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Cycle Analysis (cycle + analysis)
Kinds of Cycle Analysis Selected AbstractsUsing Trading Zones and Life Cycle Analysis to Understand Nanotechnology RegulationTHE JOURNAL OF LAW, MEDICINE & ETHICS, Issue 4 2006Ahson Wardak This article reviews the public health and environmental regulations applicable to nanotechnology using a life cycle model from basic research through end-of-life for products. Given nanotechnology's immense promise and public investment, regulations are important, balancing risk with the public good. Trading zones and earth systems engineering management assist in explaining potential solutions to gaps in an otherwise complex, overlapping regulatory system. [source] Cycle analysis of low and high H2 utilization SOFCs/gas turbine combined cycle for CO2 recoveryELECTRONICS & COMMUNICATIONS IN JAPAN, Issue 10 2008Takuya Taniuchi Abstract Global warming is mainly caused by CO2 emission from thermal power plants, which burn fossil fuel with air. One of the countermeasure technologies to prevent global warming is CO2 recovery from combustion flue gas and the sequestration of CO2 underground or in the ocean. SOFC and other fuel cells can produce high-concentration CO2, because the reformed fuel gas reacts with oxygen electrochemically without being mixed with air, or diluted by N2. Thus, we propose to operate the multistage SOFCs under high utilization of reformed fuel for obtaining high-concentration CO2. In this report, we have estimated the multistage SOFCs' performance considering H2 diffusion and the combined cycle efficiency of multistage SOFC/gas turbine/CO2 recovery power plant. The power generation efficiency of our CO2 recovery combined cycle is 68.5% and the efficiency of conventional SOFC/GT cycle is 57.8% including the CO2 recovery amine process. © 2009 Wiley Periodicals, Inc. Electron Comm Jpn, 91(10): 38,45, 2008; Published online in Wiley InterScience (www.interscience. wiley.com). DOI 10.1002/ecj.10165 [source] A Method for the Detection of Defluidized Zones in Slurry Bubble ColumnsTHE CANADIAN JOURNAL OF CHEMICAL ENGINEERING, Issue 3-4 2003Ahad Emami Abstract The formation of defluidized zones was studied in a laboratory slurry bubble column equipped with heat transfer probes. The probes were small thermistors 2.4 mm in diameter. Dionized water and air were used as a liquid and gas phase, respectively. Solids were fine ceramic particles with mean size of 19.2 ,m and density of 2244 kg/m3. The effects of solids holdup (up to 30 wt% on gas free basis), gas superficial velocity (0.01-0.09 m/s), sparger height (0.01-0.09 m) on defluidized zones formation was studied. Cycle analysis of the local heat transfer fluctuations reliably detected the local formation of defluidized zones for each condition. La formation de zones défluidisées a été étudiée dans une colonne à bulles avec bouillie, équipée de sondes de transfert de chaleur. Les sondes étaient des petits thermistors de 2.4 mm de diamètre. De l'eau déionisée et de l'air constituaient les phases liquide et gazeuse. Les solides étaient des fines particules en céramique avec une taille moyenne de 19.2 µm et une densité de 2244 kg/m3. Les effets de la rétention solide (jusqu'à 30 % en masses sur base sans gaz), de la vitesse superficielle du gaz (0.01-0.09 m/s) et de la hauteur du distributeur de gaz ont été étudiés. L'analyse de cycle du transfert de local de chaleur a détecté de façon fiable la formation locale de zones défluidisées pour chaque condition. [source] DNA ploidy and cell cycle analyses in the bone marrow cells of patients with megaloblastic anemia using laser scanning cytometry,CYTOMETRY, Issue 2 2008Takayuki Tsujioka Abstract Background: Megaloblastic anemias are characterized by several hematopoietic cells with dysplastic nuclear morphology. The analyses of DNA ploidy and cell cycle of these cells are important to understand the property of such diseases. Methods: As laser scanning cytometry (LSC) is a useful tool to evaluate the morphology of the cells fixed on the slide glass together with the quantitative analysis of the fluorescence information of each cell by rapid scanning of the specimens, the authors examined the DNA ploidy and cell cycle of six cases with megaloblastic anemia using LSC. Results: Giant neutrophilic series such as giant metamyelocytes and giant band cells were found to have extraordinarily higher DNA ploidy, while hypersegmented neutrophils represented the normal diploid pattern like normal neutrophils. As to megaloblasts, cell cycle analysis showed that the proportion of the cells in S phase was increased as compared with the case of normal erythroblasts. Conclusions: The present study clearly demonstrates the abnormal aspects of the hematopoietic cells with megaloblastic anemia from the viewpoint of the DNA ploidy and cell cycle analyzed by the use of LSC. © 2007 Clinical Cytometry Society. [source] Greenhouse gas emissions from four bioenergy crops in England and Wales: Integrating spatial estimates of yield and soil carbon balance in life cycle analysesGCB BIOENERGY, Issue 4 2009JONATHAN HILLIER Abstract Accurate estimation of the greenhouse gas (GHG) mitigation potential of bioenergy crops requires the integration of a significant component of spatially varying information. In particular, crop yield and soil carbon (C) stocks are variables which are generally soil type and climate dependent. Since gaseous emissions from soil C depend on current C stocks, which in turn are related to previous land management it is important to consider both previous and proposed future land use in any C accounting assessment. We have conducted a spatially explicit study for England and Wales, coupling