bluuebunny/crossref_metadata_2025 huggingface dataset:
Cover Picture: 1,2,3‐Triazole as a Peptide Surrogate in the Rapid Synthesis of HIV‐1 Protease Inhibitors (ChemBioChem 7/2005)
Authors: Brik Ashraf , Alexandratos Jerry , Lin Ying‐Chuan , Elder John H. , Olson Arthur J. , Wlodawer Alexander , Goodsell David S. , Wong Chi‐Huey
Published: June 2005

The cover picture shows a close up of the substrate‐bindng site of HIV protease (shown as a blue ribbon), with the NCP1 substrate (shown as a thin black backbone and transparent solvent‐excluded surface) and the backbone of the click chemistry‐based triazole inhibitor (shown as ball and stick, atoms colored). The structural water (red sphere) hydrogen bonds to a triazole nitrogen of the inhibitor and to the substrate peptide backbone. For further details, see the article by C.‐H. Wong, A. Wlodawer, D. S. Goodsell et al. on p. 1167 ff.
Oxidation States and CO Ligand Exchange Kinetics in a Self‐Assembled Monolayer of a Triruthenium Cluster Studied by In Situ Infrared Spectroscopy
Authors: Zhou Wei , Ye Shen , Abe Masaaki , Nishida Takuma , Uosaki Kohei , Osawa Masatoshi , Sasaki Yoichi
Published: June 2005

Oxidation states and CO ligand exchange kinetics in a self‐assembled monolayer (SAM) of an oxo‐centered triruthenium cluster [Ru3(μ3‐O)(μ‐CH3COO)6(CO)(L1)(L2)] (L1 = [(NC5H4)CH2NHC(O)(CH2)10S‐]2, L2 = 4‐methylpyridine) have been extensively investigated on the surface of a gold electrode in aqueous and nonaqueous solutions. The SAM exhibits three consecutive one‐electron transfers and four oxidation states, which have been characterized by electrochemistry, in situ infrared spectroscopy, and in situ sum frequency generation (SFG) vibrational spectroscopy measurements. The original electron‐localized state of the Ru cluster center was changed to electron delocalization states by oxidation or reduction of the central Ru ions. These changes are revealed by the IR absorptions of the CO ligand and the bridging acetate ligands of the triruthenium cluster in the SAM. The IR absorptions of the two kinds of ligands are strongly dependent on the oxidation state of the Ru cluster center. One‐electron oxidation of the central Ru ion in the SAM triggers a CO ligand liberation process. Solvent molecules may then occupy the CO site to result in a CO‐free SAM. One‐electron reduction of this CO‐free SAM in a CO‐saturated solution leads to re‐coordination of the CO ligand into the SAM. Both processes can be precisely controlled by tuning the electrode potential. The kinetics of the CO exchange cycle in the SAM, including liberation and coordination, has been investigated by in situ IR and SFG measurements for the first time. The CO exchange cycle is significantly dependent on the temperature. The reaction rate greatly decreases with decreasing solution temperature, which is an important factor in the CO ligand exchange process. The activation energies of both CO liberation and coordination have been evaluated from the reaction rate constants obtained at various temperatures.
Peptide Electron Transfer: More Questions than Answers
Authors: Long Yi‐Tao , Abu‐Irhayem Erfan , Kraatz Heinz‐Bernhard
Published: June 2005

Nature has specifically designed proteins, as opposed to DNA, for electron transfer. There is no doubt about the electron transfer within proteins compared with the uncertain and continuing debate about charge transfer through DNA. However, the exact mechanism of electron transfer within peptide systems has been a source of controversy. Two different mechanisms for electron transfer between a donor and an acceptor, electron hopping and bridge‐assisted superexchange, have been proposed, and are supported by experimental evidence and theoretical calculations. Several factors were found to affect the kinetics of this process, including peptide chain length, secondary structure and hydrogen bonding. Electrochemical measurements of surface‐supported peptides have contributed significantly to the debate. Here we summarize the current approaches to the study of electron transfer in peptides with a focus on surface measurements and comment on these results in light of the current and often controversial debate on electron transfer mechanisms in peptides.
Head‐Group Size or Hydrophilicity of Surfactants: The Major Regulator of Lipase Activity in Cationic Water‐in‐Oil Microemulsions
Authors: Das Debapratim , Roy Sangita , Mitra Rajendra Narayan , Dasgupta Antara , Das Prasanta Kumar
Published: June 2005

To determine the crucial role of surfactant head‐group size in micellar enzymology, the activity of Chromobacterium Viscosum (CV) lipase was estimated in cationic water‐in‐oil (w/o) microemulsions of three different series of surfactants with varied head‐group size and hydrophilicity. The different series were prepared by subsequent replacement of three methyl groups of cetyltrimethylammonium bromide (CTAB) with hydroxyethyl (1–3, series I), methoxyethyl (4–6, series II), and n‐propyl (7–9, series III) groups. The hydrophilicity at the polar head was gradually reduced from series I to series III. Interestingly, the lipase activity was found to be markedly higher for series II surfactants relative to their more hydrophilic analogues in series I. Moreover, the activity remained almost comparable for complementary analogues of both series I and III, though the hydrophilicity was drastically different. Noticeably, the head‐group area per surfactant is almost similar for comparable surfactants of both series I and III, but distinctly higher in case of series II surfactants. Thus the lipase activity was largely regulated by the surfactant head‐group size, which plays the dominant role over the hydrophilicity. The increase in head‐group size presumably allows the enzyme to attain a flexible conformation as well as increase in the local concentration of enzyme and substrate, leading to the higher efficiency of lipase. The lipase showed its best activity in the microemulsion of 6 probably because of its highest head‐group size. Furthermore, the observed activity in 6 is 2–3‐fold and 8‐fold higher than sodium bis(2‐ethyl‐1‐hexyl)sulfosuccinate (AOT) and CTAB‐based microemulsions, respectively, and in fact highest ever in any w/o microemulsions.
Are the Hydrogen Bonds of RNA (A⋅U) Stronger Than those of DNA (A⋅T)? A Quantum Mechanics Study
Authors: Pérez Alberto , Sponer Jiri , Jurecka Petr , Hobza Pavel , Luque F. Javier , Orozco Modesto
Published: June 2005

