bluuebunny/crossref_metadata_2025 huggingface dataset:
Bortezomib induces canonical nuclear factor-κB activation in multiple myeloma cells
Authors: Hideshima Teru , Ikeda Hiroshi , Chauhan Dharminder , Okawa Yutaka , Raje Noopur , Podar Klaus , Mitsiades Constantine , Munshi Nikhil C. , Richardson Paul G. , Carrasco Ruben D. , Anderson Kenneth C.
Published: May 2009

Bortezomib is a proteasome inhibitor with remarkable preclinical and clinical antitumor activity in multiple myeloma (MM) patients. The initial rationale for its use in MM was inhibition of nuclear factor (NF)-κB activity by blocking proteasomal degradation of inhibitor of κBα (IκBα). Bortezomib inhibits inducible NF-κB activity; however, its impact on constitutive NF-κB activity in MM cells has not yet been defined. In this study, we demonstrate that bortezomib significantly down-regulated IκBα expression and triggered NF-κB activation in MM cell lines and primary tumor cells from MM patients. Importantly, no inhibition of p65 (RelA) nuclear translocation was recognized after bortezomib treatment in a murine xenograft model bearing human MM cells. Bortezomib-induced NF-κB activation was mediated via the canonical pathway. Moreover, other classes of proteasome inhibitors also induced IκBα down-regulation associated with NF-κB activation. Molecular mechanisms whereby bortezomib induced IκBα down-regulation were further examined. Bortezomib triggered phosphorylation of IκB kinase (IKKβ) and its upstream receptor-interacting protein 2, whereas IKKβ inhibitor MLN120B blocked bortezomib-induced IκBα down-regulation and NF-κB activation, indicating receptor-interacting protein 2/IKKβ signaling plays crucial role in bortezomib-induced NF-κB activation. Moreover, IKKβ inhibitors enhanced bortezomib-induced cytotoxicity. Our studies therefore suggest that bortezomib-induced cytotoxicity cannot be fully attributed to inhibition of canonical NF-κB activity in MM cells.
Molecular targeting of the oncogene eIF4E in acute myeloid leukemia (AML): a proof-of-principle clinical trial with ribavirin
Authors: Assouline Sarit , Culjkovic Biljana , Cocolakis Eftihia , Rousseau Caroline , Beslu Nathalie , Amri Abdellatif , Caplan Stephen , Leber Brian , Roy Denis-Claude , Miller Wilson H. , Borden Katherine L. B.
Published: May 2009

The eukaryotic translation initiation factor eIF4E is elevated in 30% of malignancies including M4/M5 subtypes of acute myeloid leukemia (AML). The oncogenic potential of eIF4E arises from its ability to bind the 7-methyl guanosine (m7G) cap on mRNAs, thereby selectively enhancing eIF4E-dependent nuclear mRNA export and translation. We tested the clinical efficacy of targeting eIF4E in M4/M5 AML patients with a physical mimic of the m7G cap, ribavirin. Among 11 evaluable patients there were 1 complete remission (CR), 2 partial remissions (PRs), 2 blast responses (BRs), 4 stable diseases (SDs), and 2 progressive diseases (PDs). Ribavirin-induced relocalization of nuclear eIF4E to the cytoplasm and reduction of eIF4E levels were associated with clinical response. Lack of response or relapse coincided with continued or renewed nuclear localization of eIF4E. This first clinical study to target eIF4E in human malignancy demonstrates clinical activity and associated molecular responses in leukemic blasts. This trial is registered at ClinicalTrials.gov (NCT00559091).
eCOMPAGT – efficient Combination and Management of Phenotypes and Genotypes for Genetic Epidemiology
Authors: Schönherr Sebastian , Weißensteiner Hansi , Coassin Stefan , Specht Günther , Kronenberg Florian , Brandstätter Anita
Published: May 2009

Background

High-throughput genotyping and phenotyping projects of large epidemiological study populations require sophisticated laboratory information management systems. Most epidemiological studies include subject-related personal information, which needs to be handled with care by following data privacy protection guidelines. In addition, genotyping core facilities handling cooperative projects require a straightforward solution to monitor the status and financial resources of the different projects.

Description

We developed a database system for an efficient combination and management of phenotypes and genotypes (eCOMPAGT) deriving from genetic epidemiological studies. eCOMPAGT securely stores and manages genotype and phenotype data and enables different user modes with different rights. Special attention was drawn on the import of data deriving from TaqMan and SNPlex genotyping assays. However, the database solution is adjustable to other genotyping systems by programming additional interfaces. Further important features are the scalability of the database and an export interface to statistical software.

Conclusion

eCOMPAGT can store, administer and connect phenotype data with all kinds of genotype data and is available as a downloadable version at http://dbis-informatik.uibk.ac.at/ecompagt.
Up-regulation of uPARAP/Endo180 during culture activation of rat hepatic stellate cells and its presence in hepatic stellate cell lines from different species
Authors: Mousavi Seyed A , Fønhus Marita S , Berg Trond
Published: May 2009

Background

The urokinase plasminogen activator receptor associated protein (uPARAP)/Endo180 is a novel endocytic receptor that mediates collagen uptake and is implicated to play a role in physiological and pathological tissue-remodelling processes by mediating intracellular collagen degradation.

