bluuebunny/crossref_metadata_2025 huggingface dataset:
Electric Microfield Distributions in Li + Plasma With Account of the Ion Structure
Authors: Sadykova S. , Ebeling W. , Valuev I. , Sokolov I.
Published: April 2009

The electric microfield distributions at the location of an ion have been calculated using a coupling parameter integration technique for Li + plasma proposed by Ortner et al. [4] and Molecular Dynamics simulations. Electric microfield distributions are studied in a frame of the Hellmann‐Gurskii‐Krasko pseudopotential model, taking into account the quantum‐mechanical effects and the ion shell structure [34]. The screened Hellmann‐Gurskii‐Krasko pseudopotential taking into account not only the quantum‐mecanical effects, the ion shell structure but screening field effects has been derived by means of Bogoljubow method [40] and [42]. The screened pseudopotential is represented by a Fourier transform. For the Hellmann‐Gurskii‐Krasko pseudopotential model the results obtained for the microfield in the framework of the Ortner model are found in a good agreement with the Molecular Dynamics simulations (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Finite Instrumental Resolution Scales in Plasma Modeling
Authors: Minkova N. R.
Published: April 2009

The classical statistical approach is based on the assumption that coordinates of all particles are distinguishable what results in one‐particle kinetic models. By considering finite instrumental resolution scales we have to suppose that particles' coordinates are indistinguishable within a probing volume. This approach produces models based on multiparticle probability functions that are derived by integration of a probability function of total particles' system. The system is formed by separating within plasma (gas) flow a volume that is in dynamic equilibrium with surroundings. The probability function of the separated system satisfies Liouville theorem if the hypothesis of detailed dynamic equilibrium is assumed. The produced multiparticle models describe plasma flow in terms of fluctuations of macroscopic parameters. The discussed approach contributes to solution of Gibbs' paradox. It is tested by wellknown classical problems and applied to modeling of solar wind plasma expansion. The derived macroscopic parameters (density and speed) of plasma flow coincide under some assumptions with results of the two‐particle kinetic model and are consistent with observational data (in contrast, the classical one‐particle models do not provide the observed solar wind acceleration under the same assumptions). The results can be interpreted in favor of the suggested multiparticle approach (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Electrochemical Aptasensor Based on Proximity‐Dependent Surface Hybridization Assay for Protein Detection
Authors: Zhang Yan‐Li , Pang Peng‐Fei , Jiang Jian‐Hui , Shen Guo‐Li , Yu Ru‐Qin
Published: April 2009

Sensitive and selective detection of proteins is of great importance in biomedical research and clinical diagnosis. Proximity‐dependent surface hybridization assay affords a promising platform for specific and ultrasensitive electrochemical detection of proteins. An improved design of proximity‐dependent surface hybridization assay is developed. A pair of aptamer probes that recognize different sites of target platelet‐derived growth factor protein (PDGF) are designed with a short complementary sequences. Simultaneous recognition of a single PDGF molecule by the aptamer pair enables the hybridization between the complementary sequences of both aptamer probes, which keeps two tail sequences of both aptamer probes in close proximity and promotes cooperative annealing of the aptamer‐protein‐aptamer sandwiched complex on capture probes immobilized on the electrode. Thus, ferrocene tag at the terminus of one aptamer probe is drawn in close contact with the electrode with strong redox signal readily obtained in voltammetric reading. The aptasensor is shown to have high sensitivity with a detection limit as low as 0.1 pg mL−1 and excellent specificity with resistance to interference from coexisting proteins.
Electrochemical Aptasensors
Authors: Sassolas Audrey , Blum Loïc J. , Leca‐Bouvier Béatrice D.
Published: April 2009

This review presents electrochemical aptasensors reported in the literature. Their development has been growing as evidenced by the increasing number of scientific publications on this subject since 2004. Aptasensors are presented according to their transduction mode, including the most described amperometric and impedimetric devices as well as FETs and the first very recently reported potentiometric aptasensor. ‘Signal‐on’ (positive readout signal) and less sensitive ‘signal‐off’ (negative readout signal) aptasensors are reviewed based on target binding‐induced conformational change of aptamers or on target binding‐induced strand displacement or even on both processes. Aptamer‐labeled and aptamer label‐free devices are presented separately.
Characterization of Rhizobacteria Isolated from Wild Coffea arabica L.
Authors: Muleta D. , Assefa F. , Hjort K. , Roos S. , Granhall U.
Published: April 2009

Rhizobacteria from wild Arabica coffee populations (Coffea arabica L.) in southwestern Ethiopia were isolated and characterized. The main purpose was to identify coffee‐associated rhizobacteria and evaluate their potential in synthesizing the phytohormone indole acetic acid (IAA) and in degrading the ethylene precursor 1‐aminocyclopropane‐1‐carboxylate (ACC). A total of 878 bacterial isolates were screened, of which 395 (45%) isolates were preliminarily characterized using metabolic identification kits (API). Both Gram‐negative and Gram‐positive bacteria were isolated, with the former group predominating (63% of cases). Based on pre‐screening results of the biochemical tests, 51 of the isolates were subjected to PCR‐RFLP (Restriction Fragment Length Polymorphism) analysis that yielded ten groups, of which 24 isolates were identified by 16S rRNA gene sequencing. The major genera identified were Pseudomonas (six species) and Bacillus (four species). Single species of Erwinia, Ochrobactrum and Serratia were also identified. The Erwinia sp., Serratia marcescens and many Pseudomonas spp. produced IAA, and some isolates (all Pseudomonas spp.) were also able to degrade ACC. Several of the microbes found in association with wild Arabica coffee bushes have potential agronomic importance, like e.g. Bacillus thuringiensis, which deserve further testing. According to these in vitro studies, isolates of Erwinia, Serratia and Pseudomonas are of particular interest in inoculant development due to their plant growth promoting traits.
Biofuels – challenges & chances: How biofuel development can benefit from advanced process technology
Authors: Knocke Christof , Vogt Jennefer
Published: April 2009

