; Richards, S J; Fenton, J A; Davies, F E; Child, J A; Jack, A S; Morgan, G J


    The nature of the proliferating fraction in myeloma is still not known and understanding the characteristics of this fraction is central to the development of effective novel therapies. However, myeloma plasma cells typically show a very low rate of proliferation and this complicates accurate analysis. Although the level of CD45 and/or VLA-5 has been reported to identify proliferating 'precursor' plasma cells, there are discrepancies between these studies. We have therefore used a rigorous sequential gating strategy to simultaneously analyse cycle status and immunophenotype with respect to CD45, VLA-5 and a range of other integrin molecules. In 11 presentation myeloma patients, the proliferative fraction was distributed evenly between CD45+ and CD45- cells, however, cycling plasma cells were consistently VLA-5-. There was close correlation between the expression of VLA-5 and a range of other integrin molecules (CD11a, CD11c, CD103), as well as the immunoglobulin-associated molecules CD79a/b (Spearman, n = 10, P < 0.0001). In short-term culture, cells that were initially VLA-5-showed increasing VLA-5 expression with time. However, simultaneous analysis of the DNA-binding dye 7-amino-actinomycin D demonstrated that this was not as a result of differentiation, as VLA-5+ plasma cells were all non-viable. This was confirmed in freshly explanted plasma cells from nine patients. Discrete stages of plasma cell differentiation could not be distinguished by the level of CD45 or VLA-5 expression. The results indicate that there is a single stage of plasma cell differentiation, with the phenotype CD38+CD138+VLA-5-. These findings support the hypothesis that neoplastic bone marrow plasma cells represent an independent, self-replenishing population.

  17. Pretargeting CD45 enhances the selective delivery of radiation to hematolymphoid tissues in nonhuman primates

    Energy Technology Data Exchange (ETDEWEB)

    Green, Damian J.; Pagel, John M.; Nemecek, Eneida R.; Lin, Yukang; Kenoyer, Aimee L.; Pantelias, Anastasia; Hamlin, Donald K.; Wilbur, D. S.; Fisher, Darrell R.; Rajendran, Joseph G.; Gopal, Ajay K.; Park, Steven I.; Press, Oliver W.


    Pretargeted radioimmunotherapy (PRIT) is designed to enhance the directed delivery of radionuclides to malignant cells. Through a series of studies in nineteen nonhuman primates (M. fascicularis) the potential therapeutic advantage of anti-CD45 PRIT was evaluated. Anti-CD45 PRIT demonstrated a significant improvement in target-to-normal organ ratios of absorbed radiation when compared to directly radiolabeled bivalent antibody (conventional radioimmunotherapy [RIT]). Radio-DOTA-biotin administered 48 hours after anti-CD45 streptavidin fusion protein (FP) [BC8 (scFv)4SA] produced markedly lower concentrations of radiation in non-target tissues when compared to conventional RIT. PRIT generated superior target:normal organ ratios in the blood, lung and liver (10.3:1, 18.9:1 and 9.9:1 respectively) when compared to the conventional RIT controls (2.6:1, 6.4:1 and 2.9:1 respectively). The FP demonstrated superior retention in target tissues relative to comparable directly radiolabeled bivalent anti-CD45 RIT. The time-point of administration of the second step radiolabeled ligand (radio-DOTA-biotin) significantly impacted the biodistribution of radioactivity in target tissues. Rapid clearance of the FP from the circulation rendered unnecessary the addition of a synthetic clearing agent in this model. These results support proceeding to anti-CD45 PRIT clinical trials for patients with both leukemia and lymphoma.

  18. Ovarian cancer stem cells are enriched in side population and aldehyde dehydrogenase bright overlapping population.

    Directory of Open Access Journals (Sweden)

    Kazuyo Yasuda

    Full Text Available Cancer stem-like cells (CSCs/cancer-initiaiting cells (CICs are defined as a small population of cancer cells that have self-renewal capacity, differentiation potential and high tumor-initiating ability. CSCs/CICs of ovarian cancer have been isolated by side population (SP analysis, ALDEFLUOR assay and using cell surface markers. However, these approaches are not definitive markers for CSCs/CICs, and it is necessary to refine recent methods for identifying more highly purified CSCs/CICs. In this study, we analyzed SP cells and aldehyde dehydrogenese bright (ALDH(Br cells from ovarian cancer cells. Both SP cells and ALDH(Br cells exhibited higher tumor-initiating ability and higher expression level of a stem cell marker, sex determining region Y-box 2 (SOX2, than those of main population (MP cells and ALDH(Low cells, respectively. We analyzed an SP and ALDH(Br overlapping population (SP/ALDH(Br, and the SP/ALDH(Br population exhibited higher tumor-initiating ability than that of SP cells or ALDH(Br cells, enabling initiation of tumor with as few as 10(2 cells. Furthermore, SP/ADLH(Br population showed higher sphere-forming ability, cisplatin resistance, adipocyte differentiation ability and expression of SOX2 than those of SP/ALDH(Low, MP/ALDH(Br and MP/ALDH(Low cells. Gene knockdown of SOX2 suppressed the tumor-initiation of ovarian cancer cells. An SP/ALDH(Br population was detected in several gynecological cancer cells with ratios of 0.1% for HEC-1 endometrioid adenocarcinoma cells to 1% for MCAS ovary mucinous adenocarcinoma cells. Taken together, use of the SP and ALDH(Br overlapping population is a promising approach to isolate highly purified CSCs/CICs and SOX2 might be a novel functional marker for ovarian CSCs/CICs.

  19. Isolation of Side Population Cells and Detection of ABCG2 from SW480

    Institute of Scientific and Technical Information of China (English)

    LIU Hai-guang; PAN Yi-fei; GUO Gui-long; HU Xiao-qu; HUANG Ka-te; ZHANG Xiao-hua


    Objective: Side population cells (SP cells) are a new type of stem cells. They mainly express ABCG2/BCRP1 and have the ability to eliminate DNA dye Hoechst33342. Many studies showed that side population cells were able of self-renewal, differentiation and carcinogenesis in cancers. Our investigation aimed at isolation of side population cells and ABCG2 positive subpopulation from colon cancer cell line SW480 and identification of their characteristics of cancer stem cells. Methods: side population cells and non-side population cells of colon cancer cell line SW480 were isolated with DNA dye Hoechst33342 and their cell cycles were measured by flow cytometry. Expression of ABCG2 of SW480 was measured by immunohistochemistry and immunofluorescence, and its proportion was measured by flow cytometry. Results: SW480 contained 2.29% side population cells. The fraction of side population cells decreased greatly to 0.40% by treatment with verapamil. The fraction of side population cells in S-G2M cell cycle was 16.14%, which was much lower than the fraction (34.05%) of non-side population cells in S-G2M. In SW480, ABCG2 positive cells, which proportion was 9.66%, were small, circular or oval, lack of psuedopods, similar to poor differentiation. On the contrary, the ABCG2 negative cells were large, polygonal, with many psuedopods, similar to high differentiation. Conclusion: our assay identified that side population cells did exist in SW480 and had a quiescence characteristic of stem cells. ABCG2 positive subpopulation occupied about 9.66% of SW480 and may have the ability to promote cell self-renewal and inhibit cell differentiation. Therefore, to isolate ABCG2 positive subpopulation from side population cells may be an alternative to study colorectal cancer stem cells.

  20. CD45RA、CD45RO及胞间黏附分子1在扁平苔藓皮损中的表达%Expression of CD45RA, CD45RO and ICAM-1 in the lesions of patients with lichen planus

    Institute of Scientific and Technical Information of China (English)

    刘丽娟; 张国强; 贾金海; 李鑫; 丁政云


    目的:探讨扁平苔藓(LP)皮损CD45RA、CD45RO及胞间黏附分子1(ICAM-1)的表达及意义。方法应用免疫组化方法检测35例 LP 皮损和20例正常皮肤组织中 CD45RA、CD45RO及ICAM-1的表达水平。结果 LP皮损真皮内可见到CD45RO阳性表达,与正常对照组有统计学差异(P<0.05);LP皮损表皮、真皮及真皮内小血管壁内皮细胞内均可见ICAM-1阳性表达,与正常对照组有统计学差异(均P<0.05);两组均未见CD45RA阳性细胞表达。结论 LP皮损真皮内浸润细胞以记忆T细胞亚群为主,LP皮损角质形成细胞异常表达ICAM-1,推测ICAM-1参与了皮损角质形成细胞抗原呈递过程,从而促进记忆T细胞离开血管,向真皮及表皮浸润。%ObjectiveTo investigate the expression of CD45RA, CD45RO and ICAM-1 in the lesions of patients with lichen planus.Methods The expression levels of CD45RA and CD45RO and ICAM-1 were detected in 35 cases of LP lesion tissue and 20 cases of normal skin tissue by using immunohistochemical methods.Results CD45RO positive expression can be seen in the dermis of LP lesions, and had statistical difference compared with normal control group (P<0.05); the positive expression of ICAM-1 were visible within LP skin epidermis, dermis and small blood vessels endothelial cells in the dermis, and had statistical difference compared with the normal control group (allP<0.05); CD45RA positive cells expression were not found in both groups.Conclusion The dermal infiltrating cells are mainly memory T cells subset in the lesions of lichen planus, the significant expression of ICAM-1 in keratinocytes of LP patients suggest that ICAM-1 take part in the progress of the antigen-submit of keratinocytes, and promote the inflammatory cells infiltrating to epidermis.

  1. CXCR4(+) CD45(-) Cells are Niche Forming for Osteoclastogenesis via the SDF-1, CXCL7, and CX3CL1 Signaling Pathways in Bone Marrow. (United States)

    Goto, Yoh; Aoyama, Mineyoshi; Sekiya, Takeo; Kakita, Hiroki; Waguri-Nagaya, Yuko; Miyazawa, Ken; Asai, Kiyofumi; Goto, Shigemi


    Bone homeostasis comprises the balance between bone-forming osteoblasts and bone-resorbing osteoclasts (OCs), with an acceleration of osteoclastic bone resorption leading to osteoporosis. OCs can be generated from bone marrow cells (BMCs) under the tightly regulated local bone environment. However, it remained difficult to identify the critical cells responsible for providing an osteoclastogenesis niche. In this study, we used a fluorescence-activated cell sorting technique to determine the cell populations important for forming an appropriate microenvironment for osteoclastogenesis and to verify the associated interactions between osteoclast precursor cells and non-OCs. We isolated and removed a small cell population specific for osteoclastogenesis (CXCR4(+) CD45(-) ) from mouse BMCs and cultured the remaining cells with receptor activator of nuclear factor-kappa B ligand (RANKL) and macrophage-colony stimulating factor. The resulting cultures showed significantly less large osteoclast formation. Quantitative RT-PCR analysis revealed that these CXCR4(+) CD45(-) cells expressed low levels of RANK and RANKL, but high levels of critical chemokines including stromal cell derived factor 1 (SDF-1), chemokine (C-X-C motif) ligand 7 (CXCL7), and chemokine (C-X3-C motif) ligand 1 (CX3CL1). Furthermore, an SDF-1-specific antibody strongly suppressed OC formation in RAW264.7 cells and antibodies against SDF-1, CXCL7, and CX3CL1 suppressed OC formation in BMCs. These results suggest that isolated CXCR4(+) CD45(-) cells support an appropriate microenvironment for osteoclastogenesis with a direct effect on the cells expressing SDF-1, CXCL7, and CX3CL1 receptors. The regulation of CXCR4(+) CD45(-) cell function might therefore inform therapeutic strategies for diseases involving loss of bone homeostasis. Stem Cells 2016.

  2. Expression of the Memory Marker CD45RO on Helper T Cells in Macaques

    NARCIS (Netherlands)

    Valentine, Michael; Song, Kejing; Maresh, Grace A.; Mack, Heather; Huaman, Maria Cecilia; Polacino, Patricia; Ho, On; Cristillo, Anthony; Chung, Hye Kyung; Hu, Shiu-Lok; Pincus, Seth H.


    Background: In humans it has been reported that a major site of the latent reservoir of HIV is within CD4+ T cells expressing the memory marker CD45RO, defined by the mAb UCHL1. There are conflicting reports regarding the expression of this antigen in macaques, the most relevant animal species for s

  3. Astragaloside Ⅱ triggers T cell activation through regulation of CD45 protein tyrosine phosphatase activity

    Institute of Scientific and Technical Information of China (English)

    Chun-ping WAN; Li-xin GAO; Li-fei HOU; Xiao-qian YANG; Pei-lan HE; Yi-fu YANG; Wei TANG


    Aim:To investigate the immunomodulating activity of astragalosides,the active compounds from a traditional tonic herb Astragalus membranaceus Bge,and to explore the molecular mechanisms underlying the actions,focusing on CD45 protein tyrosine phosphatase (CD45 PTPase),which plays a critical role in T lymphocyte activation.Methods:Primary splenocytes and T cells were prepared from mice.CD45 PTPase activity was assessed using a colorimetric assay.Cell proliferation was measured using a [3H]-thymidine incorporation assay.Cytokine proteins and mRNAs were examined with ELISA and RT-PCR,respectively.Activation markers,including CD25 and CD69,were analyzed using flow cytometry.Activation of LCK (Tyr505) was detected using Western blot analysis.Mice were injected with the immunosuppressant cyclophosphamide (CTX,80 mg/kg),and administered astragaloside Ⅱ (50 mg/kg).Results:Astragaloside Ⅰ,Ⅱ,Ⅲ,and Ⅳ concentration-dependently increased the CD45-mediated of pNPP/OMFP hydrolysis with the EC50 values ranged from 3.33 to 10.42 μg/mL.Astragaloside Ⅱ (10 and 30 μg/mL) significantly enhanced the proliferation of primary splenocytes induced by ConA,alloantigen or anti-CD3.Astragaloside Ⅱ (30 μg/mL) significantly increased IL-2 and IFN-y secretion,upregulated the mRNA levels of IFN-y and T-bet in primary splenocytes,and promoted CD25 and CD69 expression on primary CD4+T cells upon TCR stimulation.Furthermore,astragaloside Ⅱ (100 ng/mL) promoted CD45-mediated dephosphorylation of LCK (Tyr505) in primary T cells,which could be blocked by a specific CD45 PTPase inhibitor.In CTX-induced immunosuppressed mice,oral administration of astragaloside Ⅱ restored the proliferation of splenic T cells and the production of IFN-Y and IL-2.However,astragaloside Ⅱ had no apparent effects on B cell proliferation.Conclusion:Astragaloside Ⅱ enhances T cell activation by regulating the activity of CD45 PTPase,which may explain why Astragalus membranaceus Bge is used as a tonic

  4. Different associations of CD45 isoforms with STAT3, PKC and ERK regulate IL-6-induced proliferation in myeloma.

    Directory of Open Access Journals (Sweden)

    Xu Zheng

    Full Text Available In response to interleukin 6 (IL-6 stimulation, both CD45RO and CD45RB, but not CD45RA, translocate to lipid rafts. However, the significance of this distinct translocation and the downstream signals in CD45 isoforms-participated IL-6 signal are not well understood. Using sucrose fractionation, we found that phosphorylated signal transducer and activator of transcription (STAT3 and STAT1 were mainly localized in lipid rafts in response to IL-6 stimulation, despite both STAT3 and STAT1 localizing in raft and non-raft fractions in the presence or absence of IL-6. On the other hand, extracellular signal-regulated kinase (ERK, and phosphorylated ERK were localized in non-raft fractions regardless of the existence of IL-6. The rafts inhibitor significantly impeded the phosphorylation of STAT3 and STAT1 and nuclear translocation, but had little effect on (and only postponing the phosphorylation of ERK. This data suggests that lipid raft-dependent STAT3 and STAT1 pathways are dominant pathways of IL-6 signal in myeloma cells. Interestingly, the phosphorylation level of STAT3 but not STAT1 in CD45+ cells was significantly higher compared to that of CD45- cells, while the phosphorylation level of ERK in CD45+ myeloma cells was relatively low. Furthermore, exogenously expressed CD45RO/RB significantly enhanced STAT3, protein kinase C (PKC and downstream NF-κB activation; however, CD45RA/RB inhibited IL-6-induced ERK phosphorylation. CD45 also enhanced the nuclear localization of STAT3 but not that of STAT1. In response to IL-6 stimulation, CD45RO moved into raft compartments and formed a complex with STAT3 and PKC in raft fraction, while CD45RA remained outside of lipid rafts and formed a complex with ERK in non-raft fraction. This data suggests a different role of CD45 isoforms in IL-6-induced signaling, indicating that while CD45RA/RB seems inhibit the rafts-unrelated ERK pathway, CD45RO/RB may actually work to enhance the rafts-related STAT3 and PKC

  5. Expression of the memory marker CD45RO on helper T cells in macaques.

    Directory of Open Access Journals (Sweden)

    Michael Valentine

    Full Text Available BACKGROUND: In humans it has been reported that a major site of the latent reservoir of HIV is within CD4+ T cells expressing the memory marker CD45RO, defined by the mAb UCHL1. There are conflicting reports regarding the expression of this antigen in macaques, the most relevant animal species for studying HIV pathogenesis and testing new therapies. There is now a major effort to eradicate HIV reservoirs and cure the infection. One approach is to eliminate subsets of cells housing the latent reservoir, using UCHL1 to target these cells. So that such studies may be performed in macaques, it is essential to determine expression of CD45RO. METHODS: We have used immunofluorescence and flow cytometry to study cell surface expression of CD45RO on lymphocytes from PBMC, lymphoid, and GI organs of rhesus, pigtailed, and cynomolgus macaques. Both direct and indirect immunofluorescence experiments were performed. FINDINGS: CD45RO is expressed on a subset of CD4+ lymphocytes of all pigtailed, a fraction of rhesus, and neither of the cynomolgus macaques studied. The binding of UCHL1 to macaque cells was of lower avidity than to human cells. This could be overcome by forming UCHL1 multimers. Directly conjugating fluors to UCHL1 can inhibit UCHL1 binding to macaque cells. Patterns of UCHL1 expression differ somewhat in macaques and humans, and from that of other memory markers often used in macaques. CONCLUSIONS: CD45RO, defined with mAb UCHL1, is well expressed on CD4+ cells in pigtailed macaques. Using tissues recovered from latently infected pigtailed macaques we are determining whether UCHL1, or other memory markers, can define the cellular locus of the reservoir. The low avidity of this interaction could limit the utility of UCHL1, in its conventional form, to eliminate cells in vivo and test this approach in macaque models of HIV infection.

  6. Malignant T cells exhibit CD45 resistant Stat 3 activation and proliferation in cutaneous T cell lymphoma

    DEFF Research Database (Denmark)

    Krejsgaard, T; Helvad, Rikke; Ralfkiær, Elisabeth


    CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in T and B cells via its effect on Src kinases. It has recently been shown that CD45 can also dephosphorylate Janus kinases (Jaks) and thereby regulate Signal transducer and activator of transcr......CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in T and B cells via its effect on Src kinases. It has recently been shown that CD45 can also dephosphorylate Janus kinases (Jaks) and thereby regulate Signal transducer and activator...... of transcription (Stat) activation and cytokine-induced proliferation in lymphocytes. Consequently, CD45 dysregulation could be implicated in aberrant Jak/Stat activation and proliferation in lymphoproliferative diseases. Despite high expression of the CD45 ligand, Galectin-1, in skin lesions from cutaneous T......-cell lymphoma (CTCL), the malignant T cells exhibit constitutive activation of the Jak3/Stat3 signalling pathway and uncontrolled proliferation. We show that CD45 expression is down-regulated on malignant T cells when compared to non-malignant T cells established from CTCL skin lesions. Moreover, CD45 cross...

  7. The catalytic activity of the CD45 membrane-proximal phosphatase domain is required for TCR signaling and regulation

    DEFF Research Database (Denmark)

    Desai, D M; Sap, J; Silvennoinen, O;


    Cell surface expression of CD45, a receptor-like protein tyrosine phosphatase (PTPase), is required for T cell antigen receptor (TCR)-mediated signal transduction. Like the majority of transmembrane PTPases, CD45 contains two cytoplasmic phosphatase domains, whose relative in vivo function is not...

  8. Auxiliary splice factor U2AF26 and transcription factor Gfi1 cooperate directly in regulating CD45 alternative splicing.

    NARCIS (Netherlands)

    Heyd, F.; Dam, G.B. ten; Moroy, T.


    By alternative splicing, different isoforms of the transmembrane tyrosine phosphatase CD45 are generated that either enhance or limit T cell receptor signaling. We report here that CD45 alternative splicing is regulated by cooperative action of the splice factor U2AF26 and the transcription factor G

  9. Increased expression of the CD45RO (memory) antigen on T cells in HIV-infected children. (United States)

    Froebel, K S; Doherty, K V; Whitelaw, J A; Hague, R A; Mok, J Y; Bird, A G


    Expression of the CD45RO putative memory cell antigen on CD4 (helper) and CD8 (cytotoxic/suppressor) lymphocytes of children born to HIV-infected women was investigated using the UCHL1 antibody. Significantly raised numbers of CD45RO+ CD8 lymphocytes were found in all nine of the infected children compared with uninfected and control children. Expression of CD45RO on CD4 lymphocytes was variable; absolute numbers were not increased, although the percentage was increased in four out of nine infected children. All the infected children except two (who had comparatively low numbers of CD45RO+ CD8 cells) were clinically well, which suggests that an increase in CD45RO+ CD8 cells may be indicative of a functionally active immune response against HIV.

  10. CD45RA-Foxp3(low) non-regulatory T cells in the CCR7-CD45RA-CD27+CD28+ effector memory subset are increased in synovial fluid from patients with rheumatoid arthritis. (United States)

    Matsuki, Fumichika; Saegusa, Jun; Nishimura, Keisuke; Miura, Yasushi; Kurosaka, Masahiro; Kumagai, Shunichi; Morinobu, Akio


    Increased numbers of regulatory T (Treg) cells are found in synovial fluid from patients with rheumatoid arthritis (RASF) compared with peripheral blood. However, Treg cells in RASF have been shown to have a decreased capacity to suppress T cells. Here we phenotypically classified CD4+ T cells in RASF into six subsets based on the expression of CD45RA, CCR7, CD27 and CD28, and demonstrated that the CCR7-CD45RA-CD27+CD28+ TEM subset was significantly increased in synovial fluid compared with peripheral blood. In addition, the proportion of Foxp3+ Treg cells in the CCR7-CD45RA-CD27+CD28+ TEM subset was significantly increased in RASF. Furthermore, most of the Foxp3+ Treg cells in RASF were non-suppressive CD45RA-Foxp3(low) non-Treg cells, and the frequency of the non-Treg cells in the CCR7-CD45RA-CD27+CD28+ TEM subset was significantly increased in RASF. Our findings suggest that the pro-inflammatory environment in RA joints may induce the increase of CD45RA-Foxp3(low) non-Treg cells in synovial fluid.

  11. Optimized Stem Cell Detection Using the DyeCycle-Triggered Side Population Phenotype

    Directory of Open Access Journals (Sweden)

    Maximilian Boesch


    Full Text Available Tissue and cancer stem cells are highly attractive target populations for regenerative medicine and novel potentially curative anticancer therapeutics. In order to get a better understanding of stem cell biology and function, it is essential to reproducibly identify these stem cells from biological samples for subsequent characterization or isolation. ABC drug transporter expression is a hallmark of stem cells. This is utilized to identify (cancer stem cells by exploiting their dye extrusion properties, which is referred to as the “side population assay.” Initially described for high-end flow cytometers equipped with ultraviolet lasers, this technique is now also amenable for a broader scientific community, owing to the increasing availability of violet laser-furnished cytometers and the advent of DyeCycle Violet (DCV. Here, we describe important technical aspects of the DCV-based side population assay and discuss potential pitfalls and caveats helping scientists to establish a valid and reproducible DCV-based side population assay. In addition, we investigate the suitability of blue laser-excitable DyeCycle dyes for side population detection. This knowledge will help to improve and standardize detection and isolation of stem cells based on their expression of ABC drug transporters.

  12. TCR usage, gene expression and function of two distinct FOXP3(+)Treg subsets within CD4(+)CD25(hi) T cells identified by expression of CD39 and CD45RO. (United States)

    Ye, Lingying; Goodall, Jane C; Zhang, Libin; Putintseva, Ekaterina V; Lam, Brian; Jiang, Lei; Liu, Wei; Yin, Jian; Lin, Li; Li, Ting; Wu, Xin; Yeo, Giles; Shugay, Mikhail; Chudakov, Dmitriy M; Gaston, Hill; Xu, Huji


    FOXP3+ regulatory T (Treg) cells are indispensable for immune homeostasis, but their study in humans is complicated by heterogeneity within Treg, the difficulty in purifying Tregs using surface marker expression (e.g. CD25) and the transient expression of FOXP3 by activated effector cells. Here, we report that expression of CD39 and CD45RO distinguishes three sub-populations within human CD4(+)CD25(hi) T cells. Initial phenotypic and functional analysis demonstrated that CD4(+)CD25(hi)CD39(+)CD45RO(+) cells had properties consistent with effector Treg, CD4(+)CD25(hi)CD39(-)CD45RO(-) cells were naïve Treg and CD4(+)CD25(hi)CD39(-)CD45RO(+) cells were predominantly non-Treg with effector T-cell function. Differences in these two newly identified Treg subsets were corroborated by studies of gene expression and TCR analysis. To apply this approach, we studied these two newly identified Treg subsets in ankylosing spondylitis, and showed impairment in both effector and naïve Treg. This work highlights the importance of discriminating Treg subsets to enable proper comparisons of immune regulatory capacity in healthy individuals and those with inflammatory disease.

  13. Bismuth 213-labeled anti-CD45 radioimmunoconjugate to condition dogs for nonmyeloablative allogeneic marrow grafts

    Energy Technology Data Exchange (ETDEWEB)

    Sandmaier, B M.(Fred Hutchinson Cancer Research Center, Seattle, WA); Bethge, W A.(Fred Hutchinson Cancer Research Center, Seattle, WA); Wilbur, D. Scott (Washington, Univ Of); Hamlin, Donald K.(Washington, Univ Of); Santos, E B.(Fred Hutchinson Cancer Research Center, Seattle, WA); Brechbiel, M W.(National Cancer Institute, National Institutes of Health, Bethesda, MD); Fisher, Darrell R.(BATTELLE (PACIFIC NW LAB)); Storb, R. (Fred Hutchinson Cancer Research Center)


    To lower treatment-related mortality and toxicity of conventional marrow transplantation, a nonmyeloablative regimen using 200 cGy total-body irradiation (TBI) and mycophenolate mofetil (MMF) combined with cyclosporine (CSP) for postgrafting immunosuppression was developed. To circumvent possible toxic effects of external- beam gamma irradiation, strategies for targeted radiation therapy were investigated. We tested whether the short-lived (46 minutes) alpha-emitter Bi-213 conjugated to an anti-CD45 monoclonal antibody (mAb) could replace 200 cGy TBI and selectively target hematopoietic tissues in a canine model of nonmyeloablative DLA-identical marrow transplantation. Biodistribution studies using iodine 123-labeled anti-CD45 mAb showed uptake in blood, marrow, lymph nodes, spleen, and liver. In a dose-escalation study, 7 dogs treated with the Bi-213-anti-CD45 conjugate (Bi-213 dose, 0.1-5.9 mCi/kg[3.7-218 MBq/kg]) without marrow grafts had no toxic effects other than a mild, reversible suppression of blood counts. On the basis of these studies, 3 dogs were treated with 0.5 mg/kg Bi-213-labeled anti-CD45 mAb (Bi-213 doses, 3.6, 4.6, and 8.8 mCi/kg[133, 170, and 326 MBq/kg]) given in 6 injections 3 and 2 days before grafting of marrow from DLA-identical littermates. The dogs also received MMF (10 mg/kg subcutaneously twice daily the day of transplantation until day 27 afterward) and CSP (15 mg/kg orally twice daily the day before transplantation until 35 days afterward). Therapy was well tolerated except for transient elevations in levels of transaminases in 3 dogs, followed by, in one dog, ascites. All dogs achieved prompt engraftment and stable mixed hematopoietic chimerism, with donor contributions ranging from 30% to 70% after more than 27 weeks of follow-up. These results form the basis for additional studies in animals and the design of clinical trials using Bi-213 as a nonmyeloablative conditioning regimen with minimal toxicity.

  14. Phylogeography and population dynamics of the white-sided dolphin (Lagenorhynchus acutus) in the North Atlantic

    KAUST Repository

    Banguera-Hinestroza, E.


    Highly mobile species in the marine environment may be expected to show little differentiation at the population level, but this is often not the case. Instead cryptic population structure is common, and effective conservation will require an understanding of how these patterns evolve. Here we present an assessment from both sides of the North Atlantic of differentiation among populations of a dolphin species that inhabits mainly pelagic waters, the Atlantic white-sided dolphin. We compare eleven putative populations in the western and eastern North Atlantic at mtDNA and microsatellite DNA loci and find reduced nucleotide diversity and signals for historical bottlenecks and post-bottleneck expansions in all regions. We calculate expansion times to have occurred during the early Holocene, following the last glacial maximum (LGM). We find evidence for connectivity among populations from either side of the North Atlantic, and differentiation between putative populations in the far northeast compared with all other areas sampled. Some data suggest the possibility of separate refugia during the LGM explaining this pattern, although ongoing ecological processes may also be a factor. We discuss the implications for developing effective programs of conservation and management in the context of ongoing anthropogenic impact. © 2014 Springer Science+Business Media Dordrecht.

  15. Functional possibilities for forming different inverse population distributions in diode-side-pumped laser heads

    Energy Technology Data Exchange (ETDEWEB)

    Grechin, S G; Nikolaev, P P; Sharandin, E A [N.E. Bauman Moscow State Technical University, Moscow (Russian Federation)


    The functional possibilities of diode-side-pumped laser heads of solid-state lasers for forming inverse population distributions of different types are analysed. The invariants determining the relationship between the laser head parameters upon scaling are found. The results of comparative experimental studies are presented. (lasers)

  16. Pretargeted Radioimmunotherapy Using Anti-CD45 Monoclonal Antibodies to Deliver Radiation to Murine Hematolymphoid Tissues and Human Myeloid Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Pagel, John M.; Matthews, Dana C.; Kenoyer, Aimee L.; Hamlin, Donald K.; Wilbur, D. Scott; Fisher, Darrell R.; Gopal, Ajay K.; Lin, Yukang; Saganic, Laura; Appelbaum, Frederick R.; Press, Oliver W.


    The efficacy of radioimmunotherapy (RIT) for treatment of patients with hematological malignancies frequently fails because of disease recurrence. We therefore conducted pretargeted RIT studies to augment the efficacy in mice of therapy using a pretargeted anti-human (h)CD45 antibody (Ab)-streptavidin (SA) conjugate followed by delivery of a biotinylated clearing agent and radiolabeled-DOTA-biotin. Tumor-to-blood ratios at 24 hours were 20:1 using pretargeted anti-hCD45 RIT and <1:1 with conventional RIT. In vivo imaging studies confirmed that the pretargeted RIT approach provided high-contrast tumor images with minimal blood-pool activity, whereas directly-labeled anti-hCD45 Ab produced distinct tumor images but the blood pool retained a large amount of labeled antibody for a prolonged time. Therapy experiments demonstrated that 90Y-DOTA-biotin significantly prolonged survival of mice treated pretargeted with anti-hCD45 Ab-SA compared to mice treated with conventional RIT using 90Y-labeled anti-hCD45 Ab at the maximally tolerated dose (400 µCi). Since human CD45 antigens are confined to xenograft tumor cells in this model, and all murine tissues are devoid of hCD45 and will not bind anti-hCD45 Ab, we also compared one-step and pretargeted RIT using an anti-murine (m)CD45 Ab (A20 ) in a model where the target antigen is present on normal hematopoietic tissues. After 24 hours, 27.3 ± 2.8% of the injected dose of radionuclide was delivered per gram (% ID/g) of lymph node using 131I-A20-Ab compared with 40.0 ± 5.4% ID/g for pretargeted 111In-DOTA-biotin (p value). These data suggest that multi-step pretargeted methods for delivering RIT are superior to conventional RIT when targeting CD45 for the treatment of leukemia and may allow for the intensification of therapy, while minimizing toxicities.

  17. Expression of CD45 in salivary glands of Sjogren's Syndrome patients%舍格林综合征唇腺组织中CD45的表达及意义

    Institute of Scientific and Technical Information of China (English)

    刘明; 高文信


    目的:研究舍格林综合征(Sjogren's Syndrome,简称SS)患者唇腺组织中过度浸润的淋巴细胞上的白细胞共同分化抗原(Leukocyte common antigen-45,CD45)的表达,以探讨淋巴细胞在其免疫反应中的作用.方法:通过HE染色观察淋巴细胞的浸润特点,采用免疫组织化学法检测CD45R、CD45RO在淋巴细胞上的表达.结果:唇腺组织过度浸润的淋巴细胞中CD45RO阳性表达的T细胞占65.74%,CD45R阳性表达的B细胞占27.38%. 结论:在SS病变中是以细胞免疫为主、体液免疫为辅的免疫反应.

  18. 188Re直接法标记CD45单抗及其体内生物分布研究%Direct-radiolabeling of CD45 monoclonal antibody with rhenium-188 and its biodistribution in normal mice

    Institute of Scientific and Technical Information of China (English)

    郑文莉; 李贵平; 黄宝丹; 杜丽; 黄凯


    Objective With direct-labeling method of CD45 McAb with 188Re, to investigate its bio-distribution character in normal mice. Methods The disulfide bond in the molecule of CD45 monoclonal antibody was reduced to form a mercapto group by the mercaptoethanol (2-ME). The labeling was conducted by stannous chloride used as reductant of 188Re, and sodium glucoheptonate as intermediate.weak ligands, then 188Re was directly labeled CD45 mAb alone; The reaction mixture was separated and purified throuth the PD-10 column;Labeling efficiency and radiochemical purity were measured by the paper chromatography. Then stability of 188Re labeled CD45 McAb was determined in vitro. The biodistribution in the healthy Kunming mice after intravenous injection of 188Re-CD45 McAb was determined. Results The labeling efficiency of 188Re-CD45 McAb was (85.25±2.63)%, and radiochemical purity was (92.54±3.56)%. The specific activity was (2.06±0.07) TBq/mmol;The radiochemical purity of 188Re-CD45 McAb was (64.33±1.53)% after incubating 24 h in room temperature. While mixed the saline and healthy rat serum at 37℃for 24 h, the radiochemical purity was (64. 2±3. 77)%and(56. 7±4. 16)%, respectively. The biodistribution result showed that the radioactivity in body was mainly distributed in kidney and liver, followed by lung, bone and blood. Conclusion The method of direct-labeling CD45 McAb with 188Re is not only simple, but also has high labeling efficiency. 188Re-CD45 McAb has good stability in vitro. After injected intravenously, radioactive label is mainly excreted through kidneys with a higher accumulation in liver, and it accords with the in vivo kinetics characteristic of labeled antibody.%目的:利用188Re直接法标记CD45单抗,探讨其在正常小鼠体内的生物学分布特性。方法应用2-巯基乙醇(2-ME)还原CD45单抗分子中的二硫键形成巯基;以氯化亚锡作为188Re的还原剂,葡庚糖酸钠为中间弱配体,188Re直接标记CD45

  19. Co-localization of Fyn with CD3 complex, CD45 or CD28 depends on different mechanisms. (United States)

    zur Hausen, J D; Burn, P; Amrein, K E


    The Src family protein tyrosine kinase Fyn (p59fyn) plays an important role in thymocyte development and T cell receptor (TCR) signal transduction. Fyn has been shown to associate with the TCR-CD3 complex, the protein tyrosine phosphatase CD45 and several co-receptors such as CD28 which are crucial for initiating T cell activation and proliferation. The molecular basis of how Fyn is associated with these transmembrane proteins is largely unknown. To investigate the Fyn association with the TCR-CD3 complex, CD45 and CD28 at the molecular level, various Fyn/beta-galactosidase fusion proteins were constructed and expressed in Jurkat cells. Co-localization experiments applying antibody-induced co-capping and double immunofluorescence staining techniques were used to study the association of these fusion proteins with the TCR-CD3 complex, CD45 and CD28. Our results revealed that co-localization of Fyn with the TCR-CD3 complex requires the unique N terminus whereas co-localization with CD45 depends on the unique N terminus, the Src homology (SH)3- and a functional SH2 domain. CD28 co-localizes with Fyn molecules that contain the N terminus and a functional SH2 domain. These results suggest that Fyn association with the TCR-CD3 complex, CD45 and CD28 is mediated by different molecular mechanisms.

  20. CD45/CD11b Positive Subsets of Adult Lung Anchorage-Independent Cells Harness Epithelial Stem Cells (United States)

    Peter, Yakov; Sen, Namita; Levantini, Elena; Keller, Steven; Ingenito, Edward P; Ciner, Aaron; Sackstein, Robert; Shapiro, Steven D


    Compensatory growth is mediated by multiple cell types that interact during organ repair. To elucidate the relationship between the stem/progenitor cells that proliferate or differentiate and the somatic cells of lung, we utilized a novel ex vivo pneumoexplant system. Applying this technique, we identified a sustained culture of repopulating adult progenitors in the form of free floating anchorage-independent cells (AICs). AICs did not express integrin proteins α5, β3, and β7, and constituted 37% of the total culture at day 14, yielding a mixed yet conserved population that recapitulated RNA expression patterns of the healthy lung. AICs exhibited rapid proliferation manifested by a marked 60-fold increase in cell numbers by day 21. Over 50% of the AIC population was cKit+ or double-positive for CD45+ and CD11b+ antigenic determinants, consistent with cells of hematopoietic origin. The latter subset was found to be enriched with prosurfactant protein-C and SCGB1A1 expressing putative stem cells and with aquaporin-5 producing cells, characteristic of terminally differentiated alveolar epithelial type-1 pneumocytes. AICs undergo remodeling to form a cellular lining at the air/gel interface, and TGFβ1 treatment modifies protein expression, implying direct-differentiation of this population. These data confirm the active participation of clonogenic hematopietic stem cells in a mammalian model of lung repair and validate mixed stem/somatic cell cultures, which embrace sustained cell viability, proliferation, and differentiation, for use in studies of compensatory pulmonary growth. PMID:22585451

  1. Differential gene expression in CD45 cells at para-aortic foci stage of chicken haematopoiesis. (United States)

    Säynäjäkangas, R; Uchida, T; Vainio, O


    Para-aortic foci of chicken embryos at 6-7 days of development are considered to provide a microenvironment for haematopoietic stem cell proliferation and initial differentiation similar to that of fetal liver in mammals. Here, we have investigated the genes involved in this process by constructing and analysing a subtractive cDNA library from CD45(+) cells in para-aortic region. Among 394 analysed clones 99 distinct genes were identified by sequence homology search. Classification of the identified genes according to biological processes revealed that innate immunity-related genes are highly expressed at this stage. This can be explained by the presence of yolk sac-derived macrophages in the original tissue sample but also by the indiscriminate expression of multiple lineage-specific genes in haematopoietic stem cells and primitive progenitors. Differentially expressed genes related to transcription, signalling and lymphocyte functions are potential candidates involved in lineage commitment.

  2. 侧群细胞的研究进展%Research progress of side population cells

    Institute of Scientific and Technical Information of China (English)

    李新星; 王坚


    In the occurrence and development of tumors, side population cells play an extremely important role. They have the characteristics of cancer stem cells, especially their potential of tumor originating, and stronger drug-resistance. The study of biological characteristics, sorting and training methods of side population cells and the relationship between side population cells and tumor drug-resistance may shed some light on the diagnosis and treatment of cancer.%在肿瘤的发生、发展中侧群细胞扮演着极其重要的作用。侧群细胞具有肿瘤干细胞的特性,尤其具备肿瘤的始发潜能,同时对化疗药物有较强的抵抗能力。对侧群细胞的生物学特性、分选与培养方法及侧群细胞与肿瘤耐药关系的研究,能为肿瘤的诊断和治疗提供新的思路和方法。

  3. Side population sorting separates subfractions of cycling and non-cycling intestinal stem cells

    Directory of Open Access Journals (Sweden)

    Richard J. von Furstenberg


    Full Text Available We report here that side population (SP sorting allows for the simultaneous isolation of two intestinal stem cell (ISC subsets from wild-type (WT mice which are phenotypically different and represent cycling and non-cycling pools of cells. Following 5-ethynyl-2′-deoxyuridine (EdU injection, in the upper side population (USP the percentage of EdU+ was 36% showing this fraction to be highly proliferative. In the lower side population (LSP, only 0.4% of cells were EdU+, indicating this fraction to be predominantly non-cycling. Using Lgr5-EGFP mice, we show that Lgr5-EGFPhi cells, representing actively cycling ISCs, are essentially exclusive to the USP. In contrast, using histone 2B-YFP mice, SP analysis revealed YFP label retaining cells (LRCs in both the USP and the LSP. Correspondingly, evaluation of the SP fractions for mRNA markers by qRT-PCR showed that the USP was enriched in transcripts associated with both quiescent and active ISCs. In contrast, the LSP expressed mRNA markers of quiescent ISCs while being de-enriched for those of the active ISC. Both the USP and LSP are capable of generating enteroids in culture which include the four intestinal lineages. We conclude that sorting of USP and LSP fractions represents a novel isolation of cycling and non-cycling ISCs from WT mice.

  4. Side population analysis using a violet-excited cell-permeable DNA binding dye. (United States)

    Telford, William G; Bradford, Jolene; Godfrey, William; Robey, Robert W; Bates, Susan E


    Hoechst 33342 side population (SP) analysis is a common method for identifying stem cells in mammalian hematopoietic and nonhematopoietic tissues. Although widely employed for stem cell analysis, this method requires an ultraviolet (UV) laser to excite Hoechst 33342. Flow cytometers equipped with UV sources are not common because of the cost of both the laser and optics that can transmit light UV light. Violet laser sources are inexpensive and are now common fixtures on flow cytometers, but have been previously shown to provide insufficient Hoechst dye excitation for consistent resolution of SP cells. One solution to this problem is to identify additional fluorescent substrates with the same pump specificity as Hoechst 33342, but with better violet excitation characteristics. DyeCycle Violet reagent has emission characteristics similar to those of Hoechst 33342, but with a longer wavelength excitation maxima (369 nm). When this dye is loaded into hematopoietic cells, a sharply resolved side population was also observed, similar in appearance to that seen with Hoechst 33342. Unlike Hoechst SP, DCV SP was similar in appearance with both violet and UV excitation. DCV SP could be inhibited fumitremorgin C, and showed the same membrane pump specificity as Hoechst 33342. Simultaneous immunophenotyping with stem cell markers in mouse bone marrow demonstrated that DCV SP was restricted to the stem cell lineage(-) Sca-1(+) c-kit(+) cells population, as is Hoechst SP. Pending confirmation by functional analysis of DCV SP cells, these results suggest that DCV efflux identified approximately the same stem cell population as did Hoechst 33342 efflux. Substituting DCV for Hoechst 33342 in the SP technique may, therefore, allow side population analysis on flow cytometers with violet lasers.

  5. Anti-CD45 radioimmunotherapy using 211At with bone marrow transplantation prolongs survival in a disseminated murine leukemia model

    Energy Technology Data Exchange (ETDEWEB)

    Orozco, Johnnie J.; Back, Tom; Kenoyer, Aimee L.; Balkin, Ethan R.; Hamlin, Donald K.; Wilbur, D. Scott; Fisher, Darrell R.; Frayo, Shani; Hylarides, Mark; Green, Damian J.; Gopal, Ajay K.; Press, Oliver W.; Pagel, John M.


    Anti-CD45 Radioimmunotherapy using an Alpha-Emitting Radionuclide 211At Combined with Bone Marrow Transplantation Prolongs Survival in a Disseminated Murine Leukemia Model ABSTRACT Despite aggressive chemotherapy combined with hematopoietic cell transplant (HCT), many patients with acute myeloid leukemia (AML) relapse. Radioimmunotherapy (RIT) using antibodies (Ab) labeled primarily with beta-emitting radionuclides has been explored to reduce relapse.

  6. Lenalidomide enhances antigen-specific activity and decreases CD45RA expression of T cells from patients with multiple myeloma. (United States)

    Neuber, Brigitte; Herth, Isabelle; Tolliver, Claudia; Schoenland, Stefan; Hegenbart, Ute; Hose, Dirk; Witzens-Harig, Mathias; Ho, Anthony D; Goldschmidt, Hartmut; Klein, Bernard; Hundemer, Michael


    The aim of this study was to investigate whether the specific T cell response against the multiple myeloma Ag HM1.24 is enhanced by the immunomodulatory drug lenalidomide (Revlimid). Ag-specific CD3(+)CD8(+) T cells against the HM1.24 Ag were expanded in vitro by dendritic cells in 29 healthy donors and 26 patients with plasma cell dyscrasias. Ag-specific activation was analyzed by IFN-γ, granzyme B, and perforin secretion using ELISA, ELISPOT assay, and intracellular staining, and generation of Ag-specific T cells was analyzed by tetramer staining. Expression of T cell maturation markers (CD45RA, CD45R0, CCR7, and CD28) was investigated by flow cytometry. We found that activation of HM1.24-specific T cells from healthy donors and patients with plasma cell dyscrasias was enhanced significantly by lenalidomide and furthermore that the impact of lenalidomide on T cells depends on the duration of the exposure. Notably, lenalidomide supports the downregulation of CD45RA on T cells upon activation, observed in healthy donors and in patients in vitro and also in patients during lenalidomide therapy in vivo. We showed for the first time, to our knowledge, that lenalidomide enhances the Ag-specific activation of T cells and the subsequent downregulation of CD45RA expression of T cells in vitro and in vivo.

  7. Reduced Seminal Concentration of CD45pos Cells after Follicle-Stimulating Hormone Treatment in Selected Patients with Idiopathic Oligoasthenoteratozoospermia

    Directory of Open Access Journals (Sweden)

    Rosita A. Condorelli


    Full Text Available The present study evaluated the conventional sperm parameters and the seminal concentration of CD45pos cells (pan-leukocyte marker of infertile patients with idiopathic oligoasthenoteratozoospermia (OAT. The patients were arbitrarily divided into three groups treated with recombinant follicle-stimulating hormone FSH: α (Group A = 20 patients, recombinant FSH-β (Group B = 20 patients, and highly purified human FSH (Group C = 14 patients. All treated groups achieved a similar improvement of the main sperm parameters (density, progressive motility, and morphology, but only the increase in the percentage of spermatozoa with normal morphology was significant compared to the baseline in all three examined groups. Moreover, all groups had a significant reduction of the seminal concentration of CD45pos cells and of the percentage of immature germ cells. Before and after the treatment, the concentration of CD45pos cells showed a positive linear correlation with the percentage of immature germ cells and a negative correlation with the percentage of spermatozoa with regular morphology. These results demonstrate that treatment with FSH is effective in patients with idiopathic OAT and that there are no significant differences between the different preparations. The novelty of this study is in the significant reduction of the concentration of CD45pos cells observed after the treatment.

  8. microRNA Expression Profiling of Side Population Cells in Human Lung Cancer and Preliminary Analysis


    XU, XIAOTAO; Xiao LU; Sun, Jing; Shu, Yongqian


    Background and objective Recent studies indicate that the side population (SP) which is an enriched source of cancer stem cells (CSCs) is the root cause of tumor growth and development. SP appears to be highly resistant to chemo- and radio-therapy which becomes an important factor in tumor recurrence and metastasis. The aim of this study is to determine the difference of microRNA expression profiles between SP cells and non-SP cells so as to lay necessary basis for research on the function of...

  9. CD45-mediated signaling pathway is involved in Rhizoctonia bataticola lectin (RBL)-induced proliferation and Th1/Th2 cytokine secretion in human PBMC

    Energy Technology Data Exchange (ETDEWEB)

    Pujari, Radha [National Centre for Cell Science, Ganeshkhind, Pune 411007 (India); Eligar, Sachin M. [Department of Biochemistry, Karnatak University, Dharwad, 580003 Karnataka (India); Kumar, Natesh [National Centre for Cell Science, Ganeshkhind, Pune 411007 (India); Nagre, Nagaraja N.; Inamdar, Shashikala R.; Swamy, Bale M. [Department of Biochemistry, Karnatak University, Dharwad, 580003 Karnataka (India); Shastry, Padma, E-mail: [National Centre for Cell Science, Ganeshkhind, Pune 411007 (India)


    Highlights: Black-Right-Pointing-Pointer RBL, a potent mitogenic and complex N-glycan specific lectin binds to CD45 on PBMC. Black-Right-Pointing-Pointer RBL triggers CD45-mediated signaling involved in activation of p38MAPK and STAT-5. Black-Right-Pointing-Pointer Inhibition of CD45 PTPase signaling blocks RBL-induced ZAP70 phosphorylation. Black-Right-Pointing-Pointer RBL-CD45 mediated signaling is crucial for RBL-induced immunodulatory activities. -- Abstract: We earlier reported the mitogenic and immunostimulatory activities of Rhizoctonia bataticola lectin (RBL), purified from phytopathogenic fungus R. bataticola in human PBMC. The lectin demonstrates specificity towards glycoproteins containing complex N-glycans. Since CD45-protein tyrosine phosphatase that abundantly expresses N-glycans is important in T-cell signaling, the study aimed to investigate the involvement of CD45 in the immunomodulatory activities of RBL. Flowcytometry and confocal microscopy studies revealed that RBL exhibited binding to PBMC and colocalized with CD45. The binding was comparable in cells expressing different CD45 isoforms-RA, -RB and -RO. CD45 blocking antibody reduced the binding and proliferation of PBMC induced by RBL. CD45-PTPase inhibitor dephostatin inhibited RBL-induced proliferation, expression of CD25 and pZAP-70. RBL-induced secretion of Th1/Th2 cytokines were significantly inhibited in presence of dephostatin. Also, dephostatin blocked phosphorylation of p38MAPK and STAT-5 that was crucial for the biological functions of RBL. The study demonstrates the involvement of CD45-mediated signaling in RBL-induced PBMC proliferation and Th1/Th2 cytokine secretion through activation of p38MAPK and STAT-5.

  10. Lifetimes and side-feeding population of the yrast band levels in {sup 131}La

    Energy Technology Data Exchange (ETDEWEB)

    Grodner, E.; Droste, Ch.; Morek, T.; Srebrny, J. [Warsaw University, Nuclear Physics Division, Warsaw (Poland); Pasternak, A.A. [A.F. Ioffe Physical Technical Institute, Cyclotron Laboratory, St.-Petersburg (Russian Federation); Kownacki, J.; Kordyasz, A.; Wolinska, M. [Warsaw University, Heavy Ion Laboratory, Warsaw (Poland); Plociennik, W.; Wasilewski, A.A.; Kaczarowski, R.; Ruchowska, E. [The A. Soltan Institute for Nuclear Studies, Swierk (Poland); Kowalczyk, M. [Warsaw University, Nuclear Physics Division, Warsaw (Poland); Warsaw University, Heavy Ion Laboratory, Warsaw (Poland); Kisielinski, M. [The A. Soltan Institute for Nuclear Studies, Swierk (Poland); Warsaw University, Heavy Ion Laboratory, Warsaw (Poland)


    Lifetimes of yrast levels with spins I{sup {pi}}=23/2{sup -}-43/2{sup -} in {sup 131}La populated in the {sup 122}Sn({sup 14}N,5n) reaction at a beam energy of 70 MeV are measured by the Doppler Shift Attenuation method. A model of side-feeding population is presented. The model parameters are determined in an experiment based on the lineshape of {gamma}-transitions from two highest spin levels and from the intensity distribution along the yrast band. The properties of the h{sub 11/2} band in {sup 131}La are compared with the theoretical predictions obtained in the framework of the Core-Quasi-Particle Coupling and the self-consistent Total Routhian Surface models. (orig.)

  11. Single Targeted Exon Mutation Creates a True Congenic Mouse for Competitive Hematopoietic Stem Cell Transplantation: The C57BL/6-CD45.1STEM Mouse

    Directory of Open Access Journals (Sweden)

    Francois E. Mercier


    Full Text Available Defining the molecular regulators of hematopoietic stem and progenitor cells (HSPCs requires in vivo functional analyses. Competitive bone marrow transplants (BMTs compare control and test HSPCs to demonstrate the functional role of a genetic change or chemical perturbation. Competitive BMT is enabled by antibodies that specifically recognize hematopoietic cells from congenic mouse strains due to variants of the cell surface protein CD45, designated CD45.1 and CD45.2. The current congenic competitor strain, B6.SJL-Ptprca Pepcb/BoyJ (CD45.1, has a substantial inherent disadvantage in competition against the C57BL/6 (CD45.2 strain, confounding experimental interpretation. Despite backcrossing, the congenic interval over which the B6.SJL-Ptprca Pepcb/BoyJ strain differs is almost 40 Mb encoding ∼300 genes. Here, we demonstrate that a single amino acid change determines the CD45.1 epitope. Further, we report on the single targeted exon mutant (STEM mouse strain, CD45.1STEM, which is functionally equivalent to CD45.2 cells in competitive BMT. This strain will permit the precise definition of functional roles for candidate genes using in vivo HSPC assays.

  12. Cancer Stem Cells and Side Population Cells in Breast Cancer and Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Britton, Kelly M. [Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle-upon-Tyne, NE1 3BZ (United Kingdom); Kirby, John A. [Institute of Cellular Medicine, Newcastle University, 3rd Floor William Leech Building, Framlington Place, Newcastle-upon-Tyne, NE2 4HH (United Kingdom); Lennard, Thomas W.J. [Faculty of Medical Sciences, Newcastle University, 3rd Floor William Leech Building, Framlington Place, Newcastle-upon-Tyne, NE2 4HH (United Kingdom); Meeson, Annette P., E-mail: [Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle-upon-Tyne, NE1 3BZ (United Kingdom); North East England Stem Cell Institute, Bioscience Centre, International Centre for Life, Central Parkway, Newcastle-upon-Tyne, NE1 3BZ (United Kingdom)


    In breast cancer it is never the primary tumour that is fatal; instead it is the development of metastatic disease which is the major cause of cancer related mortality. There is accumulating evidence that suggests that Cancer Stem Cells (CSC) may play a role in breast cancer development and progression. Breast cancer stem cell populations, including side population cells (SP), have been shown to be primitive stem cell-like populations, being long-lived, self-renewing and highly proliferative. SP cells are identified using dual wavelength flow cytometry combined with Hoechst 33342 dye efflux, this ability is due to expression of one or more members of the ABC transporter family. They have increased resistance to chemotherapeutic agents and apoptotic stimuli and have increased migratory potential above that of the bulk tumour cells making them strong candidates for the metastatic spread of breast cancer. Treatment of nearly all cancers usually involves one first-line agent known to be a substrate of an ABC transporter thereby increasing the risk of developing drug resistant tumours. At present there is no marker available to identify SP cells using immunohistochemistry on breast cancer patient samples. If SP cells do play a role in breast cancer progression/Metastatic Breast Cancer (MBC), combining chemotherapy with ABC inhibitors may be able to destroy both the cells making up the bulk tumour and the cancer stem cell population thus preventing the risk of drug resistant disease, recurrence or metastasis.

  13. Isolation and phenotypic characterization of cancer stem-like side population cells in colon cancer. (United States)

    Feng, Long; Wu, Jian-Bing; Yi, Feng-Ming


    Previous studies in cancer biology suggest that chemotherapeutic drug resistance and tumor relapse are driven by cells within a tumor termed 'cancer stem cells'. In the present study, a Hoechst 33342 dye exclusion technique was used to identify cancer stem‑like side population (SP) cells in colon carcinoma, which accounted for 3.4% of the total cell population. Following treatment with verapamil, the population of SP cells was reduced to 0.6%. In addition, the sorted SP cells exhibited marked multidrug resistance and enhanced cell survival rates compared with non‑SP cells. The SP cells were able to generate more tumor spheres and were CD133 positive. Subsequent biochemical analysis revealed that the levels of the adenosine triphosphate‑binding cassette sub‑family G member 2 transporter protein, B‑cell lymphoma anti‑apoptotic factor and autocrine production of interleukin‑4 were significantly enhanced in the colon cancer SP cells, which contributed to drug resistance, protection of the cells from apoptosis and tumor recurrence. Therefore, the findings suggested that treatment failure and colon tumorigenesis is dictated by a small population of SP cells, which indicate a potential target in future therapies.

  14. Conformational gel analysis and graphics: Measurement of side chain rotational isomer populations by NMR and molecular mechanics

    CERN Document Server

    Haydock, Christopher


    Conformational gel analysis and graphics systematically identifies and evaluates plausible alternatives to the side chain conformations found by conventional peptide or protein structure determination methods. The proposed analysis determines the populations of side chain rotational isomers and the probability distribution of these populations. The following steps are repeated for each side chain of a peptide or protein: first, extract the local molecular mechanics of side chain rotational isomerization from a single representative global conformation; second, expand the predominant set of rotational isomers to include all probable rotational isomers down to those that constitute just a small percentage of the population; and third, evaluate the constraints vicinal coupling constants and NOESY cross relaxation rates place on rotational isomer populations. In this article we apply conformational gel analysis to the cobalt glycyl-leucine dipeptide and detail the steps necessary to generalize the analysis to oth...

  15. Notch inhibition suppresses nasopharyngeal carcinoma by depleting cancer stem-like side population cells. (United States)

    Yu, Shudong; Zhang, Ruxin; Liu, Fenye; Wang, Hong; Wu, Jing; Wang, Yanqing


    The cancer stem cell (CSC) is responsible for the initiation, proliferation and radiation resistance. Side population (SP) cells are a rare subset of cells enriched with CSCs. The targeting of key signaling pathways that are active in CSCs is a therapeutic approach to treating cancer. Notch signaling is important for the self-renewal and maintenance of stem cells. Our previous studies demonstrated that downregulation of Notch signaling could enhance radiosensitivity of nasopharyngeal carcinoma (NPC) cells. In this study, we found that Notch signaling was highly activated in SP cells compared with that of non-SP (NSP) cells of NPC. Therefore, Notch inhibition could reduce the proportion of SP cells. As SP cells decreased, proliferation, anti-apoptosis and tumorigenesis were also decreased. This study shows that Notch inhibition may be a promising clinical approach in CSC-targeting therapy for NPC.

  16. Persistence of side population cells with high drug efflux capacity in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)


    AIM:To investigate the persistence of side population (SP) cells in pancreatic cancer and their role and mechanism in the drug resistance.METHODS:The presentation of side population cells in pancreatic cancer cell line PANC-1 and its proportion change when cultured with Gemcitabine,was detected by Hoechst 33342 staining and FACS analysis.The expression of ABCB1 and ABCG2 was detected by realtime PCR in either SP cells or non-SP cells.RESULTS:SP cells do exist in PANC-1,with a median of 3.3% and a range of 2.1-8.7%.After cultured with Gemcitabine for 3 d,the proportion of SP cells increased significantly(3.8% ± 1.9%,10.7% ± 3.7%, t = 4.616,P = 0.001 < 0.05).ABCB1 and ABCG2 expressed at higher concentrations in SP as compared with non-SP cells (ABCBI: 1.15 ± 0.72, 5.82 ± 1.16, t = 10.839,P = 0.000 < 0.05; ABCG2:1.16 ± 0.75,5.48 ± 0.94,t = 11.305,P = 0.000 < 0.05),which may contribute to the efflux of fluorescent staining and drug resistance.CONCLUSION:SP cells with inherently high resistance to chemotherapeutic agents do exist in pancreatic cancers,which may be candidate cancer stem cells contributing to the relapse of the tumor.

  17. An anti-CD45RO immunotoxin eliminates T cells latently infected with HIV-1 in vitro


    McCoig, Cynthia; Dyke, Gregory; Chou, Chin-Sheng; Picker, Louis J.; Ramilo,Octavio; Vitetta, Ellen S.


    Despite the success of highly active antiretroviral therapy (HAART) in lowering circulating HIV-1 to undetectable levels in most infected individuals, several studies have documented the presence of a small reservoir of latently infected cells in HAART patients, the majority of which are CD45RO+ memory T cells. We previously have demonstrated that latently infected, replication-competent cells can be generated in vitro after eliminating CD25+ cells with an immunotoxin (IT). The present study ...