Result

This study investigates the expression of uPARAP/Endo180 protein and messenger RNA in primary rat hepatic stellate cell (HSC) cultures. The results show that uPARAP/Endo180 protein is not expressed in freshly isolated HSCs or during the first few days of culture while the cells still display quiescent features. In contrast, uPARAP/Endo180 protein is expressed early during HSC activation when cells are transdifferentiated into myofibroblast-like cells. Very low levels of uPARAP/Endo180 mRNA are detectable during the first days of culture but uPARAP/Endo180 mRNA is strongly up-regulated with increasing time in culture. Moreover, endocytic uptake of denatured collagen increases as transdifferentiation proceeds over time and correlates with increased expression of uPARAP/Endo180. Finally, analysis of uPARAP/Endo180 expression in four hepatic stellate cell lines from three different species showed that all these cell lines express uPARAP/Endo180 and are able to take up denatured collagen efficiently.

Conclusion

These results demonstrate that uPARAP/Endo180 expression by rat HSCs is strongly up-regulated during culture activation and identify this receptor as a feature common to culture-activated HSCs.
Dynamic changes in transcripts during regeneration of the secondary vascular system in Populus tomentosa Carr. revealed by cDNA microarrays
Authors: Wang Minjie , Qi Xiaoli , Zhao Shutang , Zhang Shougong , Lu Meng-Zhu
Published: May 2009

Background

Wood is the end product of secondary vascular system development, which begins from the cambium. The wood formation process includes four major stages: cell expansion, secondary wall biosynthesis, lignification, and programmed cell death. Transcriptional profiling is a rapid way to screen for genes involved in these stages and their transitions, providing the basis for understanding the molecular mechanisms that control this process.

Results

In this study, cDNA microarrays were prepared from a subtracted cDNA library (cambium zone versus leaf) of Chinese white poplar (Populus tomentosa Carr.) and employed to analyze the transcriptional profiles during the regeneration of the secondary vascular system, a platform established in our previous study. Two hundred and seven genes showed transcript-level differences at the different regeneration stages. Dramatic transcriptional changes were observed at cambium initiation, cambium formation and differentiation, and xylem development, suggesting that these up- or downregulated genes play important roles in these stage transitions. Transcription factors such as AUX/IAA and PINHEAD, which were previously shown to be involved in meristem and vascular tissue differentiation, were strongly transcribed at the stages when cambial cells were initiated and underwent differentiation, whereas genes encoding MYB proteins and several small heat shock proteins were strongly transcribed at the stage when xylem development begins.

Conclusion

Employing this method, we observed dynamic changes in gene transcript levels at the key stages, including cambium initiation, cambium formation and differentiation, and xylem development, suggesting that these up- or downregulated genes are strongly involved in these stage transitions. Further studies of these genes could help elucidate their roles in wood formation.
Evaluation of high efficiency gene knockout strategies for Trypanosoma cruzi
Authors: Xu Dan , Pérez Brandán Cecilia , Basombrío Miguel Ángel , Tarleton Rick L
Published: May 2009

Background

Trypanosoma cruzi, a kinetoplastid protozoan parasite that causes Chagas disease, infects approximately 15 million people in Central and South America. In contrast to the substantial in silico studies of the T. cruzi genome, transcriptome, and proteome, only a few genes have been experimentally characterized and validated, mainly due to the lack of facile methods for gene manipulation needed for reverse genetic studies. Current strategies for gene disruption in T. cruzi are tedious and time consuming. In this study we have compared the conventional multi-step cloning technique with two knockout strategies that have been proven to work in other organisms, one-step-PCR- and Multisite Gateway-based systems.

Results

While the one-step-PCR strategy was found to be the fastest method for production of knockout constructs, it does not efficiently target genes of interest using gene-specific sequences of less than 80 nucleotides. Alternatively, the Multisite Gateway based approach is less time-consuming than conventional methods and is able to efficiently and reproducibly delete target genes.

Conclusion

Using the Multisite Gateway strategy, we have rapidly produced constructs that successfully produce specific gene deletions in epimastigotes of T. cruzi. This methodology should greatly facilitate reverse genetic studies in T. cruzi.
Expression of Hyaluronan Synthases (HAS1–3) and Hyaluronidases (HYAL1–2) in Serous Ovarian Carcinomas: Inverse Correlation between HYAL1 and Hyaluronan Content
Authors: Nykopp Timo K , Rilla Kirsi , Sironen Reijo , Tammi Markku I , Tammi Raija H , Hämäläinen Kirsi , Heikkinen Anna-Mari , Komulainen Marja , Kosma Veli-Matti , Anttila Maarit
Published: May 2009

Background

Hyaluronan, a tumor promoting extracellular matrix polysaccharide, is elevated in malignant epithelial ovarian tumors, and associates with an unfavorable prognosis. To explore possible contributors to the accumulation of hyaluronan, we examined the expression of hyaluronan synthases (HAS1, HAS2 and HAS3) and hyaluronidases (HYAL1 and HYAL2), correlated with hyaluronidase enzyme activity hyaluronan content and HAS1–3 immunoreactivity.

Methods

Normal ovaries (n = 5) and 34 serous epithelial ovarian tumors, divided into 4 groups: malignant grades 1+2 (n = 10); malignant grade 3 (n = 10); borderline (n = 4) and benign epithelial tumors (n = 10), were analyzed for mRNA by real-time RT-PCR and compared to hyaluronidase activity, hyaluronan staining, and HAS1–3 immunoreactivity in tissue sections of the same specimens.

Results

The levels of HAS2 and HAS3 mRNA (HAS1 was low or absent), were not consistently increased in the carcinomas, and were not significantly correlated with HAS protein or hyaluronan accumulation in individual samples. Instead, the median of HYAL1 mRNA level was 69% lower in grade 3 serous ovarian cancers compared to normal ovaries (P = 0.01). The expression of HYAL1, but not HYAL2, significantly correlated with the enzymatic activity of tissue hyaluronidases (r = 0.5; P = 0.006). An inverse correlation was noted between HYAL1 mRNA and the intensity of hyaluronan staining of the corresponding tissue sections (r = -0.4; P = 0.025).

