bluuebunny/crossref_metadata_2025 huggingface dataset:
New milliliter‐scale stirred tank bioreactors for the cultivation of mycelium forming microorganisms
Authors: Hortsch Ralf , Stratmann Ansgar , Weuster‐Botz Dirk
Published: March 2010

A novel milliliter‐scale stirred tank bioreactor was developed for the cultivation of mycelium forming microorganisms on a 10 milliliter‐scale. A newly designed one‐sided paddle impeller is driven magnetically and rotates freely on an axis in an unbaffled reaction vessel made of polystyrene. A rotating lamella is formed which spreads out along the reactor wall. Thus an enhanced surface‐to‐volume ratio of the liquid phase is generated where oxygen is introduced via surface aeration. Volumetric oxygen transfer coefficients (kLa) > 0.15 s−1 were measured. The fast moving liquid lamella efficiently prevents wall growth and foaming. Mean power consumption and maximum local energy dissipation were measured as function of operating conditions in the milliliter‐scale stirred tank bioreactor (V = 10 mL) and compared to a standard laboratory‐scale stirred tank bioreactor with six‐bladed Rushton turbines (V = 2,000 mL). Mean power consumption increases with increasing impeller speed and shows the same characteristics and values on both scales. The maximum local energy dissipation of the milliliter‐scale stirred tank bioreactor was reduced compared to the laboratory‐scale at the same mean volumetric power input. Hence the milliliter impeller distributes power more uniformly in the reaction medium. Based on these data a reliable and robust scale‐up of fermentation processes is possible. This was demonstrated with the cultivation of the actinomycete Streptomyces tendae on both scales. It was shown that the process performances were equivalent with regard to biomass concentration, mannitol consumption and production of the pharmaceutical relevant fungicide nikkomycin Z up to a process time of 120 h. A high parallel reproducibility was observed on the milliliter‐scale (standard deviation < 8%) with up to 48 stirred tank bioreactors operated in a magnetic inductive drive. Rheological behavior of the culture broth was measured and showed a highly viscous shear‐thinning non‐Newtonian behavior. The newly developed one‐sided paddle impellers operated in unbaffled reactors on a 10 milliliter‐scale with a magnetic inductive drive for up to 48 parallel bioreactors allows for the first time the parallel bioprocess development with mycelium forming microorganisms. This is especially important since these kinds of cultivations normally exhibit process times of 100 h and more. Thus the operation of parallel stirred tank reactors will have the potential to reduce process development times drastically. Biotechnol. Bioeng. 2010; 106: 443–451. © 2010 Wiley Periodicals, Inc.
Adventures in time and space: Nonlinearity and complexity of cytokine effects on stem cell fate decisions
Authors: Audet Julie
Published: March 2010

Cytokines are central factors in the control of stem cell fate decisions and, as such, they are invaluable to those interested in the manipulation of stem and progenitor cells for clinical or research purposes. In their in vivo niches or in optimized cultures, stem cells are exposed to multiple cytokines, matrix proteins and other cell types that provide individual and combinatorial signals that influence their self‐renewal, proliferation and differentiation. Although the individual effects of cytokines are well‐characterized in terms of increases or decreases in stem cell expansion or in the production of specific cell lineages, their interactions are often overlooked. Factorial design experiments in association with multiple linear regression is a powerful multivariate approach to derive response‐surface models and to obtain a quantitative understanding of cytokine dose and interactions effects. On the other hand, cytokine interactions detected in stem cell processes can be difficult to interpret due to the fact that the cell populations examined are often heterogeneous, that cytokines can exhibit pleiotropy and redundancy and that they can also be endogenously produced. This perspective piece presents a list of possible biological mechanisms that can give rise to positive and negative two‐way factor interactions in the context of in vivo and in vitro stem cell‐based processes. These interpretations are based on insights provided by recent studies examining intra‐ and extra‐cellular signaling pathways in adult and embryonic stem cells. Cytokine interactions have been classified according to four main types of molecular and cellular mechanisms: (i) interactions due to co‐signaling; (ii) interactions due to sequential actions; (iii) interactions due to high‐dose saturation and inhibition; and (iv) interactions due to intercellular signaling networks. For each mechanism, possible patterns of regression coefficients corresponding to the cytokine main effects, quadratic effects and two‐way interactions effects are provided. Finally, directions for future mechanistic studies are presented. Biotechnol. Bioeng. 2010;106: 173–182. © 2010 Wiley Periodicals, Inc.
Effect of chloride on ferrous iron oxidation by a Leptospirillum ferriphilum‐dominated chemostat culture
Authors: Gahan Chandra Sekhar , Sundkvist Jan‐Eric , Dopson Mark , Sandström Åke
Published: March 2010