  18. Identification and Characterization of Lineage(-)CD45(-)Sca-1(+) VSEL Phenotypic Cells Residing in Adult Mouse Bone Tissue. (United States)

    Nakatsuka, Ryusuke; Iwaki, Ryuji; Matsuoka, Yoshikazu; Sumide, Keisuke; Kawamura, Hiroshi; Fujioka, Tatsuya; Sasaki, Yutaka; Uemura, Yasushi; Asano, Hiroaki; Kwon, A-Hon; Sonoda, Yoshiaki


    Murine bone marrow (BM)-derived very small embryonic-like stem cells (BM VSELs), defined by a lineage-negative (Lin(-)), CD45-negative (CD45(-)), Sca-1-positive (Sca-1(+)) immunophenotype, were previously reported as postnatal pluripotent stem cells (SCs). We developed a highly efficient method for isolating Lin(-)CD45(-)Sca-1(+) small cells using enzymatic treatment of murine bone. We designated these cells as bone-derived VSELs (BD VSELs). The incidences of BM VSELs in the BM-derived nucleated cells and that of BD VSELs in bone-derived nucleated cells were 0.002% and 0.15%, respectively. These BD VSELs expressed a variety of hematopoietic stem cell (HSC), mesenchymal stem cell (MSC), and endothelial cell markers. The gene expression profile of the BD VSELs was clearly distinct from those of HSCs, MSCs, and ES cells. In the steady state, the BD VSELs proliferated slowly, however, the number of BD VSELs significantly increased in the bone after acute liver injury. Moreover, green fluorescent protein-mouse derived BD VSELs transplanted via tail vein injection after acute liver injury were detected in the liver parenchyma of recipient mice. Immunohistological analyses suggested that these BD VSELs might transdifferentiate into hepatocytes. This study demonstrated that the majority of the Lin(-)CD45(-)Sca-1(+) VSEL phenotypic cells reside in the bone rather than the BM. However, the immunophenotype and the gene expression profile of BD VSELs were clearly different from those of other types of SCs, including BM VSELs, MSCs, HSCs, and ES cells. Further studies will therefore be required to elucidate their cellular and/or SC characteristics and the potential relationship between BD VSELs and BM VSELs.

  19. Flipping the switches: CD40 and CD45 modulation of microglial activation states in HIV associated dementia (HAD

    Directory of Open Access Journals (Sweden)

    Jin Jingji


    Full Text Available Abstract Microglial dysfunction is associated with the pathogenesis and progression of a number of neurodegenerative disorders including HIV associated dementia (HAD. HIV promotion of an M1 antigen presenting cell (APC - like microglial phenotype, through the promotion of CD40 activity, may impair endogenous mechanisms important for amyloid- beta (Aβ protein clearance. Further, a chronic pro-inflammatory cycle is established in this manner. CD45 is a protein tyrosine phosphatase receptor which negatively regulates CD40L-CD40-induced microglial M1 activation; an effect leading to the promotion of an M2 phenotype better suited to phagocytose and clear Aβ. Moreover, this CD45 mediated activation state appears to dampen harmful cytokine production. As such, this property of microglial CD45 as a regulatory "off switch" for a CD40-promoted M1, APC-type microglia activation phenotype may represent a critical therapeutic target for the prevention and treatment of neurodegeneration, as well as microglial dysfunction, found in patients with HAD.

  20. Different population structure in genus Luciobarbus Heckel, 1843 (Actinopterygii, Cyprinidae on both sides of the Strait of Gibraltar

    Directory of Open Access Journals (Sweden)

    Miriam Casal-Lopez


    Here, through a phylogeographic study based on mitochondrial molecular markers, we found different structures on both sides of the Strait of Gibraltar, as well as faunistic connections probably established on both sides during Miocene. Our results show that populations may have followed different and complex histories and species have suffered diverse events of vicariance and dispersion. While north Moroccan population show a well-defined structure, showing not only unique haplotypes, but different species, the case of the southern populations of the Iberian endemism, Luciobarbus sclateri Günther, 1868, differs substantially.

  1. GADD45β Determines Chemoresistance and Invasive Growth of Side Population Cells of Human Embryonic Carcinoma

    Directory of Open Access Journals (Sweden)

    Toshihiko Inowa


    Full Text Available Side population (SP cells are an enriched population of stem, and the existence of SP cells has been reported in human cancer cell lines. In this study, we performed an SP analysis using 11 human cancer cell lines and confirmed the presence of SP cells in an embryonic carcinoma cell line, NEC8. NEC8 SP cells showed characteristics of cancer stem cells, such as high growth rate, chemoresistance and high invasiveness. To further characterize the NEC8 SP cells, we used DNA microarrays. Among 38,500 genes, we identified 12 genes that were over-expressed in SP cells and 1 gene that was over-expressed in non-SP cells. Among these 13 genes, we focused on GADD45b. GADD45b was over-expressed in non-SP cells, but the inhibition of GADD45b had no effect on non-SP cells. Paradoxically, the inhibition of GADD45b significantly reduced the viability of NEC8 SP cells. The inhibition of ABCG2, which determines the SP phenotype, had no effect on the invasiveness of NEC8 SP cells, but the inhibition of GADD45b significantly reduced invasiveness. These results suggest that GADD45b, but not ABCG2, might determine the cancer stem cell-like phenotype, such as chemoresistance and the high invasiveness of NEC8 SP cells, and might be a good therapeutic target.

  2. Mitochondrial DNA deletion mutations in adult mouse cardiac side population cells

    Energy Technology Data Exchange (ETDEWEB)

    Lushaj, Entela B., E-mail: [Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792 (United States); Lozonschi, Lucian; Barnes, Maria; Anstadt, Emily; Kohmoto, Takushi [Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792 (United States)


    We investigated the presence and potential role of mitochondrial DNA (mtDNA) deletion mutations in adult cardiac stem cells. Cardiac side population (SP) cells were isolated from 12-week-old mice. Standard polymerase chain reaction (PCR) was used to screen for the presence of mtDNA deletion mutations in (a) freshly isolated SP cells and (b) SP cells cultured to passage 10. When present, the abundance of mtDNA deletion mutation was analyzed in single cell colonies. The effect of different levels of deletion mutations on SP cell growth and differentiation was determined. MtDNA deletion mutations were found in both freshly isolated and cultured cells from 12-week-old mice. While there was no significant difference in the number of single cell colonies with mtDNA deletion mutations from any of the groups mentioned above, the abundance of mtDNA deletion mutations was significantly higher in the cultured cells, as determined by quantitative PCR. Within a single clonal cell population, the detectable mtDNA deletion mutations were the same in all cells and unique when compared to deletions of other colonies. We also found that cells harboring high levels of mtDNA deletion mutations (i.e. where deleted mtDNA comprised more than 60% of total mtDNA) had slower proliferation rates and decreased differentiation capacities. Screening cultured adult stem cells for mtDNA deletion mutations as a routine assessment will benefit the biomedical application of adult stem cells.

  3. Characterization of Side Cell Populations Obtained from Human Amnion Mesenchymal Cells

    Institute of Scientific and Technical Information of China (English)

    LI Ning; PIAO Zhengfu; Mamoru Kobayashi; Koji Sasaki; DING Shu-qin; Aiko Kikuchi; Isao Kamo; Norio Sakuragawa


    Human amnion mesenchymal cells (AMCs) contain multipotent cells. To enrich such multipotent stem cells, we applied to AMCs the new method for the isolation of side population (SP) cells used for the enrichment of multipotent stem cells from many tissues. We succeeded in obtaining SP cells from AMCs (AMC-SP cells). AMC-SP cells were found in 0.2% of AMCs, irrespective of the length of pregnant period, ranging from 37 to 40 weeks. Cell cycle analyses uggested that AMC-SP cells belonged to a cell population that proliferated very slowly and/or was in a quiescent state in the amniotic membrane. Upon culturing, they proliferated with 40 to 80 cell doublings. However, they did not form colonies in a soft agarose culture, whereas HepG2 cells, representative human hepatoma cells formed many large colonies. These results suggest that AMC-SP cells that have considerable value for the use of regenerative medicine can be managed safely in vitro.

  4. Human endometrial side population cells exhibit genotypic, phenotypic and functional features of somatic stem cells.

    Directory of Open Access Journals (Sweden)

    Irene Cervelló

    Full Text Available During reproductive life, the human endometrium undergoes around 480 cycles of growth, breakdown and regeneration should pregnancy not be achieved. This outstanding regenerative capacity is the basis for women's cycling and its dysfunction may be involved in the etiology of pathological disorders. Therefore, the human endometrial tissue must rely on a remarkable endometrial somatic stem cells (SSC population. Here we explore the hypothesis that human endometrial side population (SP cells correspond to somatic stem cells. We isolated, identified and characterized the SP corresponding to the stromal and epithelial compartments using endometrial SP genes signature, immunophenotyping and characteristic telomerase pattern. We analyzed the clonogenic activity of SP cells under hypoxic conditions and the differentiation capacity in vitro to adipogenic and osteogenic lineages. Finally, we demonstrated the functional capability of endometrial SP to develop human endometrium after subcutaneous injection in NOD-SCID mice. Briefly, SP cells of human endometrium from epithelial and stromal compartments display genotypic, phenotypic and functional features of SSC.

  5. CE法测定CD45-FITC荧光抗体溶液中的游离FITC%Determination of free fluorescein isothiocyanate in CD45-FITC fluorescent antibody by capillary electrophoresis

    Institute of Scientific and Technical Information of China (English)

    薛洪宝; 张晖; 李柏青; 梁丽丽; 陶兆林


    建立了测定CD45-FITC荧光抗体样品溶液中游离FITC浓度的毛细管电泳( CE)方法。熔融石英毛细管45 cm(有效长度30 cm)×75μm i. d.;0.05 mol·L-1磷酸氢二钠-磷酸二氢钠缓冲液(含5g·L-1 PEG4000,pH=7.14);分离电压+12 kV;进样压力0.5 psi(3.45 kPa),进样时间3.0 s;分离温度25℃;UV-Vis检测器检测波长200 nm。该方法能有效测定CD45-FITC荧光抗体样品溶液中游离的FITC含量,线性回归方程相关系数r=0.9900,检测限LOQ=0.20μg·mL-1。样品加标回收率为105.49%,相对标准偏差小于5.36%。该方法快速、灵敏、重现性好,能用于CD45-FITC荧光抗体样品溶液中游离FITC的快速测定。%A rapid capillary electrophoresis ( CE ) method was developed for the determination of free fluorescein isothiocyanate ( FITC) in CD45-FITC fluorescent antibodysolution. The analyses were carried out on a CE system equipped with an UV-Vis detector and a PDA detector. Separation was performed in a bare fused-silica capillary of 45. 0 cm long ( 30. 0 cm to the detector,75μm i. d. )at 25℃,and a 0. 05 mol·L-1 disodium hydrogen phosphate-sodium dihydrogen phosphate buffer solution(containing 5g·L-1 PEG4000,pH=7. 14)was used as background electrolyte. The samples were introduced into the capillary under a pressure of 0. 5 psi(3. 45 kPa) for 3 s,and the separation voltage was set at+12 kV. The detection wavelength was fixed at 200 nm. In this ap-proach,FITC could be determined in CD45-FITC fluorescent antibody solution. The correlation coefficient for linear regression equa-tion(r)for FITC standard sample was above 0. 9900. The detection limit was about 0. 20μg·mL-1. The spiked recoveries were about 105. 49%,and the relative standard deviation was kept within 5. 36%. The method is simple,sensitive,rapid,reliable and reproduc-ible. It can be applied for the determination of FITC in CD45-FITC fluorescent antibodysolution.

  6. MiR-888 regulates side population properties and cancer metastasis in breast cancer cells. (United States)

    Huang, Shengjian; Chen, Liangbiao


    Cancer stem cells (CSCs) have recently been reported to possess properties related to cancer metastasis. However, the mechanism by which microRNAs (miRNAs) regulate these properties remains unclear. This study aims to investigate a correlation between miRNAs and the side population (SP) of human breast cancer cell line MCF-7 with CSC properties. miR-888 was found in our previous study to be up-regulated in SP cells and predicted to target E-Cadherin directly, indicating a potential role in maintaining SP properties and regulating the epithelial-mesenchymal transition (EMT) and cancer metastasis. After the over-expression of miR-888 in MCF-7 cells and knock-down of its expression in SP cells, we found that miR-888 played a role in maintaining CSC-related properties. Next, miR-888 was found to regulate the EMT process by targeting related gene expression. Lastly, MCF-7 cells over-expressing miR-888 exhibited a significant reduction in their ability to adhere to the extracellular matrix and an increased potential for migration and invasion, whereas knock-down of miR-888 expression in SP cells reversed these trends. In conclusion, miR-888 maintains SP properties and regulates EMT and metastasis in MCF-7 cells, potentially by targeting E-Cadherin expression.

  7. Side Population Cells as Prototype of Chemoresistant, Tumor-Initiating Cells

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    Vinitha Richard


    Full Text Available Classically, isolation of CSCs from tumors exploits the detection of cell surface markers associated with normal stem cells. Invariable expression of these cell surface markers in almost all proliferating tumor cells that albeit impart specific functionality, the universality, and clinical credibility of CSC phenotype based on markers is still dubious. Side Population (SP cells, as defined by Hoechst dye exclusion in flow cytometry, have been identified in many solid tumors and cell lines and the SP phenotype can be considered as an enriched source of stem cells as well as an alternative source for the isolation of cancer stem cells especially when molecular markers for stem cells are unknown. SP cells may be responsible for the maintenance and propagation of tumors and the proportion of SP cells may be a predictor of patient outcome. Several of these markers used in cell sorting have emerged as prognostic markers of disease progression though it is seen that the development of new CSC-targeted strategies is often hindered by poor understanding of their regulatory networks and functions. This review intends to appraise the experimental progress towards enhanced isolation and drug screening based on property of acquired chemoresistance of cancer stem cells.

  8. A role for matrix stiffness in the regulation of cardiac side population cell function. (United States)

    Qiu, Yiling; Bayomy, Ahmad F; Gomez, Marcus V; Bauer, Michael; Du, Ping; Yang, Yanfei; Zhang, Xin; Liao, Ronglih


    The mechanical properties of the local microenvironment may have important influence on the fate and function of adult tissue progenitor cells, altering the regenerative process. This is particularly critical following a myocardial infarction, in which the normal, compliant myocardial tissue is replaced with fibrotic, stiff scar tissue. In this study, we examined the effects of matrix stiffness on adult cardiac side population (CSP) progenitor cell behavior. Ovine and murine CSP cells were isolated and cultured on polydimethylsiloxane substrates, replicating the elastic moduli of normal and fibrotic myocardium. Proliferation capacity and cell cycling were increased in CSP cells cultured on the stiff substrate with an associated reduction in cardiomyogeneic differentiation and accelerated cell ageing. In addition, culture on stiff substrate stimulated upregulation of extracellular matrix and adhesion proteins gene expression in CSP cells. Collectively, we demonstrate that microenvironment properties, including matrix stiffness, play a critical role in regulating progenitor cell functions of endogenous resident CSP cells. Understanding the effects of the tissue microenvironment on resident cardiac progenitor cells is a critical step toward achieving functional cardiac regeneration.


    Directory of Open Access Journals (Sweden)

    A. A. Gutsol


    Full Text Available Abstract. The aim of our study was to evaluate effects of steroid hormones upon the imbalance of Th1/Th2 cytokine production (IL-2, IFNγ, IL-4, IL-10 by CD45RO+ activated lymphocytes. In our experiments, we have shown a clear trend of multidirectional influence of steroid hormones upon secretory activity of T-lymphocytes. We have revealed that development of cellular immune responses mediated by type 1 T helper cells is regulated primarily by female sex hormones. Glucocorticoid hormones seem to exert a marked effect upon development of humoral Th2 immune response. For androgens, some controversial results have been obtained.

  10. Cigarette smoke promotes drug resistance and expansion of cancer stem cell-like side population. (United States)

    An, Yi; Kiang, Alan; Lopez, Jay Patrick; Kuo, Selena Z; Yu, Michael Andrew; Abhold, Eric L; Chen, Jocelyn S; Wang-Rodriguez, Jessica; Ongkeko, Weg M


    It is well known that many patients continue to smoke cigarettes after being diagnosed with cancer. Although smoking cessation has typically been presumed to possess little therapeutic value for cancer, a growing body of evidence suggests that continued smoking is associated with reduced efficacy of treatment and a higher incidence of recurrence. We therefore investigated the effect of cigarette smoke condensate (CSC) on drug resistance in the lung cancer and head and neck cancer cell lines A549 and UMSCC-10B, respectively. Our results showed that CSC significantly increased the cellular efflux of doxorubicin and mitoxantrone. This was accompanied by membrane localization and increased expression of the multi-drug transporter ABCG2. The induced efflux of doxorubicin was reversed upon addition of the specific ABCG2 inhibitor Fumitremorgin C, confirming the role of ABCG2. Treatment with CSC increased the concentration of phosphorylated Akt, while addition of the PI3K inhibitor LY294002 blocked doxorubicin extrusion, suggesting that Akt activation is required for CSC-induced drug efflux. In addition, CSC was found to promote resistance to doxorubicin as determined by MTS assays. This CSC-induced doxurbicin-resistance was mitigated by mecamylamine, a nicotinic acetylcholine receptor inhibitor, suggesting that nicotine is at least partially responsible for the effect of CSC. Lastly, CSC increased the size of the side population (SP), which has been linked to a cancer stem cell-like phenotype. In summary, CSC promotes chemoresistance via Akt-mediated regulation of ABCG2 activity, and may also increase the proportion of cancer stem-like cells, contributing to tumor resilience. These findings underscore the importance of smoking cessation following a diagnosis of cancer, and elucidate the mechanisms of continued smoking that may be detrimental to treatment.

  11. Cigarette smoke promotes drug resistance and expansion of cancer stem cell-like side population.

    Directory of Open Access Journals (Sweden)

    Yi An

    Full Text Available It is well known that many patients continue to smoke cigarettes after being diagnosed with cancer. Although smoking cessation has typically been presumed to possess little therapeutic value for cancer, a growing body of evidence suggests that continued smoking is associated with reduced efficacy of treatment and a higher incidence of recurrence. We therefore investigated the effect of cigarette smoke condensate (CSC on drug resistance in the lung cancer and head and neck cancer cell lines A549 and UMSCC-10B, respectively. Our results showed that CSC significantly increased the cellular efflux of doxorubicin and mitoxantrone. This was accompanied by membrane localization and increased expression of the multi-drug transporter ABCG2. The induced efflux of doxorubicin was reversed upon addition of the specific ABCG2 inhibitor Fumitremorgin C, confirming the role of ABCG2. Treatment with CSC increased the concentration of phosphorylated Akt, while addition of the PI3K inhibitor LY294002 blocked doxorubicin extrusion, suggesting that Akt activation is required for CSC-induced drug efflux. In addition, CSC was found to promote resistance to doxorubicin as determined by MTS assays. This CSC-induced doxurbicin-resistance was mitigated by mecamylamine, a nicotinic acetylcholine receptor inhibitor, suggesting that nicotine is at least partially responsible for the effect of CSC. Lastly, CSC increased the size of the side population (SP, which has been linked to a cancer stem cell-like phenotype. In summary, CSC promotes chemoresistance via Akt-mediated regulation of ABCG2 activity, and may also increase the proportion of cancer stem-like cells, contributing to tumor resilience. These findings underscore the importance of smoking cessation following a diagnosis of cancer, and elucidate the mechanisms of continued smoking that may be detrimental to treatment.

  12. Sorting and biological characteristics analysis for side population cells in human primary hepatocellular carcinoma (United States)

    Jiang, Yegui; Gao, Hucheng; Liu, Mingdong; Mao, Qing


    Hepatocellular carcinoma (HCC) is the fifth most common cause of the tumor worldwide, its incidence is increasing year by year. This study aims to investigate the sorting and biological characteristics of side population (SP) cells. Human HCC tissues used were obtained from patients undergoing surgical resection. SP cells were sorted using flow cytometry. Cell cycle assay, apoptosis assay and colony formation assay were performed to detect cell proliferation and apoptosis. Invasion assay was employed to examine SP cell invasion. Tumorigenicity assay was used to evaluate tumorigenicity. HCC related microRNAs (miRNA) were analyzed using Micro-array analysis. Target genes were predicted using miRNA database. GO analsis was employed to predict target gene function. Apoptosis percentage was lower and cell viability was higher in SP cells than non-SP (NSP) cells. Colony forming ability of SP cells was significantly higher than NSP cells. Transwell assay positive cells in SP cells were higher significantly than NSP cells. Tumorigenicity of SP cells was higher significantly than NSP cells. 107 differentially expression miRNA were discovered, including 45 up-expressed miRNAs and 62 down-expressed miRNAs in SP cells. Up-regulated hsa-miR-193b-3p and hsa-miR-505-3p predict 25 and 35 target genes, and correlated with 4 and 42 GO terms, respectively. Down-regulated hsa-miR-200a-3p, hsa-miR-194-5p, hsa-miR-130b-3p predict 133, 48 and 127 target genes, and correlate with 10, 7 and 109 GO terms, respectively. In conclusion, proliferation, colony formation, anti-apoptosis, self-renewal capavility, invasive characteristic and tumorigenicity in SP cells isolated from HCC tissues was higher compared to NSP cells. Therefore, sorted SP cells could characterize with biological functions of cancer stem cells.

  13. Effect of Bcl-2 and Bax on survival of side population cells from hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)


    AIM: To understand the role and significance of side population (SP) cells from hepatocellular carcinoma (HCC) in hepatocarcinogenesis, development, relapse and metastasis, we simulated the denutrition conditions that cancer cells experience in clinical therapy, observed the different anti-apoptosis ability of SP cells and non-SP cells under such conditions, and established the possible effects of P53, Bcl-2 and Bax on survival of SP cells.METHODS: We used flow cytometry to analyze and sort the SP and non-SP cells in established HCC lines MHCC97and hHCC. We evaluated cell proliferation by methyl thiazolyl tetrazolium (MTT) assay and investigated the expression of p53, bd-2 and bax genes during denutrition,by RT-PCR and immunofluorescence staining.RESULTS: The percentage of SP cells in the two established HCC lines was 0.25% and 0.5%, respectively.SP cells had greater anti-apoptosis and proliferation ability than non-SP cells. Expression of Bcl-2 and Bax in SP and non-SP cells differed during denutrition. The former was up-regulated in SP cells, and the latter was up-regulated in non-SP cells.CONCLUSION: It may be that different upstream molecules acted and led to different expression levels of Bcl-2 and Bax in these two cell lines. There was a direct relationship between up-regulation of Bcl-2 and down-regulation of Bax and higher anti-apoptosis ability in SP cells. It may be that the existence and activity of SP cells are partly responsible for some of the clinical phenomena which are seen in HCC, such as relapse or metastasis. Further research on SP cells may have potential applications in the field of anticancer therapy.

  14. Identification and Characterization of Side Population Cells in Human Lung Adenocarcinoma SPC-A1 Cells

    Institute of Scientific and Technical Information of China (English)

    Yan-liang Zhu; Long-bang Chen; Jing-hua Wang; Xin-yi Xia


    Objective: There has been an increasing interest in recent years in the role of stem cells.With an extensive understanding of their biology,a major role for stem cells in the malignant process has been proposed and the existence of cancer stem cells(CSCs) has been confirmed in hematopoietic malignancies and solid organ malignancies including brain cancer,breast,prostate,colon,and pancreatic cancer.Lung cancer is the leading cause of cancer mortality in most large cities of China.It is possible that lung cancer contains cancer stem cells responsible for its malignancy.The aim of this study is to identify,characterize and enrich the CSC population that drives and maintains lung adenocarcinoma growth and metastasis.Methods: Side population(SP) cell analysis and sorting were applied on human lung adenocarcinoma cell line and an attempt to further enrich them by preliminary serum-free culture before fluorescence activated cell sorting (FACS) was done.Stem cell properties of SP cells were evaluated by their proliferative index,colony-forming efficiency,tumorigenic potential,bi-differentiation capacity and the expression of common stem cell surface markers.Results: Lung cancer cells could grow in a serum-free Medium(SFM) as non-adherent spheres similar to neurospheres or mammospheres.The proportion of SP cells in cell spheres was significantly higher than that in cells grown as monolayers.SP cells had a greater proliferative index,a higher colony-forming efficiency and a greater ability to form tumor in vivo.SP cells were both CCA positive and SP-C positive while non-SP cells were only SP-C positive.Flow cytometric analysis of cell phenotype showed that SP cells expressed CD133 and CD44,the common cell surface markers of cancer stem cells,while non-SP cells only expressed CD44.Conclusion: SP cells existed in human lung adenocarcinoma cell lines and they could be further enriched by preliminary serum-free culture before FACS sorting.SP cells possessed the properties of

  15. Identification and Characterization of Side Population Cells in Human Lung Adenocarcinoma SPC-A1 Cells

    Institute of Scientific and Technical Information of China (English)

    Yan-liang Zhu; Long-bang Chen; Jing-hua Wang; Xin-yi Xia


    Objective:There has been an increasing interest in recent years in the role of stem cells.With an extensive understanding of their biology,a major role for stem cells in the malignant process has been proposed and the existence of cancer stem cells(CSCs)has been confirmed in hematopoietic malignancies and solid organ malignancies including brain cancer,breast,prostate,colon,and pancreatic cancer.Lung cancer is the leading cause of cancer mortality in most large cities of China.It is possible that lung cancer contains cancer stem cells responsible for its malignancy.The aim of this study is to identify,characterize and enrich the CSC population that drives and maintains lung adenocarcinoma growth and metastasis.Methods:Side population(SP)cell analysis and sorting were applied on human lung adenocarcinoma cell line and an attempt to further enrich them by preliminary serum-free culture before fluorescence activated cell sorting(FACS)was done.Stem cell properties of SP cells were evaluated by their proliferative index,colony-forming efficiency,tumorigenic potential,bi-differentiation capacity and the expression of common stem cell surface markers.Results:Lung cancer cells could grow in a serum-free Medium(SFM)as non-adherent spheres similar to neurospheres or mammospheres.The proportion of SP cells in cell spheres was significantly higher than that in cells grown as monolayers.SP cells had a greater proliferative index,a higher colony-forming efficiency and a greater ability to form tumor in vivo.SP cells were both CCA positive and SP-C positive while non-SP cells were only SP-C positive.Flow cytometric analysis of cell phenotype showed that SP cells expressed CD133 and CD44,the common cell surface markers of cancer stem cells,while non-SP cells only expressed CD44.Conclusion:SP cells existed in human lung adenocarcinoma cell lines and they could be further enriched by preliminary serum-free culture before FACS sorting.SP cells possessed the properties of cancer stem

  16. Increased CD45RA+ FoxP3(low regulatory T cells with impaired suppressive function in patients with systemic lupus erythematosus.

    Directory of Open Access Journals (Sweden)

    Xiujun Pan

    Full Text Available BACKGROUND: The role of naturally occurring regulatory T cells (Treg in the control of the development of systemic lupus erythematosus (SLE has not been well defined. Therefore, we dissect the phenotypically heterogeneous CD4(+FoxP3(+ T cells into subpopulations during the dynamic SLE development. METHODLOGY/PRINCIPAL FINDINGS: To evaluate the proliferative and suppressive capacities of different CD4(+ T cell subgroups between active SLE patients and healthy donors, we employed CD45RA and CD25 as surface markers and carboxyfluorescein diacetatesuccinimidyl ester (CFSE dilution assay. In addition, multiplex cytokines expression in active SLE patients was assessed using Luminex assay. Here, we showed a significant increase in the frequency of CD45RA(+FoxP3(low naive Treg cells (nTreg cells and CD45RA(-FoxP3(low (non-Treg cells in patients with active SLE. In active SLE patients, the increased proportions of CD45RA(+FoxP3(low nTreg cells were positively correlated with the disease based on SLE disease activity index (SLEDAI and the status of serum anti-dsDNA antibodies. We found that the surface marker combination of CD25(+CD45RA(+ can be used to defined CD45RA(+FoxP3(low nTreg cells for functional assays, wherein nTreg cells from active SLE patients demonstrated defective suppression function. A significant correlation was observed between inflammatory cytokines, such as IL-6, IL-12 and TNFα, and the frequency of nTreg cells. Furthermore, the CD45RA(+FoxP3(low nTreg cell subset increased when cultured with SLE serum compared to healthy donor serum, suggesting that the elevated inflammatory cytokines of SLE serum may promote nTreg cell proliferation/expansion. CONCLUSIONS/SIGNIFICANCE: Our results indicate that impaired numbers of functional CD45RA(+FoxP3(low naive Treg cell and CD45RA(-FoxP3(low non-suppressive T cell subsets in inflammatory conditions may contribute to SLE development. Therefore, analysis of subsets of FoxP3(+ T cells, using a

  17. CD45/CD8 myeloid histioid antigen and plasma cell antibody immune response in a case of malignant melanoma

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu-Velez


    Full Text Available The immune response in metastatic melanoma is not well established and therefore is of particular interest to test for recruitment of immune cells to the tumor. A 46-year-old Caucasian female was evaluated for an asymptomatic right forearm mass. The lesion had been present for at least 4 years and had become painful 4 months ago. Biopsies for hematoxylin and eosin (H and E staining, as well as immunohistochemical analysis were performed on the primary tumor and on sentinel lymph nodes. The H and E staining was consistent with metastatic melanoma. Positive staining was noted on the tumor cells with S-100, Mart-1/Melan A/CD63, PNL2, HMB45, and tyrosinase. Peritumoral and intratumoral inflammatory cells stained positive for CD8, CD45, PCNA, myeloid histoid antigen, antihuman plasma cell antibody, and focal BRCA1. The staining patterns of CD8/CD45, myeloid histoid antigen and plasma cell antibody on inflammatory cells around the melanoma cells suggest an unusual type of immune response.

  18. Protection against bronchiolitis obliterans syndrome is associated with allograft CCR7+ CD45RA- T regulatory cells.

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    Aric L Gregson

    Full Text Available Bronchiolitis obliterans syndrome (BOS is the major obstacle to long-term survival after lung transplantation, yet markers for early detection and intervention are currently lacking. Given the role of regulatory T cells (Treg in modulation of immunity, we hypothesized that frequencies of Treg in bronchoalveolar lavage fluid (BALF after lung transplantation would predict subsequent development of BOS. Seventy BALF specimens obtained from 47 lung transplant recipients were analyzed for Treg lymphocyte subsets by flow cytometry, in parallel with ELISA measurements of chemokines. Allograft biopsy tissue was stained for chemokines of interest. Treg were essentially all CD45RA(-, and total Treg frequency did not correlate to BOS outcome. The majority of Treg were CCR4(+ and CD103(- and neither of these subsets correlated to risk for BOS. In contrast, higher percentages of CCR7(+ Treg correlated to reduced risk of BOS. Additionally, the CCR7 ligand CCL21 correlated with CCR7(+ Treg frequency and inversely with BOS. Higher frequencies of CCR7(+ CD3(+CD4(+CD25(hiFoxp3(+CD45RA(- lymphocytes in lung allografts is associated with protection against subsequent development of BOS, suggesting that this subset of putative Treg may down-modulate alloimmunity. CCL21 may be pivotal for the recruitment of this distinct subset to the lung allograft and thereby decrease the risk for chronic rejection.

  19. Differential requirement for the CD45 splicing regulator hnRNPLL for accumulation of NKT and conventional T cells.

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    Mehmet Yabas

    Full Text Available Natural killer T (NKT cells represent an important regulatory T cell subset that develops in the thymus and contains immature (NK1.1(lo and mature (NK1.1(hi cell subsets. Here we show in mice that an inherited mutation in heterogeneous ribonucleoprotein L-like protein (hnRNPLL(thunder, that shortens the survival of conventional T cells, has no discernible effect on NKT cell development, homeostasis or effector function. Thus, Hnrpll deficiency effectively increases the NKT∶T cell ratio in the periphery. However, Hnrpll mutation disrupts CD45RA, RB and RC exon silencing of the Ptprc mRNA in both NKT and conventional T cells, and leads to a comparably dramatic shift to high molecular weight CD45 isoforms. In addition, Hnrpll mutation has a cell intrinsic effect on the expression of the developmentally regulated cell surface marker NK1.1 on NKT cells in the thymus and periphery but does not affect cell numbers. Therefore our results highlight both overlapping and divergent roles for hnRNPLL between conventional T cells and NKT cells. In both cell subsets it is required as a trans-acting factor to regulate alternative splicing of the Ptprc mRNA, but it is only required for survival of conventional T cells.

  20. Reishi Protein LZ-8 Induces FOXP3(+) Treg Expansion via a CD45-Dependent Signaling Pathway and Alleviates Acute Intestinal Inflammation in Mice. (United States)

    Hsu, Hsien-Yeh; Kuan, Yen-Chou; Lin, Tung-Yi; Tsao, Shu-Ming; Hsu, Jason; Ma, Li-Juan; Sheu, Fuu


    LZ-8, an immunomodulatory protein isolated from Ganoderma lucidum (also known as Ling-Zhi or Reishi), has been shown to promote cell proliferation and IL-2 production in T cells. In this study, we show that LZ-8 induces the expansion of both murine and human CD4(+) T cells into FOXP3(+) regulatory T (Treg) cells. LZ-8 treatment was found to stimulate a 4-fold and a 10-fold expansion in the Treg populations of murine and human primary CD4(+) T cells, respectively. In addition, the expression of CTLA-4 and IL-10 was induced in LZ-8-treated CD4(+) T cells. Using neutralizing antibodies and gene-deficient T-cell lines, we also found that LZ-8 promotes Treg expansion through a CD45-mediated signaling pathway and that the CD18-dependent induction of IL-2 was involved in Treg formation and IL-10 production. The suppressive activity of LZ-8 was confirmed using a murine model of DSS-induced colitis; the disease was alleviated by the adoptive transfer of LZ-8-treated CD4(+) T cells. In conclusion, a new regulatory function for LZ-8 was identified, and the molecular mechanisms underlying this function were elucidated.

  1. Reishi Protein LZ-8 Induces FOXP3+ Treg Expansion via a CD45-Dependent Signaling Pathway and Alleviates Acute Intestinal Inflammation in Mice

    Directory of Open Access Journals (Sweden)

    Hsien-Yeh Hsu


    Full Text Available LZ-8, an immunomodulatory protein isolated from Ganoderma lucidum (also known as Ling-Zhi or Reishi, has been shown to promote cell proliferation and IL-2 production in T cells. In this study, we show that LZ-8 induces the expansion of both murine and human CD4+ T cells into FOXP3+ regulatory T (Treg cells. LZ-8 treatment was found to stimulate a 4-fold and a 10-fold expansion in the Treg populations of murine and human primary CD4+ T cells, respectively. In addition, the expression of CTLA-4 and IL-10 was induced in LZ-8-treated CD4+ T cells. Using neutralizing antibodies and gene-deficient T-cell lines, we also found that LZ-8 promotes Treg expansion through a CD45-mediated signaling pathway and that the CD18-dependent induction of IL-2 was involved in Treg formation and IL-10 production. The suppressive activity of LZ-8 was confirmed using a murine model of DSS-induced colitis; the disease was alleviated by the adoptive transfer of LZ-8-treated CD4+ T cells. In conclusion, a new regulatory function for LZ-8 was identified, and the molecular mechanisms underlying this function were elucidated.

  2. Using species distribution model to estimate the wintering population size of the endangered scaly-sided merganser in China.

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    Qing Zeng

    Full Text Available Scaly-sided Merganser is a globally endangered species restricted to eastern Asia. Estimating its population is difficult and considerable gap exists between populations at its breeding grounds and wintering sites. In this study, we built a species distribution model (SDM using Maxent with presence-only data to predict the potential wintering habitat for Scaly-sided Merganser in China. Area under the receiver operating characteristic curve (AUC method suggests high predictive power of the model (training and testing AUC were 0.97 and 0.96 respectively. The most significant environmental variables included annual mean temperature, mean temperature of coldest quarter, minimum temperature of coldest month and precipitation of driest quarter. Suitable conditions for Scaly-sided Merganser are predicted in the middle and lower reaches of the Yangtze River, especially in Jiangxi, Hunan and Hubei Provinces. The predicted suitable habitat embraces 6,984 km of river. Based on survey results from three consecutive winters (2010-2012 and previous studies, we estimated that the entire wintering population of Scaly-sided Merganser in China to be 3,561 ± 478 individuals, which is consistent with estimate in its breeding ground.

  3. Side population rather than CD133+ cells distinguishes enriched tumorigenicity in hTERT-immortalized primary prostate cancer cells

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    Wolcott Karen


    Full Text Available Abstract Background Subpopulations of cancer cells with the capacity of generating solid tumors have been characterized. In various cancer types, including prostate cancer cells, a side population (SP and CD133-expressing cells have been proposed as containing a population cancer cells with stem-like ability. Therefore the aim of this work was to determine, in prostate cancer cell lines, the frequency and tumorigenic potential of SP and CD133+ cells. Results In vitro 2D colony-forming assay and sphere-forming assay, Flow cytometry analysis and magnetic cell sorting were utilized to sort CD133+, CD133- and Side population (SP cells. Our findings indicate that CD44 and integrin α-6 are uniformly expressed in the hTERT cell lines; however, CD133 is expressed only in a small population (in vitro and in vivo. Additionally, for the hTERT cells, SP rather than CD133 expression showed an 8-fold enhanced tumorigenic potential. The data suggest that SP cells, rather than those with CD133 marker, contain the rare population of CSC capable of producing prostate tumors. Conclusion Collectively, our data suggest that although CD133 is expressed only in a small population of hTERT-immortalized prostate cancer cells, it is not likely to be associated with stem cells, as CD133- and CD133+ cells exhibited similar tumorigenicity. However, SP isolated cells, appear to be enriched with tumorigenic stem-like cells capable of generating palpable tumors.

  4. Severe combined immunodeficiency mouse model of colitis induced by Transfection of CD4+CD45RBhigh T cells%CD4+CD45RBhigh T细胞转入SCID鼠诱导的结肠炎模型

    Institute of Scientific and Technical Information of China (English)

    陆丽华; 冉志华



  5. A novel lectin from Artocarpus lingnanensis induces proliferation and Th1/Th2 cytokine secretion through CD45 signaling pathway in human T lymphocytes. (United States)

    Cui, Bo; Li, Lu; Zeng, Qiyan; Lin, Faquan; Yin, Lijun; Liao, Liejun; Huang, Min; Wang, Jingping


    Lectins are carbohydrate-binding proteins and have been used for purification and characterization of glycoproteins. In this study, a novel 58.9-kDa tetrameric lectin from Artocarpus lingnanensis seeds was purified, characterized, and its mitogenic potential was evaluated. The hemagglutination inhibition assay indicated that Artocarpus lingnanensis lectin (ALL) showed specificity toward galactose. ALL was effectively purified in a single-step using affinity chromatography on a galactose-Sepharose column. ALL showed pH optima between 5.0 and 9.0, and optimal temperature between 20 and 40 °C. ALL triggered proliferation and activation of human T lymphocytes (e.g., CD4(+) T lymphocytes). Flow cytometry and laser scanning confocal microscopy revealed binding of ALL to T cells and colocalized with CD45. Affinity chromatography and Western blot suggested that CD45 isolated from human T cell membrane fraction may be the major receptor of ALL. CD45 blocking antibody attenuated the binding and proliferation of T cells induced by ALL. CD45-PTPase inhibitor dephostatin reduced ALL-induced T cells proliferation and expression of CD25 and pZAP-70. Furthermore, secretion of ALL-induced Th1/Th2 cytokines was blocked with dephostatin. Also, dephostatin inhibited phosphorylation of ALL-mediated activation of ERK and p38MAPK. This study demonstrates the involvement of CD45-mediated signaling in ALL-induced T lymphocyte proliferation and Th1/Th2 cytokine secretion through activation of p38 and ERK.

  6. Demographic perspectives on agrarian transformations and 'surplus populations': supply-side banalities versus redistributive imperatives

    NARCIS (Netherlands)

    A.M. Fischer (Andrew Martín)


    textabstractThis paper frames the discussion of agrarian transformations and 'surplus populations' in the Global South within a political economy and macro-structural consideration of the developmental challenges faced in the context of contemporary rapid population growth. The case is made that the

  7. Enhanced population of side band of {sup 155}Gd in heavy-ion Coulomb excitation

    Energy Technology Data Exchange (ETDEWEB)

    Oshima, Masumi; Hayakawa, Takehito; Hatsukawa, Yuichi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment] [and others


    In the Coulomb excitation of {sup 155}Gd with heavy projectiles, {sup 32}S, {sup 58}Ni and {sup 90}Zr, unexpectedly large enhancement of a positive-parity side band has been observed. This enhancement could not be reproduced by a Coulomb-excitation calculation taking into account the recommended upper limits of E1 or E3 transitions, which are compiled in the whole mass region, and is proportional to the electric field accomplished in the Coulomb-scattering process. (author)

  8. Population pharmacokinetics of melphalan and glutathione S-transferase polymorphisms in relation to side effects. (United States)

    Kühne, A; Sezer, O; Heider, U; Meineke, I; Muhlke, S; Niere, W; Overbeck, T; Hohloch, K; Trümper, L; Brockmöller, J; Kaiser, R


    Melphalan is associated with severe side effects such as mucositis, diarrhea, and myelosuppression. We investigated how much the individual severity of these side effects is predicted by pharmacokinetics. In addition, we studied glutathione S-transferase GSTM1, GSTT1, and GSTP1 polymorphisms in relation to adverse events. A high interindividual pharmacokinetic variability was observed in 84 patients. There was a linear correlation between creatinine and melphalan clearance (P=0.0004). Patients treated with a dose > or = 70 mg/m(2) had a 23-fold increased risk to develop mucositis (P<0.001) and a 12-fold increased risk to develop diarrhea (P<0.001) compared with lower doses. The GSTP1 codon 105 polymorphism may be relevant for development of mucositis and the GSTT1 deletion may predict diarrhea, but these findings require confirmation. Melphalan-induced side effects were significantly dependent only on dose. Therapeutic drug monitoring or genotyping for GST does not appear to be very helpful in optimizing therapy with melphalan.

  9. Concurrent hypermulticolor monitoring of CD31, CD34, CD45 and CD146 endothelial progenitor cell markers for acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Yumi [College of Pharmacy, Seoul National University, 1 Gwanak-Ro, Gwanak Gu, Seoul 151-742 (Korea, Republic of); Nam, Myung Hyun [Department of Laboratory Medicine, Korea University Ansan Hospital, Korea University College of Medicine (Korea, Republic of); Hyuk, Song Woo [Cardiology College of Medicine, Korea University (Korea, Republic of); Yoon, Soo Young [College of Medicine, Korea University, Seoul (Korea, Republic of); Song, Joon Myong, E-mail: [College of Pharmacy, Seoul National University, 1 Gwanak-Ro, Gwanak Gu, Seoul 151-742 (Korea, Republic of)


    Highlights: • We observe EPCs and HPCs in patient for AMI diagnosis. • We detect two EPC subtypes using quantum dot and AOTF. • Quantum dot has narrower emission wavelength range than fluorescence dye. • AOTF provide smaller spectral interference than bandpass filters. • Quantum dot and AOTF are suitable for detecting large number of molecular markers concurrently. - Abstract: The circulating endothelial progenitor cells (EPCs) in blood of acute myocardial infarction (AMI) patient have been monitored in many previous studies. The number of circulating EPC increases in the blood of patients at onset of the AMI. EPC is originated from bone marrow. It performs vessel regeneration. There are many markers used for detecting EPC. Four of these markers, CD31, CD34, CD45, and CD146, were concurrently detected at the single cell level for the identification of EPC in the present preliminary study. The CD45 negative cell sorting was performed to peripheral blood mononuclear cells (PBMCs) acquired from four AMI patients with a magnetic bead sorter, since, EPCs expressed CD45 negative or dim. The resultant PBMC eluents were treated with quantum-antibody conjugates for the probing four different markers of EPCs and then applied to a high-content single cell imaging cytometer using acousto-optical tunable filter (AOTF). The use of quantum dot, with narrow emission wavelength range and AOTF enabling cellular image at a particular single wavelength, is very advantageous for accurate high-content AMI diagnosis based on simultaneous monitoring of many markers. The number of EPC increased as compared with control in three of four AMI patients. In this approach, two EPC subtypes were found, CD31(+), CD34(+), CD45(−/dim), CD146(−) as early outgrowth EPCs and CD31(+), CD34(+), CD45(−/dim), CD146(+) as late outgrowth EPCs. Patient 1 had CD31(+), CD34(+), CD45(−/dim), CD146(+) cells whose percentage was 4.21% of cells. Patient 2 had 2.38% of CD31(+), CD34(+), CD45(

  10. Signal transduction by HLA-DR is mediated by tyrosine kinase(s) and regulated by CD45 in activated T cells

    DEFF Research Database (Denmark)

    Odum, Niels; Martin, P J; Schieven, G L;


    , but the inhibitory effect of CD45 dominated over the enhancing effect of CD4. These data indicate that PTK activation is obligatory for DR-induced (Ca2+)i responses, suggesting a linkage between these pathways in class II signal transduction. This conclusion is consistent with our observation that in activated human...

  11. Blood concentrations of hydroxychloroquine and its desethyl derivative correlate negatively with the percentage of CD45RO+ cells among CD4+ lymphocytes in hydroxychloroquine-treated lupus patients. (United States)

    Sailler, Laurent; Puissant, Bénédicte; Méliani, Pascal; Castex, Jean Olivier; Saivin, Sylvie; Adoue, D; Fournie, B; Arlet, Philippe; Montastruc, Jean-Louis; Lapeyre-Mestre, Maryse; Pourrat, Jacques; Blancher, Antoine


    The objective of the study was to investigate the influence of the blood concentrations of hydroxychloroquine ([HCQ]) and its derivative desethylhydroxychloroquine ([DHCQ]) on lymphocyte activation or differentiation in HCQ-treated lupus patients. We studied the correlations between [HCQ], [DHCQ], and the frequency of various lymphocyte subsets in 58 HCQ-treated lupus patients (mean HCQ dose: 4.93 +/- 1.58 mg/kg/day; mean duration of the disease: 122 +/- 64 months). [HCQ] and [DHCQ] were determined by high-performance liquid chromatography (HPLC). Lymphocyte markers were studied by flow cytometry using monoclonal anti-CD3, -CD4, -CD8, -CD25, -DR, -CD45RA, -CD45RO, -CD19, -CD38, and -CD86 antibodies. sIL2-R serum concentrations were measured by enzyme-linked immunosorbent assay (ELISA). [HCQ] and [DHCQ] were 599.9 ng/mL (median: 529.5; range: 55-1935) and 353.43 (median: 286 ng/mL; range: 118-1090). In a multiple regression analysis, [HCQ] and [DHCQ] were associated with the HCQ prescribed dose in mg/kg/day (P = 0.0002 and P = 0.03) and with compliance to the treatment (P = 0.004 and P = 0.03). We found a negative correlation between [HCQ], [DHCQ], and the CD45RO+ cell frequency among CD3+CD4+ cells (P = 0.03 and P = 0.007, respectively). Other lymphocyte subset markers (LSMs) and sIL2-R concentrations were not significantly associated with [HCQ] or [DHCQ]. In the multiple regression analysis, CD45RO+ expression was negatively influenced by [HCQ] (P = 0.005), and positively influenced by smoking habits (P = 0.005) and age (P = 0.005). Similar results were found in the multivariate model including [DHCQ]. Disease activity and taking more than 10 mg/day of corticosteroids or an immunosuppressive drug did not influence CD45RO+ expression. Lupus patients had less CD3+CD4+CD45RO+ cells than controls (P = 0.03). In lupus patients, HCQ and DHCQ may alter the generation or the blood circulation of CD4+CD45RO+ lymphocytes in a concentration-dependent pattern.

  12. Anti-CD45 radioimmunotherapy with 90Y but not 177Lu is effective treatment in a syngeneic murine leukemia model.

    Directory of Open Access Journals (Sweden)

    Johnnie J Orozco

    Full Text Available Radioimmunotherapy (RIT for treatment of hematologic malignancies has primarily employed monoclonal antibodies (Ab labeled with 131I or 90Y which have limitations, and alternative radionuclides are needed to facilitate wider adoption of RIT. We therefore compared the relative therapeutic efficacy and toxicity of anti-CD45 RIT employing 90Y and 177Lu in a syngeneic, disseminated murine myeloid leukemia (B6SJLF1/J model. Biodistribution studies showed that both 90Y- and 177Lu-anti-murine CD45 Ab conjugates (DOTA-30F11 targeted hematologic tissues, as at 24 hours 48.8 ± 21.2 and 156 ± 14.6% injected dose per gram of tissue (% ID/g of 90Y-DOTA-30F11 and 54.2 ± 9.5 and 199 ± 11.7% ID/g of 177Lu-DOTA-30F11 accumulated in bone marrow (BM and spleen, respectively. However, 90Y-DOTA-30F11 RIT demonstrated a dose-dependent survival benefit: 60% of mice treated with 300 µCi 90Y-DOTA-30F11 lived over 180 days after therapy, and mice treated with 100 µCi 90Y-DOTA-30F11 had a median survival 66 days. 90Y-anti-CD45 RIT was associated with transient, mild myelotoxicity without hepatic or renal toxicity. Conversely, 177Lu- anti-CD45 RIT yielded no long-term survivors. Thus, 90Y was more effective than 177Lu for anti-CD45 RIT of AML in this murine leukemia model.

  13. Quantitative image cytometry measurements of lipids, DNA, CD45 and cytokeratin for circulating tumor cell identification in a model system (United States)

    Futia, Gregory L.; Qamar, Lubna; Behbakht, Kian; Gibson, Emily A.


    Circulating tumor cell (CTC) identification has applications in both early detection and monitoring of solid cancers. The rarity of CTCs, expected at ~1-50 CTCs per million nucleated blood cells (WBCs), requires identifying methods based on biomarkers with high sensitivity and specificity for accurate identification. Discovery of biomarkers with ever higher sensitivity and specificity to CTCs is always desirable to potentially find more CTCs in cancer patients thus increasing their clinical utility. Here, we investigate quantitative image cytometry measurements of lipids with the biomarker panel of DNA, Cytokeratin (CK), and CD45 commonly used to identify CTCs. We engineered a device for labeling suspended cell samples with fluorescent antibodies and dyes. We used it to prepare samples for 4 channel confocal laser scanning microscopy. The total data acquired at high resolution from one sample is ~ 1.3 GB. We developed software to perform the automated segmentation of these images into regions of interest (ROIs) containing individual cells. We quantified image features of total signal, spatial second moment, spatial frequency second moment, and their product for each ROI. We performed measurements on pure WBCs, cancer cell line MCF7 and mixed samples. Multivariable regressions and feature selection were used to determine combination features that are more sensitive and specific than any individual feature separately. We also demonstrate that computation of spatial characteristics provides higher sensitivity and specificity than intensity alone. Statistical models allowed quantification of the required sensitivity and specificity for detecting small levels of CTCs in a human blood sample.

  14. Sange fra Vestkysten – en overset side af populærmusikken i Danmark

    Directory of Open Access Journals (Sweden)

    Niels Kayser Nielsen


    Full Text Available Det vestjyske musikmiljø, på kysten fra Grænsen til Skagen, henlever en stille tilværelse i den danske kulturelle offentlighed og er med enkelte markante undtagelser næsten ukendt på den populærkulturelle musikscene. Denne artikel er et forsøg på at give mæle til et populærkulturelt marginalområde af Danmark; ikke for at placere det i en offerrolle, men snarere for at komplettere billedet af dansk musikkultur ved at pege på en center/periferi-tilgang. Nærmere bestemt foretages der analyser af de tematikker – kærlighed, politik, arbejde, kristentro, hjemstedsfornemmelse – der er så fremtrædende i den vestjyske musikkultur. Det er en grundtanke, at en opmærksomhed på også denne del af dansk musikliv er ønskværdig i henseende til udformningen af et kulturelt demokrati med henblik på en ligeværdig anerkendelse. 

  15. The effects of CTLA4-Ig on the functions of CD4+ CD45 RO+ T lymphocyte of elderly patients with bronchial asthma%CTLA4-Ig对老年支气管哮喘病人CD4+ CD45 RO+ T细胞功能的影响

    Institute of Scientific and Technical Information of China (English)

    彭丽萍; 左孟华; 吕晓红


    目的 研究老年支气管哮喘病人周围血CD4+ CD45 RO+ T细胞表达IL-4及IL-13的情况及CTLA4-Ig对其影响.方法 用ELISA方法测定老年支气管哮喘病人CD4+ CD45 RO+ T细胞产生IL-4和IL-13的水平及CTLA4-Ig对其影响.结果 老年支气管哮喘病人CD4+ CD45 RO+ T细胞分泌IL-4、IL-13增多,IL-13增多较IL-4更为明显(P<0.01),CTLA4-Ig可有效抑制老年哮喘病人CD4+ CD45 RO+ T细胞分泌IL-4和IL-13(P<0.01).结论 CD4+ CD45 RO+ T细胞产生的IL-4和IL-13在老年哮喘发病中起重要作用,CTLA4-Ig可有效抑制IL-4和IL-13的分泌.

  16. 钾通道阻滞剂对多发性硬化患者CD4+T细胞CCR7及CD45RA表达的影响%Change of CCR7 and CD45RA after blocking of Kv1.3 potassium channel of CD4+T lymphocytes in multiple sclerosis

    Institute of Scientific and Technical Information of China (English)

    任晓暾; 吴卫平; 徐全刚; 黄德晖


    目的 研究Kv1.3钾通道阻滞剂海葵毒素(SHK)阻滞多发性硬化(Ms)患者急性期髓鞘反应性CIM+T淋巴细胞上的Kv1.3钾通道后,细胞表型CCR7、CD45RA表达的变化与疾病的关系.方法 对15例急性期MS患者、15例INF-B-1b治疗缓解期MS患者和15名健康对照的不同状态下的CD4+T淋巴细胞进行CD3、CIM、CCR7、CD45RA的荧光抗体及同型对照标记,用四标流式细胞仪检测3组不同状态下细胞表型CCR7、CD45RA表达的变化.结果 MS急性期组CIM+T细胞以CCR7-CIM5RA-(TEM)表型为主,其变化与病情有明显相关性,髓鞘抗原刺激后此型所占比例明显增高(P<0.05),初始细胞表型CCR7+CD45RA+减少(P<0.05),钾通道阻滞剂SHK对Ms急件期患者髓鞘反应性CD4+TEM表型有明显抑制作用(P<0.05).结论 检测CI4+TEM细胞表型可能对判断病情有一定临床意义,Kv1.3钾通道可能成为治疗MS的新靶点.%Objective To investigate the changes of CCR7 and CD45 RA expression after blocking of the potassium channel Kv1.3 in myelin specific CD4+T lymphocytes and the relation thereof with multiple sclerosis(MS).Methods Peripheral blood mononuclear cells were isolated from 15 activated MS patients.15 INF-B-1b treated MS patients,and 15 normal controls,CIM+T lymphocytes were isolated using positive selection method with anti-CD4-coated magnetic beads.To establish culturing MBP special CD4+Tlymphocyte lines,the different groups of T cell were labeled with CD3,CD4,CCR7,and CD45RA fluorescence-antibody or homotype controls and analyzed by four-color flow cytometer.Results The most part of phenotype in the activated MS patients was CD4+CCR7-CD45 RA-T cells and the percentage was increaged after myelin antigen stimulation(P<0.05),whereas the percentage of CCR7+CD45 RA+T cells was decreased(P<0.05).SHK greatly inhibited CCR7-CD45RA-in activated MS(P<0.05).CCR7-CD45 RA-and CCR7+CD45 RA-were in correlation with expanded disability status scale (EDSS)score (r=0

  17. Anti-CD45 Pretargeted Radioimmunotherapy using Bismuth-213: High Rates of Complete Remission and Long-Term Survival in a Mouse Myeloid Leukemia Xenograft Model

    Energy Technology Data Exchange (ETDEWEB)

    Pagel, John M; Kenoyer, Aimee L; Back, Tom; Hamlin, Donald K; Wilbur, D Scott; Fisher, Darrell R; Park, Steven I; Frayo, Shani; Axtman, Amanda; Orgun, Nural; Orozoco, Johnnie; Shenoi, Jaideep; Lin, Yukang; Gopal, Ajay K; Green, Damian J; Appelbaum, Frederick R; Press, Oliver W


    Pretargeted radioimmunotherapy (PRIT) using an anti-CD45 antibody (Ab)-streptavidin (SA) conjugate and DOTA-biotin labeled with β-emitting radionuclides has been explored as a strategy to decrease relapse and toxicity. α-emitting radionuclides exhibit high cytotoxicity coupled with a short path-length, potentially increasing the therapeutic index and making them an attractive alternative to β-emitting radionuclides for patients with Acute Myeloid Leukemia (AML). Accordingly, we have used 213Bi in mice with human leukemia xenografts. Results demonstrated excellent localization of 213Bi-DOTA-biotin to tumors with minimal uptake into normal organs. After 10 minutes, 4.5 ± 1.1% of the injected dose of 213Bi was delivered per gram of tumor. α imaging demonstrated uniform radionuclide distribution within tumor tissue 45 minutes after 213Bi-DOTA-biotin injection. Radiation absorbed doses were similar to those observed using a β-emitting radionuclide (90Y) in the same model. We conducted therapy experiments in a xenograft model using a single-dose of 213Bi-DOTA-biotin given 24 hours after anti-CD45 Ab-SA conjugate. Among mice treated with anti-CD45 Ab-SA conjugate followed by 800 μCi of 213Bi- or 90Y-DOTA-biotin, 80% and 20%, respectively, survived leukemia-free for >100 days with minimal toxicity. These data suggest that anti-CD45 PRIT using an α-emitting radionuclide may be highly effective and minimally toxic for treatment of AML.

  18. Participation of CD45, NKR-P1A and ANK61 antigen in rat hepatic NK cell (pit cell)-mediated target cell cytotoxicity

    Institute of Scientific and Technical Information of China (English)

    Dian Zhong Luo; David Vermijlen; B lent Ahishali; Vasilis Triantis; Eddie Wisse; Karin Vanderkerken; Peter J.K. Kuppen


    AIM Several triggering receptors have been described to be involved in natural killer (NK) cellmediated target cytotoxicity. In these studies, NK cells derived from blood or spleen were used. Pit cells are liver-specific NK cells that possess a higher level of natural cytotoxicity and a different morphology when compared to blood NK cells. The aim of this study was to characterize the role of the NK-triggering molecules NKR-P1A, ANK61 antigen, and CD45 in pit cell-mediated killing of target cells. METHODS 51 Cr-release and DNA fragmentation were used to quantify target cell lysis and apoptosis, respectively. RESULTS Flow cytometric analysis showed that pit cells expressed CD45, NKR-P1A, and ANK61 antigen. Treatment of pit cells with monoclonal antibody ( mAb ) to CD45 ( ANK74 ) not only inhibited CC531s or YAC-1 target lysis but also apoptosis induced by pit cells. The mAbs to NKRP1A (3.2.3) and ANK61 antigen (ANK61) had no effect on pit cell-mediated CC531s or YAC-1 target cytolysis or apoptosis, while they did increase the Fcγ receptor positive (FcγR+) P815 cytolysis and apoptosis. This enhanced cytotoxicity could he inhibited by 3,4-dichloroisocoumarin, an inhibitor of granzymes. CONCLUSION These results indicate that CD45 participates in pit cell-mediated CC531s and YAC-1 target cytolysis and apoptosis. NKR-P1A and ANK61 antigen on pit cells function as activation structures against FcγR+ P815 cells, which was mediated by the perforin/granzyme pathway.

  19. Identification of a novel population of human cord blood cells with hematopoietic and chondrocytic potential

    Institute of Scientific and Technical Information of China (English)

    Karen E JAY; Anne ROULEAU; T Michael UNDERHILL; Mickie BHATIA


    With the exception of mature erythrocytes, cells within the human hematopoietic system are characterized by the cell surface expression of the pan-leukocyte receptor CD45. Here, we identify a novel subset among mononuclear cord blood cells depleted of lineage commitment markers (Lin-) that are devoid of CD45 expression. Surprisingly, functional examination of Lin-CD45- cells also lacking cell surface CD34 revealed they were capable of multipotential hematopoietic progenitor capacity. Co-culture with mouse embryonic limb bud cells demonstrated that Lin-CD45-CD34- cells were capable of contributing to cartilage nodules and differentiating into human chondrocytes. BMP-4, a mesodermal factor known to promote chondrogenesis, significantly augmented Lin-CD45-CD34- differentiation into chondrocytes.Moreover, unlike CD34+ human hematopoietic stem cells, Lin-CD45-CD34- cells were unable to proliferate or survive in liquid cultures, whereas single Lin-CD45-CD34- cells were able to chimerize the inner cell mass (ICM) of murine blastocysts and proliferate in this embryonic environment. Our study identifies a novel population of Lin-CD45-CD34-cells capable of commitment into both hematopoietic and chondrocytic lineages, suggesting that human cord blood may provide a more ubiquitous source of tissue with broader developmental potential than previously appreciated.

  20. The large ectodomains of CD45 and CD148 regulate their segregation from and inhibition of ligated T-cell receptor. (United States)

    Cordoba, Shaun-Paul; Choudhuri, Kaushik; Zhang, Hao; Bridge, Marcus; Basat, Alp Bugra; Dustin, Michael L; van der Merwe, P Anton


    T-cell receptor (TCR) triggering results in a cascade of intracellular tyrosine phosphorylation events that ultimately leads to T-cell activation. It is dependent on changes in the relative activities of membrane-associated tyrosine kinases and phosphatases near the engaged TCR. CD45 and CD148 are transmembrane tyrosine phosphatases with large ectodomains that have activatory and inhibitory effects on TCR triggering. This study investigates whether and how the ectodomains of CD45 and CD148 modulate their inhibitory effect on TCR signaling. Expression in T cells of forms of these phosphatases with truncated ectodomains inhibited TCR triggering. In contrast, when these phosphatases were expressed with large ectodomains, they had no inhibitory effect. Imaging studies revealed that truncation of the ectodomains enhanced colocalization of these phosphatases with ligated TCR at the immunological synapse. Our results suggest that the large ectodomains of CD45 and CD148 modulate their inhibitory effect by enabling their passive, size-based segregation from ligated TCR, supporting the kinetic-segregation model of TCR triggering.

