Detection and characterization of the electron paramagnetic resonance-silent glutathionyl-5,5-dimethyl-1-pyrroline N-oxide adduct derived from redox cycling of phenoxyl radicals in model systems and HL-60 cells

Rapidly growing knowledge about the nature and behaviour of breast cancer has led to many treatment modalities. Consequently, the possibilities of individualizing the treatment of breast cancer increase. The major tool for the determination of an optimal treatment plan is the estimation of the extent of the disease: in other words, staging. As a consequence, together with the expected result of the treatment, the stage of the disease gives information on the prognosis of the patient. Current staging systems insufficiently describe the clinically important features of breast cancer with respect to management and outcome: local and regional extent, invasiveness, aggressiveness, the state of dissemination, and the effectiveness of different treatment modalities. For staging of the local and regional extent, histology plays a prominent role and should be incorporated in future staging systems. Histological workup therefore needs standardisation. Histological parameters as tumour size, grade, nodal status, and vascular invasion are also the most important prognostic factors. Many so-called biological prognostic factors are related to the invasiveness and aggressiveness (metastatic potential) of the tumour, and therefore to the prognosis of the patient. However, these factors do not necessarily predict the effectiveness of certain systemic treatments. Only if the biological foundation of a prognostic factor is completely clarified can treatment be based on this knowledge, and the factor will become a predictor for the treatment effect. Many "biological" prognostic factors do not fulfil this main criterion and are therefore not useful for clinical decision making. A clinically useful staging system covers three primary aims: (1) to guide locoregional treatment, (2) to prognosticate the chance of survival, and (3) to indicate who needs what kind of adjuvant treatment. For the conception of a new staging system the following steps should be taken: standardization of all aspects of histology, identification of regional nodal involvement, and validation of prognostic factors with respect to their predictive value to treatment outcome.     

The control of protein release from poly(DL-lactide co-glycolide) microparticles by variation of the external aqueous phase surfactant in the water-in oil-in water method

A unique feature of p21 that distinguishes it from the other cyclin-dependent kinase (CDK) inhibitors is its ability to associate with the proliferating cell nuclear antigen (PCNA), an auxiliary factor for DNA polymerases delta and epsilon. While it is now well established that inhibition of cyclin/CDK complexes by p21 can result in G1 cell cycle arrest, the consequences of p21/PCNA interaction on cell cycle progression have not yet been determined. Here, we show, using a tetracycline-regulated system, that expression of wild-type p21 in p53-deficient DLD1 human colon cancer cells inhibits DNA synthesis and causes G1 and G2 cell cycle arrest. Similar effects are observed in cells expressing p21CDK-, a mutant impaired in the interaction with CDKs, but not in cells expressing p21PCNA-, a mutant deficient for the interaction with PCNA. Analysis of cells treated with a p21-derived PCNA-binding peptide provides additional evidence that the growth inhibitory effects of p21 and p21CDK result from their ability to bind to PCNA. Our results suggest that p21 might inhibit cell cycle progression by two independent mechanisms, inhibition of cyclin/CDK complexes, and inhibition of PCNA function resulting in both G1 and G2 arrest.     

Role of bradykinin B2 receptors in neonatal kidney growth

OBJECTIVES: As the incidence of prostate cancer in the United States exceeds 330,000 in 1997, increasingly more men are faced with treatment choices for which there is no clear approach. At every stage of disease, these treatment choices may involve clinically equivalent modalities that differ in side effects and impact upon quality of life (QOL). Comprehensive, yet efficient, questionnaires are needed to measure QOL in patients with prostate cancer. METHODS: Developed as a disease-specific adjunct to the Functional Assessment of Cancer Therapy (FACT) measurement system, a 12-item prostate cancer subscale (PCS) was developed and tested in three independent samples: a subscale development sample (n = 43), validity sample 1 (n = 34), and validity sample 2 (n = 96). The 12 items ask about symptoms and problems specific to prostate cancer. These questions are added to the general (FACT-G) instrument, thereby comprising a 47-item questionnaire. RESULTS: Internal consistency of the PCS ranged from 0.65 to 0.69, with coefficients for FACT-G subscales and aggregated scores ranging from 0.61 to 0.90. Concurrent validity was confirmed by the ability to discriminate patients by disease stage, performance status, and baseline prostate-specific antigen (PSA) level. Sensitivity to change in performance status and PSA score over a 2-month period suggested that some subscales of the FACT-Prostate (P) (including the PCS) are sensitive to meaningful clinical change. CONCLUSIONS: Our findings support use of the FACT-P as a meaningful component of QOL evaluation in men undergoing therapy for prostate cancer.     

Interaction of c-myc with transforming growth factor alpha and hepatocyte growth factor in hepatocarcinogenesis