The intrinsic stability of Watson–Crick d(A⋅T) and r(A⋅U) hydrogen bonds was analyzed by employing a variety of quantum‐mechanical techniques, such as energy calculations, determination of reactivity indexes, and analysis of electron density topology. The analyses were performed not only for equilibrium gas‐phase geometries, but also on hundreds of conformations derived from molecular dynamics (MD) and database analysis. None of our results support the idea that r(A⋅U) hydrogen bonds are intrinsically more stable than those of d(A⋅T). Instead, our data are in accordance with the traditional view that the greater stability of RNA relative to DNA is attributable to a variety of effects (e.g., stacking, sugar puckering, solvation) rather than to a significant difference in the hydrogen bonding of DNA and RNA base pairs.
Site‐Isolated Porphyrin Catalysts in Imprinted Polymers
Authors: Burri Estelle , Öhm Margarita , Daguenet Corinne , Severin Kay
Published: June 2005

A meso‐tetraaryl ruthenium porphyrin complex having four polymerizable vinylbenzoxy groups (2) has been synthesized by reaction of pyrrole with 4‐(vinylbenzoxy)benzaldehyde and subsequent metalation with [Ru3(CO)12]. The porphyrin complex was immobilized by copolymerization with ethylene glycol dimethacrylate. The resulting polymer P2 was found to catalyze the oxidation of alcohols and alkanes with 2,6‐dichloropyridine N‐oxide without activation by mineral acids. Under similar conditions, the homogeneous catalyst 2 was completely inefficient. By using diphenylaminomethane and 1‐aminoadamantane as coordinatively bound templates during the polymerization procedure, the molecularly imprinted polymers P3 and P4 have been synthesized. Compared with the polymer P2, the imprinted catalysts displayed a significantly increased activity with rate enhancements of up to a factor of 16.
Cover Picture: Structural and Binding Features of Cofacial Bis‐Porphyrins with Calixarene Spacers: Pac‐Man Porphyrins That Can Chew (Chem. Eur. J. 14/2005)
Authors: Jokic Danica , Boudon Corinne , Pognon Grégory , Bonin Michel , Schenk Kurt J. , Gross Maurice , Weiss Jean
Published: June 2005

A new generation of cofacial bis‐porphyrins has been synthesized based on the efficient combination of calixarene spacers and acetylenic porphyrin derivatives. In the Full Paper on page 4199 ff., M. Gross, J. Weiss et al. describe the synthesis and characterization (UV‐visible and NMR spectroscopy and electrochemical studies) of pac‐man‐type porphyrins that adapt their shape to the size of bidentate guests.
Equations of Camassa‐Holm type and Jacobi ellipsoidal coordinates
Authors: Vaninsky K. L.
Published: June 2005

We consider the integrable Camassa‐Holm (CH) equation on the line with positive initial data rapidly decaying at infinity. On such a phase space we construct a one‐parameter family of integrable hierarchies that preserves the mixed spectrum of the associated string spectral problem. This family includes the CH hierarchy. We demonstrate that the constructed flows can be interpreted as Hamiltonian flows on the space of Weyl functions of the associated string spectral problem. The corresponding Poisson bracket is the Atiyah‐Hitchin bracket. Using an infinite dimensional version of the Jacobi ellipsoidal coordinates, we obtain a one‐parameter family of canonical coordinates linearizing the flows. © 2005 Wiley Periodicals, Inc.
Study of a highly accurate and fast protein–ligand docking method based on molecular dynamics
Authors: Taufer M. , Crowley M. , Price D. J. , Chien A. A. , Brooks C. L.
Published: June 2005

Few methods use molecular dynamics simulations in concert with atomically detailed force fields to perform protein–ligand docking calculations because they are considered too time demanding, despite their accuracy. In this paper we present a docking algorithm based on molecular dynamics which has a highly flexible computational granularity. We compare the accuracy and the time required with well‐known, commonly used docking methods such as AutoDock, DOCK, FlexX, ICM, and GOLD. We show that our algorithm is accurate, fast and, because of its flexibility, applicable even to loosely coupled distributed systems such as desktop Grids for docking. Copyright © 2005 John Wiley & Sons, Ltd.
Parallel protein folding with STAPL
Authors: Thomas Shawna , Tanase Gabriel , Dale Lucia K. , Moreira Jose M. , Rauchwerger Lawrence , Amato Nancy M.
Published: June 2005

The protein‐folding problem is a study of how a protein dynamically folds to its so‐called native state—an energetically stable, three‐dimensional conformation. Understanding this process is of great practical importance since some devastating diseases such as Alzheimer's and bovine spongiform encephalopathy (Mad Cow) are associated with the misfolding of proteins. We have developed a new computational technique for studying protein folding that is based on probabilistic roadmap methods for motion planning. Our technique yields an approximate map of a protein's potential energy landscape that contains thousands of feasible folding pathways. We have validated our method against known experimental results. Other simulation techniques, such as molecular dynamics or Monte Carlo methods, require many orders of magnitude more time to produce a single, partial trajectory. In this paper we report on our experiences parallelizing our method using STAPL (Standard Template Adaptive Parallel Library) that is being developed in the Parasol Lab at Texas A&M. An efficient parallel version will enable us to study larger proteins with increased accuracy. We demonstrate how STAPL enables portable efficiency across multiple platforms, ranging from small Linux clusters to massively parallel machines such as IBM's BlueGene/L, without user code modification. Copyright © 2005 John Wiley & Sons, Ltd.
Dynamic programming for LR‐PCR segmentation of bacterium genomes
Authors: Andonov Rumen , Lavenier Dominique , Veber Philippe , Yanev Nicola
Published: June 2005