The presented article highlights the process of biofuel production with a special focus on bioethanol. After a short introduction to the “problems” of biofuels – the “first generation” biofuels (in regards to their competition to feed and food production) and the “second generation” biofuels (in regards to the required more complex process technology) − the different steps in the process from natural resources towards the final product are presented and the underlying biotechnological challenges discussed: the pre‐treatment of the natural resources followed by the biotechnological processes of hydrolysis and fermentation. Topics such as enzyme screening for efficient or even multi‐step hydrolysis as well as microbial strain selection under process conditions and the optimization of the anaerobic fermentative conversion of the saccharides to bioethanol are discussed. Optimizing the production of bioethanol to be competitive with petrochemical fuels is the main challenge for the underlying process development.
Effects of nitrogen source, empty bed residence time and inlet concentration on biofilter removal of chlorobenzene
Authors: Wang Can , Xi Jin‐Ying , Hu Hong‐Ying
Published: April 2009

A new biofilter with bamboo carriers was used to remove gaseous chlorobenzene. Operating parameters such as the nitrogen source, the empty bed residence time (EBRT) and the inlet concentration of chlorobenzene were varied. The ability of the biofilter to remove chlorobenzene was evaluated under each set of conditions. The experimental results indicated that better biofilter performance was achieved using ammonium instead of nitrate nitrogen as the nitrogen source. However, an addition of excess ammonium did not further increase the removal efficiency. The optimal ratio of carbon to nitrogen supply (C/N) was 7:1−14:1. Increasing EBRT increased the biofilter efficiency from 0‐20% (EBRT=24 s) to 30‐50% (EBRT=41 s) and to 50‐70% (EBRT=122 s). The relationship between removal efficiency and EBRT indicated that the removal of chlorobenzene is a pseudo first order kinetic process below the concentration of 400 mg/m3. A substrate inhibition model, the Haldane equation, successfully described the removal rate of the biofilter at various inlet concentrations. With increasing inlet concentration, the removal rate initially rose and then declined. The highest removal rate of 18 g/m3 ×h was achieved at an inlet concentration of 1440 mg/m3.
Purification and characterization of lignin peroxidase from Loweporus lividus MTCC‐1178
Authors: Yadav Meera , Yadav Pratibha , Yadav Kapil Deo Singh
Published: April 2009

Lignin peroxidase from the culture filtrate of Loweporus lividus MTCC‐1178 has been purified to homogeneity using Amicon concentration and DEAE cellulose chromatography. The molecular weight of the purified lignin peroxidase using SDS‐PAGE analysis has been found to be 40 kDa. The Km values for veratryl alcohol and H2O2 for the purified enzyme were 58 and 83 μM, respectively. The calculated kcat value of the purified enzyme using veratryl alcohol as the substrate was 2.5 s−1. The pH and temperature optima of lignin peroxidase have been found to be 2.6 and 24°C, respectively.
Removal of synthetic dyes by an eco‐friendly strategy
Authors: Rodríguez‐Couto Susana , Osma Johann Faccelo , Toca‐Herrera José Luis
Published: April 2009

In this paper an eco‐friendly strategy for the removal of synthetic dyes from aqueous solutions was proposed. Thus, in a first step the dyes were adsorbed onto sunflower seed shells (SS) by using a batch technique. Subsequently, in a second step, these dyed SS were used as support‐substrates to produce laccase by the white‐rot fungus Trametes pubescens under semi‐solid‐state conditions. The effect of inducer addition on laccase production was studied. The optimum conditions (addition of both 0.5 mM Cu+2 and 50 μM tannic acid on the 3rd day of cultivation) led to a maximum laccase activity of 30272 U/L. Further, the system was efficiently scaled‐up to laboratory bioreactors producing a maximum activity of 40172 U/L together with a total decolouration of the adsorbed dye. In addition, SDS‐PAGE showed that laccases were the only enzymes present in the extracellular fluid. Therefore, apart from dye removal this approach allowed the production of high titres of laccase, which was obtained almost pure (only needed to be ultra‐filtrated).
The treatment of night eating: the patient's perspective
Authors: Goncalves Marcus D. , Moore Reneé H. , Stunkard Albert J. , Allison Kelly C.
Published: April 2009

Night eating (NE) is recognizable and treatable. The purpose of this study was to assess patients' satisfaction with their doctors' treatment of NE and to compare it to that of treatment of a control condition, ‘headache’. An Internet‐based questionnaire assessed patients' (n = 103) perceptions of their doctors' knowledge and treatment of NE versus headache, levels of treatment satisfaction and demographic and descriptive aspects of their NE. Most patients (61%) were ‘not at all satisfied’ with their doctors' treatment of NE. Patients reported low recognition and high levels of dismissal of NE by their doctors. Of patients who had been treated for both NE and headache by the same doctor, 29% were ‘not at all satisfied’ with their treatment of headache compared to 76% ‘not at all satisfied’ with their treatment of NE (p = 0.02). In conclusion, most patients reported that their doctors did not identify or treat NE, which led to dissatisfaction with their care. Copyright © 2009 John Wiley & Sons, Ltd and Eating Disorders Association.
Economic model‐based radio resource management with QoS guarantees in the CDMA uplink
Authors: Pei Xuebing , Zhu Guangxi , Wang Qingping , Qu Daiming , Liu Jian
Published: April 2009