  1. Colitis-inducing potency of CD4+ T cells in immunodeficient, adoptive hosts depends on their state of activation, IL-12 responsiveness, and CD45RB surface phenotype

    DEFF Research Database (Denmark)

    Claesson, M H; Bregenholt, S; Bonhagen, K


    a late-onset IBD manifest > 20 wk posttransfer. In SCID mice with IBD transplanted with IL-12-responsive CD4+ T cells, the colonic lamina propria CD4+ T cells showed a mucosa-seeking memory/effector CD45RBlow Th1 phenotype abundantly producing IFN-gamma and TNF-alpha. In SCID mice transplanted with IL-12......We studied the induction, severity and rate of progression of inflammatory bowel disease (IBD) induced in SCID mice by the adoptive transfer of low numbers of the following purified BALB/c CD4+ T cell subsets: 1) unfractionated, peripheral, small (resting), or large (activated) CD4+ T cells; 2......-unresponsive STAT-4-/- CD4+ T cells, the colonic lamina propria, mesenteric lymph node, and splenic CD4+ T cells produced very little IFN-gamma but abundant levels of TNF-alpha. The histopathologic appearance of colitis in all transplanted SCID mice was similar. These data indicate that CD45RBhigh and CD45...

  2. Photoperiodic variation in CD45-positive cells and cell proliferation in the mediobasal hypothalamus of the Soay sheep. (United States)

    Hazlerigg, D G; Wyse, C A; Dardente, H; Hanon, E A; Lincoln, G A


    The Earth's solar orbit induces annual climatic changes challenging to survival. Many animals have evolved to cope with seasonal variability through compensatory annual changes in their physiology and behavior, which involve innate long-term timing and photoperiodic synchronization to anticipate the environmental seasonal cycles. Here we considered the potential involvement of cyclical histogenesis in seasonal timing mechanisms in the sheep. Adult Soay rams were established in three distinctive seasonal states by controlled photoperiod exposure. A first group, representing the condition in late spring (long-photoperiod [LP] group), was taken indoors in May and exposed to 4 wks of 16 h light/day (LP). A second group was exposed to 20 wks of LP to establish a late-summer/long-day refractory condition (LPR group). A third group of animals was brought indoors in August and exposed to 4 wks of LP followed by 4 wks of 8 h light/day (short photoperiod [SP]) to establish an autumn-like condition (SP group). At the end of these regimes, we injected 5-bromo-2-deoxyuridine (BrdU), and animals were killed 24 h or 4 wks later. When BrdU was administered 24 h before death, more BrdU-immunopositive cells were detected in the hilus of the hippocampus in LP compared with SP animals, indicative of a higher proliferation rate. When BrdU was administered 4 wks before death, more BrdU-positive cells were detected in the hippocampus under LP, compared with SP, indicating increased cell survival. These mitotic cells were occasionally seen to adopt a neuronal phenotype in the hippocampus, but not in the hypothalamus. Approximately 10% of BrdU-positive cells in the basal hypothalamus coexpressed the pan-leukocytic marker CD45, and showed morphological features and regional distribution consistent with ameboid microglia. Increased numbers of these cells were detected in the region of the median eminence and tuberoinfundibular sulcus of animals kept in SP compared with LP or LPR. These data

  3. Identification of a novel microRNA that regulates the proliferation and differentiation in muscle side population cells. (United States)

    Motohashi, Norio; Alexander, Matthew S; Casar, Juan Carlos; Kunkel, Louis M


    Muscle satellite cells are largely responsible for skeletal muscle regeneration following injury. Side population (SP) cells, which are thought to be muscle stem cells, also contribute to muscle regeneration. SP cells exhibit high mesenchymal potential, and are a possible cell source for therapy of muscular dystrophy. However, the mechanism by which muscle SP cells are committed to differentiation is poorly understood. microRNAs (miRNAs) play key roles in modulating a variety of cellular processes through repression of their mRNA targets. In skeletal muscle, miRNAs are known to be involved in myoblast proliferation and differentiation. To investigate mechanisms of SP cell regulation, we profiled miRNA expression in SP cells and main population (MP) cells in muscles using quantitative real-time polymerase chain reaction-based expression assays. We identified a set of miRNAs that was highly expressed in SP cells as compared with MP cells. One miRNA, miR-128a, was elevated in expression in SP cells, but decreased in expression during continued culture in vitro. Overexpression of miR-128a in SP cells resulted in inhibited cell proliferation. The differentiation potential of SP cells was also decreased when miR-128a was overexpressed. MiR-128a was found to regulate the target genes involved in the regulation of adipogenic-, osteogenic- and myogenic genes that include: PPARγ, Runx1, and Pax3. Overexpression of miR-128a suppressed the activity of a luciferase reporter fused to the 3'-untranslated region of each gene. These results demonstrate that miR-128a contributes to the maintenance of the quiescent state, and it regulates cellular differentiation by repressing individual genes in SP cells.

  4. Characterization of cancer stem-like cells in the side population cells of human gastric cancer cell line MKN-45

    Institute of Scientific and Technical Information of China (English)

    Hai-hong ZHANG; Ai-zhen CAI; Xue-ming WEI; Li DING; Feng-zhi LI; Ai-ming ZHENG; Da-jiang DAI


    Objective:Side population (SP) cells may play a crucial role in tumorigenesis and the recurrence of cancer.Many kinds of cell lines and tissues have demonstrated the presence of SP cells,including several gastric cancer cell lines.This study is aimed to identify the cancer stem-like cells in the SP of gastric cancer cell line MKN-45.Methods:We used fluorescence activated cell sorting (FACS) to sort SP cells in the human gastric carcinoma cell line MKN-45 (cells labeled with Hoechst 33342) and then characterized the cancer stem-like properties of SP cells.Results:This study found that the SP cells had higher clone formation efficiency than major population (MP) cells.Five stemness-related gene expression profiles,including OCT-4,SOX-2,NANOG,CD44,and adenosine triphosphate (ATP)-binding cassette transporters gene ABCG2,were tested in SP and MP cells using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR).Western blot was used to show the difference of protein expression between SP and MP cells.Both results show that there was significantly higher protein expression in SP cells than in MP cells.When inoculated into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice,SP cells show higher tumorigenesis tendency than MP cells.Conclusions:These results indicate that SP cells possess cancer stem cell properties and prove that SP cells from MKN-45 are gastric cancer stem-like cells.

  5. Enhancement of 5-aminolevulinic acid-based fluorescence detection of side population-defined glioma stem cells by iron chelation (United States)

    Wang, Wenqian; Tabu, Kouichi; Hagiya, Yuichiro; Sugiyama, Yuta; Kokubu, Yasuhiro; Murota, Yoshitaka; Ogura, Shun-ichiro; Taga, Tetsuya


    Cancer stem cells (CSCs) are dominantly responsible for tumor progression and chemo/radio-resistance, resulting in tumor recurrence. 5-aminolevulinic acid (ALA) is metabolized to fluorescent protoporphyrin IX (PpIX) specifically in tumor cells, and therefore clinically used as a reagent for photodynamic diagnosis (PDD) and therapy (PDT) of cancers including gliomas. However, it remains to be clarified whether this method could be effective for CSC detection. Here, using flow cytometry-based analysis, we show that side population (SP)-defined C6 glioma CSCs (GSCs) displayed much less 5-ALA-derived PpIX fluorescence than non-GSCs. Among the C6 GSCs, cells with ultralow PpIX fluorescence exhibited dramatically higher tumorigenicity when transplanted into the immune-deficient mouse brain. We further demonstrated that the low PpIX accumulation in the C6 GSCs was enhanced by deferoxamine (DFO)-mediated iron chelation, not by reserpine-mediated inhibition of PpIX-effluxing ABCG2. Finally, we found that the expression level of the gene for heme oxygenase-1 (HO-1), a heme degradation enzyme, was high in C6 GSCs, which was further up-regulated when treated with 5-ALA. Our results provide important new insights into 5-ALA-based PDD of gliomas, particularly photodetection of SP-defined GSCs by iron chelation based on their ALA-PpIX-Heme metabolism. PMID:28169355

  6. Bortezomib reduces the tumorigenicity of multiple myeloma via downregulation of upregulated targets in clonogenic side population cells.

    Directory of Open Access Journals (Sweden)

    Miho Nara

    Full Text Available Side population (SP cells in cancers, including multiple myeloma, exhibit tumor-initiating characteristics. In the present study, we isolated SP cells from human myeloma cell lines and primary tumors to detect potential therapeutic targets specifically expressed in SP cells. We found that SP cells from myeloma cell lines (RPMI 8226, AMO1, KMS-12-BM, KMS-11 express CD138 and that non-SP cells include a CD138-negative population. Serial transplantation of SP and non-SP cells into NOD/Shi-scid IL-2γnul mice revealed that clonogenic myeloma SP cells are highly tumorigenic and possess a capacity for self-renewal. Gene expression analysis showed that SP cells from five MM cell lines (RPMI 8226, AMO1, KMS-12-BM, KMS-11, JJN3 express genes involved in the cell cycle and mitosis (e.g., CCNB1, CDC25C, CDC2, BIRC5, CENPE, SKA1, AURKB, KIFs, TOP2A, ASPM, polycomb (e.g., EZH2, EPC1 and ubiquitin-proteasome (e.g., UBE2D3, UBE3C, PSMA5 more strongly than do non-SP cells. Moreover, CCNB1, AURKB, EZH2 and PSMA5 were also upregulated in the SPs from eight primary myeloma samples. On that basis, we used an aurora kinase inhibitor (VX-680 and a proteasome inhibitor (bortezomib with RPMI 8226 and AMO1 cells to determine whether these agents could be used to selectively target the myeloma SP. We found that both these drugs reduced the SP fraction, though bortezomib did so more effectively than VX-680 due to its ability to reduce levels of both phospho-histone H3 (p-hist. H3 and EZH2; VX-680 reduced only p-hist. H3. This is the first report to show that certain oncogenes are specifically expressed in the myeloma SP, and that bortezomib effectively downregulates expression of their products. Our approach may be useful for screening new agents with which to target a cell population possessing strong tumor initiating potential in multiple myeloma.


    Directory of Open Access Journals (Sweden)

    O. P. Shevchenko


    Full Text Available Aim. To determine the relationship between CD34/CD45 positive cells number in peripheral blood before and after heart transplantation (HTx and plasma level of the biomarkers. Materials and methods. We studied 27 pts. (23 men; 40 ± 13 years with heart failure caused by dilated (17 cases or ischemic cardiomyopathy (10 cases before and after HTx. CD34/CD45 positive cells were measured in peripheral blood before and 2–4 days after the operation by flow cytometry and expressed in number of the cells per 106 events, plasma level of the biomar- kers – by ELISA. Results. The number of CD34/CD45+ cells in pts. with heart failure (224 ± 166 was similar to those in healthy individuals (233 ± 120 and there was no significant difference in the cell number between pts. with dilated (253 ± 188 and ischemic cardiomyopathy (169 ± 100. The cell number did not correlate with age, sex, body weight, blood cells counts and preoperative levels of the biomarkers: PlGF, sCD40L, PAPP-A. In 2–5 days after HTx the cell number decreased to 103 ± 102. The cell number after HTx did not correlate with demographic and laboratory parameters, anesthesia, operation, ischemia and hypothermia duration, blood loss volume and preoperative levels of PlGF and PAPP-A but correlated with sCD40L level in pts. with ischemic cardiomyopathy. Conclusion: Circulating HSC number in patients with heart failure does not differ from those in healthy individuals and decreases after HTx. In patients with ischemic cardiomyopathy the cell number after transplantation associates with preoperative level of sCD40L – the negative predictor of vasculopathy. 


    Directory of Open Access Journals (Sweden)

    Yu. I. Rovda


    Full Text Available Thymectomy is a stage of surgery when treating some congenital heart defects. Thymus gland is the central organ of immune system. This organ is the primary site of T-cell lymphopoiesis and central tolerance to autoantigens during fetal and early postnatal life. If performed neonatally or in infancy, the thymectomy may cause restriction of these immune functions. Suppression of T-cell lymphopoiesis in children with thymectomy can be estimated as a subpopulation of thymic naive T helper cells (CD3+CD4+CD45RA+CD31+. To perform this task, we evaluated subpopulations of thymic naive T helper lymphocytes with CD3+CD4+CD45RA+CD31+ phenotype in the children (n = 40 who underwent thymectomy during surgical treatment of congenital heart diseases in neonates, or in early postnatal life. Their data were compared with children who underwent surgical treatment of congenital heart disease without thymectomy at the same age periods (n = 12, and healthy children (n = 23. We have revealed that thymectomy in frames of surgery of congenital heart disease leads to reduced thymic naive T helper lymphocytes with CD3+CD4+CD45RA+CD31+ phenotype in peripheral blood. Early execution of thymectomy is associated with deficiency of the thymic naive T helper lymphocytes in the peripheral blood, as well as a decrease in T helper cells (CD3+CD4+. The number thymic naive T helper lymphocytes in peripheral blood negatively corrrelated with terms elapsed after the surgery of congenital heart defects in children.

  9. Analysis of CD45- [CD34+/KDR+] endothelial progenitor cells as juvenile protective factors in a rat model of ischemic-hemorrhagic stroke.

    Directory of Open Access Journals (Sweden)

    Julius L Decano

    Full Text Available BACKGROUND: Identification of juvenile protective factors (JPFs which are altered with age and contribute to adult-onset diseases could identify novel pathways for reversing the effects of age, an accepted non-modifiable risk factor to adult-onset diseases. Since endothelial progenitor cells (EPCs have been observed to be altered in stroke, hypertension and hypercholesterolemia, said EPCs are candidate JPFs for adult-onset stroke. A priori, if EPC aging plays a 'master-switch JPF-role' in stroke pathogenesis, juvenile EPC therapy alone should delay stroke-onset. Using a hypertensive, transgenic-hyperlipidemic rat model of spontaneous ischemic-hemorrhagic stroke, spTg25, we tested the hypothesis that freshly isolated juvenile EPCs are JPFs that can attenuate stroke progression and delay stroke onset. METHODOLOGY/PRINCIPAL FINDINGS: FACS analysis revealed that CD45- [CD34+/KDR+] EPCs decrease with progression to stroke in spTg25 rats, exhibit differential expression of the dual endodthelin-1/VEGFsp receptor (DEspR and undergo differential DEspR-subtype specific changes in number and in vitro angiogenic tube-incorporation. In vivo EPC infusion of male, juvenile non-expanded cd45-[CD34+/KDR+] EPCs into female stroke-prone rats prior to stroke attenuated progression and delayed stroke onset (P<0.003. Detection of Y-chromosome DNA in brain microvessels of EPC-treated female spTg25 rats indicates integration of male EPCs into female rat brain microvessels. Gradient-echo MRI showed delay of ischemic-hemorrhagic lesions in EPC-treated rats. Real-time RT-PCR pathway-specific array-analysis revealed age-associated gene expression changes in CD45-[CD34+/KDR]EPC subtypes, which were accelerated in stroke-prone rats. Pro-angiogenic genes implicated in intimal hyperplasia were increased in stroke-prone rat EPCs (P<0.0001, suggesting a maladaptive endothelial repair system which acts like a double-edged sword repairing while predisposing to age

  10. An endogenous inhibitor of angiogenesis inversely correlates with side population phenotype and function in human lung cancer cells. (United States)

    Han, H; Bourboulia, D; Jensen-Taubman, S; Isaac, B; Wei, B; Stetler-Stevenson, W G


    The side population (SP) in human lung cancer cell lines and tumors is enriched with cancer stem cells. An endogenous inhibitor of angiogenesis known as tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), characterized for its ability to inhibit matrix metalloproteinases (MMPs), has been shown by several laboratories to impede tumor progression through MMP-dependent or -independent mechanisms. We recently reported that forced expression of TIMP-2, as well as the modified form Ala+TIMP-2 (that lacks MMP inhibitory activity) significantly blocks growth of A549 human lung cancer cells in vivo. However, the mechanisms underlying TIMP-2 antitumor effects are not fully characterized. Here, we examine the hypothesis that the TIMP-2 antitumor activity may involve regulation of the SP in human lung cancer cells. Indeed, using Hoechst dye efflux assay and flow cytometry, as well as quantitative reverse transcriptase-PCR analysis, we found that endogenous TIMP-2 mRNA levels showed a significant inverse correlation with SP fraction size in six non-small cell lung cancer cell lines. In A549 cells expressing increased levels of TIMP-2, a significant decrease in SP was observed, and this decrease was associated with lowered gene expression of ABCG2, ABCB1 and AKR1C1. Functional analysis of A549 cells showed that TIMP-2 overexpression increased chemosensitivity to cytotoxic drugs. The SP isolated from TIMP-2-overexpressing A549 cells also demonstrated impaired migratory capacity compared with the SP from empty vector control. More importantly, our data provide strong evidence that these TIMP-2 functions occur independent of MMP inhibition, as A549 cells overexpressing Ala+TIMP-2 exhibited identical behavior to those overexpressing TIMP-2 alone. Our findings provide the first indication that TIMP-2 modulates SP phenotype and function, and suggests that TIMP-2 may act as an endogenous suppressor of the SP in human lung cancer cells.

  11. Molecular basis of mouse bone marrow mesenchymal stem cells subsets SCA-1+/CD45+/CD31+ differentation to cardiomyocyte-like cells%小鼠骨髓间充质干细胞SCA-1+/CD45+/CD31+亚群向心肌样细胞分化的分子基础

    Institute of Scientific and Technical Information of China (English)

    贺继刚; 李洪荣; 桂龙升; 李永武; 严丹; 王平


    目的:探讨小鼠骨髓间充质干细胞(mBMSCs)亚群SCA-1+/CD45+/CD31+向心肌样细胞分化的分子基础.方法:以小鼠心脏干细胞表面分化抗原检测mBMSCs后以CD45、CD31为标准分选得到4个亚群.各亚群和心肌细胞共培养后检测α-actin、Cx43、Desmin、cTnI的表达.并采用基因芯片完成Agilent小鼠全基因4* 44K芯片从分子水平对各亚群和心肌细胞共培养结果进行探讨.结果:SCA-1+/CD45+/CD31+亚群和心肌细胞共培养后更易表达出心肌细胞标志性分子.通过Agilent小鼠全基因4*44K芯片将SCA-1+/CD45+/CD31+与其他组的心血管发育基因的聚类分析及Network结果共同比较可见两者无交集,以差异基因均为4倍表达为标准,因而以Network结果为主.可见:SETD2、NCL、EPOR、Rock2为感兴趣基因.结论:mBMSCs为多克隆的细胞群体.SCA-1+/CD45+/CD31+在向心肌定向分化及改善心功能方面优于其他亚群,其分子机制在于SETD2、NCL、EPOR、Rock2基因表达较其他亚组多见.

  12. SPARC, FOXP3, CD8 and CD45 correlation with disease recurrence and long-term disease-free survival in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Angela Chew

    Full Text Available BACKGROUND: SPARC is a matricellular protein involved in tissue remodelling, cell migration and angiogenesis, while forkhead box P3 (FOXP3 protein functions as a transcription factor involved in immune cell regulation. Both SPARC and FOXP3 can play an anti-tumorigenic role in cancer progression. The aim was to determine if SPARC, FOXP3, CD8 and CD45RO expression levels are associated with colorectal cancer (CRC stage, disease outcome and long-term cancer-specific survival (CSS in stage II and III CRC. METHODS AND FINDINGS: SPARC expression was initially assessed in 120 paired normal and stage I-IV CRCs. Subsequently, approximately 1000 paired patient samples of stage II or III CRCs in tissue microarrays were stained for SPARC, FOXP3, CD8 or CD45RO. Proportional hazards modelling assessed correlations between these markers and clinicopathological data, including disease outcome and cancer specific survival (CSS. Both SPARC and FOXP3 expression were significantly greater in CRC than normal colon (p<0.0001. High SPARC expression correlated with good disease outcome (≥60 mths without disease recurrence, p = 0.0039 and better long-term CSS in stage II CRC (<0.0001. In stage III CRC, high SPARC expression correlated with better long-term CSS (p<0.0001 and less adjuvant chemotherapy use (p = 0.01. High FOXP3 correlated with a good disease outcome, better long-term CSS and less adjuvant chemotherapy use in stage II (p<0.0037, <0.0001 and p = 0.04 respectively, but not in stage III CRC. High CD8 and CD45RO expression correlated with better disease outcome in stage II CRC, and better CSS, but the differences were not as marked as for SPARC and FOXP3. CONCLUSIONS: These data suggest that high SPARC and FOXP3 are associated with better disease outcome in stage II CRC and may be prognostic indicators of CSS. Further assessment of whether these markers predict patients at high risk of recurrence with stage II CRC and functional studies of these

  13. 131I-Anti-CD45 Antibody Plus Busulfan and Cyclophosphamide before Allogeneic Hematophoietic Cell Transplantation for Treatment of Acute Myeloid Leukemia in First Remission

    Energy Technology Data Exchange (ETDEWEB)

    Pagel, John M.; Appelbaum, Frederick R.; Eary, Janet F.; Rajendran, Joseph G.; Fisher, Darrell R.; Gooley, Ted; Ruffner, Katherine; Nemecek, Eneida; Sickle, Eileen; Durack, Larry; Carreras, Jeanette; Horowitz, Mary; Press, Oliver W.; Gopal, Ajay K.; Martin, Paul J.; Bernstein, Irwin D.; Matthews, Dana C.


    In an attempt to improve outcomes for patients with acute myeloid leukemia (AML) after allogeneic hematopoietic cell transplantation (HCT), we conducted a Phase I/II study in which targeted irradiation delivered by 131I-anti-CD45 antibody was combined with targeted busulfan (BU; area-under-curve, 600-900 ng/ml) and cyclophosphamide (CY; 120 mg/kg). Fifty-two of 59 patients (88%) receiving a trace 131I-labeled dose of 0.5 mg/kg anti-CD45 murine antibody had higher estimated absorbed radiation in bone marrow and spleen than in any other organ. Forty-six patients were treated with 102-298 mCi 131I delivering an estimated 5.3-19 (mean 11.3) Gy to marrow, 17-72 (mean 29.7) Gy to spleen, and 3.5 Gy (n=4) to 5.25 Gy (n=42) to the liver. The estimated 3-year non-relapse mortality and disease-free survival (DFS) were 21% and 61%, respectively. These results were compared to those from 509 similar International Bone Marrow Transplant Registry patients transplanted using BU/CY alone. After adjusting for differences in age and cytogenetics-risk, the hazard of mortality among all antibody-treated patients was 0.65 times that of the Registry patients (95% CI 0.39-1.08; p=.09). The addition of targeted hematopoietic irradiation to conventional BU/CY is feasible and well tolerated, and Phase II results are sufficiently encouraging to warrant further study.

  14. IgG/IgE bullous pemphigoid with CD45 lymphocytic reactivity to dermal blood vessels, nerves and eccrine sweat glands

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu-Velez


    Full Text Available Context: Bullous pemphigoid (BP, the most common autoimmune blistering disease, is mediated by autoantibodies. BP primarily affects the elderly and is characterized by the development of urticarial plaques surmounted by subepidermal blisters, and the deposition of immunoglobulins and complement at the basement membrane zone (BMZ of the skin. BP is immunologically characterized by the development of autoantibodies targeting two structural proteins of the hemidesmosomes, BP180 (collagen XVII and BP230 (BPAG1. Case Report: A 63 -year-old Caucasian female patient was evaluated for a 4 day history of several itching, erythematous blisters on her extremities. Biopsies for hematoxylin and eosin (H&E examination, as well as Periodic acid-Schiff (PAS, immunohistochemistry (IHC and direct immunofluorescence (DIF analysis were performed. Results: H&E demonstrated a subepidermal blister, with partial re-epithelialization of the blister floor. Within the blister lumen, numerous neutrophils were present, with occasional eosinophils and lymphocytes also noted. Within the dermis, a mild, superficial, perivascular and periadnexal infiltrate of lymphocytes, histiocytes and occasional eosinophils was identified, with mild perivascular leukocytoclastic debris. The PAS stain was positive at the BMZ, and around selected blood vessels, nerves and sweat glands. DIF revealed linear deposits of IgG and Complement/C3 and fibrinogen at the BMZ, and around selected dermal nerves, blood vessels and sweat glands. Strong granular deposits of IgE were also observed, colocalizing with monoclonal antibodies to Collagen IV (CIV. By IHC, positive CD45 staining of lymphocytes was seen surrounding selected dermal blood vessels, eccrine sweat glands, and nerves. Conclusion : The patient displayed IgG, IgE, and fibrinogen autoantibodies against the BMZ, as well as around some dermal nerves and sweat glands; their binding in the skin could trigger complement activation. In addition, the

  15. Evaluating the impact of demand-side management on water resources under changing climatic conditions and increasing population. (United States)

    Dawadi, Srijana; Ahmad, Sajjad


    This study investigated the effect of increasing population and changing climatic conditions on the water resources of a semi-arid region, the Las Vegas Valley (LVV) in southern Nevada. A system dynamics model was developed for the LVV from 1989 to 2035. The impact of climate change on water demand and the water supply from the Colorado River was modeled, using projections from 16 global climate models for 3 emission scenarios. Variability in water demand and supply under different scenarios of population growth and demand management, including water conservation and water pricing, was evaluated. With the population growth that was projected, if no further demand management policies were implemented, the LVV would not be able to meet the water demand in the near future. However, by combining water conservation and pricing policies, the available supply could last well into the future. The reduction in water demand in 2035 was predicted to be 327 million cubic meters (MCM) for 'status quo' population growth, or 30.6%; 408 MCM for 50% of the projected growth, or 38%; and 511 MCM for no population growth, or 47.8%. Water supply reliability decreased significantly with changing climatic conditions. Therefore, major challenges to water sustainability in the LVV would be due to rapid population growth as well as to climate variability. However, with the combination of reduced population growth rate and water conservation policies, the Colorado River supply could meet the future demand of the LVV most of the time.

  16. Energy-restricted diets result in higher numbers of CD4+, CD8+, immunoglobulins (A, M, and G), and CD45RA cells in spleen and CD4+, immunoglobulin A, and CD45RA cells in colonic lamina propria of rats. (United States)

    Nayak, Bob N; Friel, James K; Rempel, Curtis B; Jones, Peter J H


    Dietary energy restriction (ER) offers certain health benefits, particularly when ER is controlled through manipulation of dietary fats. Our hypothesis is that cellular immunity is modulated by dietary ER. Furthermore, we believe that the immune response may differ between spleen and colon because their lymphatic and vascular organization is different. The objective of the study was to test this hypothesis by determining the effects of dietary ER through manipulation of energy intake from high-fat (HF) diets on the expression and frequency of the CD4(+) (T-helper/T-inducer) and CD8(+) (T-cytotoxic/T-suppressor) cells, CD45RA (B-cell-specific marker), and immunoglobulins (Ig) A-, G-, and M-bearing cells in spleen and colon in rats by immunohistochemical method. Rats fed the HF diet had a significantly (P < .05) reduced number of immune cells as compared with those fed ER diets. Energy-restricted diet-fed rats showed higher (P < .05) numbers of CD4(+), CD8(+), IgA, IgM, IgG, and CD45RA cells in spleen and CD4(+), IgA, and CD45RA cells in colonic lamina propria. The IgA-containing cells were markedly higher in the colon compared with the spleen. No change occurred in the number of IgM- and IgG-containing cells in colonic tissues between groups, except for the 20% ER group where IgM-labeled cells were higher (P < .05) compared with HF and 40% ER groups. These findings suggest that ER may modulate adaptive immune function and that CD4(+) and IgA cells may serve as biological indicators for dietary energy-modulated immunoresponse in spleen and colon, respectively.

  17. Crickets are not a free lunch: protein capture from scalable organic side-streams via high-density populations of Acheta domesticus.

    Directory of Open Access Journals (Sweden)

    Mark E Lundy

    Full Text Available It has been suggested that the ecological impact of crickets as a source of dietary protein is less than conventional forms of livestock due to their comparatively efficient feed conversion and ability to consume organic side-streams. This study measured the biomass output and feed conversion ratios of house crickets (Acheta domesticus reared on diets that varied in quality, ranging from grain-based to highly cellulosic diets. The measurements were made at a much greater population scale and density than any previously reported in the scientific literature. The biomass accumulation was strongly influenced by the quality of the diet (p99% mortality without reaching a harvestable size. Therefore, the potential for A. domesticus to sustainably supplement the global protein supply, beyond what is currently produced via grain-fed chickens, will depend on capturing regionally scalable organic side-streams of relatively high-quality that are not currently being used for livestock production.

  18. Application of a four antibody (cMPO/cCD79α/cCD3/CD45) combination to the diagnosis of acute leukemia expressing cross-lineage antigens

    Institute of Scientific and Technical Information of China (English)



    Objective To explore the diagnostic value of intracellular antibody combination in acute leukemia (AL) expressing cross-lineage cell-surface antigens. Methods Flow cytometric immunophenotyping using intracellular antibody combination (cMPO/eCD79α/cCD3/CD45) was performed additionally in 60 patients who expressed

  19. Radiolabeled anti-CD45 antibody with reduced-intensity conditioning and allogeneic transplantation for younger patients with advanced acute myeloid leukemia or myelodysplastic syndrome. (United States)

    Mawad, Raya; Gooley, Ted A; Rajendran, Joseph G; Fisher, Darrell R; Gopal, Ajay K; Shields, Andrew T; Sandmaier, Brenda M; Sorror, Mohamed L; Deeg, Hans Joachim; Storb, Rainer; Green, Damian J; Maloney, David G; Appelbaum, Frederick R; Press, Oliver W; Pagel, John M


    We treated patients under age 50 years with iodine-131 ((131)I)-anti-CD45 antibody combined with fludarabine and 2 Gy total body irradiation to create an improved hematopoietic cell transplantation (HCT) strategy for advanced acute myeloid leukemia or high-risk myelodysplastic syndrome patients. Fifteen patients received 332 to 1561 mCi of (131)I, delivering an average of 27 Gy to bone marrow, 84 Gy to spleen, and 21 Gy to liver. Although a maximum dose of 28 Gy was delivered to the liver, no dose-limiting toxicity was observed. Marrow doses were arbitrarily capped at 43 Gy to avoid radiation-induced stromal damage; however, no graft failure or evidence of stromal damage was observed. Twelve patients (80%) developed grade II graft-versus-host disease (GVHD), 1 patient developed grade III GVHD, and no patients developed grade IV GVHD during the first 100 days after HCT. Of the 12 patients with chronic GVHD data, 10 developed chronic GVHD, generally involving the skin and mouth. Six patients (40%) are surviving after a median of 5.0 years (range, 4.2 to 8.3 years). The estimated survival at 1 year was 73% among the 15 treated patients. Eight patients relapsed, 7 of whom subsequently died. The median time to relapse among these 8 patients was 54 days (range, 26 to 1364 days). No cases of nonrelapse mortality were observed in the first year after transplantation. However, 2 patients died in remission from complications of chronic GVHD and cardiomyopathy, at 18 months and 14 months after transplantation, respectively. This study suggests that patients may tolerate myeloablative doses >28 Gy delivered to the liver using (131)I-anti-CD45 antibody in addition to standard reduced-intensity conditioning. Moreover, the arbitrary limit of 43 Gy to the marrow may be unnecessarily conservative, and continued escalation of targeted radioimmunotherapy doses may be feasible to further reduce relapse.

  20. Aging induced loss of stemness with concomitant gain of myogenic properties of a pure population of CD34(+)/CD45(-) muscle derived stem cells. (United States)

    Bose, Bipasha; Shenoy, P Sudheer


    Aging is accompanied by the functional decline of cells, tissues, and organs, as well as, a striking increase in susceptibility to a wide range of diseases. Within a tissue, both differentiated cells and adult stem cells are susceptible to intrinsic and extrinsic changes while aging. Muscle derived stem cells (MDSCs) are tissue specific stem cells which have been studied well for their multipotential nature. Although there are reports relating to diminished function and regenerative capacity of aged MDSCs as compared to their young counterparts, not much has been reported relating to the concomitant gain in unipotent nature of aged MDSCs. In this study, we report an inverse correlation between aging and expression of adult/mesenchymal stem cell markers and a direct correlation between aging and myogenecity in MDSCs. Aged MDSCs were able to generate a greater number of dystrophin positive myofibres, as compared to, the young MDSCs when transplanted in muscle of dystrophic mice. Our data, therefore, suggests that aging stress adds to the decline in stem cell characteristics with a concomitant increase in unipotency, in terms of, myogenecity of MDSCs. This study, hence, also opens the possibilities of using unipotent aged MDSCs as potential candidates for transplantation in patients with muscular dystrophies.

  1. The physics of the radio emission in the quiet side of the AGN population with the SKA

    CERN Document Server

    Orienti, M; Giroletti, M; Giovannini, G; Panessa, F


    Despite targets of many multiwavelength campaigns, the main physical processes at work in AGN are still under debate. In particular the origin of the radio emission and the mechanisms involved are among the open questions in astrophysics. In the radio-loud AGN population the radio emission is linked to the presence of bipolar outflows of relativistic jets. However, the large majority of the AGN population do not form powerful highly-relativistic jets on kpc scales and are characterized by radio luminosity up to 10^23 W/Hz at 1.4 GHz, challenging our knowledge on the physical processes at the basis of the radio emission in radio-quiet objects. The main mechanisms proposed so far are synchrotron radiation from mildly relativistic mini-jets, thermal cyclo-synchrotron emission by low-efficiency accretion flow (like ADAF or ADIOS), or thermal free-free emission from the X-ray heated corona or wind. The difficulty in understanding the main mechanism involved is related to the weakness of these objects, which preclu...

  2. Inhibitory effect 0f melatonin on the elevation 0f CD45 expression induced by hypoxia in BV-2 microglia%褪黑素对低氧诱导的BV-2小胶质细胞CD45表达增高的抑制作用

    Institute of Scientific and Technical Information of China (English)

    姚景春; 张庆柱; 张世玲; 程艳娜; 纪建波


    目的研究褪黑素对低氧激活的小胶质细胞CD45表达的影响,以探讨褪黑素的抗衰老和抗阿尔茨海默病的作用机制。方法体外培养BV-2小胶质细胞,用终浓度为2.0 mmol·L-1的连二亚硫酸钠作用48 h,造成慢性低氧模型,药物处理组在低氧的同时给予褪黑素。相差显微镜下观察小胶细质胞形态学变化,流式细胞术测定缺氧状态下BV-2小胶质细胞表面CD45的表达;体外培养BV-2小胶质细胞用终浓度为0.01,0.1,1.0 μmol·L-1的褪黑素作用5 min,加入20mg·L-1的脂多糖37℃孵育12 h,Griess试剂法检测培养上清中NO的含量。结果连二亚硫酸钠引起的低氧可明显增加BV-2小胶质细胞CD45的表达,荧光强度增至23.9±14.2(对照组为0.80±0.73),低氧也可使小胶质细胞的形态发生阿米巴样变,而0.01,0.1,1.0 pmol·L-1的褪黑素可剂量依赖性地减少低氧诱导的CD45表达,抑制由低氧引起的小胶质细胞的阿米巴样变。但褪黑素对脂多糖诱导的BV-2小胶质细胞培养液中NO的升高无明显抑制作用。结论褪黑素抑制小胶质细胞的激活与其抗氧化作用密切相关,可能是其抗炎和防治阿尔茨海默病作用的重要理论基础。%AIM To study the action of melatonin on the expression of CDA5 in BV-2 microglia and the influence of melatonin on BV-2 microglia activation so as to explore the antiaging and anti-Alzheimer's disease mechanisms of melatonin.METHODS Hypoxia in cultured BV-2 microglia was induced by sodium dithionite 2.0 mmol· L- 1for 48 h.The expression of CD45 on the BV-2 microglia surface was measured by flow cytometry,the morphological changes of BV-2 microglia were photographed with the phase-contrast microscope.BV-2 microglia were exposed to 20 mg· L-1 lipopolysaccharides 5 min after treated with 0.01,0.1,1.0 μmol· L- 1 of melatonin,then incubated for 12 h.NO level in the medium was determined by Griess reagent.RESULTS The

  3. PLGA-PEG Nanoparticles Coated with Anti-CD45RO and Loaded with HDAC Plus Protease Inhibitors Activate Latent HIV and Inhibit Viral Spread (United States)

    Tang, Xiaolong; Liang, Yong; Liu, Xinkuang; Zhou, Shuping; Liu, Liang; Zhang, Fujina; Xie, Chunmei; Cai, Shuyu; Wei, Jia; Zhu, Yongqiang; Hou, Wei


    Activating HIV-1 proviruses in latent reservoirs combined with inhibiting viral spread might be an effective anti-HIV therapeutic strategy. Active specific delivery of therapeutic drugs into cells harboring latent HIV, without the use of viral vectors, is a critical challenge to this objective. In this study, nanoparticles of poly(lactic-co-glycolic acid)-polyethylene glycol diblock copolymers conjugated with anti-CD45RO antibody and loaded with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and/or protease inhibitor nelfinavir (Nel) were tested for activity against latent virus in vitro. Nanoparticles loaded with SAHA, Nel, and SAHA + Nel were characterized in terms of size, surface morphology, zeta potential, entrapment efficiency, drug release, and toxicity to ACH-2 cells. We show that SAHA- and SAHA + Nel-loaded nanoparticles can target latently infected CD4+ T-cells and stimulate virus production. Moreover, nanoparticles loaded with SAHA + NEL were capable of both activating latent virus and inhibiting viral spread. Taken together, these data demonstrate the potential of this novel reagent for targeting and eliminating latent HIV reservoirs.

  4. IL-18Rα-deficient CD4+T cells induce intestinal inflammation in the CD45RBhitransfer model of colitis despite impaired innate responsiveness

    DEFF Research Database (Denmark)

    Holmkvist, Petra; Pool, Lieneke; Hägerbrand, Karin;


    IL-18 has been implicated in inflammatory bowel disease (IBD), however its role in the regulation of intestinal CD4+ T-cell function remains unclear. Here we show that murine intestinal CD4+ T cells express high levels of IL-18Rα and provide evidence that IL-18Rα expression is induced on these ce......IL-18 has been implicated in inflammatory bowel disease (IBD), however its role in the regulation of intestinal CD4+ T-cell function remains unclear. Here we show that murine intestinal CD4+ T cells express high levels of IL-18Rα and provide evidence that IL-18Rα expression is induced...... on these cells subsequent to their entry into the intestinal mucosa. Using the CD45RBhi T-cell transfer colitis model, we show that IL-18Rα is expressed on IFN-γ+, IL-17+ and IL-17+IFN-γ+ effector CD4+ T cells in the inflamed colonic lamina propria (cLP) and mesenteric lymph node (MLN) and is required...... for the optimal generation and/or maintenance of IFN-γ-producing cells in the cLP. In the steady state and during colitis, TCR-independent cytokine-induced IFN-γ and IL-17 production by intestinal CD4+ T cells was largely IL-18Rα−dependent. Despite these findings however, IL-18Rα−deficient CD4+ T cells induced...

  5. Dose dependent side effect of superparamagnetic iron oxide nanoparticle labeling on cell motility in two fetal stem cell populations.

    Directory of Open Access Journals (Sweden)

    Valentina Diana

    Full Text Available Multipotent stem cells (SCs could substitute damaged cells and also rescue degeneration through the secretion of trophic factors able to activate the endogenous SC compartment. Therefore, fetal SCs, characterized by high proliferation rate and devoid of ethical concern, appear promising candidate, particularly for the treatment of neurodegenerative diseases. Super Paramagnetic Iron Oxide nanoparticles (SPIOn, routinely used for pre-clinical cell imaging and already approved for clinical practice, allow tracking of transplanted SCs and characterization of their fate within the host tissue, when combined with Magnetic Resonance Imaging (MRI. In this work we investigated how SPIOn could influence cell migration after internalization in two fetal SC populations: human amniotic fluid and chorial villi SCs were labeled with SPIOn and their motility was evaluated. We found that SPIOn loading significantly reduced SC movements without increasing production of Reactive Oxygen Species (ROS. Moreover, motility impairment was directly proportional to the amount of loaded SPIOn while a chemoattractant-induced recovery was obtained by increasing serum levels. Interestingly, the migration rate of SPIOn labeled cells was also significantly influenced by a degenerative surrounding. In conclusion, this work highlights how SPIOn labeling affects SC motility in vitro in a dose-dependent manner, shedding the light on an important parameter for the creation of clinical protocols. Establishment of an optimal SPIOn dose that enables both a good visualization of grafted cells by MRI and the physiological migration rate is a main step in order to maximize the effects of SC therapy in both animal models of neurodegeneration and clinical studies.

  6. Lin28a is a putative factor in regulating cancer stem cell-like properties in side population cells of oral squamous cell carcinoma

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    Hayashi, S.; Tanaka, J.; Okada, S.; Isobe, T.; Yamamoto, G.; Yasuhara, R.; Irie, T.; Akiyama, C.; Kohno, Y.; Tachikawa, T.; Mishima, K., E-mail:


    Cancer stem cells (CSCs) are among the target cells of cancer therapy because they are uniquely involved in both cancer progression and sensitivity to chemotherapeutic agents. We identified side population (SP) cells, which are known to be an enriched population of CSC, in five oral squamous cell carcinoma (OSCC) cells (SCC9, SCC25, TOSCC7, TOSCC17, and TOSCC23). The percentages of SP cells ranged from 0% to 3.3%, with TOSCC23 cells showing the highest percentages of SP cells (3.3% of the total cell population). The SP cells isolated from TOSCC23 cells also showed greater cell proliferation and invasion compared to non-SP (MP) cells. Therefore, our initial findings suggested that SP cells were enriched for CSC-like cells. Furthermore, DNA microarray analysis revealed that the expression of cell proliferation-related and anti-apoptotic genes was greater in SP cells compared to MP cells. We focused on Lin28a, which showed the highest expression (approximately 22-fold) among the upregulated genes. The overexpression of Lin28a in TOSCC23 cells increased their proliferation, colony formation, and invasion. These findings suggest that Lin28a is an appropriate CSC target molecule for OSCC treatment - Highlights: ► Lin28a is a SP cell-specific factor in oral squamous cell carcinoma (OSCC) cells. ► SP cells in OSCC cells show cancer stem cell-like properties. ► Lin28a regulates OSCC proliferative and invasive activities.

  7. Stem cell-like differentiation potentials of endometrial side population cells as revealed by a newly developed in vivo endometrial stem cell assay.

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    Kaoru Miyazaki

    Full Text Available BACKGROUND: Endometrial stem/progenitor cells contribute to the cyclical regeneration of human endometrium throughout a woman's reproductive life. Although the candidate cell populations have been extensively studied, no consensus exists regarding which endometrial population represents the stem/progenitor cell fraction in terms of in vivo stem cell activity. We have previously reported that human endometrial side population cells (ESP, but not endometrial main population cells (EMP, exhibit stem cell-like properties, including in vivo reconstitution of endometrium-like tissues when xenotransplanted into immunodeficient mice. The reconstitution efficiency, however, was low presumably because ESP cells alone could not provide a sufficient microenvironment (niche to support their stem cell activity. The objective of this study was to establish a novel in vivo endometrial stem cell assay employing cell tracking and tissue reconstitution systems and to examine the stem cell properties of ESP through use of this assay. METHODOLOGY/PRINCIPAL FINDINGS: ESP and EMP cells isolated from whole endometrial cells were infected with lentivirus to express tandem Tomato (TdTom, a red fluorescent protein. They were mixed with unlabeled whole endometrial cells and then transplanted under the kidney capsule of ovariectomized immunodeficient mice. These mice were treated with estradiol and progesterone for eight weeks and nephrectomized. All of the grafts reconstituted endometrium-like tissues under the kidney capsules. Immunofluorescence revealed that TdTom-positive cells were significantly more abundant in the glandular, stromal, and endothelial cells of the reconstituted endometrium in mice transplanted with TdTom-labeled ESP cells than those with TdTom-labeled EMP cells. CONCLUSIONS/SIGNIFICANCE: We have established a novel in vivo endometrial stem cell assay in which multi-potential differentiation can be identified through cell tracking during in vivo

  8. Expression of CD 68, CD 45 and human leukocyte antigen-DR in central and peripheral giant cell granuloma, giant cell tumor of long bones, and tuberculous granuloma: An immunohistochemical study

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    Anoop Kumar


    Conclusion: CD 68 and CD 45 expression was found in central giant cell granuloma, peripheral giant cell granuloma and GCT, suggesting the origin from mononuclear phagocyte system and considering their clinical behavior of osteoclast type. High expressivity of HLA-DR in tuberculous granulomas which is an essential factor for presentation of the microbial antigen to CD 4 helper cells thus reassuring the fact that they are up-regulated in response to infection.

  9. Side population cells of common tumor%常见恶性肿瘤侧群细胞的研究进展

    Institute of Scientific and Technical Information of China (English)

    朱超; 钱军


    侧群细胞(SP)是指利用荧光染料Hoechst33342外排特性而筛选出来的细胞群体.SP具有肿瘤干细胞特性,在肿瘤的发生、发展中发挥极其重要的作用.目前国内外对于各类常见恶性肿瘤SP都进行了较为广泛的研究.对SP的研究可为肿瘤的诊断和治疗提供新的思路和方法.%Side population cells (SPs) are selected by the efflux features of fluorescent dye Hoechst33342.SPs have the characteristics of cancer stem cells,and play an extremely important role in the occurrence and development of tumors.At present,the SPs in common types of malignant tumor have been studied extensively at home and abroad.The study of SPs may shed some light on the diagnosis and treatment of cancer.

  10. Evaluation of the impact of Exomite Pro on Varroa mite (Varroa destructor) populations and honeybee (Apis mellifera) colonies: efficacy, side effects and residues. (United States)

    Tananaki, Chrysoula; Goras, Georgios; Huggett, Nicola; Karazafiris, Emmanouel; Dimou, Maria; Thrasyvoulou, Andreas


    In this research, we examined the application of thymol-based powder, directly over the top of the brood frames in colonies with different population in a 2-year study. The efficacy against mites, the side effects on bees and the contamination of honey were studied comparably to thymol-based gel treatment. In one-store colonies, thymol-based powder treatment gave average efficacy 64.5% and did not differ significantly from thymol-based gel treatment (65.4%). The natural mortality in control colonies was 41.4% and the corrected efficacy (E T) during 2 years was 39.4 and 40.9%, respectively. In two-store bee colonies, the application of thymol-based powder on top of each hive body gave higher E T (45,4%) than on top of the double body hive (40.4%), without statistically significant differences. The average concentration of thymol residues in honey 24 days after the application was 368 and 1,119 μg kg(-1) for the honey of colonies treated with thymol-based powder and thymol-base gel, respectively.

  11. The effects of ABCG2 on the viability, proliferation and paracrine actions of kidney side population cells under oxygen-glucose deprivation. (United States)

    Liu, Hong-Bao; Meng, Qiu-Hong; Du, De-Wei; Sun, Ji-Feng; Wang, Jian-Bo; Han, Hua


    Bcrp1/ABCG2 is exclusively expressed in side population (SP) cells, however, it has not been fully elucidated whether it has an impact on the viability, proliferation and paracrine actions in kidney SP cells under oxygen-glucose deprivation (OGD) followed by reoxygenation. In this study, we found that 2-h OGD did not injure SP cells (sub-lethal OGD) but induced SP cells proliferation 48 and 72 h after reoxygenation; whereas 4-h OGD markedly injured the cells (lethal OGD) and led to apoptosis 24-72 h after reoxygenation. Fumitremorgin C, an inhibitor of ABCG2, attenuated both the proliferation and viability of SP cells. Sub-lethal and lethal OGD induced the increase in the secretion of vascular endothelial growth factor, insulin-like growth factor 1, hepatocyte growth factor, and stromal cell-derived factor-1α in kidney SP cells, which was inhibited by Fumitremorgin C. Collectively, these findings provide evidence for a crucial role for the ABCG2 expression in the viability, proliferation and paracrine actions of kidney SP cells after OGD.

  12. Up-regulation of lymphocyte antigen 6 complex expression in side-population cells derived from a human trophoblast cell line HTR-8/SVneo. (United States)

    Inagaki, Tetsunori; Kusunoki, Soshi; Tabu, Kouichi; Okabe, Hitomi; Yamada, Izumi; Taga, Tetsuya; Matsumoto, Akemi; Makino, Shintaro; Takeda, Satoru; Kato, Kiyoko


    The continual proliferation and differentiation of trophoblasts are critical for the maintenance of pregnancy. It is well known that the tissue stem cells are associated with the development of tissues and pathologies. It has been demonstrated that side-population (SP) cells identified by fluorescence-activated cell sorting (FACS) are enriched with stem cells. The SP cells in HTR-8/SVneo cells derived from human primary trophoblast cells were isolated by FACS. HTR-8/SVneo-SP cell cultures generated both SP and non-SP (NSP) subpopulations. In contrast, NSP cell cultures produced NSP cells and failed to produce SP cells. These SP cells showed self-renewal capability by serial colony-forming assay. Microarray expression analysis using a set of HTR-8/SVneo-SP and -NSP cells revealed that SP cells overexpressed several stemness genes including caudal type homeobox2 (CDX2) and bone morphogenic proteins (BMPs), and lymphocyte antigen 6 complex locus D (LY6D) gene was the most highly up-regulated in HTR-8/SVneo-SP cells. LY6D gene reduced its expression in the course of a 7-day cultivation in differentiation medium. SP cells tended to reduce its fraction by treatment of LY6D siRNA indicating that LY6D had potential to maintain cell proliferation of HTR-8/SVneo-SP cells. On ontology analysis, epithelial-mesenchymal transition (EMT) pathway was involved in the up-regulated genes on microarray analysis. HTR-SVneo-SP cells showed enhanced migration. This is the first report that LY6D was important for the maintenance of HTR-8/SVneo-SP cells. EMT was associated with the phenotype of these SP cells.

  13. Side population cells isolated from porcine dental pulp tissue with self-renewal and multipotency for dentinogenesis, chondrogenesis, adipogenesis, and neurogenesis. (United States)

    Iohara, Koichiro; Zheng, Li; Ito, Masataka; Tomokiyo, Atsushi; Matsushita, Kenji; Nakashima, Misako


    Dental pulp has the potential to form dentin as a regenerative response to caries. This regeneration is mediated by stem/progenitor cells. Thus, stem cell therapy might be of potential utility in induction of reparative dentin. We isolated side population (SP) cells from dental pulp based on the exclusion of the DNA binding dye Hoechst 33342 by flow cytometry and compared its self-renewal capacities and multipotency with non-SP cells and primary pulp cells. The cumulative cell number of the SP cells was greater than the non-SP cells and primary pulp cells. Bmi1 was continuously expressed in SP cells, suggesting longer proliferative lifespan and self-renewal capacity of SP cells. Next, the maintenance of the multilineage differentiation potential of pulp SP cells was investigated. Expression of type II collagen and aggrecan confirmed chondrogenic conversion (30%) of SP cells. SP cells expressed peroxisome proliferator-activated receptor gamma and adaptor protein 2, showing adipogenic conversion. Expression of mRNA and proteins of neurofilament and neuromodulin confirmed neurogenic conversion (90%). These results demonstrate that pulp SP cells maintain multilineage differentiation potential. We further examined whether bone morphogenetic protein 2 (BMP2) could induce differentiation of pulp SP cells into odontoblasts. BMP2 stimulated the expression of dentin sialophosphoprotein (Dspp) and enamelysin in three-dimensional pellet cultures. Autogenous transplantation of the Bmp2-supplemented SP cells on the amputated pulp stimulated the reparative dentin formation. Thus, adult pulp contains SP cells, which are enriched for stem cell properties and useful for cell therapy with BMP2 for dentin regeneration.

  14. Cisplatin in 5% Ethanol Eradicates Cisplatin-Resistant Lung Tumor by Killing Lung Cancer Side Population (SP Cells and Non-SP Cells

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    Qi eNiu


    Full Text Available Cancer side population (SP cells with cancer stem cell-like properties are thought to be responsible for lung cancer chemotherapy resistance and currently no drug can efficiently target them. Breast cancer resistance protein (BRCP/ABCG2 is a major drug transporter in protecting lung cancer SP cells from cytotoxic agents. We showed that a low concentration of ethanol, which inhibits many membrane proteins, inhibits ABCG2 in lung cancer SP cells. Furthermore, cytotoxic cisplatin (DDP in 5% (vol/vol ethanol kills SP plus non-SP cancer cells better than either treatment alone in eradicating chemoresistant lung tumors. We found that 5% ethanol did not reduce ABCG2 protein levels, but significantly reduced ABCG2 protein function by a Hoechst 33342 extrusion assay, an ATPase activity assay, and transmission electron microscopy. Further, DDP in 5% ethanol (5% ethanol-DDP induced apoptosis of the SP plus non-SP cancer cells both in vitro and in vivo. In DDP-resistant A549/DDP lung tumor-bearing Balb/C nude mice, intratumoral injection of 5% ethanol-DDP regressed tumors and significantly improved survivals compared with 5% ethanol, DDP alone, or control. Intratumoral injection of 5% ethanol-DDP helped eradicate tumors in 30% (3/10 of the mice after 4 weeks treatment. By killing SP and non-SP cancer cells, 5% ethanol-DDP could eradicate DDP-resistant lung tumor and extend survival, providing a novel way to improve chemoresistant lung cancer survival for clinic.

  15. Effects of Withania somnifera and Tinospora cordifolia extracts on the side population phenotype of human epithelial cancer cells: toward targeting multidrug resistance in cancer. (United States)

    Maliyakkal, Naseer; Appadath Beeran, Asmy; Balaji, Sai A; Udupa, Nayanabhirama; Ranganath Pai, Sreedhara; Rangarajan, Annapoorni


    Recent reports suggest the existence of a subpopulation of stem-like cancer cells, termed as cancer stem cells (CSCs), which bear functional and phenotypic resemblance with the adult, tissue-resident stem cells. Side population (SP) assay based on differential efflux of Hoechst 33342 has been effectively used for the isolation of CSCs. The drug resistance properties of SP cells are typically due to the increased expression of ABC transporters leading to drug efflux. Conventionally used chemotherapeutic drugs may often leads to an enrichment of SP, revealing their inability to target the drug-resistant SP and CSCs. Thus, identification of agents that can reduce the SP phenotype is currently in vogue in cancer therapeutics. Withania somnifera (WS) and Tinospora cordifolia (TC) have been used in Ayurveda for treating various diseases, including cancer. In the current study, we have investigated the effects of ethanolic (ET) extracts of WS and TC on the cancer SP phenotype. Interestingly, we found significant decrease in SP on treatment with TC-ET, but not with WS-ET. The SP-inhibitory TC-ET was further fractionated into petroleum ether (TC-PET), dichloromethane (TC-DCM), and n-butyl alcohol (TC-nBT) fractions using bioactivity-guided fractionation. Our data revealed that TC-PET and TC-DCM, but not TC-nBT, significantly inhibited SP in a dose-dependent manner. Furthermore, flow cytometry-based functional assays revealed that TC-PET and TC-DCM significantly inhibited ABC-B1 and ABC-G2 transporters and sensitized cancer cells toward chemotherapeutic drug-mediated cytotoxicity. Thus, the TC-PET and TC-DCM may harbor phytochemicals with the potential to reverse the drug-resistant phenotype, thus improving the efficacy of cancer chemotherapy.

  16. Allogeneic hematopoietic cell transplantation after conditioning with I-131-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome.

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    Pagel, John M.; Gooley, T. A.; Rajendran, Joseph G.; Fisher, Darrell R.; Wilson, Wendy A.; Sandmaier, B. M.; Matthews, D. C.; Deeg, H. Joachim; Gopal, Ajay K.; Martin, P. J.; Storb, R.; Press, Oliver W.; Appelbaum, Frederick R.


    We conducted a study to estimate the maximum tolerated dose (MTD) of I-131-anti-CD45 antibody (Ab; BC8) that can be combined with a standard reduced-intensity conditioning regimen before allogeneic hematopoietic cell transplantation. Fifty-eight patients older than 50 years with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were treated with (131)I-BC8 Ab and fludarabine plus 2 Gy total body irradiation. Eighty-six percent of patients had AML or MDS with greater than 5% marrow blasts at the time of transplantation. Treatment produced a complete remission in all patients, and all had 100% donor-derived CD3(+) and CD33(+) cells in the blood by day 28 after the transplantation. The MTD of I-131-BC8 Ab delivered to liver was estimated to be 24 Gy. Seven patients (12%) died of nonrelapse causes by day 100. The estimated probability of recurrent malignancy at 1 year is 40%, and the 1-year survival estimate is 41%. These results show that CD45-targeted radiotherapy can be safely combined with a reduced-intensity conditioning regimen to yield encouraging overall survival for older, high-risk patients with AML or MDS. This study was registered at as #NCT00008177.

  17. Allogeneic hematopoietic cell transplantation after conditioning with 131I-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome. (United States)

    Pagel, John M; Gooley, Theodore A; Rajendran, Joseph; Fisher, Darrell R; Wilson, Wendy A; Sandmaier, Brenda M; Matthews, Dana C; Deeg, H Joachim; Gopal, Ajay K; Martin, Paul J; Storb, Rainer F; Press, Oliver W; Appelbaum, Frederick R


    We conducted a study to estimate the maximum tolerated dose (MTD) of (131)I-anti-CD45 antibody (Ab; BC8) that can be combined with a standard reduced-intensity conditioning regimen before allogeneic hematopoietic cell transplantation. Fifty-eight patients older than 50 years with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were treated with (131)I-BC8 Ab and fludarabine plus 2 Gy total body irradiation. Eighty-six percent of patients had AML or MDS with greater than 5% marrow blasts at the time of transplantation. Treatment produced a complete remission in all patients, and all had 100% donor-derived CD3(+) and CD33(+) cells in the blood by day 28 after the transplantation. The MTD of (131)I-BC8 Ab delivered to liver was estimated to be 24 Gy. Seven patients (12%) died of nonrelapse causes by day 100. The estimated probability of recurrent malignancy at 1 year is 40%, and the 1-year survival estimate is 41%. These results show that CD45-targeted radiotherapy can be safely combined with a reduced-intensity conditioning regimen to yield encouraging overall survival for older, high-risk patients with AML or MDS. This study was registered at as #NCT00008177.

  18. EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like side-population cells in non-small cell lung cancer

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    Singh Sandeep


    Full Text Available Abstract Background Cancer stem cells are thought to be responsible for the initiation and progression of cancers. In non-small cell lung cancers (NSCLCs, Hoechst 33342 dye effluxing side population (SP cells are shown to have stem cell like properties. The oncogenic capacity of cancer stem-like cells is in part due to their ability to self-renew; however the mechanistic correlation between oncogenic pathways and self-renewal of cancer stem-like cells has remained elusive. Here we characterized the SP cells at the molecular level and evaluated its ability to generate tumors at the orthotopic site in the lung microenvironment. Further, we investigated if the self-renewal of SP cells is dependent on EGFR mediated signaling. Results SP cells were detected and isolated from multiple NSCLC cell lines (H1650, H1975, A549, as well as primary human tumor explants grown in nude mice. SP cells demonstrated stem-like properties including ability to self-renew and grow as spheres; they were able to generate primary and metastatic tumors upon orthotopic implantation into the lung of SCID mice. In vitro study revealed elevated expression of stem cell associated markers like Oct4, Sox2 and Nanog as well as demonstrated intrinsic epithelial to mesenchymal transition features in SP cells. Further, we show that abrogation of EGFR, Src and Akt signaling through pharmacological or genetic inhibitors suppresses the self-renewal growth and expansion of SP-cells and resulted in specific downregulation of Sox2 protein expression. siRNA mediated depletion of Sox2 significantly blocked the SP phenotype as well as its self-renewal capacity; whereas other transcription factors like Oct4 and Nanog played a relatively lesser role in regulating self-renewal. Interestingly, Sox2 was elevated in metastatic foci of human NSCLC samples. Conclusions Our findings suggest that Sox2 is a novel target of EGFR-Src-Akt signaling in NSCLCs that modulates self-renewal and expansion of

  19. Rapamycin combined with anti-CD45RB mAb and IL-10 or with G-CSF induces tolerance in a stringent mouse model of islet transplantation.