empirical yield maps with the RothC soil C turnover model to simulate soil C dynamics. We estimate soil C changes under proposed planting of four bioenergy crops, Miscanthus (Miscanthus×giganteus), short rotation coppice (SRC) poplar (Populus trichocarpa Torr. & Gray ×P. trichocarpa, var. Trichobel), winter wheat, and oilseed rape. This is then related to the former land use , arable, pasture, or forest/seminatural, and the outputs are then assessed in the context of a life cycle analysis (LCA) for each crop. By offsetting emissions from management under the previous land use, and considering fossil fuel C displaced, the GHG balance is estimated for each of the 12 land use change transitions associated with replacing arable, grassland, or forest/seminatural land, with each of the four bioenergy crops. Miscanthus and SRC are likely to have a mostly beneficial impact in reducing GHG emissions, while oilseed rape and winter wheat have either a net GHG cost, or only a marginal benefit. Previous land use is important and can make the difference between the bioenergy crop being beneficial or worse than the existing land use in terms of GHG balance. [source] The knockdown of endogenous replication factor C4 decreases the growth and enhances the chemosensitivity of hepatocellular carcinoma cellsLIVER INTERNATIONAL, Issue 1 2009Masaaki Arai Abstract Aims: To identify differentially expressed genes and thereby detect potential molecular targets for future therapies directed against hepatocellular carcinoma (HCC). Methods: To isolate differentially expressed genes between HCC and adjacent non-cancerous liver tissues, cDNA microarray and quantitative reverse transcriptase polymerase chain reaction analyses were performed. Gene knockdown experiments in HepG2 cells were also performed using small interfering RNAs (siRNAs). Proteins were detected by immunostaining, and cell proliferation was analysed using the MTT/WST-8 assay. Apoptosis and cell cycle analyses were performed using flow cytometry. Results: After an intensive screening for differentially expressed genes in HCC tissues, we isolated 23 upregulated genes in these lesions. Among these, we focused on the replication factor C4 (RFC4) gene. The expression of endogenous RFC4 proteins in HepG2 cells was found to be significantly reduced by RFC4 -specific siRNA. This inhibition of RFC4 expression correlated with a decrease in cellular proliferation, increased levels of apoptosis and a sensitizing of the cells to the DNA-damaging chemotherapeutic agents, doxorubicin and camptothecin. Conclusion: The replication factor C4 gene may be a novel target for developing cancer therapeutics, which can enhance the antitumour activity of chemotherapeutic agents that induce DNA damage. [source] Monodemethylated polymethoxyflavones from sweet orange (Citrus sinensis) peel Inhibit growth of human lung cancer cells by apoptosisMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 3 2009Hang Xiao Abstract Polymethoxyflavones (PMFs) are almost exclusively found in the Citrus genus, particularly in the peels of sweet orange (Citrus sinensis L. Osbeck) and mandarin (C. reticulate Blanco). We studied the effects of two major PMFs, namely, nobiletin and 3,5,6,7,8,3,,4,-heptamethoxyflavone (HMF), and two major monodemethylated PMFs, namely 5-hydroxy-3,7,8,3,,4,-pentamethoxyflavone (5HPMF), and 5-hydroxy-3,6,7,8,3,,4,-hexamethoxyflavone (5HHMF), on the growth of human lung cancer H1299, H441, and H460 cells. Monodemethylated PMFs were much more potent in growth inhibition of lung cancer cells than their permethoxylated counterpart PMFs. In H1299 cells, cell cycle analyses further revealed that monodemethylated PMFs caused significant increase in sub-G0/G1 phase, suggesting possible role of apoptosis in the growth inhibition observed, whereas the permethoxylated counterpart PMFs did not affect cell cycle distribution at same concentrations tested. These results strongly suggested that the phenolic group is essential for the growth inhibitory activity of monodemethylated PMFs. Further studies in H1299 cells demonstrated that monodemethylated PMFs downregulated oncogenic proteins, such as iNOS, COX-2, Mcl-1, and K-ras, as well as induced apoptosis evidenced by activation of caspase-3 and cleavage of PARP. Our results provide rationale to develop orange peel extract enriched with monodemethylated PMFs into value-added nutraceutical products for cancer prevention. [source] Cell Cycle Arrest and Apoptosis Induction by an Anticancer Chalcone EpoxideARCHIV DER PHARMAZIE, Issue 8 2010Haiyong Han Abstract Safe and effective chemotherapeutic agents for the treatment of pancreatic cancer remain elusive. We found that chalcone epoxides (1,3-diaryl-2,3-epoxypropanones) inhibited growth in two pancreatic cancer cell lines, BxPC-3 and MIA PaCa-2. Three compounds were active, with GI50 values of 5.6 to 15.8,µM. Compound 4a, 1,3-bis-(3,4,5-trimethoxyphenyl)-2,3-epoxypropanone, had an average GI50 of 14.1,µM in the NCI 60-cell-line panel. To investigate the mode of action, cell cycle analyses of BxPC-3 cells were carried out. Treatment of cells with 50,µM 4a resulted in dramatic accumulation at G2/M (61% after 12,h for 4avs. 15% for untreated cells). The cells rapidly entered apoptosis. After 12,h, 26% of cells treated with 50,µM 4a had entered apoptosis vs. 4% for cells treated with 100,µM etoposide and 2% for untreated cells. Compound 4a interfered with paclitaxel enhancement of tubulin polymerization, suggesting microtubules as the site of action. Reaction of thiol nucleophiles with 4a under basic conditions resulted in epoxide ring-opening and retroaldol fragmentation, yielding alkylated thiol. MALDI mass spectrometry showed that retroaldol reaction