Conclusion

The results indicate that in serous epithelial ovarian malignancies HAS expression is not consistently elevated but HYAL1 expression is significantly reduced and correlates with the accumulation of hyaluronan. (233 words)
The -271 G>A polymorphism of kinase insert domain-containing receptor gene regulates its transcription level in patients with non-small cell lung cancer
Authors: An She-Juan , Chen Zhi-Hong , Lin Qiu-Xiong , Su Jian , Chen Hua-Jun , Lin Jia-Ying , Wu Yi-Long
Published: May 2009

Background

Kinase insert domain-containing receptor (KDR) plays a critical role in the metastasis of cancer and is used as a molecular target in cancer therapy. We investigated the characteristics of the -271 G>A polymorphism of the KDR gene to gain information that may benefit the development of individualized therapies for patients with non-small cell lung cancer (NSCLC).

Methods

The -271 G>A polymorphism of the KDR gene in 106 lung cancer patients and 203 healthy control individuals was analyzed by polymerase chain reaction (PCR) and DNA sequencing methods. Real-time quantitative PCR and immunohistochemical methods were used to evaluate KDR mRNA and protein expression levels, respectively, in frozen tumor specimens.

Results

The -271 G>A polymorphism was associated with the mRNA expression level of the KDR gene in tumor tissues (t = 2.178, P = 0.032, independent samplest-test). Compared with the AG/GG genotype, the AA genotype was associated with higher KDR mRNA expression in tumor tissues. We found no relationship between the genotype and the KDR protein expression level and no significant difference in the distribution of the KDR gene polymorphism genotypes between lung cancer patients and the control group (χ2= 1.269, P = 0.264, Fisher's exact test).

Conclusion

This study is the first to show that the -271 G>A polymorphism of the KDR gene may be a functional polymorphism related to the regulation of gene transcription. These findings may have important implications for therapies targeting KDR in patients with NSCLC.
The ADDITION-Cambridge trial protocol: a cluster – randomised controlled trial of screening for type 2 diabetes and intensive treatment for screen-detected patients
Authors: Echouffo-Tcheugui Justin B , Simmons Rebecca K , Williams Kate M , Barling Roslyn S , Prevost A Toby , Kinmonth Ann Louise , Wareham Nicholas J , Griffin Simon J
Published: May 2009

Background

The increasing prevalence of type 2 diabetes poses a major public health challenge. Population-based screening and early treatment for type 2 diabetes could reduce this growing burden. However, the benefits of such a strategy remain uncertain.

Methods and design

The ADDITION-Cambridge study aims to evaluate the effectiveness and cost-effectiveness of (i) a stepwise screening strategy for type 2 diabetes; and (ii) intensive multifactorial treatment for people with screen-detected diabetes in primary care. 63 practices in the East Anglia region participated. Three undertook the pilot study, 33 were allocated to three groups: no screening (control), screening followed by intensive treatment (IT) and screening plus routine care (RC) in an unbalanced (1:3:3) randomisation. The remaining 27 practices were randomly allocated to IT and RC. A risk score incorporating routine practice data was used to identify people aged 40–69 years at high-risk of undiagnosed diabetes. In the screening practices, high-risk individuals were invited to take part in a stepwise screening programme. In the IT group, diabetes treatment is optimised through guidelines, target-led multifactorial treatment, audit, feedback, and academic detailing for practice teams, alongside provision of educational materials for newly diagnosed participants. Primary endpoints are modelled cardiovascular risk at one year, and cardiovascular mortality and morbidity at five years after diagnosis of diabetes. Secondary endpoints include all-cause mortality, development of renal and visual impairment, peripheral neuropathy, health service costs, self-reported quality of life, functional status and health utility. Impact of the screening programme at the population level is also assessed through measures of mortality, cardiovascular morbidity, health status and health service use among high-risk individuals.

Discussion

ADDITION-Cambridge is conducted in a defined high-risk group accessible through primary care. It addresses the feasibility of population-based screening for diabetes, as well as the benefits and costs of screening and intensive multifactorial treatment early in the disease trajectory. The intensive treatment algorithm is based on evidence from studies including individuals with clinically diagnosed diabetes and the education materials are informed by psychological theory. ADDITION-Cambridge will provide timely evidence concerning the benefits of early intensive treatment and will inform policy decisions concerning screening for type 2 diabetes.

Trial registration

Current Controlled trials ISRCTN86769081
A comparison of the sensitivities of detection of Plasmodium falciparum gametocytes by magnetic fractionation, thick blood film microscopy, and RT-PCR
Authors: Karl Stephan , Davis Timothy ME , St-Pierre Tim G
Published: May 2009

Background

The magnetic properties of Plasmodium-infected erythrocytes have been exploited for different clinical and research purposes. A recent study in a rural clinical setting in Papua New Guinea has demonstrated that Plasmodium falciparum gametocyte detection is facilitated by magnetic deposition microscopy but no study has yet determined the relative sensitivity and limit of detection of a magnetic fractionation technique. The present study compares the detection limit and sensitivity of a technique based on the use of commercially available magnetic fractionation columns with those for thick blood film microscopy and reverse transcriptase polymerase chain reaction (RT-PCR) methods.

Methods

Gametocyte detection in six series of dilutions of cultured P. falciparum parasites with known gametocytaemia was conducted using magnetic fractionation, thick blood film, and RT-PCR techniques.