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    Nicola Gagliani

    Full Text Available BACKGROUND: A large pool of preexisting alloreactive effector T cells can cause allogeneic graft rejection following transplantation. However, it is possible to induce transplant tolerance by altering the balance between effector and regulatory T (Treg cells. Among the various Treg-cell types, Foxp3(+Treg and IL-10-producing T regulatory type 1 (Tr1 cells have frequently been associated with tolerance following transplantation in both mice and humans. Previously, we demonstrated that rapamycin+IL-10 promotes Tr1-cell-associated tolerance in Balb/c mice transplanted with C57BL/6 pancreatic islets. However, this same treatment was unsuccessful in C57BL/6 mice transplanted with Balb/c islets (classified as a stringent transplant model. We accordingly designed a protocol that would be effective in the latter transplant model by simultaneously depleting effector T cells and fostering production of Treg cells. We additionally developed and tested a clinically translatable protocol that used no depleting agent. METHODOLOGY/PRINCIPAL FINDINGS: Diabetic C57BL/6 mice were transplanted with Balb/c pancreatic islets. Recipient mice transiently treated with anti-CD45RB mAb+rapamycin+IL-10 developed antigen-specific tolerance. During treatment, Foxp3(+Treg cells were momentarily enriched in the blood, followed by accumulation in the graft and draining lymph node, whereas CD4(+IL-10(+IL-4(- T (i.e., Tr1 cells localized in the spleen. In long-term tolerant mice, only CD4(+IL-10(+IL-4(- T cells remained enriched in the spleen and IL-10 was key in the maintenance of tolerance. Alternatively, recipient mice were treated with two compounds routinely used in the clinic (namely, rapamycin and G-CSF; this drug combination promoted tolerance associated with CD4(+IL-10(+IL-4(- T cells. CONCLUSIONS/SIGNIFICANCE: The anti-CD45RB mAb+rapamycin+IL-10 combined protocol promotes a state of tolerance that is IL-10 dependent. Moreover, the combination of rapamycin+G-CSF induces

  20. Isolation of side population cells from gallbladder carcinoma of human being and the expression of ABCG2 gene%人胆囊癌SP细胞的分离及ABCG2的表达

    Institute of Scientific and Technical Information of China (English)


    Objective: To investigate whether the side population cells (SP cells) exist in human gallbladder carcinoma cell line and the differences of drug resistance gene ABCG2 expression in SP cells, non-SP cells and GBC-SD cell lines. Methods:Fluorescence activated cell sorter (FACS) was used to sort the SP and non-SP cells from GBC-SD cell line of gallbladder carcinoma of human being. Then, the sorting cells were cultured and detected the expression of ABCG2 gene among the SP cells, non-SP cells and GBC-SD cell lines by using reverse transcription polymerase chain reaction (RT-PCR), immunofluorescence chemistry, western blot and flow cytometry techniques. Results:A very small fraction cells (0.64 ± 0.08%) were isolated through FACS analysis which had the potency of stem cells and highly expressed ABCG2 gene (89.56 ± 3.86%). On the contrary, there were nearly no expression in non-SP cells (1.32 ± 0.49%) and lower expression in GBC-SD cell line (12.37 ±1.61%). Conclusion: The side population cells that had the potency of stem ceils existed in human gallbladder carcinoma cell line and over-expressed the drug resistance gene ABCG2. They may be play an important role in drug resistance of tumor.

  1. Characterization of highly frequent epitope-specific CD45RA+/CCR7+/- T lymphocyte responses against p53-binding domains of the human polyomavirus BK large tumor antigen in HLA-A*0201+ BKV-seropositive donors

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    Zajac Paul


    Full Text Available Abstract Human polyomavirus BK (BKV has been implicated in oncogenic transformation. Its ability to replicate is determined by the binding of its large tumor antigen (LTag to products of tumor-suppressor genes regulating cell cycle, as specifically p53. We investigated CD8+ T immune responses to BKV LTag portions involved in p53 binding in HLA-A*0201+ BKV LTag experienced individuals. Peptides selected from either p53-binding region (LTag351–450 and LTag533–626 by current algorithms and capacity to bind HLA-A*0201 molecule were used to stimulate CD8+ T responses, as assessed by IFN-γ gene expression ex vivo and detected by cytotoxicity assays following in vitro culture. We observed epitope-specific immune responses in all HLA-A*0201+ BKV LTag experienced individuals tested. At least one epitope, LTag579–587; LLLIWFRPV, was naturally processed in non professional antigen presenting cells and induced cytotoxic responses with CTL precursor frequencies in the order of 1/20'000. Antigen specific CD8+ T cells were only detectable in the CD45RA+ subset, in both CCR7+ and CCR7- subpopulations. These data indicate that widespread cellular immune responses against epitopes within BKV LTag-p53 binding regions exist and question their roles in immunosurveillance against tumors possibly associated with BKV infection.

  2. Synthesis and characterization of La11+xHg45-x and RE11Hg44.5 (RE = Nd, Sm) as hettotypes of the Sm11Cd45 structure type (United States)

    Tambornino, Frank; Schwärzer, Kuno; Hoch, Constantin


    The mercury-rich amalgams La11+xHg45-x and RE11Hg44.5 (space group F4bar3m (No. 216), La11+xHg45-x : a = 21.9342(19) Å, RE = Nd: a = 21.7384(14) Å; RE = Sm: a = 21.6555(4) Å), were synthesized by dissolving the respective rare earth metals in a mercury surplus and subsequently distilling off the excess. The compounds were characterized by single crystal and powder X-ray methods together with ab-initio band structure calculations. Both crystal structures deviate significantly and in different ways from their common aristotype, the Sm11Cd45 structure type. In La11+xHg45-x (x = 0.7(1)) two crystallographic sites show mixed occupancy, whereas in RE11Hg44.5 one of the Hg positions is fully unoccupied. Their band structures exhibit typical broad Hg d states at low energies, and a strong mixing of s and p states indicates a mercury sublattice with high connectivity.

  3. Método imunomagnético associado ao meio MesenCult® na obtenção de células mononucleares da medula óssea de coelhos negativas para o anticorpo monoclonal CD45

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    Luiz A. de Souza


    Full Text Available Resumo O objetivo detse artigo é de descrever um protocolo de isolamento das células mononucleares da medula óssea de coelhos, seguido de purificação celular por depleção negativa com o anticorpo monoclonal CD45 e posterior expansão em meio de cultura MesenCult®. Dez coelhos machos adultos, da raça Nova Zelândia, com idade média de 1,0±0,2 anos e peso médio 3,5±0,24kg, foram utilizados para padronização da metodologia. O isolamento das células mononuclares da medula óssea foi realizado pelo gradiente de densidade Ficoll-paque® e a purificação e obtenção das células- pela depleção negativa com o anticorpo monoclonal CD45 em base imunomagnética. A população celular obtida foi expandida posteriormente em meio de cultura MesenCult®. No isolamento pelo gradiente de icoll-Paque® foi obtido um rendimento médio de 7,31x106 células/mL. Após purificação e obtenção das possíveis células-tronco mesenquimais pela base imunomagnética, houve um decréscimo do rendimento para 2,28x106 células/mL, mas o processo de expansão foi incrementado pelo cultivo celular. Os resultados indicaram que as células obtidas da fração mononuclear da medula óssea, cultivadas in vitro foram capazes de gerar células aderentes 24 horas após o cultivo, com predominância de células fibroblastóides sugestivas de células-tronco mesenquimais. Concluiu-se que a obtenção de células-tronco mesenquimais pode ser alcançada após purificação das células mononucleares da medula óssea de coelhos pelo método imunomagético, o meio de cultura MesenCult® proporciona um ambiente adequado para a rápida expansão in vitro e o número de passagens exerce influência negativa sobre as características morfológicas das células.

  4. Validation of a single-platform, volumetric, CD45-assisted PanLeucogating Auto40 flow cytometer to determine the absolute number and percentages of CD4 T cells in resource-constrained settings using Cameroonian patients' samples. (United States)

    Mbopi-Kéou, François-Xavier; Mion, Stefano; Sagnia, Bertrand; Bélec, Laurent


    The study evaluated the single-platform, volumetric, CD45-assisted PanLeucogating Auto40 flow cytometer (Apogee Flow Systems Ltd., Hemel Hempstead, United Kingdom) for CD4 T cell numeration, compared to the reference FACSCalibur flow cytometer. Results of absolute counts and percentages of CD4 T cells by Auto40 and FACSCalibur of 234 tripotassium EDTA (K3-EDTA)-blood samples from 146 adults and 88 children (aged from 18 months to 5 years), living in Yaoundé, Cameroon, were highly correlated (r(2) = 0.97 and r(2) = 0.98, respectively). The mean absolute bias and relative bias between Apogee Auto40 and FACSCalibur absolute CD4 T cell counts were +9.6 cells/μl, with limits of agreement from -251 to 270 cells/μl, and +4.1%, with limits of agreement from -16.1 to 24.4%, respectively. The mean absolute bias and relative bias between Apogee Auto40 and FACSCalibur CD4 T cell results expressed as percentages were +0.05% CD4 (95% confidence interval [CI], -0.03 to 0.41), with limits of agreement from -6.0 to 5.9% CD4, and +1.0%, with limits of agreement from -32.3 to 34.4%, respectively. The Auto40 counting allowed identification of the majority of adults with CD4 T cell counts below 200 cells/μl (sensitivity, 87%; specificity, 98%) or below 350 cells/μl (sensitivity, 92%; specificity, 98%) and of children with CD4 T cell counts below 750 cells/μl (sensitivity, 82%; specificity, 98%) or below 25% CD4(+) (sensitivity, 96%; specificity, 99%). The Auto40 analyzer is a reliable alternative flow cytometer for CD4 T lymphocyte enumeration to be used in routine immunological monitoring according to the WHO recommendations for HIV-infected adults as well as children living in resource-constrained settings.

  5. A comparison of the biodistribution and biokinetics of {sup 99m}Tc-anti-CD66 mAb BW 250/183 and {sup 99m}Tc-anti-CD45 mAb YTH 24.5 with regard to suitability for myeloablative radioimmunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Buchmann, Inga [Department of Nuclear Medicine, University Hospital, Ulm (Germany); Klinik und Poliklinik fuer Nuklearmedizin, Gebaeude 210, Johannes-Gutenberg-Universitaet Mainz, 55101, Mainz (Germany); Kull, Thomas; Glatting, Gerhard; Kotzerke, Jorg; Rattat, Dirk; Reske, Sven N. [Department of Nuclear Medicine, University Hospital, Ulm (Germany); Bunjes, Donald; Dohner, Hartmut [Department of Hematology, University Hospital, Ulm (Germany); Hale, Geoffrey [Sir William Dunn School of Pathology, Oxford (United Kingdom)


    Radioimmunotherapy (RIT) with radiolabelled monoclonal antibodies (mAbs) is an effective method of achieving myeloablation in leukaemia patients prior to stem cell transplantation (SCT). We wished to compare the approaches of specific binding to leukaemic blasts and non-specific binding to benign red marrow cells, which results in a myeloablative ''cross-fire'' effect. Therefore, we prospectively evaluated the biodistribution and biokinetics of the anti-CD45 mAb YTH 24.5 and the anti-CD66 mAb BW 250/183 with regard to their suitability for myeloablative RIT. The red marrow selective anti-CD66 mAb BW 250/183 (IgG1) binds to normal granulopoietic cells. In contrast, the anti-CD45 mAb YTH 24.5 (IgG2b) binds to 85-90% of acute leukaemic blasts and almost all haematopoietic white cells. Patients with leukaemic blast infiltration of the marrow <25% and assigned for RIT and SCT were included. Twelve patients (eight male, four female; median age 46{+-}7 years) with AML (5), CML (5) or ALL (2) were examined. Both mAbs were labelled with technetium-99m. Within 48 h, 906{+-}209 MBq {sup 99m}Tc-anti-CD66 mAb and 760{+-}331 MBq {sup 99m}Tc-anti-CD45 mAb were injected consecutively. Scintigraphic and urinary measurements were performed 1, 2, 4 and 24 h after injection. Serum activities were evaluated 2, 5, 10, 15, 30 and 60 min and 2, 4 and 24 h after injection. Compared with the anti-CD45 mAb, the anti-CD66 mAb showed an approximately fourfold higher accumulation in the red marrow, a 2.5-fold lower accumulation in the liver and similar accumulation in the kidneys. The serum activity (% of the injected dose) initially decreased faster for the anti-CD45 mAb but was similar for the two mAbs 24 h after injection: 3.3%{+-}1.2% (anti-CD66 mAb) and 2.4%{+-}1.1% (anti-CD45 mAb). The cumulated urinary excretion was 17%{+-}6.6% (anti-CD66 mAb) and 27.3%{+-}7.9% (anti-CD45 mAb) 24 h after application. In these patients with low tumour load, the anti-CD66 mAb BW 250

  6. Side Effects (Management) (United States)

    ... cancer care is relieving side effects, called symptom management, palliative care, or supportive care. It is important ... treat them. To learn about the symptoms and management of the long-term side effects of cancer ...

  7. A standardized cytological and immunochemical method for the analysis of fine-needle spleen aspirates: assessment of leukocyte population changes in canine visceral leishmaniosis. (United States)

    Barrouin-Melo, Stella Maria; Larangeira, Daniela Farias; Santos, Silvana Ornelas; Chagas-Júnior, Adenizar Delgado; Paixão, Mariza; Aguiar, Paulo Henrique Palis; dos-Santos, Washington Luís Conrado; Pontes-de-Carvalho, Lain


    A method for the evaluation of splenic cellularity using samples collected by fine-needle aspirative biopsy was standardized in this work. The procedure includes erythrocyte lysing, preparation of cytospin films and staining by histochemical and immunocytochemical techniques. The cellular profiles of spleen preparations were compared with those observed in peripheral blood samples subjected to the same procedure. Two groups were compared, one consisting of 14 healthy uninfected and the other of 15 polysymptomatic Leishmania chagasi/infantum-infected dogs, from an endemic area for visceral leishmaniosis. Cell populations were identified by conventional hematoxilin-eosin and Wright' stainings, and by immunocytochemistry using monoclonal antibodies against canine CD45RA and CD45RB, phagocytes and a pan-leukocyte antigen. Larger neutrophil (P < 0.0001) and monocyte/macrophage (P = 0.0036) relative counts and lower lymphocyte relative counts (P < 0.0001) were found in the spleen, and not in the blood, of the animals with leishmaniosis than in those of the healthy animals. The proportions of CD45RB+ cells were higher, and of CD45RA+ cells were lower, both in the spleen and in the blood of animals with leishmaniosis than in those of healthy dogs (P < 0.05). Additionally, hematoxilin-eosin-stained cytospins of spleen aspirates from Leishmania-infected animals permitted the easy visualization of amastigote forms inside phagocytes, under light microscopy.

  8. Isolation and identification of side population cells in human cervical cancer and analysis of biological characteristics%人宫颈癌侧群细胞的分选及其生物学特性的研究

    Institute of Scientific and Technical Information of China (English)

    宋菁华; 王克芳; 李斌; 张军


    Objective To isolate side population (SP) cells from human cervical cancer cells and to determine the characteristics of cancer stem cells, so as to investigate the feasibility of starting research on cervical cancer stem cells from the SP cells. Methods The human cervical cancer cells were obtained from fresh human cervical cancer tissue of 40 patients who were diagnosed as cervical cancer. Flow cytometry and Hoechst 33342 dye efflux assay were used to isolate SP cells and NSP cells from the cervical cancer cells. The proliferation and differentiation of the two sub - population cells were observed. The two sub - population cells were injected into nude mice subcutaneously to observe their tumorigenesis ability. The inhibition rates of SP and NSP cells were assessed after treatment with chemotherapy drugs ( cisplatin) to evaluate the resistance. Results The proportion of SP cells excluding Hoechst 33342 dye in the human cervical cancer cells was 2. 04% ±0. 93% , and the proportion of the SP cells was decreased with the the degree of reduction of differentiation(P <0. 05). Cell growth curve indicated that proliferative capacity of the SP cells was better than the NSP cells (P<0. 05). The SP cells demonstrated stronger tumorigenesis ability in nude mice. As few as 1 x 103 SP cells could give rise to new tumors in xenotransplantation, with a tumorigenesis ability 100 times as high as that of the NSP cells. The time of tumor formation was significantly reduced. After treatment with different concentrations of chemotherapy drugs (cisplatin) for 24h, the SP cells had significantly lower inhibition rate than the NSP cells ( P < 0. 05 ). Conclusion Human cervical cancer cells contains a small subpopulation of cells excluding Hoechst 33342 dye. The more poorly the cell line differentiated, the fewer the proportion it contained. The SP cells has better proliferative capacity in vitro and stronger tumorigenicity than the NSP cells, with strongly resistant to chemotherapy


    Institute of Scientific and Technical Information of China (English)

    孟泳圳; 李力; 钟艳平; 张玮


    Objective:To sorting side group (side population,SP) cells in ovarian cancer cell line SKOV3,discusses the best dyeing concentration of Hoechst33342 and the optimal cell density of SKOV3 suspension.Methods:Preparation SKOV3 single cell suspension,with fluorescent dye Hoechst33342 and 7-AAD dyeing,adding verapamil toantagonism group,incubation1×106/mL SKOV3 cell 90 min with different concentration of Hoechst33342 (2.5,3,4,5,and 6 mg/L),flow cytometry instrument detection proportion of SP cell and living cells choosing different cell density (6× 105,7×105,8×105,9×105,1×106 cells/mL) of SKOV3 cell suspension,3 mg/L Hoechst33342 incubation 90 minutes,flow cytometry instrument detection proportion of SP cell and living cell.Results:Hoechst33342 blue and red double parameter map showed that SP cells located in the lower left corner of the two fluorescences were weaker areas.For the same hoechst33342 concentration,with the increase of cell density,SP cell proportion increased;for the same SKOV3 cell suspension,with the increase of hoechst33342 concentration,proportion of SP cell and living cell decreased.The best dyeing conditions of ovarian cancer cell line SKOV3 were cell density of 8× 105 cells/mL,join Hoechst33342 final concentration was 3 mg/L,37℃ water bath for 90 min.The SP cell ratio was (1.12±0.104)%,and cell can maintain good activity.Conclusion:SP cell subsets exist in human ovarian cancer cell line SKOV3,Hoechst33342 concentration and SKOV3 cell density is an important factor affecting in SP cell proportion and the activity of the cells.%目的:探讨分选卵巢癌细胞株SKOV3中的侧群(side population,SP)细胞的荧光染料Hoechst33342的最佳染色浓度及SKOV3的最适细胞密度.方法:制备SKOV3细胞悬液,以荧光染料Hoechst33342和7-AAD染色,维拉帕米拮抗对照,选择不同浓度的Hoechst33342(2.5,3,4,5,6 mg/L)孵育1×106个/mL SKOV3细胞90 min,流式细胞仪检测SP细胞比例及活细胞比例;

  10. Phenotypic characterization of CD8+ T cell populations in HIV disease and in anti-HIV immunity. (United States)

    Watret, K C; Whitelaw, J A; Froebel, K S; Bird, A G


    The CD8+ T cell population is believed to play an important role in the control of viral infection, both for suppression of viral replication and for cytotoxic activity against viral infected cells. Elevated numbers of CD8+ T cells have been demonstrated in HIV infection, and CD8+ cytotoxic T cell (CTL) activity is associated with the early, asymptomatic stage of disease. We investigated the phenotypic characteristics of the CD8 population, in whole blood, in HIV disease and determined the predominant CD8+ subpopulation involved in anti-HIV CTL activity. We found that CD8+ T cells co-expressing markers of activation (HLA-DR), memory (CD45RO, CD29), and cytotoxic activity (S6F1) were significantly elevated in the early stages of disease, while the numbers of naive (CD45RA) cells remained unchanged. Progression to AIDS resulted in an overall loss of absolute CD8+ T cells, though the percentages of CD8+ HLA-DR+ and CD8+ S6F1+ remained elevated. In contrast to patients in the late stages of disease, anti-HIVgag CTL activity, following in vitro stimulation, was present in most HIV+ asymptomatic subjects and was associated with an expansion of CD8+ HLA-DR+ and CD8+ CD45RO+ cells. The absence of CTL activity was associated with a reduced ability of these populations to expand in vitro and with a significant loss of peripheral CD4+ T cells, independent of clinical stage. We suggest that CD8+ expressing HLA-DR+ CD45RO+ and S6F1+ play an important role in anti-HIV cytotoxicity.

  11. Working the Dark Side

    DEFF Research Database (Denmark)

    Bjering, Jens Christian Borrebye

    A few days after the terror attacks of 9/11, then Vice President Dick Cheney appeared on television with a call for “working the dark side.” While still unclear what this expression entailed at the time, Cheney's comment appears in retrospect to almost have been prophetic for the years to come...... – years where parts of the U.S. Army and intelligence community set up a rampant torture regime all across the world. Yet, the connection between a so-called “dark side,” “working” this “dark side,” and the torture that followed is not a given, but, instead, a consequence of a set of very specific legal...... boundaries and came to define what it meant to “work” the “dark side.”...

  12. Side Effects of Chemotherapy (United States)

    ... Jacket Fashion Show Contact Us Side Effects of Chemotherapy Each of the chemotherapy drugs available today works in a slightly different ... few rules of thumb when it comes to chemotherapy that should always be kept in mind. Ignore ...

  13. 乳腺癌MCF-7细胞系中侧群细胞分选及其生物学特性%Sorting of side population cells from breast cancer MCF-7 cell line and its biological characteristics

    Institute of Scientific and Technical Information of China (English)

    孙鑫; 李平; 张梅; 陈娇


    Objective To separate the side population cells(SP) from breast cancer MCF-7 cell line,and observe its biological characteristics.Methods Flow cytometry and Hcechst 33342 dye efflux assay were used to isolate SP cells and non-SP cells from the MCF-7 cell line of human breast cancer.Tumorigenicity of the two subpopulations was observed by a soft agar cloning method.Results The results of FACS analysis indicated that (6.5 ± 0.4 ) %of the MCF-7 cells were SP cells;The vitro colony formation rate of SP cells was(38.5 ±9.4)%,and higher than that of non-SP cells ( 8.4 ± 2.6 ) % ( t =5.34,P < 0,05 ).Concluslon The SP cells sorted from MCF-7 cell line enriched tunor stem cells,which exhibited high tumorigenicity.It indicated that SP cells should play a principal role in breast cancer.%目的 分离乳腺癌MCF-7细胞系中的侧群细胞(SP)并观察其生物学特性.方法 利用流式细胞荧光分选法将乳腺癌MCF-7细胞系分成SP和非SP细胞两个亚群.对两个亚群细胞采用软琼脂克隆形成实验观察其增殖能力.结果 MCF-7细胞株中分选出SP细胞占(6.5±0.4)%;SP细胞的体外克隆形成率为(38.5±9.4)%,高于非SP细胞的(8.4±2,6)%(t=5.34,P<0.05).结论 乳腺癌MCF-7细胞中的SP细胞富集了乳腺癌于细胞,其增殖能力强于非SP细胞,表明SP表型的肿瘤细胞在乳腺癌的生长中具有重要的地位.

  14. Isolation and identiffcation of cancer stem-like side population cells in pancreatic cancer%胰腺癌肿瘤干细胞样侧群细胞的分离鉴定

    Institute of Scientific and Technical Information of China (English)

    周静; 王春友; 周峰; 刘涛; 吴河水; 熊炯圻; 赵刚; 陶京; 杨明; 周蒙滔


    目的 分离鉴定胰腺癌中的侧群(SP)细胞亚群.方法 应用Hoechst33342染色,流式细胞仪检测5个胰腺癌细胞系及3个原代培养的临床胰腺癌标本中sP细胞的含量.以PANC-1为例,通过平板克隆形成试验和NOD-SCID小鼠异种移植成瘤实验比较SP细胞与non-SP细胞的克隆形成能力及成瘤能力,通过对体外培养的SP细胞和SP细胞衍生肿瘤的HoechsG3342复染SP再分析判断其是否具有分化潜能.结果 除了BXPC-3,其他胰腺癌细胞系及原代培养标本都存在Verapamil敏感的SP细胞.SP细胞与non-SP细胞比较具有较高的克隆形成能力[(43.67±3.10)%比(8.33±1.63)%,P<0.01],并且能够分化产生non-SP细胞并维持自身SP细胞的比例在一个较稳定的水平.SP细胞的成瘤能力是non-SP细胞的100倍以上.而且SP细胞在体内亦可发生不对称分裂生成SP细胞和non-SP细胞.结论 SP细胞可能是胰腺癌干细胞的候选细胞之一.%Objective To isolate and identify side population(SP)cells in pancreatic cancer.Methods We detected the number of SP cells in 5 pancreatic cancer cell lines and 3 clinical samples by Hoechst33342 dyeing and FACS analysis.The clone formation efficiency and tumorigenicity were compared between SP cels and non-SP ceils by clone formation assay and NOD/SCID xenograft transplantation experiment.The differentiation ability of SP ceils was studied by flow cytometry reanalysis of SP-derived tumors and cultured SP ceils.Results All cell lines and clinical samples were found to exhibit verapamilsensitive SP cells except BXPC-3.Using SP cells sorted from PANC-1 as a model.SP ceUs were demonstratcd to exhibit higher colony-formation ability than non-SP cells [(43.67±3.10)% vs (8.33±1.63)%.P<0.01].And flow cytometry reanalysis indicated SP ceHs could generate both SP and non-SP cells with a fraction size comparable with the original population.In addition.SP cells were enriched in tumorigenicity by at least 100-fold

  15. Expression of stem cell markers in side population cells sorted from SMMC-7721 cell line%肝癌SMMC-7721细胞中侧群细胞干细胞标记的表达

    Institute of Scientific and Technical Information of China (English)

    黄涛; 宫东伟; 高全立; 张旭华; 吕晓东; 周进学


    Objective To study the expression of stem cell markers in side population cells sorted from SMMC-7721 cell line. Methods Fluorescence-activated cell sorting (FACS) was used to sort side population (SP) cells and non-SP (NSP) cells from SMMC-7721 cell line. Real-time polymerase chain reaction (PCR) and flow cytometry (FCM) were used to evaluate the expression of several stem cell markers such as ABCG2, CD133, Oct4, Sox2 and NANOG in SP cells and NSP cells. Results FACS analysis indicated that (9.2 ±0. 2)% of the SMMC-7721 cells were SP cells. Real-time PCR analysis suggested that ABCG2, CD133, Oct4, Sox2 and NANOG were expressed in the SP cells at higher levels than the NSP cells by about 7. 132, 4. 985, 8. 642, 5.095 and 5. 164 folds, respectively ( P <0. 01 ). FCM analysis revealed that the expression of ABCG2, CD133, Oct4, Sox2 and NANOG proteins in SP cells was (92. 65 ±3.92)%, (12.75 ±1.62)%, (17.35 ±2.31)%, (9.57 ± 1.71)% and (28.39 ±5.28)% respectively,while in NSP cells that was (0. 26 ±0. 06)%, (2. 51 ±0. 17)%, ( 1.74 ±0. 38)%, ( 1.52 ±0. 41 )% and ( 3.37 ± 1.02) % respectively ( P < 0. 01 ). Conclusion The SP cells sorted from SMMC-7721 cell line may enrich tumor stem cells. Purified liver cancer stem cells may be obtained by screening SP cells using a variety of stem cell markers.%目的 分选肝癌细胞株SMMC-7721中的侧群(SP)细胞,并分析其干细胞标记的表达.方法 采用流式细胞荧光激活分选(FACS)技术将SMMC-7721细胞分为SP细胞和非侧群(NSP)细胞两个亚群,以实时荧光定量聚合酶链反应(real-time PCR)技术和流式细胞术对两个亚群细胞干细胞标记mRNA和蛋白表达进行分析.结果 SMMC-7721细胞株中分选出的SP细胞比例为(9.2±0.2)%.SP细胞ABCG2、CD133、Oct4、Sox2和NANOG等干细胞标记mRNA的表达水平分别是NSP细胞的7.132倍、4.985倍、8.642倍、5.095倍和5.164倍,差异均有统计学意义(P<0.01);ABCG2、CD133、Oct4、Sox2和NANOG蛋白在

  16. [Psychoanalysis and Side Effect]. (United States)

    Shirahase, Joichiro


    A study of psychoanalysis from the perspective of side effects reveals that its history was a succession of measures to deal with its own side effects. This, however, does not merely suggest that, as a treatment method, psychoanalysis is incomplete and weak: rather, its history is a record of the growth and development of psychoanalysis that discovered therapeutic significance from phenomena that were initially regarded as side effects, made use of these discoveries, and elaborated them as a treatment method. The approach of research seen during the course of these developments is linked to the basic therapeutic approach of psychoanalysis. A therapist therefore does not draw conclusions about a patient's words and behaviors from a single aspect, but continues to make efforts to actively discover a variety of meanings and values from them, and to make the patient's life richer and more productive. This therapeutic approach is undoubtedly one of the unique aspects of psychoanalysis. I discuss the issue of psychoanalysis and side effects with the aim of clarifying this unique characteristic of psychoanalysis. The phenomenon called resistance inevitably emerges during the process of psychoanalytic treatment. Resistance can not only obstruct the progress of therapy; it also carries the risk of causing a variety of disadvantages to the patient. It can therefore be seen as an adverse effect. However, if we re-examine this phenomenon from the perspective of transference, we find that resistance is in fact a crucial tool in psychoanalysis, and included in its main effect, rather than a side effect. From the perspective of minimizing the character of resistance as a side effect and maximizing its character as a main effect, I have reviewed logical organization, dynamic evaluation, the structuring of treatment, the therapist's attitudes, and the training of therapists. I conclude by stating that psychoanalysis has aspects that do not match the perspective known as a side

  17. Working the Dark Side

    DEFF Research Database (Denmark)

    Bjering, Jens Christian Borrebye

    half—dark side—documents the making and nature of the dark side by analyzing a series of legal memos from the Department of Justice's Office of Legal Council and from the White House and concludes by relating its findings to traditional ideas about emergency action, national security, and torture....... By analyzing official reports and testimonies from soldiers partaking in the War On Terror, the dissertation's second part—dark arts—focuses on the transformation of the dark side into a productive space in which “information” and the hunt for said information overshadowed all legal, ethical, or political...

  18. Substrate affinity of photosensitizers derived from chlorophyll-a: the ABCG2 transporter affects the phototoxic response of side population stem cell-like cancer cells to photodynamic therapy. (United States)

    Morgan, Janet; Jackson, Jennifer D; Zheng, Xiang; Pandey, Suresh K; Pandey, Ravindra K


    Photosensitizers (PS) synthesized with the aim of optimizing photodynamic therapy (PDT) of tumors do not always fulfill their potential when tested in vitro and in vivo in different tumor models. The ATP-dependent transporter ABCG2, a multidrug resistant pump expressed at variable levels in cancerous cells, can bind and efflux a wide range of structurally different classes of compounds including several PS used preclinically and clinically such as porphyrins and chlorins. ABCG2 may lower intracellular levels of substrate PS below the threshold for cell death in tumors treated by PDT, leaving resistant cells to repopulate the tumor. To determine some of the structural factors that affect substrate affinity of PS for ABCG2, we used an ABCG2-expressing cell line (HEK 293 482R) and its nonexpressing counterpart, and tyrosine kinase ABCG2 inhibitors in a simple flow cytometric assay to identify PS effluxed by the ABCG2 pump. We tested a series of conjugates of substrate PS with different groups attached at different positions on the tetrapyrrole macrocycle to examine whether a change in affinity for the pump occurred and whether such changes depended on the position or the structure/type of the attached group. PS without substitutions including pyropheophorbides and purpurinimides were generally substrates for ABCG2, but carbohydrate groups conjugated at positions 8, 12, 13, and 17 but not at position 3 abrogated ABCG2 affinity regardless of structure or linking moiety. At position 3, affinity was retained with the addition of iodobenzene, alkyl chains and monosaccharides, but not with disaccharides. This suggests that structural characteristics at position 3 may offer important contributions to requirements for binding to ABCG2. We examined several tumor cell lines for ABCG2 activity, and found that although some cell lines had negligible ABCG2 activity in bulk, they contained a small ABCG2-expressing side population (SP) thought to contain cells which are responsible

  19. Side effects of ergotamine

    NARCIS (Netherlands)

    Meyler, WJ


    Ergotamine has been used for many years in the treatment of migraine, although there is Little formal clinical evidence that it is significantly more efficacious than placebo. A number of side effects associated with ergotamine have been reported in the literature, including myocardial infarction, i

  20. Colorectal cancers choosing sides

    NARCIS (Netherlands)

    Albuquerque, Cristina; Bakker, Elvira R. M.; van Veelen, Wendy; Smits, Ron


    In contrast to the majority of sporadic colorectal cancer which predominantly occur in the distal colon, most mismatch repair deficient tumours arise at the proximal side. At present, these regional preferences have not been explained properly. Recently, we have screened colorectal tumours for mutat

  1. Combined use of immunomagnetic activated cell sorting technique enrichment and immunocytochemistry with hematoxylin and eosin staining for identification of circulating tumor cells in peripheral blood mononuclcar cells of hepatocellular carcinoma patients%应用免疫激活磁珠分选技术CD45去除方法富集——免疫细胞化学联合苏木素-伊红染色检测肝癌患者循环肿瘤细胞

    Institute of Scientific and Technical Information of China (English)

    郭立民; 鲁岩; 彭吉润; 蒋力


    Objective To estimate the applied value of magnetic activated cell sorting (MACS) techniques with CD45 depletion and immunocytochemistry in combination with hematoxylin and eosin (HE) staining in identifying circulating tumor cells (CTCs) in peripheral blood mononuclear cells (PBMC) of hepatocellular carcinoma (HCC) patients.Methods The expression of CK (CK8,CK18,and CK19) was detected in 18 epithelia-derived tumor cell lines including 9 human hepatocellular carcinoma cell lines.The peripheral blood of HCC patients and healthy volunteers was collected for determination of CTCs in PBMC from HCC patients using MACS techniques with CD45 depletion and immunocytochemstry in combination with HE staining.Results The expression rate of CK8,CK18 and CK19 in the selected CTCs was 72.22%,83.33% and 66.67% respectively.CKs were detected in most of the 9 hepatocelluar carcinoma cell lines.We found intact CTCs in PBMC from HCC patients using HE staining and immunocytochemistry after PBMC enrichment by MACS techniques with CD45 + depletion.The sensitivity of this method was up to 63.15%,and no CTCs were detected in PBMC from 20 healthy controls.Conclusion CKs could be a tumor marker for detection of CTCs in HCC patients.The method of HE staining and immunocytochemistry after PBMC enrichment by MACS technique with CD45 + depletion has potentials in detection of circulating HCC cells.%目的 探讨免疫激活磁珠分选(MACS) CD45去除方法富集后,以细胞角蛋白(CK)为标记联合苏木素-伊红(HE)染色检测肝癌患者外周血肿瘤细胞(CTC)的价值.方法 应用逆转录-聚合酶链反应(RT-PCR)检测18种上皮肿瘤细胞株的CK(CK8、CK18、CK19)表达;采集健康志愿者、肝癌患者外周血,以MACS技术CD45去除方法对外周血单个核细胞(PBMC)进行富集,以CK为标记,采用免疫组织化学染色联合HE染色检测肿瘤细胞.结果 在18种上皮性肿瘤细胞株中CK8、CK18、CK19表达率分别为72.22%、83.33%和66

  2. 人卵巢癌细胞株侧群细胞的生物学特征%Biological characteristics of the side population of human ovarian epithelial cancer cell line

    Institute of Scientific and Technical Information of China (English)

    林琳; 王沂峰; 黄奕俊


    目的 研究人卵巢癌细胞株细胞中乳腺癌耐药蛋白与侧群细胞表型的关系,并探讨侧群细胞在卵巢癌病理牛理中的作用以及卵巢癌细胞株在卵巢癌肿瘤干细胞研究中的应用. 方法 利用流式细胞术从人卵巢浆液腺癌细胞株OVCAR3中分离排斥双苯酰亚胺(Hoechst 33342)染色的侧群细胞以及能被其染色的非侧群细胞,比较两个亚群的细胞集落形成率,并检验其在软琼脂平板生长的能力.同时以免疫印迹和免疫荧光染色检测两种细胞的乳腺癌耐药蛋白表达情况. 结果 OVCAR3细胞株中排斥Hoechst 33342的细胞占2.0%,此活动对维拉帕米(verapamil)敏感.侧群细胞和非侧群细胞克隆形成率分别为46.17%±23.27%和6.17%±3.06%,侧群细胞克隆形成率高于非侧群细胞(P<0.05),并能在软琼脂平板中生长、形成球形的细胞集落.侧群细胞表达乳腺癌耐药蛋白. 结论 人卵巢浆液腺癌细胞株中存在排斥Hoechst 33342染色、对维拉帕米敏感的侧群细胞,是维持细胞株的主要因素,其表型与乳腺癌耐药蛋白相关.OVCAR3可用于卵巢癌肿瘤干细胞的研究.%Objectives Existence of side population (SP) in human ovarian cancer cell line OVCAR3 and characteristics of both stem cells and cancer cells were detected. Relation between SP phenotype and ABCG2 protein( ATP-binding cassette superfamily G member 2/breast cancer resistance protein, BCRP) was examined,and the potential to use OVCAR3 as tools for investigating the characteristics of cancer stem cells (CSCs)was estimated as well. Methods Hoechst 33342 efflux SP cells and dye-uptaking non-SP cells were separated by flow cytometry from human serous ovarian adenocarcinoma cell line OVCAR3. Cell colonyforming efficiency (CFE) of both subgroups ware evaluated. Soft agar assay was performed to compare the growth capacity of SP cells and non-SP cells. ABCG2 expression was detected by Western blotting and immunofluoreacence using

  3. Isolation and Tumorigenicity of Side Population Cells Sorted from Hepatocellular Carcinoma Bel-7402 Cell Line%肝癌细胞株Bel-7402中侧群细胞的分离和致瘤能力

    Institute of Scientific and Technical Information of China (English)

    陈伟; 姜楠; 张彤; 李华; 张琪; 陈规划; 曾宪成


    [Objective] To study the biological characteristics of side population (SP) cells sorted from hepatocellular carcinoma Bel-7402 cell line. [Methods] Fluorescence-activated cell sorter (FACS) was used to sort SP cells and non-SP (NSP) cells from Bel-7402 cell line. Groups were: SP group and NSP group. The colony formation and proliferation ability were compared between SP cells and NSP cells by plate colony and growth curve assay. ATP-binding cassette superfamily G member 2 (ABCG2) and CD133 mRNA levels in SP and NSP cells were examined by RT-PCR. The apoptosis was analyzed by flow cytometry. The sphere rate was counted for SP cells and NSP cells in serum-free medium. The oncogenicity of the SP and NSP cells were analyzed by tumor formation in nonobese diabeti- c/severe combined immune- deficient (NOD/SCID) mice. [Results] (2.4 ?.0) % SP cells were sorted from the Bel-7402 cells by FACS. Growth curve assay showed that the proliferation ability of SP cells was higher than NSP cells (P 0.05, P < 0.05,and P < 0.05). [Conclusion] The SP cells sorted from Bel-7402 cell line may enrich tumor stem cells.%[目的]分选肝癌Bel-7402细胞中的侧群(SP)细胞并分析其生物学特性.[方法]采用流式细胞荧光激活分选(FACS)技术将Bel-7402细胞分为SP细胞和非侧群(NSP)细胞2亚群.实验分组:SP组与NSP组.细胞生长曲线法和平板克隆法比较SP细胞和NSP细胞的增殖能力和克隆形成能力;RT-PCR法检测SP细胞和NSP细胞的CD133、三磷酸腺苷结合盒转动蛋白G2(ABCG2)表达;流式细胞术分析细胞凋亡率;无血清培养法检测SP细胞及NSP细胞成球率;非肥胖糖尿病/严重联合免疫缺陷(NOD/SCID)小鼠体内成瘤实验比较SP细胞和NSP细胞的致瘤性.[结果]Bel-7402细胞中分选出的SP细胞比例为(2.4±0.0)%.生长曲线表明SP细胞的增殖速度快于NSP细胞(P<0.05).SP、NSP细胞的克隆形成率分别为(20.5±2.6)%、(5.1±0.9)%,两者差异明显(P<0.05).SP

  4. HIV Medicines and Side Effects (United States)

    Side Effects of HIV Medicines HIV Medicines and Side Effects (Last updated 1/17/2017; last reviewed 1/17/2017) Key Points HIV medicines help people with ... will depend on a person’s individual needs. Can HIV medicines cause side effects? HIV medicines help people ...

  5. Opiates and elderly: Use and side effects

    Directory of Open Access Journals (Sweden)

    Diane L Chau


    Full Text Available Diane L Chau1, Vanessa Walker2, Latha Pai3, Lwin M Cho4University of Nevada School of Medicine, Reno, NV, USA 1Division Geriatric Medicine, 2Internal Medicine, 3Psychiatry, 4Geriatric Medicine, Sierra Nevada Healthcare System, Veterans Affairs Medical Center, Reno, NV, USAAbstract: The evaluation of pain and the subsequent issue of pain control is a clinical challenge that all healthcare providers face. Pain in the elderly population is especially difficult given the myriad of physiological, pharmacological, and psychological aspects of caring for the geriatric patient. Opiates are the mainstay of pain treatment throughout all age groups but special attention must be paid to the efficacy and side effects of these powerful drugs when prescribing to a population with impaired metabolism, excretion and physical reserve. In a random chart review of 300 US veterans, 44% of those receiving an analgesic also received opioids. The increasing use of opiates for pain management by healthcare practitioners requires that those prescribing opioids be aware of the special considerations for treating the elderly. This article will address the precautions one must take when using opiates in the geriatric population, as well as the side effects and ways to minimize them.Keywords: opiates, pain, elderly, side effects

  6. The Dark Side of Creativity (United States)

    Cropley, David H., Ed.; Cropley, Arthur J., Ed.; Kaufman, James C., Ed.; Runco, Mark A., Ed.


    With few exceptions, scholarship on creativity has focused on its positive aspects while largely ignoring its dark side. This includes not only creativity deliberately aimed at hurting others, such as crime or terrorism, or at gaining unfair advantages, but also the accidental negative side effects of well-intentioned acts. This book brings…

  7. Managing Chemotherapy Side Effects: Diarrhea (United States)

    ... such as Pedialyte ® ••Tea (without caffeine) ••Water ••Applesauce ••Bananas ••Crackers ••Cream of wheat or rice cereal ••Eggs •• ... has a series of 18 Chemotherapy Side Effects Sheets at:

  8. Analysis of cancer stem like cell characteristic in MKN-45 side population%MKN-45侧群细胞的肿瘤干细胞干性特征分析

    Institute of Scientific and Technical Information of China (English)


    Objective We tried to ascertain gastric cancer cell line MKN-45 contain SP cells, and learned about wether gastric cancer SP cells possess cancer stem-like characteristic. Method We used fluorescence activated cell sorting (FACS) to sort SP cells in human gastric carcinoma (GC) cell line MKN-45 cells labeled with Hoechst 33342, and then characterized the cancer stem-like properties of SP cells. Result The SP cells had higher clone formation efficiency than major population (MP) cells. Five stemness–related genes expression profiles, including OCT-4, SOX-2, NANOG, CD44 and ATP-binding cassette transporters gene ABCG-2, were tested in SP and MP cells using quantitative real-time RT-PCR. Western blot was chosen to show the difference of protein expression between SP and MP cells. Both results showed that there was significantly higher expression in SP cells than in MP cells. When inoculated into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, SP cells showed higher tumorigenesis tendency than MP cells. Conclusion SP cells possess cancer stem cell properties and proved that SP cells from MKN-45 were gastric cancer stem-like cells.%  目的探讨胃癌细胞系中是否存在SP细胞及SP细胞的生物学特征。方法采用荧光活化的细胞分选技术(FACS)从胃癌MKN-45细胞株获得SP细胞,进而分析这些SP细胞有无肿瘤干细胞特性;采用实时定量的RT-PCR检测5个干性相关基因OCT-4, SOX-2, NANOG, CD44和ABCG-2的mRNA在SP和MP 细胞中的表达水平,并进行统计学差异分析。结果发现二者之间具有显著差异。进一步使用蛋白印迹法(Western blot)定性分析发现:5个干性相关基因在SP和MP细胞中的蛋白表达水平亦有差异;体内实验结果显示,当SP细胞和MP细胞注射非糖尿病联合重度免疫缺陷(NOD/SCID)的小鼠,SP 细胞较MP细胞具有更强的成瘤性。结论综合分析本实验相关结果,可以推测SP细胞具有

  9. Blind loop perforation after side-to-side ileocolonic anastomosis

    Institute of Scientific and Technical Information of China (English)

    Raffaele; Dalla; Valle; Roberto; Zinicola; Maurizio; Iaria


    Blind loop syndrome after side-to-side ileocolonic anas-tomosis is a well-recognized entity even though its in-cidence and complication rates are not clearly defined. The inevitable dilation of the ileal cul-de-sac leads to stasis and bacterial overgrowth which eventually leads to mucosal ulceration and even full-thickness perfora-tion. Blind loop syndrome may be an underestimated complication in the setting of digestive surgery. It should always be taken into account in cases of acute abdomen in patients who previously underwent right hemicolectomy. We herein report 3 patients who were diagnosed with perforative blind loop syndrome a few years after standard right hemicolectomy followed by a side-to-side ileocolonic anastomosis.

  10. Blind loop perforation after side-to-side ileocolonic anastomosis. (United States)

    Valle, Raffaele Dalla; Zinicola, Roberto; Iaria, Maurizio


    Blind loop syndrome after side-to-side ileocolonic anastomosis is a well-recognized entity even though its incidence and complication rates are not clearly defined. The inevitable dilation of the ileal cul-de-sac leads to stasis and bacterial overgrowth which eventually leads to mucosal ulceration and even full-thickness perforation. Blind loop syndrome may be an underestimated complication in the setting of digestive surgery. It should always be taken into account in cases of acute abdomen in patients who previously underwent right hemicolectomy. We herein report 3 patients who were diagnosed with perforative blind loop syndrome a few years after standard right hemicolectomy followed by a side-to-side ileocolonic anastomosis.

  11. Two-Sided Tests and One-Sided Confidence Bounds



    Based on the duality between tests and confidence sets we introduce a new method to derive one-sided confidence bounds following the rejection of a null hypothesis with two-sided alternatives. This method imputes that the experimenter is only interested in confidence bounds if the null hypothesis is rejected. Furthermore, we suppose that he is only interested in the direction and a lower confidence bound concerning the distance of the true parameter value to the parameter values in the null h...

  12. Managing Chemotherapy Side Effects: Constipation (United States)

    N ational C ancer I nstitute Managing Chemotherapy Side Effects Constipation Take these steps: Eat high-fiber foods such as: ● ● Whole-grain breads and cereals ● ● Fruits and vegetables ● ● Nuts and seeds ...

  13. Novel side branch ostial stent. (United States)

    Chen, Shao-Liang; Lv, Shu-Zheng; Kwan, Tak W


    Bifurcation lesions are technically challenging and plagued by a high incidence of restenosis, especially at the side branch orifice, which results in a more frequent need for revascularization during the follow-up period. This report discusses two clinical experiences with a novel side branch ostial stent, the BIGUARD stent, designed for the treatment of bifurcation lesions; procedural success with no in-hospital complications was observed in types IVb and Ia lesions.

  14. The Moon's near side megabasin and far side bulge

    CERN Document Server

    Byrne, Charles


    Since Luna and Lunar Orbiter photographed the far side of the Moon, the mysterious dichotomy between the face of the Moon as we see it from Earth and the side of the Moon that is hidden has puzzled lunar scientists. As we learned more from the Apollo sample return missions and later robotic satellites, the puzzle literally deepened, showing asymmetry of the crust and mantle, all the way to the core of the Moon. This book summarizes the author’s successful search for an ancient impact feature, the Near Side Megabasin of the Moon and the extensions to impact theory needed to find it. The implications of this ancient event are developed to answer many of the questions about the history of the Moon.

  15. Wake flow behind two side-by-side square cylinders

    Energy Technology Data Exchange (ETDEWEB)

    Yen, Shun C., E-mail: [Department of Mechanical and Mechatronic Engineering, National Taiwan Ocean University, Keelung 202, Taiwan (China); Liu, Jung H. [Department of Mechanical and Mechatronic Engineering, National Taiwan Ocean University, Keelung 202, Taiwan (China)


    This study investigates the flow structures, form drag coefficients and vortex-shedding characteristics behind a single-square cylinder and two side-by-side cylinders in an open-loop wind tunnel. The Reynolds number (Re) and gap ratio (g*) are 2262 < Re < 28,000 and 0 {<=} g* {<=} 12, respectively. The flow patterns around the square cylinders are determined using the smoke-wire scheme. Experimental results indicate that the flow structures behind two side-by-side square cylinders are classified into three modes -single mode, gap-flow mode and couple vortex-shedding. The gap-flow mode displays anti-phase vortex shedding induced from the interference between the two square cylinders. However, the couple vortex-shedding mode exhibits in-phase vortex shedding that is caused by the independent flow behavior behind each square cylinder. The surface-pressure profile, form drag coefficient for each square cylinder (C{sub D}-bar) and vortex-shedding frequency were measured and calculated using a pressure transducer and a hot-wire anemometer. For two side-by-side cylinder configurations, the maximum C{sub D}-bar of 2.24 occurs in the single mode, while the minimum C{sub D}-bar of 1.68 occurs in the gap-flow mode. Additionally, the C{sub D}-bar in the coupled vortex-shedding mode is intermediate and approximately equal to that of a single (isolated) square cylinder. Moreover, the single mode has the highest Strouhal number (St) and the gap-flow mode has the lowest St.

  16. Brushless machine having ferromagnetic side plates and side magnets (United States)

    Hsu, John S


    An apparatus is provided having a cylindrical stator and a rotor that is spaced from a stator to define an annular primary air gap that receives AC flux from the stator. The rotor has a plurality of longitudinal pole portions disposed parallel to the axis of rotation and alternating in polarity around a circumference of the rotor. Each longitudinal pole portion includes portions of permanent magnet (PM) material and at least one of the longitudinal pole portions has a first end and an opposing second end and a side magnet is disposed adjacent the first end and a side pole is disposed adjacent the second end.

  17. Side Effects of Side Effects Information in Drug Information Leaflets. (United States)

    Maat, H. Pander; Klaassen, R.


    Describes a study in which drug information leaflets given to patients were improved in two ways, first by adding a short introductory paragraph on the nature of side effects generally, and second by adjusting frequency descriptors to more accurately reflect pretesting of the drug. Explains that participants in the study were less likely to…

  18. Running away from side effects

    DEFF Research Database (Denmark)

    Casla, S; Hojman, P; Márquez-Rodas, I


    be an integrative complementary intervention to improve physiological, physical and psychological factors that affect survival and quality of life of these patients. For that reason, the main objective of this review is to provide a general overview of exercise benefits in breast cancer patients and recommendations......The number of breast cancer survivors increases every year, thanks to the development of new treatments and screening techniques. However, patients present with numerous side effects that may affect their quality of life. Exercise has been demonstrated to reduce some of these side effects......, but in spite of this, few breast cancer patients know and follow the exercise recommendations needed to remain healthy. In this review, we describe the different breast cancer treatments and the related side effects and implications of exercise in relation to these. We propose that exercise could...

  19. A Typology of Multi-sided Platforms

    DEFF Research Database (Denmark)

    Staykova, Kalina Stefanova; Damsgaard, Jan


    which evolved several steps into being multi-sided (Facebook). Our analysis shows a structural difference between one-sided, two-sided and multi-sided platforms and that platforms consist of a core and potentially also a periphery. The sides of a platform and the ties which connect them can be arranged...

  20. Dark Side of the Universe

    CERN Document Server


    The Dark Side of the Universe (DSU) workshops bring together a wide range of theorists and experimentalists to discuss current ideas on models of the dark side, and relate them to current and future experiments. This year's DSU will take place in the colorful Norwegian city of Bergen. Topics include dark matter, dark energy, cosmology, and physics beyond the standard model. One of the goals of the workshop is to expose in particular students and young researchers to the fascinating topics of dark matter and dark energy, and to provide them with the opportunity to meet some of the best researchers in these areas .

  1. 人前列腺癌细胞系DU145中肿瘤干细胞样侧群细胞的分离%Identification of cancer stem cell -like side population cells in human prostate cancer cell line DU 145

    Institute of Scientific and Technical Information of China (English)

    殷波; 刘岗; 张辉; 李明; 隋文印; 宋永胜


    Objective;To identify the side population (SP) cells from human prostate cancer cell line DU 145 and characterize DU 145 SP cells preliminary. Methods: Fluorescence activated cell sorting (FACS) was applied to isolate SP cells from DU 145 cell line. The isolated SP cells were cultured in serum - free medium to observe the growth pattern. Reverse transcription - polymerase chain reaction (RT - PCR) was used to detect the expression of ABCG2 in DU 145 SP cells and parental DU 145 cells. Results: SP cells were isolated from DU 145 cells by flow cytometry, with a proportion of 1.1%. When cultured in serum -free medium, SP cells showed a clustered growth pattern compared to the parental DU 145 cells. Furthermore, a higher expression of ABCG2 in SP cells was detected by RT -PCR in contrast to parental DU 145 cells. Conclusion; DU 145 cell line contained SP cells with cancer stem cell properties.%目的:分离人前列腺癌细胞系DU 145中的侧群(side population, SP)细胞,并初步分析其生物学特性.方法:采用荧光激活细胞分类(fluorescence activated cell sorting,FACS)技术,从DU 145细胞中分离出侧群细胞,并检测其比例;继而培养于无血清培养基中,观察其生长特性.采用反转录聚合酶链反应( RT-PCR)技术检测侧群细胞中ABCG2的表达水平.结果:DU 145细胞中存在含量极少的侧群细胞,比例约1.1%;培养于无血清培养基中成簇生长.和对应的母系DU 145细胞相比,DU 145侧群细胞的ABCG2表达增高.结论:人前列腺癌细胞系DU 145中存在具有肿瘤干细胞特性的侧群细胞.

  2. Side-View Face Recognition

    NARCIS (Netherlands)

    Santemiz, Pinar; Spreeuwers, Luuk J.; Veldhuis, Raymond N.J.; Biggelaar , van den Olivier


    As a widely used biometrics, face recognition has many advantages such as being non-intrusive, natural and passive. On the other hand, in real-life scenarios with uncontrolled environment, pose variation up to side-view positions makes face recognition a challenging work. In this paper we discuss th

  3. The DarkSide Program

    Directory of Open Access Journals (Sweden)

    Rossi B.


    Full Text Available DarkSide-50 at Gran Sasso underground laboratory (LNGS, Italy, is a direct dark matter search experiment based on a liquid argon TPC. DS-50 has completed its first dark matter run using atmospheric argon as target. The detector performances and the results of the first physics run are presented in this proceeding.

  4. Reported Sildenafil Side Effects in Pediatric Pulmonary Hypertension Patients

    Directory of Open Access Journals (Sweden)

    Stephanie Leigh Siehr


    Full Text Available Background: Sildenafil, a phosphodiestase type 5 inhibitor, was approved in 2005 for the treatment of pulmonary arterial hypertension (PAH in adults, and is commonly used off-label for pediatric patients. Little is known, however, about sildenafil’s side effects in this population.Methods: Single institution, longitudinal survey-based study performed in an outpatient pediatric cardiology clinic. Pediatric patients on sildenafil (alone or in combination with other PH therapies completed questionnaires regarding frequency of vascular, gastrointestinal, neurologic and hematologic side effects. Results: Between January 2011 and May 2014, 66 pediatric patients with PH on sildenafil filled out 214 surveys, 32 patients (96 surveys on monotherapy, and 43 patients (118 surveys on sildenafil plus an endothelin receptor antagonist (bosentan or ambrisentan and/or a prostacyclin (epoprostenol or treprostinil. Overall, 30% of respondents identified at least one side effect. For all patients on sildenafil, incidence of side effects by system was 37% gastrointestinal, 35% vascular and 22% neurologic. For patients on sildenafil monotherapy, incidence of side effects by system was 24% gastrointestinal, 21% vascular and 18% neurologic compared to patients on combination therapy who reported an incidence of 48% gastrointestinal, 45% vascular and 25% neurologic.Conclusion: Incidence of vascular, gastrointestinal and neurologic side effect in pediatric patients on sildenafil therapy for pulmonary arterial hypertension was 30%. Side effects were more common in patients on combination therapy with an endothelin receptor antagonist and/or prostacyclin than in patients on sildenafil monotherapy.

  5. [Side effects of third generation progestins]. (United States)

    Sitruk-Ware, R


    A large number of publications on oral contraceptives (OC) can be found in the medical literature. These reports deal not only with mode of action or efficacy of OCs but also with side effects. Adverse drug reactions (ADR) are not accepted nor acceptable from a population of young women free of disease who expect from their mode of contraception to be fully efficient and devoid from side effects. In most instances, side effects observed with OCs as well as their efficacy are related to the total dose of steroïds contained in the combination, to the balance between the estrogen and the progestin content and to the specific characteristics of the molecules. Cardiovascular morbidity and mortality reported in OC users have been related firstly to the ethinylestradiol (EE) and as a first step, the estrogen dose has been reduced in the OCs synthesized in the 70s. Later on, cardiovascular risk has been correlated to lipid profile changes and progestins with androgenic properties have been made responsible for cardiovascular events reported in OC users. In order to minimize the incidence of ADRs and to induce beneficial changes in lipid patterns, new progestational molecules devoid of androgenic properties have been recently synthesized. Three compounds called "third generation" progestins, derived from levonorgestrel are presently available in Europe. These three gonane progestins demonstrate affinity for the androgenic receptor, but when administered together with EE do not oppose the estrogenic effect observed on protein markers such as the Sex Hormone Binding Globulin (SHBG) or the High Density Lipoprotein (HDL).(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Narrating narcolepsy--centering a side effect. (United States)

    Lundgren, Britta


    The mass-vaccination with Pandemrix was the most important preventive measure in Sweden during the A(H1N1) influenza pandemic of 2009-2010, and covered 60% of the population. From 2010, an increased incidence of the neurological disease narcolepsy was reported, and an association with Pandemrix was affirmed for more than 200 children and young adults. The parental experience of this side effect provided a starting point for a collectively shaped critical narrative to be acted out in public, but also personalized narratives of continual learning about the disease and its consequences. This didactic functionality resulted in active meaning-making practices about how to handle the aftermath--using dark humor, cognitive tricks, and making themselves and their children's bodies both objects and subjects of knowledge. Using material from interviews with parents, this mixing of knowledge work and political work, and the potential for reflective consciousness, is discussed.

  7. The Dark Side of Management

    DEFF Research Database (Denmark)

    Hanlon, Gerard; Dunne, Stephen; Johnsen, Christian Garmann


    Towards the end of 2015, the ephemera collective organised, chaired and participated within two separate Q+A panels celebrating the launch of Gerard Hanlon’s The dark side of management: A secret history of management theory. The events took place in The University of Leicester’s School...... of Management and Copenhagen Business School’s Management, Politics and Philosophy Department. Each of the events were recorded, transcribed, edited and amalgamated into the following feature....

  8. Metabolic Side Effects of Lithium

    Directory of Open Access Journals (Sweden)

    M. Cagdas Eker


    Full Text Available Lithium is an alkaline ion being used since 19th century. After its widespread use in psychiatric disorders, observed side effects caused skepticism about its therapeutic efficacy. Despite several disadvantages, lithium is one of the indispensible drugs used in affective disorders, especially in bipolar disorder. It became a necessity for physicians to recognize its side effects since lithium is still accepted as a gold standard in the treatment of bipolar disorder. Adverse effects of chronic administration of lithium on several organ systems are widely known. In this article metabolic effects of lithium on thyroid and parathyroid glands, body mass index and kidneys will be discussed along with their mechanisms, clinical findings, possible risk factors and treatment. One of the most common side effect of lithium is hypothyroidism. It has the same clinical and biochemical properties as primary hypothyroidism and observed as subclinical hypothyroidism in the first place. Hypothyroidism, even its subclinical form, may be associated with non-response or inadequate response and is indicated as a risk factor for development of rapid cycling bipolar disorder. Therefore, hypothyroidism should be screened no matter how severe it is and should be treated with thyroid hormone in the presence of clinical hypothyroidism. Weight gain due to lithium administration disturbs the compliance to treatment and negatively affects the course of the illness. Increased risk for diabetes, hypertension, ischemic heart disease and stroke because of weight gain constitute other centers of problem. Indeed, it is of importance to determine the risk factors before treatment, to follow up the weight, to re-organize nutritional habits and to schedule exercises. Another frequent problematic side effect of lithium treatment is renal dysfunction which clinically present as nephrogenic diabetes insipidus with the common symptoms of polyuria and polydipsia. Nephrogenic diabetes

  9. Flapping propulsion with side-by-side pitching foils (United States)

    Huera-Huarte, Francisco


    Fish schools are one of the most common types of collective behaviour observed in nature. One of the reasons why fish swim in groups, is to reduce the cost of transport of the school. In this work we explore the propulsive performance of two foils flapping in a symmetric configuration, i.e. with an out-of-phase flapping motion. Direct thrust measurements and Particle Image Velocimetry (PIV) allowed a detailed examination of the forces and the wake generated by the system, for different kinematics (swept angles and frequencies) and shaft separations. For certain specific cases, volumetric PIV shows major differences on how the different structures in the wake of the system evolve, depending on the imposed kinematics and the side-by-side separation between the foils. Results obtained will be compared against data produced with isolated flapping foils with similar imposed kinematics, with the aim to better understand the interactions between both and the performance of the system as a whole. The author would like to acknowledge the financial support provided by the Spanish Ministerio de Economia y competitividad (MINECO) through Grant DPI2015-71645-P.