occurred upon treatment of ,-tubulin with 4a. The site of alkylation was identified as Cys354. Chalcone epoxides warrant further study as potential agents for treatment of cancer. [source] Limited LCAs of pharmaceutical products: merits and limitations of an environmental management toolCORPORATE SOCIAL RESPONSIBILITY AND ENVIRONMENTAL MANAGEMENT, Issue 2 2003Anne Marie de Jonge This article explores both the merits and the limitations of life cycle analysis (LCA) as an environmental management tool in the framework of the pharmaceutical industry. In this study, limited LCAs in the form of product lifecycle-oriented energy balances were established for two rather different pharmaceutical products. Primary energy requirements served as the single indicator for the products' direct and indirect environmental impacts. The functional units of the products were defined as the one year treatments of average patients. The results of the case studies indicate that the portion of the active substance in the pharmaceutical end product is an important predictor for the breakdown of energy requirements and thus environmental impacts over the life cycle. Despite its limitations, the energy balances provide first-hand indications of where eco-efficiency measures should be taken. In this sense, the limited LCAs served as a useful environmental management tool. Copyright © 2003 John Wiley & Sons, Ltd. and ERP Environment [source] DNA ploidy and cell cycle analyses in the bone marrow cells of patients with megaloblastic anemia using laser scanning cytometry,CYTOMETRY, Issue 2 2008Takayuki Tsujioka Abstract Background: Megaloblastic anemias are characterized by several hematopoietic cells with dysplastic nuclear morphology. The analyses of DNA ploidy and cell cycle of these cells are important to understand the property of such diseases. Methods: As laser scanning cytometry (LSC) is a useful tool to evaluate the morphology of the cells fixed on the slide glass together with the quantitative analysis of the fluorescence information of each cell by rapid scanning of the specimens, the authors examined the DNA ploidy and cell cycle of six cases with megaloblastic anemia using LSC. Results: Giant neutrophilic series such as giant metamyelocytes and giant band cells were found to have extraordinarily higher DNA ploidy, while hypersegmented neutrophils represented the normal diploid pattern like normal neutrophils. As to megaloblasts, cell cycle analysis showed that the proportion of the cells in S phase was increased as compared with the case of normal erythroblasts. Conclusions: The present study clearly demonstrates the abnormal aspects of the hematopoietic cells with megaloblastic anemia from the viewpoint of the DNA ploidy and cell cycle analyzed by the use of LSC. © 2007 Clinical Cytometry Society. [source] Viability study of HL60 cells in contact with commonly used microchip materialsELECTROPHORESIS, Issue 24 2006Floor Wolbers Abstract This paper presents a study in which different commonly used microchip materials (silicon oxide, borosilicate glass, and PDMS) were analyzed for their effect on human promyelocytic leukemic (HL60) cells. Copper-coated silicon was analyzed for its toxicity and therefore served as a positive control. With quantitative PCR, the expression of the proliferation marker Cyclin D1 and the apoptosis marker tissue transglutaminase were measured. Flow cytometry was used to analyze the distribution through the different phases of the cell cycle (propidium iodide, PI) and the apoptotic cascade (Annexin V in combination with PI). All microchip materials, with the exception of Cu, appeared to be suitable for HL60 cells, showing a ratio apoptosis/proliferation (Rap) comparable to materials used in conventional cell culture (polystyrene). These results were confirmed with cell cycle analysis and apoptosis studies. Precoating the microchip material surfaces with serum favor the proliferation, as demonstrated by a lower Rap as compared to uncoated surfaces. The Cu-coated surface appeared to be toxic for HL60 cells, showing over 90% decreased viability within 24,h. From these results, it can be concluded that the chosen protocol is suitable for selection of the cell culture material, and that the most commonly used microchip materials are compatible with HL60 culturing. [source] BSc2118 is a novel proteasome inhibitor with activity against multiple myelomaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2010Jan Sterz Abstract Objectives:, The ubiquitin,proteasome system emerged as a new therapeutic target in cancer treatment. The purpose of this study was to elucidate the effects of the novel proteasome inhibitor BSc2118 on t(4;14) positive and negative multiple myeloma (MM) cells and normal peripheral blood mononuclear cells (PBMNC). Methods:, Human MM cell lines OPM-2, RPMI-8226, and U266 and primary MM cells from bone marrow aspirates were exposed to BSc2118. Cytotoxicity levels were evaluated using the MTT-test. BSc2118-induced apoptosis was analyzed by annexin-V assay. Further methods used included proteasomal activity determination, cell cycle analysis, western blot, and transcription factor assays. Results:, In OPM-2, RPMI-8226, U266 cell lines and primary MM cells, BSc2118 caused dose-dependent growth inhibitory effects. After 48 h, dose-dependent apoptosis occurred both in cell lines and primary myeloma cells irrespective of t(4;14). A significant G2-M cell cycle arrest occurred after 24 h. Furthermore, we observed a marked inhibition of intracellular proteasome activity, an increase in intracellular p21 levels, and an inhibition of NF-,B activation. The toxicity against PBMNC remained low, suggesting a broad therapeutic range of this