bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical modeling of cohesive sediments dynamics in estuaries: Part I—Description of the model and simulations in the Po River Estuary
Authors: Leupi C. , Altinakar M. S. , Deville M.
Published: October 2007

The present work contributes to the numerical modeling of complex turbulent multiphasic fluid flows occurring in estuarine channels. This research finds its motivation in the increasing need for efficient management of estuaries by taking into account the complex turbulent stratified flows encountered in estuaries and costal zones. A time‐dependent, 3D finite element model of suspended sediment transport taking into account the effects of cohesiveness between sediments is presented. The model estuary is the forced time‐dependent winds, time elevation at open boundaries and river discharge. To cope with the stiffness problems a decoupling method is employed to solve the shallow‐water equations of mass conservation, momentum and suspended sediment transport with the conventional hydrostatic pressure. The decoupling method partitions a time step into three subcycles according to the physical phenomena. In the first sub‐cycle thepure hydrodynamicsincluding thek–ε turbulence model is solved, followed by the advection–diffusion equations for pollutants (salinity, temperature, suspended sediment concentration, (SSC)), and finally the bed evolution is solved. The model uses a mass‐preserving method based on the so‐called Raviart–Thomas finite element on the unstructured mesh in the horizontal plane, while the multi‐layers system is adopted in vertical with the conventional conforming finite element method, with the advantage that the lowermost and uppermost layers of variable height allow a faithful representation of the time‐varying bed and free surface, respectively. The model has been applied to investigate the SSC and seabed evolution in Po River Estuary (PRE) in Italy. The computed results mimic the field data well. Copyright © 2007 John Wiley & Sons, Ltd.
Im Wettlauf um die besten Köpfe
Authors: Finetti Marco
Published: October 2007

DFG fordert mehr Geld und mehr Freiheit für die Wissenschaft – Kleiner: Bezahlung unserer Forscher ist eine Schande für ein hochentwickeltes Land
Irreführend und gefährlich
Authors: Hacker Jörg Hinrich
Published: October 2007

Wissenschaft wider Kreationismus und Intelligent Design: Die biblische Schöpfungslehre eignet sich nicht zur Beschreibung der Evolution
Die Geheimnisse des „gläsernen Berges”︁
Authors: Heide Klaus
Published: October 2007

Auch in der Natur kommen Gläser vor. Wenn ihre Entstehungsmechanismen und Eigenschaften erforscht werden, ist das zugleich für die Schaffung neuer Materialien und für technische Anwendungen von großem Wert
Was brauchen die Geisteswissenschaften?
Authors: Honemann Volker , Schlögl Rudolf
Published: October 2007

„Selbstbewusst und exzellent”︁ – der Kommentar der Frankfurter Neuzeithistorikerin und DFG‐Vizepräsidentin Luise Schorn‐Schütte zur Lage und Zukunft der Geisteswissenschaften in „forschung 1/2007”︁ löste ein vielfältiges Echo aus. Im Folgenden dokumentieren wir zwei ausgewählte Zuschriften, die die wichtigsten Kritikpunkte bündeln. Die damit begonnene Debatte wird Luise Schorn‐Schütte in der nächsten „forschung”︁ fortführen.
Acquired genomic aberrations associated with methotrexate resistance vary with background genomic instability
Authors: Snijders Antoine M. , Hermsen Mario A. , Baughman Joshua , Buffart Tineke E. , Huey Bing , Gajduskova Pavla , Roydasgupta Ritu , Tokuyasu Taku , Meijer Gerrit A. , Fridlyand Jane , Albertson Donna G.
Published: October 2007

Tumors vary widely in chromosomal level genome instability. To gain a better understanding of the underlying defects which foster specific types of aberrations, we investigated the response of cells of related genetic backgrounds to challenge with methotrexate. We studied mismatch repair deficient HCT116 cells, two derivatives also deficient in XRCC5 (HCT116 Ku86+/−) or BLM (HCT116 BLM−/−), and mismatch repair competent HCT116+chr3 cells. We show that colony formation occurred at a significantly higher frequency in HCT116 cells and HCT116 Ku86+/− cells compared to HCT116 BLM−/− and HCT116+chr3 cells. Visible colonies arose most rapidly in HCT116 Ku86+/− cells, whereas they formed most slowly in HCT116+chr3 cells. Copy number changes acquired by the methotrexate resistant HCT116 and HCT116 BLM−/− cells most often included whole chromosome gains or losses or no acquired copy number changes, whereas resistance in HCT116+chr3 and HCT116 Ku86+/− cells was associated with amplification of DHFR and copy number transitions leading to increased copy number of DHFR, respectively. The additional copies of DHFR were present on unstable chromosomes and organized as inverted repeats in HCT116+chr3 cells, while they were most often present as direct repeats in HCT116 Ku86+/− cells. These observations suggest that different mutational mechanisms promote drug resistance in these genetic backgrounds; mismatch repair deficiency in HCT116, high rates of chromosomal instability in HCT116 Ku86+/−, and low rates of chromosomal instability in HCT116+chr3. On the other hand, it appears that loss of BLM function suppresses the mismatch repair mutator mechanism in mismatch repair and BLM deficient HCT116 BLM−/− cells. © 2007 Wiley‐Liss, Inc.
Pegylated interferon alpha-2b plus ribavirin in patients with genotype 4 chronic hepatitis C: The role of rapid and early virologic response
Authors: Kamal Sanaa M. , El Kamary Samer S. , Shardell Michelle D. , Hashem Mohamed , Ahmed Imad N. , Muhammadi Mohamed , Sayed Khalifa , Moustafa Ashraf , Hakem Sarah Abdel , Ibrahiem Amany , Moniem Mohamed , Mansour Hoda , Abdelaziz Mohamed
Published: October 2007