  10. Demographic side effects of selective hunting in ungulates and carnivores. (United States)

    Milner, Jos M; Nilsen, Erlend B; Andreassen, Harry P


    Selective harvesting regimes are often implemented because age and sex classes contribute differently to population dynamics and hunters show preferences associated with body size and trophy value. We reviewed the literature on how such cropping regimes affect the demography of the remaining population (here termed demographic side effects). First, we examined the implications of removing a large proportion of a specific age or sex class. Such harvesting strategies often bias the population sex ratio toward females and reduce the mean age of males, which may consequently delay birth dates, reduce birth synchrony, delay body mass development, and alter offspring sex ratios. Second, we reviewed the side effects associated with the selective removal of relatively few specific individuals, often large trophy males. Such selective harvesting can destabilize social structures and the dominance hierarchy and may cause loss of social knowledge, sexually selected infanticide, habitat changes among reproductive females, and changes in offspring sex ratio. A common feature of many of the reported mechanisms is that they ultimately depress recruitment and in some extreme cases even cause total reproductive collapse. These effects could act additively and destabilize the dynamics of populations, thus having a stronger effect on population growth rate than first anticipated. Although more experimental than observational studies reported demographic side effects, we argue that this may reflect the quite subtle mechanisms involved, which are unlikely to be detected in observational studies without rigorous monitoring regimes. We call for more detailed studies of hunted populations with marked individuals that address how the expression of these effects varies across mating systems, habitats, and with population density. Theoretical models investigating how strongly these effects influence population growth rates are also required.

  11. Increased Proportion of Hematopoietic Stem and Progenitor Cell Population in Cord Blood of Neonates Born to Mothers with Gestational Diabetes Mellitus (United States)

    Hadarits, Orsolya; Zóka, András; Barna, Gábor; Al-Aissa, Zahra; Rosta, Klára; Rigó, János; Kautzky-Willer, Alexandra; Somogyi, Anikó


    We assessed the hematopoietic stem and progenitor cell (HSPC) population in the cord blood of neonates born to mothers with gestational diabetes mellitus (GDM) in a hypothesis generating pilot study, due to that, neonatal polycythemia may be the consequence of GDM pregnancy. Forty-five pregnant women with GDM (last trimester mean HbA1C = 33.9 mmol/mol) and 42 (nondiabetic) control pregnant women were enrolled after their routine 75 g oral glucose tolerance test (OGTT) between the 24th and 28th gestational week (with expected differences in their mean routine clinical characteristics: plasma glucose at OGTT: 0′ = 5.07 vs. 4.62 mM, 120′ = 8.9 vs. 5.76 mM, age = 35.07 vs. 31.66 years, prepregnancy body mass index = 27.9 vs. 23.9 kg/m2, GDM vs. control, respectively) on a voluntary basis after signing the informed consent. EDTA-treated cord blood samples were analyzed by flow cytometry and the software Kaluza1.2 using CD45 and CD34-specific fluorescent antibodies to identify the HSPC population (CD34+ cells within the CD45dim blast gate). The proportion of CD34+CD45dim HSPCs among the nucleated cells was significantly (P < 0.05, statistical power = 60.8%) higher in the cord blood samples of neonates born to mothers with GDM (median 0.38%) compared to neonates born to nondiabetic mothers (median 0.32%) and according to treatment types (P < 0.05) median: control 0.32%, GDM-diet only 0.37%, GDM-on insulin 0.45%; control versus GDM on insulin (P < 0.05). The increased proportion of circulating CD34+CD45dim cells in the cord blood may possibly be related to altered fetal stem cell mobilization in GDM pregnancy, yet these results should be interpreted only as preliminary due to the small sample sizes. PMID:26494027

  12. Lighter side of adaptive optics

    CERN Document Server

    Tyson, Robert K


    Adaptive optics has been under development for well over 40 years. It is an indisputable necessity for all major ground-based astronomical telescopes and is the foundation for laser and wavefront sensor design. Lighter Side of Adaptive Optics is a nontechnical explanation of optics, the atmosphere, and the technology for ""untwinkling"" the stars. While interweaving a fictional romantic relationship as an analogy to adaptive optics, and inserting satire, humor, and philosophical rants, Tyson makes a difficult scientific topic understandable. The ""why"" and ""how"" of adaptive optics has never

  13. Complementary populations of human adipose CD34+ progenitor cells promote growth, angiogenesis, and metastasis of breast cancer. (United States)

    Orecchioni, Stefania; Gregato, Giuliana; Martin-Padura, Ines; Reggiani, Francesca; Braidotti, Paola; Mancuso, Patrizia; Calleri, Angelica; Quarna, Jessica; Marighetti, Paola; Aldeni, Chiara; Pruneri, Giancarlo; Martella, Stefano; Manconi, Andrea; Petit, Jean-Yves; Rietjens, Mario; Bertolini, Francesco


    Obesity is associated with an increased frequency, morbidity, and mortality of several types of neoplastic diseases, including postmenopausal breast cancer. We found that human adipose tissue contains two populations of progenitors with cooperative roles in breast cancer. CD45(-)CD34(+)CD31(+)CD13(-)CCRL2(+) endothelial cells can generate mature endothelial cells and capillaries. Their cancer-promoting effect in the breast was limited in the absence of CD45(-)CD34(+)CD31(-)CD13(+)CD140b(+) mesenchymal progenitors/adipose stromal cells (ASC), which generated pericytes and were more efficient than endothelial cells in promoting local tumor growth. Both endothelial cells and ASCs induced epithelial-to-mesenchymal transition (EMT) gene expression in luminal breast cancer cells. Endothelial cells (but not ASCs) migrated to lymph nodes and to contralateral nascent breast cancer lesions where they generated new vessels. In vitro and in vivo, endothelial cells were more efficient than ASCs in promoting tumor migration and in inducing metastases. Granulocyte colony-stimulating factor (G-CSF) effectively mobilized endothelial cells (but not ASCs), and the addition of chemotherapy and/or of CXCR4 inhibitors did not increase endothelial cell or ASC blood mobilization. Our findings suggest that adipose tissue progenitor cells cooperate in driving progression and metastatic spread of breast cancer.

  14. Enter the DarkSide (United States)

    Davini, Stefano


    A wide range of astrophysical measurements evidence that the stars and gas in all galaxies are immersed in a much larger cloud of non-luminous and non-baryonic dark matter. The nature of the dark matter is still totally unknown, and the resolution of the dark matter puzzle is of fundamental importance to cosmology, astrophysics, and elementary particle physics. One of the major lines of researches directing their efforts at detection of dark matter is direct searches of Weakly Interacting Massive Particles (WIMPs) with detectors operated in deep underground laboratories. The new generation of direct searches of WIMPs promises to probe the most interesting region of parameters for the dark matter candidates. I will review and describe the DarkSide-50 underground Argon detector at Laboratori Nazionali del Gran Sasso.

  15. Shortest Paths With Side Sensors

    CERN Document Server

    Salaris, Paolo; Bicchi, Antonio


    We present a complete characterization of shortest paths to a goal position for a vehicle with unicycle kinematics and a limited range sensor, constantly keeping a given landmark in sight. Previous work on this subject studied the optimal paths in case of a frontal, symmetrically limited Field--Of--View (FOV). In this paper we provide a generalization to the case of arbitrary FOVs, including the case that the direction of motion is not an axis of symmetry for the FOV, and even that it is not contained in the FOV. The provided solution is of particular relevance to applications using side-scanning, such as e.g. in underwater sonar-based surveying and navigation.

  16. The dark side of technology

    CERN Document Server

    Townsend, Peter


    Technological progress comes with a dark side where good ideas and intentions produce undesirable results (extreme downsides include atomic and biological weapons). The many and various unexpected outcomes of technology span humorous to bizarre, to situations that threaten human survival. Development can be positive for some, but negative and isolating for others (e.g. older or poorer people). Progress is often transient, as faster electronics and computers dramatically shorten retention time of data, knowledge, and information loss (e.g. even photos may be unreadable within a generation). Progress and globalization are also destroying past languages and cultures. Advances cut across all areas of science and life, and the scope is vast from biology, medicine, agriculture, transport, electronics, computers, long-range communications, to a global economy. Reliance on technology causes unexpected technology-driven vulnerability to natural events (e.g. intense sunspot activity) that could annihilate advanced soci...

  17. 49 CFR 238.217 - Side structure. (United States)


    ... 49 Transportation 4 2010-10-01 2010-10-01 false Side structure. 238.217 Section 238.217 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Equipment § 238.217 Side structure. Each passenger car shall comply with the following: (a) Side posts...

  18. Unbanked Households: Evidence of Supply-Side Factors


    Matray , Adrien; Celerier , Claire


    This paper provides evidence that supply-side factors significantly drive the high share of unbanked households. Using interstate branching deregulation in the U.S. after 1994 as an exogenous shock, the authors show that an increase in bank competition is associated with a large drop in the share of unbanked households. The authors find that the effect is even stronger for populations that are more likely to be rationed by banks, such as black households living in "high racial bias'' states. ...

  19. Distributed video coding with multiple side information

    DEFF Research Database (Denmark)

    Huang, Xin; Brites, C.; Ascenso, J.;


    Distributed Video Coding (DVC) is a new video coding paradigm which mainly exploits the source statistics at the decoder based on the availability of some decoder side information. The quality of the side information has a major impact on the DVC rate-distortion (RD) performance in the same way...... the quality of the predictions had a major impact in predictive video coding. In this paper, a DVC solution exploiting multiple side information is proposed; the multiple side information is generated by frame interpolation and frame extrapolation targeting to improve the side information of a single...

  20. A Novel Population of Mesenchymal Progenitors with Hematopoietic Potential Originated from CD14- Peripheral Blood Mononuclear Cells

    Directory of Open Access Journals (Sweden)

    Gang Hu, Peng Liu, Jie Feng, Yan Jin


    Full Text Available Hemopoietic system derived progenitor cells with mesenchymal features have been identified including CD14+ monocyte-derived progenitors. However, it is unclear whether there are mesenchyme derived progenitors with hematopoietic potential. Herein, we identified a novel CD14- cell-derived population with both mesenchymal and hematopoietic features in rat peripheral blood, and this cell population is different from the CD14+ monocyte-derived progenitors but designated peripheral blood multipotential mesenchymal progenitors (PBMMPs. Phenotype analysis demonstrated expression of mesenchymal markers in PBMMPs including BMPRs, Endoglin/CD105, Fibronectin (Fn, Vimentin (Vim, Collagen (Col I/II/III along with hematopoietic marker CD34. CD14+ cell-derived population shared the same characteristics with CFs. In mixed culture of CD14+ and CD14- cells, PBMMPs were a predominant component and expressed CD29high, CD73high, CD34high, CD45low and CD90. Except for the value of mixed T lymphocytes and CD14+ cell-derived population, hematopoietic characters of cultured PBMMPs were indicated by CD14-/CD34+/CD45-/CD90+. The mesenchymal origin was further confirmed by comparing PBMMPs with bone marrow stromal cells. Finally, we transplanted PBMMPs into a skin wound model, and results showed the specific potential of PBMMPs in not only extracellular matrix secretion but epidermal regeneration. This study provides evidence that peripheral blood contains common hematopoietic-mesenchymal progenitors from both hematopoietic and mesenchymal lineages, and CD34+ mesenchymal progenitors are a possible alternative source of epidermal cells in wound healing.

  1. Car Side Structure Crashworthiness in Pole and Moving Deformable Barrier Side Impacts

    Institute of Scientific and Technical Information of China (English)

    WANG Dazhi; DONG Guang; ZHANG Jinhuan; HUANG Shilin


    To clearly understand passenger car structure's crashworthiness in typical side impacts of pole and moving deformable barrier (MDB) impact modes, which could assist the establishment of Chinese vehicle side impact safety regulations, a full midsized car finite element model, calibrated by pole side impact test, was built and the pole side impact according to European New Car Assessment Program (EuroNCAP) and the MDB side impact according to ECE R95 regulations were simulated with LS-DYNA. The accelerations and the structure deformations from simulations were compared. It can be concluded that the pole side impact focuses primarily on side structure crashworthiness as a result of large intrusions, while the MDB side impact focuses primarily on full side structure crashworthiness. Accordingly, occupant protection strategies focus on different aspects to improve side impact safety. In the pole side impact the objective is to maintain the passenger compartment and protect the passenger's head from impacting the pole, while in the MDB side impact the objective is to protect the full human body. In the design of the car side structures, at least these two tests should be considered for assessing their side impact crashworthiness. Conducting these two side impact tests as certified tests provides insights into car safety during side impacts.

  2. Physiological and skill demands of 'on-side' and 'off-side' games. (United States)

    Gabbett, Tim J; Jenkins, David G; Abernethy, Bruce


    This study investigated the physiological and skill demands of 'on-side' and 'off-side' games in elite rugby league players. Sixteen male rugby league players participated in 'on-side' and 'off-side' games. Both small-sided games were played in a 40- × 40-m playing area. The 'off-side' game permitted players to have 3 'plays' while in possession of the ball. Players were permitted to pass backward or forward (to an 'off-side' player). The 'on-side' game also permitted players to have 3 'plays' while in possession of the ball. However, players were only permitted to pass backward to players in an 'on-side' position. Heart rate and movement patterns (via global positioning system) were recorded continuously throughout both games. Data were collected on the distance covered, number of high-acceleration and velocity efforts, and recovery between efforts. Video footage was also taken to track the performance of the players. Post hoc inspection of the footage was undertaken to count the number of possessions and the number and quality of disposals. In comparison to 'on-side' games, 'off-side' games had a greater number of involvements ("touches"), passes, and effective passes. However, the cognitive demands of 'on-side' games were greater than 'off-side' games. 'Off-side' games resulted in a greater total distance covered, greater distance covered in mild and moderate accelerations, and greater distance covered in low, moderate, and high-velocity efforts. There were also a greater number of short duration recovery periods between efforts in 'off-side' games. The results of this study demonstrate that 'off-side' games provide greater physiological and skill demands than 'on-side' games. 'Off-side' games may provide a practical alternative to 'on-side' games for the development of skill and fitness in elite rugby league players.

  3. Sexual side effects induced by psychotropic drugs

    DEFF Research Database (Denmark)

    Kristensen, Ellids


    The majority of psychotropic drugs entail sexual side effects. The sexual side effects may reduce quality of life and may give rise to non-compliance. For example, 30-60 per cent of patients treated with antidepressants are known to develop a sexual dysfunction. However, some psychotropic drugs...... with no or very few sexual side effects have begun to emerge. The treatment of sexual side effects induced by psychotropic drugs may consist of: modified sexual habits, reduction in dosage, switching to another medication, possibly in combination with different psychotropic agents, other varieties...

  4. Laterality and flight: concurrent tests of side-bias and optimality in flying tree swallows. (United States)

    Mandel, James T; Ratcliffe, John M; Cerasale, David J; Winkler, David W


    Behavioural side-bias occurs in many vertebrates, including birds as a result of hemispheric specialization and can be advantageous by improving response times to sudden stimuli and efficiency in multi-tasking. However, behavioural side-bias can lead to morphological asymmetries resulting in reduced performance for specific activities. For flying animals, wing asymmetry is particularly costly and it is unclear if behavioural side-biases will be expressed in flight; the benefits of quick response time afforded by side-biases must be balanced against the costs of less efficient flight due to the morphological asymmetry side-biases may incur. Thus, competing constraints could lead to context-dependent expression or suppression of side-bias in flight. In repeated flight trials through an outdoor tunnel with obstacles, tree swallows (Tachycineta bicolor) preferred larger openings, but we did not detect either individual or population-level side-biases. Thus, while observed behavioural side-biases during substrate-foraging and copulation are common in birds, we did not see such side-bias expressed in obstacle avoidance behaviour in flight. This finding highlights the importance of behavioural context for investigations of side-bias and hemispheric laterality and suggests both proximate and ultimate trade-offs between species-specific cognitive ecology and flight biomechanics.

  5. Laterality and flight: concurrent tests of side-bias and optimality in flying tree swallows.

    Directory of Open Access Journals (Sweden)

    James T Mandel

    Full Text Available Behavioural side-bias occurs in many vertebrates, including birds as a result of hemispheric specialization and can be advantageous by improving response times to sudden stimuli and efficiency in multi-tasking. However, behavioural side-bias can lead to morphological asymmetries resulting in reduced performance for specific activities. For flying animals, wing asymmetry is particularly costly and it is unclear if behavioural side-biases will be expressed in flight; the benefits of quick response time afforded by side-biases must be balanced against the costs of less efficient flight due to the morphological asymmetry side-biases may incur. Thus, competing constraints could lead to context-dependent expression or suppression of side-bias in flight. In repeated flight trials through an outdoor tunnel with obstacles, tree swallows (Tachycineta bicolor preferred larger openings, but we did not detect either individual or population-level side-biases. Thus, while observed behavioural side-biases during substrate-foraging and copulation are common in birds, we did not see such side-bias expressed in obstacle avoidance behaviour in flight. This finding highlights the importance of behavioural context for investigations of side-bias and hemispheric laterality and suggests both proximate and ultimate trade-offs between species-specific cognitive ecology and flight biomechanics.

  6. Isolation and characterisation of human gingival margin-derived STRO-1/MACS1 and MACS2 cell populations

    Institute of Scientific and Technical Information of China (English)

    Karim M Fawzy El-Sayed; Sebastian Paris; Christian Graetz; Neemat Kassem; Mohamed Mekhemar; Hendrick Ungefroren; Fred Fandrich; Christof Dorfer


    Recently, gingival margin-derived stem/progenitor cells isolated via STRO-1/magnetic activated cell sorting (MACS) showed remarkable periodontal regenerative potential in vivo. As a second-stage investigation, the present study’s aim was to perform in vitro characterisation and comparison of the stem/progenitor cell characteristics of sorted STRO-1-positive (MACS1) and STRO-1-negative (MACS2) cell populations from the human free gingival margin. Cells were isolated from the free gingiva using a minimally invasive technique and were magnetically sorted using anti-STRO-1 antibodies. Subsequently, the MACS1 and MACS2 cell fractions were characterized by flow cytometry for expression of CD14, CD34, CD45, CD73, CD90, CD105, CD146/MUC18 and STRO-1. Colony-forming unit (CFU) and multilineage differentiation potential were assayed for both cell fractions. Mineralisation marker expression was examined using real-time polymerase chain reaction (PCR). MACS1 and MACS2 cell fractions showed plastic adherence. MACS1 cells, in contrast to MACS2 cells, showed all of the predefined mesenchymal stem/progenitor cell characteristics and a significantly higher number of CFUs (P,0.01). More than 95%of MACS1 cells expressed CD105, CD90 and CD73;lacked the haematopoietic markers CD45, CD34 and CD14, and expressed STRO-1 and CD146/MUC18. MACS2 cells showed a different surface marker expression profile, with almost no expression of CD14 or STRO-1, and more than 95%of these cells expressed CD73, CD90 and CD146/MUC18, as well as the haematopoietic markers CD34 and CD45 and CD105. MACS1 cells could be differentiated along osteoblastic, adipocytic and chondroblastic lineages. In contrast, MACS2 cells demonstrated slight osteogenic potential. Unstimulated MACS1 cells showed significantly higher expression of collagen I (P,0.05) and collagen III (P,0.01), whereas MACS2 cells demonstrated higher expression of osteonectin (P,0.05;Mann–Whitney). The present study is the first to compare gingival

  7. 7 CFR 29.6035 - Side. (United States)


    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Side. 29.6035 Section 29.6035 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... INSPECTION Standards Definitions § 29.6035 Side. A certain phase of quality as contrasted with some...

  8. European side markers effect on traffic safety

    NARCIS (Netherlands)

    Roelfsema, A.; Theeuwes, J.; Alferdinck, J.W.A.M


    In 1993 new European legislation regarding side-markers for passenger cars became effective. Volvo requested the TNO-Human Factors Research Institute (HFRI) to investigate the possible safety benefit of this European side-markers configuration. A test panel at TNO- HFRI was used to determine the dif

  9. Identifying Cross-Sided Liquidity Externalities

    NARCIS (Netherlands)

    J.A. Skjeltorp (Johannes); E. Sojli (Elvira); W.W. Tham (Wing Wah)


    markdownabstract__Abstract__ We study the relevance of the cross-sided externality between liquidity makers and takers from the two-sided market perspective. We use exogenous changes in the make/take fee structure, minimum tick-size and technological shocks for liquidity takers and makers, as exper

  10. Managing Chemotherapy Side Effects: Nausea and Vomiting (United States)

    ... boiled, without the skin ••White rice ••White toast ••Bananas ••Canned fruit such as applesauce, peaches, and pears •• ... has a series of 18 Chemotherapy Side Effects Sheets at:

  11. Back-side readout semiconductor photomultiplier (United States)

    Choong, Woon-Seng; Holland, Stephen E


    This disclosure provides systems, methods, and apparatus related to semiconductor photomultipliers. In one aspect, a device includes a p-type semiconductor substrate, the p-type semiconductor substrate having a first side and a second side, the first side of the p-type semiconductor substrate defining a recess, and the second side of the p-type semiconductor substrate being doped with n-type ions. A conductive material is disposed in the recess. A p-type epitaxial layer is disposed on the second side of the p-type semiconductor substrate. The p-type epitaxial layer includes a first region proximate the p-type semiconductor substrate, the first region being implanted with p-type ions at a higher doping level than the p-type epitaxial layer, and a second region disposed on the first region, the second region being doped with p-type ions at a higher doping level than the first region.

  12. A Typology of Multi-sided Platforms

    DEFF Research Database (Denmark)

    Staykova, Kalina Stefanova; Damsgaard, Jan


    exemplary cases which allow us to illustrate the platform heterogeneity and to support new MSPs typology. As examples we include a physical two-sided platform (Gatwick Airport) that adds a third side, a digital one-sided platform transformed into being two-sided (Pingit) and a digital one-sided platform......In this paper we address how the composition of a platform impacts the platform’s business model. By platform’s business model we mean platform features, platform architecture and platform governance. To this end, we construct the Platform Business Model Framework. We apply the framework to three...... in several configurations. The particular platform architecture can explain the difficulties in designing a viable business models for platforms....


    Directory of Open Access Journals (Sweden)

    N. A. Onishchenko


    Full Text Available In this review article the necessity of adaptation and introduction into clinical practice of simultaneous monitoring of immune blood cells and cytokines in patients with grafted organs for a choice of individual tactic of immuno- suppressive therapy, determination of its efficiency and forecasting is proved. It is emphasized, that with the spe- cial attention it ought to concern to characteristic of CD4 + T-lymphocytes and to definition of an interrelation of their separate populations in peripheral blood (Treg, Th17, Tact memory cells – CD4+CD25hiCD127hiCD45RO since they are the basic participants of immune system reaction on grafts. 

  14. Footballers' movement behaviour during 2-, 3-, 4- and 5-a-side small-sided games

    NARCIS (Netherlands)

    Aguiar, Marco; Goncalves, Bruno; Botelho, Goreti; Lemmink, Koen; Sampaio, Jaime


    The aim of this study was to compare footballers' movement behaviour during 2-, 3-, 4- and 5-a-side small-sided games. Ten young professional players (age=18.0 +/- 0.67years) participated in 3 bouts of each small-sided games for 6min with 1min of active rest between bouts. Positional data were colle

  15. Decision making in right-sided diverticulitis

    Institute of Scientific and Technical Information of China (English)

    Li-Rung Shyung; Shee-Chan Lin; Shou-Chuan Shih; Chin-Roa Kao; Sun-Yen Chou


    AIM: To evaluate systematically our nine-year experience in treating right-sided diverticulitis of the colon, and to explore its clinical and radiological relationship.METHODS: The clinical and radiological data of 40 patients with colonic diverticulitis treated in Mackay Memorial Hospital,Taipei, from 1993 through 2002 were reviewed retrospectively.RESULTS: The average age of the patients with right-sided diverticulitis was 53.1 years, which was 11.6 years younger than that of the patients with left-sided diverticulitis. The preoperative diagnosis of appendicitis was made in 8 of 13 right-sided diverticulitis patients. Nine (69 %) had right lower quadrant abdominal pain for more than 48 hours, and ten patients (77 %) presented with fever. CT findings suggesting acute right-sided diverticulitis including thickening of the intestinal wall and pericolonic inflammation were present in five patients.CONCLUSION: Right-sided diverticulitis is easily confused with acute appendicitis because it occurs at a somewhat younger age than that in left-sided diverticulitis. Barium enema and CT are helpful for the early diagnosis of rightsided diverticulitis. While clearly not required in the majority of patients with right lower quadrant abdominal pain, barium enema and CT may be helpful in making the decision with a clinical history or physical examinations atypical of acute appendicitis.

  16. Effect of knee joint angle on side-to-side strength ratios. (United States)

    Krishnan, Chandramouli; Williams, Glenn N


    Isometric knee extensor and flexor strength are typically tested at different joint angles due to the differences in length-tension relationships of the quadriceps and hamstring muscles. The efficiency of strength testing can be improved if the same angle can be used to test both the knee extensor and flexor muscle groups. The aim of this study was to determine an optimal angle for isometric knee strength testing by examining the effect of knee angle on side-to-side peak torque ratios. Eighteen active young people (9 males and 9 females) participated in this study. Knee extensor and knee flexor strength were tested on both sides at 30°, 60°, and 90° of knee flexion. The effect of knee flexion angle on side-to-side peak torque ratios, raw torque values, and side-to-side flexor-to-extensor torque ratios were assessed. Side-to-side knee extensor peak torque ratios and knee flexor-to-extensor torque ratios differed significantly by knee flexion angle (p = 0.024 and p = 0.011, respectively), but side-to-side knee flexor peak torque ratios did not differ significantly (p = 0.311). When considering both side-to-side peak torque ratios and flexor-to-extensor torque ratios, the values were more symmetrical (i.e., closer to 100%) only at 60° of knee flexion. Our results indicate that both the knee flexors and the knee extensors can be tested clinically at 60° of knee flexion. Our results also indicate that the hamstrings can be tested at any of the 3 angles if the examiner is interested in side-to-side ratios rather than raw torque values. These results may facilitate more efficient and flexible clinical knee strength testing.

  17. Neglected Side Effects After Radical Prostatectomy

    DEFF Research Database (Denmark)

    Frey, Anders Ullmann; Sønksen, Jens; Fode, Mikkel


    INTRODUCTION: A series of previously neglected sexually related side effects to radical prostatectomy (RP) has been identified over the recent years. These include orgasm-associated incontinence (OAI), urinary incontinence in relation to sexual stimulation (UISS), altered perception of orgasm......, and the online Cochrane library. The PRISMA guidelines for systematic reviews were followed, and protocol as well as search strategies was registered at (RN: CRD42012003165). MAIN OUTCOME MEASURE: The main outcome measure was incidence rates for the relevant side effects...... been shown to double the risk of OAP. PS occurs in 15-68% of RP patients. Nerve sparing and preservation of erectile function may help preserve penile length. With regard to all side effects, studies indicate that they are reduced over time. CONCLUSIONS: The sexually related side effects summarized...

  18. Side- ja turvanguamet / Indrek Süld

    Index Scriptorium Estoniae

    Süld, Indrek


    Ilmunud ka: 2003 : annual report : [Eesti Raudtee]. - Tallinn, 2004, lk. 34-35; 2003 : godovoi ottshjot : [Eesti Raudtee]. - Tallinn, 2004, lk. 34-35. Ülevaade AS-i Eesti Raudtee side- ja turvanguameti tegevusest 2003. aastal. Skeem

  19. Lymphedema as a Cancer Treatment Side Effect (United States)

    ... Navigating Cancer Care > Side Effects > Lymphedema Request Permissions Lymphedema Approved by the Cancer.Net Editorial Board , 05/ ... years after cancer treatment has ended. Symptoms of lymphedema People with lymphedema in their arm or leg ...

  20. Possible Side-Effects from Vaccines (United States)

    ... her at risk of contracting a potentially deadly disease. Adenovirus vaccine side-effects What are the risks from Adenovirus vaccine? A vaccine, like any medicine, could cause a serious reaction. But the risk ...

  1. Side Stream Filtration for Cooling Towers

    Energy Technology Data Exchange (ETDEWEB)



    This technology evaluation assesses side stream filtration options for cooling towers, with an objective to assess key attributes that optimize energy and water savings along with providing information on specific technology and implementation options. This information can be used to assist Federal sites to determine which options may be most appropriate for their applications. This evaluation provides an overview of the characterization of side stream filtration technology, describes typical applications, and details specific types of filtration technology.

  2. Hematological Side Effects of Atypical Antipsychotic Drugs

    Directory of Open Access Journals (Sweden)

    Serap Erdogan


    Full Text Available Atypical antipsychotics cause less frequently extrapyramidal system symptoms, neuroleptic malignant syndrome and hyperprolactinemia than typical antipsychotics. However hematological side effects such as leukopenia and neutropenia could occur during treatment with atypical antipsychotics. These side effects could lead to life threatening situations and the mortality rate due to drug related agranulocytosis is about 5-10%. There are several hypothesis describing the mechanisms underlying drug induced leukopenia and/or neutropenia such as direct toxic effects of these drugs upon the bone marrow or myeloid precursors, immunologic destruction of the granulocytes or supression of the granulopoiesis. Clozapine is the antipsychotic agent which has been most commonly associated with agranulocytosis. A nitrenium ion which is formed by the bioactivation of clozapine is thought to have an important role in the pathophysiogy of this adverse effect. Aside from clozapine, there are several case reports reporting an association between olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole and leukopenia. We did not find any study or case report presenting amisulpride or sulpride related hematological side effects in our literature search. Patients who had hematological side effects during their previous antipsychotic drug treatments and who had lower baseline blood leukocyte counts, have higher risk to develop leukopenia or neutropenia during their current antipsychotic treatment. Once leukopenia and neutropenia develops, drugs thought to be responsible for this side effect should be discontinued or dosages should be lowered. In some cases iniatition of lithium or G-CSF (granulocyte colony-stimulating factor therapy may be helpful in normalizing blood cell counts. Clinicans should avoid any combination of drugs known to cause hematological side effects. Besides during antipsychotic treatment, infection symptoms such as fever, cough, sore throat or

  3. Temporomandibular disorders: the habitual chewing side syndrome.

    Directory of Open Access Journals (Sweden)

    Urbano Santana-Mora

    Full Text Available BACKGROUND: Temporomandibular disorders are the most common cause of chronic orofacial pain, but, except where they occur subsequent to trauma, their cause remains unknown. This cross-sectional study assessed chewing function (habitual chewing side and the differences of the chewing side and condylar path and lateral anterior guidance angles in participants with chronic unilateral temporomandibular disorder. This is the preliminary report of a randomized trial that aimed to test the effect of a new occlusal adjustment therapy. METHODS: The masticatory function of 21 randomly selected completely dentate participants with chronic temporomandibular disorders (all but one with unilateral symptoms was assessed by observing them eat almonds, inspecting the lateral horizontal movement of the jaw, with kinesiography, and by means of interview. The condylar path in the sagittal plane and the lateral anterior guidance angles with respect to the Frankfort horizontal plane in the frontal plane were measured on both sides in each individual. RESULTS: Sixteen of 20 participants with unilateral symptoms chewed on the affected side; the concordance (Fisher's exact test, P = .003 and the concordance-symmetry level (Kappa coefficient κ = 0.689; 95% confidence interval [CI], 0.38 to 0.99; P = .002 were significant. The mean condylar path angle was steeper (53.47(10.88 degrees versus 46.16(7.25 degrees; P = .001, and the mean lateral anterior guidance angle was flatter (41.63(13.35 degrees versus 48.32(9.53 degrees P = .036 on the symptomatic side. DISCUSSION: The results of this study support the use of a new term based on etiology, "habitual chewing side syndrome", instead of the nonspecific symptom-based "temporomandibular joint disorders"; this denomination is characterized in adults by a steeper condylar path, flatter lateral anterior guidance, and habitual chewing on the symptomatic side.

  4. Experimental study on the near wake behind two side-by-side cylinders of unequal diameters (United States)

    Gao, Yangyang; Yu, Dingyong; Tan, Soonkeat; Wang, Xikun; Hao, Zhiyong


    The wake structure behind two side-by-side circular cylinders with unequal diameter was investigated using the particle image velocimetry (PIV) technique. This investigation focused on the asymmetrical flow within the subcritical Reynolds number regime. A comparison between the time-averaged mean flow field of one cylinder and that of two side-by-side cylinders of unequal diameter was made for elucidating the mean flow characteristics attributable to the latter. The distribution of mean velocity behind two side-by-side unequal cylinders was distinctly different from that behind one cylinder, and an asymmetric combination was observed behind the two cylinders. The present paper also presents the authors' interpretation of the generation mechanism of gap flow deflection based on the instantaneous vorticity contours and velocity distribution. The effect of Reynolds number on flow structure was studied by analyzing the mean velocity distribution and time-averaged wake structures. The results showed that vortex formation length decreases with Reynolds number.

  5. Counting Populations (United States)

    Damonte, Kathleen


    Scientists use sampling to get an estimate of things they cannot easily count. A population is made up of all the organisms of one species living together in one place at the same time. All of the people living together in one town are considered a population. All of the grasshoppers living in a field are a population. Scientists keep track of the…

  6. Immunity to experimental Salmonella typhimurium infections in rats. Transfer of immunity with primed CD45RC+ and CD45RC- CD4 T-cell subpopulations

    DEFF Research Database (Denmark)

    Thygesen, P; Christensen, H B; Hougen, H P


    The protective effect of primed CD4 T cells against a lethal dose of Salmonella typhimurium was studied in Lewis rats. Primed CD4 T cells were obtained by inoculating Lewis rats with a non-lethal dose of S. typhimurium. Four weeks after the infection, spleen CD4 T cells were separated by antibody...

  7. Communication technologies for demand side management

    Energy Technology Data Exchange (ETDEWEB)

    Uuspaeae, P. [VTT Energy, Espoo (Finland)


    The scope of this research is data communications for electric utilities, specifically for the purposes of Demand Side Management (DSM). Demand Side Management has the objective to change the customer`s end use of energy in a manner that benefits both the customer and the utility. For example, peak demand may be reduced, and the peak demand may be relocated to off peak periods. Thus additional investments in generation and network may be avoided. A number of Demand Side Management functions can be implemented if a communication system is available between the Electric Utility and the Customer. The total communication capacity that is needed, will depend on several factors, such as the functions that are chosen for DSM, and on the number and type of customers. Some functions may be handled with one-way communications, while some other functions need to have two-way communication

  8. DarkSide search for dark matter

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, T.; Alton, D.; Arisaka, K.; Back, H. O.; Beltrame, P.; Benziger, J.; Bonfini, G.; Brigatti, A.; Brodsky, J.; Bussino, S.; Cadonati, L.; Calaprice, F.; Candela, A.; Cao, H.; Cavalcante, P.; Chepurnov, A.; Chidzik, S.; Cocco, A. G.; Condon, C.; D' Angelo, D.; Davini, S.; Vincenzi, M. De; Haas, E. De; Derbin, A.; Pietro, G. Di; Dratchnev, I.; Durben, D.; Empl, A.; Etenko, A.; Fan, A.; Fiorillo, G.; Franco, D.; Fomenko, K.; Forster, G.; Gabriele, F.; Galbiati, C.; Gazzana, S.; Ghiano, C.; Goretti, A.; Grandi, L.; Gromov, M.; Guan, M.; Guo, C.; Guray, G.; Hungerford, E. V.; Ianni, Al; Ianni, An; Joliet, C.; Kayunov, A.; Keeter, K.; Kendziora, C.; Kidner, S.; Klemmer, R.; Kobychev, V.; Koh, G.; Komor, M.; Korablev, D.; Korga, G.; Li, P.; Loer, B.; Lombardi, P.; Love, C.; Ludhova, L.; Luitz, S.; Lukyanchenko, L.; Lund, A.; Lung, K.; Ma, Y.; Machulin, I.; Mari, S.; Maricic, J.; Martoff, C. J.; Meregaglia, A.; Meroni, E.; Meyers, P.; Mohayai, T.; Montanari, D.; Montuschi, M.; Monzani, M. E.; Mosteiro, P.; Mount, B.; Muratova, V.; Nelson, A.; Nemtzow, A.; Nurakhov, N.; Orsini, M.; Ortica, F.; Pallavicini, M.; Pantic, E.; Parmeggiano, S.; Parsells, R.; Pelliccia, N.; Perasso, L.; Perasso, S.; Perfetto, F.; Pinsky, L.; Pocar, A.; Pordes, S.; Randle, K.; Ranucci, G.; Razeto, A.; Romani, A.; Rossi, B.; Rossi, N.; Rountree, S. D.; Saggese, P.; Saldanha, R.; Salvo, C.; Sands, W.; Seigar, M.; Semenov, D.; Shields, E.; Skorokhvatov, M.; Smirnov, O.; Sotnikov, A.; Sukhotin, S.; Suvarov, Y.; Tartaglia, R.; Tatarowicz, J.; Testera, G.; Thompson, J.; Tonazzo, A.; Unzhakov, E.; Vogelaar, R. B.; Wang, H.; Westerdale, S.; Wojcik, M.; Wright, A.; Xu, J.; Yang, C.; Zavatarelli, S.; Zehfus, M.; Zhong, W.; Zuzel, G.


    The DarkSide staged program utilizes a two-phase time projection chamber (TPC) with liquid argon as the target material for the scattering of dark matter particles. Efficient background reduction is achieved using low radioactivity underground argon as well as several experimental handles such as pulse shape, ratio of ionization over scintillation signal, 3D event reconstruction, and active neutron and muon vetos. The DarkSide-10 prototype detector has proven high scintillation light yield, which is a particularly important parameter as it sets the energy threshold for the pulse shape discrimination technique. The DarkSide-50 detector system, currently in commissioning phase at the Gran Sasso Underground Laboratory, will reach a sensitivity to dark matter spin-independent scattering cross section of 10-45 cm2 within 3 years of operation.

  9. Areeda-turner in two-sided markets

    NARCIS (Netherlands)

    Behringer, S.; Filistrucchi, L.


    We extend the Areeda–Turner rule to two-sided markets. We show that a two-sided monopolist may find it short-run profit-maximizing to charge a price below marginal cost on one side of the market. Hence showing that the price is below marginal cost on one side of a two-sided market cannot be consider

  10. Left-sided omental torsion: CT appearance

    Energy Technology Data Exchange (ETDEWEB)

    Aoun, N.; Haddad-Zebouni, S.; Slaba, S.; Ghossain, M. [Hotel-Dieu de France Hospital, Beirut (Lebanon). Dept. of Radiology; Noun, R. [Hotel-Dieu de France Hospital, Beirut (Lebanon). Dept. of General Surgery


    A 34-year-old male presented with exquisite left flank pain. Computed tomography showed a hyperdense vascular structure surrounded by whirling linear streaks situated in the greater omentum under the splenic flexure of the colon. Omental stranding extended caudally into the pelvis where part of the inflamed omentum entered a left inguinal hernia sac. Surgery revealed left-sided torsion of the greater omentum. Left-sided omental torsion is infrequent and pre-operative diagnosis is rarely established. The CT findings of an omental fatty mass with a whirling pattern is characteristic of omental torsion. Preoperative diagnosis is important because conservative management has been suggested. (orig.)

  11. Update on side effects from common vaccines. (United States)

    Song, Benjamin J; Katial, Rohit K


    Vaccines have had a tremendous impact on public health by reducing morbidity and mortality from a variety of virulent pathogens. However, unintended side effects continue to pose a potential risk that may outweigh the vaccine's protective attributes. In this review, we discuss recent articles and controversies pertaining to vaccine-associated adverse events. Included in the discussion are influenza, hepatitis B, measles-mumps-rubella, diphtheria-tetanus-pertussis, polio, Haemophilus influenzae type b, and rotavirus vaccines. The importance and contribution of vaccine constituents (such as thimerosal) to side effects is also reviewed.

  12. The acute side effects of bright light therapy: a placebo-controlled investigation.

    Directory of Open Access Journals (Sweden)

    Yevgeny Botanov

    Full Text Available Despite the emergence of numerous clinical and non-clinical applications of bright light therapy (LT in recent decades, the prevalence and severity of LT side effects have not yet been fully explicated. A few adverse LT effects-headache, eye strain, irritability, and nausea-have been consistently reported among depressed individuals and other psychiatric cohorts, but there exists little published evidence regarding LT side effects in non-clinical populations, who often undergo LT treatment of considerably briefer duration. Accordingly, in the present study we examined, in a randomized sample of healthy young adults, the acute side effects of exposure to a single 30-minute session of bright white light (10,000 lux versus dim red light (< 500 lux. Across a broad range of potential side effects, repeated-measures analyses of variance revealed no significant group-by-time (Pre, Post interactions. In other words, bright light exposure was not associated with a significantly higher incidence of any reported side effect than was the placebo control condition. Nevertheless, small but statistically significant increases in both eye strain and blurred vision were observed among both the LT and control groups. Overall, these results suggest that the relatively common occurrence of adverse side effects observed in the extant LT literature may not fully extend to non-clinical populations, especially for healthy young adults undergoing LT for a brief duration.

  13. Illinois Early Childhood Program Standards Matrix. (A Side-by-Side Comparison). (United States)

    Illinois State Dept. of Human Services, East St. Louis. Head Start State Collaboration Office.

    This document contains a matrix offering a side-by-side comparison of almost 40 criteria among 7 sets of early childhood program standards. The standards are: (1) Head Start Program Performance Standards; (2) Illinois Department of Children and Family Services Child Care Licensing Standards; (3) Illinois Department of Human Services (IDHS) Center…

  14. Computer-mediated communication as a channel for social resistance : The strategic side of SIDE

    NARCIS (Netherlands)

    Spears, R; Lea, M; Corneliussen, RA; Postmes, T; Ter Haar, W


    In two studies, the authors tested predictions derived from the social identity model of deindividuation effects (SIDE) concerning the potential of computer-mediated communication (CMC) to serve as a means to resist powerful out-groups. Earlier research using the SIDE model indicates that the anonym

  15. Water Quality Performance of Three Side-by-Side Permeable Pavement Surface Materials: Three Year Update (United States)

    Communities are increasingly installing structural low impact development (LID) practices to mange stormwater and reduce pollutant loads associated with stormwater runoff. Permeable pavement is a LID practice that has limited research on working-scale, side-by-side performance o...

  16. Photon side-bands in mesoscopics

    DEFF Research Database (Denmark)

    Jauho, Antti-Pekka


    This paper reviews several applications of photonic side bands, used by Buttiker and Landauer (Phys. Rev. Lett. 49, 1739 (1982)) in their theory of traversal time in tunneling, in transport and optics of mesoscopic systems. Topics include generalizations of the transmission theory of transport...

  17. Compressive video sensing with side information. (United States)

    Yuan, Xin; Sun, Yangyang; Pang, Shuo


    Our temporally compressive imaging system reconstructs a high-speed image sequence from a single, coded snapshot. The reconstruction quality, similar to that of other compressive sensing systems, often depends on the structure of the measurement, as well as the choice of regularization. In this paper, we report a compressive video system that also captures the side information to aid in the reconstruction of high-speed scenes. The integration of the side information not only improves the quality of reconstruction, but also reduces the dependence of the reconstruction on regularization. We have implemented a system prototype that splits the field of view of a single camera into two channels: one channel captures the coded, low-frame-rate measurement for high-speed video reconstruction, and the other channel captures a direct measurement without coding as the side information. A joint reconstruction model is developed to recover the high-speed videos from the two channels. By analyzing both the experimental and the simulation results, the reconstructions with side information have demonstrated superior performances in terms of both the peak signal-to-noise ratio and structural similarity.

  18. Protection of the side of the head. (United States)

    Gilchrist, A; Mills, N J


    The side of the head is a frequent impact site for pedal cyclists, motorcyclists, and industrial workers. It is vulnerable to impact, yet many helmet standards do not have impact tests at the side of the helmet. Laboratory impact tests should reproduce the phenomena in real impacts, but usually they do not allow the headform to rotate, or ignore the effect of the neck on the motion of the head. The authors designed a linkage, simulating the flexibility of the neck, for use with anthropomorphic dummies in helmet testing. Impacts at the side of the helmet, normal to the helmet surface, were made with flat and hemispherical strikers. Head rotation during impacts caused the impact site to move, in some cases to below the level protected by the helmet. The peak angular head acceleration correlated with the peak linear accelerations. Neck flexibility means that helmets can protect the head from higher kinetic energy impacts than those specified in standards using immovable headforms or impact anvils. The load spreading efficiency of polypropylene foam, used in soft shell bicycle helmets, is better than that of polystyrene foam. The authors conclude that the side of the head can be protected by a suitable helmet design.

  19. Solar cell with back side contacts

    Energy Technology Data Exchange (ETDEWEB)

    Nielson, Gregory N; Okandan, Murat; Cruz-Campa, Jose Luis; Resnick, Paul J; Wanlass, Mark Woodbury; Clews, Peggy J


    A III-V solar cell is described herein that includes all back side contacts. Additionally, the positive and negative electrical contacts contact compoud semiconductor layers of the solar cell other than the absorbing layer of the solar cell. That is, the positive and negative electrical contacts contact passivating layers of the solar cell.

  20. On one-sided torsion pair

    Institute of Scientific and Technical Information of China (English)


    Motivated by the concept of a torsion pair in a pre-triangulated category induced by Beligiannis and Reiten, the notion of a left (right) torsion pair in the left (right) triangulated category is introduced and investigated. We provide new connections between different aspects of torsion pairs in one-sided triangulated categories, pre-triangulated categories, stable categories and derived categories.

  1. The Dark Side of Bank Wholesale Funding

    NARCIS (Netherlands)

    Huang, R.; Ratnovksi, L.


    Commercial banks increasingly use short-term wholesale funds to supplement traditional retail deposits. Existing literature mainly points to the "bright side" of wholesale funding: sophisticated financiers can monitor banks, disciplining bad ones but refinancing solvent ones. This paper models a "da

  2. Demand Side Management for Multiple Devices

    NARCIS (Netherlands)

    Molderink, Albert; Bakker, Vincent; Smit, Gerard J.M.


    Steering a heterogeneous set of devices in a Smart Grid using cost functions: Demand Side Management (DSM) is an important element in smart grids. DSM is already in operation for large consumers, but thorough research is required into DSM on a building level within the distribution grid.

  3. Side chain conformational averaging in human dihydrofolate reductase. (United States)

    Tuttle, Lisa M; Dyson, H Jane; Wright, Peter E


    The three-dimensional structures of the dihydrofolate reductase enzymes from Escherichia coli (ecDHFR or ecE) and Homo sapiens (hDHFR or hE) are very similar, despite a rather low level of sequence identity. Whereas the active site loops of ecDHFR undergo major conformational rearrangements during progression through the reaction cycle, hDHFR remains fixed in a closed loop conformation in all of its catalytic intermediates. To elucidate the structural and dynamic differences between the human and E. coli enzymes, we conducted a comprehensive analysis of side chain flexibility and dynamics in complexes of hDHFR that represent intermediates in the major catalytic cycle. Nuclear magnetic resonance relaxation dispersion experiments show that, in marked contrast to the functionally important motions that feature prominently in the catalytic intermediates of ecDHFR, millisecond time scale fluctuations cannot be detected for hDHFR side chains. Ligand flux in hDHFR is thought to be mediated by conformational changes between a hinge-open state when the substrate/product-binding pocket is vacant and a hinge-closed state when this pocket is occupied. Comparison of X-ray structures of hinge-open and hinge-closed states shows that helix αF changes position by sliding between the two states. Analysis of χ1 rotamer populations derived from measurements of (3)JCγCO and (3)JCγN couplings indicates that many of the side chains that contact helix αF exhibit rotamer averaging that may facilitate the conformational change. The χ1 rotamer adopted by the Phe31 side chain depends upon whether the active site contains the substrate or product. In the holoenzyme (the binary complex of hDHFR with reduced nicotinamide adenine dinucleotide phosphate), a combination of hinge opening and a change in the Phe31 χ1 rotamer opens the active site to facilitate entry of the substrate. Overall, the data suggest that, unlike ecDHFR, hDHFR requires minimal backbone conformational rearrangement as

  4. Promoting Population

    Institute of Scientific and Technical Information of China (English)


    THE world's population reached 5 billion in 1987,then 6 billion in 1999;now,in 2011,it is 7 billion.For a country with a set birth control policy,the way in which Chinese people and the media view this number has greatly changed.People are increasingly reflecting on the concept of population from a more scientific and rational perspective.This shift is a change from how people perceived population in the past.

  5. The Social Side Effects of Acetaminophen (United States)

    Mischkowski, Dominik

    About 23% of all adults in the US take acetaminophen during an average week (Kaufman, Kelly, Rosenberg, Anderson, & Mitchell, 2002) because acetaminophen is an effective physical painkiller and easily accessible over the counter. The physiological side effects of acetaminophen are well documented and generally mild when acetaminophen is consumed in the appropriate dosage. In contrast, the psychological and social side effects of acetaminophen are largely unknown. Recent functional neuroimaging research suggests that the experience of physical pain is fundamentally related to the experience of empathy for the pain of other people, indicating that pharmacologically reducing responsiveness to physical pain also reduces cognitive, affective, and behavioral responsiveness to the pain of others. I tested this hypothesis across three double-blind between-subjects drug intervention studies. Two experiments showed that acetaminophen had moderate effects on empathic affect, specifically personal distress and empathic concern, and a small effect on empathic cognition, specifically perceived pain, when facing physical and social pain of others. The same two experiments and a third experiment also showed that acetaminophen can increase the willingness to inflict pain on other people, i.e., actual aggressive behavior. This effect was especially pronounced among people low in dispositional empathic concern. Together, these findings suggest that the physical pain system is more involved in the regulation of social cognition, affect, and behavior than previously assumed and that the experience of physical pain and responsiveness to the pain of others share a common neurochemical basis. Furthermore, these findings suggest that acetaminophen has unappreciated but serious social side effects, and that these side effects may depend on psychological characteristics of the drug consumer. This idea is consistent with recent theory and research on the context-dependency of neurochemical

  6. Vaccine demand driven by vaccine side effects: dynamic implications for SIR diseases. (United States)

    d'Onofrio, Alberto; Manfredi, Piero


    For infections for which the perceived risk of serious disease is steadily low, the perceived risk of suffering some vaccine side effects might become the driving force of the vaccine demand. We investigate the dynamics of SIR infections in homogeneously mixing populations where the vaccine uptake is a decreasing function of the current (or past) incidence, or prevalence, of vaccine side effects. We define an appropriate model where vaccine side-effects are modelled as functions of the age since vaccination. It happens that the vaccine uptake follows its own dynamics independent of epidemiological variables. We show the conditions under which the vaccine uptake lands on a globally stable equilibrium, or steadily oscillates, and the implications of such behaviour for the dynamics of epidemiological variables. We finally report some unexpected scenarios caused by trends in vaccine side effects.

  7. Immunological network activation by low-dose rate irradiation. Analysis of cell populations and cell surface molecules in whole body irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Ina, Yasuhiro; Sakai, Kazuo [Central Research Inst. of Electric Power Industry, Low Dose Radiation Research Center, Komae, Tokyo (Japan)


    The effects of low-dose rate whole body irradiation on biodefense and immunological systems were investigated using female C57BL/6 (B6) mice. These B6 mice were exposed continuously to {gamma}-rays from a {sup 137}Cs source in the long-term low-dose rate irradiation facility at CRIEPI for 0 - 12 weeks at a dose rate of 0.95 mGy/hr. In the bone marrow, thymus, spleen, lymph nodes, and peripheral blood of the irradiated mice, changes in cell populations and cell surface molecules were examined. The cell surface functional molecules (CD3, CD4, CD8, CD19, CD45R/B220, ICAM-1, Fas, NK-1.1, CXCR4, and CCR5), and activation molecules (THAM, CD28, CD40, CD44H, CD70, B7-1, B7-2, OX-40 antigen, CTLA-4, CD30 ligand, and CD40 ligand) were analyzed by flow cytometry. The percentage of CD4{sup +} T cells and cell surface CD8 molecule expressions on the CD8{sup +} T cells increased significantly to 120-130% after 3 weeks of the irradiation, compared to non-irradiated control mice. On the other hand, the percentage of CD45R/B220{sup +} CD40{sup +} B cells, which is one of the immunological markers of inflammation, infection, tumor, and autoimmune disease, decreased significantly to 80-90% between the 3rd to 5th week of irradiation. There was no significant difference in other cell population rates and cell surface molecule expression. Furthermore, abnormal T cells bearing mutated T cell receptors induced by high-dose rate irradiation were not observed throughout this study. These results suggest that low-dose rate irradiation activates the immunological status of the whole body. (author)

  8. On Two-Sided Confidence and Tolerance Limits for Normal Distributions. (United States)


    363 (1959). Correa Po’lit, I. Statistical inference about the parameters of nonnormal populations (confidence intervals). Trabajos Estadist 9:118-140...Publishing Co., 1952. Owen, D. B. Factors for one-sided tolerance limits and for variables sampling plans . Sandia Corporation Monograph SCR-6U7 (1963). Wilks

  9. Traditional Jewelry on Both Sides of the Danube River

    Directory of Open Access Journals (Sweden)

    P. Chaushev


    Full Text Available From the Ancient times Danube River acts as stabile and almost uncontested Northern border of Bulgarian lands. For a very long period it divides different populations speaking different languages, developing different cultures and political units. In the same times Danube River unites it is both banks by cheap and easy to manage transportation. More than this Danube as a liquid border connects populations from the both banks with Central Europe serving as a vehicle for people, goods, money and ideas. The aim of this article is to explore one particular segment of culture connections - the evolution of traditional jewelry from 19th to early 20th century in the region of Northern Bulgaria and Southern Romania. The focus is on snake or dragon motifs carved on belt buckles originated from both sides of the border. This and related believes and cult practices reveals close cultural and commercial ties crossing Danube River. During my research I came across material that showed that those motifs were found in several Balkan countries (Serbia and Greece. The decoration of this traditional jewelry is typical for the Orient, but it is common among the Christian population of the Balkan Peninsula. It shows that in those times the Danube River was acting mostly as natural, not as a political or cultural border.

  10. Medicated Janus fibers fabricated using a Teflon-coated side-by-side spinneret. (United States)

    Yu, Deng-Guang; Yang, Chen; Jin, Miao; Williams, Gareth R; Zou, Hua; Wang, Xia; Bligh, S W Annie


    A family of medicated Janus fibers that provides highly tunable biphasic drug release was fabricated using a side-by-side electrospinning process employing a Teflon-coated parallel spinneret. The coated spinneret facilitated the formation of a Janus Taylor cone and in turn high quality integrated Janus structures, which could not be reliably obtained without the Teflon coating. The fibers prepared had one side consisting of polyvinylpyrrolidone (PVP) K60 and ketoprofen, and the other of ethyl cellulose (EC) and ketoprofen. To modulate and tune drug release, PVP K10 was doped into the EC side in some cases. The fibers were linear and had flat morphologies with an indent in the center. They provide biphasic drug release, with the PVP K60 side dissolving very rapidly to deliver a loading dose of the active ingredient, and the EC side resulting in sustained release of the remaining ketoprofen. The addition of PVP K10 to the EC side was able to accelerate the second stage of release; variation in the dopant amount permitted the release rate and extent this phase to be precisely tuned. These results offer the potential to rationally design systems with highly controllable drug release profiles, which can complement natural biological rhythms and deliver maximum therapeutic effects.

  11. Population Blocks. (United States)

    Smith, Martin H.


    Describes an educational game called "Population Blocks" that is designed to illustrate the concept of exponential growth of the human population and some potential effects of overpopulation. The game material consists of wooden blocks; 18 blocks are painted green (representing land), 7 are painted blue (representing water); and the remaining…

  12. Server-side Statistics Scripting in PHP

    Directory of Open Access Journals (Sweden)

    Jan de Leeuw


    Full Text Available On the UCLA Statistics WWW server there are a large number of demos and calculators that can be used in statistics teaching and research. Some of these demos require substantial amounts of computation, others mainly use graphics. These calculators and demos are implemented in various different ways, reflecting developments in WWW based computing. As usual, one of the main choices is between doing the work on the client-side (i.e. in the browser or on the server-side (i.e. on our WWW server. Obviously, client-side computation puts fewer demands on the server. On the other hand, it requires that the client downloads Java applets, or installs plugins and/or helpers. If JavaScript is used, client-side computations will generally be slow. We also have to assume that the client is installed properly, and has the required capabilities. Requiring too much on the client-side has caused browsing machines such as Netscape Communicator to grow beyond all reasonable bounds, both in size and RAM requirements. Moreover requiring Java and JavaScript rules out such excellent browsers as Lynx or Emacs W3. For server-side computing, we can configure the server and its resources ourselves, and we need not worry about browser capabilities and configuration. Nothing needs to be downloaded, except the usual HTML pages and graphics. In the same way as on the client side, there is a scripting solution, where code is interpreted, or a ob ject-code solution using compiled code. For the server-side scripting, we use embedded languages, such as PHP/FI. The scripts in the HTML pages are interpreted by a CGI program, and the output of the CGI program is send to the clients. Of course the CGI program is compiled, but the statistics procedures will usually be interpreted, because PHP/FI does not have the appropriate functions in its scripting language. This will tend to be slow, because embedded languages do not deal efficiently with loops and similar constructs. Thus a first

  13. Scrutable Mobile Client-side Personalization

    Directory of Open Access Journals (Sweden)

    Muhammad Asif


    Full Text Available Personalization has become an essential feature of mobile services of different domains. On the other hand, users have conflicting needs of personalized experience and privacy. This leads to the question of how to maximize the user’s experience of personalized mobile services while keeping privacy. One possible solution is to provide user’s control of their personal data by keeping their user model on their personal mobile devices. In this way, a user can scrutinize the data while sharing with service providers depending on her/his requirements. The client-side personalization approach can shift the control of privacy to the users and can involve them in personalization process. Transparency and user control can increase the user’s trust. In this paper, we have proposed a solution with the objective of scrutable client-side personalization while keeping the user in control of both privacy and personalization process.

  14. Side Chain Cyclized Aromatic Amino Acids

    DEFF Research Database (Denmark)

    Van der Poorten, Olivier; Knuhtsen, Astrid; Sejer Pedersen, Daniel


    Constraining the conformation of flexible peptides is a proven strategy to increase potency, selectivity, and metabolic stability. The focus has mostly been on constraining the backbone dihedral angles; however, the correct orientation of the amino acid side chains (χ-space) that constitute...... the peptide pharmacophore is equally important. Control of χ-space utilizes conformationally constrained amino acids that favor, disfavor, or exclude the gauche (-), the gauche (+), or the trans conformation. In this review we focus on cyclic aromatic amino acids in which the side chain is connected...... to the peptide backbone to provide control of χ(1)- and χ(2)-space. The manifold applications for cyclized analogues of the aromatic amino acids Phe, Tyr, Trp, and His within peptide medicinal chemistry are showcased herein with examples of enzyme inhibitors and ligands for G protein-coupled receptors....

  15. Methylphenidate Abuse and Psychiatric Side Effects


    Morton, W. Alexander; Stockton, Gwendolyn G.


    Methylphenidate is a central nervous system stimulant drug that has become the primary drug of choice in treating attention-deficit/hyperactivity disorder in children. Side effects are usually mild and are generally well tolerated by patients. Along with increases in prescribing frequency, the potential for abuse has increased. Intranasal abuse produces effects rapidly that are similar to the effects of cocaine in both onset and type. The clinical picture of stimulant abuse produces a wide ar...

  16. Integrated double-sided silicon microstrip detectors

    Directory of Open Access Journals (Sweden)

    Perevertailo V. L.


    Full Text Available The problems of design, technology and manufacturing double-sided silicon microstrip detectors using standard equipment production line in mass production of silicon integrated circuits are considered. The design of prototype high-energy particles detector for experiment ALICE (CERN is presented. The parameters of fabricated detectors are comparable with those of similar foreign detectors, but they are distinguished by lesser cost.

  17. Demand side management of electric car charging

    DEFF Research Database (Denmark)

    Finn, P.; Fitzpatrick, C.; Connolly, David


    in terms of distributed energy storage and flexible load. This paper examines how optimising the charging cycles of an electriccar using DSM (DemandSideManagement) based on a number of criteria could be used to achieve financial savings, increased demand on renewable energy, reduce demand on thermal...... generation plant, and reduce peak load demand. The results demonstrate that significant gains can be achieved using currently available market data which highlights the point that DSM can be implemented without any further technological advents....

  18. Client-side Skype forensics: an overview (United States)

    Meißner, Tina; Kröger, Knut; Creutzburg, Reiner


    IT security and computer forensics are important components in the information technology. In the present study, a client-side Skype forensics is performed. It is designed to explain which kind of user data are stored on a computer and which tools allow the extraction of those data for a forensic investigation. There are described both methods - a manual analysis and an analysis with (mainly) open source tools, respectively.