agent. Conclusion:, Taken together, BSc2118 shows significant antimyeloma activity and may be considered as a promising agent in cancer drug development. [source] Functional epitope of common , chain for interleukin-4 bindingFEBS JOURNAL, Issue 5 2002Jin-Li Zhang Interleukin 4 (IL-4) can act on target cells through an IL-4 receptor complex consisting of the IL-4 receptor , chain and the common , chain (,c). An IL-4 epitope for ,c binding has previously been identified. In this study, the ,c residues involved in IL-4 binding were defined by alanine-scanning mutational analysis. The epitope comprises ,c residues I100, L102, and Y103 on loop EF1 together with L208 on loop FG2 as the major binding determinants. These predominantly hydrophobic determinants interact with the hydrophobic IL-4 epitope composed of residues I11, N15, and Y124. Double-mutant cycle analysis revealed co-operative interaction between ,c and IL-4 side chains. Several ,c residues involved in IL-4 binding have been previously shown to be mutated in X-linked severe combined immunodeficiency. The importance of these binding residues for ,c function is discussed. These results provide a basis for elucidating the molecular recognition mechanism in the IL-4 receptor system and a paradigm for other ,c -dependent cytokine receptor systems. [source] Pharmacological screening of bryophyte extracts that inhibit growth and induce abnormal phenotypes in human HeLa cancer cellsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2009Lucie Krzaczkowski Abstract Antitumor activities of substances from natural sources apart from vascular plants and micro-organisms have been poorly investigated. Here we report on a pharmacological screening of a bryophyte extract library using a phenotypic cell-based assay revealing microtubules, centrosomes and DNA. Among the 219 moss extracts tested, we identified 41 extracts acting on cell division with various combinations of significant effects on interphasic and mitotic cells. Seven extracts were further studied using a cell viability assay, cell cycle analysis and the phenotypic assay. Three distinct pharmacological patterns were identified including two unusual phenotypes. [source] Greenhouse gas emissions from four bioenergy crops in England and Wales: Integrating spatial estimates of yield and soil carbon balance in life cycle analysesGCB BIOENERGY, Issue 4 2009JONATHAN HILLIER Abstract Accurate estimation of the greenhouse gas (GHG) mitigation potential of bioenergy crops requires the integration of a significant component of spatially varying information. In particular, crop yield and soil carbon (C) stocks are variables which are generally soil type and climate dependent. Since gaseous emissions from soil C depend on current C stocks, which in turn are related to previous land management it is important to consider both previous and proposed future land use in any C accounting assessment. We have conducted a spatially explicit study for England and Wales, coupling empirical yield maps with the RothC soil C turnover model to simulate soil C dynamics. We estimate soil C changes under proposed planting of four bioenergy crops, Miscanthus (Miscanthus×giganteus), short rotation coppice (SRC) poplar (Populus trichocarpa Torr. & Gray ×P. trichocarpa, var. Trichobel), winter wheat, and oilseed rape. This is then related to the former land use , arable, pasture, or forest/seminatural, and the outputs are then assessed in the context of a life cycle analysis (LCA) for each crop. By offsetting emissions from management under the previous land use, and considering fossil fuel C displaced, the GHG balance is estimated for each of the 12 land use change transitions associated with replacing arable, grassland, or forest/seminatural land, with each of the four bioenergy crops. Miscanthus and SRC are likely to have a mostly beneficial impact in reducing GHG emissions, while oilseed rape and winter wheat have either a net GHG cost, or only a marginal benefit. Previous land use is important and can make the difference between the bioenergy crop being beneficial or worse than the existing land use in terms of GHG balance. [source] Does nicotine influence cytokine profile and subsequent cell cycling/apoptotic responses in inflammatory bowel disease?INFLAMMATORY BOWEL DISEASES, Issue 11 2008Marian C. Aldhous PhD Abstract Background: Smoking differentially influences susceptibility to the inflammatory bowel diseases (IBDs) Crohn's disease (CD) and ulcerative colitis (UC). We investigated the effects of nicotine on cytokine, cell cycle, and apoptotic responses in peripheral blood mononuclear cells (PBMCs) from IBD patients and healthy controls (HCs). Methods: PBMCs from IBD patients and HC were stimulated with lipopolysaccharide (LPS; 1 ,g/mL) or phytohemagglutinin (PHA, 5 or 0.5 ,g/mL), ± nicotine (1, 10, 100 ,g/mL). Cytokines (IL1,, IL2, IL10, IL12/IL23p40, TGF,, TNF,) were measured in supernatants at 24 hours. After 72 hours cells were analyzed by flow cytometry for cell cycle and apoptosis. Statistical modeling was used to identify interactions between cytokines and cell cycle / apoptosis and minimize confounding effects. Results: Stimulation by LPS and PHA (5 ,g/mL) increased IL12/IL23p40 production from CD and UC versus HC (P < 0.05); PHA (0.5 ,g/mL) increased IL1, in UC and decreased TGF, from CD and UC (P < 0.01). In all groups, nicotine reduced LPS- and PHA (0.5 ,g/mL)-stimulated production of IL1,, IL10, TGF,, and TNF, (P < 0.001). Cell cycle analysis showed that PHA, but not LPS, induced proliferation and decreased G0/G1 resting cells in CD and UC versus HC (P < 0.001). Nicotine decreased PHA-stimulated S-phase proliferation and increased G0/G1 resting cells (P < 0.01). Modeling showed