In patients chronically infected with hepatitis C virus (HCV) genotype 4, the optimum duration of therapy and the predictors of sustained virologic response (SVR) have not been adequately determined. In this study, 358 patients with chronic hepatitis C genotype 4 were randomly assigned to pegylated interferon (PEG-IFN) alpha-2b (1.5 μg/kg/week) plus oral ribavirin (10.6 mg/kg/day) for a fixed duration of 48 weeks (control group, n = 50) or for a variable duration (n = 318). In the variable-duration group, patients with undetectable HCV RNA at week 4 were treated for 24 weeks (group A, n = 69), patients with undetectable HCV RNA at week 12 were treated for 36 weeks (group B, n = 79), and the rest of the patients were treated for 48 weeks (group C, n = 160). The primary endpoint was SVR (undetectable HCV RNA 24 weeks after treatment cessation). Groups A-C and the control group had SVR rates of 86%, 76%, 56%, and 58%, respectively. After the study was controlled for predictors, a low baseline histologic grade and stage were associated with SVR (

P

< 0.029) in all groups. In addition, among patients in group C, older age (

P

= 0.04), a higher baseline body mass index (

P

= 0.013), and low baseline HCV RNA (

P

< 0.001) were also associated with SVR attainment. The incidence of adverse events and the rate of discontinuation were higher in patients in the variable-duration and fixed-duration groups treated for 48 weeks.

Conclusion:

In patients with chronic hepatitis C genotype 4 and undetectable HCV RNA at weeks 4 and 12, treatment with PEG-IFN alpha-2b and ribavirin for 24 weeks and 36 weeks, respectively, is sufficient. (Hepatology 2007.)
Hepatitis C virus cell-cell transmission in hepatoma cells in the presence of neutralizing antibodies
Authors: Timpe Jennifer M. , Stamataki Zania , Jennings Adam , Hu Ke , Farquhar Michelle J. , Harris Helen J. , Schwarz Anne , Desombere Isabelle , Roels Geert Leroux , Balfe Peter , McKeating Jane A.
Published: October 2007

Hepatitis C virus (HCV) infection of Huh-7.5 hepatoma cells results in focal areas of infection where transmission is potentiated by cell-cell contact. To define route(s) of transmission, HCV was allowed to infect hepatoma cells in the presence or absence of antibodies that neutralize cell-free virus infectivity. Neutralizing antibodies (nAbs) reduced cell-free virus infectivity by >95% and had minimal effect(s) on the frequency of infected cells in the culture. To assess whether cell-cell transfer of viral infectivity occurs, HCV-infected cells were cocultured with fluorescently labeled naïve cells in the presence or absence of nAbs. Enumeration by flow cytometry demonstrated cell-cell transfer of infectivity in the presence or absence of nAbs and immunoglobulins from HCV+ patients. The host cell molecule CD81 and the tight junction protein Claudin 1 (CLDN1) are critical factors defining HCV entry. Soluble CD81 and anti-CD81 abrogated cell-free infection of Huh-7.5 and partially inhibited cell-cell transfer of infection. CD81-negative HepG2 hepatoma cells were resistant to cell-free virus infection but became infected after coculturing with JFH-infected cells in the presence of nAb, confirming that CD81-independent routes of cell-cell transmission exist. Further experiments with 293T and 293T-CLDN1 targets suggested that cell-cell transmission is dependent on CLDN1 expression.

Conclusion:

These data suggest that HCV can transmit

in vitro

by at least two routes, cell-free virus infection and direct transfer between cells, with the latter offering a novel route for evading nAbs. (Hepatology 2007.)
A study on thermal conductivity of a quasi‐ordered liquid layer on a solid substrate
Authors: Shi Xiao‐Yan , Zeng Dan‐Ling , Li You‐Rong
Published: October 2007

In the present paper, a study on thermal conductivity of a quasi‐ordered liquid layer on a solid surface was performed by molecular dynamic simulation. Results showed that the motion of the molecules and their radial distribution function in the quasi‐ordered liquid layer were similar to those of solid molecules. By using the Green–Kubo formula, the thermal conductivity of the layer was calculated. It was found that it increased with the increase of the parameters of ordering. The size effect and the influence of the boundary condition were also discussed. © 2007 Wiley Periodicals, Inc. Heat Trans Asian Res, 36(7): 429–434, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20171
A study on membrane distillation by a solar thermal‐driven system
Authors: Chen Tsung‐Ching , Ho Chii‐Dong , Guo Jia‐Jan , Tu Jr‐Wei
Published: October 2007

Membrane distillation (MD) is a membrane separation process that has long been investigated in small scale laboratory studies and has the potential to become a viable tool for water desalination. MD is a separation process that combines simultaneous mass and heat transfer through a hydrophobic microporous membrane. A solar collector is used in direct contact membrane distillation (DCMD) to heat seawater as a temperature driving force in heat transfer to establish seawater desalting systems. The effect of the temperature difference makes the brine vaporize in the hot fluid side and condense in the cold fluid side. The optimal operating parameters on the pure water production rate will also be examined in this study. The purposes of this study are to develop the theoretical heat and mass transfer formulations, simulate heat transfer rate of solar collector with internal fins in membrane distillation, and investigate the mass‐transfer efficiency improvement in membrane distillation with the brine flow rate, solar collector efficiency, and temperature difference between both sides of membrane as parameters. © 2007 Wiley Periodicals, Inc. Heat Trans Asian Res, 36(7): 417–428, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20172
Experimental and numerical investigation of circularly lobed ejector with bend mixers
Authors: Liu You‐Hong , Liu Wei
Published: October 2007