  19. The Dark Side of the Moon

    Institute of Scientific and Technical Information of China (English)


    A combo photo released by the China National Space Administration(CNSA)on December 11 shows a crater on the dark side of the moon.This image was reportedly taken by Chang’e-1, the country’s first lunar probe,on December 4. On December 12,a grand ceremony was held in Beijing to celebrate the success of the first stage of China’s lunar probe program.President Hu Jintao announced on the occasion that the

  20. Side abutment pressure distribution by field measurement

    Institute of Scientific and Technical Information of China (English)

    WANG Lian-guo; SONG Yang; HE Xing-hua; ZHANG Jian


    Given the 7123 working face in the Qidong Coal Mine of the Wanbei Mining Group, nine dynamic roof monitors were installed in the crossheading to measure the amount and velocity of roof convergence in different positions and at different times and three steel bored stress sensors were installed in the return airway to measure rock stress at depth. On the basis of this arrangement, the rule of change of the distribution of the side abutment pressure with the advance of the working face and movement of overlying strata was studied. The rule of change and the stability of rock stress at depth were measured. Secondly, the affected area and stability time of the side abutment pressure were also studied. The results show that: 1) During working, the face advanced distance was from 157 m to 99 m, the process was not effected by mining induced pressure. When the distance was 82 m, the position of peak stress was 5 m away from the coal wall. When the distance was 37 m, the position of peak stress away from the coal wall was about 15 m to 20 m and finally reached a steady state; 2) the time and the range of the peak of side rock pressure obtained from stress sensors were consistent with the results from the dynamic roof monitors; 3) the position of the peak pressure was 25 m away from the coal wall.

  1. Imaginary populations

    Directory of Open Access Journals (Sweden)

    A. Martínez–Abraín


    Full Text Available A few years ago, Camus & Lima (2002 wrote an essay to stimulate ecologists to think about how we define and use a fundamental concept in ecology: the population. They concluded, concurring with Berryman (2002, that a population is "a group of individuals of the same species that live together in an area of sufficient size to permit normal dispersal and/or migration behaviour and in which population changes are largely the results of birth and death processes". They pointed out that ecologists often forget "to acknowledge that many study units are neither natural nor even units in terms of constituting a population system", and hence claimed that we "require much more accuracy than in past decades in order to be more effective to characterize populations and predict their behaviour". They stated that this is especially necessary "in disciplines such as conservation biology or resource pest management, to avoid reaching wrong conclusions or making inappropriate decisions". As a population ecologist and conservation biologist I totally agree with these authors and, like them, I be¬lieve that greater precision and care is needed in the use and definition of ecological terms. The point I wish to stress here is that we ecologists tend to forget that when we use statistical tools to infer results from our sample to a population we work with what statisticians term "imaginary", "hypothetical" or "potential" popula¬tions. As Zar (1999 states, if our sample data consist of 40 measurements of growth rate in guinea pigs "the population about which conclusions might be drawn is the growth rates of all the guinea pigs that conceivably might have been administered the same food supplement under identical conditions". Such a population does not really exist, and hence it is considered a hypothetical or imaginary population. Compare that definition with the population concept that would be in our minds when performing such measurements. We would probably

  2. Safety Assessment for a Side-by-side Offloading Mooring System

    Institute of Scientific and Technical Information of China (English)

    Liping Sun; Qiang He; Shangmao Ai


    In order to improve the safety properties of an offloading system with side-by-side (SBS) mooring in which the FPSO is moored by a yoke system in the field of BZ25-1,it is necessary to analyze those properties.According to the experience of similar projects,tow strategies of different offloading arrangements were discussed by using the 3-D radiation/diffraction theory and quasi-static time domain method to assess their respective safety properties.Through the safety assessment analysis of different arrangement comparisons,various ways to improve the safety properties of offloading systems with side-by-side mooring were verified by analyzing the tension in the mooring lines and the fender deflection.Through comparison it can be concluded that by enlarging the key factors properly,including the size of the fenders and the hawsers as well as the number of hawsers,a better satiety performance can be achieved.

  3. Functionally Graded Ceramics Fabricated with Side-by-Side Tape Casting for Use in Magnetic Refrigeration

    DEFF Research Database (Denmark)

    Bulatova, Regina; Bahl, Christian; Andersen, Kjeld Bøhm;


    variations of solvent and binder system concentrations have a substantial effect on slurry viscosity. Varying these parameters showed that side-by-side tape casting with a well-defined interface area is possible for slurries with viscosities above 3500 mPa s at a casting shear rate of 3.3 s -1......Functionally graded ceramic tapes have been fabricated by a side-by-side tape casting technique. This study shows the possibility and describes the main principles of adjacent coflow of slurries resulting in formation of thin plates of graded ceramic material. Results showed that the small...... of developing this graded ceramic tape casting was applications of these specific magnetocaloric properties within the magnetic refrigeration technology....

  4. Population policy. (United States)


    Participants in the Seminar on Population Policies for Top-level Policy Makers and Program Managers, meeting in Thailand during January 1987, examined the challenges now facing them regarding the implementation of fertility regulation programs in their respective countries -- Bangladesh, China, India, Indonesia, Malaysia, Nepal, Pakistan, the Philippines, the Republic of Korea, and Thailand. This Seminar was organized to coincide with the completion of an Economic and Social Commission for Asia and the Pacific (ESCAP) study investigating the impact and efficiency of family planning programs in the region. Country studies were reviewed at the Seminar along with policy issues about the status of women, incentive and disincentive programs, and socioeconomic factors affecting fertility. In Bangladesh the government recognizes population growth as its top priority problem related to the socioeconomic development of the country and is working to promote a reorientation strategy from the previous clinic-oriented to a multidimensional family welfare program. China's family planning program seeks to postpone marraige, space the births of children between 3-5 years, and promote the 1-child family. Its goal is to reduce the rate of natural increase from 12/1000 in 1978 to 5/1000 by 1985 and 0 by 2000. India's 7th Five-Year-Plan (1986-90) calls for establishing a 2-child family norm by 2000. In Indonesia the government's population policy includes reducing the rate of population growth, achieving a redistribution of the population, adjusting economic factors, and creating prosperous families. The government of Indonesia reversed its policy to reduce the population growth rate in 1984 and announced its goal of achieving a population of 70 million by 2100 in order to support mass consumption industries. It has created an income tax deduction system favoring large families and maternity benefits for women who have up to 5 children as incentives. Nepal's official policy is to

  5. Left-Sided Patent Ductus Arteriosus in a Right-Sided Aortic Arch

    Directory of Open Access Journals (Sweden)

    Ming-Yen Ng


    Full Text Available We present a 31-year-old female with repaired tetralogy of Fallot (TOF and right-sided aortic arch (RAA with left-sided patent ductus arteriosus (PDA originating from the left brachiocephalic artery. This is a rare finding but most common site for a PDA in TOF and a RAA. To the best of our knowledge, this is the first demonstration of this rare finding on MRI in the literature.

  6. Aerodynamic drag from two tubes in side-by-side arrangement for different tube shapes

    Directory of Open Access Journals (Sweden)

    Олександр Михайлович Терех


    Full Text Available Experimental investigations of aerodynamic drag from two tubes in side-by-side arrangement for different tube shapes in the range of Reynolds numbers from 4000 to16000 are performed. Comparison of experimental data is executed. It is set, that the tubes of drop-shaped form have less aerodynamic drag and the tubes of flat-oval and dumb-bell forms have greater drag as compared to drag of circular tubes

  7. Experimental study on the near wake behind two side-by-side cylinders of unequal diameters

    Energy Technology Data Exchange (ETDEWEB)

    Gao Yangyang; Yu Dingyong [College of Engineering, Ocean University of China, Qingdao 266100 (China); Tan, Soonkeat [School of Civil and Environmental Engineering, Nanyang Technological University, Singapore 639798 (Singapore); Wang Xikun [Maritime Research Center, Nanyang Technological University, Singapore 639798 (Singapore); Hao Zhiyong, E-mail: [Shanghai Maritime University, Shanghai 200135 (China)


    The wake structure behind two side-by-side circular cylinders with unequal diameter was investigated using the particle image velocimetry (PIV) technique. This investigation focused on the asymmetrical flow within the subcritical Reynolds number regime. A comparison between the time-averaged mean flow field of one cylinder and that of two side-by-side cylinders of unequal diameter was made for elucidating the mean flow characteristics attributable to the latter. The distribution of mean velocity behind two side-by-side unequal cylinders was distinctly different from that behind one cylinder, and an asymmetric combination was observed behind the two cylinders. The present paper also presents the authors' interpretation of the generation mechanism of gap flow deflection based on the instantaneous vorticity contours and velocity distribution. The effect of Reynolds number on flow structure was studied by analyzing the mean velocity distribution and time-averaged wake structures. The results showed that vortex formation length decreases with Reynolds number.

  8. Stabilization of Gob-Side Entry with an Artificial Side for Sustaining Mining Work

    Directory of Open Access Journals (Sweden)

    Hong-sheng Wang


    Full Text Available A concrete artificial side (AS is introduced to stabilize a gob-side entry (GSE. To evaluate the stability of the AS, a uniaxial compression failure experiment was conducted with large and small-scale specimens. The distribution characteristics of the shear stress were obtained from a numerical simulation. Based on the failure characteristics and the variation of the shear stress, a failure criterion was determined and implemented in the strengthening method for the artificial side. In an experimental test, the distribution pattern of the maximum shear stress showed an X shape, which contributed to the failure shape of the specimen. The shear stress distribution and failure shape are induced by a combination of two sets of shear stresses, which implies that failure of the AS follows the twin shear strength theory. The use of anchor bolts, bolts, and anchor bars enhances the shear strength of the artificial side. When this side is stable, the components can constrain the lateral deformation as well as improve the internal friction angle and cohesion. When the AS is damaged, the components prevent the sliding of broken blocks along the shear failure plane and improve the residual strength of the artificial side. When reinforced with an anchor bar, the AS is still stable even after mining operations for three years.

  9. Angle Specific Analysis of Side-to-Side Asymmetry in the Shoulder Rotators

    Directory of Open Access Journals (Sweden)

    Cassio V. Ruas


    Full Text Available Although side-to-side asymmetry of the shoulder rotators calculated by independent peak torque (IPT has been used for interpretation of injury risks in athletes, it may not measure strength through the entire range of motion (ROM tested. The aim of this study was to compare side-to-side asymmetry of the shoulder rotators between independent peak torque (IPT and ten-degree angle specific torque (AST. Twenty healthy adult males (24.65 ± 2.4 years performed concentric and eccentric internal rotation (IR and external rotation (ER of the preferred and non-preferred arms on an isokinetic dynamometer at 60°/s through 150° of total ROM. The total ROM was divided into 14 ten-degree angles of the physiological ROM from −90° of ER to 60° of IR. Concentric and eccentric IR IPT (10.5% ± 8.7% and 12.1% ± 7.2% and ER IPT (13.6% ± 9.8% and 8.7% ± 5.6% were significantly less than AST at several angles (p < 0.05. IPT might lead to erroneous interpretations of side-to-side asymmetry in the shoulder rotators and does not represent the entire ROM tested. This information could be used to prescribe strength exercises to enhance overhead performance and reduce risk of shoulder injuries.

  10. [Population education]. (United States)

    Niang, M


    Africa has the highest population growth rate in the world (3%). It has 650 million people (about 900 million in 2000). Rapid population growth has serious consequences which, if not addressed, will be disastrous. This worrisome situation has led some governments to adopt demographic policies to slow down population growth. The UN Economic, Scientific and Cultural Organization (UNESCO) recommends that schools provide population education. Various population conferences have popularized population education in schools among African countries. UNESCO began its regional program on population education in Africa in 1969. National family life and population education (FL/PE) projects have increased from 4 in 1970 to 32 in 1990 (17 in French- and Portuguese-speaking Africa and 5 in English-speaking Africa). These projects teach students about the links between demographic problems and socioeconomic factors and contemporary culture. They aim for total development of the individual and improvement of the quality of life for the individual, family, and community. Topics covered in FL/PE are birth rate; fertility; health; and maternal, infant, and child mortality; unwanted pregnancy; illegal abortion; sexually transmitted diseases; rural-urban migration; and urbanization. Benin introduced FL/PE at all levels of its education system while Senegal, Guinea, Mauritania, and Zaire introduced it to only the primary and secondary school levels. Some countries teach FL/PE as one discipline while most countries (e.g., Senegal) have integrated it into other disciplines (e.g., geography). FL/PE should begin in primary schools because they have the most students and prepare students for middle schools, which provide FL/PE. Elementary education in Senegal is being overhauled to introduce current major problems bit by bit. Senegal also wants to incorporate FL/PE into literacy and adult education programs. Integration of FL/PE into other disciplines should be encouraged.

  11. Does contraceptive treatment in wildlife result in side effects? A review of quantitative and anecdotal evidence. (United States)

    Gray, Meeghan E; Cameron, Elissa Z


    The efficacy of contraceptive treatments has been extensively tested, and several formulations are effective at reducing fertility in a range of species. However, these formulations should minimally impact the behavior of individuals and populations before a contraceptive is used for population manipulation, but these effects have received less attention. Potential side effects have been identified theoretically and we reviewed published studies that have investigated side effects on behavior and physiology of individuals or population-level effects, which provided mixed results. Physiological side effects were most prevalent. Most studies reported a lack of secondary effects, but were usually based on qualitative data or anecdotes. A meta-analysis on quantitative studies of side effects showed that secondary effects consistently occur across all categories and all contraceptive types. This contrasts with the qualitative studies, suggesting that anecdotal reports are insufficient to investigate secondary impacts of contraceptive treatment. We conclude that more research is needed to address fundamental questions about secondary effects of contraceptive treatment and experiments are fundamental to conclusions. In addition, researchers are missing a vital opportunity to use contraceptives as an experimental tool to test the influence of reproduction, sex and fertility on the behavior of wildlife species.

  12. The dark side of food addiction. (United States)

    Parylak, Sarah L; Koob, George F; Zorrilla, Eric P


    In drug addiction, the transition from casual drug use to dependence has been linked to a shift away from positive reinforcement and toward negative reinforcement. That is, drugs ultimately are relied on to prevent or relieve negative states that otherwise result from abstinence (e.g., withdrawal) or from adverse environmental circumstances (e.g., stress). Recent work has suggested that this "dark side" shift also is a key in the development of food addiction. Initially, palatable food consumption has both positively reinforcing, pleasurable effects and negatively reinforcing, "comforting" effects that can acutely normalize organism responses to stress. Repeated, intermittent intake of palatable food may instead amplify brain stress circuitry and downregulate brain reward pathways such that continued intake becomes obligatory to prevent negative emotional states via negative reinforcement. Stress, anxiety and depressed mood have shown high comorbidity with and the potential to trigger bouts of addiction-like eating behavior in humans. Animal models indicate that repeated, intermittent access to palatable foods can lead to emotional and somatic signs of withdrawal when the food is no longer available, tolerance and dampening of brain reward circuitry, compulsive seeking of palatable food despite potentially aversive consequences, and relapse to palatable food-seeking in response to anxiogenic-like stimuli. The neurocircuitry identified to date in the "dark" side of food addiction qualitatively resembles that associated with drug and alcohol dependence. The present review summarizes Bart Hoebel's groundbreaking conceptual and empirical contributions to understanding the role of the "dark side" in food addiction along with related work of those that have followed him.

  13. Cardiologic side effects of psychotropic drugs

    Institute of Scientific and Technical Information of China (English)

    Giuseppe Marano; Gianandrea Traversi; Enrico Romagnoli; Valeria Catalano; Marzia Lotrionte; Antonio Abbate; Giuseppe Biondi-Zoccai; Marianna Mazza


    Psychotropic drugs can produce cardiovascular side effects associated with a degree of cardiotoxicity.The coexistence of a heart disease complicates the management of mental illness,can contribute to a reduced quality of life and a worse illness course.The co-occurrence of psychiatric disorders in cardiac patients might affect the clinical outcome and morbidity.Moreover,the complex underlying mechanism that links these two conditions remains unclear.This paper discusses the known cardiovascular complications of psychotropic drugs and analyzes the important implications of antidepressive treatment in patients with previous cardiac history.

  14. Right-Sided Sigmoid Diverticular Perforation

    Directory of Open Access Journals (Sweden)

    Andrew Little


    Full Text Available Diverticulosis is a common disorder among geriatric patients, of whom 10% to 25% go on to develop diverticulitis. Known complications of diverticulitis include formation of phlegmon, fistula, bowel obstruction, bleeding, perforation, and colonic abscess. A less common complication is perforation with formation of an extra-abdominal necrotizing abscess. This case is a report of an 83-year-old female who presented to the emergency department with a necrotizing abdominal wall abscess secondary to right-sided diverticular microperforation. [West J Emerg Med. 2012;13(1:103–105.

  15. The Other Side of GDP Growth

    Institute of Scientific and Technical Information of China (English)

    Zhan Yong; Cai Fang


    @@ THE rise of China's GDP ranking has not only led the world to rediscover China, but also reminded China to examine its own development.Both sides of the issue should be considered. On the one hand, China topping Japan [the world's previous second largest economy] in terms of GDP marks the rising of Chinas economic status, which is a milestone in the modern world economic history since Japan replaced the former Federal Republic of Germany as the world's second largest economy in 1968.

  16. Side effects of external tooth bleaching

    DEFF Research Database (Denmark)

    E.M., Bruzell; Pallesen, Ulla; Thoresen, N.R.


    -office = 39.3% [n = 28]; p >0.05; 95% CI [OR]: 0.198‑1.102) whereas prevalence of gingival irritation was higher after in-office treatment (at-home = 14.0%; in-office = 35.7%; p ... attributed to the bleaching treatment in the at-home and in-office groups, respectively. Predictors for side effects were tooth sensitivity, surface loss and gingivitis when observed at inclusion. Treatment-related predictors were bleaching concentration and contact between tray and gingiva. Conclusions...

  17. Illegal immigration: a supply side analysis. (United States)

    Bandyopadhyay, S; Bandyopadhyay, S C


    "This paper analyzes the supply-side determinants of illegal immigration using a three-sector general equilibrium model of the source country. Agricultural liberalization raises illegal immigration while liberalization of the high tech sector reduces it. In contrast, capital mobility in the source country renders trade policy ineffective for controlling illegal immigration. Paradoxically, increased enforcement (by the host country) may raise source country unskilled wages, although illegal immigration falls. Finally, under capital mobility, a rise in the source country restrictions on capital inflow raises the level of illegal immigration and reduces the effectiveness of border enforcement efforts by the host country."

  18. Side chain polysiloxanes with phthalocyanine moieties

    Directory of Open Access Journals (Sweden)

    T. Ganicz


    Full Text Available Side chain polysiloxane with 5-(pentyloxy-3-methyloxy-9,10,16,17,23,24-hexakis(octenyloxyphthalocyanine moieties is synthesized by hydrosilylation reaction. The phase behavior and thermooptical properties of the polysiloxane and starting 2-(pent-4-enyloxy-3-methyloxy-9,10,16,17,23,24-hexakis(octenyloxyphthalocyanine is examined by POM (Polarizing optical microscopy, TOA (thermooptical analysis, DSC (differential scanning calorimetry, AFM (atomic force microscopy and SAXS (small angle X-ray scattering studies. The effect of the attachment of phthalocyanine to polysiloxane chains over phase transitions and phase morphology is discussed in details.


    Directory of Open Access Journals (Sweden)

    Corina – Maria ENE


    Full Text Available The mainly goal of money laundering is to carry out more and more illegal economic transactions or activities to produce individual or groups gains and then to legitimate them. Money laundering converts illicit source of money generated by criminal activities in order to hide the connection between money and their original illegal activities. This is one of money laundering side. The second side implies corruption. While money laundering is a passing channel for illicit funds due to its criminal origin source, such funds may derive from corruption offences. All corruption’s forms represent the most important illicit funds branches for money laundering process. Corrupt people methods used to exploit the national and international financial system reflect the relationship between those two criminal activities. Criminals achieve their personal interests by hiding their corruption proceeds and transfer these gains to official economies. Corruption spread in any society entails money laundering spread, and the converse, too. There is a quite “indecent” relationship between money laundering and corruption. This paper tries to identify the multiple connections between the two phenomenons showing the negative impacts these criminal behaviours are having on the national and international economy. We conclude by highlighting the necessity of a multidisciplinary approach in order to fight against money laundering and corruption by integrating these problem frameworks at national level. International community must focus their resources on money laundering and corruption risks areas and maximize their response impact.

  20. Industrial demand side management status report - synopsis

    Energy Technology Data Exchange (ETDEWEB)

    Hopkins, M.E.F.; Conger, R.L.; Foley, T.J. [and others


    Industrial demand side management (DSM) programs, though not as developed or widely implemented as residential and commercial programs, hold the promise of significant energy savings-savings that will benefit industrial firms, utilities and the environment. This paper is a synopsis of a larger research report, Industrial Demand Side Management: A Status Report, prepared for the U.S. Department of Energy. The report provides an overview of and rationale for DSM programs. Benefits and barriers are described, and data from the Manufacturing Energy Consumption Survey are used to estimate potential electricity savings from industrial energy efficiency measures. Overcoming difficulties to effective program implementation is worthwhile, since rough estimates indicate a substantial potential for electricity savings. The report categorizes types of DSM programs, presents several examples of each type, and explores elements of successful programs. Two in-depth case studies (of Boise Cascade and of Eli Lilly and Company) illustrate two types of effective DSM programs. Interviews with staff from state public utility commissions indicate the current thinking about the status and future of industrial DSM programs. Finally, the research report also includes a comprehensive bibliography, a description of technical assistance programs, and an example of a methodology for evaluating potential or actual savings from projects.

  1. Industrial demand side management status report: Synopsis

    Energy Technology Data Exchange (ETDEWEB)

    Hopkins, M.E.F.; Conger, R.L.; Foley, T.J.; Parker, J.W.; Placet, M.; Sandahl, L.J.; Spanner, G.E.; Woodruff, M.G.; Norland, D.


    Industrial demand side management (DSM) programs, though not as developed or widely implemented as residential and commercial programs, hold the promise of significant energy savings-savings that will benefit industrial firms, utilities and the environment. This paper is a synopsis of a larger research report, Industrial Demand Side Management. A Status Report, prepared for the US Department of Energy. The report provides an overview of and rationale for DSM programs. Benefits and barriers are described, and data from the Manufacturing Energy Consumption Survey are used to estimate potential electricity savings from industrial energy efficiency measures. Overcoming difficulties to effective program implementation is worthwhile, since rough estimates indicate a substantial potential for electricity savings. The report categorizes types of DSM programs, presents several examples of each type, and explores elements of successful programs. Two in-depth case studies (of Boise Cascade and of Eli Lilly and Company) illustrate two types of effective DSM programs. Interviews with staff from state public utility commissions indicate the current thinking about the status and future of industrial DSM programs. Finally, the research report also includes a comprehensive bibliography, a description of technical assistance programs, and an example of a methodology for evaluating potential or actual savings from projects.

  2. Nonlinear electron acoustic structures generated on the high-potential side of a double layer

    Directory of Open Access Journals (Sweden)

    R. Pottelette


    Full Text Available High-time resolution measurements of the electron distribution function performed in the auroral upward current region reveals a large asymmetry between the low- and high-potential sides of a double-layer. The latter side is characterized by a large enhancement of a locally trapped electron population which corresponds to a significant part (~up to 30% of the total electron density. As compared to the background hot electron population, this trapped component has a very cold temperature in the direction parallel to the static magnetic field. Accordingly, the differential drift between the trapped and background hot electron populations generates high frequency electron acoustic waves in a direction quasi-parallel to the magnetic field. The density of the trapped electron population can be deduced from the frequency where the electron acoustic spectrum maximizes. In the auroral midcavity region, the electron acoustic waves may be modulated by an additional turbulence generated in the ion acoustic range thanks to the presence of a pre-accelerated ion beam located on the high-potential side of the double layer. Electron holes characterized by bipolar pulses in the electric field are sometimes detected in correlation with these electron acoustic wave packets.

  3. Side-Chain-Induced Rigid Backbone Organization of Polymer Semiconductors through Semifluoroalkyl Side Chains. (United States)

    Kang, Boseok; Kim, Ran; Lee, Seon Baek; Kwon, Soon-Ki; Kim, Yun-Hi; Cho, Kilwon


    While high-mobility p-type conjugated polymers have been widely reported, high-mobility n-type conjugated polymers are still rare. In the present work, we designed semifluorinated alkyl side chains and introduced them into naphthalene diimide-based polymers (PNDIF-T2 and PNDIF-TVT). We found that the strong self-organization of these side chains induced a high degree of order in the attached polymer backbones by forming a superstructure composed of "backbone crystals" and "side-chain crystals". This phenomenon was shown to greatly enhance the ordering along the backbone direction, and the resulting polymers thus exhibited unipolar n-channel transport in field-effect transistors with remarkably high electron mobility values of up to 6.50 cm(2) V(-1) s(-1) and with a high on-off current ratio of 10(5).

  4. Population dynamics

    Directory of Open Access Journals (Sweden)

    Cooch, E. G.


    Full Text Available Increases or decreases in the size of populations over space and time are, arguably, the motivation for much of pure and applied ecological research. The fundamental model for the dynamics of any population is straightforward: the net change over time in the abundance of some population is the simple difference between the number of additions (individuals entering the population minus the number of subtractions (individuals leaving the population. Of course, the precise nature of the pattern and process of these additions and subtractions is often complex, and population biology is often replete with fairly dense mathematical representations of both processes. While there is no doubt that analysis of such abstract descriptions of populations has been of considerable value in advancing our, there has often existed a palpable discomfort when the ‘beautiful math’ is faced with the often ‘ugly realities’ of empirical data. In some cases, this attempted merger is abandoned altogether, because of the paucity of ‘good empirical data’ with which the theoretician can modify and evaluate more conceptually–based models. In some cases, the lack of ‘data’ is more accurately represented as a lack of robust estimates of one or more parameters. It is in this arena that methods developed to analyze multiple encounter data from individually marked organisms has seen perhaps the greatest advances. These methods have rapidly evolved to facilitate not only estimation of one or more vital rates, critical to population modeling and analysis, but also to allow for direct estimation of both the dynamics of populations (e.g., Pradel, 1996, and factors influencing those dynamics (e.g., Nichols et al., 2000. The interconnections between the various vital rates, their estimation, and incorporation into models, was the general subject of our plenary presentation by Hal Caswell (Caswell & Fujiwara, 2004. Caswell notes that although interest has traditionally

  5. Analysis of wave resonant effects in-between offshore vessels arranged side-by-side


    Dinoi, Pasquale


    La predicción de la interacción hidrodinámica entre dos cuerpos flotantes en la configuración side-by-side (lado-a-lado) se ha convertido en un importante y complicado problema en los últimos años. Esta situación es relevante cuando se trata de tomar decisiones sobre la viabilidad de una serie de operaciones offshore, principalmente relacionadas con el proceso de transferencia de carga líquida entre dos cascos. Esta tesis se profundiza en algunos aspectos hidrodinámico relevantes que surgen c...

  6. The Variation of Interface Formation with Slurry Viscosity Change in Side-By-Side Tape Casting

    DEFF Research Database (Denmark)

    Bulatova, Regina; Jabbari, Masoud; Andersen, Kjeld Bøhm;

    Homogenous and flexible adjacently graded tapes were produced by casting the organic-based slurries simultaneously. To develop side-by-side tape casing (SBSTC), the material optimization, modernization of the doctor blade design, and parameters control of such processes as casting, drying, de......-bindering and sintering were studied. Solvent and binder concentrations were varied in order to optimize co-casting flow, as well as the drying and sintering shrinkage. Tapes were evaluated in terms of rheological behavior of the slurries, the green and sintered tape microstructure, the quality of the interface area...

  7. Stellar Populations

    NARCIS (Netherlands)

    Peletier, Reynier F.


    This is a summary of my lectures during the 2011 Canary Islands Winter School in Puerto de la Cruz. I give an introduction to the field of stellar populations in galaxies, and highlight some new results. Since the title of the Winter School is Secular Evolution in Galaxies I mostly concentrate on ne

  8. Metabolic and Endocrine Side Effects of Atypical Antipsychotic Drugs in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Aysegul Tahiroglu


    Full Text Available omorbid psychiatric disorders, frequent hospitalization, multiple outpatient treatment, prior history of hypertension, obesity and lipid dysregulation are associated with higher risk of metabolic syndrome in children. Side effects of antipsychotic drugs and their management have recently become a major subject of research due to enhanced antipsychotic drug usage in child and adolescents. Prevention strategies are usually preferred to secondary or tertiary strategies in the management of metabolic syndrome associated with antipsychotic drugs. Clinicians should present multidisciplinary approach to endocrine and metabolic side effects due to antipsychotic use in pediatric patient groups and avoid multiple drug use in such patients. In this paper, we briefly reviewed metabolic side effects of second generation antipsychotic drugs in child and adolescent population, possible mechanisms of susceptibility to metabolic syndrome and pharmacological and non pharmacological treatment approach to prevention of weight gain.

  9. Grammars with two-sided contexts

    Directory of Open Access Journals (Sweden)

    Mikhail Barash


    Full Text Available In a recent paper (M. Barash, A. Okhotin, "Defining contexts in context-free grammars", LATA 2012, the authors introduced an extension of the context-free grammars equipped with an operator for referring to the left context of the substring being defined. This paper proposes a more general model, in which context specifications may be two-sided, that is, both the left and the right contexts can be specified by the corresponding operators. The paper gives the definitions and establishes the basic theory of such grammars, leading to a normal form and a parsing algorithm working in time O(n^4, where n is the length of the input string.

  10. Constraining the dark side with observations

    Energy Technology Data Exchange (ETDEWEB)

    Diez-Tejedor, Alberto [Dpto. de Fisica Teorica, Universidad del PaIs Vasco, Apdo. 644, 48080, Bilbao (Spain)


    The main purpose of this talk is to use the observational evidences pointing out to the existence of a dark side in the universe in order to infer some of the properties of the unseen material. We will work within the Unified Dark Matter models, in which both, Dark Matter and Dark Energy appear as the result of one unknown component. By modeling effectively this component with a classical scalar field minimally coupled to gravity, we will use the observations to constrain the form of the dark action. Using the flat rotation curves of spiral galaxies we will see that we are restringed to the use of purely kinetic actions, previously studied in cosmology by Scherrer. Finally we arrive to a simple action which fits both cosmological and astrophysical observations.

  11. Pathologic overproduction: the bad side of adenosine. (United States)

    Borea, Pier Andrea; Gessi, Stefania; Merighi, Stefania; Vincenzi, Fabrizio; Varani, Katia


    Adenosine is an endogenous ubiquitous purine nucleoside, increased by hypoxia, ischemia and tissue damage that mediates a number of physiopathological effects by interacting with four G-protein-coupled receptors, identified as A1 , A2A , A2B , and A3 . Physiological and acutely-increased adenosine is associated with beneficial effects mostly including vasodilation and decrease of inflammation. In contrast chronic overproduction of adenosine occurs in important pathological states, where long lasting increases in the nucleoside levels are responsible for the bad side of adenosine associated with chronic inflammation, fibrosis and organ damage. In this review we describe and critically discuss the pathologic overproduction of adenosine analysing when, where and how adenosine exerts its detrimental effects through the body.

  12. Development of Crashworthy Bottom and Side Structures

    DEFF Research Database (Denmark)

    Naar, H.; Kujala, P.; Simonsen, Bo Cerup;


    structures. The first structure is a conventional double bottom. In the second structure (presently protected through a patent) the bottom plating is stiffened with hat-profiles instead of bulb profiles. In the third structure the outer shell is an all-steel sandwich panel. In the fourth structure the bottom......The purpose of this work is to compare the resistance to damage of various types of double bottom structures in a stranding event. The results can also be interpreted as the crashworthiness of side structures penetrated by a striking vessel in a collision event. The comparative analyses are made...... by use of a commercial, explicit finite element program. The ship bottom is loaded with a conical indenter with a rounded tip, which is forced laterally into the structures in different positions. The aim is to compare resistance forces, energy absorption and penetration to fracture for four different...

  13. Industrial demand side management: A status report

    Energy Technology Data Exchange (ETDEWEB)

    Hopkins, M.F.; Conger, R.L.; Foley, T.J. [and others


    This report provides an overview of and rationale for industrial demand side management (DSM) programs. Benefits and barriers are described, and data from the Manufacturing Energy Consumption Survey are used to estimate potential energy savings in kilowatt hours. The report presents types and examples of programs and explores elements of successful programs. Two in-depth case studies (from Boise Cascade and Eli Lilly and Company) illustrate two types of effective DSM programs. Interviews with staff from state public utility commissions indicate the current thinking about the status and future of industrial DSM programs. A comprehensive bibliography is included, technical assistance programs are listed and described, and a methodology for evaluating potential or actual savings from projects is delineated.

  14. The quantum capacity with symmetric side channels

    CERN Document Server

    Smith, G; Winter, A; Smith, Graeme; Smolin, John A.; Winter, Andreas


    We present an upper bound for the quantum channel capacity that is both additive and convex. Our bound can be interpreted as the capacity of a channel for high-fidelity communication when assisted by the family of all channels mapping symmetrically to their output and environment. The bound seems to be quite tight, and for degradable quantum channels it coincides with the unassisted channel capacity. Using this symmetric side channel capacity, we find new upper bounds on the capacity of the depolarizing channel. We also briefly indicate an analogous notion for distilling entanglement using the same class of (one-way) channels, yielding one of the few genuinely 1-LOCC monotonic entanglement measures.

  15. The dark side of SAPHO syndrome. (United States)

    Henriques, Celia Coelho; Sousa, Mónica; Panarra, António; Riso, Nuno


    SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteitis) is a relatively rare entity. The therapeutic approach of patients with SAPHO syndrome has included multiple drugs with varying success and incoherence responses. The therapy is still empirical today. SAPHO syndrome is commonly treated with non-steroidal anti-inflammatory drugs, bisphophonates and non-biologic disease modifying antirheumatic drugs. Recent reports showed successful treatment with tumour necrosis factor α (TNF α) antagonists, but there is still a dark side of SAPHO syndrome including a subgroup of patient's refractory to all the treatments that have been empirically experienced. A clinical report of a patient with SAPHO syndrome with 12 years of evolution is described. All the therapeutic approaches, including anti TNF α therapy, have not prevented the clinical and radiographic progression of the disease. Given that the disease affects mostly younger patients, new therapeutic strategies are necessary in order to avoid potentially irreversible joint and bone lesions.

  16. The Siding Spring Hazard at Mars (United States)

    Kelley, Michael; Bauer, James; Bodewits, Dennis; Farnham, Tony; Li, Jian-Yang; Samarasinha, Nalin; Stevenson, Rachel; Tricarico, Pasquale


    Comet C/2013 A1 (Siding Spring) will pass Mars at the extremely close distance of 136,000 km in Oct 2014, giving Mars orbiting spacecraft an up-close and unprecedented view of this dynamically new comet. However, 100 minutes after the closest approach to the nucleus, Mars passes within 30,000 km of the comet's orbit. Here, large dust grains may be found on impacting trajectories, potentially posing a fatal hazard to the spacecraft. Such large grains must be ejected from the comet nucleus well before the time of encounter. Therefore, we propose IRAC imaging of this comet to assess the present-day gas production rate, which will aid dust impact hazard assessment.

  17. Esomeprazole induced galactorrhea: a novel side effect. (United States)

    Pipaliya, Nirav; Solanke, Dattatray; Rathi, Chetan; Patel, Ruchir; Ingle, Meghraj; Sawant, Prabha


    Proton pump inhibitors (PPIs) are one of the most frequently prescribed medications across the globe. Esomeprazole is the S-isomer of omeprazole, and it is currently the most widely prescribed PPI. The safety profile of esomeprazole is extremely favorable with only minor side effects, like headache and diarrhea, that are encountered in day to day practice. We report a case of a young female with symptoms of gastroesophageal reflux disease who developed galactorrhea after starting esomeprazole therapy. Resolution of galactorrhea after stopping the drug and self-rechallenge by the patient herself with reappearance of galactorrhea confirmed the culprit to be esomeprazole only. We postulate that esomeprazole may have a mild inhibitory effect on CYP3A4, which leads to decreased metabolism of estrogen, thereby increasing serum estrogen levels. Estrogen causes stimulation and production of prolactin release, which results in development of galactorrhea. This is the first case of esomeprazole induced galactorrhea, to the best of our knowledge.

  18. The two sides of silicon detectors

    CERN Document Server

    Devine, S R


    /p/n sup + and essentially two p-n junctions within one device. With increasing bias voltage, as the electric field is extending into the detector bulk from opposite sides of the silicon detector, there are two distinct depletion regions that collect charge signal independently. Summing the signal charge from the two regions, one is able to reconstruct the initial energy of the incident particle. From Transient Current measurements it is apparent that E-field manipulation is possible by excess carrier injection, enabling a high enough E-field to extend across the width of the detector, allowing for efficient charge collection. Results are presented on in situ irradiation of silicon detector's at cryogenic temperature. The results show that irradiation at cryogenic temperatures does not detrimentally effect a silicon detectors performance when compared to its irradiation at room temperature. Operation of silicon devices at cryogenic temperatures offers the advantage of reducing radiation-induced leakage curren...

  19. Side-Scan-Sonar Points for Hudson River, NY (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Side Scan Point Files. These points correspond to individual pings which produced hte side-scan-sonar backscatter imagery. Sonar data were collected November 6 to...

  20. Managing Chemotherapy Side Effects: Fatigue (Feeling Weak and Very Tired) (United States)

    ... nurse about other exercises that can help. Stretching, yoga, or Tai Chi help some people. Questions to ... NCI has a series of 18 Chemotherapy Side Effects Sheets at:


    Institute of Scientific and Technical Information of China (English)

    魏英杰; 朱蒙生; 何钟怡


    Large eddy simulation cooperated with the second order full extension ETG (Euler-Taylor-Galerkin) finite element method was applied to simulate the flow around two square cylinders arranged side by side at a spacing ratio of 1.5. The second order full extension ETG finite element method was developed by Wang and He. By means of Taylor expansion of terms containing time derivative, time derivative is replaced by space derivative. The function of it is equal to introducing an artificial viscosity term. The streamlines of the flow at different moments were obtained. The time history of drag coefficient, lift coefficient and the streamwise velocity on the symmetrical points were presented. Furthermore, the symmetrical problem of the frequency spectrum of flow around two square cylinders arranged side by side were studied by using the spectral analysis technology. The data obtained at the initial stage are excluded in order to avoid the influence of initial condition on the results. The power spectrums of drag coefficient, lift coefficient, the streamwise velocity on the symmetrical points were analyzed respectively.The results show that although the time domain process of dynamic parameters is nonsymmetrical, the frequency domain process of them is symmetrical under the symmetrical boundary conditions.


    Institute of Scientific and Technical Information of China (English)

    ZHAO Wen-hua; YANG Jian-min; HU Zhi-qiang


    The Floating Liquefied Natural Gas (FLNG) is a new type of floating platform for the exploitation of stranded offshore oil/gas fields.The side by side configuration for the FLNG vessel and the LNG carrier arranged in parallel is one of the possible choices for the LNG offloading.During the offioading operations,the multiple floating bodies would have very complex responses due to their hydrodynamic interactions.In this study,numerical simulations of multiple floating bodies in close proximity in the side by side offioading configuration are carried out with the time domain coupled analysis code SIMO.Hydrodynamic interactions between the floating bodies and the mechanical coupling effects between the floating bodies and their connection systems are included in the coupled analysis model.To clarify the hydrodynamic effects of the two vessels,numerical simulations under the same environmental condition are also conducted without considering the hydrodynamic interactions,for comparison.It is shown that the hydrodynamic interactions play an important role in the low frequency motion responses of the two vessels,but have little effect on the wave frequency motion responses.In addition,the comparison results also show that the hydrodynamic interactions can affect the loads on the connection systems.

  3. The Light Side and The Dark Side of the Milky Way Halo (United States)

    Kafle, Prajwal R.; Sharma, Sanjib; Lewis, Geraint F.; Bland-Hawthorn, Joss


    We present our recent measurement of the kinematics of the Milky Way stellar halo (Light Side) and the derived mass of the dark matter halo (Dark Side) using the Jeans analysis. A tangential dip in the velocity anisotropy profile at r ~ 17 kpc (Kafle et al. 2012), and a distinct difference of ~65 kms-1 in the mean azimuthal velocity and the r.m.s dispersion of the most metal-rich and the metal-poor Blue Horizontal Branch stars we find (Kafle et al. 2013) are reported. The implications of this on the current controversial issue of an existence of the two-components in the halo are also discussed. Aided with the kinematic measurements of the light side, we demonstrate how we infer the dynamical property of the dark side. Considering a realistic three component galaxy model (Hernquist bulge, Miyamoto-Nagai disk and NFW halo), we estimate the virial mass of the Galaxy to be M vir = 1.2+0.5 -0.4 × 1012 M ⊙ (Kafle et al. 2012). We also show that the rotation curve of the Galaxy has undulations similar to what have also been seen in the studies of the HI gas (Sofue et al. 2009).

  4. Interaction of Gap Flow With Flapping Dynamics of Two Side-by-Side Elastic Foils (United States)

    Gurugubelli, Pardha S.; Jaiman, Rajeev K.


    We present a numerical analysis on the interaction between two side-by-side elastic foils with their leading edges clamped and the gap flow between them. We perform systematic parametric direct numerical simulations as a function of nondimensional bending rigidity, KB ∈ [ 1 ×10-4 , 3 ×10-3 ] and mass-ratio, m* ∈ [ 0 . 05 , 0 . 2 ] , for a fixed gap, dp = 0 . 2 / L , at the leading edge and Reynolds number, Re = 1000 to explain the underlying physical mechanism behind the in-phase and out-of-phase coupled flapping modes. The parametric simulations show that the parallel foil system exhibits predominant out-of-phase coupling for low mass-ratio m* 0 . 1 . We also show that the two side-by-side elastic foils always exhibit out-of-phase coupling initially irrespective of whether the fully developed flapping show out-of-phase or in-phase coupled mode. Finally, we show that the transition from the initial out-of-phase to stable in-phase is characterized by loss of gap flow symmetric stability to undergo oscillations at the gap exit.

  5. Three--dimensional Instability in the Wake of Two Side--by--side Square Cylinders (United States)

    Choi, Choon-Bum; Jang, Yong-Jun; Yang, Kyung-Soo


    Three-dimensional instability in the flow past two square cylinders in side-by-side arrangements has been numerically studied via a Floquet stability analysis. The distance between the neighboring faces of the two cylinders (G) is the key parameter which affects the secondary instability under consideration. In this talk, we present the critical Reynolds number for the 3D instability and the spanwise wave number corresponding to the most unstable (or least stable) wave for each G. When the two cylinders are close to each other, the Floquet mode resembles mode A of flow past a single cylinder. For large G, the Floquet mode for each cylinder is independent of the neighboring cylinder as expected. In the range of intermediate G, interference of the two wakes is clearly reflected in the Floquet mode. We also discuss about the effect of gap flow, and visualization of the dominant 3D vortical structures is provided by using Q contours. Our results shed light on a complete understanding of the onset of 3D instability in the presence of two side-by-side square cylinders. This work was supported by Korea Railroad Research Institute (Research Title: The study of standardization for urban railway facilities (SW 11002)).

  6. Quantitative flow characteristics for side-by-side square cylinders via PIV

    Directory of Open Access Journals (Sweden)

    Dogan Sercan


    Full Text Available In this study, instantaneous and time-averaged flow structures downstream of the sharp-edged single and two and three side-by-side square cylinders (SCs immersed in a uniform open channel water flow were studied by a technique of particle image velocimetry (PIV. Experimental results of wake flow structures were presented for gap ratios (G/D in the range of 1.0”G/D”3.0 for Reynolds number values of 1050, 2450 and 3400. Flow structures depending on the square cylinder (SC configurations and Reynolds number were discussed. It has been found that the development of the vortex shedding as well as the flow structure were substantially altered for side-by-side SCs comparing to the single SC. Asymmetrical and biased wake structures were observed because of the jetlike flow between the SCs for two SCs cases for the gap ratio less than 2.0. Depending on the gap spacing between the SCs, the interaction results of time2 averaged vorticity, velocity vector field, Reynolds stress correlations and streamline patterns in the wake region form a distinguished flow structure. Strouhal numbers for the single square cylinder for 1050≤Re≤3400 are found in the range of 0.12-0.13. The present results have supported the previous works by providing detailed quantitative experimental information with PIV in the wake region of the SC and might be helpful for validation of numerical studies and designers.


    Institute of Scientific and Technical Information of China (English)



    In the present paper,the unsteady,viscous,incompressible and 2-D flow around two side-by-side circular cylinders was simulated using a Cartesian-staggered grid finite volume based method.A great-source term technique was employed to identify the solid bodies (cylinders) located in the flow field and boundary conditions were enforced by applying the ghost-cell technique.Finally,the characteristics of the flow around two side-by-side cylinders were comprehensively obtained through several computational simulations.The computational simulations were performed for different transverse gap ratios (1.5≤T/D≤4) in laminar (Re =100,200 ) and turbulent (Re =104) regimes,where T and D are the distance between the centers of cylinders and the diameter of cylinders,respectively.The Reynolds number is based on the diameter of cylinders,D.The pressure field and vorticity distributions along with the associated streamlines and the time histories of hydrodynamic forces were also calculated and analyzed for different gap ratios.Generally,different flow patterns were observed as the gap ratio and Reynolds number varied.Accordingly,the hydrodynamic forces showed irregular variations for small gaps while they took a regular pattern at higher spacing ratios.

  8. [Investigation of permeability of intranasal formulations using Side-Bi-Side horizontal diffusion cell]. (United States)

    Horváth Tamás; Ambrus, Rita; Szabóné, Révész Piroska


    Nowadays the nasal route has received a great attention as a reliable administration for the systemic administration. In the Department of Pharmaceutical Technology, University of Szeged, the main research work is the design and development of innovative nasal formulations, which can open new possibilities for some well-known agents and may also help some drug-candidates delivery problems. The aim of this work was to present some reliable models for investigation of permeability, such as Spectra/Por Dialisys Membran, ZelluTrans/Roth Mini Dialyzer, μFLUX diffusion Cell, Navicyte Vertical and Horizontal Diffusion Chamber System and In-line Cell. In addition, the horizontal membrane diffusion model (Side-Bi-Side) was used to investigate in vitro and ex vivo studies of permeability of meloxicam in comparison with the vertical diffusion cell (Franz). The present study investigated the meloxicam in different dosage forms (powder, spray, gel). It was found that the Side-Bi-Side cell is suitable to test the nasal formulations, but the uniform distribution of the active substance cannot be ensured in donor place by increasing the viscosity of the compositions, therefore the Franz cell is recommended for investigation of nasal gel. Previous measurement cannot be found related to this topic.

  9. Supplementation with Vitamin B6 Reduces Side Effects in Cambodian Women Using Oral Contraception

    Directory of Open Access Journals (Sweden)

    Chivorn Var


    Full Text Available Hormonal contraceptives may produce side effects that deter women from their use as a method of family planning. In nutritionally vulnerable populations these effects may be more pronounced due to micronutrient deficiencies and health status. Previous studies have been unable to resolve whether micronutrient supplementation may reduce such side effects. Aim: In a longitudinal study, 1011 women obtaining oral contraception through the public health system in rural Cambodia were allocated to either intervention or control groups, receiving either daily Vitamin B6 supplement or care as usual (without placebo. Results: The intervention participants (n = 577 reported fewer side effects in three categories: nausea/no appetite, headache, and depression compared with control group participants (n = 434. Conclusion: Women taking Vitamin B6 supplement were less likely to report side effects in a nutritionally vulnerable population. Underlying nutrition status should be considered by clinicians and reproductive health policy makers in the context of providing contraceptive services. Further investigation into micronutrient supplementation, particularly with B6, in reproductive-aged women using hormonal contraception should be conducted in other settings to determine the potential for widespread adoption.

  10. The Karavanke range - from its dividing to the uniting role between the Slovenians on the both sides of the border

    Directory of Open Access Journals (Sweden)

    Jernej Zupančič


    Full Text Available Paper deals on socio-political development of Karavanke mountains, which had changing the division- and conecting role in historical development, especialy for slovene population, living on both sides of border. This mountain barriere became in 19th century conecting area for Slovenes of Carniola and Carinthia. After World War I., Karavanke became a border zone with strong division- function. Even though, the local population of both sides found some posibilities to comunicate with each other, what finnaly led to the today's larger transborder cooperation. In frame of this, slovene minority in Carinthia has a visible role and function.

  11. Molecular dynamics studies of side chain effect on the beta-1,3-D-glucan triple helix in aqueous solution. (United States)

    Okobira, Tadashi; Miyoshi, Kentaro; Uezu, Kazuya; Sakurai, Kazuo; Shinkai, Seiji


    beta-1,3-D-glucans have been isolated from fungi as right-handed 6(1) triple helices. They are categorized by the side chains bound to the main triple helix through beta-(1-->6)-D-glycosyl linkage. Indeed, since a glucose-based side chain is water soluble, the presence and frequency of glucose-based side chains give rise to significant variation in the physical properties of the glucan family. Curdlan has no side chains and self-assembles to form an water-insoluble triple helical structure, while schizophyllan, which has a 1,6-D-glucose side chain on every third glucose unit along the main chain, is completely water soluble. A thermal fluctuation in the optical rotatory dispersion is observed for the side chain, indicating probable co-operative interaction between the side chains and water molecules. This paper documents molecular dynamics simulations in aqueous solution for three models of the beta-1,3-D-glucan series: curdlan (no side chain), schizophyllan (a beta-(1-->6)-D-glycosyl side-chain at every third position), and a hypothetical triple helix with a side chain at every sixth main-chain glucose unit. A decrease was observed in the helical pitch as the population of the side chain increased. Two types of hydrogen bonding via water molecules, the side chain/main chain and the side chain/side chain hydrogen bonding, play an important role in determination of the triple helix conformation. The formation of a one-dimensional cavity of diameter about 3.5 A was observed in the schizophyllan triple helix, while curdlan showed no such cavity. The side chain/side chain hydrogen bonding in schizophyllan and the hypothetical beta-1,3-D-glucan triple helix could cause the tilt of the main-chain glucose residues to the helix.

  12. Market definition in two-sided markets : Theory and practice

    NARCIS (Netherlands)

    Filistrucchi, L.; Geradin, D.A.A.G.; van Damme, E.E.C.; Affeldt, P.


    Drawing from the economics of two-sided markets, we provide suggestions for the definition of the relevant market in cases involving two-sided platforms, such as media outlets, online intermediaries, payment cards companies, and auction houses. We also discuss when a one-sided approach may be harmle

  13. Organizational mediators siding with or against the powerful party?

    NARCIS (Netherlands)

    de Dreu, C.K.W.; Laskewitz, P.; van de Vliert, E.


    Examined whether, instead of being impartial, a mediator may side with one party as a function of the disputants' power differences (power balancing theory), the mediator's legitimacy judgments (siding theory), or the disputants' capacity to sanction the mediator (siding theory). A questionnaire stu

  14. Improved side information generation for distributed video coding

    DEFF Research Database (Denmark)

    Huang, Xin; Forchhammer, Søren


    As a new coding paradigm, distributed video coding (DVC) deals with lossy source coding using side information to exploit the statistics at the decoder to reduce computational demands at the encoder. The performance of DVC highly depends on the quality of side information. With a better side info...

  15. 14 CFR 23.363 - Side load on engine mount. (United States)


    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Side load on engine mount. 23.363 Section....363 Side load on engine mount. (a) Each engine mount and its supporting structure must be designed for a limit load factor in a lateral direction, for the side load on the engine mount, of not less...

  16. Stickleback Population

    Directory of Open Access Journals (Sweden)

    Ulrika Candolin


    Full Text Available Human-induced eutrophication has increased offspring production in a population of threespine stickleback Gasterosteus aculeatus in the Baltic Sea. Here, we experimentally investigated the effects of an increased density of juveniles on behaviours that influence survival and dispersal, and, hence, population growth—habitat choice, risk taking, and foraging rate. Juveniles were allowed to choose between two habitats that differed in structural complexity, in the absence and presence of predators and conspecific juveniles. In the absence of predators or conspecifics, juveniles preferred the more complex habitat. The preference was further enhanced in the presence of a natural predator, a perch Perca fluviatilis (behind a transparent Plexiglas wall. However, an increased density of conspecifics relaxed the predator-enhanced preference for the complex habitat and increased the use of the open, more predator-exposed habitat. Foraging rate was reduced under increased perceived predation risk. These results suggest that density-dependent behaviours can cause individuals to choose suboptimal habitats where predation risk is high and foraging rate low. This could contribute to the regulation of population growth in eutrophicated areas where offspring production is high.

  17. Population aging. (United States)


    This paper focuses on the impact of population aging in China, the most densely populated country in the world. Statistics indicate that by the end of 1998, 83.75 million out of the 1.248 billion Chinese people will be over 65 years old. According to the UN standards, China will soon become an aging society. The aging population poses several challenges to the country with the greatest challenge being the increasing social responsibility to care for the aged. With the undeveloped legislative framework to protect the interests of the aged and the serious drawbacks in the pension system to cater only to the income part and not the service part of the aged, China is not yet ready for the advent of aging. Violation of the rights of senior citizens is still very rampant despite enactment of the law on Protection of the Rights of the Elderly in 1996. Moreover, China is not economically ready to become an aging society. China faces this challenge by adopting a three-pronged approach to solve the problem namely: family support, establishment of nursing homes, and creating a social security framework that addresses the needs of the society suited to the Chinese condition. It is believed that with the growing economy of the country and the rising income of its people, a comprehensive social security net will be created to take care of the aged.

  18. The Other Side of GDP Growth

    Institute of Scientific and Technical Information of China (English)


    Zhan Yong,commentator of People’s Daily,and Cai Fang,Director of the Institute of Population and Labor Economics,Chinese Academy of Social Sciences(CASS),recently expressed their views on China’s elevation to the world’s second largest economy and its $5.88 trillion GDP value which grew at a year-on-year rate of 9.8 percent in 2010, saying in an analysis that China is still a developing

  19. Putative population of adipose-derived stem cells isolated from mediastinal tissue during cardiac surgery. (United States)

    Patel, Amit N; Yockman, James; Vargas, Vanessa; Bull, David A


    Mesenchymal stem cells have been isolated from various adult human tissues and are valuable for not only therapeutic applications but for the study of tissue homeostasis and disease progression. Subcutaneous adipose depots have been shown to contain large amounts of stem cells. There is little information that has been reported to date describing the isolation and characterization of mesenchymal stem cells from visceral adipose tissue. In this study, we describe a mesenchymal stem cell population isolated from mediastinal adipose depots. The cells express CD44, CD105, CD166, and CD90 and are negative for hematopoietic markers CD34, CD45, and HLA-DR. In addition, the cells have a multilineage potential, with the ability to differentiate into adipogenic, osteogenic, and chondrogenic cell types. The biological function of visceral adipose tissue remains largely unknown and uncharacterized. However, the proximity of adipose tissue to the heart suggests a potential role in the pathogenesis of cardiovascular disease in obesity. In addition, with the ability of fat to regulate metabolic activity in humans, this novel stem cell source may be useful to further study the mechanisms involved in metabolic disorders.

  20. Side-to-side growth discrepancies in children with hemiplegic cerebral palsy: association with function, activity and social participation


    Marise Bueno Zonta; Amâncio Ramalho-Júnior; Marilene Puppi; Isac Bruck,; Neiva Magdalena; Muzzolon, Sandra Regina B.; Arnolfo Carvalho-Neto; Lúcia H Coutinho dos Santos


    Objective: Evaluate side-to-side discrepancies in children with hemiplegic cerebral palsy (HCP), and investigate associations of these discrepancies with patients’ age at initiation of physical therapy, motor and cognitive function, and degree of activities and social participation. Method: We obtained eight side-to-side measurements from 24 HCP children with mean age 49.3±5.2 months. Results: Early initiation of physical therapy was associated with lower discrepancy in hand length (p=0.037)....

  1. Flow and wall shear stress in end-to-side and side-to-side anastomosis of venous coronary artery bypass grafts

    Directory of Open Access Journals (Sweden)

    Poulikakos Dimos


    Full Text Available Abstract Purpose Coronary artery bypass graft (CABG surgery represents the standard treatment of advanced coronary artery disease. Two major types of anastomosis exist to connect the graft to the coronary artery, i.e., by using an end-to-side or a side-to-side anastomosis. There is still controversy because of the differences in the patency rates of the two types of anastomosis. The purpose of this paper is to non-invasively quantify hemodynamic parameters, such as mass flow and wall shear stress (WSS, in end-to-side and side-to-side anastomoses of patients with CABG using computational fluid dynamics (CFD. Methods One patient with saphenous CABG and end-to-side anastomosis and one patient with saphenous CABG and side-to-side anastomosis underwent 16-detector row computed tomography (CT. Geometric models of coronary arteries and bypasses were reconstructed for CFD analysis. Blood flow was considered pulsatile, laminar, incompressible and Newtonian. Peri-anastomotic mass flow and WSS were quantified and flow patterns visualized. Results CFD analysis based on in-vivo CT coronary angiography data was feasible in both patients. For both types of CABG, flow patterns were characterized by a retrograde flow into the native coronary artery. WSS variations were found in both anastomoses types, with highest WSS values at the heel and lowest WSS values at the floor of the end-to-side anastomosis. In contrast, the highest WSS values of the side-to-side anastomosis configuration were found in stenotic vessel segments and not in the close vicinity of the anastomosis. Flow stagnation zones were found in end-to-side but not in side-to-side anastomosis, the latter also demonstrating a smoother stream division throughout the cardiac cycle. Conclusion CFD analysis of venous CABG based on in-vivo CT datasets in patients was feasible producing qualitative and quantitative information on mass flow and WSS. Differences were found between the two types of anastomosis

  2. Side Chain Engineering in Solution-Processable Conjugated Polymers

    KAUST Repository

    Mei, Jianguo


    Side chains in conjugated polymers have been primarily utilized as solubilizing groups. However, these side chains have roles that are far beyond. We advocate using side chain engineering to tune a polymer\\'s physical properties, including absorption, emission, energy level, molecular packing, and charge transport. To date, numerous flexible substituents suitable for constructing side chains have been reported. In this Perspective article, we advocate that the side chain engineering approach can advance better designs for next-generation conjugated polymers. © 2013 American Chemical Society.

  3. Radio on the Other Side of Time

    Directory of Open Access Journals (Sweden)

    Alicia TAPIA LÓPEZ


    Full Text Available On October 30, 1938, Orson Welles aired the radio drama The War of the Worlds on the CBS Radio network, adapting the science-fiction novel by the British writer H. G. Wells. During the broadcast, listeners became stricken with panic, believing that the Earth was actually being invaded by giant snake-like Martians launching rays of fire down on humans. Welles was a groundbreaking figure whose trickery exploited the technological novelty of the radio to its fullest, adapting classic texts in ways that exploited the opportunities afforded by this new medium. Over the years, this radio classic has been adapted a number of times, though none has seized on the technological advances of our times. Drawing on the most salient innovations seen in Internet radio, this article creates an imaginary scenario that replicates Orson Welles’s work in the present day, when the Internet has become a channel for broadcasting and hyperlinks have brought different media together. The text is an exploration of the other side of time, where transmedia storytelling facilitates the exchange of stories among consumers, and broadcast programming is no longer linear.

  4. The Darker Side of the Renaissance

    Directory of Open Access Journals (Sweden)

    Walter Mignolo


    Full Text Available The Darker Side of the Renaissance focuses on coloniality rather than on Europe’s witch and alchemist hunt. Today I would dare to say also that this expression refers us to the historical foundation of coloniality. At the same time, coloniality statement is called into question, as well as the distinction between the known object and the knowing subject, an assumption on which the Eurocentric project of “modernity” and “modernization” disciplines lie. The preface marks the enunciation with which the statement is stated. That is, it rejects the "point zero epistemology" denounced by Santiago Castro-Gómez. This means the reader should be always pay attention to the ennunciation s/he states him/herself, to the hand drawing the hand. Those of us dwelling at Abya-Yala/America are surrounded by the historical foundation of modernity/coloniality, we are a living part of that process, which only “scientific” alignment can make us believe we are looking at something (e.g., colonization touching what we are today

  5. Adaptive Optics Simulations for Siding Spring

    CERN Document Server

    Goodwin, Michael; Lambert, Andrew


    Using an observational derived model optical turbulence profile (model-OTP) we have investigated the performance of Adaptive Optics (AO) at Siding Spring Observatory (SSO), Australia. The simulations cover the performance for AO techniques of single conjugate adaptive optics (SCAO), multi-conjugate adaptive optics (MCAO) and ground-layer adaptive optics (GLAO). The simulation results presented in this paper predict the performance of these AO techniques as applied to the Australian National University (ANU) 2.3 m and Anglo-Australian Telescope (AAT) 3.9 m telescopes for astronomical wavelength bands J, H and K. The results indicate that AO performance is best for the longer wavelengths (K-band) and in the best seeing conditions (sub 1-arcsecond). The most promising results are found for GLAO simulations (field of view of 180 arcsecs), with the field RMS for encircled energy 50% diameter (EE50d) being uniform and minimally affected by the free-atmosphere turbulence. The GLAO performance is reasonably good over...