independent associations between IL12/IL23p40 and apoptosis (P = 0.01), IL1, and resting cells (P = 0.006), TNF, and proliferating cells (P < 0.001). Disease activity and smoking habit had no effect. Conclusions: Dysregulated cytokine profiles in UC and CD are associated with specific alterations in cell cycle responses; these effects may be modified by nicotine, and potentially by anticytokine therapies. (Inflamm Bowel Dis 2008) [source] Seliciclib (CYC202, R-roscovitine) enhances the antitumor effect of doxorubicin in vivo in a breast cancer xenograft modelINTERNATIONAL JOURNAL OF CANCER, Issue 2 2009Maria Virginia C.L. Appleyard Abstract We sought to determine whether seliciclib (CYC202, R-roscovitine) could increase the antitumor effects of doxorubicin, with no increase in toxicity, in an MCF7 breast cancer xenograft model. The efficacy of seliciclib combined with doxorubicin was compared with single agent doxorubicin or seliciclib administered to MCF7 cells and to nude mice bearing established MCF7 xenografts. Post-treatment cells and tumors were examined by cell cycle analysis, immunohistochemistry and real-time PCR. Seliciclib significantly enhanced the antitumor effect of doxorubicin without additional murine toxicity. MIB1 (ki67) immunohistochemistry demonstrated reduced proliferation with treatment. The levels of p21 and p27 increased after treatment with doxorubicin or seliciclib alone or in combination, compared to untreated controls. However, no changes in p53 protein (DO1, CM1), survivin or p53 phosphorylation (SER15) were observed in treated tumors compared with controls. In conclusion, the CDK inhibitor seliciclib (R-roscovitine) enhances the antitumor effect of doxorubicin in MCF7 tumors without increased toxicity with a mechanism that involves cell cycle arrest rather than apoptosis. © 2008 Wiley-Liss, Inc. [source] Relevance of a new rat model of osteoblastic metastases from prostate carcinoma for preclinical studies using zoledronic acidINTERNATIONAL JOURNAL OF CANCER, Issue 4 2008François Lamoureux Abstract Animal models that mimic osteoblastic metastases associated with prostate carcinoma are required to improve the therapeutic options in humans. A new model was then developed and characterized in immunocompetent rats. The bisphosphonate zoledronic acid (ZOL) was tested to validate this model as a therapeutic application. Rat AT6-1 prostate tumor cells were characterized in vitro at the transcriptional (bone and epithelial markers) and functional (induction of mineralized nodules) levels. The bone lesions induced after their direct injection into the femur bone marrow were characterized by radiography, microscanner and histology analyses. ZOL effects were studied in vivo on bone lesion development and in vitro on AT6-1 cell proliferation, apoptosis and cell cycle analysis. Apart from epithelial markers, AT6-1 cells express an osteoblast phenotype as they express osteoblastic markers and are able to induce mineralized nodule formation in vitro. A disorganization of the trabecular bone at the growth zone level was observed in vivo after intraosseous AT6-1 cell injection as well as cortical erosion. The tumor itself is associated with bone formation as revealed by SEM analysis and polarized light microscopy. ZOL prevents the development of such osteoblastic lesions, related to a direct inhibitory effect on tumor cell proliferation independent of caspase 3 activation, but associated with cell cycle arrest. A new rat model of osteoblastic bone metastases was validated in immunocompetent rats and used to show the relevance of using ZOL in such lesions, as this compound shows bifunctional effects on both bone remodelling and tumor cell proliferation. © 2007 Wiley-Liss, Inc. [source] The use of histone deacetylase inhibitor FK228 and DNA hypomethylation agent 5-azacytidine in human bladder cancer therapyINTERNATIONAL JOURNAL OF CANCER, Issue 8 2007Jose A. Karam Abstract The long-term disease-free survival in patients with metastatic transitional cell carcinoma (TCC) is still considerably low. Novel chemotherapeutic agents are needed to decrease the morbidity and mortality of TCC. In this study, we have evaluated several epigenetic modifiers for their therapeutic application in bladder cancer. Both histone deacetylase inhibitors (FK228, TSA) and DNA hypomethylating agent (5-Azacytidine) were tested using in vitro assays such as cell viability, cell cycle analysis and western blot to determine their mechanisms of action. Drug combination experiments were also designed to study any additive or synergistic effects of these agents. In addition, two bladder cancer xenograft models (one subcutaneous and one orthotopic) were employed to assess the therapeutic efficacy of these agents in vivo. Three agents exhibited various growth inhibitory effects on 5 different TCC cell lines in a dose- and time-dependent manner. In addition to G2/M cell cycle arrest, FK228 is more potent in inducting apoptosis than the two other single agents, and combination of both FK228 and 5-Aza further enhances this effect. p21 induction is closely associated with FK228 or TSA but not 5-Aza, which is mediated via p53-independent pathway. Consistent with in vitro results, FK228 exhibited a significant in vivo growth inhibition of TCC tumor in both subcutaneous and orthotopic xenograft models. FK228 is a potent chemotherapeutic agent for TCC in vivo with minimal undesirable side effects. The elevated p21 level mediated via p53 independent pathway is a hallmark of FK228 mechanism of action. © 2007 Wiley-Liss, Inc. [source] Thermodynamic analysis of spark-ignition engine using a gas mixture model for the working fluidINTERNATIONAL JOURNAL OF ENERGY RESEARCH, Issue 11 2007E. Abu-Nada