The vent pipe for a turbo shaft engine may be required to have a lobed nozzle installed and to bend for the purpose of infrared stealth. The experimental setup was a circular 12‐lobed nozzle with bend mixers to study the effects on the pumping performance of the lobed bend mixer parameters. The experimental results show that the pumping ratio of the secondary mass flow to the primary mass flow for a mixer bend angle equal to 40° is the same as that for the same lobed nozzle with the same diameter cylindrical mixer that was used in the author's previous papers. There is a great decrease of the pumping ratio for a mixer bend angle larger than 40°. The higher the bend angles, the lower the pumping ratios. The pumping ratios initially increase and then decrease with the increasing of the cross‐area ratio of mixer to lobe. The optimal cross‐area ratio that corresponds to the maximum pumping ratio is strangely nearly equal to the optimal cross‐area ratio of a cylindrical mixer, although the maximum pumping ratio is less than that for a cylindrical mixer. The pumping ratios increase approximately linearly with the cross‐area ratio of the secondary inlet to the lobed nozzle. To investigate the flow characteristics and the pumping ratio changing mechanism, the flow field inside the ejector is numerically simulated. The numerical results show that the main reason for the great decrease of the pumping ratio when the mixer bend angle is larger than 40° is due to the great static pressure around the bend part, which is caused by the primary flow jet. The great static pressure around the bend section chokes back the exhausted secondary fluid flow. There is a good agreement between the calculated and the measured wall static pressure coefficients in the mixer wall along the lobe crest symmetry plane of the lobed ejector. © 2007 Wiley Periodicals, Inc. Heat Trans Asian Res, 36(7): 387–397, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20175
Effect of growing watershed imperviousness on hydrograph parameters and peak discharge
Authors: Huang Huang‐jia , Cheng Shin‐jen , Wen Jet‐chau , Lee Ju‐huang
Published: October 2007

An increasing impervious area is quickly extending over the Wu‐Tu watershed due to the endless demands of the people. Generally, impervious paving is a major result of urbanization and more recently has had the potential to produce more enormous flood disasters than those of the past. In this study, 40 available rainfall–runoff events were chosen to calibrate the applicable parameters of the models and to determine the relationships between the impervious surfaces and the calibrated parameters. Model inputs came from the outcomes of the block kriging method and the non‐linear programming method. In the optimal process, the shuffled complex evolution method and three criteria were applied to compare the observed and simulated hydrographs. The tendencies of the variations of the parameters with their corresponding imperviousness were established through regression analysis. Ten cases were used to examine the established equations of the parameters and impervious covers. Finally, the design flood routines of various return periods were furnished through use of approaches containing a design storm, block kriging, the SCS model, and a rainfall‐runoff model with established functional relationships. These simulated flood hydrographs were used to compare and understand the past, present, and future hydrological conditions of the watershed studied. In the research results, the time to peak of flood hydrographs for various storms was diminished approximately from 11 h to 6 h in different decrements, whereas peak flow increased respectively from 127 m3 s−1 to 629 m3 s−1 for different storm intensities. In addition, this study provides a design diagram for the peak flow ratio to help engineers and designers to construct hydraulic structures efficiently and prevent possible damage to human life and property. Copyright © 2007 John Wiley & Sons, Ltd.
A conceptual hydrologic model for a forested Carolina bay depressional wetland on the Coastal Plain of South Carolina, USA
Authors: Pyzoha Jennifer E. , Callahan Timothy J. , Sun Ge , Trettin Carl C. , Miwa Masato
Published: October 2007

This paper describes how climate influences the hydrology of an ephemeral depressional wetland. Surface water and groundwater elevation data were collected for 7 years in a Coastal Plain watershed in South Carolina USA containing depressional wetlands, known as Carolina bays. Rainfall and temperature data were compared with water‐table well and piezometer data in and around one wetland. Using these data a conceptual model was created that describes the hydrology of the system under wet, dry, and drought conditions. The data suggest this wetland operates as a focal point for groundwater recharge under most climate conditions. During years of below‐normal to normal rainfall the hydraulic gradient indicated the potential for groundwater recharge from the depression, whereas during years of above‐normal rainfall, the hydraulic gradient between the adjacent upland, the wetland margin, and the wetland centre showed the potential for groundwater discharge into the wetland. Using high‐resolution water‐level measurements, this groundwater discharge condition was found to hold true even during individual rainfall events, especially under wet antecedent soil conditions. The dynamic nature of the hydrology in this Carolina bay clearly indicates it is not an isolated system as previously believed, and our groundwater data expand upon previous hydrologic investigations at similar sites which do not account for the role of groundwater in estimating the water budget of such systems. Copyright © 2007 John Wiley & Sons, Ltd.
Delineation of spatial redox zones using discriminant analysis and geochemical modelling in arsenic‐affected alluvial aquifers
Authors: Lee Jin‐Jing , Jang Cheng‐Shin , Wang Sheng‐Wei , Liang Chin‐Ping , Liu Chen‐Wuing
Published: October 2007