Bacterium genome plasticity can efficiently be studied by the long‐range polymerase chain reaction (LR‐PCR) technique: genomes of different strains are split into hundreds of short segments which, after LR‐PCR amplification, are used to sketch profiles. The segments have to: (1) cover the entire genome; (2) overlap each other; and (3) be of nearly identical size. This paper addresses the problem of finding a list of segments satisfying these constraints ‘as much as possible’. Two algorithms based on dynamic programming approach are presented. They differ on the optimization criteria for measuring the quality of the covering. The first considers the maximal deviation of the segment lengths relatively to an ideal length. The second automatically finds a segment length that minimizes the maximal deviation. Copyright © 2005 John Wiley & Sons, Ltd.
Parallel RNA secondary structure prediction using stochastic context‐free grammars
Authors: Liu Tong , Schmidt Bertil
Published: June 2005

With the growing number of known RNA genes efficient and accurate computational analysis of RNA sequences is becoming increasingly important. Stochastic context‐free grammars (SCFGs) are used as a popular tool to model RNA secondary structures. However, algorithms for aligning a RNA sequence to a SCFG are highly compute‐intensive. This has so far limited applications of SCFGs to relatively small problem sizes. In this paper we present the design of a parallel RNA sequence‐structure alignment algorithm. Its implementation on parallel systems leads to significant runtime savings. This makes it possible to compute sequence‐structure alignments of even the largest RNAs such as small subunit ribosomal rRNAs and long subunit ribosomal rRNAs in reasonable time. Copyright © 2005 John Wiley & Sons, Ltd.
Peptide identification via constrained multi‐objective optimization: Pareto‐based genetic algorithms
Authors: Malard J. M. , Heredia‐Langner A. , Cannon W. R. , Mooney R. , Baxter D. J.
Published: June 2005

Automatic peptide identification from collision‐induced dissociation tandem mass spectrometry data using optimization techniques is made difficult by large plateaus in the fitness landscapes of scoring functions, by the fuzzy nature of constraints from noisy data and by the existence of diverse but equally justifiable probabilistic models of peak matching. Here, two different scoring functions are combined into a parallel multi‐objective optimization framework. It is shown how multi‐objective optimization can be used to empirically test for independence between distinct scoring functions. The loss of selection pressure during the evolution of a population of putative peptide sequences by a Pareto‐driven genetic algorithm is addressed by alternating between two definitions of fitness according to a numerical threshold. Copyright © 2005 John Wiley & Sons, Ltd.
RAxML‐II: a program for sequential, parallel and distributed inference of large phylogenetic trees
Authors: Stamatakis Alexandros , Ludwig Thomas , Meier Harald
Published: June 2005

Inference of phylogenetic trees comprising hundreds or even thousands of organisms based on the maximum likelihood method is computationally intensive. We present simple heuristics which yield accurate trees for synthetic as well as real data and significantly reduce execution time. Those heuristics have been implemented in a sequential, parallel, and distributed program called RAxML‐II, which is freely available as open source code. We compare the performance of the sequential program with PHYML and MrBayes which—to the best of our knowledge—are currently the fastest and most accurate programs for phylogenetic tree inference based on statistical methods. Experiments are conducted using 50 synthetic 100 taxon alignments as well as nine real‐world alignments comprising 101 up to 1000 sequences. RAxML‐II outperforms MrBayes for real‐world data both in terms of speed and final likelihood values. Furthermore, for real data RAxML‐II requires less time (a factor of 2–8) than PHYML to reach PHYML's final likelihood values and yields better final trees due to its more exhaustive search strategy. For synthetic data MrBayes is slightly more accurate than RAxML‐II and PHYML but significantly slower. The non‐deterministic parallel program shows good speedup values and has been used to infer a 10 000‐taxon tree comprising organisms from the domains Eukarya, Bacteria, and Archaea. Copyright © 2005 John Wiley & Sons, Ltd.
Life course determinants of insulin secretion and sensitivity at age 50 years: the Newcastle thousand families study
Authors: Pearce Mark S , Unwin Nigel C , Parker Louise , Alberti K. George M. M.
Published: June 2005

Background

Suboptimal nutrition during fetal life and infancy is suggested to increase insulin resistance in adulthood. This study investigated the proportion of variance in insulin secretion and resistance accounted for by factors operating at different stages of life using a cohort of all 1142 births in the city of Newcastle, UK in May and June 1947.

Methods

Detailed information was collected prospectively during childhood, including birth weight, growth and socio‐economic circumstances. At age 50, 412 study members attended for clinical examination. Fasting and 30‐min plasma insulin and glucose levels were determined and HOMA‐IR and insulin secretion derived.

Results

Birth weight was not a significant predictor of HOMA‐IR after adjustment for percent body‐fat and waist‐hip ratio. Duration of breastfeeding was significantly negatively associated with HOMA‐IR in men. For both genders, fetal life explained directly little variation in either HOMA‐IR or insulin secretion (0.1–5.6%). Compared to early life, adult lifestyle and body composition directly explained larger proportions of the variances for insulin secretion and HOMA‐IR for men (11 and 22% respectively) and women (5.9 and 34%).