Results

The preparations obtained by the magnetic fractionation method were of thin film quality allowing easy gametocyte identification by light microscopy. Magnetic fractionation had a higher sensitivity and approximately two orders of magnitude better limit of detection than thick blood film microscopy. Gametocytes were also more readily detectable on the magnetically fractionated preparations. Magnetic fractionation had a similar limit of detection to that of RT-PCR.

Conclusion

Magnetic fractionation is a highly sensitive and convenient method for gametocyte detection in comparison with the standard thick blood film and RT-PCR methods, and could readily be adapted to field application.
Identification of the B-Raf/Mek/Erk MAP kinase pathway as a target for all-trans retinoic acid during skin cancer promotion
Authors: Cheepala Satish B , Yin Weihong , Syed Zanobia , Gill Jennifer N , McMillian Alaina , Kleiner Heather E , Lynch Mark , Loganantharaj Rasiah , Trutschl Marjan , Cvek Urska , Clifford John L
Published: May 2009

Background

Retinoids have been studied extensively for their potential as therapeutic and chemopreventive agents for a variety of cancers, including nonmelanoma skin cancer (NMSC). Despite their use for many years, the mechanism of action of retinoids in the prevention of NMSC is still unclear. In this study we have attempted to understand the chemopreventive mechanism of all-trans retinoic acid (ATRA), a primary biologically active retinoid, in order to more efficiently utilize retinoids in the clinic.

Results

We have used the 2-stage dimethylbenzanthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) mouse skin carcinogenesis model to investigate the chemopreventive effects of ATRA. We have compared the gene expression profiles of control skin to skin subjected to the 2-stage protocol, with or without ATRA, using Affymetrix 430 2.0 DNA microarrays. Approximately 49% of the genes showing altered expression with TPA treatment are conversely affected when ATRA is co-administered. The activity of these genes, which we refer to as 'counter-regulated', may contribute to chemoprevention by ATRA. The counter-regulated genes have been clustered into functional categories and bioinformatic analysis has identified the B-Raf/Mek/Erk branch of the MAP kinase pathway as one containing several genes whose upregulation by TPA is blocked by ATRA. We also show that ATRA blocks signaling through this pathway, as revealed by immunohistochemistry and Western blotting. Finally, we found that blocking the B-Raf/Mek/Erk pathway with a pharmacological inhibitor, Sorafenib (BAY43-9006), induces squamous differentiation of existing skin SCCs formed in the 2-stage model.

Conclusion

These results indicate that ATRA targets the B-Raf/Mek/Erk signaling pathway in the 2-stage mouse skin carcinogenesis model and this activity coincides with its chemopreventive action. This demonstrates the potential for targeting the B-Raf/Mek/Erk pathway for chemoprevention and therapy of skin SCC in humans. In addition our DNA microarray results provide the first expression signature for the chemopreventive effect of ATRA in a mouse skin cancer model. This is a potential source for novel targets for ATRA and other chemopreventive and therapeutic agents that can eventually be tested in the clinic.
Synergistic effect of human CycT1 and CRM1 on HIV-1 propagation in rat T cells and macrophages
Authors: Okada Hiroyuki , Zhang Xianfeng , Ben Fofana Ismael , Nagai Mika , Suzuki Hajime , Ohashi Takashi , Shida Hisatoshi
Published: May 2009

Background

In vivo studies of HIV-1 pathogenesis and testing of antiviral strategies have been hampered by the lack of an immunocompetent small animal model that is highly susceptible to HIV-1 infection. Although transgenic rats that express the HIV-1 receptor complex hCD4 and hCCR5 are susceptible to infection, HIV-1 replicates very poorly in these animals. To demonstrate the molecular basis for developing a better rat model for HIV-1 infection, we evaluated the effect of human CyclinT1 (hCycT1) and CRM1 (hCRM1) on Gag p24 production in rat T cells and macrophages using both established cell lines and primary cells prepared from hCycT1/hCRM1 transgenic rats.

Results

Expression of hCycT1 augmented Gag production 20–50 fold in rat T cells, but had little effect in macrophages. Expression of hCRM1 enhanced Gag production 10–15 fold in macrophages, but only marginally in T cells. Expression of both factors synergistically enhanced p24 production to levels approximately 10–40% of those detected in human cells. R5 viruses produced in rat T cells and macrophages were fully infectious.

Conclusion

The expression of both hCycT1 and hCRM1 appears to be fundamental to developing a rat model that supports robust propagation of HIV-1.
Intrathecal Delivery of PDGF Produces Tactile Allodynia through its Receptors in Spinal Microglia
Authors: Masuda Junya , Tsuda Makoto , Tozaki-Saitoh Hidetoshi , Inoue Kazuhide
Published: May 2009