In this paper, radio resource management based on economic model is investigated in detail in the CDMA uplink. A novel economic model is proposed to allocate the radio resources with QoS guarantees in an efficient manner. Firstly, we deduce the resources usage constraint that takes the multi‐cell interference power into account in the CDMA uplink. Then a novel utility function is designed to evaluate the total network revenue from the limited radio resources, it considers the factors of both network resources and user preferences such as data rate or signal quality. Under the resources usage constraint of considering multi‐cell interference, the radio resource allocation is formulated into an optimisation problem with the objective function of maximising the total network revenue, which is solved to get the optimal transmission rate for each user while guaranteeing the level of signal quality. Numerical results show that approximately more than 20% number of users and another 5% network revenue are achieved according to our resource allocation algorithm compared with traditional ones; meanwhile, signal quality of each mobile user is guaranteed effectively. Copyright © 2009 John Wiley & Sons, Ltd.
New estimates of the demand for physical and mental health treatment
Authors: Meyerhoefer Chad D. , Zuvekas Samuel H.
Published: April 2009

Consumers' price responsiveness is central to US health‐care reform proposals, but the best available estimates are now more than 25 years old. We estimate health‐care demands by calculating expected end‐of‐year prices and incorporating them into a zero‐inflated ordered probit model applied to several overlapping panels of data from 1996 to 2003. Results from our correlated random effects specification indicate that the price responsiveness of ambulatory mental health treatment has decreased substantially and is now slightly lower than physical health treatment. This suggests that concerns over moral hazard alone do not warrant less generous coverage for mental health. However, prescription drug demand is more price elastic. Published in 2009 by John Wiley & Sons, Ltd.
Supplemental health insurance and equality of access in Belgium
Authors: Schokkaert Erik , Van Ourti Tom , De Graeve Diana , Lecluyse Ann , Van de Voorde Carine
Published: April 2009

The effects of supplemental health insurance on health‐care consumption crucially depend on specific institutional features of the health‐care system. We analyse the situation in Belgium, a country with a very broad coverage in compulsory social health insurance and where supplemental insurance mainly refers to extra‐billing in hospitals. Within this institutional background, we find only weak evidence of adverse selection in the coverage of supplemental health insurance. We find much stronger effects of socio‐economic background. We estimate a bivariate probit model and cannot reject the assumption of exogeneity of insurance availability for the explanation of health‐care use. A count model for hospital care shows that supplemental insurance has no significant effect on the number of spells, but a negative effect on the number of nights per spell. We comment on the implications of our findings for equality of access to health care in Belgium. Copyright © 2009 John Wiley & Sons, Ltd.
Synthesis of 5,7‐Dihydrodibenzo[b,f][1,7]naphthyridine‐6,12‐dione, an Unexpected Isolate from Isatis tintoria
Authors: Riepl Herbert M. , Kellermann Melanie
Published: April 2009

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The dye plant Isatis tinctoria yields a number of heterocyclic compounds with interesting anti‐inflammatory and cytotoxic properties, formed mainly in an unknown manner by post‐harvest treatment. A synthesis of the incidently isolated 5,7‐dihydrodibenzo[b,f][1,7]naphthyridine‐6,12‐dione (4a) is presented. Starting from different 1,2‐diarylhydrazines, adducts 11 with acetylenedicarboxylates (=but‐2‐ynedioates) are thermally treated (Scheme). In a Fischer‐type rearrangement, 3‐(arylamino)quinolinecarboxylic acids 9 are obtained, which can be cyclized under Friedel–Crafts conditions to yield a number of analoga 4 of the title compound.
Molecular Rearrangement of 9b‐Hydroxy‐1H‐imidazo[4,5‐c]quinoline‐2,4‐diones – A Convenient Pathway to Spiro‐Linked Imidazolidine–Oxindole Derivatives
Authors: Klásek Antonín , Lyčka Antonín , Mikšík Ivan , Růžička Aleš
Published: April 2009

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The 1‐substituted 3‐alkyl/aryl‐3‐aminoquinoline‐2,4(1H,3H)‐diones 1 react with alkyl/aryl isocyanates to give novel 3‐alkyl/aryl‐3‐ureidoquinoline‐2,4(1H,3H)‐diones (=N‐(3‐alkyl/aryl‐1,2,3,4‐tetrahydro‐2,4‐dioxoquinolin‐3‐yl)ureas) 2 and/or 3a‐alkyl/aryl‐3,3a,5,9b‐tetrahydro‐9b‐hydroxy‐1H‐imidazo[4,5‐c]quinoline‐2,4‐diones 3 in high yields. Compounds 2 and 3 rearrange by boiling in AcOH or concentrated HCl solution to give three different types of spiro[imidazolidine‐4,3′‐[3H]indole]‐2,2′(1′H)‐diones, i.e., 10, 11, and 12, depending on the kind of substituents at C(3) and C(3a), respectively. All compounds were characterized by 1H‐ and 13C‐NMR and IR spectroscopy as well as by atmospheric‐pressure chemical‐ionization (APCI) mass spectra. The structures of compounds 11c and 12Al were investigated by single‐crystal X‐ray diffraction analysis.
Fused Isothiazole S‐Oxide Systems from Cycloaddition Reactions of N‐Benzylisothiazol‐3‐amine 1‐Oxide
Authors: Clerici Francesca , Casoni Alessandro , Contini Alessandro , Gelmi Maria L. , Pellegrino Sara
Published: April 2009

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The racemic N‐benzylisothiazol‐3‐amine 1‐oxide (2) was demonstrated to be an efficient partner in Diels–Alder reactions (Schemes 2–4) and a good dipolarophile in 1,3‐dipolar cycloaddition reactions with nitrile oxides (Scheme 5). Polycyclic isothiazole S‐oxides with different substitution patterns were obtained from 2 in good yield and in a fully regioselective way. Improved diastereoselection was observed performing the Diels–Alder or 1,3‐dipolar cycloaddition reactions in H2O.
Diterpenoid and Norditerpenoid Alkaloids from the Roots of Aconitum yesoense var. macroyesoense
Authors: Wada Koji , Kawahara Norio
Published: April 2009