Biomining is the use of microorganisms to catalyze metal extraction from sulfide ores. However, the available water in some biomining environments has high chloride concentrations and therefore, chloride toxicity to ferrous oxidizing microorganisms has been investigated. Batch biooxidation of Fe2+ by a Leptospirillum ferriphilum‐dominated culture was completely inhibited by 12 g L−1 chloride. In addition, the effects of chloride on oxidation kinetics in a Fe2+ limited chemostat were studied. Results from the chemostat modeling suggest that the chloride toxicity was attributed to affects on the Fe2+ oxidation system, pH homeostasis, and lowering of the proton motive force. Modeling showed a decrease in the maximum specific growth rate (µmax) and an increase in the substrate constant (Ks) with increasing chloride concentrations, indicating an effect on the Fe2+ oxidation system. The model proposes a lowered maintenance activity when the media was fed with 2–3 g L−1 chloride with a concomitant drastic decrease in the true yield (Ytrue). This model helps to understand the influence of chloride on Fe2+ biooxidation kinetics. Biotechnol. Bioeng. 2010; 106: 422–431. © 2010 Wiley Periodicals, Inc.
Motif‐based search for a novel fructosyl peptide oxidase from genome databases
Authors: Kim Seungsu , Ferri Stefano , Tsugawa Wakako , Mori Kazushige , Sode Koji
Published: March 2010

The measurement of glycated hemoglobin A1c (HbA1c) has important implications for diagnosis of diabetes and assessment of treatment effectiveness. We proposed specific sequence motifs to identify enzymes that oxidize glycated compounds from genome database searches. The gene encoding a putative fructosyl amino acid oxidase was found in the Phaeosphaeria nodorum SN15 genome and successfully expressed in Escherichia coli. The recombinant protein (XP_001798711) was confirmed to be a novel fructosyl peptide oxidase (FPOX) with high specificity for α‐glycated compounds, such as HbA1c model compounds fructosyl‐αN‐valine (f‐αVal) and fructosyl‐αN‐valyl‐histidine (f‐αVal‐His). Unlike previously reported FPOXs, the P. nodorum FPOX has a Km value for f‐αVal‐His (0.185 mM) that is considerably lower than that for f‐αVal (0.458 mM). Based on amino acid sequence alignment, three dimensional structural modeling, and site‐directed mutagenesis, Gly60 was found to be a determining residue for the activity towards f‐αVal‐His. A flexible surface loop region was also found to likely play an important role in accepting f‐αVal‐His. Biotechnol. Bioeng. 2010; 106: 358–366. © 2010 Wiley Periodicals, Inc.
Scaling‐up of complex whole‐cell bioconversions in conventional and non‐conventional media
Authors: Marques Marco P.C. , de Carvalho Carla C.C.R. , Cabral Joaquim M.S. , Fernandes Pedro
Published: March 2010

The use of whole cells is becoming a more common approach in pharmaceutical and agrochemical industries in order to obtain pure compounds with fewer production steps, higher yields, and cleaner processes, as compared to those achieved with traditional strategies. Whole cells are often used as enzymes pools, in particular when multi‐step reactions and/or co‐factor regeneration are envisaged. Nonetheless, published information on the scale‐up of such systems both in aqueous and in two‐phase aqueous–organic systems is relatively scarce. The present work aims to evaluate suitable scale‐up criteria in conventional and non‐conventional medium for a whole‐cell bioconversion that uses resting cells of Mycobacterium sp. NRRL B‐3805 to cleave the side chain of β‐sitosterol, a poorly water‐soluble substrate. The experiments were performed in 24‐well microtiter plates and in 250 mL shaken flasks as orbital stirred systems, and in 300 mL stirred tanks as mechanically stirred systems. Results show that productivity yields were similar in all scales tested, when maintaining oxygen mass transfer coefficients constant in aqueous systems, or when maintaining constant volumetric power consumption in aqueous–organic two‐phase systems. Biotechnol. Bioeng. 2010;106: 619–626. © 2010 Wiley Periodicals, Inc.
Characterization of a whole‐cell catalyst co‐expressing glycerol dehydrogenase and glucose dehydrogenase and its application in the synthesis of L‐glyceraldehyde
Authors: Richter Nina , Neumann Markus , Liese Andreas , Wohlgemuth Roland , Weckbecker Andrea , Eggert Thorsten , Hummel Werner
Published: March 2010

A whole‐cell catalyst using Escherichia coli BL21(DE3) as a host, co‐expressing glycerol dehydrogenase (GlyDH) from Gluconobacter oxydans and glucose dehydrogenase (GDH) from Bacillus subtilis for cofactor regeneration, has been successfully constructed and used for the reduction of aliphatic aldehydes, such as hexanal or glyceraldehyde to the corresponding alcohols. This catalyst was characterized in terms of growth conditions, temperature and pH dependency, and regarding the influence of external cofactor and permeabilization. In the case of external cofactor addition we found a 4.6‐fold increase in reaction rate caused by the addition of 1 mM NADP+. Due to the fact that pH and temperature are also factors which may affect the reaction rate, their effect on the whole‐cell catalyst was studied as well. Comparative studies between the whole‐cell catalyst and the cell‐free system were investigated. Furthermore, the successful application of the whole‐cell catalyst in repetitive batch conversions could be demonstrated in the present study. Since the GlyDH was recently characterized and successfully applied in the kinetic resolution of racemic glyceraldehyde, we were now able to transfer and establish the process to a whole‐cell system, which facilitated the access to L‐glyceraldehyde in high enantioselectivity at 54% conversion. All in all, the whole‐cell catalyst shows several advantages over the cell‐free system like a higher thermal, a similar operational stability and the ability to recycle the catalyst without any loss‐of‐activity. The results obtained making the described whole‐cell catalyst an improved catalyst for a more efficient production of enantiopure L‐glyceraldehyde. Biotechnol. Bioeng. 2010;106: 541–552. © 2010 Wiley Periodicals, Inc.
Fabrication of Fluorescent Silica Nanoparticles Hybridized with AIE Luminogens and Exploration of Their Applications as Nanobiosensors in Intracellular Imaging
Authors: Faisal Mahtab , Hong Yuning , Liu Jianzhao , Yu Yong , Lam Jacky W. Y. , Qin Anjun , Lu Ping , Tang Ben Zhong
Published: March 2010