Neuropathic pain is a debilitating pain condition that occurs after nerve damage. Such pain is considered to be a reflection of the aberrant excitability of dorsal horn neurons. Emerging lines of evidence indicate that spinal microglia play a crucial role in neuronal excitability and the pathogenesis of neuropathic pain, but the mechanisms underlying neuron-microglia communications in the dorsal horn remain to be fully elucidated. A recent study has demonstrated that platelet-derived growth factor (PDGF) expressed in dorsal horn neurons contributes to neuropathic pain after nerve injury, yet how PDGF produces pain hypersensitivity remains unknown. Here we report an involvement of spinal microglia in PDGF-induced tactile allodynia. A single intrathecal delivery of PDGF B-chain homodimer (PDGF-BB) to naive rats produced a robust and long-lasting decrease in paw withdrawal threshold in a dose-dependent manner. Following PDGF administration, the immunofluorescence for phosphorylated PDGF β-receptor (p-PDGFRβ), an activated form, was markedly increased in the spinal dorsal horn. Interestingly, almost all p-PDGFRβ-positive cells were double-labeled with an antibody for the microglia marker OX-42, but not with antibodies for other markers of neurons, astrocytes and oligodendrocytes. PDGF-stimulated microglia in vivo transformed into a modest activated state in terms of their cell number and morphology. Furthermore, PDGF-BB-induced tactile allodynia was prevented by a daily intrathecal administration of minocycline, which is known to inhibit microglia activation. Moreover, in rats with an injury to the fifth lumbar spinal nerve (an animal model of neuropathic pain), the immunofluorescence for p-PDGFRβ was markedly enhanced exclusively in microglia in the ipsilateral dorsal horn. Together, our findings suggest that spinal microglia critically contribute to PDGF-induced tactile allodynia, and it is also assumed that microglial PDGF signaling may have a role in the pathogenesis of neuropathic pain.
Waterborne GPR survey for estimating bottom-sediment variability: A survey on the Po River, Turin, Italy
Authors: Sambuelli Luigi , Calzoni Corrado , Pesenti Manuele
Published: May 2009

We conducted an integrated geophysical survey on a stretch of the river Po in order to check the GPR ability to discriminate the variability of riverbed sediments through an analysis of the bottom reflection amplitudes. We conducted continuous profiles with a [Formula: see text] GPR system and a handheld broadband EM sensor. A conductivity meter and a TDR provided punctual measurements of water conductivity, permittivity, and temperature. The processing and interpretation of the GEM-2 and GPR data were enhanced by reciprocal results and by integration with the punctual measurements of the EM properties of the water. We used a processing flow that improved the radargram images and preserved the amplitude ratios among the different profiles and the frequency content at the bottom reflection signal. We derived the water attenuation coefficient both from the punctual measurements using the Maxwell formulas and from the interpretation of the GPR data, finding an optimal matching between the two values. The GPR measurements provided maps of the bathymetry and of the bottom reflection amplitude. The high reflectivity of the riverbed, derived from the GPR interpretation, agreed with the results of the direct sampling campaign that followed the geophysical survey. The variability of the bottom-reflection-amplitudes map, which was not confirmed by the direct sampling, could also have been caused by scattering phenomena due to the riverbed clasts which are dimensionally comparable to the wavelength of the radar pulse.
Ultrasonic moduli for fluid-saturated rocks: Mavko-Jizba relations rederived and generalized
Authors: Gurevich Boris , Makarynska Dina , Pervukhina Marina
Published: May 2009

Mavko and Jizba propose a quantitative model for squirt dispersion of elastic-wave velocities between seismic and ultrasonic frequencies in granular rocks. Their central results are the expressions for the so-called unrelaxed frame bulk and shear moduli computed under an assumption that the stiff pores are drained (or dry) but the soft pores are filled with fluid. Mavko-Jizba expressions are limited to liquid-saturated rocks but become inaccurate when the fluid-bulk modulus is small (e.g., for gas-saturated rocks). We have derived new expressions for unrelaxed moduli of fluid-saturated porous rocks using Sayers-Kachanov discontinuity formalism. The derived expressions generalize the established Mavko-Jizba relations to gas-saturated rocks, reduce to Mavko-Jizba results when the pore fluid is liquid, and yield dry moduli when fluid-bulk modulus tends to zero. We tested this by comparing our model and the model of Mavko and Jizba against laboratory measurements on a sample of Westerly granite.
Phase III Postoperative Adjuvant Radiotherapy After Radical Prostatectomy Compared With Radical Prostatectomy Alone in pT3 Prostate Cancer With Postoperative Undetectable Prostate-Specific Antigen: ARO 96-02/AUO AP 09/95
Authors: Wiegel Thomas , Bottke Dirk , Steiner Ursula , Siegmann Alessandra , Golz Reinhard , Störkel Stephan , Willich Norman , Semjonow Axel , Souchon Rainer , Stöckle Michael , Rübe Christian , Weißbach Lothar , Althaus Peter , Rebmann Udo , Kälble Tilman , Feldmann Horst Jürgen , Wirth Manfred , Hinke Axel , Hinkelbein Wolfgang , Miller Kurt
Published: May 2009

Purpose

Local failure after radical prostatectomy (RP) is common in patients with cancer extending beyond the capsule. Two randomized trials demonstrated an advantage for adjuvant radiotherapy (RT) compared with a wait-and-see policy. We conducted a randomized, controlled clinical trial to compare RP followed by immediate RT with RP alone for patients with pT3 prostate cancer and an undetectable prostate-specific antigen (PSA) level after RP.

Methods

After RP, 192 men were randomly assigned to a wait-and-see policy, and 193 men were assigned to immediate postoperative RT. Eligible patients had pT3 pN0 tumors. Patients who did not achieve an undetectable PSA after RP were excluded from treatment according to random assignment (n = 78; 20%). Of the remaining 307 patients, 34 patients on the RT arm did not receive RT and five patients on the wait-and-see arm received RT. Therefore, 114 patients underwent RT and 154 patients were treated with a wait-and-see policy. The primary end point was biochemical progression-free survival.

Results

Biochemical progression-free survival after 5 years in patients with undetectable PSA after RP was significantly improved in the RT group (72%; 95% CI, 65% to 81%; v 54%, 95% CI, 45% to 63%; hazard ratio = 0.53; 95% CI, 0.37 to 0.79; P = .0015). On univariate analysis, Gleason score more than 6 and less than 7, PSA before RP, tumor stage, and positive surgical margins were predictors of outcome. The rate of grade 3 to 4 late adverse effects was 0.3%.