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A new diterpenoid alkaloid, macroyesoenline (1), and a new norditerpenoid alkaloid, 9‐hydroxyvirescenine (2), have been isolated from the roots of Aconitum yesoense var. macroyesoense. Their structures were elucidated on the basis of spectral data (1D‐ and 2D‐NMR experiments) and mass spectrometry. The known norditerpenoid and diterpenoid alkaloids delphinifoline (3) and cochlearenine (13) were isolated for the first time from this plant.
Photocleavage of Peptides and Oligodeoxynucleotides Carrying 2‐Nitrobenzyl Groups
Authors: Ramos Roger , Manning Brendan , Aviñó Anna , Gargallo Raimundo , Eritja Ramon
Published: April 2009

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Peptides and oligodeoxynucleotides containing photolabile 2‐nitrobenzyl groups as mid‐sequences were prepared. Photocleavage of aqueous solutions of these compounds neared completion within 30 min to a few hours depending on the photolabile group used. A photolabile group was introduced in the loop of an intramolecular oligodeoxynucleotide hairpin. Melting curves of the hairpin with and without the complementary oligodeoxynucleotide showed a preference for the intramolecular hairpin form, but an intermolecular duplex was observed after photolysis. These results open the possibility of using photolabile DNA hairpins for the fabrication of patterned surfaces.
Ecdysteroids from Silene viridiflora
Authors: Simon András , Tóth Noémi , Tóth Gábor , Kele Zoltán , Groska Judit , Báthori Mária
Published: April 2009

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Two new ecdysteroid acetonide derivatives, 5α‐2‐deoxy‐20‐hydroxyecdysone 20,22‐acetonide (6) and makisterone C 2,3;20,22‐diacetonide (8), were isolated from the dried herb of Silene viridiflora. The already known 5β‐2‐deoxy‐20‐hydroxyecdysone 20,22‐acetonide (7) is additionally reported here as a new constituent of S. viridiflora. Five earlier described S. viridiflora ecdysteroids, integristerone A (1), 5,20,26‐trihydroxyecdysone (26‐hydroxypolipodine B; 2), 20,26‐dihydroxyecdysone (3), 2‐deoxy‐20‐hydroxyecdysone (4), 2‐deoxyintegristerone A (5), are also included because of their improved characterization. The structures were established via spectroscopic analyses, including one‐ and two‐dimensional NMR and mass spectrometry.
New C20‐Diterpenoid Alkaloids from Delphinium anthriscifolium var. savatieri
Authors: Liu Xiao‐Yu , Chen Qiao‐Hong , Wang Feng‐Peng
Published: April 2009

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Five new vakognavine‐type C20‐diterpenoid alkaloids, anthriscifolmines D–H (1–5, resp.), were isolated from the whole herb of Delphinium anthriscifolium var. savatieri. The structures of these new alkaloids were determined by spectroscopic techniques, including HR‐ESI‐MS, 1D‐, and 2D‐NMR experiments.
Scalarane Sesterterpenes from the Chinese Sponge Phyllospongia foliascens
Authors: Zhang Hong‐Jun , Tang Hai‐Feng , Yi Yang‐Hua , Lin Hou‐Wen
Published: April 2009

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Three new scalarane sesterterpenes, phyllofolactone L (1), phyllofenone D (2) and phyllofenone E (3), were isolated from the acetone extract of the South China Sea sponge Phyllospongia foliascens. Their structures were elucidated on the basis of spectroscopic analysis. Phyllofenone D (2) was cytotoxic against the P388 leukemia cell line with an IC50 value of 6.5 μg/ml.
Selectivity Enhancement for the Jacobsen–Katsuki Epoxidation in Fluorinated Solvents
Authors: Havare Nizam , Plattner Dietmar A.
Published: April 2009

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In 1,1,1,2,3,4,4,5,5,5‐Decafluoropentane using 2‐phenylpyridine N‐oxide as donor ligand, the enantioselectivity of the Jacobsen–Katsuki epoxidation is improved up to 10% ee as compared to established protocols.
FAK overexpression and p53 mutations are highly correlated in human breast cancer
Authors: Golubovskaya Vita M. , Conway‐Dorsey Kathleen , Edmiston Sharon N. , Tse Chiu‐Kit , Lark Amy A. , Livasy Chad A. , Moore Dominic , Millikan Robert C. , Cance William G.
Published: April 2009

Focal adhesion kinase (FAK) is overexpressed in a number of tumors, including breast cancer. Another marker of breast cancer tumorigenesis is the tumor suppressor gene p53 that is frequently mutated in breast cancer. In the present study, our aim was to find a correlation between FAK overexpression, p53 expression and mutation status in a population‐based series of invasive breast cancer tumors from the Carolina Breast Cancer Study. Immunohistochemical analyses of 622 breast cancer tumors revealed that expression of FAK and p53 were highly correlated (p = 0.0002) and FAK positive tumors were 1.8 times more likely to be p53 positive compared to FAK negative tumors [odds ratio (OR) = 1.8; 95% Confidence Interval (CI) 1.2–2.8, adjusted for age, race and stage at diagnosis]. Tumors positive for p53 expression showed higher intensity of FAK staining (p < 0.0001) and higher percent of FAK positive staining (p < 0.0005). From the same study, we evaluated 596 breast tumors for mutations in the p53 gene, using single strand conformational polymorphism and sequencing. Statistical analyses were performed to determine the correlation between p53 mutation status and FAK expression in these tumors. We found that FAK expression and p53 mutation were positively correlated (p < 0.0001) and FAK positive tumors were 2.5 times more likely to be p53 mutation positive compared to FAK negative tumors [adjusted OR = 2.5, 95% CI 1.6–3.9]. This is the first analysis demonstrating a high correlation between FAK expression and p53 mutations in a population‐based series of breast tumors. © 2009 UICC
Single nucleotide polymorphism of rs430397 in the fifth intron of GRP78 gene and clinical relevance of primary hepatocellular carcinoma in Han Chinese: Risk and prognosis
Authors: Zhu Xiao , Chen Min‐Shan , Tian Lin‐Wei , Li Dong‐Pei , Xu Pei‐Lin , Lin Marie C. M. , Xie Dan , Kung Hsiang‐Fu
Published: April 2009