Conclusions

Insulin secretion is largely unexplained by these data. For insulin resistance, the evidence suggests a limited impact of early life and a larger impact of adult factors. Copyright © 2005 John Wiley & Sons, Ltd.
Simultaneous Determination of Copper and Bismuth by Anodic Stripping Voltammetry Using H‐Point Standard Addition Method with Simultaneous Addition of Analytes
Authors: Shams Esmaeil , Abdollahi Hamid , Hajian Reza
Published: June 2005

Simultaneous determination of bismuth and copper by anodic stripping voltammetry using H‐point standard addition method (HPSAM) with simultaneous addition of analytes is described. The effect of various parameters including acid concentration, accumulation time, accumulation potential and concentration ratio of analytes in the standard solution on the sensitivity and accuracy of method were investigated. The results of applying the H‐point standard addition method showed that Cu2+ and Bi3+ could be determined simultaneously with the concentration ratios of Cu2+ to Bi3+ varying from 1 : 15 to 16 : 1 in the mixed sample. The method was successfully applied to the simultaneous determination of copper and bismuth in some synthetic mixtures.
Magnet Incorporated Carbon Electrodes: Methods for Construction and Demonstration of Increased Electrochemical Flux
Authors: Dunwoody Drew C. , Ünlü Murat , Wolf Angela K. H. , Gellett Wayne L. , Leddy Johna
Published: June 2005

Magnetic fields at electrodes increase flux through dynamics. Magnetically modified electrodes sustain a permanent magnetic field because magnetic materials are either attached to the electrode surface or incorporated into the electronic conductor of the electrode. Thus far, magnetically modified electrodes have been produced by coating electrode surfaces with composites of Nafion and magnetic microparticles. Glassy carbon and platinum electrodes as well as fuel cell electrodes modified with Nafion and magnetic microparticles exhibit enhanced flux as compared to similar nonmagnetic composites. Here, magnet incorporated carbon electrodes (MICEs) are presented. Two examples are described: magnet incorporated carbon paste electrodes (MICE‐Ps) and magnet incorporated carbon epoxy electrodes (MICE‐Es). Voltammetrically driven fluxes for MICEs are higher than those for the corresponding nonmagnetic controls (carbon paste (CPEs) and carbon epoxy (CEEs) electrodes).
Investigation of two‐dimensional channel flow with a partially compliant wall using finite volume–finite difference approach
Authors: Zhang X. , Ajaykumar R. , Sudharsan N. M. , Kumar K.
Published: June 2005

This paper presents a numerical simulation of steady two‐dimensional channel flow with a partially compliant wall. Navier–Stokes equation is solved using an unstructured finite volume method (FVM). The deformation of the compliant wall is determined by solving a membrane equation using finite difference method (FDM). The membrane equation and Navier–Stokes equation are coupled iteratively to determine the shape of the membrane and the flow field. A spring analogy smoothing technique is applied to the deformed mesh to ensure good mesh quality throughout the computing procedure. Numerical results obtained in the present simulation match well with that in the literature. Copyright © 2005 John Wiley & Sons, Ltd.
Cytogenetic evaluation of a large series of hepatoblastomas: Numerical abnormalities with recurring aberrations involving 1q12–q21
Authors: Tomlinson Gail E. , Douglass Edwin C. , Pollock Brad H. , Finegold Milton J. , Schneider Nancy R.
Published: June 2005

Hepatoblastoma is a malignant embryonal liver tumor that occurs almost exclusively in infants and very young children. Previous cytogenetic studies of hepatoblastoma have investigated small series or individual cases. This report is on the cytogenetics of a large series of 111 hepatoblastoma specimens, with cytogenetic results consecutively karyotyped over a 12‐year period. Abnormal karyotypes were observed in 55 cases (∼50% of the total). Numerical aberrations were observed in 41 cases (36% of the total), particularly trisomies of chromosomes 2, 8, and 20. Chromosome losses were less common than chromosome gains. Structural abnormalities were observed in 43 cases (39% of the total). Unbalanced translocations resulting in trisomy 1q and involving breakpoints at 1q12–21 were the most common structural abnormality, observed in 20 tumors (18% of total cases); the corresponding translocated chromosome was highly varied. The previously reported t(1;4) was observed in seven cases. Most tumors with translocations involving 1q12–21 also displayed numerical chromosome aberrations, the most common of which were chromosomal trisomies, whereas tumors with other structural rearrangements had fewer numerical abnormalities. Supplementary material for this article can be found on the Genes, Chromosomes, and Cancer website at http://www.interscience.wiley.com/jpages/1045‐2257/suppmat/index.html. © 2005 Wiley‐Liss, Inc.
Identification of steroid derivatives that function as potent antiandrogens
Authors: Miyamoto Hiroshi , Marwah Padma , Marwah Ashok , Yang Zhiming , Chung Chin‐Ying , Altuwaijri Saleh , Chang Chawnshang , Lardy Henry
Published: June 2005

We have hypothesized that some steroid derivatives bind to the androgen receptor (AR) with very low androgenic activity and therefore potentially function as better AR antagonists than clinically used antiandrogens, such as flutamide. Indeed, we previously found such a compound, 3β‐acetoxyandrosta‐1,5‐diene‐17‐one ethylene ketal (ADEK), with some estrogenic activity. Here we report the identification of 2 additional steroid derivatives, 3β‐hydroxyandrosta‐5,16‐diene (HAD) and androsta‐1,4‐diene‐3,17‐dione‐17‐ethylene ketal (OAK), as new potent antiandrogens. Like ADEK, HAD and OAK could interrupt androgen binding to the AR and suppress both dihydrotestosterone‐ and androstenediol‐induced transactivations of wild‐type and mutant ARs in prostate cancer cells. These 2 compounds also inhibited prostate‐specific antigen expression in LNCaP as well as growth of different AR‐positive prostate cancer cell lines stimulated by androgen. Significantly, HAD and OAK had only marginal agonist effects, as compared to hydroxyflutamide. More importantly, in contrast to ADEK, OAK was shown to possess marginal estrogenic activity. These results strengthen our hypothesis and suggest that selective steroid derivatives could be potent antiandrogenic drugs with less unfavorable effects for the treatment of prostate cancer. © 2005 Wiley‐Liss, Inc.
Differential MHC class II component expression in HPV‐positive cervical cancer cells: Implication for immune surveillance
Authors: Zehbe Ingeborg , Höhn Hanni , Pilch Henryk , Neukirch Claudia , Freitag Kirsten , Maeurer Markus J.
Published: June 2005