This study characterized the redox conditions in arsenic‐affected groundwater aquifers of the Lanyang plain, Taiwan. Discriminant analysis was adopted to delineate three redox zones (oxidative, transitional and reductive zones) in different aquifers and yielded 92·3% correctness on groundwater quality data. Arsenic is mainly distributed in the reductive zone, and arsenic distribution in the shallow aquifer is mainly affected by surface activities. According to PHREEQC modelling results, possible mechanisms for arsenic release to groundwater in Lanyang plain are explored. Arsenic released to groundwater in the oxidative zone (zone 1) is primarily caused by the oxidations of arsenic‐bearing pyrite minerals, and arsenate is the predominant species. While the reductive dissolution of Fe‐oxides are responsible for the high arsenic concentration found in the transitional and reductive zones (zones 2 and 3), arsenite is the predominant species. The reduction potential of groundwater rises as the depths and zones increase. Some sulphates may be reduced to form sulphide ions, which then react with arsenic to form arseno‐sulphide deposits (such as realgar, orpiment) and then slightly lower groundwater arsenic concentrations. A conceptual diagram which summarized the possible release processes of arsenic in different redox zones along groundwater flow in Lanyang plain is postulated. Arsenic‐bearing pyrite and arsenopyrite (FeAsS) are oxidized as they are exposed to the infiltrated oxygenated rainwater, releasing soluble arsenate Fe(II) and SO42− into zone 1. The dissolution of arsenic‐rich Fe‐oxides due to the onset of reducing conditions in zones 2 and 3 is responsible for the mobility of arsenic and likely to be the primary mechanism of arsenic release to groundwater in the Lanyang plain Copyright © 2007 John Wiley & Sons, Ltd.
Estimation of suspended sediment loads and delivery in an incised upland headwater catchment, south‐eastern Australia
Authors: Smith Hugh G.
Published: October 2007

Historically upland headwater catchments in south‐eastern Australia have undergone extensive gully erosion that has removed large amounts of sediment to lowlands. Recent research suggests these upland areas may continue to dominate fine sediment loads in lowland rivers. Improved understanding of sediment transfer through upland headwater catchments may have implications for interpreting downstream sediment supply. In this study a nested catchment design was utilized to examine suspended sediment yields and delivery from a small tributary sub‐catchment (1·64 km2) to the study catchment outlet (53·5 km2). Monitoring of suspended sediment concentration and discharge was undertaken for a period of nearly two years and used to estimate suspended sediment loads. Estimated total suspended sediment exports over the period of monitoring were 24·16 t from the sub‐catchment and 550·3 t from the catchment, which are generally less than previous reported small catchment yields in south‐eastern Australia. The extent of sediment delivery was examined using between‐site ratios of specific sediment yield per unit area and incised channel length. Sediment delivery was high under average rainfall conditions, but seasonally dependent. Both suspended sediment yields and the extent of delivery peaked over spring months, supplemented by remobilization of sediment stored during summer months in the main catchment channel. The findings of this study suggest much of the suspended sediment exported from small incised upland sub‐catchments (1–2 km2) may be delivered to downstream reaches under average rainfall conditions, which, in conjunction with the findings of previous research supports the potential importance of contributions from these areas to suspended sediment loads in lowland rivers during high flow periods. Copyright © 2007 John Wiley & Sons, Ltd.
Cannabinoids in pancreatic cancer: Correlation with survival and pain
Authors: Michalski Christoph W. , Oti Florian E. , Erkan Mert , Sauliunaite Danguole , Bergmann Frank , Pacher Pal , Batkai Sandor , Müller Michael W. , Giese Nathalia A. , Friess Helmut , Kleeff Jörg
Published: October 2007

Cannabinoids exert antiproliferative properties in a variety of malignant tumors, including pancreatic ductal adenocarcinoma (PDAC). In our study, we quantitatively evaluated the immunoreactivity for cannabinoid‐1 (CB1) and cannabinoid‐2 (CB2) receptors as well as for the endocannabinoid metabolizing enzymes fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MGLL). Furthermore, quantitative real‐time RT‐PCR for CB1, CB2, FAAH and MGLL in normal pancreas and pancreatic cancer tissues was performed. Levels of endocannabinoids were determined by liquid chromatography/mass spectrometry. Immunoreactivity scores and QRT‐PCR expression levels were correlated with the clinico‐pathological (TNM, survival, pain) status of the patients. Evaluation of endocannabinoid levels revealed that these remained unchanged in PDAC compared to the normal pancreas. Patients with high CB1 receptor levels in enlarged nerves in PDAC had a lower combined pain score (intensity, frequency, duration; p = 0.012). There was a significant relationship between low CB1 receptor immunoreactivity or mRNA expression levels (p = 0.0011 and p = 0.026, respectively), or high FAAH and MGLL cancer cell immunoreactivity (p = 0.036 and p = 0.017, respectively) and longer survival of PDAC patients. These results are underlined by a significant correlation of high pain scores and increased survival (p = 0.0343). CB2 receptor immunoreactivity, CB2 receptor, FAAH and MGLL mRNA expression levels did not correlate with survival. Therefore, changes in the levels of endocannabinoid metabolizing enzymes and cannabinoid receptors on pancreatic cancer cells may affect prognosis and pain status of PDAC patients. © 2007 Wiley‐Liss, Inc.
E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition
Authors: Matsui Junji , Yamamoto Yuji , Funahashi Yasuhiro , Tsuruoka Akihiko , Watanabe Tatsuo , Wakabayashi Toshiaki , Uenaka Toshimitsu , Asada Makoto
Published: October 2007