Highly emissive inorganic–organic nanoparticles with core–shell structures are fabricated by a one‐pot, surfactant‐free hybridization process. The surfactant‐free sol–gel reactions of tetraphenylethene‐ (TPE) and silole‐functionalized siloxanes followed by reactions with tetraethoxysilane afford fluorescent silica nanoparticles FSNP‐1 and FSNP‐2, respectively. The FSNPs are uniformly sized, surface‐charged and colloidally stable. The diameters of the FSNPs are tunable in the range of 45–295 nm by changing the reaction conditions. Whereas their TPE and silole precursors are non‐emissive, the FSNPs strongly emit in the visible vision, as a result of the novel aggregation‐induced emission (AIE) characteristics of the TPE and silole aggregates in the hybrid nanoparticles. The FSNPs pose no toxicity to living cells and can be utilized to selectively image cytoplasm of HeLa cells.
Nanostructure Copper‐exchanged ZSM‐5 Catalytic Activity for Conversion of Volatile Organic Compounds (Toluene and Ethyl Acetate)
Authors: Hosseini S. Ali , Niaei Aligholi , Salari Dariush , Aghazadeh Faezeh
Published: March 2010

Gas phase catalytic oxidation of ethyl acetate and toluene was examined over copper modified ZSM‐5 catalysts under atmospheric pressure. Nanostructure of ZSM‐5 was characterized by XRD, SEM and TEM techniques. Elemental composition of ZSM‐5 was determined using EDX, ICP‐AES and XPS techniques. Results of catalytic studies showed better catalytic activity of Cu‐ZSM‐5 catalysts than those of parent ZSM‐5 and HZSM‐5, which revealed catalytic role of copper ions in the Cu‐ZSM‐5 catalysts. Effects of some parameters over catalytic conversion of these compounds were also studied. Ethyl acetate showed more reactivity than toluene over the Cu‐ZSM‐5 catalysts. Furthermore, the catalytic activity of Cu‐ZSM‐5 catalysts increased with increasing the copper loadings. The conversion behavior of a binary mixture of ethyl acetate and toluene was different from that of a single form. A promotive and inhibitive behavior was observed for conversion of ethyl acetate and toluene in the binary mixture, respectively. Water vapor as co‐feed had an inhibitive effect on conversion of organic compounds over the Cu‐ZSM‐5 catalysts.
A Thermodynamic Study on the Binding of Human Serum Albumin with Lanthanum Ion
Authors: Rezaei Behbehani G. , Divsalar A. , Saboury A. A. , Faridbod F. , Ganjali M. R.
Published: March 2010

Thermodynamics of the interaction between lanthanum(III) ion, La3+, and human serum albumin (HSA), was investigated at pH 7.0 and 300 K in Tris‐HCl buffer by isothermal titration calorimetry. A solvation model was used to reproduce the enthalpies of HSA interaction with La3+. The solvation parameters recovered from our new model were attributed to the structural change of HSA and its biological activity. The interaction of HSA with La3+ showed a set of two binding sites with negative cooperativity.
Orientation of the Azobenzene Spacer of Carboxylic Methyl Ester Gemini Surfactants in Langmuir Monolayer
Authors: Song Binglei , Zhao Jianxi
Published: March 2010

The Langmuir monolayer of carboxylic methyl ester Gemini surfactants with the azobenzene spacer, referred to as MCm(azo)MCm, was prepared and the π‐A isotherms were measured. The result revealed an orientational picture of the azobenzene spacer at the air/water interface. Before irradiation, the planar trans‐azobenzene group adopted an approximate configuration parallel to the interface and lay on the air/water interface. After UV‐light irradiation, the spacer became the twisted cis‐one. Because of the location of the polar headgroups at the air/water interface, the two phenyl rings were also forced to take a near‐parallel orientation with the interface to reduce the free energy. As a result, the spacer thin‐layer was "thickened", which caused an elevation in collapse pressure.
Ultrasound‐enhanced Green Synthesis of 5,5‐Diphenylhydantoin Derivatives Using Symmetrical or Unsymmetrical Benzils
Authors: Safari Javad , Moshtael Arani Naimeh , Ramezan Isfahani Anousheh
Published: March 2010

A rapid, highly efficient and mild green synthesis of 5,5‐diphenylhydantoin derivatives was achieved from the reaction of symmetrical or unsymmetrical benzil derivatives with urea in the presence of ethanolic KOH under ultrasound irradiation. This simple method affords 5,5‐diphenylhydantoin derivatives at room temperature in short reaction time with high yield and purity. This study aimed to overcome the limitations and drawbacks of the reported methods such as tedious work‐up, low yield and long reaction time.
Fast and Eco‐friendly Synthesis of Dipyrromethanes by H2SO4·SiO2 Catalysis under Solvent‐free Conditions
Authors: Zhang Yan , Liang Jun , Shang Zhicai
Published: March 2010