Large number of data showed that allele variants in certain genes are markers for hepatocellular carcinoma (HCC). GRP78 is a stress‐associated protein which is a central regulator of endoplasmic reticulum homeostasis due to its multiple functional roles in the folding, maturation and transport of proteins. A case‐control study was conducted on 576 HCC patients, and 539 age‐ and gender‐matched healthy subjects to examine whether rs430397 polymorphism in the fifth intron of GRP78 gene is associated with the development and prognosis of HCC. Polymorphism in rs430397 was analyzed by resequencing and TaqMan real‐time PCR. Allele A, genotype AA and combined genotypes (AG+AA) displayed significantly increased risk for HCC (OR = 1.48, 95%CI = 1.07–1.79, p = 0.010; OR = 2.25, 95%CI= 1.08–3.38, p = 0.019; and OR = 1.50, 95%CI = 1.09–1.85, p = 0.012, respectively). Genotypes AA and AG were mainly associated with HBV‐related HCC (85.8%; p < 0.00001 versus HBV noncarriers with HCC) and cirrhosis‐related HCC (90%; p = 0.011 versus noncirrhosis HCC). Patients carrying the AA genotype had a shorter survival time (median 23.0 months in all cases; median 21.0 months in the cases carrying HBsAg). Like HBV and cirrhosis, the rs430397 is an independent prognostic factor influencing the survival of HCC. In conclusion, allele A and genotypes AA and AG of rs430397 may represent high risk and poor prognosis for HCC. © 2009 UICC
Photodynamic therapy with 5‐aminolevulinic acid and diamino acid derivatives of protoporphyrin IX reduces papillomas in mice without eliminating transformation into squamous cell carcinoma of the skin
Authors: Kwitniewski Mateusz , Jankowski Dawid , Jaskiewicz Kazimierz , Dziadziuszko Halina , Juzeniene Asta , Moan Johan , Ma Li‐Wei , Peksa Rafal , Kunikowska Danuta , Graczyk Alfreda , Kwasny Miroslaw , Kaliszewski Miron , Glosnicka Renata
Published: April 2009

Photodynamic therapy (PDT) is used to treat malignant and nonmalignant diseases. It is also used for cosmetological skin treatment. PDT is generally considered to have a low risk of carcinogenicity. However, instances of nonmalignant human tumors turning malignant have been linked to PDT. In this study, we used 5‐aminolevulinic (ALA) acid and 3 water soluble photosensitizers‐PP(Arg)2, PP(Ser)2Arg2, PP(Ala)2Arg2, all diamino acid derivatives of protoporphyrin IX‐to treat benign papillomas in FVB/N mice induced by 7,12‐dimethylbenz(a)anthracene (DMBA)‐12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA). Of these drugs, ALA and PP(Arg)2 were found the most efficient. PDT reduced the number of papillomas, but with increasing effectiveness of the drugs, the risk of malignant transformation of the papillomas into squamous cell carcinomas increased. The underlying mechanisms are not clear and further investigations are needed. © 2009 UICC
TOB suppresses breast cancer tumorigenesis
Authors: O'Malley Sean , Su Hua , Zhang Tao , Ng Crystal , Ge Hong , Tang Careen K.
Published: April 2009

Transducer of ErbB‐2 (TOB) is a member of the TOB/Btg gene family. A role for TOB in the suppression of human tumorigenesis has been proposed, based on the observations that TOB‐knockout mice spontaneously form tumors and TOB expression is lost in human lung and thyroid cancers. However, the role of TOB in human breast cancer remains unknown. To evaluate the this role, we screened a panel of breast cancer cell lines for TOB expression levels and found that they are inversely correlated with the tumorigenicity and metastatic potential of the cell lines. In addition, we demonstrated for the first time that TOB expression is inversely correlated with breast cancer progression in clinical specimens. These results strongly indicate that the loss of TOB expression plays a role in breast cancer progression. We have also provided the first evidence that TOB functions as a tumor suppressor in breast cancer MCF‐7 cells, using gain‐of‐function and loss‐of‐function approaches to manipulate TOB expression. Cell‐cycle analysis further revealed that TOB can prolong the G1‐S phase transition by inducing arrest at G1‐S phase. Moreover, upregulation of the cyclin‐dependent kinase inhibitor p27 and downregulation of the antiapoptotic proteins Bcl‐2 and Bcl‐XL were observed in MCF7/TOB transfectants. Conversely, opposite results were observed in shRNA‐TOB transfectants. Furthermore, decreased activity of Erk2, AKT, CrkL, PDK1, and Smads were observed in TOB‐overexpressing cells. Taken together, these data provide evidence that TOB can function as a tumor suppressor in breast cancer through modulation and regulation of multiple signaling pathways. © 2009 UICC
Down‐regulation of the transcriptional mediator subunit Med1 contributes to the loss of expression of metastasis‐associated dapk1 in human cancers and cancer cells
Authors: Gade Padmaja , Singh Ashish K. , Roy Sanjit K. , Reddy Sekhar P. , Kalvakolanu Dhananjaya V.
Published: April 2009