Abstract This paper presents thermodynamic analysis of spark-ignition engine. A theoretical model of Otto cycle, with a working fluid consisting of various gas mixtures, has been implemented. It is compared to those which use air as the working fluid with variable temperature specific heats. A wide range of engine parameters were studied, such as equivalence ratio, engine speed, maximum and outlet temperatures, brake mean effective pressure, gas pressure, and cycle thermal efficiency. For example, for the air model, the maximum temperature, brake mean effective pressure (BMEP), and efficiency were about 3000 K, 15 bar, and 32%, respectively, at 5000 rpm and 1.2 equivalence ratio. On the other hand, by using the gas mixture model under the same conditions, the maximum temperature, BMEP, and efficiency were about 2500 K, 13.7 bar, and 29%. However, for the air model, at lower engine speeds of 2000 rpm and equivalence ratio of 0.8, the maximum temperature, BMEP, and efficiency were about 2000 K, 8.7 bar, and 28%, respectively. Also, by using the gas mixture model under these conditions, the maximum temperature, BMEP, and efficiency were about 1900 K, 8.4 bar, and 27%, i.e. with insignificant differences. Therefore, it is more realistic to use gas mixture in cycle analysis instead of merely assuming air to be the working fluid, especially at high engine speeds. Copyright © 2007 John Wiley & Sons, Ltd. [source] Analysis of an unconventional cycle as a new comparison standard for practical heat engines: the circular/elliptical cycle in T,S diagramINTERNATIONAL JOURNAL OF ENERGY RESEARCH, Issue 13 2004Bahri Sahin Abstract An unconventional cycle analysis in the T,S diagram has been carried out and the cycle characteristics such as thermal efficiency, work density (defined as the ratio of the network output to the maximum volume in the cycle), maximum volume and maximum pressure are determined. The obtained results for the unconventional cycle are compared with those of the Carnot cycle. It is proposed that the analysed unconventional cycle may be used as a better comparison standard than the Carnot cycle for practical heat engines when both size and thermal efficiency are considered. Copyright © 2004 John Wiley & Sons, Ltd. [source] Importance of C16 ceramide accumulation during apoptosis in prostate cancer cellsINTERNATIONAL JOURNAL OF UROLOGY, Issue 2 2006MASATOSHI ETO Aim:, Adenocarcinoma of the prostate is one of the most frequently diagnosed non-cutaneous cancers and the second leading cause of cancer-related deaths among men in the United States. To fully understand the role of ceramide during apoptosis induced by androgen ablation, we modified the levels of intracellular ceramide by pharmacological agents as well as through serum deprivation in androgen-dependent and independent cell lines. Methods:, Ceramide levels were modified using N-oleoylethanolamine (NOE), sphingosine-1-phosphate (S1P) as well as through serum deprivation, in LNCaP, DU145 and PC-3 prostate cancer cells. Various methods including nonyl acridine orange staining, propidium iodide staining/cell cycle analysis and lipid analysis were utilized. Results:, Our results demonstrate that the inhibition of acid ceramidase by NOE enhances the intracellular ceramide levels induced by androgen ablation in androgen-dependent LNCaP cells, and is accompanied by an increase in apoptotic cells. Sphingosine 1-phosphate had no effect in rescuing LNCaP cells from apoptosis induced by androgen ablation. Our results also show that serum deprivation causes intracellular ceramide accumulation and apoptosis in androgen-independent prostate cancer cells. Conclusions:, Our studies indicate that the increase in intracellular ceramide itself, but not the balance between ceramide and S1P, determines whether LNCaP cells undergo apoptosis. Our results also show that the increase in intracellular ceramide strongly correlates with apoptosis induced by serum deprivation even in androgen-independent prostate cancer cell lines. [source] Estimating Trends with Percentage of Smoothness Chosen by the UserINTERNATIONAL STATISTICAL REVIEW, Issue 2 2008Victor M. Guerrero Summary This work presents a method for estimating trends of economic time series that allows the user to fix at the outset the desired percentage of smoothness for the trend. The calculations are based on the Hodrick-Prescott (HP) filter usually employed in business cycle analysis. The situation considered here is not related to that kind of analysis, but with describing the dynamic behaviour of the series by way of a smooth curve. To apply the filter, the user has to specify a smoothing constant that determines the dynamic behaviour of the trend. A new method that formalizes the concept of trend smoothness is proposed here to choose that constant. Smoothness of the trend is measured in percentage terms with the aid of an index related to the underlying statistical model of the HP filter. Empirical illustrations are provided using data on Mexico's GDP. Résumé Ce travail présente un méthode pour estimer les tendances des séries de temps économiques qui permet à l'usager fixer dès début le pourcentage désiré de douceur pour la tendance. Les calculs ont fondement en le filtre de Hodrick et Prescott que s'emploie généralement dans l'analyse de cycles économiques. La situation ici considéré n'a pas relation avec ce type d'analyse, mais comment la description du comportement dynamique des séries avec une courbe douce. Pour appliquer le filtre, l'usager a besoin de spécifier une constante de douceur que détermine le comportement dynamique de la tendance. Un nouveau méthode que formalise le concept de douceur de la tendance est ici proposé pour choisir la