Effective eradication of human papillomavirus (HPV)‐positive tumors may require CD8+ and CD4+ T‐cell‐mediated immune responses. Ectopic expression of MHC class II surface molecules has been described in the context of cervical cancer, but coexpression with other components of the MHC class II antigen presentation pathway has not been addressed. We have evaluated the MHC class II antigen presentation pathway in malignant squamous epithelium of HPV+ cervical cancer lesions by in situ costaining HLA‐DR with CLIP or DMA/DMB. Cervical cancer cells exhibit 3 MHC class II phenotypes: (i) DR+/CLIP+ or DM+; (ii) DR+/CLIP‐ or DM‐; and (iii) DR‐/CLIP+ or DM+. The identical profile has been identified in HPV+ ME180 cells, which serve as a target for HLA‐DR4‐restricted and HPV68, E7‐specific CD4+ T cells. IFN‐γ pretreatment of ME180 cells, associated with differential trafficking of MHC class II molecules, is necessary for effective T‐cell recognition. Although proinflammatory cytokines may facilitate MHC class II‐restricted antigen recognition in tumor cells, different phenotypes of the MHC class II antigen presentation pathway may be associated with evasion from CD4+‐mediated cellular immune responses. © 2005 Wiley‐Liss, Inc.
Alcohol intake in adolescence and mammographic density
Authors: Vachon Celine M. , Sellers Thomas A. , Janney Carol A. , Brandt Kathleen R. , Carlson Erin E. , Pankratz Vernon S. , Wu Fang‐Fang , Therneau Terry M. , Cerhan James R.
Published: June 2005

Adolescent exposures may be important in the development of breast cancer later in life. We examined the association of adolescent alcohol consumption and adult mammographic density, a strong risk factor for breast cancer. Women within the Minnesota Breast Cancer Family Cohort with detailed mammogram and risk factor information (n = 1,893) formed our sample. Breast cancer cases were excluded. Adolescent alcohol consumption (before age 18) was solicited through a mailed questionnaire. Percent density (PD) was estimated using the computer‐assisted thresholding program, Cumulus. Statistical analyses were performed using linear mixed effect models. Women who reported ever drinking alcohol before age 18 (n = 390; 21%) had a higher unadjusted PD than women who never drank during adolescence (
$\hat{\mu}$unadj = 26.5% vs. 22.2%), but this difference disappeared with adjustment for risk factors for mammographic density ($\hat{\mu}$adj = 21.0% vs. 21.2%, p = 0.94). Adult PD was not associated with age at initiation, amount of alcohol consumed at one sitting or frequency of alcohol use before age 18. The lack of differences was seen across strata of menopausal status. There was suggestion of higher PD among heavy and more frequent drinkers (24.0%, 95% CI 21.1–26.8%) compared to lighter (21.3%, 95% CI 20.3–22.3%) and never drinkers (21.4%, 95% CI 20.9–21.9%) and also among regular adolescent drinkers who were daily or weekly adult drinkers (25.0%, 95% CI 23.0–27.0%) compared to less regular drinkers in these 2 time periods (23.0–23.4%). However, these associations were not statistically significant (p = 0.27 and p = 0.22, respectively). In summary, there was no evidence that adolescent alcohol use was associated with large and persistent effects on adult PD. © 2005 Wiley‐Liss, Inc.
B7‐1 and B7‐2 act differentially in the induction of a T cell response: Their impact for a HLA‐matched and HLA‐mismatched anti‐tumor immunotherapy
Authors: Kronfeld Kai , Abken Hinrich , Seliger Barbara
Published: June 2005

The efficacy of T cell‐based immunotherapy is primarily due to efficient cellular activation that requires the engagement of 2 separate signals, i.e., via the T cell receptor complex and via co‐stimulatory molecules the prototype of which is CD28. In cellular activation, the CD28 ligands B7‐1 (CD80) and B7‐2 (CD86) are thought to play nearly identical roles in T cell activation. We monitored the T cell response upon co‐culture with HLA Class I‐matched and mismatched renal carcinoma cells, respectively, that express different levels of B7‐1 and B7‐2, respectively. In a HLA Class I‐mismatched co‐culture, T cell proliferation, IFN‐γ and GM‐CSF secretion equally depend on the levels of B7‐1 and B7‐2 on tumor cells. In contrast, in a HLA Class I‐matched situation, B7‐2 is more effective in the induction of IFN‐γ and GM‐CSF secretion than B7‐1, but both B7 molecules induce T cell proliferation equally efficient. B7‐2 is more effective than B7‐1 in inducing TNF‐α and IL‐10 secretion in both HLA Class I‐matched and mismatched situations. The distinct patterns of cytokine induction by B7‐1 and B7‐2 obviously depend on the HLA Class I compatibility. These conclusions have substantial implications for the development of B7‐based vaccines used for immunotherapies. © 2005 Wiley‐Liss, Inc.
Correlation of DNA damage in epidemic dropsy patients to carcinogenic potential of argemone oil and isolated sanguinarine alkaloid in mice
Authors: Das Mukul , Ansari Kausar M. , Dhawan Alok , Shukla Yogeshwer , Khanna Subhash K.
Published: June 2005