Conclusion

Adjuvant RT for pT3 prostate cancer with postoperatively undetectable PSA significantly reduces the risk of biochemical progression. Further follow-up is needed to assess the effect on metastases-free and overall survival.
Gleason Score and Lethal Prostate Cancer: Does 3 + 4 = 4 + 3?
Authors: Stark Jennifer R. , Perner Sven , Stampfer Meir J. , Sinnott Jennifer A. , Finn Stephen , Eisenstein Anna S. , Ma Jing , Fiorentino Michelangelo , Kurth Tobias , Loda Massimo , Giovannucci Edward L. , Rubin Mark A. , Mucci Lorelei A.
Published: May 2009

Purpose

Gleason grading is an important predictor of prostate cancer (PCa) outcomes. Studies using surrogate PCa end points suggest outcomes for Gleason score (GS) 7 cancers vary according to the predominance of pattern 4. These studies have influenced clinical practice, but it is unclear if rates of PCa mortality differ for 3 + 4 and 4 + 3 tumors. Using PCa mortality as the primary end point, we compared outcomes in Gleason 3 + 4 and 4 + 3 cancers, and the predictive ability of GS from a standardized review versus original scoring.

Patients and Methods

Three study pathologists conducted a blinded standardized review of 693 prostatectomy and 119 biopsy specimens to assign primary and secondary Gleason patterns. Tumor specimens were from PCa patients diagnosed between 1984 and 2004 from the Physicians' Health Study and Health Professionals Follow-Up Study. Lethal PCa (n = 53) was defined as development of bony metastases or PCa death. Hazard ratios (HR) were estimated according to original GS and standardized GS. We compared the discrimination of standardized and original grading with C-statistics from models of 10-year survival.

Results

For prostatectomy specimens, 4 + 3 cancers were associated with a three-fold increase in lethal PCa compared with 3 + 4 cancers (95% CI, 1.1 to 8.6). The discrimination of models of standardized scores from prostatectomy (C-statistic, 0.86) and biopsy (C-statistic, 0.85) were improved compared to models of original scores (prostatectomy C-statistic, 0.82; biopsy C-statistic, 0.72).

Conclusion

Ignoring the predominance of Gleason pattern 4 in GS 7 cancers may conceal important prognostic information. A standardized review of GS can improve prediction of PCa survival.
SPEC Process III. Synthesis of a Macroporous Silica-Based Crown Ether-Impregnated Polymeric Composite Modified with 1-Octanol and its Adsorption Capacity for Sr(II) Ions and Some Typical Co-Existent Metal Ions
Authors: Zhang Anyun , Chen Chunmei , Chai Zhifang , Kumagai Mikio
Published: May 2009

A macroporous silica-based 4,4′,(5′)-di(t-butylcyclohexano)-18-crown-6 (DtBuCH18C6)-impregnated polymeric composite, (DtBuCH18C6 + Oct)/SiO2-P, was synthesized by molecular modification of DtBuCH18C6 with 1-octanol through hydrogen bonding. This was achieved by impregnating and immobilizing DtBuCH18C6 and 1-octanol molecules in the pores of macroporous SiO2-P particles possessing a mean pore diameter of 50 μm. The adsorption of some fission and non-fission products contained in highly active liquid waste (HLW) such as Ru(III), Mo(VI), Pd(II), Na(I), K(I), Cs(I), Sr(II), Ba(II), La(III) and Y(III) onto (DtBuCH18C6 + Oct)/SiO2-P was investigated at 298 K. The effects of contact time and HNO3 concentration within the range 0.1–5.0 M were examined. Increasing the HNO3 concentration from 0.1 M to 2.0 M led to a significant increase in the adsorption of Sr(II), followed by a decrease when the HNO3 concentration was increased further to 5.0 M. The optimum concentration of HNO3 in the adsorption of Sr(II) onto (DtBuCH18C6 + Oct)/SiO2-P was determined as 2.0 M. For the other ions examined with the exception of Ba(II), very weak or almost non-existent adsorption capacities were observed at all HNO3concentrations. The leaching of total organic carbon (TOC) from (DtBuCH18C6 + Oct)/SiO2-P into the aqueous phase was evaluated. Over the HNO3 concentration range 0.1–3.0 M, the quantity of TOC leached was ca. 40 ppm compared with 355.8–373.3 ppm at HNO3 concentrations above 4.0 M. Significant reduction of TOC leaching from the macroporous silica-based DtBuCH18C6-impregnated polymeric composite was achieved in 2.0 M HNO3. Such behaviour could be of great benefit in using (DtBuCH18C6 + Oct)/SiO2-P for the partitioning of Sr(II) from HLW by extraction chromatography.
Treatment of Alhagi Residues with Tartaric Acid for the Removal of Zn(II) Ions from Aqueous Solution
Authors: Hashem A. , Abdel-Lateff A. , Farag S. , Hussein D.M.
Published: May 2009

Alhagi cellulose tartrate (ACT) with a high carboxyl group content was prepared by treatment of Alhagi residues (AR) with tartaric acid (TA) at high temperature. Factors influencing the reaction were investigated, viz. tartaric acid concentration, dehydration temperature, particle size and dehydration time. The prepared Alhagi cellulose tartrate samples were characterized using FT-IR spectroscopy and by estimation of the carboxyl group content. The esterified samples were utilized for the adsorptive removal of Zn(II) ions from aqueous solution with all the factors influencing the process being studied. These factors were the pH value of the adsorbate solution, the adsorbent concentration, agitation time and temperature.