E7080 is an orally active inhibitor of multiple receptor tyrosine kinases including VEGF, FGF and SCF receptors. In this study, we show the inhibitory activity of E7080 against SCF‐induced angiogenesis in vitro and tumor growth of SCF‐producing human small cell lung carcinoma H146 cells in vivo. E7080 inhibits SCF‐driven tube formation of HUVEC, which express SCF receptor, KIT at the IC50 value of 5.2 nM and it was almost identical for VEGF‐driven one (IC50 = 5.1 nM). To assess the role of SCF/KIT signaling in tumor angiogenesis, we evaluated the effect of imatinib, a selective KIT kinase inhibitor, on tumor growth of H146 cells in nude mice. Imatinib did not show the potent antitumor activity in vitro (IC50 = 2,200 nM), because H146 cells did not express KIT. However, oral administration of imatinib at 160 mg/kg clearly slowed tumor growth of H146 cells in nude mice, accompanied by decreased microvessel density. Oral administration of E7080 inhibited tumor growth of H146 cells at doses of 30 and 100 mg/kg in a dose‐dependent manner and caused tumor regression at 100 mg/kg. While anti‐VEGF antibody also slowed tumor growth, it did not cause tumor regression. These results indicate that KIT signaling has a role in tumor angiogenesis of SCF‐producing H146 cells, and E7080 causes regression of H146 tumors as a result of antiangiogenic activity mediated by inhibition of both KIT and VEGF receptor signaling. E7080 may provide therapeutic benefits in the treatment of SCF‐producing tumors. © 2007 Wiley‐Liss, Inc.
Noggin blocks invasive growth of murine B16‐F1 melanoma cells in the optic cup of the chick embryo
Authors: Busch Christian , Drews Ulrich , Eisele Stefan R. , Garbe Claus , Oppitz Matthias
Published: October 2007

Melanoma cells originate from the neural crest and are characterized by high migratory potential and invasive growth. After transplantation into the neural tube of the chick embryo, melanoma cells spontaneously emigrate along the neural crest pathways without tumor formation or malignant growth. This emigration depends on the constitutive over‐expression of bone morphogenetic protein‐2 (BMP‐2) and can be ablated by the BMP‐antagonist noggin. When transplanted into the embryonic optic cup, melanoma cells invade the host tissue and form malignant tumors. Here, we asked if the invasive growth of melanoma cells in the optic cup could be influenced by BMP‐2 or noggin. Mouse B16‐F1 cells were grown as aggregates, treated with BMP‐2 or noggin during aggregation and transplanted into the optic cup of 3‐day chick embryos. After 3 days of subsequent incubation, embryos were evaluated for melanoma cell invasiveness. Immunohistochemical examination revealed that untreated and BMP‐2‐treated melanoma cells had grown malignantly into the host tissue. However, noggin pretreatment of the aggregates had blocked melanoma cell invasiveness and tumor formation. We conclude that invasive growth of melanoma cells in vivo is BMP‐dependent and can be ablated by noggin, thus rendering noggin a promising agent for the treatment of BMP‐over‐expressing melanoma. © 2007 Wiley‐Liss, Inc.
Caveolin‐1 secreting LNCaP cells induce tumor growth of caveolin‐1 negative LNCaP cells in vivo
Authors: Bartz René , Zhou Jian , Hsieh Jer‐Tsong , Ying Yunshu , Li Weiping , Liu Pingsheng
Published: October 2007

Caveolin‐1 (Cav‐1) was originally identified as a structural protein of caveolae, which is a plasma membrane domain that regulates a variety of signaling pathways involved in cell growth and migration. Here, we show that expression of Cav‐1 in the Cav‐1‐deficient human prostate cancer cell line LNCaP both stimulates cell proliferation and promotes tumor growth in nude mice. Unexpectedly, Cav‐1 expressing LNCaP (LNCaPCav‐1) cells injected into one side of a nude mouse promoted tumor growth of Cav‐1 negative LNCaP cells injected on the contralateral side of the same animal. The LNCaP tumors were positive for Cav‐1, however, this signal was not caused by migrated LNCaPCav‐1 cells, but we show that this Cav‐1 was secreted by the LNCaPCav‐1 tumors. We demonstrate that conditioned media from LNCaPCav‐1 cells contained Cav‐1 that was associated with a lipoprotein particle ranging in size from 15 to 30 nm and a density similar to high density lipoprotein particle. These results suggest that LNCaPCav‐1 cells secreting Cav‐1 particle produce an endocrine factor that stimulates tumor growth. © 2007 Wiley‐Liss, Inc.
Inhibitory effects of olive oil phenolics on invasion in human colon adenocarcinoma cells in vitro
Authors: Hashim Yumi Z.H‐Y. , Rowland Ian R. , McGlynn Hugh , Servili Maurizio , Selvaggini Roberto , Taticchi Agnese , Esposto Sonia , Montedoro GianFrancesco , Kaisalo Leena , Wähälä Kristiina , Gill Chris I.R.
Published: October 2007

Studies in human, animal and cellular systems suggest that phenols from virgin olive oil are capable of inhibiting several stages in carcinogenesis, including metastasis. The invasion cascade comprises cell attachment to extracellular matrix components or basement membrane, degradation of basement membrane by proteolytic enzymes and migration of cells through the modified matrix. In the present study, we investigated the effect of phenolics extracted from virgin olive oil (OVP) and its main constituents: hydroxytyrosol (3,4‐dihydroxyphenylethanol), tyrosol (p‐hydroxyphenylethanol), pinoresinol and caffeic acid. The effects of these phenolics were tested on the invasion of HT115 human colon carcinoma cells in a Matrigel invasion assay. OVP and its compounds showed different dose‐related anti‐invasive effects. At 25 μg/ml OVP and equivalent doses of individual compounds, significant anti‐invasive effects were seen in the range of 45–55% of control. Importantly, OVP, but not the isolated phenolics, significantly reduced total cell number in the Matrigel invasion assay. There were no significant effects shown on cell viability, indicating the reduction of cell number in the Matrigel invasion assay was not due to cytotoxicity. There were also no significant effects on cell attachment to plastic substrate, indicating the importance of extracellular matrix in modulating the anti‐invasive effects of OVP. In conclusion, the results from this study indicate that phenols from virgin olive oil have the ability to inhibit invasion of colon cancer cells and the effects may be mediated at different levels of the invasion cascade. © 2007 Wiley‐Liss, Inc.
MYCN regulates oncogenic MicroRNAs in neuroblastoma
Authors: Schulte Johannes H. , Horn Sebastian , Otto Tobias , Samans Birgit , Heukamp Lukas C. , Eilers Ursula‐Christa , Krause Michael , Astrahantseff Kathy , Klein‐Hitpass Ludger , Buettner Reinhard , Schramm Alexander , Christiansen Holger , Eilers Martin , Eggert Angelika , Berwanger Bernd
Published: October 2007