In recent times, a higher incidence of gall bladder carcinoma in the Indo‐Gangetic basin has been linked with the consumption of contaminated mustard oil. Consumption of mustard oil contaminated with argemone oil (AO) is well known to cause clinical manifestation referred to as “epidemic dropsy.” Because sanguinarine, an active alkaloid of AO, has been shown to intercalate DNA, a possible correlation of DNA damage in epidemic dropsy patients to tumorigenic potential of AO and isolated sanguinarine alkaloid in mice was investigated in the present study. Single topical application of AO (0.15–0.3 ml) or isolated sanguinarine (4.5–18 μmol) followed by twice‐weekly application of tetradecanoylphorbolmyristate acetate (TPA) for 25 weeks resulted in formation of tumors. Histopathologically these tumors were of squamous cell carcinoma type and similar to those found in the positive control group using dimethylbenzanthracene (DMBA)/TPA. The activities of cutaneous γ‐glutamyl transpeptidase (GGT) and glutathione‐S‐transferase P (GST‐P), marker enzymes of tumorigenesis, were found to exhibit higher expression in AO or isolated sanguinarine/TPA treated groups when compared to control. The higher expression of p53 and p21/WAF1 in skin after single topical application of AO or isolated sanguinarine further confirms the tumorigenic response. Single topical application of AO or isolated sanguinarine alkaloid to mice showed significant DNA damage in terms of Olive tail moment (89–129%), tail length (54%) and tail DNA (153–205%) using Comet assay in skin cells. Further, the extent of DNA damage in blood cells of epidemic dropsy patients in alkaline Comet assay was found to be significantly higher as compared to normal population, indicating the genotoxic response of AO exposure. Although the genotoxic lesions may be repaired to some extent on withdrawal of consumption of AO contaminated mustard oil and the residual genotoxic effects caused by AO may not be expressed as signs of carcinogenesis. Environmental factors or hormonal changes during aging process may lead to stimulate/promote the genetically altered latent cells to form neoplastic lesions and can act as one of the etiological factors responsible for higher incidence of gall bladder carcinoma in the population of Indo‐Gangetic basin. © 2005 Wiley‐Liss, Inc.
Antibody response to a non‐conserved C‐terminal part of human histone deacetylase 3 in colon cancer patients
Authors: Shebzukhov Yuriy V. , Koroleva Ekaterina P. , Khlgatian Svetlana V. , Belousov Pavel V. , Kuz'mina Ksenia E. , Radko Boris V. , Longpre Fanny , Lagarkova Maria A. , Kadachigova Tatiana S. , Gurova Olga V. , Meshcheryakov Andrey A. , Lichinitser Mikhail R. , Knuth Alexander , Jager Elke , Kuprash Dmitry V. , Nedospasov Sergei A.
Published: June 2005

Antibodies to cancer antigens can often be detected in the sera of patients, although the mechanism of the underlying humoral immune response is poorly understood. Using immunoscreening of tumor‐derived cDNA expression libraries (SEREX), we identified human histone deacetylase 3 (HDAC3) as serologically defined antigen in colon cancer. Closely related HDAC1 and HDAC2 do not elicit humoral response in colon cancer patients. We show that the C‐terminal region of HDAC3 protein lacking the homology to other Class I HDAC contains at least 3 distinct B‐cell epitopes that are recognized by the serum antibodies. HDAC3 in combination with other SEREX antigens may become a useful molecular biomarker with diagnostic or prognostic value for a subset of colon cancer patients. Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience. wiley.com/jpages/0020‐7136/suppmat/index.html. © 2005 Wiley‐Liss, Inc.
Hyperforin, a bio‐active compound of St. John's Wort, is a new inhibitor of angiogenesis targeting several key steps of the process
Authors: Martínez‐Poveda Beatriz , Quesada Ana R. , Medina Miguel Ángel
Published: June 2005

Hyperforin, a phloroglucinol derivative found in St. John's wort related mainly to its antidepressant effects, has been reported recently to induce apoptosis in tumour cells and to inhibit cancer invasion and metastasis. We show that hyperforin inhibits angiogenesis in vitro in bovine aortic endothelial cells and in vivo in the chorioallantoic membrane assay. In a variety of experimental systems representing the sequential events of the angiogenic process, hyperforin treatment of endothelial cells resulted in strong inhibitory effects. Hyperforin inhibited the growth of endothelial cells in culture. Capillary tube formation on Matrigel was abrogated completely by addition of hypeforin at the low micromolar range. Hyperforin also exhibited a clear inhibitory effect on the invasive capabilities of endothelial cells. Zymographic assays showed that hyperforin treatment produced a complete inhibition of urokinase and a remarkable inhibition of matrix metalloproteinase 2. Our data indicates that hyperforin is a compound that interferes with key events in angiogenesis, confirming the recent and growing evidence about a potential role of this compound in cancer and metastasis inhibition and making it a promising drug for further evaluation in the treatment of angiogenesis‐related pathologies. © 2005 Wiley‐Liss, Inc.
RNASEL germline variants are associated with pancreatic cancer
Authors: Bartsch Detlef K. , Fendrich Volker , Slater Emily P. , Sina‐Frey Mercedes , Rieder Harald , Greenhalf William , Chaloupka Brunhilde , Hahn Stephan A. , Neoptolemos John P. , Kress Ralf
Published: June 2005