For the first time, sillica‐supported sulfuric acid has been used as a heterogeneous, reusable and efficient catalyst at room temperature to give the corresponding dipyrromethanes in a very short reaction time. The new reaction procedure is simple and solvent is not required.
Synthesis, Structure and in vitro Antitumor Activity of a Multinuclear Diorganotin(IV) Complex [(n‐Bu)4Sn2{2,5‐F2C6H3C(O)NHO}2{2,5‐F2C6H3C(NO)O}]2
Authors: Shang Xianmei , Meng Xianggao , Li Qingshan
Published: March 2010

A new multinuclear dibutyltin(IV) complex [(n‐Bu)4Sn2{2,5‐F2C6H3C(O)NHO}2{2,5‐F2C6H3C(NO)O}]2 1, was synthesized and structurally characterized by melting point measurement, elemental analysis, FT‐IR, 1H, 13C, 119Sn NMR spectroscopies, and X‐ray diffraction analysis. The complex exhibited in vitro antitumor activity against a murine sarcoma carcinoma cell line (S‐180), which was higher than that of 5‐fluorouracil (5‐Fu), currently used clinically as an antitumor agent.
One‐pot Synthesis of 3‐Aminoimidazo[1,2‐a]pyridines Catalyzed by Heteropolyacids
Authors: Oskooie Hossein A. , Amini Maryam , Heravi Majid M. , Bamoharram Fatemeh F.
Published: March 2010

Condensation of aldehydes, isonitriles and 2‐aminopyridines in the presence of H3PMo12O40 affords different derivatives of 3‐aminoimidazo[1,2‐a]pyridine in good to excellent yields.
Simultaneous Determination of Phenolic Additives in Cosmetics by Micellar Electrokinetic Capillary Chromatography with Electrochemical Detection
Authors: Wang Jinyan , Zhang Dongli , Chu Qingcui , Ye Jiannong
Published: March 2010

A micellar electrokinetic capillary chromatography method with electrochemical detection (MECC‐ED) has been developed for the simultaneous determination of eight phenolic additives, including propyl gallate (PG), tert‐butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), methylparaben (MP), ethylparaben (EP), propylparaben (PP) and butylparaben (BP) in cosmetic products. Method development involved optimization of the working electrode, the pH value of running buffer, the concentration of sodium dodecyl sulfate (SDS), the separation voltage, and the sample injection time. Under the optimum conditions, all analytes can be well separated within 26 min at the separation voltage of 18 kV in a 9 mmol·L−1 sodium dodecyl sulfate (SDS) −60 mmol·L−1 borate running buffer (pH 8.0). A 300 μm diameter carbon disk electrode generated good response at +0.90 V (vs. SCE) for all analytes. Linearity of the present method was over three orders of magnitude of analyte concentration with detection limits (S/N=3) ranging from 1.1×10−7 to 1.2×10−6 g·mL−1 for all analytes. This proposed method has been successfully applied to the simultaneous determination of the above additives in commercial cosmetics, and the assay results were satisfactory.
Prognostic factors for survival in metastatic renal cell carcinoma
Authors: Bukowski Ronald M.
Published: March 2010

A variety of prognostic factor models to predict survival in patients with metastatic renal cell carcinoma have been developed. Diverse populations of patients with variable treatments have been used for these analyses. A variety of clinical, pathologic, and molecular factors have been studied, but current models use predominantly easily obtained clinical factors. These approaches are reviewed, and current approaches to further refine and develop these techniques are reviewed. Cancer 2009;115(10 suppl):2273‐81. © 2009 American Cancer Society.
Treatment of kidney cancer
Authors: Kaelin William G.
Published: March 2010

Germline inactivation of theVHLtumor suppressor gene is associated with an increased risk of clear cell carcinoma of the kidney in the context of von Hippel‐Lindau (VHL) disease. SomaticVHLmutations are also common in nonhereditary (sporadic) clear cell carcinomas. The VHL protein (pVHL) has multiple functions that might be linked to tumor suppression, including targeting the hypoxia inducible factor (HIF) transcription factor for polyubiquitylation and proteasomal degradation. HIF, especially HIF2α, appears to play a causal role in clear cell renal carcinogenesis based on genotype‐phenotype correlations in VHL disease, laboratory experiments with humanVHL−/− renal carcinoma cell lines, and genetically engineered mouse models. Deregulation of HIF almost certainly accounts for the high levels of vascular endothelial growth factor (VEGF) observed in kidney cancer and relates to their sensitivity to VEGF inhibitors. In addition, the beneficial effects of mammalian target of rapamycin (mTOR) inhibitors are likely due to, at least partly, their ability to down‐regulate HIF. pVHL, in a HIF‐independent manner, also regulates a specialized structure called the primary cilium and regulates apoptosis via factors such as NFκB. Loss of the primary cilium probably facilitates the development of preneoplastic renal cysts, whereas increased NFκB might contribute to the resistance of kidney cancers to conventional cytotoxic agents. Cancer 2009;115(10 suppl):2262‐72. © 2009 American Cancer Society.
Magnetic resonance imaging as a biomarker in renal cell carcinoma
Authors: Pedrosa Ivan , Alsop David C. , Rofsky Neil M.
Published: March 2010