The Langmuir and Freundlich models were applied to the data obtained from the adsorption studies. It was demonstrated that the Alhagi cellulose tartrate samples could be used effectively for the adsorption of Zn(II) ions from aqueous solutions. The thermodynamics constants of the adsorption process, viz. ΔH0, ΔS0 and ΔG0, were evaluated. The results showed that the adsorption of Zn(II) ions onto ACT was exothermic and spontaneous. The adsorption data followed second-order kinetics, with the equilibrium data being only satisfactorily described by the Langmuir isotherm.
Synthesis and Characterization of Mesoporous Cerium Oxide Prepared Using an Organic Base and a Templating Agent
Authors: Tillirou Aphrodite A. , Theocharis Charis R.
Published: May 2009

This paper discusses the effect on the surface properties of precipitated cerium oxide of using a mixed alcohol–water solvent as well as an organic base instead of the ammonia solution used hitherto. It further discusses the influence of the presence of a templating agent, such as CTAB, on the pore structure of ceria. It was found that the use of a template leads to a more well-defined pore system. Furthermore, in addition to any mesopores, an interesting network of secondary macropores was developed.
Removal of Hexavalent Chromium Ions from Aqueous Solutions by an Anion-Exchange Resin
Authors: Kumar P. Senthil , Kirthika K. , Kumar K. Sathish
Published: May 2009

The removal of hexavalent chromium, Cr(VI), from aqueous solutions under different conditions using an anion-exchange resin (AXR) as an adsorbent was investigated under batch conditions. Such studies indicated that the percentage adsorption decreased with increasing initial Cr(VI) concentration, with the maximum removal of such ions occurred at a pH value of ca. 2.0. Both the Langmuir and Freundlich isotherm models were capable of reproducing the isotherms obtained experimentally. The sorption process was rapid during the first 20 min with equilibrium being attained within 30 min. The process followed first-order kinetics. The results demonstrate that such anion-exchange resins can be used for the efficient removal of Cr(VI) ions from water and wastewater.
Measurement and Prediction of the Pedestrian-Induced Vibrations of a Footbridge
Authors: Van den Broeck P. , De Roeck G. , Reynders E. , Degrauwe D. , Georgieva I. Bojidarova , Borisova N. Damyanova
Published: May 2009

Vibration serviceability has become an important issue in the design of modern slender footbridges with large spans. This paper presents the measurements and the numerical predictions of the footfall-induced vibrations of a pedestrian bridge. A series of experiments were carried out with different-sized groups crossing the bridge, varying in number from 10 up to 50 participants and recording the vertical and lateral accelerations at different locations on the bridge. Two types of tests were performed: free walking and synchronized walking by means of a metronome signal, recorded on a tape recorder carried by the group of students. The effect of the test type is analyzed and shows a magnitude in difference between the vertical accelerations caused by the free and the synchronized walking. The increasing trend of the acceleration levels with increasing group size is also clearly observed. A numerical prediction method is used to simulate the synchronized walking experiments based on an updated finite element model of the bridge and a single pedestrian load model. It is shown that the predicted acceleration level is sensitive to the assumptions made regarding the level of synchronization between the pedestrians and the magnitude of the dynamic load generated by each pedestrian. Taking into account these specific measurement conditions, a fair agreement is obtained between the predicted and the observed vertical acceleration levels at seven positions along the length of the footbridge.
Shaking Table Experimental Study of the Short Pier RC Shear Wall Structures with Concealed Bracing
Authors: Cao W. L. , Zhao C. J. , Xue S. D. , Zhang J. W.
Published: May 2009

Short pier RC shear wall structure with concealed bracings is put forward in this paper. Two 1/6 scale models of short pier RC shear wall structure with and without concealed bracings are tested on shaking table. Dynamic properties and responses of the two structures at different stages are studied, and the comparison of failure modes between the two models is also made. Results from the experiments indicate that at elastic stage, seismic performance of short pier shear wall structure with concealed bracing is similar to that of structure without concealed bracing. After concrete cracks appearing, the seismic performance of the former is much better than that of the latter. The displacement responses of the former are much smaller than that of the latter, and the cracks distribution areas in walls of the former is much wider than that of the latter. The energy dissipation capacity of the former is significantly improved compared with that of the latter. Nonlinear time history analysis is carried out and the calculating results agree well with the results from the experiments.
Performance of FRP-Strengthened RC Beams with Surface Out-Of-Flatness
Authors: Yalim Baris , Kalayci Ahmet Serhat , Mirmiran Amir
Published: May 2009

Fiber reinforced polymer (FRP) has become increasingly popular for the repair and retrofit of reinforced concrete structures. Surface condition of the substrate, in particular its flatness, plays a significant role on the performance of retrofitted structure. This paper reports on the effects of out-of-flatness as a surface defect on the flexural performance of FRP repair systems. The experimental program includes a total of nineteen specimens with two different FRP repair systems (wet lay-up and precured), and two different levels of surface unevenness in the form of peaks or valleys. Tests showed that the peaks on concrete surface, in the range studied, did not have a significant effect on the performance of FRP systems. However, valleys or depressions deeper than 1.6 mm over a length of 305 mm (1.38 × 10−4 mm−1 curvature) could reduce the strength of FRP systems. Typical failure mode was FRP debonding observed in both FRP repair systems. Test results and threshold recommendations were verified using a nonlinear finite element analysis. Bond-dependent coefficient for various surface flatness levels were analyzed and compared with the results available in the literature.
Performance Evaluation of Hexagonal Array Adaptive Beamforming Algorithm Based on Inverse QR-RLS for Active Sonar Application
Authors: Wang Q. , Pan X.
Published: May 2009