The RNASEL (encoding ribonuclease L) gene Glu265X mutation has been implicated in familial prostate cancer, and an association between the RNASEL Arg462Gln variant and sporadic and familial prostate cancer, has also been suggested. Because prostate cancer occurs in some familial pancreatic cancer families, we evaluated the role of the RNASEL gene variants Glu265X and Arg462Gln in the etiology of pancreatic cancer. Exon 2 of the RNASEL gene was directly sequenced in the germline of 36 familial and 75 sporadic pancreatic cancer patients and in 108 controls. The Glu265X mutation was identified in one (2.8%) familial and one (1.3%) sporadic pancreatic cancer case, but not in any of the controls. Arg462Gln variants were identified in 61 (56%) controls and in 55 (73%) sporadic pancreatic cancer cases with 8 (7%) and 12 (16%) homozygotes, respectively (p = 0.009). For homozygous carriers the increased risk for pancreatic cancer was 3.5 (odds ratio [OR] = 3.53, 95% confidence interval [CI] = 1.11–11.46, p = 0.03). The population attributable fraction (PAF) was 38.7% (95% CI = 0.08–0.80). In familial pancreatic cancer no association between Arg462Gln genotypes and pancreatic cancer risk was evident. In sporadic pancreatic cancer there were no significant differences between Arg462Gln genotypes regarding clinical characteristics. In familial pancreatic cancer, however, patients with Arg462Gln variants had more aggressive tumors with more high grade cancers (OR = 15.40, p = 0.009) and more distant metastases (OR = 7.00, p = 0.04) than patients with the wild‐type genotype. Our results suggest that RNASEL variants Glu265X and Arg462Gln may contribute to the tumorigenesis of sporadic and familial pancreatic cancer, which has to be proven in large scale studies. © 2005 Wiley‐Liss, Inc.
Involvement of the immune response in the cure of metastatic murine CT‐26 colon carcinoma by low electric field‐enhanced chemotherapy
Authors: Plotnikov Alexander , Tichler Thomas , Korenstein Rafi , Keisari Yona
Published: June 2005

Low electric field cancer treatment‐enhanced chemotherapy (LEFCT‐EC) is a new treatment modality that combines chemotherapeutic agents and low electric field stimulation. LEFCT‐EC was found to destroy malignant mouse tumors and cause massive death of tumor cells. This may enable the immune system cells to efficiently recognize and eliminate tumor cells at the primary tumor site and at metastatic foci. Mice with 15 mm diameter intracutaneous colon carcinomas (CT‐26) were injected with BCNU (35 mg/kg), and 2 min later the tumors were exposed to low electric fields (intensity 40 V/cm, pulse duration 180 μs, frequency 500 Hz) for 12 min (LEFCT‐EC). We found that treatment with LEFCT‐EC achieved complete cure of 93% of the animals. In comparison, electric fields alone (13% cure), chemotherapy alone (0%), surgery (15%) or a combination of surgery and bis‐chloroethyl‐nitrosurea, carmustine (BCNU; 84%) treatments resulted in lower cure rates. After treatment and cure with LEFCT‐EC, 50% of the cured mice developed resistance to a tumor challenge (surgery + BCNU only 15%). Furthermore, splenocytes from cured animals protected naive animals from a tumorigenic dose of tumor cells. Separation of spleen cells into lymphocyte subpopulations indicated a major role for CD4 and CD8 T cells in this protection. FACS analysis revealed restoration of normal splenocyte subpopulation proportions impaired by cytotoxic chemotherapy. Our results suggest that LEFCT‐EC can directly destroy primary tumors and facilitate the destruction of metastatic disease by enforcement of antitumor immune responses. © 2005 Wiley‐Liss, Inc.
Risk assessment of p53 genotypes and haplotypes in tobacco‐associated leukoplakia and oral cancer patients from eastern india
Authors: Mitra Sayan , Sikdar Nilabja , Misra Chaitali , Gupta Shalini , Paul Ranjan Rashmi , Roy Bidyut , Panda Chinmay Kumar , Roychoudhury Susanta
Published: June 2005

The role of 3 p53 polymorphisms (16 bp duplication at intron 3, codon 72 Arg/Pro and intron 6 NciI RFLP at np 13494) as potential markers for indicating cancer risk remains inconclusive. In our case‐control study consisting of 197 leukoplakia and 310 oral squamous cell carcinoma (SCC) patients and 348 controls, genotype frequencies at these 3 p53 loci were determined by PCR‐RFLP method and analyzed by multiple logistic regression to determine the risks of the diseases. The 2/2 genotype at codon 72 of p53 was at risk for developing leukoplakia (OR = 1.6, 95% CI 1.1–2.3), whereas the combination of 1/2 and 2/2 genotypes at intron 3 and 1/1 and 1/2 genotypes at intron 6 conferred a protective effect against leukoplakia and oral SCC development, respectively (OR = 0.5, 95% CI 0.4–0.8 and OR = 0.6, 95% CI 0.5–0.9, respectively). When subjects were stratified according to specific tobacco habit, the risk/protection estimates improved significantly in some cases. Specifically, the exclusive smokers with p53 codon 72 2/2 genotype showed a higher risk of developing leukoplakia (OR = 2.7, 95% CI 1.2–6.3). Furthermore, a particular p53 haplotype 1‐2‐2 was at risk for both tobacco‐associated leukoplakia and oral SCC (OR = 1.5, 95% CI 1.1–1.9 and OR = 1.3, 95% CI 1.1–1.7, respectively). Our results show that both specific p53 genotype and haplotype can indicate risk of tobacco‐associated leukoplakia, but risk of development of tobacco‐associated oral SCC can be predicted by specific p53 haplotype only. © 2005 Wiley‐Liss, Inc.
Clinical significance of CXCR3 and CXCR4 expression in primary melanoma
Authors: Longo‐Imedio M. Isabel , Longo Natividad , Treviño Isabel , Lázaro Pablo , Sánchez‐Mateos Paloma
Published: June 2005