The ability to noninvasively discriminate the most common types of renal cell carcinoma (RCC) based on their magnetic resonance imaging (MRI) appearances or their magnetic resonance phenotypes is achievable. Intracellular lipids, a histologic characteristic of the clear cell RCC, can be identified on chemical shift MRI. Intratumoral hemosiderin deposition, as observed histologically with papillary RCC, correlates to the low signal intensity on T2‐weighted images. In addition to morphologic imaging features, the different subtypes of RCC have distinct patterns of enhancement on dynamic contrast‐enhanced MRI. Clear cell tumors demonstrate much greater enhancement than papillary and chromophobe RCCs during the corticomedullary and nephrographic phases. The MRI technique arterial spin labeling (ASL) uses magnetic fields to label the water protons in arterial blood and measures blood flow into tissue; quantitative images of blood flow can be generated without exogenous contrast media. Multiple measurements of tumor perfusion may be repeated before and after a physiologic or drug challenge (ie, antiangiogenic therapy). In RCC xenografts and in patients with metastatic RCC, ASL MRI assessments can be used to monitor blood flow changes in response to antiangiogenic therapies. High blood flow on ASL MRI in RCC xenografts correlates with viable tumor at histopathologic analysis, whereas zones of absent or diminished signal correspond to necrosis. ASL MRI has the potential to serve as a biomarker for patients with metastatic RCC by offering a noninvasive measure of tumor blood flow changes accompanying antiangiogenic therapy. Cancer 2009;115(10 suppl):2334‐45. © 2009 American Cancer Society.
Complexity of tumor vasculature in clear cell renal cell carcinoma
Authors: Qian Chao‐Nan , Huang Dan , Wondergem Bill , Teh Bin Tean
Published: March 2010

Clear cell renal cell carcinoma (CCRCC) is a highly vascularized cancer resistant to conventional chemotherapy and radiotherapy. Antiangiogenic therapy has achieved some effectiveness against this unique malignancy. The complexity of the tumor vasculature in CCRCC has led to differences in correlating tumor microvessel density with patient prognosis. The authors' recent findings demonstrated that there were at least 2 major categories of tumor vessels in CCRCC—namely, undifferentiated and differentiated—correlating with patient prognosis in contrasting ways, with higher undifferentiated vessel density indicating poorer prognosis, and higher differentiated vessel density correlating with better prognosis. Furthermore, the presence of pericytes supporting the differentiated vessels varied in CCRCC. The distributions of pericyte coverage and differentiated vessels in CCRCC were uneven. The tumor margin had a higher pericyte coverage rate for differentiated vessels than did the inner tumor area. The uneven distributions of pericyte coverage and differentiated vessels in CCRCC prompted the authors to revisit the mechanism of tumor central necrosis, which was also known to be a prognostic indicator for CCRCC. The discrepancy of prognostic correlation between protein and messenger RNA levels of vascular endothelial growth factor in CCRCC was discussed. The complexity of the tumor vasculature in CCRCC also led the authors to begin to re‒evaluate the therapeutic effects of antiangiogenic agents for each type of tumor vessel, which will in turn significantly broaden understanding of tumor angiogenesis and improve therapeutic effect. Cancer 2009;115(10 suppl):2282‐9. © 2009 American Cancer Society.
Neoadjuvant (presurgical) therapy for renal cell carcinoma: A new treatment paradigm for locally advanced and metastatic disease
Authors: Wood Christopher G. , Margulis Vitaly
Published: March 2010

BACKGROUND:

Although upfront cytoreductive nephrectomy followed by systemic therapy remains the standard of care for metastatic renal cell carcinoma, the addition of novel targeted therapy has prompted a reevaluation of this treatment paradigm. The authors reviewed their experience with neoadjuvant systemic therapy administered before cytoreductive surgery for metastatic, locally recurrent, or regionally advanced renal cell carcinoma.

METHODS:

The authors compared patients treated with presurgical targeted therapy (with sunitinib, sorafenib, or bevacizumab) with a contemporary group that underwent up‐front cytoreductive surgery.

RESULTS:

The authors found no difference in any perioperative surgical parameters indicative of morbidity or mortality between the 2 groups. Laboratory models of renal cell carcinoma treated with systemic targeted therapy demonstrate specific protein expression profiles that correlate with response to therapy and the development of therapy resistance.

CONCLUSIONS:

Neoadjuvant (presurgical) targeted therapy before cytoreductive surgery appears safe in the setting of metastatic renal cell carcinoma. It identifies patients who respond to systemic therapy before surgery, thus avoiding highly morbid surgery in patients destined for a poor outcome. Further studies are needed to identify the molecular endpoints associated with treatment response and the development of the resistant phenotype, which will in turn identify novel transduction pathways worthy of therapeutic development. Cancer 2009;115(10 suppl):2355‐60. © 2009 American Cancer Society.
Sequential therapy in renal cell carcinoma
Authors: Escudier Bernard , Goupil Marine Gross , Massard Christophe , Fizazi Karim
Published: March 2010

Because of the recent approval of several drugs for the treatment of renal cell carcinoma (including sorafenib, sunitinib, temsirolimus, and, in Europe, bevacizumab plus interferon), the use of sequential therapy has become routine practice. There is now evidence that administering these targeted agents sequentially provides clinical benefit by inducing tumor shrinkage and prolonged progression‐free survival (PFS) in a large number of patients. However, data regarding overall survival (OS) are still pending. By adding these drugs in an adequate order, one can expect an increase in overall PFS of up to 27 months and a subsequent improvement in the OS of patients with renal cell carcinoma. It has been recently reported that the OS of patients treated with sunitinib in the first‐line setting was 26 months. Expecting a survival of 40 months does appear possible based on currently available data, although this assumption will have to be proven in the future. Cancer 2009;115(10 suppl):2321‐6. © 2009 American Cancer Society.
Conclusions and reflections
Authors: Denis Louis J. , Gospodarowicz Mary K.
Published: March 2010