  6. Side effects of endobronchial laser treatment

    Energy Technology Data Exchange (ETDEWEB)

    Dierkesmann, R.; Huzly, A.


    Side effects that have occurred in over 250 endobronchial laser treatments are reported. The laser has been used in severe tracheal and in bronchial obstructions. In two cases significant bleeding had to be treated with tamponade. In one patient an emphysema of the mediastinum developed, in 2 further patients a small pneumothorax. Perforation of the airway was not detected and no special treatment was necessary. Three patients with life-threatening tracheal stenoses and one patient with severe stenosis of both the mainstem bronchi due to metastasis in the bifurcation lymph node had a large defect in the tracheal or bronchial wall with a deep necrosis five to twelve weeks after laser treatment; all these patients had extensive radiotherapy in addition. One patient died due to severe respiratory insufficiency, probably caused by smoke intoxication. After the laser treatment, rubber-like fibrin-rich plaques may develop, which can lead to life-threatening obstructions of the airway. It is recommended that laser bronchoscopy should be performed with the rigid bronchoscope. After treatment of tracheal lesion an endoscopic check must be performed within 24 hours. The combination of laser treatment and radiotherapy seems to involve a certain risk of large defects in the bronchial wall due to necrosis of the tumor.

  7. Interference Alignment: A one-sided approach

    CERN Document Server

    Ghauch, Hadi G


    Interference Alignment (IA) is the process of designing signals in such a way that they cast overlapping shadows at their unintended receivers, while remaining distinguishable at the intended ones. Our goal in this paper is to come up with an algorithm for IA that runs at the transmitters only (and is transparent to the receivers), that doesn't require channel reciprocity, and that alleviates the need to alternate between the forward and reverse network as is the case in Distributed IA (Gomadam, Cadambe, Jafar 08'), thereby inducing significant overhead in certain environments where the channel changes frequently. Most importantly, our effort is focused on ensuring that this one-sided approach does not degrade the performance of the system w.r.t. Distributed IA (since it cannot improve it). As a first step, we model the interference in each receiver's desired signal as a function of the transmitters' beamforming vectors. We then propose a simple steepest descent (SD) algorithm and use it to minimize the inter...

  8. Incentives for demand-side management

    Energy Technology Data Exchange (ETDEWEB)

    Reid, M.W.; Brown, J.B. [Barakat and Chamberlin, Inc., Oakland, CA (United States)


    This report is the first product of an ongoing project to monitor the efforts of states to remove regulatory barriers to, and provide financial incentives for, utility investment in demand-side management (DSM) resources. The project was commissioned by the National Association of Regulatory Utility Commissioners (NARUC) in response to growing interest among regulators for a comprehensive survey of developments in this area. Each state report beings with an overview of the state`s progress toward removing regulatory barriers and providing incentives for DSM. Information is organized under five headings: status; IRP regulations and practice; current treatment of DSM, directions and trends; commission contact person. Where applicable, each overview is followed by one or more sections that report on specific incentive proposals or mechanisms within the state. Information on each proposal or mechanism is organized under eight headings. A notation on each page identifies the utility or other group associated with the proposal or mechanism. The eight headings are as follows: status; background; treatment of cost recovery; treatment of lost revenues/decoupling; treatment of profitability; other features; issues, and additional observations.

  9. Incentives for demand-side management

    Energy Technology Data Exchange (ETDEWEB)

    Reid, M.W.; Brown, J.B. (Barakat and Chamberlin, Inc., Oakland, CA (United States))


    This report is the first product of an ongoing project to monitor the efforts of states to remove regulatory barriers to, and provide financial incentives for, utility investment in demand-side management (DSM) resources. The project was commissioned by the National Association of Regulatory Utility Commissioners (NARUC) in response to growing interest among regulators for a comprehensive survey of developments in this area. Each state report beings with an overview of the state's progress toward removing regulatory barriers and providing incentives for DSM. Information is organized under five headings: status; IRP regulations and practice; current treatment of DSM, directions and trends; commission contact person. Where applicable, each overview is followed by one or more sections that report on specific incentive proposals or mechanisms within the state. Information on each proposal or mechanism is organized under eight headings. A notation on each page identifies the utility or other group associated with the proposal or mechanism. The eight headings are as follows: status; background; treatment of cost recovery; treatment of lost revenues/decoupling; treatment of profitability; other features; issues, and additional observations.

  10. The Dark side of World of Warcraft

    DEFF Research Database (Denmark)

    Larsen, Lasse Juel

    the look of ‘the other’. ‘The look’ can following this argument be perceived as an instrument of (self)-becoming. Becoming aware of ourselves through the look of ‘the other’ also means ‘the other’ holds a formative power over us which can be understood as an instrument of control, an always present way...... understand, perceive or conceptualise fellow players in-side the game world. The analysis of ‘the other’ in WoW rests upon Jean-Paul Sartre’s phenomenological description of ‘the other’ through ‘the look’ in Being and Nothingness (1992). According to Sartre do living beings become aware of themselves through......’s epistemology not only serve to describe the state of ‘the other’ and the social disciplining impact of the spatial design on player perception and behaviour in WoW, it also aims at showing a connection between Sartre and Foucault’s analysis of ‘the look’. This leads to the tentative conclusion that ‘the look...

  11. [The democratic side of science-fiction]. (United States)

    Lecellier, Charles-Henri


    Suspicion towards technological advances has progressively grown during the xx(th) century. However, in the XXI(st) century, reading the NBIC (nanotechnology, biotechnology, information technology and cognitive science) report of the National Science Foundation, we can note that science has caught up with science fiction. These changes in public mentality on one side and in scientific capacities on the other argue for an evolution of the debate on sciences. The recent example of the national debate on nanotechnology in France has clearly shown that the public is no longer waiting for additional sources of scientific knowledge but rather waiting for the recognition of its authority to participate in the definition of the national R&D priority and associated scientific strategies. This is all the more legitimate that these strategies will have profound impact on the future of our societies and therefore cannot be decided only by scientists. Hence, it is crucial to identify innovative tools promoting debate on sciences and their technological spin-off. Here, we contend that science fiction has major assets that could face this challenge and facilitate the dialogue between sciences and society.

  12. The effectiveness of side marker lamps: an experimental study. (United States)

    Theeuwes, J; Alferdinck, J W


    The present experiment investigated the effect of small amber lamps mounted near the front and rear on each side of a passenger car-so called side marker lamps-on visual detection and recognition of passenger cars in complex nighttime environments. It was determined whether cars equipped with side marker lamps are detected and recognized earlier and more accurately than cars without side marker lamps. Subjects were presented with slides of natural nighttime scenes in which a car, either with or without side marker lamps, viewed from its side, approaching from a side street, was either present or not. Subjects determined as fast as possible whether a car was present or not. Reaction time measures (speed and accuracy) indicated that both under clear and fog visibility conditions, a car equipped with side marker lamps was detected and recognized earlier and more accurately than a car without side marker lamps. The results indicate that side marker lamps increase both lateral conspicuity and recognizability suggesting that side marker lamps may be effective in reducing the number of nighttime angle collisions.

  13. Indian populations

    CERN Document Server



    Le Prof. J.C. Spahni qui a parcouru les Andes, Vénezuela etc. parle de ses expériences et connaissances qu'il a vécu au cours des 14 ans parmi les populations indiennes de la Cordillière des Andes. Il a ramené des objets artisanals indiens lesquels l'auditoire peut acquérir. L'introduction-conférence est suivi d'un film, commenté par lui-même; après l'entracte il y un débat-dialogue avec le public.

  14. Measured Data Processing Method For Relative Motions Between Two Side-by-side Ships

    Directory of Open Access Journals (Sweden)

    Ping-an Shi


    Full Text Available In order to design and implement a wave compensation system to reduce the relative motion between two side-by-side ships in waves, a new method to process measured data of ship model test with contact measurement to study the characteristics of relative motion was presented. The reference co-ordinate systems and relative motions were defined, and the scheme of the model test was described. Then the Empirical Mode Decomposition(EMD adaptive filter were designed, the frequency domain integration transform method based upon Fast Fourier Transform(FFT were established. The procedure to transform acceleration signal into displacement was proposed and verified, and the processing results with and without EMD adaptive filter were compared. Finally, the relative motions consistent with reality were acquired, which indicates this method is effective for measured data processing.

  15. Wave Drift Forces on Two Floating Bodies Arranged Side by Side

    Institute of Scientific and Technical Information of China (English)

    Wenyang Duan; Binbin Zhao


    An innovative hydrodynamic theory and numerical model were developed to help improve the efficiency,accuracy,and convergence of the numerical prediction of wave drift forces on two side-by-side deepwater floating bodies.The wave drift forces were expressed by the double integration of source strength and the corresponding Green function on the body surface,which is consistent with the far field formula based on momentum conservation and sharing the advantage of near field calculations providing the drift force on each body.Numerical results were validated through comparing the general far field model and pressure integral model,as well as the middle field model developed using the software HydroStar.

  16. Detection of Left-Sided and Right-Sided Hearing Loss via Fractional Fourier Transform

    Directory of Open Access Journals (Sweden)

    Shuihua Wang


    Full Text Available In order to detect hearing loss more efficiently and accurately, this study proposed a new method based on fractional Fourier transform (FRFT. Three-dimensional volumetric magnetic resonance images were obtained from 15 patients with left-sided hearing loss (LHL, 20 healthy controls (HC, and 14 patients with right-sided hearing loss (RHL. Twenty-five FRFT spectrums were reduced by principal component analysis with thresholds of 90%, 95%, and 98%, respectively. The classifier is the single-hidden-layer feed-forward neural network (SFN trained by the Levenberg–Marquardt algorithm. The results showed that the accuracies of all three classes are higher than 95%. In all, our method is promising and may raise interest from other researchers.

  17. Flow Features of Three Side-by-side Circular Cylinders at Low Reynolds Number

    Directory of Open Access Journals (Sweden)

    Liu Junkao


    Full Text Available In order to study the fluctuation of kinetic parameter of cylinder matrix in incompressible stationary flow, the flow fluid around three side-by-side circular cylinders are simulated using Immersed Boundary–Lattice Boltzmann method (IB-LBM. Drag and lift force of the three cylinders are investigated as the interval between each cylinder varied from zero to five times of the cylinder diameter. Five flow patterns are defined according to the vortices structure in the downstream of the cylinders. Power spectrum analysis of lift force is developed to explain the vortex patterns. Through the research, we find the strength and phase of the gap flow play an important role in the vortex formatting process. The vortices shedding from different cylinders neutralize and combine in the near wake, contributing a lot to the variation of forces.

  18. Integrated planning in supply chains with buy-side and sell-side marketplaces

    Indian Academy of Sciences (India)

    Roshan Gaonkar; N Viswanadham


    In this paper we develop a quadratic programming model for partner selection and planning in integrated supply chain networks embedded with both sell-side and buy-side electronic marketplaces. Such a scenario arises in several practical applications. In particular, we consider a contract manufacturer who procures components from suppliers through a component marketplace and sells its manufactured sub-assemblies to original equipment manufacturers (OEMs), through a sub-assembly marketplace. In these web-enabled supply chains, embedded with upstream and downstream electronic marketplaces, we need methods for online supply-chain partner selection based on pricing and delivery schedules. In this paper, we develop and present such a model that selects partners, synchronizes supply chain activities and optimizes the profit through optimal revenue pricing and cost minimization.

  19. Is right-sided colon cancer different to left-sided colorectal cancer? - a systematic review. (United States)

    Lee, G H; Malietzis, G; Askari, A; Bernardo, D; Al-Hassi, H O; Clark, S K


    Colorectal cancer (CRC) exhibits differences in incidence, pathogenesis, molecular pathways and outcome depending on the location of the tumor. This review focuses on the latest developments in epidemiological and scientific studies, which have enhanced our understanding on the underlying genetic and immunological differences between the proximal (right-sided) colon and the distal (left-sided) colorectum. The different ways in which environmental risk factors influence the pathogenesis of CRC depending on its location and the variations in surgical and oncological outcomes are also discussed in this review. In the current era of personalized medicine, we aim to reiterate the importance of tumor location in management of CRC and the implication on future clinical and scientific research.

  20. Side by side tests of two SDHW systems with solar collectors with and without antireflection treatment

    DEFF Research Database (Denmark)

    Kong, Weiqiang; Han, Jiangong; Perers, Bengt


    Two low flow SDHW systems based on mantle tanks are tested side by side in a laboratory test facility for solar heating systems under the same weather and operation conditions. The systems are identical with the exception that one system is equipped with a solar collector with antireflection...... treated glass while the other system has a collector with a normal glass. Measurements of the thermal performance of the two systems have been carried out for a long measuring period. The thermal performances of the systems have also been calculated with a detailed simulation model. There is a good...... agreement between measured and calculated thermal performances for both systems. The extra thermal performance of the system with the solar collector with the anti reflection treated glass cover is a strong function of the solar fraction. In sunny periods with high solar fractions the percentage extra...


    DEFF Research Database (Denmark)

    Fan, Jianhua; Dragsted, Janne; Furbo, Simon


    Six differently designed evacuated tubular collectors, ETCs, utilizing solar radiation from all directions, have been investigated experimentally. The evacuated tubular solar collectors investigated include one SLL all-glass ETC from Tshinghua Solar Co., four heat pipe ETCs from Sunda Technolgoy Co....... and one all-glass ETC with heat pipe from Exoheat AB. The collectors have been investigated side-by-side in an outdoor test facility for a long period. During the measurements, the operating conditions – such as weather conditions, inlet and mean solar collector fluid temperatures have been the same. Thus...... a direct performance comparison is possible. The results of the measurements will be presented in this paper. Among other things, the influence on the thermal performance of the absorber design will be explained. Further, it will be illustrated how the thermal performances of the different collector types...

  2. The Dark Side of Neutron Stars

    DEFF Research Database (Denmark)

    Kouvaris, Christoforos


    We review severe constraints on asymmetric bosonic dark matter based on observations of old neutron stars. Under certain conditions, dark matter particles in the form of asymmetric bosonic WIMPs can be eectively trapped onto nearby neutron stars, where they can rapidly thermalize and concentrate...... in the core of the star. If some conditions are met, the WIMP population can collapse gravitationally and form a black hole that can eventually destroy the star. Based on the existence of old nearby neutron stars, we can exclude certain classes of dark matter candidates....

  3. The Dark Side of Neutron Stars

    Directory of Open Access Journals (Sweden)

    Chris Kouvaris


    Full Text Available We review severe constraints on asymmetric bosonic dark matter based on observations of old neutron stars. Under certain conditions, dark matter particles in the form of asymmetric bosonic WIMPs can be effectively trapped onto nearby neutron stars, where they can rapidly thermalize and concentrate in the core of the star. If some conditions are met, the WIMP population can collapse gravitationally and form a black hole that can eventually destroy the star. Based on the existence of old nearby neutron stars, we can exclude certain classes of dark matter candidates.

  4. A Survey of Caffeine Use and Associated Side Effects in a College Population. (United States)

    Johnson-Greene, Douglas; And Others


    Surveyed 270 college students concerning their caffeine consumption. Results suggest there is identifiable group using excessive amounts of caffeine. Identified several deleterious effects possibly related to caffeine use. Approximately 75 percent of caffeine users surveyed rarely sought information on caffeine content of products or avoided…

  5. Comparison of the Side Populations in Pretreatment and Postrelapse Neuroblastoma Cell Lines (United States)


    needed if we are to improve outcomes in high- risk neuroblastoma. References [1] Maris JM, Hogarty MD, Bagatell R, and Cohn SL (2007). Neuroblastoma...stem– like cells are enriched partly but not exclusively. Endocrinology 148, 1797–1803. [26] Kondo T, Setoguchi T, and Taga T (2004). Persistence of

  6. The side-to-side fashion for individual distal coronary anastomosis using venous conduit. (United States)

    Kato, Takayoshi; Tsunekawa, Tomohiro; Motoji, Yusuke; Hirakawa, Akihiro; Okawa, Yasuhide; Tomita, Shinji


    Regarding to coronary artery bypass grafting (CABG), the end-to-side anastomosis (ESA) has been performed as a gold standard. Recently, the effectiveness of the distal side-to-side anastomosis (SSA) in CABG using internal mammary artery has been reported. The benefit of SSA comparing to ESA also has been disclosed by computing simulation. However, use of SSA by venous conduit for individual CABG has not been reported. In this study, we investigated feasibility of SSA. From January 2013 to October 2014, we conducted 114 CABGs. There were 92 venous distal anastomoses without sequential anastomotic site (61 SSA and 31 ESA). The anastomosis was evaluated before discharge and at 1 year after the procedure by angiography or multi-detector row computed tomographic coronary angiography. The median values for time to anastomosis were 13 min in the two group (p = 0.89). There was no revision of anastomosis in both groups. Additional stitches for hemostasis were required significantly less in SSA than ESA (18.0 vs 45.2 %, respectively, p fashion is easy to perform and maybe beneficial in blood flow pattern.

  7. CD26 Expression on T Helper Populations and sCD26 Serum Levels in Patients with Rheumatoid Arthritis (United States)

    Cordero, Oscar J.; Varela-Calviño, Rubén; López-González, Tania; Calviño-Sampedro, Cristina; Viñuela, Juan E.; Mouriño, Coral; Hernández-Rodríguez, Íñigo; Rodríguez-López, Marina; Aspe de la Iglesia, Bruno; Pego, José María


    We studied dipeptidyl peptidase IV (DPP-IV, CD26) expression in different T helper cells and serum soluble DPP-IV/sCD26 levels in rheumatoid arthritis (RA) patients, correlated these with disease activity score (DAS), and examined how they were affected by different therapies, conventional or biological (anti-TNF, anti-CD20 and anti-IL6R or Ig-CTLA4). The percentage of CD4+CD45R0+CD26- cells was greatly reduced in patients (up to 50%) when compared with healthy subjects. Three other subsets of CD4 cells, including a CD26high Th1-associated population, changed variably with therapies. Data from these subsets (frequency and staining density) significantly correlated with DAS28 or DAS28 components but different in each group of patients undergoing the different therapies. Th17 and Th22 subsets were implicated in RA as independent CCR4+ and CCR4- populations each, with distinct CD26 expression, and were targeted with varying efficiency by each therapy. Serum DPP-IV activity rather than sCD26 levels was lower in RA patients compared to healthy donors. DPP-IV and sCD26 serum levels were found related to specific T cell subsets but not to disease activity. We conclude that, according to their CD26 expression, different cell subsets could serve to monitor RA course, and an uncharacterized T helper CD26- subset, not targeted by therapies, should be monitored for early diagnosis. PMID:26177310

  8. Why fruits go to the dark side (United States)

    Schaefer, H. Martin


    The colours of fleshy fruits are usually attributed to attract seed dispersers to the plant. A cursory look at the gaudy colours of fleshy fruits on offer in a local fruit stall gives the impression that plants use primarily bright colours to attract fruit consumer. This impression is misleading; many small fruits 'go to the dark side' and become dark purple or black when ripe. Intermingled in foliage, these colours, which are produced by anthocyanins, can be fairly inconspicuous and are thus not easily reconciled with a signalling function to attract seed dispersers. In this review I therefore discuss complementary hypotheses on the function and evolution of fruit colouration. First, I focus on the evidence that fruit colours indeed function as signals to attract seed dispersers. I then show that anthocyanins, the most prevalent fruit pigments, are important dietary antioxidants that can be selected by blackcaps ( Sylvia atricapilla) which are important avian seed dispersers of many European plants. Moreover, the consumption of anthocyanins increases the likelihood that blackcaps mount an immune response during immune challenges. As a next step, I review evidence that anthocyanins accumulate in fruit skin in response to abiotic factors, in particular high illumination coupled with low temperature favour the increase of anthocyanins. Finally, I show that anthocyanins can also be selected for by fruit antagonists, consumers that do not disperse seeds. In particular, high contents of anthocyanins strongly reduce fungal growth in fruit tissue. Taken together, there are various selective pressures which likely influence fruit colour evolution. Currently, the relative importance of each of these selective agents is unknown. There is consequently a need to develop a more encompassing framework on fruit colour evolution.

  9. The Dark Side of the Earth (United States)

    Frankel, Henry


    Wood's The Dark Side of the Earth is another addition to the growing list of books on the recent revolution in the earth sciences. Wood rightly points out that any new book on the topic should break new ground. In the preface, he writes of himself and his book that he has benefited from previous accounts by saving himself research time, and that his book, unlike others, “attempts to tell one complete story of the study of the Earth, geologists, geophysicists, dreamers and all” (p. vi). Wood is ambitious, for his work covers much of 19th-century geology as well as the development, reception, rejection, and eventual acceptance of mobilist ideas. Before discussing the work of the German meteorologist and geophysicist Alfred L. Wegener, American glacial geomorphologist Frank Taylor, and several of their predecessors who proposed “mobilist” ideas, he manages to string together brief descriptions of the contributions of (among others) German mineralogist Abraham Gottlob Werner, British geologists James Hutten and John Playfair, British engineer William Smith, British geologist Charles Lyell, American geologists James Hall and James Dwight Dana, British volcanologist William Lowthian Green, American geologist Grove Karl Gilbert, French geologist Elie de Beaumont, British geologist and mathematician Osmond Fisher, American geologist Clarence Dutton, British mathematician and physicist Lord Kelvin, Austrian geologist Eduard Suess, French geologist Marcel Bertrand, and American geologist Thomas Chrowder Chamberlin. Moreover, Wood offers an interesting thesis about the revolution in the earth sciences. He claims that the real revolution was not the replacement of fixist views with the mobilist ones of sea floor spreading and plate tectonics, but rather the replacement of geology with the new discipline of the earth sciences in which geophysics and geochemistry play the central role.

  10. 发电侧如何促进需求侧管理%How to Improve Demand Side Management in Generation Side

    Institute of Scientific and Technical Information of China (English)



    Combining with the practice of DSM in China, the paper analyzes the role of engaging demand side management in generation side. Also it deeply studies how to promote demand side management in generation side, which rarelyinvolves in the published literature all over the world. Besides, it discovers the interactions of interdependence and competition between demand side managenent and generation side operation. Lastly it studies the example of demand side management in generation side in Shenzhen.

  11. Side effects as influencers of treatment outcome. (United States)

    Sharif, Zafar


    Research relative to the efficacy of a therapeutic agent commands a clinician's greatest interest, but treatment decisions are made based on optimizing efficacy and tolerability/safety considerations. Second-generation atypical antipsychotic drugs are a study in the importance of taking a careful look at the full benefit-risk profile of each drug. The disorders that atypical antipsychotics are approved to treat--schizophrenia, schizoaffective disorder, and bipolar disorder--are associated with an increased rate of certain medical comorbidities compared to the general population. Between-drug differences in efficacy are relatively modest for the atypicals, or between atypicals and conventionals, while differences in safety and tolerability are larger and more clinically relevant. The current article will provide a brief summary of safety-related issues that influence treatment outcome and choice of drug.

  12. Soy and phytoestrogens: possible side effects. (United States)

    Jargin, Sergei V


    Phytoestrogens are present in certain edible plants being most abundant in soy; they are structurally and functionally analogous to the estrogens. Phytoestrogens have been applied for compensation of hormone deficiency in the menopause. At the same time, soy products are used in infant food and other foodstuffs. Furthermore, soy is applied as animal fodder, so that residual phytoestrogens and their active metabolites such as equol can remain in meat and influence the hormonal balance of the consumers. There have been only singular reports on modified gender-related behavior or feminization in humans in consequence of soy consumption. In animals, the intake of phytoestrogens was reported to impact fertility, sexual development and behavior. Feminizing effects in humans can be subtle and identifiable only statistically in large populations.

  13. Soy and phytoestrogens: possible side effects

    Directory of Open Access Journals (Sweden)

    Jargin, Sergei V.


    Full Text Available [english] Phytoestrogens are present in certain edible plants being most abundant in soy; they are structurally and functionally analogous to the estrogens. Phytoestrogens have been applied for compensation of hormone deficiency in the menopause. At the same time, soy products are used in infant food and other foodstuffs. Furthermore, soy is applied as animal fodder, so that residual phytoestrogens and their active metabolites such as equol can remain in meat and influence the hormonal balance of the consumers. There have been only singular reports on modified gender-related behavior or feminization in humans in consequence of soy consumption. In animals, the intake of phytoestrogens was reported to impact fertility, sexual development and behavior. Feminizing effects in humans can be subtle and identifiable only statistically in large populations.

  14. Population Genetics with Fluctuating Population Sizes

    CERN Document Server

    Chotibut, Thiparat


    Standard neutral population genetics theory with a strictly fixed population size has important limitations. An alternative model that allows independently fluctuating population sizes and reproduces the standard neutral evolution is reviewed. We then study a situation such that the competing species are neutral at the equilibrium population size but population size fluctuations nevertheless favor fixation of one species over the other. In this case, a separation of timescales emerges naturally and allows adiabatic elimination of a fast population size variable to deduce the fluctuations-induced selection dynamics near the equilibrium population size. The results highlight the incompleteness of the standard population genetics with a strictly fixed population size.

  15. Nonlinear dynamics of interacting populations

    CERN Document Server

    Bazykin, Alexander D


    This book contains a systematic study of ecological communities of two or three interacting populations. Starting from the Lotka-Volterra system, various regulating factors are considered, such as rates of birth and death, predation and competition. The different factors can have a stabilizing or a destabilizing effect on the community, and their interplay leads to increasingly complicated behavior. Studying and understanding this path to greater dynamical complexity of ecological systems constitutes the backbone of this book. On the mathematical side, the tool of choice is the qualitative the

  16. Double Sided Si(Ge)/Sapphire/III-Nitride Hybrid Structure (United States)

    Park, Yeonjoon (Inventor); Choi, Sang Hyouk (Inventor)


    One aspect of the present invention is a double sided hybrid crystal structure including a trigonal Sapphire wafer containing a (0001) C-plane and having front and rear sides. The Sapphire wafer is substantially transparent to light in the visible and infrared spectra, and also provides insulation with respect to electromagnetic radio frequency noise. A layer of crystalline Si material having a cubic diamond structure aligned with the cubic direction on the (0001) C-plane and strained as rhombohedron to thereby enable continuous integration of a selected (SiGe) device onto the rear side of the Sapphire wafer. The double sided hybrid crystal structure further includes an integrated III-Nitride crystalline layer on the front side of the Sapphire wafer that enables continuous integration of a selected III-Nitride device on the front side of the Sapphire wafer.

  17. Compressed sensing with side information on the feasible region

    CERN Document Server

    Rostami, Mohammad


    This book discusses compressive sensing in the presence of side information. Compressive sensing is an emerging technique for efficiently acquiring and reconstructing a signal. Interesting instances of Compressive Sensing (CS) can occur when, apart from sparsity, side information is available about the source signals. The side information can be about the source structure, distribution, etc. Such cases can be viewed as extensions of the classical CS. In these cases we are interested in incorporating the side information to either improve the quality of the source reconstruction or decrease the number of samples required for accurate reconstruction. In this book we assume availability of side information about the feasible region. The main applications investigated are image deblurring for optical imaging, 3D surface reconstruction, and reconstructing spatiotemporally correlated sources. The author shows that the side information can be used to improve the quality of the reconstruction compared to the classic...

  18. The study of CD side to side error in line/space pattern caused by post-exposure bake effect (United States)

    Huang, Jin; Guo, Eric; Ge, Haiming; Lu, Max; Wu, Yijun; Tian, Mingjing; Yan, Shichuan; Wang, Ran


    In semiconductor manufacturing, as the design rule has decreased, the ITRS roadmap requires crucial tighter critical dimension (CD) control. CD uniformity is one of the necessary parameters to assure good performance and reliable functionality of any integrated circuit (IC) [1] [2], and towards the advanced technology nodes, it is a challenge to control CD uniformity well. The study of corresponding CD Uniformity by tuning Post-Exposure bake (PEB) and develop process has some significant progress[3], but CD side to side error happening to some line/space pattern are still found in practical application, and the error has approached to over the uniformity tolerance. After details analysis, even though use several developer types, the CD side to side error has not been found significant relationship to the developing. In addition, it is impossible to correct the CD side to side error by electron beam correction as such error does not appear in all Line/Space pattern masks. In this paper the root cause of CD side to side error is analyzed and the PEB module process are optimized as a main factor for improvement of CD side to side error.

  19. Intrinsic features of flow around two side-by-side square cylinders (United States)

    Alam, Md. Mahbub; Zhou, Y.


    The wake of two side-by-side square cylinders is investigated in detail based on flow visualization at a Reynolds number (Re) of 300. The cylinder center-to-center spacing ratio T* (= T/W, W is the cylinder width) is varied from 1.0 to 5.0. The intrinsic features of the wake are explored, including the gap vortices, flow switch, stability, merging of two streets into one, etc. The qualitative information on these features is further complemented by the quantitative information extracted from hotwire data at Re = 4.7 × 104 using both spectral and cross-wavelet analyses. Four flow regimes are identified: (i) the single bluff body regime (T* 2.4). The gap flow is found to switch at two distinct time scales, referred to as macro and micro switches. Macro switch occurs at 1.2 gap flow is slim in width and biased for a long duration ranging from several vortex shedding periods in the wide street to several hours. Micro switch is observed at 2.1 gap flow is thick in width and switches at a frequency of twice the frequency of vortex shedding from the free-stream side of the cylinders. The two streets formed immediately behind the cylinders merge to a single street at a downstream location x_c^* that depends on T*. A larger T* corresponds to a larger x_c^*. Regime (iv) is characterized by two streets either inphased or antiphased. The antiphased streets persist longer than the inphased.

  20. Wake structures of two side by side spheres in a tripped boundary layer flow (United States)

    Canli, Eyüb; Özgören, Muammer; Dogan, Sercan; Hilmi Aksoy, Muharrem; Akilli, Huseyin


    Two independent spheres were placed in a side by side arrangement and flow structure in the wake region of the spheres was investigated with a Particle Image Velocimetry (PIV) system when the spheres were in a boundary layer over a flat plate as a special case. Reynolds number was 5000 based on the sphere diameter which was 42.5 mm. Boundary layer was tripped 8mm away from the leading edge of the flat plate with a 5 mm trip wire. The thickness of the hydrodynamically developed boundary layer was determined as 63mm which was larger than the sphere diameter of D=42.5mm. Wake region of the spheres was examined from point of flow physics for the different sphere locations in the ranges of 0≤G/D ≤1.5 and 0≤S/D ≤1.5 where G and S were the distance between the spheres and the distance between the bottom point of the spheres and the flat plate surface, respectively. Depending on the different sphere locations, instantaneous and time averaged vorticity data, scalar values of time-averaged velocity components and their root mean square (rms) values and time averaged vorticity data are presented in the study for the evaluation of wake region of the spheres. It is demonstrated that the gap between the two spheres and the interaction between the gap and the boundary layer greatly affects flow pattern, especially when spheres are located near to the flat plate surface, i.e. S/D=0.1 for 0≤G/D ≤1.5. Different distances between the spheres resulted in various flow patterns as the spheres were approached to the flat plate. The distance S/D=0.1 for all gap values has the strongest effect on the wake structures. Beyond G/D=1.0, the sphere wakes tend to be similar to single sphere case. The instantaneous vorticity fields of the side by side arrangements comprised wavy structures in higher level comparing to an individual sphere case. The gap flow intensifies the occurrence of small scale eddies in the wake region. The submersion rate of the spheres actually determines the

  1. Wake structures of two side by side spheres in a tripped boundary layer flow

    Directory of Open Access Journals (Sweden)

    Canli Eyüb


    Full Text Available Two independent spheres were placed in a side by side arrangement and flow structure in the wake region of the spheres was investigated with a Particle Image Velocimetry (PIV system when the spheres were in a boundary layer over a flat plate as a special case. Reynolds number was 5000 based on the sphere diameter which was 42.5 mm. Boundary layer was tripped 8mm away from the leading edge of the flat plate with a 5 mm trip wire. The thickness of the hydrodynamically developed boundary layer was determined as 63mm which was larger than the sphere diameter of D=42.5mm. Wake region of the spheres was examined from point of flow physics for the different sphere locations in the ranges of 0≤G/D ≤1.5 and 0≤S/D ≤1.5 where G and S were the distance between the spheres and the distance between the bottom point of the spheres and the flat plate surface, respectively. Depending on the different sphere locations, instantaneous and time averaged vorticity data, scalar values of time-averaged velocity components and their root mean square (rms values and time averaged vorticity data are presented in the study for the evaluation of wake region of the spheres. It is demonstrated that the gap between the two spheres and the interaction between the gap and the boundary layer greatly affects flow pattern, especially when spheres are located near to the flat plate surface, i.e. S/D=0.1 for 0≤G/D ≤1.5. Different distances between the spheres resulted in various flow patterns as the spheres were approached to the flat plate. The distance S/D=0.1 for all gap values has the strongest effect on the wake structures. Beyond G/D=1.0, the sphere wakes tend to be similar to single sphere case. The instantaneous vorticity fields of the side by side arrangements comprised wavy structures in higher level comparing to an individual sphere case. The gap flow intensifies the occurrence of small scale eddies in the wake region. The submersion rate of the spheres

  2. On Cascade Source Coding with A Side Information "Vending Machine"

    CERN Document Server

    Ahmadi, Behzad; Choudhuri, Chiranjib; Mitra, Urbashi


    The model of a side information "vending machine" accounts for scenarios in which acquiring side information is costly and thus should be done efficiently. In this paper, the three-node cascade source coding problem is studied under the assumption that a side information vending machine is available either at the intermediate or at the end node. In both cases, a single-letter characterization of the available trade-offs among the rate, the distortions in the reconstructions at the intermediate and at the end node, and the cost in acquiring the side information are derived under given conditions.

  3. Review: Tales from Both Sides of the Brain (United States)

    Landis, Theodor


    Our brain has two hemispheres that specialize in different jobs—the right side processes spatial and temporal information, and the left side controls speech and language. How these two sides come together to create one mind is explained by pioneering neuroscientist Michael Gazzaniga in his new book, Tales from Both Sides of the Brain : A Life in Neuroscience (Ecco/Harper Collins, 2015). Gazzaniga is director of the SAGE Center for the Study of the Mind at the University of California, Santa Barbara, and a Dana Alliance member. PMID:27408671

  4. "Source Coding With a Side Information ""Vending Machine"""


    Weissman, Tsachy; Permuter, Haim H.


    We study source coding in the presence of side information, when the system can take actions that affect the availability, quality, or nature of the side information. We begin by extending the Wyner-Ziv problem of source coding with decoder side information to the case where the decoder is allowed to choose actions affecting the side information. We then consider the setting where actions are taken by the encoder, based on its observation of the source. Actions may have costs that are commens...

  5. Meta-heuristic algorithm to solve two-sided assembly line balancing problems (United States)

    Wirawan, A. D.; Maruf, A.


    Two-sided assembly line is a set of sequential workstations where task operations can be performed at two sides of the line. This type of line is commonly used for the assembly of large-sized products: cars, buses, and trucks. This paper propose a Decoding Algorithm with Teaching-Learning Based Optimization (TLBO), a recently developed nature-inspired search method to solve the two-sided assembly line balancing problem (TALBP). The algorithm aims to minimize the number of mated-workstations for the given cycle time without violating the synchronization constraints. The correlation between the input parameters and the emergence point of objective function value is tested using scenarios generated by design of experiments. A two-sided assembly line operated in an Indonesia's multinational manufacturing company is considered as the object of this paper. The result of the proposed algorithm shows reduction of workstations and indicates that there is negative correlation between the emergence point of objective function value and the size of population used.

  6. Metabolic disturbances, side effect profile and effectiveness of clozapine in adolescents

    Directory of Open Access Journals (Sweden)

    Sandeep Grover


    Full Text Available Introduction: Data on effect of clozapine on metabolic syndrome in adolescent patients with psychosis are limited. This study aimed to evaluate the prevalence and incidence of metabolic syndrome in children and adolescents with psychotic disorders prior to clozapine and while receiving clozapine. Secondary aims were to study the effectiveness and side effect profile of clozapine. Materials and Methods: Thirteen child and adolescent patients were evaluated at baseline, 3 months, and a follow-up beyond 6 months. Assessments were made for metabolic profile, effectiveness by positive and negative syndrome scale (PANSS, and side effects. Results: Prior to starting of clozapine, the prevalence of metabolic syndrome was 23%. After 3 months on clozapine, 38.5% (5/13 patients fulfilled criteria of metabolic syndrome and further on follow-up beyond 6 months (with last observation carried forward 46.2% (6/13 had developed metabolic syndrome. There was a significant reduction in PANSS scores at 3 months and follow-up more so in those who developed metabolic syndrome at 3 months. Among the other side effects, hypersalivation was the most common side effect (100% followed by sedation (69%. Conclusion: Half the prevalence of metabolic syndrome in adolescents on clozapine can be attributed to other factors prior to starting of clozapine, and another half can be attributed to clozapine. Clozapine is effective in an adolescent population.

  7. Terrorism, civil war, one-sided violence and global burden of disease. (United States)

    Kerridge, Bradley T; Khan, Maria R; Sapkota, Amir


    Armed conflict and related violence, including terrorism and one-sided violence, has profound effects on people's health and lives. The purpose of this study was to determine the relationship between deaths due to terrorism, civil war and one-sided violence from 1994-2000 and disability-adjusted life years (DALYs) occurring in 2002 attributable to all causes and specific communicable and noncommunicable diseases. Deaths resulting from terrorism, war and one-sided violence were positively associated with all cause as well as a number of communicable and noncommunicable disease-specific DALYs across the majority of sex and age subgroups of the populace, controlling for an array of economic factors empirically shown to affect public health. Overall, a 1.0% increase in deaths due to terrorism, civil war and one-sided violence from 1994-2000 was associated with a 0.16% increase in DALYs lost to all causes in 2002 in the total world population. There was little variation in the magnitude of these associations between males and females and between communicable and noncommunicable diseases. The results of the present study can begin to guide post-conflict recovery by focusing on interventions targeting both noncommunicable as well as communicable diseases, thereby highlighting the full health costs of war and ultimately providing a strong rationale for promoting peace.

  8. Mitochondrial DNA haplotyping of Testudo graeca on both continental sides of the Straits of Gibraltar. (United States)

    Alvarez, Y; Mateo, J A; Andreu, A C; Díaz-Paniagua, C; Diez, A; Bautista, J M


    Testudo graeca is an endangered species of tortoise that inhabits Mediterranean areas of Africa, Asia, and Europe. Western populations are found on both sides of the Straits of Gibraltar. The effects of geographical isolation on genetic divergence were assessed by the sequence analysis of two mitochondrial DNA regions of the 12S rRNA and cytochrome b genes. Four different haplotypes were identified. A single haplotype was shared by all Spanish and some east Moroccan specimens. Two haplotypes were unique to the west Moroccan T. graeca populations and allowed the clear discrimination between individual specimens found west of the Moulouya River. Phylogenetic analysis based on the estimation of nucleotide sequence distances of the haplotypes suggests an African origin for the Spanish populations and a subspecies status for the west Moroccan pool.

  9. Side-to-side growth discrepancies in children with hemiplegic cerebral palsy: association with function, activity and social participation

    Directory of Open Access Journals (Sweden)

    Marise Bueno Zonta


    Full Text Available Objective: Evaluate side-to-side discrepancies in children with hemiplegic cerebral palsy (HCP, and investigate associations of these discrepancies with patients’ age at initiation of physical therapy, motor and cognitive function, and degree of activities and social participation. Method: We obtained eight side-to-side measurements from 24 HCP children with mean age 49.3±5.2 months. Results: Early initiation of physical therapy was associated with lower discrepancy in hand length (p=0.037. Lower foot length discrepancy was associated with lower requirement for caregiver assistance in activities related to mobility. Increased side-to-side discrepancy was associated with reduced wrist extension and increased spasticity. Discrepancy played a larger role in children with hemineglect and in those with right involvement. Conclusion: Increased discrepancy in HCP children was associated with reduced degree of activity/social participation. These results suggest an association between functional use of the extremities and limb growth.

  10. Identification of New Rat Bone Marrow-Derived Population of Very Small Stem Cell with Oct-4A and Nanog Expression by Flow Cytometric Platforms

    Directory of Open Access Journals (Sweden)

    Anna Labedz-Maslowska


    Full Text Available Very small embryonic-like stem cells (VSELs represent a unique rare population of adult stem cells (SCs sharing several structural, genetic, biochemical, and functional properties with embryonic SCs and have been identified in several adult murine and human tissues. However, rat bone marrow- (BM- derived SCs closely resembling murine or human VSELs have not been described. Thus, we employed multi-instrumental flow cytometric approach including classical and imaging cytometry and we established that newly identified population of nonhematopoietic cells expressing CD106 (VCAM-I antigen contains SCs with very small size, expressing markers of pluripotency (Oct-4A and Nanog on both mRNA and protein levels that indicate VSEL population. Based on our experience in both murine and human VSEL isolation procedures by fluorescence-activated cell sorting (FACS, we also optimized sorting protocol for separation of CD45−/Lin−/CD106+ rat BM-derived VSELs from wild type and eGFP-expressing rats, which are often used as donor animals for cell transplantations in regenerative studies in vivo. Thus, this is a first study identifying multiantigenic phenotype and providing sorting protocols for isolation VSELs from rat BM tissue for further examining of their functional properties in vitro as well as regenerative capacity in distinct in vivo rat models of tissue injury.

  11. Microfluidic conceived drug loaded Janus particles in side-by-side capillaries device. (United States)

    Khan, Ikram Ullah; Serra, Christophe A; Anton, Nicolas; Li, Xiang; Akasov, Roman; Messaddeq, Nadia; Kraus, Isabelle; Vandamme, Thierry F


    A side-by-side capillaries microfluidic device was developed to fabricate drug loaded poly(acrylamide)/poly(methyl acrylate) Janus particles in the range of 59-240 μm by UV-assisted free radical polymerization. This system was characterized in terms of continuous and dispersed phases flow rates (Qc/Qd), monomer composition of the two compartments, surfactant nature and concentration, outlet tube diameter and UV intensity. These factors were adequately controlled to get different particle shapes ranging from core-shell to bi-compartmental particles. For the latter, a low surfactant concentration (0.75 wt.%) was necessary when the two dispersed phases were pumped at equal flow rate, while at high surfactant concentration, dispersed phases flow rates have to be changed. FTIR analysis suggested complete polymerization of monomers and cytotoxicity test showed these particles were biocompatible having LD 50 of 9 mg/mL. Both ketoprofen and sodium fluorescein were released in sustained release manner at pH 6.8 by following a diffusion type release mechanism. Drug release was faster for bigger particles and found to result from the irregular distribution of the two phases and indentation on bigger particles as revealed by SEM analysis. In comparison, sodium fluorescein release was slower which was attributed to low encapsulation but could be modified by decreasing crosslinker concentration.

  12. Order, Disorder and Stretching of a Smectic Elastomer with ‘side-on’ Mesogenic Side Groups

    Energy Technology Data Exchange (ETDEWEB)

    de Jeu, W.; Komp, A; Obraztsov, E; Ostrovskii, B; Finkelmann, H


    We report an X-ray study of the order in a 'side-on' smectic-A elastomer in which both the polymer backbone and the mesogenic side groups are, on average, parallel to the smectic layer normal. The present system shows in all phases locally correlated structures as evidenced by systematic diffuse scattering at small angles, attributed to the fluorinated end groups of the mesogens. The elastomer shows order of the smectic layers over a limited range in spite of the relatively low crosslink concentration (4%). Upon stretching along the layer normal we find a linear increase of the smectic layer period for small loading (elastic regime). These changes parallel the stress variation for the elastic part of the macroscopic stress-strain curve and saturate at larger strains. The attendant increase in the width of the X-ray peaks indicates a decrease of the average domain dimensions. In the plastic regime no distortion of the smectic monodomain structure or layer rotation is observed. Instead the stress is relieved by 'melting' of the layer structure giving rise to a nematic-like state with short-range layer correlations: at the final stage about four smectic layers.

  13. Study of fluid resonance between two side-by-side floating barges

    Institute of Scientific and Technical Information of China (English)

    李欣; 徐亮瑜; 杨建民


    The hydrodynamic interaction between two vessels in a side-by-side configuration attracted research attentions in recent years. However, because the conventional potential flow theory does not consider the fluid viscosity, in the hydrodynamic results, the wave elevations were overestimated in the narrow gap under resonance conditions. To overcome this limitation and investigate the complex fluid flow around multiple bodies in detail, this study examines the fluid resonance between two identical floating barges using a viscous flow analysis program FLOW-3D. The volume of fluid method is implemented for tracking the free surface, and a porous media model is used near the outflow boundary to enhance the wave absorption. A three-dimensional numerical wave basin is established and validated by comparison with the waves generated using theoretical values. On this basis, a computational fluid dynamics (CFD) simulation of the two barges in a resonance wave period is performed, and the wave elevations, the fluid flow around the barges, and the motions of the barges are discussed. The numerical simulation is verified by comparison with results of corresponding experimental data.


    Institute of Scientific and Technical Information of China (English)

    GUO Xiao-hui; LIN Jian-zhong; TU Cheng-xu; WANG Hao-li


    Measurements were performed using Particle Image Velocimetry (PIV) to analyze the modification of flow by the combined effects of the rotation and the Reynolds number on the flow past two rotating circular cylinders in a side-by-side-arrangement at a range of , (α is the rotational speed) at one gap spacing of (T and d are the distance between the centers of two cylinders and the cylinder diameter, respectively). A new Immersed-Lattice Boltzmann Method (ILBM) scheme was used to study the effect of the gap spacing on the flow. The results show that the vortex shedding is suppressed as rotational speed increases. The flow reaches a steady state when the vortex shedding for both cylinders is completely suppressed at critical rotational speed. As the rotational speed further increases, the separation phenomenon in the boundary layers disappears at the attachment rotational speed. The critical rotational speed and attachment rotational speed become small as Reynolds number increases. The absolute rotational speed of cylinders should be large at same critical rotational speed and attachment rotational speed in the case of large Reynolds number. The gap spacing has an important role in changing the pattern of vortex shedding. It is very different in the mechanism of vortex shedding suppression for the flows around two rotating cylinders and single rotating cylinder.

  15. Modality-specific communication enabling gait synchronization during over-ground side-by-side walking. (United States)

    Zivotofsky, Ari Z; Gruendlinger, Leor; Hausdorff, Jeffrey M


    An attentive observer will notice that unintentional synchronization of gait between two walkers on the street seems to occur frequently. Nonetheless, the rate of occurrence and motor-sensory mechanisms underlying this phase-locking of gait have only recently begun to be investigated. Previous studies have either been qualitative or carried out under non-natural conditions, e.g., treadmill walking. The present study quantitatively examined the potential sensory mechanisms that contribute to the gait synchronization that occurs when two people walk side by side along a straight, over-ground, pathway. Fourteen pairs of subjects walked 70 m under five conditions that manipulated the available sensory feedback. The modalities studied were visual, auditory, and tactile. Movement was quantified using a trunk-mounted tri-axial accelerometer. A gait synchronization index (GSI) was calculated to quantify the phase synchronization of the gait rhythms. Overall, 36% of the walks exhibited synchrony. Tactile and auditory feedback showed the greatest ability to synchronize, while visual feedback was the least effective. The results show that gait synchronization during natural walking is common, quantifiable, and has modality-specific properties.

  16. Numerical Study on Interaction Between Two Bubbles Rising Side by Side in CMC Solution

    Institute of Scientific and Technical Information of China (English)

    FAN Wenyuan; YIN Xiaohong


    A numerical simulation was performed to investigate the interaction of two bubbles rising side by side in shear-thinning fluid using volume of fluid (VOF) method coupled with continuous surface force (CSF) method.By considering rheological characteristics of fluid,this approach was able to accurately capture the deformation of bubble interface,and validated by comparing with the experimental results.The rising of bubble pairs with different configurations,including horizontal alignment and oblique alignment,was simulated by the method.The influences of the bubble initial distance and the bubble alignment were studied by analyzing the bubble deformation,rising paths and flow fields surrounding bubbles.The results indicate that within certain initial bubble spacing of S* =3.3(S* =SI/D,SI initial distance between bubbles,and D bubble diameter),the dynamic interaction between two bubbles aligned horizontally shows repulsive effect that decreases with the increase of initial bubble spacing,but weakens to certain degree by the shear-thinning properties of fluid.However,the interaction between two bubbles aligned obliquely presents a repulsive effect for the small angle involved but an attractive impact for the large one,which is yet strengthened by the rheological characteristics of fluid.

  17. Propulsive performance of unsteady tandem hydrofoils in a side-by-side configuration (United States)

    Dewey, Peter A.; Quinn, Daniel B.; Boschitsch, Birgitt M.; Smits, Alexander J.


    Experimental and analytical results are presented on two identical bio-inspired hydrofoils oscillating in a side-by-side configuration. The time-averaged thrust production and power input to the fluid are found to depend on both the oscillation phase differential and the transverse spacing between the foils. For in-phase oscillations, the foils exhibit an enhanced propulsive efficiency at the cost of a reduction in thrust. For out-of-phase oscillations, the foils exhibit enhanced thrust with no observable change in the propulsive efficiency. For oscillations at intermediate phase differentials, one of the foils experiences a thrust and efficiency enhancement while the other experiences a reduction in thrust and efficiency. Flow visualizations reveal how the wake interactions lead to the variations in propulsive performance. Vortices shed into the wake from the tandem foils form vortex pairs rather than vortex streets. For in-phase oscillation, the vortex pairs induce a momentum jet that angles towards the centerplane between the foils, while out-of-phase oscillations produce vortex pairs that angle away from the centerplane between the foils.

  18. Interface Oscillation in the Side-by-Side (SBS) Tape Casting of Functionally Graded Ceramics (FGCs) (United States)

    Jabbari, Masoud; Bulatova, Regina; Hattel, Jesper; Bahl, Christian


    Room temperature magnetic refrigeration is a new highly efficient and environmentally protective technology. Although it has not been maturely developed, it shows great applicable prosperity and seems to be a potential substitute for the traditional vapor compression technology. Tape Casting is a common process in producing multilayer ceramics, which now is used for producing side-by-side (SBS) functionally graded ceramics (FGCs). These FGCs are mostly used in the magnetic refrigeration sectors due to the varying composition of the magnetocaloric materials so that the magnetic transition temperature of the magnetic regenerator varies along the paths. The main goal of this research is to study the multiple material flow in SBS tape casting and analyze its influence on the interface between the stripes. The materials used for the experimental part are La0 . 85 Sr0 . 15 MnO3 and Ce0 . 9 Gd0 . 1O2 ceramic slurries. The rheological behavior of the slurries are extracted from experiments and used in the ANSYS FLUENT commercial code to develop a fluid flow model for the non-Newtonian ceramic slurries and evaluate the interface oscillation between the stripes in SBS tape casting. The Numerical results show reasonable agreement with corresponding experimental results.

  19. Side-by-side ANFIS as a useful tool for estimating correlated thermophysical properties (United States)

    Grieu, Stéphane; Faugeroux, Olivier; Traoré, Adama; Claudet, Bernard; Bodnar, Jean-Luc


    In the present paper, an artificial intelligence-based approach dealing with the estimation of correlated thermophysical properties is designed and evaluated. This new and "intelligent" approach makes use of photothermal responses obtained when homogeneous materials are subjected to a light flux. Commonly, gradient-based algorithms are used as parameter estimation techniques. Unfortunately, such algorithms show instabilities leading to non-convergence in case of correlated properties to be estimated from a rebuilt impulse response. So, the main objective of the present work was to simultaneously estimate both the thermal diffusivity and conductivity of homogeneous materials, from front-face or rear-face photothermal responses to pseudo random binary signals. To this end, we used side-by-side neuro-fuzzy systems (adaptive network-based fuzzy inference systems) trained with a hybrid algorithm. We focused on the impact on generalization of both the examples used during training and the fuzzification process. In addition, computation time was a key point to consider. That is why the developed algorithm is computationally tractable and allows both the thermal diffusivity and conductivity of homogeneous materials to be simultaneously estimated with very good accuracy (the generalization error ranges between 4.6% and 6.2%).

  20. SLAR = USGS Side Looking Airborne Radar Mosaics: 1981 - 1990 (United States)

    U.S. Geological Survey, Department of the Interior — The Side-Looking Airborne Radar (SLAR) is an image-producing system that derives its name from the fact that the radar beam is transmitted from the side of the...

  1. Role of bicarbonate at the acceptor side of photosystem II

    NARCIS (Netherlands)

    Rensen, van J.J.S.


    Besides being the substrate for the carboxylation reaction of photosynthesis, CO2 (bicarbonate) is required for the activity of Photosystem II (water plastoquinone oxido-reductase). It plays a role on the electron donor side as well as the electron acceptor side. In this contribution, attention will

  2. Side Effects of Chemotherapy and Radiation (For Parents) (United States)

    ... 1- to 2-Year-Old Side Effects of Chemotherapy and Radiation KidsHealth > For Parents > Side Effects of Chemotherapy and Radiation Print A A A What's in ... and can no longer do their jobs efficiently. Chemotherapy (or "chemo") and radiation , the two most common ...

  3. The relationship between rational drug design and drug side effects. (United States)

    Wang, Juan; Li, Zhi-xin; Qiu, Cheng-xiang; Wang, Dong; Cui, Qing-hua


    Previous analysis of systems pharmacology has revealed a tendency of rational drug design in the pharmaceutical industry. The targets of new drugs tend to be close with the corresponding disease genes in the biological networks. However, it remains unclear whether the rational drug design introduces disadvantages, i.e. side effects. Therefore, it is important to dissect the relationship between rational drug design and drug side effects. Based on a recently released drug side effect database, SIDER, here we analyzed the relationship between drug side effects and the rational drug design. We revealed that the incidence drug side effect is significantly associated with the network distance of drug targets and diseases genes. Drugs with the distances of three or four have the smallest incidence of side effects, whereas drugs with the distances of more than four or smaller than three show significantly greater incidence of side effects. Furthermore, protein drugs and small molecule drugs show significant differences. Drugs hitting membrane targets and drugs hitting cytoplasm targets also show differences. Failure drugs because of severe side effects show smaller network distances than approved drugs. These results suggest that researchers should be prudent on rationalizing the drug design. Too small distances between drug targets and diseases genes may not always be advantageous for rational design for drug discovery.

  4. Organizational mediators siding with or against the powerful party

    NARCIS (Netherlands)

    Laskewitz, P; Van de Vliert, E; De Dreu, C K W


    Instead of being impartial, a mediator may side with one party as a function of the disputants' power differences, the mediator's legitimacy judgments, or the disputants' capacity to sanction the mediator. According to the power balancing theory, a mediator sides with the party that has a power disa

  5. Rare combination of dextrocardia with right-sided Poland syndrome. (United States)

    Lee, Seung Hyun; Kim, Jae Bum; Park, Nam Hee; Keum, Dong Yoon; Kim, Yeo Hyang


    The combination of right-sided Poland syndrome and dextrocardia is rare. To our knowledge, reports regarding this subject are lacking in the published literature to date. Previous reports suggested that dextrocardia may be part of the left sided Poland syndrome. We report and discuss this rare combination.

  6. Weakening of a Polyethylene Chain by Methyl Side Groups

    NARCIS (Netherlands)

    Hageman, J.C.L.; Wijs, G.A. de; Groot, R.A. de; Meier, Robert J.


    The effect of methyl side groups on the strength of a single polyethylene chain is calculated with Density Functional Theory. Using transition state theory, the scission rate is calculated as function of stress for bonds next to a methyl side group. The increase in the scission rate due to the prese

  7. Effects and Side Effects of Flemish School Inspection (United States)

    Penninckx, Maarten; Vanhoof, Jan; De Maeyer, Sven; Van Petegem, Peter


    Despite the increased importance of school inspection in recent years, the current knowledge base does not provide a clear view on the effects and side effects of being inspected. More evidence is needed in more diverse educational contexts. This article responds to this need with a quantitative study on the effects and side effects of school…

  8. Side effects of azathioprine in patients with Crohn's disease.

    NARCIS (Netherlands)

    Jong, Dirk de; Goullet, M.; Naber, A.H.J.


    OBJECTIVE: In clinical trials 0-15% of patients discontinued azathioprine due to side effects. The aim of this study was to assess the rate of side effects leading to discontinuation of azathioprine and to determine predictive factors for discontinuation. DESIGN: A retrospective cohort analysis of c

  9. The incidence of side effects after laser hair removal (United States)

    Lanigan, Sean W.


    Despite the widespread use of lasers for hair removal there is little data published on the incidence of side effects from this treatment. We aimed to generate data on a large number of patients receiving laser hair removal to obtain an accurate assessment of the incidence and type of side effects resulting from treatment. A multicentre prospective study of patients attending for laser hair removal was conducted to determine incidence of side effects in relation to skin type and laser(s) used. Laser hair removal is associated with a low incidence of side effects which are self-limiting in the majority of cases. Highest incidence of side effects was seen in darker skinned patients treated with the long pulsed ruby laser. Laser hair removal is inherently safe. For darker Fitzpatrick skin types the long pulsed Nd:YAG laser is preferred to the ruby laser.

  10. Status and Results from DarkSide-50

    CERN Document Server

    Fan, Alden


    DarkSide-50 is the first physics detector of the DarkSide dark matter search program. The detector features a dual-phase underground-argon Time Projection Chamber (TPC) of 50 kg active mass surrounded by an organic liquid-scintillator neutron veto (30 tons) and a water-Cherenkov muon detector (1000 tons). The TPC is currently fully shielded and operating underground at Gran Sasso National Laboratory. A first run of 1422 kg-day exposure with atmospheric argon represents the most sensitive dark matter search using a liquid argon target. The TPC is now filled with underground argon, greatly reduced in 39Ar, and DarkSide-50 is in its final configuration for an extended dark matter search. Overviews of the design, performance, and results obtained so far with DarkSide-50 will be presented, along with future prospects for the DarkSide program.

  11. Ecological engineering of bioaugmentation from side-stream nitrification. (United States)

    Smith, R C; Saikaly, P E; Zhang, K; Thomatos, S; Oerther, D B


    Wastewater treatment relies on careful integration of environmental engineering with microbial ecology. This would seem to be particularly the case when attempting to enhance survivability of organisms introduced from outside the main-stream reactor, i.e. bioaugmentation. Molecular biology tools were utilised in this study to assist in understanding the mechanisms of successful bioaugmentation. Molecular fingerprinting showed that side-stream reactor configuration strongly influenced ammonia-oxidising bacteria (AOB) community structure. In both lab-scale and full-scale systems, AOB communities in the side-stream and main-stream were very similar. The experimental systems revealed that a PFR side-stream produced greater diversity of AOB than a CSTR side-stream in a PFR main-stream system, whereas the full-scale side-stream resulted in essentially an AOB monoculture. Phylogenetic analysis revealed less diversity than molecular fingerprinting perhaps due to biases in the cloning/transformation procedure.

  12. Collusion in Markets with Imperfect Price Information on Both Sides

    DEFF Research Database (Denmark)

    Schultz, Christian

    The paper considers tacit collusion in markets which are not fully transparent on both sides. Consumers only detect prices with some probability before deciding which firm to purchase from, and each firm only detects the other firm's price with some probability. Increasing transparency on the pro......The paper considers tacit collusion in markets which are not fully transparent on both sides. Consumers only detect prices with some probability before deciding which firm to purchase from, and each firm only detects the other firm's price with some probability. Increasing transparency...... on the producer side facilitates collusion, while increasing transparency on the consumer side makes collusion more difficult. Conditions are given under which increases in a common factor, affecting transparency positively on both sides, are pro-competitive. With two standard information technologies, this is so...

  13. A side effect resource to capture phenotypic effects of drugs

    DEFF Research Database (Denmark)

    Kuhn, Michael; Campillos, Monica; Letunic, Ivica


    The molecular understanding of phenotypes caused by drugs in humans is essential for elucidating mechanisms of action and for developing personalized medicines. Side effects of drugs (also known as adverse drug reactions) are an important source of human phenotypic information, but so far research...... on this topic has been hampered by insufficient accessibility of data. Consequently, we have developed a public, computer-readable side effect resource (SIDER) that connects 888 drugs to 1450 side effect terms. It contains information on frequency in patients for one-third of the drug-side effect pairs. For 199...... drugs, the side effect frequency of placebo administration could also be extracted. We illustrate the potential of SIDER with a number of analyses. The resource is freely available for academic research at

  14. The nocebo effect: patient expectations and medication side effects. (United States)

    Faasse, Kate; Petrie, Keith J


    Expectation of treatment side effects is consistently linked with those symptoms being realised. Patient expectations, including those generated by the informed consent process, can have a large influence on the side effects that patients feel after starting a new medical treatment. Such symptoms may be the result of the nocebo effect, whereby the expectation of side effects leads to them being experienced. Side effects may also be due to the misattribution of pre-existing or unrelated symptoms to the new medication. Medical professionals' own negative beliefs about a treatment, especially generic drugs, may further enhance patients' expectations of adverse effects. The news media may also influence expectations, particularly when media attention is directed towards a health or medication scare. This field of research has ethical and clinical implications for both medical professionals and the news media with respect to the level and type of information about treatment side effects that is provided to patients or members of the public.