DAPK1, a ca+2/calmodulin regulated serine/threonine kinase, is a major tumor suppressor, whose expression is lost in multiple tumor types. However, the mechanisms contributing to it are unclear. We have recently shown that CCAAT/Enhancer binding protein‐β (C/EBP‐β) is required for the basal and interferon γ (IFN‐γ)‐induced expression of dapk1 in many cell types. C/EBP‐β interacts with the transcriptional Mediator, a multisubunit complex that couples enhancer bound transcription factors to the basal transcriptional machinery in an IFN‐γ dependent manner for regulating dapk1 expression. Specifically, the Med1 (TRAP220/PBP/DRIP220/CRSP220) subunit associates with the enhancer bound C/EBP‐β at the CRE/ATF site of dapk1 in an IFN‐γ dependent manner for stimulating gene expression. Therefore, we investigated if the mechanism responsible for the loss of dapk1 expression in human cancers involves a failure to recruit C/EBP‐β and/or Med1 to the dapk1 promoter. We compared the relative occupancy of these factors at the dapk1 promoter at CRE/ATF sites in normal and cancer cell lines. A significantly lower binding of these factors to the CRE/ATF site of dapk1 promoter occurred in human cancer cell lines than in normal cells. We show that loss of Med1 expression correlates with a corresponding loss of dapk1 expression in a number of primary human lung carcinomas. Med1 levels were significantly lower in cancer cell lines than in normal controls. Importantly, we show that restoration of Med1 induces the expression of dapk1 in these cancer cells and also attenuates their metastatic potential in vivo. Our studies reveal a critical parameter limiting dapk1 expression in cancer cell lines. © 2009 UICC
Parity and age at first childbirth in relation to the risk of different breast cancer subgroups
Authors: Butt Salma , Borgquist Signe , Anagnostaki Lola , Landberg Göran , Manjer Jonas
Published: April 2009

The aim of the present study was to examine parity and age at first childbirth, in relation to the risk of specific breast cancer subgroups. A prospective cohort, The Malmö Diet and Cancer Study, including 17,035 women were followed with linkage to Swedish Cancer Registry until December 31, 2004. A total of 622 incident breast cancers were diagnosed during follow‐up and were evaluated regarding invasiveness, tumour size, axillary lymph node status, Nottingham grade, tumour proliferation (Ki67), HER2, cyclin D1 and p27. The tumours were also examined for WHO type and hormone receptor status. Nulliparity was associated with an overall increased risk of breast cancer, although not statistically significant (the relative risk was 1.39 with a 95% confidence interval of 0.92–2.08). Nulliparity was also associated with large tumours (>20 mm) (1.89: 0.91–3.91), high Ki67 levels (1.95: 0.93–4.10), high cyclin D1 levels (2.15: 0.88–5.27), grade III (2.93: 1.29–6.64) and HER2 positive tumours (3.24: 1.02–10.25). High parity was not statistically significantly associated with any specific breast cancer subgroup. Older age at first childbirth (>30) was associated with a slightly increased risk of breast cancer (1.39: 0.94–2.07). There was a statistically significant association between late first childbirth and lobular type (2.51: 1.01–6.28), grade III tumours (2.67: 1.19–6.02), high levels of cyclin D1 (2.69: 1.18–6.12) and low levels of p27 (2.23: 1.15–4.35). We conclude that nulliparity and late first childbirth are associated with relatively more aggressive breast cancer subgroups. © 2009 UICC
Artemisinin dimer anticancer activity correlates with heme‐catalyzed reactive oxygen species generation and endoplasmic reticulum stress induction
Authors: Stockwin Luke H. , Han Bingnan , Yu Sherry X. , Hollingshead Melinda G. , ElSohly Mahmoud A. , Gul Waseem , Slade Desmond , Galal Ahmed M. , Newton Dianne L.
Published: April 2009

Analogs of the malaria therapeutic, artemisinin, possess in vitro and in vivo anticancer activity. In this study, two dimeric artemisinins (NSC724910 and 735847) were studied to determine their mechanism of action. Dimers were >1,000 fold more active than monomer and treatment was associated with increased reactive oxygen species (ROS) and apoptosis induction. Dimer activity was inhibited by the antioxidant L‐NAC, the iron chelator desferroxamine and exogenous hemin. Similarly, induction of heme oxygenase (HMOX) with CoPPIX inhibited activity, whereas inhibition of HMOX with SnPPIX enhanced it. These results emphasize the importance of iron, heme and ROS in activity. Microarray analysis of dimer treated cells identified DNA damage, iron/heme and cysteine/methionine metabolism, antioxidant response, and endoplasmic reticulum (ER) stress as affected pathways. Detection of an ER‐stress response was relevant because in malaria, artemisinin inhibits pfATP6, the plasmodium orthologue of mammalian sarcoplasmic/endoplasmic reticulum Ca2+‐ATPases (SERCA). A comparative study of NSC735847 with thapsigargin, a specific SERCA inhibitor and ER‐stress inducer showed similar behavior in terms of transcriptomic changes, induction of endogenous SERCA and ER calcium mobilization. However, thapsigargin had little effect on ROS production, modulated different ER‐stress proteins and had greater potency against purified SERCA1. Furthermore, an inactive derivative of NSC735847 that lacked the endoperoxide had identical inhibitory activity against purified SERCA1, suggesting that direct inhibition of SERCA has little inference on overall cytotoxicity. In summary, these data implicate indirect ER‐stress induction as a central mechanism of artemisinin dimer activity. © 2009 UICC
Pretreatment frequency of circulating IL‐17+CD4+ T‐cells, but not Tregs, correlates with clinical response to whole‐cell vaccination in prostate cancer patients
Authors: Derhovanessian Evelyna , Adams Victoria , Hähnel Karin , Groeger Andrea , Pandha Hardev , Ward Stephen , Pawelec Graham
Published: April 2009