MYCN amplification is a common feature of aggressive tumour biology in neuroblastoma. The MYCN transcription factor has been demonstrated to induce or repress expression of numerous genes. MicroRNAs (miRNA) are a recently discovered class of short RNAs that repress translation and promote mRNA degradation by sequence‐specific interaction with mRNA. Here, we sought to analyse the role of MYCN in regulation of miRNA expression. Using a miRNA microarray containing 384 different miRNAs and a set of 160 miRNA real‐time PCR assays to validate the microarray results, 7 miRNAs were identified that are induced by MYCN in vitro and are upregulated in primary neuroblastomas with MYCN amplification. Three of the seven miRNAs belong to the miR‐106a and miR‐17 clusters, which have previously been shown to be regulated by c‐Myc. The miR‐17–92 polycistron also acts as an oncogene in haematopoietic progenitor cells. We show here that miR‐221 is also induced by MYCN in neuroblastoma. Previous studies have reported miR‐221 to be overexpressed in several other cancer entities, but its regulation has never before been associated with Myc. We present evidence of miRNA dysregulation in neuroblastoma. Additionally, we report miRNA induction to be a new mechanism of gene expression downregulation by MYCN. © 2007 Wiley‐Liss, Inc.
Modifying network chemistry in thiol‐acrylate photopolymers through postpolymerization functionalization to control cell‐material interactions
Authors: Rydholm Amber E. , Held Nicole L. , Benoit Danielle S.W. , Bowman Christopher N. , Anseth Kristi S.
Published: October 2007

Thiol‐acrylate photopolymers often contain pendant, unreacted thiol groups even following complete reaction of the acrylate functional groups. The results presented herein demonstrate a high throughput method for quantifying pendant thiol group concentrations using FTIR spectra of thiol‐acrylate microspot arrays. Using this technique, more than 25% of the original thiol groups were detected as pendant groups in microspots made from monomer solutions containing at least 40 mol % thiol functional groups. Subsequent modification reactions allowed postpolymerization tailoring of the network chemistry. The extent of modification was controlled by the concentration of the pendant thiols (ranging from 0.01 to 0.4M) and the duration of the modification reaction (0–10 min for photocoupling reactions, 0–24 h for Michael‐type addition reactions). Further, when photocoupling was used to modify the networks, spatial and temporal control of the light exposure facilitated the formation of chemical patterns on the surface and throughout the material. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Application of porous glycosaminoglycan‐based scaffolds for expansion of human cord blood stem cells in perfusion culture
Authors: Cho Cheul H. , Eliason James F. , Matthew Howard W.T.
Published: October 2007

In vitro expansion of hematopoietic stem cells (HSCs) has been employed to obtain sufficient numbers of stem cells for successful engraftment after HSC transplantation. A three‐dimensional perfusion bioreactor system with a heparin‐chitosan scaffold was designed and evaluated for its capability to support maintenance and expansion of HSCs. Porous chitosan scaffolds were fabricated by a freeze‐drying technique and N‐desulfated heparin was covalently immobilized within the scaffolds using carbodiimide chemistry. CD34+ HSCs isolated from umbilical cord blood by immunomagnetic separation were cultured within the porous scaffold in a perfusion bioreactor system. Control cultures were maintained on dishes coated with similar heparin‐chitosan films. Oxygen uptake was measured during the culture period. After 7 days of culture, scaffolds were harvested for analysis. Cellular phenotype and HSC characteristics were evaluated via flow cytometry and colony forming unit assays. The results indicate good cell retention and proliferation within the perfused scaffolds. Oxygen consumption in the perfusion bioreactor system increased continuously during the culture, indicating steady cell growth. Cells from the perfused scaffold cultures showed higher percentages of primitive progenitors and exhibited superior colony forming unit performance as compared to cells from static cultures. In addition, perfusion culture at low oxygen (5%) enhanced the expansion of CD34+ cells and colony‐forming activity compared to high oxygen (19%) cultures. The results suggest that perfusion culture of cord blood CD34+ cells under bone marrow‐like conditions enhances HSC expansion compared to static cultures. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
The electrochemical behavior of nitinol in simulated physiological solutions
Authors: Pound Bruce G.
Published: October 2007

The electrochemical behavior of nitinol in simulated human bile and phosphate‐buffered saline (PBS) was examined using electrochemical impedance spectroscopy. In addition, cyclic potentiodynamic polarization tests were performed in the simulated bile and salt‐only bile, and the results compared with those obtained previously in PBS. The potentiodynamic tests showed that electropolishing was effective in providing nitinol with a high resistance to pitting corrosion in the bile solutions, as found in PBS. Differences between the breakdown potential and the corrosion potential indicated that mechanically polished nitinol should be more susceptible to pitting corrosion in simulated bile than in the salt‐only bile and PBS. The impedance spectra showed near‐capacitive behavior in both PBS and simulated bile, and the data could be fitted by a parallel resistance–capacitance (as a constant phase element) circuit associated with the passive oxide film. The thickness of the oxide was determined from the capacitive component and found to be consistent with surface analytical results reported in the literature. Resistivities obtained from resistance values indicated that compositional features of the oxide were similar for PBS and simulated bile. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Biological activity of recombinant human growth factors released from biocompatible bone implants
Authors: Ziegler Joerg , Anger Dominique , Krummenauer Frank , Breitig Dieter , Fickert Stefan , Guenther Klaus‐Peter
Published: October 2007