Tumor cell migration involved in metastases is a tightly regulated, nonrandom process. Chemokines have been identified as critical molecules guiding cell migration. We performed a prospective study to analyze a possible association between the expression of chemokine receptors CXCR3 and CXCR4 by primary melanoma and clinical outcome. Forty primary melanomas were available for analysis; 57% of the tumors expressed CXCR3 and 35% expressed CXCR4 by melanoma cells. At initial diagnosis, 5 patients had subclinical lymph node involvement and after a median follow‐up time of 32 months, 2 additional patients developed regional lymph node metastases and 5 patients developed distant metastases. The expression of CXCR4, but not CXCR3, by melanoma cells in primary lesions was significantly associated with the presence of ulceration, increased tumor thickness, a greater risk of developing regional and distant metastases and a higher mortality rate. Our study underscores the value of CXCR4 expression as a useful marker for predicting outcome in patients with localized melanoma. In addition, our findings support that, among chemokine receptors, CXCR4 might be an appropriate therapeutic target for adjuvant therapy in patients at risk for metastatic disease. © 2005 Wiley‐Liss, Inc.
Dual‐specificity phosphatase 1 and serum/glucocorticoid‐regulated kinase are downregulated in prostate cancer
Authors: Rauhala Hanna E. , Porkka Kati P. , Tolonen Teemu T. , Martikainen Paula M. , Tammela Teuvo L.J. , Visakorpi Tapio
Published: June 2005

Inactivation of tumor suppressor genes through deletion, mutation and epigenetic silencing has been shown to occur in cancer. In our study, we combined DNA demethylation and histone deacetylation inhibition treatments with suppression subtraction hybridization (SSH) and cDNA microarrays to identify potentially epigenetically downregulated genes in PC‐3 prostate cancer cell line. We found 11 genes whose expression was upregulated after relieving epigenetic regulation. Expression of 3 genes [dual‐specificity phosphatase 1 (DUSP1), serum/glucocorticoid regulated kinase (SGK) and spermidine/spermine N1‐acetyltransferase (SAT)] was subsequently studied in clinical sample material using real‐time quantitative RT‐PCR and immunohistochemistry. TheDUSP1andSGKmRNA expression was lower in hormone‐refractory prostate carcinomas compared to benign prostate hyperplasia (BPH) or untreated prostate carcinomas. BPH, normal prostate and high‐grade prostate intraepithelial neoplasia (PIN) expressed high levels of DUSP1 and SGK proteins. Ninety‐two percent and 48% of the prostate carcinomas showed almost complete lack of DUSP1 and SGK proteins, respectively, indicating common downregulation of these genes. The genomic bisulphite sequencing did not reveal dense hypermethylation in the promoter regions of eitherDUSP1orSGK. In conclusion, the data suggest that downregulation ofDUSP1andSGKis an early event and could be important in the tumorigenesis of prostate cancer. © 2005 Wiley‐Liss, Inc.
A novel osteotropic biomaterial OG‐PLG: Synthesis and in vitro release
Authors: Whang Kyumin , McDonald Jonathan , Khan Ambereen , Satsangi Neera
Published: June 2005

Statins (e.g., simvastatin) have shown to induce expression of the bone morphogenic protein‐2 gene in bone cells, but they are not used clinically because of a lack of a suitable delivery device. The overall objective is to develop optimized statin delivery devices for bone regeneration. The specific objective was to determine the effect of grafting statins to biodegradable poly[lactide‐co‐glycolide] (PLG) on release kinetics. Simvastatin was grafted to PLG (OG‐PLG) and characterized using contact‐angle measurements, attenuated total reflectance–Fourier transform infrared, and ultraviolet–visible spectroscopy to determine success of the synthesis. An ultraviolet–visible assay for measuring release of statins and degraded OG‐PLG in media was also developed. In vitro release studies using films and scaffolds made with PLG, PLG blended with simvastatin (PLG + Sim), and OG‐PLG (simvastatin grafted to PLG) blended into PLG at different concentrations showed that release rate of OG‐PLG from films was significantly greater than that of PLG + Sim. However, release rate from scaffolds showed PLG + Sim to be significantly higher than that of OG‐PLG. The diffusion‐controlled release kinetics of simvastatin from PLG + Sim seems to be more heavily affected by device morphology, whereas the degradation‐controlled release kinetics seem to be less affected. In short, release kinetics can be modulated by grafting statins to PLG. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Composite prostheses used to repair abdominal wall defects: Physical or chemical adhesion barriers?
Authors: Bellón J. M. , Serrano N. , Rodríguez M. , García‐Honduvilla N. , Pascual G. , Buján J.
Published: June 2005

In a composite prosthesis, the component placed at the peritoneal interface takes the form of a physical or chemical barrier. In this experimental study performed on the white New Zealand rabbit, several composites were examined to establish the effectiveness of these barriers at impeding adhesion formation. The biomaterials tested were two polypropylene prostheses (PP) with the physical barriers of expanded polytetrafluoroethylene or polyurethane (PP + ePTFE and PP + PU) and two prostheses (one polyester and the other PP) with the absorbable chemical barriers of polyethylene glycol/glycerol and hyaluronate, respectively (PO + gl and PP + hy). The composites were used to repair 7 × 5 cm defects created in the abdominal wall of the animals by placing the implant in contact with the visceral peritoneum and the subcutaneous tissue and fixing it to recipient tissue by 4/0 polypropylene running suture. Fourteen days after surgery the animals were sacrificed and specimens were taken for light microscopy and scanning electron microscopy. Adhesions developing at the prosthesis/visceral peritoneal interface were quantified. All the prostheses induced optimal mesothelialization. Composites with physical barriers behaved similarly in terms of provoking adhesions. However, the prostheses with chemical barriers differed in their effectiveness at preventing adhesions. Overall, the best results were obtained with the PP + PU composite. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2005