In shallow water areas, to enhance underwater targets detection performance improve computation efficiency of active sonar, a computationally efficient adaptive beamformer (spatial filter) based on inverse QR (IQR) and recursive least-squares (RLS) is developed under fast Fourier transform framework, for standard hexagonal receiving array implementation. The IQR-RLS algorithm has good numerical stability and can be mapped onto coordinate rotation digital computer processor-based systolic arrays, which is suitable for real time applications. Using the proposed scheme to construct beamformer, which reduces computational complexity significantly and offers better converge rate than conventional adaptive beamformer. The simulation and lake test results demonstrates the algorithm improves interference (reverberation) suppression ability. It improves SNR about 2dB of still bottom target detection in reverberation limited area.
Combined Simulation of Spark Ignition Internal Combustion Engines and Heat Conduction within Piston
Authors: Farzaneh-Gord Mahmood , Hajializadeh Hamid
Published: May 2009

A combined thermodynamic simulation and transient conduction heat transfer through piston has been carried out in this study. In thermodynamic simulation, A computer programme has been developed to study the full operation cycle of a four stroke internal combustion engine. The simulation used to calculate the pressure and temperature field existing in realistic engine combustion chambers for various engine parameters. The one dimensional conduction heat transfer equation has been solved numerically. The results show a good agreement with previous studies where applicable.
A Stochastic Approach for Parameterizing Unresolved Scales in a System with Memory
Authors: Du Aijun , Duan Jinqiao
Published: May 2009

Complex systems display variability over a broad range of spatial and temporal scales. Some scales are unresolved due to computational limitations. The impact of these unresolved scales on the resolved scales needs to be parameterized or taken into account. One stochastic parameterization scheme is devised to take the effects of unresolved scales into account, in the context of solving a nonlinear partial differential equation with memory (a time-integral term), via large eddy simulations. The obtained large eddy simulation model is a stochastic partial differential equation. Numerical experiments are performed to compare the solutions of the original system and of the stochastic large eddy simulation model.
The European Economic Constitution, Freedom of Contract and the DCFR
Authors: Rutgers Jacobien W.
Published: May 2009

In the literature on European Contract Law and German contract law, a number of authors claim that the free movement of goods (Article 28 EC), services (Article 49 EC), capital (Article 56 EC) and persons (Article 39 EC) guarantee party autonomy and freedom of contract. In this paper, the opposite will be argued. It is submitted that ‘freedom of contract is taken for granted’ within the European Union. However, it is also generally accepted that there are restraints to freedom of contract to protect societal interests, as for instance protection of weaker parties, the environment and the capital market. Thus, the real question concerns the balance between on the one hand, freedom of contract and, on the other, restrictions to freedom of contract.

The issue whether freedom of contract is a constitutionally protected right within the European Union is relevant, since if freedom of contract is taken as point of departure ‘… collective interests [are put] to the background’.

In order to show that the free movements do not guarantee freedom of contract, first, the origin of the claim that the free movements guarantee party autonomy will be explored and will be placed against a historical background. Then, it will be discussed to what extent the Treaty provisions reflect the idea that the free movements guarantee freedom of contract and whether it can be inferred from the ECJ case law.
Automated Acid Content Determination in Lubricants by FTIR Spectroscopy as an Alternative to Acid Number Determination
Authors: Li D. , Sedman J. , García-González D. L. , van de Voort F. R.
Published: May 2009

A new instrumental method for the quantitative measurement of acid content (AC) in mineral-based lubricants was devised by employing FTIR spectroscopy, with AC serving as an alternative to traditional acid number (AN) measures commonly made to assess lubricant quality. The method involves the addition of an oil-immiscible ethanolic solution of the base sodium hydrogen cyanamide (NaHN–CN) to the lubricant to extract and react with the acids present. After separation of the phases, the FTIR spectrum of the ethanol layer is recorded, and a differential spectrum is generated by subtracting out the spectrum of the reagent solution. AC is determined by measuring the absorbance of NaHN–CN at 2109 cm−1 (νCN) in the differential spectrum, which is proportional to the extent to which the reagent has been consumed by reaction with acidic constituents in the oil. Calibration standards were prepared by direct addition of oleic acid to the NaHN–CN/ethanol solution, and a calibration equation for the determination of AC was obtained by a quadratic fit of the concentration data to the FTIR νCN absorbance data. The equivalent response of the νCN band to strong inorganic acids and oleic acid demonstrated that NaHN–CN, a somewhat weaker base than KOH, fully ionizes organic acids. Comparison between FTIR AC values and titrimetric AN values (obtained by ASTM D664-89) for a set of used oils spanning an AN range of 0.3–5 mg KOH/g showed a reasonably good linear relationship (R=0.985), with the FTIR method generally producing lower values. This tendency was attributed to the presence of weakly acidic species, which would be less extensively ionized by NaHN–CN than by KOH. Implementation of the FTIR AC method on an autosampler-equipped spectrometer allows for the automated analysis of up to 120 preprepared samples/h, representing a significant increase in analytical throughput relative to traditional titrimetric procedures as well as substantive reductions in consumables and waste oil.
Buchbesprechung
Authors: Voß Christian
Published: May 2009

STEINKE, KLAUS, XHELAL, YLLI, Die slavischen Minderheiten in Albanien (SMA): 1. Teil: Prespa  Vërnik  Boboshtica. München: Otto Sagner 2007 (=Slavistische Beiträge, 458), 374 S. ISBN 978-3-87690-989-9