The present investigation was performed to study the bioactivity of osteoinductive and osteoproliferative growth factors after release from biocompatible bone implants. Three types of porous carriers were used in this study: hydroxyapatite, alpha tricalcium phosphate, and a neutralized glass ceramic. Implants were loaded with recombinant human bone morphogenetic protein 2 (rh‐BMP‐2) and recombinant human basic fibroblast growth factor (rh‐bFGF) in a concentration of 2 μg/150 μL PBS each. The released growth factors were then applicated into SAOS‐2‐cell cultures. After 3, 5, and 7 days cell differentiation was measured by the activity of alkaline phosphatase (ALP), cell proliferation by using a MTT assay as well as a cell counter. Rh‐BMP‐2 released during the first hour from the scaffolds led to a significant increase of the activity of ALP in the incubated SAOS‐2‐cell culture after 3, 5, and 7 days. However, the incubation with rh‐BMP‐2 released after 24 h was not found to increase the expression of ALP. The incubation of cell cultures with rh‐bFGF released during the first hour led to a significant increase of cell number and of extinction in the MTT assay, whereas this increase was not observed after incubation with rh‐bFGF released after 24 h. The in vitro measured biological activity of released growth factors from the surface of synthetic implants is time‐depending. If prolonged osteoinductive and osteoproliferative potency of growth factors is desired, a modified application technique should be chosen to stabilize those proteins. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Intracellular Ca2+stores are essential for injury induced Ca2+signaling and re‐endothelialization
Authors: Zhao Zhiqiang , Walczysko Petr , Zhao Min
Published: October 2007

Endothelialization repairs the lining of damaged vasculature and is a key process in preventing thrombosis and restenosis. It has been demonstrated that extracellular calcium ([Ca2+]o) influx is important for subsequent endothelialization. The role of intracellular Ca2+stores in mechanical denudation induced intracellular calcium ([Ca2+]i) rise and endothelialization remains to be demonstrated. Using monolayer culture of a human endothelial cell line (human umbilical vein endothelial cell, HUVEC), we investigated [Ca2+]iwave propagation and re‐endothelialization following mechanical denudation. Consistent with previous reports for other types of cells, mechanical denudation induces calcium influx, which is essential for [Ca2+]irise and endothelialization. Moreover, we found that intracellular Ca2+stores are also essential for denudation induced [Ca2+]iwave initiation and propagation, and the subsequent endothelialization. Thapsigargin which depletes intracellular Ca2+stores completely abolished [Ca2+]iwave generation and endothelialization. Xestospongin C (XeC), which prevents Ca2+release from intracellular Ca2+stores by inhibition of inositol 1,4,5‐trisphosphate (IP3) receptor, inhibited intercellular Ca2+wave generation and endothelialization following denudation. Purinergic signaling through a suramin sensitive mechanism and gap junction communication also contribute to in intercellular Ca2+wave propagation and re‐endothelialization. We conclude that intracellular Ca2+stores, in addition to extracellular Ca2+, are essential for intracellular Ca2+signaling and subsequent endothelialization following mechanical denudation. J. Cell. Physiol. 214: 595–603, 2008. © 2007 Wiley‐Liss, Inc.
Sodium arsenite induces heat shock protein 70 expression and protects against secretagogue‐induced trypsinogen and NF‐κB activation
Authors: Bhagat Lakshmi , Singh Vijay P. , Dawra Rajinder K. , Saluja Ashok K.
Published: October 2007

Heat shock proteins (HSPs), induced by a variety of stresses, are known to protect against cellular injury. Recent studies have demonstrated that prior β‐adrenergic stimulation as well as thermal or culture stress induces HSP70 expression and protects against cerulein‐induced pancreatitis. The goal of our current studies was to determine whether or not a non‐thermal, chemical stressor like sodium arsenite also upregulates HSP70 expression in the pancreas and prevents secretagogue‐induced trypsinogen and NF‐κB activation. We examined the effects of sodium arsenite preadministration on the parameters of cerulein‐induced pancreatitis in rats and then monitored the effects of preincubating pancreatic acini with sodium arsenite in vitro. Our results showed that sodium arsenite pretreatment induced HSP70 expression both in vitro and in vivo and significantly ameliorated the severity of cerulein‐induced pancreatitis, as evidenced by the markedly reduced degree of hyperamylasemia, pancreatic edema, and acinar cell necrosis. Sodium arsenite pretreatment not only inhibited trypsinogen activation and the subcellular redistribution of cathepsin B, but also prevented NF‐κB translocation to the nucleus by inhibiting the IκBα degradation both in vivo and in vitro. We also examined the effect of sodium arsenite pretreatment in a more severe model of pancreatitis induced by L‐arginine and found a similarly protective effect. Based on our observations we conclude that, like thermal stress, chemical stressors such as sodium arsenite also induce HSP70 expression in the pancreas and protect against acute pancreatitis. Thus, non‐thermal pharmacologically induced stress can help prevent or treat pancreatitis. J. Cell. Physiol. 215: 37–46, 2008. © 2007 Wiley‐Liss, Inc.
High glucose suppresses expression of equilibrative nucleoside transporter 1 (ENT1) in rat cardiac fibroblasts through a mechanism dependent on PKC‐ζ and MAP kinases
Authors: Grden Marzena , Podgorska Marzena , Kocbuch Katarzyna , Rzepko Robert , Szutowicz Andrzej , Pawelczyk Tadeusz
Published: October 2007