Validated prognostic factors are an integral part of any cancer diagnosis. The available proliferation of new markers and randomized clinical trial results leads to a complex decision making looking for optimal treatment and outcome results. Advanced mathematic models have been developed to weigh each specific prognostic factor into a single outcome number in nomograms modeled for specific predictive accuracy in key phases of the treated history of the disease. Despite this progress, it is important to realize that the results are an outcome stratification for groups rather than for the individual patient. It is clear that in the tumor prognosis, host and environmental factors need to be evaluated before any clinical decision is made. Cancer 2009;115(13 suppl):3160–2. © 2009 American Cancer Society.
Nomograms for staging, prognosis, and predicting treatment outcomes
Authors: Touijer Karim , Scardino Peter T.
Published: March 2010

Prostate cancer is a heterogeneous disease with a wide prognostic spectrum and a variety of treatment options. Such a complex clinical scenario has led to uncertainty in risk assessment and prediction of outcome. Nomograms have served as scientific formulas designed to maximize the predictive accuracy. The use of nomograms in prostate cancer has been applied to many clinical states and outcomes and has provided the most accurate predictions. Cancer 2009;115(13 suppl):3107–11. © 2009 American Cancer Society.
Systems pathology
Authors: Donovan Michael J. , Costa Jose , Cordon‐Cardo Carlos
Published: March 2010

Diagnostic tumor pathology in the context of personalized medicine has progressed from an interpretive, subjective science to a more objective, evidence‐based practice. This has resulted in the development of several tissue‐based, molecular‐driven tests that provide information regarding prognosis and response to therapy. The challenge, however, for both the pathologist and the treating physician is how best to effectively integrate this data into a comprehensive treatment plan that includes a patient‐specific risk assessment. To address this need, the authors developed a systems pathology approach to the practice of clinical molecular medicine through technical advances in object‐oriented image analysis, and phenotyping at the microanatomical level using deparaffinized tissue section and quantitative biomarker multiplexing. With support vector regression for censored data, they have been able to integrate complex information and provide a patient‐specific risk profile based on the clinical endpoint under investigation. Cancer 2009;115(13 suppl):3078–84. © 2009 American Cancer Society.
Predictive models of toxicity in external radiotherapy
Authors: Fiorino Claudio , Rancati Tiziana , Valdagni Riccardo
Published: March 2010

Dose‐volume modeling of late and acute toxicity in radiotherapy for prostate cancer is a rapidly evolving field of investigation. The availability of individual, 3‐dimensional dose distribution and dose‐volume histograms (DVHs) permits the quantitative assessment of dose‐volume relations for specific endpoints by investigating the correlation between individual dose‐volume data and clinical outcomes. These studies often entail a huge effort in collecting data from large populations that have been followed properly for long time. The rectum is the most investigated organ, especially concerning late bleeding, and a good consensus regarding serial‐like behavior for this endpoint comes from various investigations. Concerning the bladder, the existence of a clear dose effect when the organ is wholly or partially irradiated is well known. Concerning erectile dysfunctions, the wide use of hormone therapy and drugs against impotence suggests that large, prospectively scored populations will be necessary to definitively assess dose‐volume relations. Bowel irradiation during prostate cancer radiotherapy occurs during pelvic lymph node irradiation, and severe acute toxicity has yet to be modeled clearly. Evidence of a correlation between the DVH of the intestinal cavity and bowel toxicity recently was reported, providing important information about optimal dose‐volume constraints to be used during whole‐pelvis irradiation with intensity‐modulated radiotherapy. Cancer 2009;115(13 suppl):3135–40. © 2009 American Cancer Society.
Predictive models of toxicity with external radiotherapy for prostate cancer
Authors: Valdagni Riccardo , Rancati Tiziana , Fiorino Claudio
Published: March 2010

The objective of the current study was to analyze the state of the art and present limitations of available predictive clinical models (when available) estimating the risk of genitourinary tract and small bowel complications, erectile dysfunction, and acute and late symptoms of the rectal syndrome caused by prostate cancer external irradiation. An analysis of the literature indicated that very limited attention has been devoted to the development of “integrated,” patient‐tailored, user‐friendly, and clinically usable tools for the prediction of external beam radiotoxicity. In this article, the authors reported on the multivariate correlation between late genitourinary and gastrointestinal toxicities and clinical/dosimetric risk factors, as well as on the first set of nomograms developed to predict acute and late rectal side effects. At the present state of knowledge, the use of nomograms as predictive instruments of radiotoxicity appears to be particularly attractive for several main reasons. They are “user friendly” and easily developed using the results of multivariate analyses, as they weigh the combined effects of multiple independent factors found to be correlated with the selected clinical endpoint. The integrated evaluation of clinical and dosimetric parameters in the single patient can help to provide a tailored probability of the specific outcome considered. Predicting a high probability of toxicity could avoid unnecessary daily costs for the individual patient in terms of quality of life modification during and after treatment, helping patients in the decision‐making process of choosing the best individual, quality of life–related treatment, and clinicians in better tailoring the treatment to patient's characteristics. Cancer 2009;115(13 suppl):3141–9. © 2009 American Cancer Society.
Techniques and predictive models to improve prostate cancer detection
Authors: Herman Michael P. , Dorsey Philip , John Majnu , Patel Nishant , Leung Robert , Tewari Ashutosh
Published: March 2010