  15. Research Needs: Glass Solar Reflectance and Vinyl Siding

    Energy Technology Data Exchange (ETDEWEB)

    Hart, Robert; Curcija, Charlie; Arasteh, Dariush; Goudey, Howdy; Kohler, Christian; Selkowitz, Stephen


    The subject of glass solar reflectance and its contribution to permanent vinyl siding distortion has not been extensively studied, and some phenomena are not yet well understood. This white paper presents what is known regarding the issue and identifies where more research is needed. Three primary topics are discussed: environmental factors that control the transfer of heat to and from the siding surface; vinyl siding properties that may affect heat build-up and permanent distortion; and factors that determine the properties of reflected solar radiation from glass surfaces, including insulating window glass. Further research is needed to fully characterize the conditions associated with siding distortion, the scope of the problem, physical properties of vinyl siding, insulating window glass reflection characteristics, and possible mitigation or prevention strategies.

  16. Are peripheral opioid antagonists the solution to opioid side effects?

    LENUS (Irish Health Repository)

    Bates, John J


    Opioid medication is the mainstay of therapy for severe acute and chronic pain. Unfortunately, the side effects of these medications can affect patient comfort and safety, thus limiting their proven therapeutic potential. Whereas the main analgesic effects of opioids are centrally mediated, many of the common side effects are mediated via peripheral receptors. Novel peripheral opioid antagonists have been recently introduced that can block the peripheral actions of opioids without affecting centrally mediated analgesia. We review the clinical and experimental evidence of their efficacy in ameliorating opioid side effects and consider what further information might be useful in defining their role. IMPLICATIONS: The major analgesic effects of opioid medication are mediated within the brain and spinal cord. Many of the side effects of opioids are caused by activation of receptors outside these areas. Recently developed peripherally restricted opioid antagonists have the ability to block many opioid side effects without affecting analgesia.

  17. Analysis of Kirk effect of an innovated high side Side-Isolated N-LDMOS device

    Directory of Open Access Journals (Sweden)

    Lai Ciou Jhong


    Full Text Available An ESOA of LDMOS device is very critical for power device performance. Kirk effect is the one of the major problem which leads to poor ESOA performance. The cause of the problem mainly due to the high beta value of parasitic NPN transistor in the p-body. In this study, we proposed a new 3D high side Side–Isolated N-Channel LDMOS which we have obtained not only benchmark Ron and breakdown performance, but also better ESOA without Kirk effect. We have compared the analysis of Kirk effect between the new device and the conventional N–LDMOS structure with LATID technique for the formation of the p–body of both device structures.


    Directory of Open Access Journals (Sweden)



    Full Text Available The first important economic recession in this century started in USA with the burst of real estate bubble followed by the bankruptcy of some investment and commercial banks and the collapse of capital market. The financial-banking crisis spilt over the world economy and caused the second deepest economic recession in the last 80 years. The financial crisis has badly affected almost all market economies and was the result of a combination between market failures and mistakes made in macroeconomic policies. In the financial sector there was not enough regulation and supervision of corporate governance while in goods industry the pressure of over-regulation led to higher factor costs and supply contraction. The direct result of supply side policies and particularly of monetarist instruments is seen now clearly in the USA: large deficits, huge debts, reduced savings, heavy dependence on foreign money (capital and resources, relatively low domestic output and supply.

  19. Immediate Small Side Branch Occlusion after Percutaneous Coronary Intervention

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Ostovan


    Full Text Available Background: Small side branches, albeit less important than their larger counterparts, have not yet received due attention in the literature. Nor has there ever been a comparison between drug-eluting stents and bare metal stents apropos side branch occlusion. The aim of this study was to compare the patency of small (≥0.5 and ≤1.5 mm in diameter side branches with respect to bare metal vs. drug-eluting stents immediately after their deployment.Methods: This prospective bi-center study, conducted between June 2005 and January 2007, enrolled 82 patients treated with ≥1 of two stents (TAXUSTM LiberteTM or LiberteTM. Side branches ≥0.5 and <1.5 mm in diameter arising from the main vessel at the lesion site were evaluated. Results: Thirty-eight patients were treated with 42 LiberteTM stents (58 side branches and forty-four patients with 50 TAXUSTM LiberteTM (102 side branches. The rate of small side branch occlusion was 35.3% (36 in the TAXUSTM LiberteTM group compared to 29.31% (15 in the LiberteTM group (P-value= 0.7. The presence of type 1 side branch morphology (Lefevre classification was the most powerful predictor of small side branch occlusion (P-value=0.03. Conclusion: This study shows that drug-eluting stents are not inferior to bare metal stents as regards small side branch occlusion during coronary stenting

  20. Criticality of flow transition behind two side-by-side elliptic cylinders (United States)

    Peng, Y. F.; Sau, Amalendu; Hwang, Robert R.; Yang, W. C.; Hsieh, Chih-Min


    In this study, near-critical bifurcations of low Reynolds number (Re) flows past a pair of elliptic cylinders in the side-by-side arrangement are numerically investigated, and onsets of several distinct transition scenarios are addressed. A nested Cartesian-grid formulation, in combination with an effective immersed boundary method and a two-step fractional-step procedure, has been adopted to simulate the flows. The transition scenarios associated with various periodic, quasi-periodic, and biased flows, their bifurcation characteristics, corresponding critical Reynolds numbers, and phase-portraits are exploited to better understand the governing physics. From the global point of view, there appear variety of flow patterns within the investigated parameter space, 40 ⩽ Re ⩽ 300, 0.2 ⩽ G ⩽ 3.0 (G being the gap-ratio of the cylinders), and 1.5 ⩽ A ⩽ 3 (A is the cylinder aspect-ratio), which include, symmetric vortex shedding mode, semi-single/twin vortex street formations, asymmetric/deflected flows, stationary/biased flip-flopped-type vortex shedding, weakly-chaotic flows, and in-phase/anti-phase vortex synchronizations. We numerically present these flows by tuning Re quasi-stationary, and provide a broader understanding of the entire transition process. A comprehensive analysis of effects of Reynolds number, the gap-ratio, and the angle of incidence on different flow-induced forces on the cylinders is included in this regard. On the other hand, our simulated wakes with various non-zero incidence-angles are found to reveal a rich variety of instability induced weakly synchronized physical evolution characteristics, which remained virtually unexplored.

  1. Total colectomy in older patients with acute malignant obstruction of the left-sided colons

    Institute of Scientific and Technical Information of China (English)

    Milivoje Vukovi; Neboja Moljevi; Sinia Crnogorac


    Objective: The older population is one of the fastest growing segments of Serbian society. The aging population is also present in developed countries. Demographics the oldest region in the world is Europe. Serbia by the number colorectal cancer suffering among the countries with high risk of disease. In 2006. the number of new cases was around 4 000. Methods: In study retrospective review of 81 patients with malignant obstruction of the left-sided colon, where it underwent a total colectomy. Symptoms and signs of acute obstruction of the left-sided colon are complemented with radiological examination in all patients. The compulsory part of the preoperative examination digitorectal exam how to assess the function of the sphincter apparatus in terms of continence, and to view the rectum and the exclusion of the tumor. In poorly functioning sphincter apparatus was performed Hartmann's procedure, in order to avoid postoperative incontinence. Results: The primary anastomosis rate of 81% in the elderly and 83% of younger patients. In younger group 31 patients underwent a total colectomy with anastomosis and 6 total colectomy with end ileostomy. In older group there were 36 total colectomy with anastomosis and 8 with total colectomy with end ileostomy. Anastomotic leak occurred in 4 patients of elderly group and 2 patients in the younger group. Mortality (30 d) in the older group was 3 patients who had ASA IV, and younger group 2 patients (1 patient ASA III, 1 patients ASA IV). Of the 3 patients died from the older group, 2 patients were end ileostomy.Conclusions:Emergency resection and primary anastomosis for left-sided colon carcinoma can be performed with favorable outcome in the elderly. Years of age are not a decisive prognostic factor in colorectal surgery. The surgeon has a duty of careful selection of patients for resection with anastomosis for malignant obstruction of the left-sided colon, with adequate preoperative preparation and postoperative monitoring.

  2. A nationwide Danish cohort study challenging the categorisation into right-sided and left-sided colon cancer

    DEFF Research Database (Denmark)

    Jess, Per; Hansen, Iben Onsberg; Gamborg, Michael;


    The categorisation of colon cancer (CC) into right-sided (RCC) and left-sided (LCC) disease may not capture more subtle variances in aetiology and prognosis. In a nationwide study, we investigated differences in clinical characteristics and survival of RCC versus LCC and of the complete range of CC...

  3. Supply-side and demand-side cost sharing in deregulated social health insurance: which is more effective? (United States)

    Trottmann, Maria; Zweifel, Peter; Beck, Konstantin


    Microeconomic theory predicts that if patients are fully insured and providers are paid fee-for-service, utilization of medical services exceeds the efficient level ('moral hazard effect'). In Switzerland, both demand-side and supply-side cost sharing have been introduced to mitigate this problem. Analyzing a panel dataset of about 160,000 adults, we find both types of cost sharing to be effective in curtailing the use of medical services. However, when moral hazard mitigation is traded off against risk selection, the minimum-deductible, supply-side cost sharing option ranks first, followed by the medium-deductible demand-side alternative, making the supply-side option somewhat more effective.

  4. Population Based Assessment of MHC Class I Antigens Down Regulation as Markers of Increased Risk for Development and Progression of Breast Cancer from Benign Breast Lesions (United States)


    retrieved by incubating tissue sections in antigen retrieval solution in the microwave . Lastly, tissue sections were stained with anti-CD45 mAb to...The quality of the staining and the overall results were similar despite variations to the protocol. Microwave and citrate buffer antigen-retrieval...for noting any non-specific reactivity. CD45 staining as employed in Lab 1 may be helpful in identifying the infiltrating lymphocytes in germinal

  5. Systematic analysis of reportedly distinct populations of multipotent bone marrow-derived stem cells reveals a lack of distinction. (United States)

    Lodie, Tracey A; Blickarz, Courtney E; Devarakonda, Tara J; He, Chufa; Dash, Ajeeta B; Clarke, Jennifer; Gleneck, Kristen; Shihabuddin, Lamya; Tubo, Ross


    Adult human bone marrow-derived stem cells, having the ability to differentiate into cells of multiple lineages, have been isolated and propagated by varied protocols, including positive (CD105(+))/negative (CD45(-)GlyA(-)) selection with immunomagnetic beads, or direct plating into selective culture media. Each substratum-adherent cell population was subjected to a systematic analysis of their cell surface markers and differentiation potential. In the initial stages of culture, each cell population proliferated slowly, reaching confluence in 10-14 days. Adherent cells proliferated at similar rates whether cultured in serum-free medium supplemented with basic fibroblast growth factor, medium containing 2% fetal bovine serum (FBS) supplemented with epidermal growth factor and platelet-derived growth factor, or medium containing 10% FBS alone. Cell surface marker analysis revealed that more than 95% of the cells were positive for CD105/endoglin, a putative mesenchymal stem cell marker, and negative for CD34, CD31, and CD133, markers of hematopoietic, endothelial, and neural stem cells, respectively, regardless of cell isolation and propagation method. CD44 expression was variable, apparently dependent on serum concentration. Functional similarity of the stem cell populations was also observed, with each different cell population expressing the cell type-specific markers beta-tubulin, type II collagen, and desmin, and demonstrating endothelial tube formation when cultured under conditions favoring neural, cartilage, muscle, and endothelial cell differentiation, respectively. On the basis of these data, adult human bone marrow-derived stem cells cultured in adherent monolayer are virtually indistinguishable, both physically and functionally, regardless of the method of isolation or proliferative expansion.

  6. Rational Design of Coordination Polymers with Flexible Oxyethylene Side Chains

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Eun Young; Gao, Chunji; Lee, Suck Hyun; Kwon, O Pil [Ajou University, Suwon (Korea, Republic of)


    We rationally designed and synthesized metallopolymers with organic 1,4-benzenedicarboxylic acid (BDC) linkers with different lengths of oxyethylene side chains in order to examine the influence of side chains on the coordination characteristics. While in a previous report the BDC linkers with alkyl side chains were found to form three-dimensional (3D) isoreticular metal-organic framework (IRMOF) structures or one-dimensional (1D) coordination polymeric structures with short -O(CH{sub 2}){sub 6}CH{sub 3} or long -O(CH{sub 2}){sub 9}CH{sub 3} side chains, respectively, new BDC linkers with oxyethylene side chains of the same lengths, -(OCH{sub 2}CH{sub 2}){sub 2}CH{sub 3} and -(OCH{sub 2}CH{sub 2}){sub 3}CH{sub 3}, form only 3D IRMOF structures. This result is attributed to the higher flexibility and smaller volume of oxyethylene side chains compared to alkyl side chains

  7. A gecko-inspired double-sided adhesive. (United States)

    Wang, Zhengzhi; Gu, Ping; Wu, Xiaoping


    Geckos' outstanding abilities to adhere to various surfaces are widely credited to the large actual contact areas of the fibrillar and hierarchical structures on their feet. These special features regulate the essential structural compliance for every attachment and thus provide robust yet reversible adhesions. Inspired by gecko's feet and our commonly used double-faced tape, we have successfully fabricated a gecko-inspired double-sided dry adhesive by using porous anodic alumina template assisted nano-wetting on a stiff polymer. It was determined that the obtained 2-sided structure showed largely decreased effective stiffness compared with its 1-sided counterpart, which favored better compliance and interfacial integrity. We also demonstrated that the repeatable double-sided adhesive improved the macroscopic normal and shear adhesion capacities over the widely-studied 1-side structure by ~50% and ~85%, respectively. By using the synthetic double-sided adhesive, the usage of traditional pressure-sensitive/chemical adhesives could be well avoided. Besides, the double-sided nanostructures showed great potential in finding new interesting properties and practical applications for the synthetic dry adhesives.

  8. Effective population size of korean populations. (United States)

    Park, Leeyoung


    Recently, new methods have been developed for estimating the current and recent changes in effective population sizes. Based on the methods, the effective population sizes of Korean populations were estimated using data from the Korean Association Resource (KARE) project. The overall changes in the population sizes of the total populations were similar to CHB (Han Chinese in Beijing, China) and JPT (Japanese in Tokyo, Japan) of the HapMap project. There were no differences in past changes in population sizes with a comparison between an urban area and a rural area. Age-dependent current and recent effective population sizes represent the modern history of Korean populations, including the effects of World War II, the Korean War, and urbanization. The oldest age group showed that the population growth of Koreans had already been substantial at least since the end of the 19th century.

  9. Coding with Side Information for Radiation-Tolerant Memory Devices (United States)

    Hwang, E.; Jeon, S.; Negi, R.; Vijaya Kumar, B. V. K.; Cheng, M. K.


    Memory devices aboard spacecraft experience radiation-induced errors either in the form of temporary upsets (soft errors) or permanent defects (hard or stuck-at errors). Error-correcting codes (ECCs) are used to recover memory content from errors where defective cells are either regarded as erasures by the decoder or entire blocks containing defective cells are marked as unusable. In this article, alternative coding schemes are investigated for memory devices in space, where the encoder is provided with the locations of the defective cells, denoted by side information. This coding approach has the potential to improve the overall storage capacity of memory devices, since the information theoretic capacity of a channel where side information is only available at the encoder is the same as the capacity where side information is available at both the encoder and decoder. Spacecraft memory controllers typically scrub memory devices periodically for errors. Partial side information can be obtained during this scrubbing process by comparing the ECC decoder output with its input and thereby avoid the need for additional cell tests or storage overhead. In between scrubbings, the encoder can use this partial side information to account for permanent defects to improve reliability or to increase the storage capacity of onboard memory devices. In order to achieve performance gains for practical memory systems, several coding schemes that adaptively incorporate the codeword with the known side information are proposed in this article. The proposed coding schemes are evaluated by numerical simulations on a memory channel model characterized by soft and hard errors. Simulation results show that while coding with complete side information at the encoder offers the most performance gain compared to when coding without side information is used, coding with partial side information can close the gap between the optimal and current approach without incurring much additional overhead

  10. Left-sided gall bladder: Report of two cases

    Directory of Open Access Journals (Sweden)

    Chrungoo R


    Full Text Available Left-sided gall bladder without situs inversus viscerum is a rare albeit recognized clinical entity. We report our experience of two cases of left-sided gall bladder in two women aged 36 and 48 who underwent laparoscopic cholecystectomy for chronic calculous cholecystitis. Left-sided gall bladder may provide an unusual surprise to the surgeons during laparoscopy as routine pre-operative studies may not always detect the anomaly. Awareness of the unpredictable confluence of the cystic duct into the common bile duct (CBD and selective use of intraoperative cholangiography aid in the safe laparoscopic management of this unusual entity.

  11. In vivo assessment of antiretroviral therapy-associated side effects

    Directory of Open Access Journals (Sweden)

    Eduardo Milton Ramos-Sanchez


    Full Text Available Antiretroviral therapy has been associated with side effects, either from the drug itself or in conjunction with the effects of human immunodeficiency virus infection. Here, we evaluated the side effects of the protease inhibitor (PI indinavir in hamsters consuming a normal or high-fat diet. Indinavir treatment increased the hamster death rate and resulted in an increase in triglyceride, cholesterol and glucose serum levels and a reduction in anti-oxLDL auto-antibodies. The treatment led to histopathological alterations of the kidney and the heart. These results suggest that hamsters are an interesting model for the study of the side effects of antiretroviral drugs, such as PIs.

  12. Side Effects and Complications of Dental Materials on Oral Cavity

    Directory of Open Access Journals (Sweden)

    Z. Atai


    Full Text Available Development of dental materials has had a great impact on the modern dentistry. The materials ranging from polymers to metals have different applications in dentistry. Besides their important role in healing or improving the function of oral tissues, the materials may show side effects which may, in some cases, lead to severe lesions. In this review the side effects have been summarized considering a new classification for dental materials according to the duration of their applications as temporary or permanent materials. The side effects of the materials are then discussed based on clinical and cellular views.

  13. Double Sided Watermark Embedding and Detection with Perceptual Analysis

    CERN Document Server

    Zhong, Jidong


    In our previous work, we introduced a double-sided technique that utilizes but not reject the host interference. Due to its nice property of utilizing but not rejecting the host interference, it has a big advantage over the host interference schemes in that the perceptual analysis can be easily implemented for our scheme to achieve the locally bounded maximum embedding strength. Thus, in this work, we detail how to implement the perceptual analysis in our double-sided schemes since the perceptual analysis is very important for improving the fidelity of watermarked contents. Through the extensive performance comparisons, we can further validate the performance advantage of our double-sided schemes.

  14. Pinning Synchronization of One-Sided Lipschitz Complex Networks

    Directory of Open Access Journals (Sweden)

    Fang Liu


    Full Text Available This paper studies the pinning synchronization in complex networks with node dynamics satisfying the one-sided Lipschitz condition which is less conservative than the well-known Lipschitz condition. Based on M-matrix theory and Lyapunov functional method, some simple pinning conditions are derived for one-sided Lipschitz complex networks with full-state and partial-state coupling, respectively. A selective pinning scheme is further provided to address the selection of pinned nodes and the design of pinning feedback gains for one-sided Lipschitz complex networks with general topologies. Numerical results are given to illustrate the effectiveness of the theoretical analysis.

  15. Elementary affine {\\lambda}-calculus with multithreading and side effects

    CERN Document Server

    Madet, Antoine


    Linear logic provides a framework to control the complexity of higher-order functional programs. We present an extension of this framework to programs with multithreading and side effects focusing on the case of elementary time. Our main contributions are as follows. First, we provide a new combinatorial proof of termination in elementary time for the functional case. Second, we develop an extension of the approach to a call-by-value \\lambda-calculus with multithreading and side effects. Third, we introduce an elementary affine type system that guarantees the standard subject reduction and progress properties. Finally, we illustrate the programming of iterative functions with side effects in the presented formalism.

  16. [Cardiovascular side effects of non-steroidal anti-inflammatory drugs in the light of recent recommendations. Diclofenac is not more dangerous]. (United States)

    Horváth, Viktor József; Tabák, Gy Ádám; Szabó, Gergely; Putz, Zsuzsanna; Koós, Csaba Géza; Lakatos, Péter


    Among their beneficial effects, non-steroidal anti-inflammatory drugs may also exert several side effects which depend on the dosage and the type of these medications. The most frequent gastrointestinal side effects usually develop shortly after the beginning of their administration, but others such as cardiovascular interactions (which are present much less frequently than gastrointestinal side effects) can also occur after the beginning of drug administration without a latency period. For a long-term treatment, non-steroidal anti-inflammatory drugs are most frequently used in the elderly population where patients typically have high cardiovascular risk and take other medicines, e.g. low dose acetylsalicylic acid that can interact with non-steroidal anti-inflammatory drugs; in this aspect diclofenac may cause less side effects. In this review, the authors briefly review cardiovascular side effects of non-steroidal anti-inflammatory drugs, the processes which potentially influence them, therapeutic consequences and their interaction with acetylsalicylic acid.

  17. FLARE: The Far Side Lunar Research Expedition. A design of a far side lunar observatory (United States)

    Bishop, David W.; Chakrabarty, Rudhmala P.; Hannula, Dawn M.; Hargus, William A., Jr.; Melendrez, A. Dean; Niemann, Christopher J.; Neuenschwander, Amy L.; Padgett, Brett D.; Patel, Sanjiv R.; Wiesehuegel, Leland J.


    This document outlines the design completed by members of Lone Star Aerospace, Inc. (L.S.A.) of a lunar observatory on the far side of the Moon. Such a base would not only establish a long term human presence on the Moon, but would also allow more accurate astronomical data to be obtained. A lunar observatory is more desirable than an Earth based observatory for the following reasons: instrument weight is reduced due to the Moon's weaker gravity; near vacuum conditions exist on the Moon; the Moon has slow rotation to reveal the entire sky; and the lunar surface is stable for long baseline instruments. All the conditions listed above are favorable for astronomical data recording. The technical aspects investigated in the completion of this project included site selection, mission scenario, scientific instruments, communication and power systems, habitation and transportation, cargo spacecraft design, thermal systems, robotic systems, and trajectory analysis. The site selection group focused its efforts on finding a suitable location for the observatory. Hertzsprung, a large equatorial crater on the eastern limb, was chosen as the base site.

  18. Total Limb Rotation after Unilateral Total Knee Arthroplasty: Side-to-Side Discrepancy. (United States)

    Oh, Kwang-Jun; Yoon, Seok-Tae; Ko, Young-Bong


    Total limb rotation, an important anatomical feature of the lower limb, is defined as any rotation of the lower limb on its longitudinal axis. The aim of the present study was to evaluate the discrepancies of rotational profiles of total limb between nonoperated and operated limb following unilateral total knee arthroplasty. We conducted an analysis of the computed tomography (CT) data from 32 patients undergoing primary unilateral total knee arthroplasty. Using these CT scan, rotational profiles of total limb, such as femoral neck anteversion angle expressed as femoral torsion angle (FTA), tibial torsion angle (TTA), knee joint rotation angle (KJRA), and total limb rotation (TLR) were measured. There were significant discrepancies of FTA and KJRA between operated and nonoperated limb following unilateral total knee arthroplasty. The mean difference of operated and nonoperated side for FTA and KJRA were -6.51 ± 11.88 degrees (p = 0.0041) and -6.83 ± 5.04 degrees (p knee joint can lead to a total limb rotational discrepancy in patient undergoing unilateral total knee arthroplasty.

  19. Side-Scan-Sonar Lines for Hudson River, NY (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Side Scan Sonar and Subbottom Profiler Tracklines. Data was collected November 5 to December 15, 2009, in the estuary north from Saugerties to Troy. Fugro utilized...

  20. Managing Chemotherapy Side Effects: Sexual and Fertility Changes in Women (United States)

    N ational C ancer I nstitute Managing Chemotherapy Side Effects Sexual and Fertility Changes in Women “Talk with your doctor before you start treatment. Ask how chemotherapy could affect your ability ...

  1. Flow characteristics at trapezoidal broad-crested side weir

    Directory of Open Access Journals (Sweden)

    Říha Jaromír


    Full Text Available Broad-crested side weirs have been the subject of numerous hydraulic studies; however, the flow field at the weir crest and in front of the weir in the approach channel still has not been fully described. Also, the discharge coefficient of broad-crested side weirs, whether slightly inclined towards the stream or lateral, still has yet to be clearly determined. Experimental research was carried out to describe the flow characteristics at low Froude numbers in the approach flow channel for various combinations of in- and overflow discharges. Three side weir types with different oblique angles were studied. Their flow characteristics and discharge coefficients were analyzed and assessed based on the results obtained from extensive measurements performed on a hydraulic model. The empirical relation between the angle of side weir obliqueness, Froude numbers in the up- and downstream channels, and the coefficient of obliqueness was derived.

  2. Graphene-based side-polished optical fiber amplifier. (United States)

    Karimi, Mohammad; Ahmadi, Vahid; Ghezelsefloo, Masoud


    We demonstrate a novel design for optical fiber amplifiers, utilizing side-polished fibers with a single-layer graphene overlay as the active medium and carrier injection in the graphene layer to provide the required inversion. We study the effects of an electrically induced graphene p-i-n heterojunction in the forward bias regime on optical modes of side-polished fibers and show that gain values of 0.51, 1.81, and 1.79 dB/cm for wavelengths 1064, 1330, and 1550 nm can be obtained for single-mode side-polished fibers. Our results show that in multi-mode side-polished fibers, higher order modes experience higher values of gain, and gain can be increased by increasing polished depth. The proposed system is a tunable wideband optical amplifier that can operate for wavelengths larger than 1000 nm.

  3. Incorporating Side Information in Probabilistic Matrix Factorization with Gaussian Processes

    CERN Document Server

    Adams, Ryan Prescott; Murray, Iain


    Probabilistic matrix factorization (PMF) is a powerful method for modeling data associated with pairwise relationships, finding use in collaborative filtering, computational biology, and document analysis, among other areas. In many domains, there is additional information that can assist in prediction. For example, when modeling movie ratings, we might know when the rating occurred, where the user lives, or what actors appear in the movie. It is difficult, however, to incorporate this side information into the PMF model. We propose a framework for incorporating side information by coupling together multiple PMF problems via Gaussian process priors. We replace scalar latent features with functions that vary over the space of side information. The GP priors on these functions require them to vary smoothly and share information. We successfully use this new method to predict the scores of professional basketball games, where side information about the venue and date of the game are relevant for the outcome.

  4. The SIDER database of drugs and side effects

    DEFF Research Database (Denmark)

    Kuhn, Michael; Letunic, Ivica; Jensen, Lars Juhl;


    Unwanted side effects of drugs are a burden on patients and a severe impediment in the development of new drugs. At the same time, adverse drug reactions (ADRs) recorded during clinical trials are an important source of human phenotypic data. It is therefore essential to combine data on drugs......, targets and side effects into a more complete picture of the therapeutic mechanism of actions of drugs and the ways in which they cause adverse reactions. To this end, we have created the SIDER ('Side Effect Resource', database of drugs and ADRs. The current release, SIDER 4......, contains data on 1430 drugs, 5880 ADRs and 140 064 drug-ADR pairs, which is an increase of 40% compared to the previous version. For more fine-grained analyses, we extracted the frequency with which side effects occur from the package inserts. This information is available for 39% of drug-ADR pairs, 19...

  5. U.S. electric utility demand-side management 1993

    Energy Technology Data Exchange (ETDEWEB)



    This report presents comprehensive information on electric power industry demand-side management activities in the United States at the national, regional, and utility levels. Data is included for energy savings, peakload reductions, and costs.

  6. A Case Report of Left-Sided Headache with Rhinocleisis

    Institute of Scientific and Technical Information of China (English)


    @@ Case Report A patient, with a complaint of a left-sided headache plus a rhinocleisis for a month, was admitted to our hospital. The clinical diagnosis showed that it was a primary adenoid cystic carcinoma (ACC) of the nasopharynx.

  7. Strength Training May Prevent Side Effect of Breast Cancer Surgery (United States)

    ... page: Strength Training May Prevent Side Effect of Breast Cancer Surgery ... 9, 2016 FRIDAY, Dec. 9, 2016 (HealthDay News) -- Strength training might benefit breast cancer survivors who've undergone ...

  8. Liraglutide and DPP-4 inhibitors - side effects comparative clinical study. (United States)

    Timofte, Luminiţa; Stratmann, Bernd; Quester, Wulf; Bojiţă, Marius Traian; Tschoepe, Diethelm


    The objective of this study was to monitor the side effects of the GLP-1 receptor agonist liraglutide in comparison to those of DPP-4 inhibitors (sitagliptin and vildagliptin), in order to determine their safety, tolerability and therapeutic efficiency. The study was carried out in the "Heart and Diabetes Center NRW" and included overweight patients with type 2 diabetes whose therapeutic regimen was switched to liraglutide or DPP-4 inhibitors. A validated questionnaire method was used to monitor the side effects during the hospitalization period, then again at 3, and 6 months after the beginning of the therapy. The therapy with liraglutide was associated with more side effects than the one with DPP-4 inhibitors. In general, side effects were declining with time, thus only few patients stopped therapy. The incretin therapy turned out to be a safe and effective therapeutic option for patients with type 2 diabetes mellitus.

  9. Effect of Overlaid Material on Optical Transmission of Side-Polished Fiber Made by Wheel Side Polishing

    Institute of Scientific and Technical Information of China (English)

    Zhe Chen; Chun-He Bai


    The performance of optical power transmission through a side-polished fiber on which materials of different refractive indices were overlaid is investigated. The experiments show that the transmitted optical power through the side-polished fiber varies with the refractive index of the overlaid material. The result of our experiments fits well the theoretical calculation.Side-polished fiber manufactured by wheel polishing method can be used not only to control optical power transmission through the fiber core but also as a refractive index sensor.

  10. Comment gouverner une population invisible ?



    S’inspirant des recherches sur les liens entre composition socioéconomique des villes et formes localisées de régulation politique, cet article analyse une ville caractérisée par la présence de structures militaires d’envergure, Toulon, et la population militaire qui y travaille et réside. Il montre les relations entre une population urbaine (et un groupe professionnel), ses formes d’organisation et d’expression d’intérêts, et son influence sur la sphère politique et les politiques publiques ...

  11. Persisting asymmetries of vision after right side lesions

    DEFF Research Database (Denmark)

    Habekost, Thomas; Rostrup, Egill


    Visual neglect and extinction are well-known effects of lesions in the right hemisphere. This study shows that even with minor or no clinical signs of these deficits, and in the stable phase of recovery, asymmetric visual perception is common after right side lesions. Whole, partial and colour re...... occurred selectively with bilateral stimulation. Overall, the study provided an overview of the cognitive structure and lesion anatomy of subtle visual asymmetries after right side stroke...

  12. Single Sided Messaging v. 0.6.6

    Energy Technology Data Exchange (ETDEWEB)


    Single-Sided Messaging (SSM) is a portable, multitransport networking library that enables applications to leverage potential one-sided capabilities of underlying network transports. It also provides desirable semantics that services for highperformance, massively parallel computers can leverage, such as an explicit cancel operation for pending transmissions, as well as enhanced matching semantics favoring large numbers of buffers attached to a single match entry. This release supports TCP/IP, shared memory, and Infiniband.

  13. Side Effects and Complications of Dental Materials on Oral Cavity


    Z. Atai; M. Atai


    Development of dental materials has had a great impact on the modern dentistry. The materials ranging from polymers to metals have different applications in dentistry. Besides their important role in healing or improving the function of oral tissues, the materials may show side effects which may, in some cases, lead to severe lesions. In this review the side effects have been summarized considering a new classification for dental materials according to the duration of their applications as te...

  14. Regional renal venous hypertension and left-sided varicocele


    O. B. Zhukov; A. V. Verzin; P. L. Penkov


    One of the most frequent correctable causes of male infertility is a varicocele. The etiology and pathogenesis of varicocele to date is a matter of debate. The aim of our study was to determine the causes and incidence of regional renal hypertension in patients with leftsided varicocele. The study involved 110 patients with left-sided varicocele in age from 18 to 35 years. Algorithm for evaluation of patients with left-sided varicocele included: physical examination, ultrasound with Doppler k...

  15. Holographic Gratings in Azobenzene Side-Chain Polymethacrylates

    DEFF Research Database (Denmark)

    Andruzzi, Luisa; Altomare, Angelina; Ciardelli, Francesco


    Optical storage properties of thin unoriented liquid crystalline and amorphous side-chain azobenzene polymethacrylate films are examined by polarization holographic measurements. The investigated materials are free radical copolymers derived from two photochromic monomers, 6-(4-oxy-4'-cyanoazoben......Optical storage properties of thin unoriented liquid crystalline and amorphous side-chain azobenzene polymethacrylate films are examined by polarization holographic measurements. The investigated materials are free radical copolymers derived from two photochromic monomers, 6-(4-oxy-4...

  16. Harmonic measures of slit sides perpendicular to the domain boundary

    CERN Document Server

    Prokhorov, Dmitri


    The article is devoted to the geometry of solutions to the chordal Loewner equation which is based on comparison of singular solutions and harmonic measures for the sides of a slit in domains generated by a driving term. It is proved that harmonic measures of two sides of a slit in the upper half-plane which is perpendicular to the real axis are asymptotically equal to each other.

  17. Population genomics reveals that an anthropophilic population of Aedes aegypti mosquitoes in West Africa recently gave rise to American and Asian populations of this major disease vector

    KAUST Repository

    Crawford, Jacob E.


    BackgroundThe mosquito Aedes aegypti is the main vector of dengue, Zika, chikungunya and yellow fever viruses. This major disease vector is thought to have arisen when the African subspecies Ae. aegypti formosus evolved from being zoophilic and living in forest habitats into a form that specialises on humans and resides near human population centres. The resulting domestic subspecies, Ae. aegypti aegypti, is found throughout the tropics and largely blood-feeds on humans.ResultsTo understand this transition, we have sequenced the exomes of mosquitoes collected from five populations from around the world. We found that Ae. aegypti specimens from an urban population in Senegal in West Africa were more closely related to populations in Mexico and Sri Lanka than they were to a nearby forest population. We estimate that the populations in Senegal and Mexico split just a few hundred years ago, and we found no evidence of Ae. aegypti aegypti mosquitoes migrating back to Africa from elsewhere in the tropics. The out-of-Africa migration was accompanied by a dramatic reduction in effective population size, resulting in a loss of genetic diversity and rare genetic variants.ConclusionsWe conclude that a domestic population of Ae. aegypti in Senegal and domestic populations on other continents are more closely related to each other than to other African populations. This suggests that an ancestral population of Ae. aegypti evolved to become a human specialist in Africa, giving rise to the subspecies Ae. aegypti aegypti. The descendants of this population are still found in West Africa today, and the rest of the world was colonised when mosquitoes from this population migrated out of Africa. This is the first report of an African population of Ae. aegypti aegypti mosquitoes that is closely related to Asian and American populations. As the two subspecies differ in their ability to vector disease, their existence side by side in West Africa may have important implications for

  18. Left-sided gallbladder: Its clinical significance and imaging presentations

    Institute of Scientific and Technical Information of China (English)


    AIM: To assess the importance of preoperative diagnosis and presentation of left-sided gallbladder using ultrasound (US), CT and angiography.METHODS: Retrospective review of 1482 patients who underwent enhanced CT scanning was performed. Left-sided gallbladder was diagnosed if a right-sided ligamentum teres was present. The image presentations on US, CT and angiography were also reviewed.RESULTS: Left-sided gallbladder was diagnosed in nine patients. The associated abnormalities on CT imaging included portal vein anomalies, absence of umbilical portion of the portal vein in the left lobe of the liver,club-shaped portal vein in the right lobe of the liver, and difficulty in identifying segment Ⅳ. Angiography in six of nine patients demonstrated abnormal portal venous system (trifurcation type in four of six patients). The main hepatic arteries followed the portal veins in all six patients. The segment Ⅳ artery was identified in four of six patients using angiography, although segment Ⅳ was difficult to define on CT imaging. Hepatectomy was performed in three patients with concomitant liver tumor and the diagnosis of left-sided gallbladder was confirmed intraoperatively.CONCLUSION: Left-sided gallbladder is an important clinical entity in hepatectomy due to its associated portal venous and biliary anomalies. It should be considered in US, CT and angiography images that demonstrate no definite segment IV, absence of umbilical portion of the portal vein in the left lobe, and club-shaped right anterior portal vein.

  19. Perceived side effects of oral contraceptives among adolescent girls. (United States)

    Herold, E S; Goodwin, M S


    Knowledge and attitudes of adolescent females regarding the side effects of oral contraceptives were investigated. The data source was a large study of sexual and contraceptive attitudes and experience. The questionnaire responses of 486 single females attending 10 birth control and pregnancy counseling centers in Ontario, Canada were examined. The age range of the subjects was from 13-20; 71% were attending school and 69% were living at home. They were attending the centers in order to obtain contraceptives (55%), to renew OC prescriptions (20%), or to receive pregnancy counseling (25%). 29% of the subjects had used OCs before coming to the clinic, but 91% planned to use OC after their clinic visit. 8% were planning to use an IUD; 1% were planning to use a diaphragm; and less than 1% were planning to have their boyfriend use condoms. 85% of the subjects indicated that they had heard abut side effcts of OCs with weight gain as the best known side effect. Other side effects familiar to many included nausea, circulatory disorders, headaches, emotional changes, menstrual problems and cancer. About 1/2 of the subjects had learned about these side effects from the mass media or female friends, 25% from a school sex education class, 15% from their mothers, and 3% from a physician. Despite knowledge regarding side effects, most of the subjects had positive attitudes toward OCs with 59% believing that the advnatages outweighed any disadvantages.

  20. A framework for assessing supply-side wildlife conservation. (United States)

    Phelps, J; Carrasco, L R; Webb, E L


    Market-based, supply-side interventions such as domestication, cultivation, and wildlife farming have been proposed as legal substitutes for wild-collected plants and animals in the marketplace. Based on the literature, we devised a list of the conditions under which supply-side interventions may yield positive conservation outcomes. We applied it to the trade of the orchid Rhynchostylis gigantea, a protected ornamental plant. We conducted a survey of R. gigantea at Jatujak Market in Bangkok, Thailand. Farmed (legal) and wild (illegal, protected) specimens of R. gigantea were sold side-by-side at market. These results suggest farmed specimens are not being substituted for wild plants in the marketplace. For any given set of physical plant characteristics (size, condition, flowers), the origin of the plants (wild vs. farmed) did not affect price. For all price classes, farmed plants were of superior quality to wild-collected plants on the basis of most physical variables. These results suggest wild and farmed specimens represent parallel markets and may not be substitutable goods. Our results with R. gigantea highlight a range of explanations for why supply-side interventions may lack effectiveness, for example, consumer preferences for wild-collected products and low financial incentives for farming. Our results suggest that market-based conservation strategies may not be effective by themselves and may be best utilized as supplements to regulation and education. This approach represents a broad, multidisciplinary evaluation of supply-side interventions that can be applied to other plant and animal species.

  1. Interaction dynamics of gap flow with vortex-induced vibration in side-by-side cylinder arrangement (United States)

    Liu, Bin; Jaiman, Rajeev K.


    A numerical investigation of the vortex-induced vibration (VIV) in a side-by-side circular cylinder arrangement has been performed in a two-dimensional laminar flow environment. One of the cylinders is elastically mounted and only vibrates in the transverse direction, while its counterpart remains stationary in a uniform flow stream. When the gap ratio is sufficiently small, the flip-flopping phenomenon of the gap flow can be an additional time-dependent interference to the flow field. This phenomenon was reported in the experimental work of Bearman and Wadcock ["The interaction between a pair of circular cylinders normal to a stream," J. Fluid Mech. 61(3), 499-511 (1973)] in a side-by-side circular cylinder arrangement, in which the gap flow deflects toward one of the cylinders and switched its sides intermittently. Albeit one of the two cylinders is free to vibrate, the flip-flop of a gap flow during VIV dynamics can still be observed outside the lock-in region. The exact moments of the flip-flop phenomenon due to spontaneous symmetry breaking are observed in this numerical study. The significant characteristic vortex modes in the near-wake region are extracted via dynamic modal analysis and the interference between the gap flow and VIV is found to be mutual. In a vibrating side-by-side arrangement, the lock-in region with respect to reduced velocity becomes narrower due to the interference from its stationary counterpart. The frequency lock-in occurs and ends earlier than that of an isolated vibrating circular cylinder subjected to an identical flow environment. Similar to a tandem cylinder arrangement, in the post-lock-in region, the maximum vibration amplitudes are escalated compared with those of an isolated circular cylinder configuration. On the other hand, subjected to the influence from VIV, the biased gap flow deflects toward the vibrating cylinder quasi-stably during the frequency lock-in process. This behavior is different from the reported bi

  2. Meta-sided Exchange Rings and Their Extensions%Meta-sided exchange环及其扩张

    Institute of Scientific and Technical Information of China (English)

    郭莉琴; 何建伟; 卲海琴


    讨论了meta-sided exchange环的性质.证明了如果R是Abelian meta-sided exchange环,则对R的任意素理想P,都有R/P是局部环;如果R是Abelian环,(S,≤)是严格序幺半群且对任意s∈S,都有0≤s,则广义幂级数环[[RS,≤

  3. Application of side-to-side anastomosis of the lesser curvature of stomach and jejunum in gastric bypass (United States)

    Bai, Ri-Xing; Yan, Wen-Mao; Li, You-Guo; Xu, Jun; Zhong, Zhi-Qiang; Yan, Ming


    AIM To evaluate the feasibility of side-to-side anastomosis of the lesser curvature of stomach and jejunum in laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS Seventy-seven patients received side-to-side anastomosis of the lesser curvature of stomach and jejunum by utilization of linear stapler in LRYGB from April 2012 to July 2015 were retrospectively analyzed. RESULTS All patients were successfully completed laparoscopic gastric bypass with the side-to-side anastomosis of the lesser curvature of stomach and jejunum. No patient was switched to laparotomy during operation. No early complications including gastrointestinal anastomotic bleeding, fistula, obstruction, deep vein thrombosis, incision infections, intra-abdominal hernia complications were found. One patient complicated with stricture of gastrojejunal anastomosis (1.3%) and six patients complicated with incomplete intestinal obstruction (7.8%). BMI and HbA1c determined at 3, 6, 12, 24 mo during follow up period were significantly reduced compared with preoperative baselines respectively. The percentage of patients who maintain HbA1c (%) < 6.5% without taking antidiabetic drugs reached to 61.0%, 63.6%, 75.0%, and 63.6% respectively. The outcome parameters of concomitant diseases were significantly improved too. CONCLUSION Present surgery is a safety and feasibility procedure. It is effective to lighten the body weight of patients and improve type 2 diabetes and related complications. PMID:27729746

  4. Education Vital Signs: Population. (United States)

    Zakariya, Sally Banks


    Population changes and demographics shape the future of public schools. Includes statistics on ethnic makeup of student population, the projected baby boomlet, children of working mothers, households without children, and the aging population. (MD)

  5. Developing STR databases on structured populations: the native South Siberian population versus the Russian population. (United States)

    Zhivotovsky, Lev A; Malyarchuk, Boris A; Derenko, Miroslava V; Wozniak, Marcin; Grzybowski, Tomasz


    Developing a forensic DNA database on a population that consists of local ethnic groups separated by physical and cultural barriers is questionable as it can be genetically subdivided. On the other side, small sizes of ethnic groups, especially in alpine regions where they are sub-structured further into small villages, prevent collecting a large sample from each ethnic group. For such situations, we suggest to obtain both a total population database on allele frequencies across ethnic groups and a list of theta-values between the groups and the total data. We have genotyped 558 individuals from the native population of South Siberia, consisting of nine ethnic groups, at 17 autosomal STR loci of the kit packages AmpFlSTR SGM Plus i, Cyrillic AmpFlSTR Profiler Plus. The groups differentiate from each other with average theta-values of around 1.1%, and some reach up to three to four percent at certain loci. There exists between-village differentiation as well. Therefore, a database for the population of South Siberia is composed of data on allele frequencies in the pool of ethnic groups and data on theta-values that indicate variation in allele frequencies across the groups. Comparison to additional data on northeastern Asia (the Chukchi and Koryak) shows that differentiation in allele frequencies among small groups that are separated by large geographic distance can be even greater. In contrast, populations of Russians that live in large cities of the European part of Russia are homogeneous in allele frequencies, despite large geographic distance between them, and thus can be described by a database on allele frequencies alone, without any specific information on theta-values.

  6. A protein-dependent side-chain rotamer library.

    KAUST Repository

    Bhuyan, M.S.


    Protein side-chain packing problem has remained one of the key open problems in bioinformatics. The three main components of protein side-chain prediction methods are a rotamer library, an energy function and a search algorithm. Rotamer libraries summarize the existing knowledge of the experimentally determined structures quantitatively. Depending on how much contextual information is encoded, there are backbone-independent rotamer libraries and backbone-dependent rotamer libraries. Backbone-independent libraries only encode sequential information, whereas backbone-dependent libraries encode both sequential and locally structural information. However, side-chain conformations are determined by spatially local information, rather than sequentially local information. Since in the side-chain prediction problem, the backbone structure is given, spatially local information should ideally be encoded into the rotamer libraries. In this paper, we propose a new type of backbone-dependent rotamer library, which encodes structural information of all the spatially neighboring residues. We call it protein-dependent rotamer libraries. Given any rotamer library and a protein backbone structure, we first model the protein structure as a Markov random field. Then the marginal distributions are estimated by the inference algorithms, without doing global optimization or search. The rotamers from the given library are then re-ranked and associated with the updated probabilities. Experimental results demonstrate that the proposed protein-dependent libraries significantly outperform the widely used backbone-dependent libraries in terms of the side-chain prediction accuracy and the rotamer ranking ability. Furthermore, without global optimization/search, the side-chain prediction power of the protein-dependent library is still comparable to the global-search-based side-chain prediction methods.

  7. Dirac cones, Floquet side bands, and theory of time-resolved angle-resolved photoemission (United States)

    Farrell, Aaron; Arsenault, A.; Pereg-Barnea, T.


    Pump-probe techniques with high temporal resolution allow one to drive a system of interest out of equilibrium and at the same time probe its properties. Recent advances in these techniques open the door to studying new, nonequilibrium phenomena such as Floquet topological insulators and superconductors. These advances also necessitate the development of theoretical tools for understanding the experimental findings and predicting new ones. In the present paper, we provide a theoretical foundation to understand the nonequilibrium behavior of a Dirac system. We present detailed numerical calculations and simple analytic results for the time evolution of a Dirac system irradiated by light. These results are framed by appealing to the recently revitalized notion of side bands [A. Farrell and T. Pereg-Barnea, Phys. Rev. Lett. 115, 106403 (2015), 10.1103/PhysRevLett.115.106403; Phys. Rev. B 93, 045121 (2016), 10.1103/PhysRevB.93.045121], extended to the case of nonperiodic drive where the fast oscillations are modified by an envelope function. We apply this formalism to the case of photocurrent generated by a second probe pulse. We find that, under the application of circularly polarized light, a Dirac point only ever splits into two copies of side bands. Meanwhile, the application of linearly polarized light leaves the Dirac point intact while producing side bands. In both cases the population of the side bands are time dependent through their nonlinear dependence on the envelope of the pump pulse. Our immediate interest in this work is in connection to time- and angle-resolved photoemission experiments, where we find excellent qualitative agreement between our results and those in the literature [Wang et al., Science 342, 453 (2013), 10.1126/science.1239834]. However, our results are general and may prove useful beyond this particular application and should be relevant to other pump-probe experiments.

  8. Raltegravir use in special populations

    Directory of Open Access Journals (Sweden)

    Johnson Margaret


    Full Text Available Abstract Raltegravir, the first approved integrase inhibitor, has been shown to be virologically effective in Phase II and Phase III clinical trials in both treatment naïve and triple class resistant patients. It also has an excellent tolerability profile and lacks significant drug-drug interactions making it an important drug in the treatment of a number of special patient populations. In this review its use in patients undergoing solid organ and bone marrow transplantation and patients receiving cancer chemotherapy, will be discussed. In addition other indications including patients with metabolic complications of existing antiretroviral drugs as well as patients with side effects on current HAART regimens. Other groups of patients where raltegravir may play an important role are patients with renal disease and tuberculosis. Finally, although not licensed for use in pregnancy, raltegravir may need to be considered in some pregnant women with antiretroviral resistance or tolerability issues with current HAART regimens.

  9. Demand Side Management Performance Evaluation for Commercial Enterprises

    Directory of Open Access Journals (Sweden)

    Jun Dong


    Full Text Available Demand Side Management in power systems plays an important role in ensuring a reliable power supply and protecting the environment. Demand Side Management in the commercial sector is vital for sustainable development during China’s industrial restructuring. A hybrid multi-criteria decision making framework for evaluating Demand Side Management performance of commercial enterprises is proposed from a sustainability perspective. A fuzzy Analytic Hierarchy Process is employed to determine the weights of the criteria and a fuzzy technique for order preference by similarity to an ideal solution is applied to rank Demand Side Management performance. An evaluation index system is built, containing economic, social, environmental and technical criteria associated with 15 sub-criteria. Four groups of expert panels from government departments, research institutions, electricity utilities and commercial enterprises gave judgments on criteria weights and criteria performances for alternatives. The effectiveness of the proposed hybrid framework was demonstrated through a case study in Beijing, in which Demand Side Management performances of four alternatives were ranked. Sensitivity analysis results indicate that the hybrid framework is robust.

  10. Sex differences in substance use disorders: focus on side effects. (United States)

    Agabio, Roberta; Campesi, Ilaria; Pisanu, Claudia; Gessa, Gian Luigi; Franconi, Flavia


    Although sex differences in several aspects of substance use disorders (SUDs) have been identified, less is known about the importance of possible sex differences in side effects induced by substances of abuse or by medications used to treat SUDs. In the SUD field, the perception of certain subjective effects are actively sought, while all other manifestations might operationally be considered side effects. This article was aimed at reviewing sex differences in side effects induced by alcohol, nicotine, heroin, marijuana and cocaine and by medications approved for alcohol, nicotine and heroin use disorders. A large body of evidence suggests that women are at higher risk of alcohol-induced injury, liver disease, cardiomyopathy, myopathy, brain damages and mortality. The risk of tobacco-induced coronary heart disease, lung disease and health problems is higher for women than for men. Women also experience greater exposure to side effects induced by heroin, marijuana and cocaine. In addition, women appear to be more vulnerable to the side effects induced by medications used to treat SUDs. Patients with SUDs should be advised that the risk of developing health problems may be higher for women than for men after consumption of the same amount of substances of abuse. Doses of medications for SUD women should be adjusted at least according to body weight. The sex differences observed also indicate an urgent need to recruit adequate numbers of female subjects in pre-clinical and clinical studies to improve our knowledge about SUDs in women.

  11. Novel high torque bearingless two-sided rotary ultrasonic motor

    Institute of Scientific and Technical Information of China (English)

    LI Xia; CHEN Wei-shan; XIE Tao; LIU Jun-kao


    Applications are limited at present because the currently available ultrasonic motors (USMs) do not provide sufficiently high torque and power. The conventional travelling-wave USM needs the bearing to support, which required lubricant. To solve the above problem, a bearingless travelling-wave USM is designed. First, a novel structure of the two-sided USM consisting ora two-sided teeth stator and two disk-type rotors is designed. And the excitation principle of the two-sided travelling-wave USM is analyzed. Then, using ANSYS software, we set up the model of the stator to predict the excitation frequency and modal response of the stator. The shape of the vibration mode was obtained. Last, the load characteristics of the USM are measured using experimental method. The maximum stall torque and the no-load speed were obtained. The results showed that the characteristics of the two-sided USM are better than those of the conventional one-sided USM.

  12. Predicting bed form roughness: the influence of lee side angle (United States)

    Lefebvre, Alice; Winter, Christian


    Flow transverse bedforms (ripples and dunes) are ubiquitous in rivers and coastal seas. Local hydrodynamics and transport conditions depend on the size and geometry of these bedforms, as they constitute roughness elements at the bed. Bedform influence on flow energy must be considered for the understanding of flow dynamics, and in the development and application of numerical models. Common estimations or predictors of form roughness (friction factors) are based mostly on data of steep bedforms (with angle-of-repose lee slopes), and described by highly simplified bedform dimensions (heights and lengths). However, natural bedforms often are not steep, and differ in form and hydraulic effect relative to idealised bedforms. Based on systematic numerical model experiments, this study shows how the hydraulic effect of bedforms depends on the flow structure behind bedforms, which is determined by the bedform lee side angle, aspect ratio and relative height. Simulations reveal that flow separation behind bedform crests and, thus, a hydraulic effect is induced at lee side angles steeper than 11 to 18° depending on relative height, and that a fully developed flow separation zone exists only over bedforms with a lee side angle steeper than 24°. Furthermore, the hydraulic effect of bedforms with varying lee side angle is evaluated and a reduction function to common friction factors is proposed. A function is also developed for the Nikuradse roughness (k s), and a new equation is proposed which directly relates k s to bedform relative height, aspect ratio and lee side angle.

  13. Early and Late Side Effects Associated with Photo(chemotherapy

    Directory of Open Access Journals (Sweden)

    Günseli Öztürk


    Full Text Available Phototherapy (PUVA ve UVB is a widely used and effective treatment method for a variety of dermatological diseases. Adverse effects associated with phototherapy can be classified as acute and chronic side effects. Acute side effects are mostly related with UV doses and drug intolerance, and include itching, nausea, erythema, edema and phototoxic reactions that sometimes blister formation is seen. Acute side effects are usually moderate and transient. Chronic side effects of phototherapy are early aging of skin, pigmentary changes and increased risk of skin carcinogenesis. The major concern is development of skin cancer. This risk is especially related to long-term exposure and high cumulative doses of PUVA, increase in time and is persistent. Therefore, risk/advantage ratio of phototherapy should be carefully evaluated in each patient, and treatment protocols with minimal UV exposure should be chosen according to the phototherapy guides. Follow-up of the patients for long terms is important in prevention or in reduction of this risk by detecting and treating any premalignant or malignant lesion early. In this article, acute and chronic side effects of phototherapy are reviewed with recent literature findings.

  14. Source Coding When the Side Information May Be Delayed

    CERN Document Server

    Simeone, Osvaldo


    For memoryless sources, delayed side information at the decoder does not improve the rate-distortion function. However, this is not the case for more general sources with memory, as demonstrated by a number of works focusing on the special case of (delayed) feedforward. In this paper, a setting is studied in which the encoder is potentially uncertain about the delay with which measurements of the side information are acquired at the decoder. Assuming a hidden Markov model for the sources, at first, a single-letter characterization is given for the set-up where the side information delay is arbitrary and known at the encoder, and the reconstruction at the destination is required to be (near) lossless. Then, with delay equal to zero or one source symbol, a single-letter characterization is given of the rate-distortion region for the case where side information may be delayed or not, unbeknownst to the encoder. The characterization is further extended to allow for additional information to be sent when the side ...

  15. 'Side effects' of health promotion: an example from Austrian schools. (United States)

    Gugglberger, Lisa; Flaschberger, Edith; Teutsch, Friedrich


    While the existence of side effects of medical interventions is common knowledge and widely investigated, possible unintended effects of health promotion (HP) interventions are only sparsely discussed in the HP literature. Drawing on qualitative evaluation data generated within an on-going process evaluation of a regional health-promoting schools network in Austria, we demonstrate which desirable and undesirable effects HP practice can have for teachers. Thirteen group discussions with teachers (n = 63) and headteachers (n = 9) acting as health coordinators in the network schools were conducted between 2010 and 2013. These data were analysed using systems and thematic analyses. In our example, desirable side effects included health coordinators gaining new relationships, new skills and benefiting from improved infrastructure. The undesirable side effects centred on stress, work overload and frustration, due to the additional work brought about by HP practice, negative reactions by colleagues as well as by technicalities of the network. The undesirable side effects of HP predominated in our study, pointing to several implications like the need to accommodate the concept of HP in the teachers' core responsibilities; the participation of all staff members and students in a whole-school approach toward SHP, and the need for changes on an organizational level. Based on this study, we come to the conclusion that a systematic approach to investigating and analysing side effects of HP is currently lacking in HP research and suggest that theoretical examination and more empirical research is needed.

  16. Side Channel Passive Quantum Key Distribution with One Uninformative State (United States)

    Kang, Guo-Dong; Zhou, Qing-Ping; Fang, Mao-Fa


    In most of quantum key distribution schemes, real random number generators are required on both sides for preparation and measurement bases choice. In this paper, via entangled photon pairs, we present a side channel passive quantum key distribution scheme, in which random number generator is unneeded on the receiver side. On the sender Alice side, along with massive of signal photons, small amount of uninformative photons are randomly sent to her partner Bob for eavesdropper-presence testing and error estimation. While on the other side channel, without using random number generator Bob do not actively measure the income signals randomly in two non-orthogonal bases. Instead, he just passively register photon click events, in two settled symmetric (i.e. X) bases, and the raw key(click events) is the probable outcomes of a special quantum measurement module constructed by Alice and Bob. Further, security analysis and formulas of security bounds for this scheme is also investigated under reasonable assumptions. Our work shows that the uninformative state employed in this paper is powerful to fight against eavesdropper Eve.

  17. Assessment of palatal rugae patterns in Manipuri and Kerala population

    Directory of Open Access Journals (Sweden)

    R Surekha


    Full Text Available Background: Palatal rugae comprises three to seven ridges radiating out tangentially from the incisive papilla on the anterior part of the palate. These rugae patterns are studied for various reasons, mainly in the fields of anthropology, genetics, orthodontics, prosthodontics, and forensic science. Objective: To compare the palatal rugae pattern in two different populations (Manipuri and Kerala, and to assess the predominant pattern if any in the selected groups. Materials and Methods: Sixty maxillary study models (30 from each group including males and females were examined in the age group ranging from 17 to 23 years. Palatal rugae pattern were analyzed on the right and left sides of the palate for total number, length, shape, direction, and unification. Results: After analyzing the rugae patterns in both the groups and between the two sides of the palate, the wavy pattern was found to be predominant followed by curved, straight, and circular in overall population. Manipuri population showed predominant curved shape than the Kerala population and was statistically significant. Females in general had slightly more rugae than males and the left side of the palate showed comparatively more number of rugae than on the right side. Conclusion: A statistically significant association between the shape of the rugae and population exists although, subtle. Parameters like direction and unification need more attention for better understanding.

  18. Interstrand side chain--side chain interactions in a designed beta-hairpin: significance of both lateral and diagonal pairings. (United States)

    Syud, F A; Stanger, H E; Gellman, S H


    The contributions of interstrand side chain-side chain contacts to beta-sheet stability have been examined with an autonomously folding beta-hairpin model system. RYVEV(D)PGOKILQ-NH2 ((D)P = D-proline, O = ornithine) has previously been shown to adopt a beta-hairpin conformation in aqueous solution, with a two-residue loop at D-Pro-Gly. In the present study, side chains that display interstrand NOEs (Tyr-2, Lys-9, and Leu-11) are mutated to alanine or serine, and the conformational impact of the mutations is assessed. In the beta-hairpin conformation Tyr-2 and Leu-11 are directly across from one another (non-hydrogen bonded pair). This "lateral" juxtaposition of two hydrophobic side chains appears to contribute to beta-hairpin conformational stability, which is consistent with results from other beta-sheet model studies and with statistical analyses of interstrand residue contacts in protein crystal structures. Interaction between the side chains of Tyr-2 and Lys-9 also stabilizes the beta-hairpin conformation. Tyr-2/Lys-9 is a "diagonal" interstrand juxtaposition because these residues are not directly across from one another in terms of the hydrogen bonding registry between the strands. This diagonal interaction arises from the right-handed twist that is commonly observed among beta-sheets. Evidence of diagonal side chain-side chain contacts has been observed in other autonomously folding beta-sheet model systems, but we are not aware of other efforts to determine whether a diagonal interaction contributes to beta-sheet stability.

  19. Pattern of antibiotic abuse – a population based study in Cairo

    Directory of Open Access Journals (Sweden)

    Ahmed Abdel Gawad Elmasry


    Conclusion: This study showed high rates of antibiotic abuse among Cairo population. This needs to be guided through different strategies. An easy access to an affordable health care service with a considerable quality is the first step side by side with establishing a national antibiotic policy to be followed by all healthcare workers.

  20. Alaska Department of Fish and Game Juneau, Alaska: South Central Moose Population Studies (United States)

    US Fish and Wildlife Service, Department of the Interior — A study aiming to delineate populations and subpopulations of moose on the west side of the lower Susitna Valley and to assess their seasonal movement patterns