constante. La douceur de la tendance est mesuré en termes de pourcentage avec l'aide d'un index rapporté avec le modèle statistique après le filtre. Quelques illustrations empiriques sont munies avec données de l'économie mexicaine. [source] S100A6 (calcyclin) deficiency induces senescence-like changes in cell cycle, morphology and functional characteristics of mouse NIH 3T3 fibroblastsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2010omnicki, ukasz P. S Abstract S100A6 (calcyclin) is a calcium binding protein with two EF-hand structures expressed mostly in fibroblasts and epithelial cells. We have established a NIH 3T3 fibroblast cell line stably transfected with siRNA against S100A6 to examine the effect of S100A6 deficiency on non-transformed cell physiology. We found that NIH 3T3 fibroblasts with decreased level of S100A6 manifested altered cell morphology and proliferated at a much slower pace than the control cells. Cell cycle analysis showed that a large population of these cells lost the ability to respond to serum and persisted in the G0/G1 phase. Furthermore, fibroblasts with diminished S100A6 level exhibited morphological changes and biochemical features of cellular senescence as revealed by ,-galactosidase and gelatinase assays. Also, S100A6 deficiency induced changes in the actin cytoskeleton and had a profound impact on cell adhesion and migration. Thus, we have shown that the S100A6 protein is involved in multiple aspects of fibroblast physiology and that its presence ensures normal fibroblast proliferation and function. J. Cell. Biochem. 109: 576,584, 2010. © 2009 Wiley-Liss, Inc. [source] Effects of histone deacetylase inhibitors on p55CDC/Cdc20 expression in HT29 cell lineJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2006Giuseppe Iacomino Abstract In a previous work, taking advantage of the gene-array screening technology, we analysed the effects of histone deacetylase (HDAC) inhibitor sodium butyrate (NaBt), on gene transcription in HT29 human adenocarcinoma cell line. In this study, we focused our attention on p55CDC/Cdc20 gene, whose expression was dramatically reduced by NaBt treatment. Mammalian p55CDC/Cdc20 interacts with the anaphase promoting complex/cyclosome (APC/C), and is involved in regulating anaphase onset and late mitotic events. Using NaBt and trichostatin A (TSA), a member of the HDAC inhibitor family, we showed that both HDAC inhibitors totally downregulated p55CDC/Cdc20 transcription and expression. Cell cycle analysis demonstrated that NaBt arrested HT29 cells in G0/G1 phase, while TSA caused a double block in G0/G1 and G2/M phases. Moreover, p55CDC/Cdc20 showed maximal expression in S and G2/M phases of HT29 cell division cycle. Based on this evidence, and by means of specific cell cycle modulators, such as nocodazole and hydroxyurea, we demonstrated that both TSA and NaBt were responsible for loss of p55CDC/Cdc20 expression, but with different mechanisms of action. Taken together, these results suggest that targeting molecules involved in spindle mitotic checkpoint, such as p55CDC/Cdc20, might account for the high cytotoxicity of HDAC inhibitors versus malignant cells. J. Cell. Biochem. 99: 1122,1131, 2006. © 2006 Wiley-Liss, Inc. [source] Forecast accuracy and economic gains from Bayesian model averaging using time-varying weightsJOURNAL OF FORECASTING, Issue 1-2 2010Lennart Hoogerheide Abstract Several Bayesian model combination schemes, including some novel approaches that simultaneously allow for parameter uncertainty, model uncertainty and robust time-varying model weights, are compared in terms of forecast accuracy and economic gains using financial and macroeconomic time series. The results indicate that the proposed time-varying model weight schemes outperform other combination schemes in terms of predictive and economic gains. In an empirical application using returns on the S&P 500 index, time-varying model weights provide improved forecasts with substantial economic gains in an investment strategy including transaction costs. Another empirical example refers to forecasting US economic growth over the business cycle. It suggests that time-varying combination schemes may be very useful in business cycle analysis and forecasting, as these may provide an early indicator for recessions. Copyright © 2009 John Wiley & Sons, Ltd. [source] Molecular determinants of ginkgolide binding in the glycine receptor poreJOURNAL OF NEUROCHEMISTRY, Issue 2 2006Rebecca Hawthorne Abstract Ginkgolides are potent blockers of the glycine receptor Cl, channel (GlyR) pore. We sought to identify their binding sites by comparing the effects of ginkgolides A, B and C and bilobalide on ,1, ,2, ,1, and ,2, GlyRs. Bilobalide sensitivity was drastically reduced by incorporation of the , subunit. In contrast, the sensitivities to ginkgolides B and C were enhanced by , subunit expression. However, ginkgolide A sensitivity was increased in the ,2, GlyR relative to the ,2 GlyR but not in the ,1, GlyR relative to the ,1 GlyR. We hypothesised that the subunit-specific differences were mediated by residue differences at the second transmembrane domain 2, and 6, pore-lining positions. The increased ginkgolide A sensitivity of the ,2, GlyR was transferred to the ,1, GlyR by the G2,A (,1 to ,2 subunit) substitution. In addition, the ,1 subunit T6,F mutation abolished inhibition by all ginkgolides. As the ginkgolides share closely related structures, their molecular interactions with pore-lining residues were amenable to mutant cycle analysis. This identified an interaction between the variable R2 position of the ginkgolides and the 2, residues of both ,1 and , subunits. These findings provide strong evidence for ginkgolides binding at