The use of prostate‐specific antigen (PSA) as a screening test remains controversial. There have been several attempts to refine PSA measurements to improve its predictive value. These modifications, including PSA density, PSA kinetics, and the measurement of PSA isoforms, have met with limited success. Therefore, complex statistical and computational models have been created to assess an individual's risk of prostate cancer more accurately. In this review, the authors examined the methods used to modify PSA as well as various predictive models used in prostate cancer detection. They described the mathematical underpinnings of these techniques along with their intrinsic strengths and weaknesses, and they assessed the accuracy of these methods, which have been shown to be better than physicians' judgment at predicting a man's risk of cancer. Without understanding the design and limitations of these methods, they can be applied inappropriately, leading to incorrect conclusions. These models are important components in counseling patients on their risk of prostate cancer and also help in the design of clinical trials by stratifying patients into different risk categories. Thus, it is incumbent on both clinicians and researchers to become familiar with these tools. Cancer 2009;115(13 suppl):3085–99. © 2009 American Cancer Society.
Mucosal melanoma of the nose and paranasal sinuses, a contemporary experience from the M. D. Anderson Cancer Center
Authors: Moreno Mauricio A. , Roberts Dianna B. , Kupferman Michael E. , DeMonte Franco , El‐Naggar Adel K. , Williams Michelle , Rosenthal David S. , Hanna Ehab Y.
Published: March 2010

BACKGROUND:

Sinonasal mucosal melanoma is a rare disease associated with a very poor prognosis. Because most of the series extend retrospectively several decades, we sought to determine prognostic factors and outcomes with recent treatment modalities.

METHODS:

A retrospective chart review of 58 patients treated for sinonasal melanoma at a tertiary cancer center between 1993 and 2004. The patients were retrospectively staged according to the sinonasal American Joint Committee on Cancer (AJCC) staging system. Demographic, clinical and pathological parameters were identified and correlated with outcomes.

RESULTS:

There were 35 males and 23 females with a median age of 63 years; 56 patients were treated surgically and 33 received radiation therapy. According to Ballantyne's clinical staging system, 88% of the patients presented with stage I (local) disease. Classification by the AJCC staging classified yielded 27% of the patients with T1, 33% with T2, 21% with T3, and 19% with T4. T‐stage and the degree of tumor pigmentation were associated with a worse survival (P = .0096 and P = .018, respectively), while pseudopapillary architecture was associated with a higher locoregional failure (P = .0144). Postoperative radiation therapy improved locoregional control when a total dose greater than 54 Gy was used (P = .0215), but did not affect overall survival.

CONCLUSIONS:

Tumor stage according to sinonasal AJCC staging system is an effective outcome predictor and should be the staging system of choice. Postoperative radiation therapy improves locoregional control when a higher dose and standard fractionations are used. Histological features such as pigmentation and pseudopapillary architecture are associated with worse outcome. Cancer 2010. © 2010 American Cancer Society.
Quality of end‐of‐life care in low‐income, uninsured men dying of prostate cancer
Authors: Bergman Jonathan , Chi Amanda C. , Litwin Mark S.
Published: March 2010

BACKGROUND:

The quality of end‐of‐life care was assessed in disadvantaged men prospectively enrolled in a public assistance program. That end‐of‐life care would be aggressive, moreso than recommended by quality‐of‐care guidelines, was hypothesized.

METHODS:

Included in the study were all 60 low‐income, uninsured men in a state‐funded public assistance program who had died since its inception in 2001. To measure quality of end‐of‐life care, information was collected regarding timing of the institution of new chemotherapeutic regimens, time from administration of last chemotherapy dose to death, the number of inpatient admissions and intensive care unit stays made in the 3 months preceding death, and the number of emergency room visits made in the 12 months before dying. Also noted were hospice use and the timing of hospice referrals.

RESULTS:

Eighteen men (30%) enrolled in hospice before death and the average hospice stay lasted 45 days (standard deviation, 32; range, 2‐143 days; median, 41 days). Two patients (11%) were enrolled for fewer than 7 days, and none were enrolled for more than 180 days. The average time from administration of the last dose of chemotherapy to death was 104 days. Chemotherapy was never initiated within 3 months of death, and in only 2 instances (6%) was the final chemotherapeutic regimen administered within 2 weeks of dying. Use of hospital resources (emergency room visits, inpatient admissions, and intensive care unit stays) was uniformly low (mean, 1.0 ± 1.0, 0.65 ± 0.82, and 0.03 ± 0.18, respectively).