The aim of this study was to determine the prognostic implications of the pretreatment level of Th17 cells compared with regulatory T‐cell status in prostate cancer patients receiving active whole cell immunotherapy. Ten‐color flow cytometry was used to analyze IL‐17‐producing CD4+ T‐cells in the peripheral blood of hormone‐resistant non‐bone metastatic prostate cancer patients prior to immunotherapy with an allogeneic whole‐cell vaccine. Surface expression of the chemokine receptors CCR4 and CCR6 was used to further subdivide IL‐17‐producing cells into subsets with distinct homing properties. The frequency of circulating regulatory T‐cells (Tregs), defined as CD3+CD4+CD127loFoxp3+CD25+ was compared in the same patients. The frequency of CCR4−IL‐17+CD4+ T‐cells prevaccination inversely correlated with time to disease progression (TTP) in 23 prostate cancer patients. Furthermore, responder (R) patients with statistically significant reductions in PSA velocity (PSAV) in response to the immunotherapy (n = 9), showed a Th17 profile similar to healthy male controls and significantly different from non‐responder (NR) patients (n = 14) (i.e., those without any significant reduction in PSAV). In contrast, the frequency of Tregs in peripheral blood in PSA‐R (n = 11) and ‐NR (n = 14) patients was similar (but in both cases, significantly higher than in age‐matched healthy men). Accordingly, there was no significant correlation between frequency of Tregs and TTP in these late‐stage prostate cancer patients undergoing active immunotherapy. These data imply an important role for IL‐17‐producing helper T‐cells in cancer immunology and highlight their potential use as a pretreatment screen to ensure appropriate treatment is offered to hormone‐resistant prostate cancer patients. © 2009 UICC
JAM‐A expression positively correlates with poor prognosis in breast cancer patients
Authors: McSherry Elaine A. , McGee Sharon F. , Jirstrom Karin , Doyle Emma M. , Brennan Donal J. , Landberg Goran , Dervan Peter A. , Hopkins Ann M. , Gallagher William M.
Published: April 2009

The cell–cell adhesion protein junctional adhesion molecule‐A (JAM‐A) influences epithelial cell morphology and migration. As migration is required for tumor cell invasion and metastasis, we sought to elucidate the role of JAM‐A in invasive breast cancer. A breast cancer tissue microarray was analyzed for JAM‐A protein expression, in parallel with analysis of JAM‐A gene expression data from a breast cancer clinical dataset. Our data demonstrate a novel association between JAM‐A gene and protein upregulation and poor prognosis in breast cancer. To mechanistically dissect this process, we used lentiviral technology to stably knock down JAM‐A gene expression by shRNA in MCF7 breast cancer cells, which express high‐endogenous levels of JAM‐A. We also antagonized JAM‐A function in wild‐type MCF7 cells using an inhibitory antibody that blocks JAM‐A dimerization. Knockdown or functional antagonism of JAM‐A decreased breast cancer cell migration in scratch‐wound assays. Reductions in β1‐integrin protein levels were observed after JAM‐A‐knockdown in MCF7 cells, suggesting a mechanism for reduced motility after loss of JAM‐A. Consistent with this hypothesis, tissue microarray analysis of β1‐integrin protein expression in invasive breast cancer tissues revealed a trend toward high β1‐integrin protein levels being indicative of poor prognosis. Twenty‐two percent of patients were observed to coexpress high levels of JAM‐A and β1‐integrin protein, and MDA‐MB‐231 breast cells stably overexpressing JAM‐A showed an increase in β1‐integrin protein expression. Our results are consistent with a previously unreported role for JAM‐A overexpression as a possible mechanism contributing to progression in primary breast cancer; and a potential therapeutic target. © 2009 UICC
An in situ and in vitro investigation for the transglutaminase potential in tissue engineering
Authors: Zeugolis D. I. , Panengad P. P. , Yew E. S. Y. , Sheppard C. , Phan T. T. , Raghunath M.
Published: April 2009

Transglutaminases (TGases) constitute a family of enzymes that stabilize protein assemblies by γ‐glutamyl‐ε‐lysine crosslinks. The role of tissue transglutaminase (TGase 2) in several pathophysiologies, wound healing applications, biomaterials functionalization, and drug delivery systems provides grounds for its use in tissue engineering. Herein, we initially studied the endogenous TGase activity and expression under normal (skin, duodenum, colon, and small bowel) and pathophysiological (keloid scar) conditions on cadaveric human tissues. Successful inhibition was achieved using low concentrations of BOC‐DON‐QIV‐OMe (0.1 mM and 1 mM for normal skin and keloid scar, respectively), iodoacetamide (0.1 mM and 1 mM for normal skin and keloid scar, respectively), and cystamine dihydrochloride (1 mM and 10 mM for normal skin and keloid scar, respectively), whilst di‐BOC‐cystamine was found ineffective even at 100 mM concentration. Secondly, the addition of exogenous guinea pig liver transglutaminase (gpTGase) onto the inhibited tissues and collagen scaffolds was studied, and results presented advocate its use as potential tissue adhesive and drug delivery tool. However, the investigation of its crosslinking extent using second harmonic generation microscopy and differentially scanning calorimetry revealed rather poor stabilization function. Overall, our study indicates that TGase 2 has a role as a biological glue to consolidate various micro‐structural components of tissues and biomaterials. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010
Effect of surface wettability and charge on protein adsorption onto implantable alginate‐chitosan‐alginate microcapsule surfaces
Authors: Xie Hong‐Guo , Li Xiao‐Xia , Lv Guo‐Jun , Xie Wei‐Yang , Zhu Jing , Luxbacher Thomas , Ma Ron , Ma Xiao‐Jun
Published: April 2009