the 2, pore-lining position. [source] Effects of adenoviral-mediated coexpression of bone morphogenetic protein-7 and insulin-like growth factor-1 on human periodontal ligament cellsJOURNAL OF PERIODONTAL RESEARCH, Issue 4 2010L. Yang Yang L, Zhang Y, Dong R, Peng L, Liu X, Wang Y, Cheng X. Effects of adenoviral-mediated coexpression of bone morphogenetic protein-7 and insulin-like growth factor-1 on human periodontal ligament cells. J Periodont Res 2010; 45: 532,540. © 2010 John Wiley & Sons A/S Background and Objective:, Bone morphogenetic protein-7 (BMP-7) and insulin-like growth factor-1 (IGF-1) are important in periodontal reconstruction. However, their synergistic effect in periodontal regeneration by gene delivery has not been reported. In this study, gene delivery of these two growth factors to human periodontal ligament cells (hPDLCs) was examined for its effects on cell proliferation and differentiation. Material and Methods:, Recombinant adenoviruses containing both human BMP-7 and IGF-1 cDNA created by introducing the internal ribosome entry site (IRES) sequence were used to transfer the genes into hPDLCs. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell cycle analysis were used to observe their effects on cell proliferation, while alkaline phosphatase activity measurement, RT-PCR and in vivo tests were conducted to investigate their effects on cell differentiation. Results:, The proliferation of hPDLCs transduced by adenoviruses coexpressing BMP-7 and IGF-1 was suppressed while their differentiation ability was enhanced. There was a synergism of BMP-7 and IGF-1 in up-regulating alkaline phosphatase activity and mRNA levels of collagen type I and Runx2. Implantation in vivo with scaffolds illustrated that the transduced cells exhibited osteogenic differentiation and formed bone-like structures. Conclusion:, The combined delivery of BMP-7 and IGF-1 genes using an IRES-based strategy synergistically enhanced differentiation of hPDLCs. It is suggested that this could be a new potential method in gene therapy for periodontal reconstruction. [source] Hydrogen sulfide inhibits cell proliferation and induces cell cycle arrest via an elevated p21Cip1 level in Ca9-22 cellsJOURNAL OF PERIODONTAL RESEARCH, Issue 1 2008H. Takeuchi Background and Objective:, Volatile sulfur compounds such as hydrogen sulfide (H2S) and methyl mercaptan (CH3SH) are the main causes of oral malodor. However, the physiological functions of H2S have not been investigated in oral tissues. The aim of this study was to evaluate the effect of H2S on cell proliferation and the cell cycle in oral epithelial-like cells. Material and Methods:, Ca9-22 cells were used in this study. Cells were cultured in 5% CO2/95% air with (5 or 10 ng/mL) or without H2S. DNA synthesis was measured using a 5-bromo-2-deoxyuridine enzyme-linked immunosorbent assay. The cell cycle was analyzed using a flow cytometer. The expressions of phosphorylated retinoblastoma protein (Rb), p21Cip1 and p27Kip1 were evaluated by western blotting. Results:, Exposure to 5 and 10 ng/mL of H2S significantly decreased DNA synthesis (p < 0.05). Cell cycle analysis also showed that exposure to both concentrations of H2S significantly increased the proportion of cells in G1 phase (p < 0.001) and significantly decreased the proportion of cells in S phase (p < 0.01). Western blotting showed that Rb phosphorylation was reduced and p21Cip1 was enhanced by exposure to H2S. Conclusion:, The results indicated that H2S inhibits cell proliferation and induces cell cycle arrest via the expression of p21Cip1 in Ca9-22 cells. [source] Differential expression of periodontal ligament-specific markers and osteogenic differentiation in human papilloma virus 16-immortalized human gingival fibroblasts and periodontal ligament cellsJOURNAL OF PERIODONTAL RESEARCH, Issue 2 2007S.-H. Pi Background and Objective:, Periodontal ligament cells and gingival fibroblasts are important in the remodeling of periodontal tissue, but human papilloma virus (HPV)16-immortalized cell lines derived from human periodontal ligament cells and gingival fibroblasts has not been characterized. The purpose of this study was to establish and differentially characterize the immortalized cell lines from gingival fibroblasts and periodontal ligament by HPV16 transfection. Material and Methods:, Cell growth, cell cycle analysis, western blot for cell cycle regulatory proteins and osteogenic differentiation markers, and reverse transcription,polymerase chain reaction for periodontal ligament-specific markers were performed. Results:, Both immortalized cell lines (immortalized gingival fibroblasts and immortalized periodontal ligament cells) grew faster than primary cultured gingival fibroblasts or periodontal ligament cells. Immortalized gingival fibroblasts and immortalized periodontal ligament cells overexpressed proteins p16 and p21, and exhibited degradation of proteins pRb and p53, which normally cause cell cycle arrest in G2/M-phase. Western blotting and reverse transcription,polymerase chain reaction for periodontal ligament-specific and osteogenic differentiation marker studies demonstrated that a cell line, designated IPDL, mimicked periodontal ligament gene expression for alkaline phosphatase, osteonectin, osteopontin, bone sialoprotein, bone morphogenic protein-2, periostin, S-100A4 and PDLs17. Conclusion:, These results indicate that IPDL and immortalized gingival fibroblast cell lines consistently retain normal periodontal ligament and gingival fibroblast phenotypes, respectively, and periodontal ligament markers and osteogenic differentiation in IPDL are distinct from immortalized gingival fibroblast cells. [source] | ||||||||||||||||||||||||||||||||||||||||