Recently it was demonstrated that the elevated concentration of glucose but not lack of insulin is responsible for suppression of equilibrative nucleoside transporter (ENT1) in diabetic rat cardiac fibroblasts (CFs). The present study was undertaken to determine the signaling pathway utilized by glucose to regulate the expression of ENT1 in the primary culture of rat CFs. Pretreatment of CFs with Go 6983, an isozyme non‐selective PKC inhibitor, prevented the high glucose (25 mM) effect on ENT1 mRNA level and nitrobenzylthioinosine (NBTI)‐sensitive adenosine uptake. Similar effect was observed with a cell‐permeable PKC‐ζ pseudosubstrate, whereas Go 6976 a selective inhibitor of Ca2+‐dependent PKC‐α and PKC‐β isozymes had little effect on high glucose‐induced suppression of ENT1 mRNA level. Incubation of CFs with nitric oxide (NO) donors (SNAPE, SNP) or NO synthase inhibitors (L‐NAME, L‐NMMA) prior to exposition of CFs to high glucose did not change the glucose effect on ENT1 mRNA level. The high glucose‐induced suppression of ENT1 expression was blocked by PD9859 (an inhibitor of MEK), whereas neither wortmannin (an inhibitor of PI3K) nor rapamycin (an inhibitor of mTOR) affected the glucose action on ENT1 transcript level. Highly effective in preventing the high glucose effect on ENT1 mRNA level were GW 5074 (an inhibitor of Raf kinase) and SB 203580 (selective p38 MAPK inhibitor). These findings indicate that high glucose suppresses the expression of ENT1 in CFs by NO independent manner involving the signaling through PKC‐ζ, Raf‐1, MEK, and p38 MAPK pathways. J. Cell. Physiol. 215: 151–160, 2008. © 2007 Wiley‐Liss, Inc.
Regulation of human cripto‐1 gene expression by TGF‐β1 and BMP‐4 in embryonal and colon cancer cells
Authors: Mancino Mario , Strizzi Luigi , Wechselberger Christian , Watanabe Kazuhide , Gonzales Monica , Hamada Shin , Normanno Nicola , Salomon David S. , Bianco Caterina
Published: October 2007

Human Cripto‐1 (CR‐1) is a cell membrane protein that is overexpressed in several different types of human carcinomas. In the present study we investigated the mechanisms that regulate the expression of CR‐1 gene in cancer cells. We cloned a 2,481 bp 5′‐flanking region of the human CR‐1 gene into a luciferase reporter vector and transfected NTERA‐2 human embryonal carcinoma cells and LS174‐T colon cancer cells to test for promoter activity. Activity of CR‐1 promoter in both cell lines was modulated by two TGF‐β family members, TGF‐β1 and BMP‐4. In particular, TGF‐β1 significantly up‐regulated CR‐1 promoter activity, whereas a dramatic reduction in CR‐1 promoter activity was observed with BMP‐4 in NTERA‐2 and LS174‐T cells. Changes in the CR‐1 promoter activity following TGF‐β1 and BMP‐4 treatments correlated with changes in CR‐1 mRNA and protein expression in NTERA‐2 and LS174‐T cells. We also identified three Smad binding elements (SBEs) within the CR‐1 promoter and point mutation of SBE1 (−2,197/−2,189) significantly reduced response of the CR‐1 promoter to both TGF‐β1 and BMP‐4 in NTERA‐2 and LS174‐T cells. Chromatin immunoprecipitation assay also demonstrated binding of Smad‐4 to a CR‐1 promoter DNA sequence containing SBE1 in LS174‐T cells. Finally, BMP‐4 inhibited migration of LS174‐T cells and F9 mouse embryonal carcinoma cells by downregulation of CR‐1 protein. In conclusion, these results suggest a differential modulation of CR‐1 gene expression in embryonal and colon cancer cells by two different members of the TGF‐β family. J. Cell. Physiol. 215: 192–203, 2008. © 2007 Wiley‐Liss, Inc.
Ultrasound stimulates MMP‐13 expression through p38 and JNK pathway in osteoblasts
Authors: Chiu Yung‐Cheng , Huang Tsang‐Hai , Fu Wen‐Mei , Yang Rong‐Sen , Tang Chih‐Hsin
Published: October 2007

It has been shown that ultrasound (US) stimulation accelerates fracture healing, bone maturation, and remodeling in the animal models and in clinical studies. One of the major factor involves in remodeling process is matrix metalloproteinases (MMPs) such as MMP‐13 that has been shown to degrade the native interstitial collagens in several tissues. Here we found that US stimulation increased the secretion of MMP‐13 in cultured rat osteoblasts, as shown by zymographic analysis. US stimulation also increased the mRNA level of MMP‐13, c‐Fos, and c‐Jun. Cycloheximide (an inhibitor of protein translocation) and actinomycin D (an inhibitor of gene transcription) did not inhibit the MMP‐13, c‐Fos, and c‐Jun mRNA expression, suggesting that such expression does not require de novo protein synthesis and not change their stabilities. p38 inhibitor, SB203580 or JNK inhibitor, SP600125 but not ERK inhibitor, PD98059 attenuated the US‐induced MMP‐13, c‐Fos, and c‐Jun expression; these results were further substantiated by transfecting with the dominant negative mutants of p38 or JNK. The binding of c‐Fos and c‐Jun to the AP‐1 element on the MMP‐13 promoter and the enhancement of AP‐1 luciferase activity was enhanced by US stimulation. Taken together, our results provide evidence that US stimulation increases MMP‐13 expression through p38 and JNK signaling pathway to regulate bone remodeling. J. Cell. Physiol. 215: 356–365, 2008. © 2007 Wiley‐Liss, Inc.