Alginate‐chitosan‐alginate (ACA) microcapsules have been developed as a device for the transplantation of living cells. However, protein adsorption onto the surface of microcapsules immediately upon their implantation decides their ultimate biocompatibility. In this work, the chemical composition of the ACA membranes was determined using X‐ray photoelectron spectroscopy (XPS). The surface wettability and charge were determined by contact angle and zeta potential measurements, respectively. Then, the effects of surface wettability and charge on bovine fibrinogen (Fgn) and gamma globulin (IgG) adsorption onto ACA microcapsules were evaluated. The results showed that ACA microcapsules had a hydrophilic membrane. So, the surface wettability of ACA microcapsules had little effect on protein adsorption. There was a negative zeta potential of ACA microcapsules which varies with the viscosity or G content of alginate used, indicating a varying degree of net negatively charged groups on the surface of ACA microcapsules. The amount of adsorbed protein increased with increasing of positive charge. Furthermore, the interaction between proteins and ACA microcapsules is dominated by electrostatic repulsion at pH 7.4 and that is of electrostatic attraction at pH 6.0. This work could help to explain the bioincompatibility of ACA microcapsules and will play an important role in the optimization of the microcapsule design. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010
Development of tissue‐engineered substitutes of the ear ossicles: PORP‐shaped poly(propylene fumarate)‐based scaffolds cultured with human mesenchymal stromal cells
Authors: Danti Serena , D'Alessandro Delfo , Pietrabissa Andrea , Petrini Mario , Berrettini Stefano
Published: April 2009

This is a novel study aimed at exploring possible tissue engineering (TE) options for fabricating middle ear ossicle replacements. Alternatives to prosthetic replacements currently used in ossiculoplasty are desirable, considering that current devices are known to suffer from a persistent rejection phenomenon, known as extrusion. In this study a biocompatible and biodegradable polymer, poly(propylene fumarate)/poly(propylene fumarate)‐diacrylate (PPF/PPF‐DA), was chosen to assess the fabrication feasibility of highly porous devices shaped as partial ossicular replacement prostheses (PORPs). PORP‐like scaffolds were produced, and their poral features (porosity and pore interconnectivity) were evaluated via micro‐CT. In addition, their capability to support human mesenchymal stromal cell (hMSC) colonization and osteoblastic differentiation in vitro was investigated with both quantitative and qualitative analyses. This report summarizes and discusses all the fundamental issues associated with ossicle prosthetization as well as the challenging opportunities potentially offered to middle ear reconstruction by TE; moreover it demonstrates that PPF/PPF‐DA PORP‐like scaffolds can be appropriately fabricated to allow both the colonization of hMSCs and their osteoblastic maturation in vitro. Specifically, the expression patterns of the main osteogenic markers (alkaline phosphatase, calcium) and of various matrix biomolecules (glycoproteins, glycosaminoglycans, collagen I) were studied. These preliminarily obtained outcomes may launch a new trend in otology dedicated to TE ossicle development to improve on the performance of current prosthetic replacements. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010
Evaluation of thrombogenic potential of electrospun bioresorbable vascular graft materials: Acute monocyte tissue factor expression
Authors: Wolfe Patricia S. , Madurantakam Parthasarathy , Garg Koyal , Sell Scott A. , Beckman Matthew J. , Bowlin Gary L.
Published: April 2009

The purpose of this study was to quantify the acute expression of tissue factor (TF) by monocytes on interaction with electrospun bioresorbable constructs. A minimal expression of TF will demonstrate the potential for scaffolds to be used as a vascular graft without enhanced risk of failure from acute thrombotic occlusion. Polydioxanone (PDO) (60, 80, 120, and 160 mg/mL) and polycaprolactone (PCL) (80, 10, and 160 mg/mL) dissolved in 1,1,1,3,3,3 hexafluoro‐2‐propanol (HFP) were electrospun to form fibrous scaffolds. Circular discs (10 mm diameter) of each scaffold were disinfected and seeded with human monocytes (50,000 cells/well). The discs were statically cultured under standard conditions (37°C and 5% CO2), and removed after 24 h for TF analysis with an In‐Cell Western assay. Fiber diameter was calculated through ImageTool analysis of scanning electron micrographs. Acute monocyte interaction with scaffolds of PCL (120 mg/mL) resulted in the lowest amount of TF expressed (4 ng/disc), whereas scaffolds of 160 mg/mL PDO elicited the highest amount of TF expressed (51 ng/disc). TF levels expressed on all scaffolds were comparable with the amount expressed on e‐PTFE (20 ng/disc). Preliminary data for TF expression on scaffolds of silk (70 mg/mL and 150 mg/mL) and silk:PCL (100 mg/mL, v/v) blends (50:50 and 70:30) resulted in values of TF expression ranging from 0 to 24 ng. Results from this study reveal electrospun grafts composed of PDO and PCL provide no greater risk of failure from an acute thrombotic occlusion due to TF expression when compared with that of the standard e‐PTFE graft. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Modulation of cell growth on exposure to silkworm and spider silk fibers
Authors: Hakimi Osnat , Gheysens Tom , Vollrath Fritz , Grahn Michael F. , Knight David P. , Vadgama Pankaj
Published: April 2009

Recent years have seen an increased interest in the use of natural and modified silks for tissue engineering. Despite longstanding concerns regarding the biocompatibility of silk sutures, only a few studies have been carried out to investigate the biocompatibility of natural silk fibers. Here, we report an in vitro assessment of the effect of nonmodified, degummed silks on cells. We describe the effects of degummed silk fibers as well as extracted sericin on cell metabolism and proliferation. Endothelial cells directly exposed to native degummed Bombyx mori and Antheraea pernyi silks showed lower rates of proliferation and metabolism than nonexposed cells. A similar but milder effect was observed for cells in direct contact with Nephila edulis egg sack fibers. Sericin and silk‐conditioned medium had no negative effect on cell proliferation except in medium supplemented with 5% bovine serum prior to conditioning with A. pernyi silk. The toxicity of A. pernyi was negligible after thorough enzymatic treatment of the fibers with trypsin. It is, therefore, proposed that A. pernyi silk contain one or more cytotoxic components, which need to be removed prior to medical use. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010