CONCLUSIONS:

End‐of‐life care in disadvantaged men dying of prostate cancer, who enroll in a comprehensive statewide assistance program, is high‐quality. Cancer 2010. © 2010 American Cancer Society.
Gaussian curvature estimates for the convex level sets of p‐harmonic functions
Authors: Ma Xi‐Nan , Ou Qianzhong , Zhang Wei
Published: March 2010

We give a positive lower bound for the Gaussian curvature of the convex level sets of p‐harmonic functions with the Gaussian curvature of the boundary and the norm of the gradient on the boundary. Combining the deformation process, this estimate gives a new approach to studying the convexity of the level sets of the p‐harmonic function. © 2010 Wiley Periodicals, Inc.
Influence of Radiation‐Induced Grafting Process on Mechanical Properties of ETFE‐Based Membranes for Fuel Cells
Authors: Ben youcef H. , Alkan Gürsel S. , Buisson A. , Gubler L. , Wokaun A. , Scherer G. G.
Published: March 2010

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.
New synthesis of glycerol carbonate from glycerol using sulfur‐assisted carbonylation with carbon monoxide
Authors: Mizuno Takumi , Nakai Takeo , Mihara Masatoshi
Published: March 2010

The glycerol carbonate synthesis from glycerol, which is an inevitable by‐product of biodiesel production, was established. By combined sulfur‐assisted carbonylation of glycerol under 1.0 MPa of carbon monoxide at 80°C in DMF with oxidation by copper bromide(II), a facile synthetic method for glycerol carbonate in good yield was developed. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:99–102, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20583
Dendritic Cells in Liver Fibrosis: Conductor of the Inflammatory Orchestra?
Authors: Aloman Costica , Tacke Frank
Published: March 2010

Abstract

Hepatic fibrosis occurs during most chronic liver diseases and is driven by inflammatory responses to injured tissue. Because DCs are central to modulating liver immunity, we postulated that altered DC function contributes to immunologic changes in hepatic fibrosis and affects the pathologic inflammatory milieu within the fibrotic liver. Using mouse models, we determined the contribution of DCs to altered hepatic immunity in fibrosis and investigated the role of DCs in modulating the inflammatory environment within the fibrotic liver. We found that DC depletion completely abrogated the elevated levels of many inflammatory mediators that are produced in the fibrotic liver. DCs represented approximately 25% of the fibrotic hepatic leukocytes and showed an elevated CD11b+CD8- fraction, a lower B220+ plasmacytoid fraction, and increased expression of MHC II and CD40. Moreover, after liver injury, DCs gained a marked capacity to induce hepatic stellate cells, NK cells, and T cells to mediate inflammation, proliferation, and production of potent immune responses. The proinflammatory and immunogenic effects of fibrotic DCs were contingent on their production of TNF-α. Therefore, modulating DC function may be an attractive approach to experimental therapeutics in fibro-inflammatory liver disease. © 2010 American Society for Clinical Investigation.
Association between plasma nitric oxide metabolites levels and negative symptoms of schizophrenia: a pilot study
Authors: Nakano Yuichiro , Yoshimura Reiji , Nakano Hideki , Ikenouchi‐Sugita Atsuko , Hori Hikaru , Umene‐Nakano Wakako , Ueda Nobuhisa , Nakamura Jun
Published: March 2010

Nitric oxide (NO) is involved in pathophysiology of psychiatric disorders such as depression and schizophrenia. We hypothesize that plasma levels of NO and its metabolites (NOx) are decreased in patients with schizophrenia. To examine the hypothesis, we compared plasma NOx levels between 30 schizophrenic patients (M/F: 18/12, age: 38 ± 15 years) and age‐ and sex‐matched 30 healthy controls (M/F: 18/12, age: 41 ± 19 years), and we also examined the effects of risperidone on plasma NOx levels in schizophrenic patients. The baseline plasma NOx levels were significantly lower in the schizophrenia group (1.85 ± 0.70 µM) than those in control group (3.37 ± 2.27 µM). A significantly negative correlation was found between plasma NOx levels and PANSS‐N scores before risperidone administration (ρ = −0.385, p = 0.0416). Treatment with risperidone significantly increased the plasma NOx levels by 8 weeks (before; 1.85 ± 0.70 µM, after; 2.25 ± 1.00 µM, p = 0.0491). These results suggest that NO might be one of the candidates factors which are associated with the pathophysiology of negative symptoms of schizophrenia. Copyright © 2010 John Wiley & Sons, Ltd.
Similarity search and pattern discovery in hydrological time series data mining
Authors: Ouyang Rulin , Ren Liliang , Cheng Weiming , Zhou Chenghu
Published: March 2010

The rapid development of data mining provides a new method for water resource management, hydrology and hydroinformatics research. In the paper, based on data mining theory and technology, we analyse hydrological daily discharge time series of the Shaligunlanke Station in the Tarim River Basin in China from the year 1961 to 2000. Firstly, according to the four monthly statistics, namely mean monthly discharge, monthly maximum discharge, monthly amplitude and monthly standard deviation, K‐mean clustering was used to segment the annual process of the daily discharge. The clustering result showed that the annual process of the daily discharge can be divided into five segments: snowmelt period I (April), snowmelt period II (May), rainfall period I (June–August), rainfall period II (September) and dry period (October–December and January–March). Secondly, dynamic time warping (DTW), which is a different distance metric method from the traditional Euclidian distance metric, was used to look for similarities in the discharge process. On the basis of the similarity matrix, the similar discharge processes can be mined in each period. Thirdly, agglomerative hierarchical clustering was used to cluster and discover the discharge patterns in terms of the autoregressive model. It was found that the discharge had a close relationship with the temperature and the precipitation, and the discharge processes were more similar under the same climatic condition. Our study shows that data mining is a feasible and efficient approach to discover the hidden information in the historical hydrological data and mining the implicative laws under the hydrological process. Copyright © 2010 John Wiley & Sons, Ltd.