Double transgenic mice bearing fusion genes consisting of mouse albumin enhancer/promoter-mouse c-myc cDNA and mouse metallothionein 1 promoter-human TGF-alpha cDNA were generated to investigate the interaction of these genes in hepatic oncogenesis and to provide a general paradigm for characterizing the interaction of nuclear oncogenes and growth factors in tumorigenesis. Coexpression of c-myc and TGF-alpha as transgenes in the mouse liver resulted in a tremendous acceleration of neoplastic development in this organ as compared to expression of either of these transgenes alone. The two distinct cellular reactions that occurred in the liver of the double transgenic mice prior to the appearance of liver tumors were dysplastic and apoptotic changes in the existing hepatocytes followed by emergence of multiple focal lesions composed of both hyperplastic and dysplastic cell populations. These observations suggest that the interaction of c-myc and TGF-alpha, during development of hepatic neoplasia contributes to the selection and expansion of the preneoplastic cell populations which consequently increases the probability of malignant conversion. These studies have now been extended to examine the interaction of hepatocyte growth factor (HGF) with c-myc during hepatocarcinogenesis in the transgenic mouse model. While sustained overexpression of c-myc in the liver leads to cancer, coexpression of HGF and c-myc in the liver delayed the appearance of preneoplastic lesions and prevented malignant conversion. Similarly, tumor promotion by phenobarbital was completely inhibited in the c-myc/HGF double transgenic mice whereas phenobarbital was an effective tumor promoter in the c-myc single transgenic mice. The results indicate that HGF may function as a tumor suppressor during early stages of liver carcinogenesis, and suggest the possibility of therapeutic application for this cytokine. Furthermore, we show for the first time that interaction of c-myc with HGF or TGF-alpha results in profoundly different outcomes of the neoplastic process in the liver.     

Discrete element analysis of experiments on mixing and stoking of monodisperse spheres on a grate

Understanding the details of the mixing and stoking process on grate firing systems is crucial for the optimization of the combustion process in waste or biomass incineration plants. The Discrete Element Method (DEM) can help to obtain further information on the mixing process within a bed of fuel particles. Especially the influence of a change in operational parameters can be examined avoiding large experimental effort. In the current paper five simulations for a generic grate are compared with the corresponding experiments. The experiments were carried out throughout an anterior parameter study on mixing and stoking on a grate [Sudbrock F.; Simsek E.; Wirtz S.; Scherer V.: “An experimental analysis of the influence of operational parameters on mixing and stoking of a monodisperse granulate on a grate”, Powder Technology 198, Issue 1, 29-37, 2010] [19]. The system considered is equipped with vertically moving bars which induce stoking. In a first approach monodisperse plastic spheres are used. The grate is encased by a transparent polycarbonate housing which provides optical access to the movement of the particles in the wall planes. The mixing process is measured and quantified by image analysis of the front wall of the grate. The mixing behaviour of the particle assembly observed in experiments and simulation appears to be very similar indicating that DEM is able to predict the particle mixing in the bed. In order to quantify the visual observations the mixing behaviour has been evaluated by different mixing parameters. They are compared in dependence of the number of strokes of the grate bars. A good agreement between measurements and simulations could be observed.     

Biochemical methane potential (BMP) of solid organic substrates: evaluation of anaerobic biodegradability using data from an international interlaboratory study

BACKGROUND: This paper describes results obtained for different participating research groups in an interlaboratory study related to biochemical methane potential (BMP). In this research work, all experimental conditions influencing the test such as inoculum, substrate characteristics and experimental conditions were investigated. The study was performed using four substrates: three positive control substrates (starch, cellulose and gelatine), and one raw biomass material (mung bean) at two different inoculum to substrate ratios (ISR). RESULTS: The average methane yields for starch, cellulose, gelatine and mung bean at ISR of 2 and 1 were 350 ± 33, 350 ± 29, 380 ± 42, 370 ± 36 and 370 ± 35 mL CH₄ g^?1 VS_added, respectively. The percentages of biotransformation of these substrates into methane were 85 ± 8, 85 ± 7, 88 ± 9, 85 ± 8 and 85 ± 8%, respectively. On the other hand, the first‐order rate constants obtained from the experimental data were 0.24 ± 0.14, 0.23 ± 0.15, 0.27 ± 0.13, 0.31 ± 0.17 and 0.23 ± 0.13 d^?1, respectively. CONCLUSION: The influence of inocula and experimental factors was nearly insignificant with respect to the extents of the anaerobic biodegradation, while the rates differed significantly according to the experimental approaches. Copyright © 2011 Society of Chemical Industry     

Mechanisms of cement hydration

The current state of knowledge of cement hydration mechanisms is reviewed, including the origin of the period of slow reaction in alite and cement, the nature of the acceleration period, the role of calcium sulfate in modifying the reaction rate of tricalcium aluminate, the interactions of silicates and aluminates, and the kinetics of the deceleration period. In addition, several remaining controversies or gaps in understanding are identified, such as the nature and influence on kinetics of an early surface hydrate, the mechanistic origin of the beginning of the acceleration period, the manner in which microscopic growth processes lead to the characteristic morphologies of hydration products at larger length scales, and the role played by diffusion in the deceleration period. The review concludes with some perspectives on research needs for the future.     

Influence of Radiation‐Induced Grafting Process on Mechanical Properties of ETFE‐Based Membranes for Fuel Cells

The mechanical stability is, in addition to thermal and chemical stability, a primary requirement of polymer electrolyte membranes in fuel cells. In this study, the impact of grafting parameters and preparation steps on stress–strain properties of ETFE‐based proton conducting membranes, prepared by radiation‐induced grafting and subsequent sulphonation, was studied. No significant change in the mechanical properties of the ETFE base film was observed below an irradiation dose of 50 kGy. It was shown that the elongation at break decreases with increasing both the crosslinker concentration and graft level (GL). However, the tensile strength was positively affected by the crosslinker concentration. Yield strength and modulus of elasticity are almost unaffected by the introduction of crosslinker. Interestingly, yield strength and modulus of elasticity increase gradually with GL without noticeable change of the inherent crystallinity of grafted films. The most brittle membranes are obtained via the combination of high GL and crosslinker concentration. The optimised ETFE‐based membrane (GL of ∼25%, 5% DVB v/v), shows mechanical properties superior to those of Nafion® 112 membrane. The obtained results were correlated qualitatively to the other ex situ properties, including crystallinity, thermal properties and water uptake of the grafted membranes.