bluuebunny/crossref_metadata_2025 huggingface dataset:
Time‐resolved Luminescence and Singlet Oxygen Formation After Illumination of the Hypericin–Low‐density Lipoprotein Complex
Authors: Gbur Peter , Dedic Roman , Chorvat Jr Dusan , Miskovsky Pavol , Hala Jan , Jancura Daniel
Published: December 2008

Time‐resolved fluorescence and phosphorescence study of hypericin (Hyp) in complex with low‐density lipoproteins (LDL) as well as the evolution of singlet oxygen formation and annihilation after illumination of Hyp/LDL complexes at room temperature are presented in this work. The observed shortening of the fluorescence lifetime of Hyp at high Hyp/LDL molar ratios (>25:1) proves the self‐quenching of the excited singlet state of monomeric Hyp at these concentration ratios. The very short lifetime (∼0.5 ns) of Hyp fluorescence at very high Hyp/LDL ratios (>150:1) suggests that at high local Hyp concentration inside LDL molecules fast and ultrafast nonradiative decay processes from excited singlet state of Hyp become more important. Contrary to the lifetime of the singlet excited state, the lifetime (its shorter component) of Hyp phosphorescence is not dependent on Hyp/LDL ratio in the studied concentration range. The amount of singlet oxygen produced as well as the integral intensity of Hyp phosphorescence after illumination of Hyp/LDL complexes resemble the dependence of the concentration of molecules of Hyp in monomeric state on Hyp/LDL until a concentration ratio of 60:1. This fact confirms that only monomeric Hyp is able to produce the excited triplet state of Hyp, which in aerobic conditions leads to singlet oxygen production. The value of singlet oxygen lifetime (∼8 μs) after its formation from the excited triplet state of Hyp in LDL proves that molecules of singlet oxygen remain for a certain period of time inside LDL particles and are not immediately released to the aqueous surrounding. That Hyp exists in the complex with LDL in the monodeprotonated state is also demonstrated.
Challenges in Applying Photoemission Electron Microscopy to Biological Systems†
Authors: Peles Dana N. , Simon John D.
Published: December 2008

Photoemission electron microscopy (PEEM) is a unique surface‐sensitive instrument capable of providing real‐time images with high spatial resolution. While similar to the more common electron microscopies, scanning electron microscopy and transmission electron microscopy, the imaging technology relies on the photogeneration of electrons emitted from a sample through light excitation. This imaging technique has found prominence in surface and materials sciences, being well suited for imaging flat surfaces, and changes that occur to that surface as various parameters are changed (e.g. temperature, exposure to reactive gases). Biologically focused PEEM received significant attention in the 1970s, but was not aggressively advanced since that pioneering work. PEEM is capable of providing important insights into biological systems that extend beyond simple imaging. In this article, we identify and establish important issues that affect the acquisition and analysis of biological samples with PEEM. We will briefly review the biological impact and importance of PEEM with respect to our work. The article also concludes with a discussion of some of the current challenges that must be addressed to enable PEEM to achieve its maximum potential with biological samples.
Trajectory Optimization for DDE Models of Supercavitating Underwater Vehicles
Authors: Bottasso Carlo L. , Scorcelletti Francesco , Ruzzene Massimo , Ahn Seong S.
Published: December 2008

In this study we first develop a flight mechanics model for supercavitating vehicles, which is formulated to account for the dependence of the cavity shape from the past history of the system. This mathematical model is governed by a particular class of delay differential equations, featuring time delays on the states of the system. Next, flight trajectories and maneuvering strategies for supercavitating vehicles are obtained by solving an optimal control problem, whose solution, given a cost function and general constraints and bounds on states and controls, yields the control time histories that maneuver the vehicle according to a desired strategy, together with the associated flight path. The optimal control problem is solved using a novel direct multiple shooting approach, which is formulated to properly handle conditions dictated by the delay differential equation formulation governing the dynamic behavior of the vehicle. Specifically, the new formulation enforces the state continuity line conditions in a least-squares sense using local interpolations, which supports local time stepping and drastically reduces the number of optimization unknowns. Examples of maneuvers and resulting trajectories demonstrate the effectiveness of the proposed methodology and the generality of the formulation. The results are also compared with those obtained from a previously developed model governed by ordinary differential equations to highlight the differences and demonstrate the need for the current formulation.
Experimental Testing and Analysis of Inerter Devices
Authors: Papageorgiou Christos , Houghton Neil E. , Smith Malcolm C.
Published: December 2008

This paper presents a first in-depth experimental study of mechanical devices that are designed to approximate the dynamics of the ideal inerter, which is a two-terminal mechanical element analogous to the ungrounded capacitor. The focus of the paper is experimental testing and identification of stand-alone inerter devices as well as the study of practical issues involved in their feedback control using standard hydraulic damper test rigs. Two contrasting inerter embodiments are studied, one in which a flywheel is driven by a rack-and-pinion mechanism and the other employing a ballscrew. Due to the fact that the ideal inerter is a dynamic element whose admittance function is 90 deg out of phase with that of the ideal damper, particular attention is needed to ensure closed-loop stability in testing using standard hydraulic damper test rigs. As expected, instability is observed in default configurations, and it is seen to manifest itself in a nonlinear manner with backlash playing a significant role. By using a basic model of the hydraulic rig and a model of an ideal inerter with backlash, the nature of the instability is reproduced and explained in a qualitative way. To achieve closed-loop stability without the need to redesign the controller as a function of the load, a methodology is proposed involving the design of a mechanical buffer network to be connected in series with the inerter device. It is demonstrated that this approach removes the instability problem for a wide range of inertance loads. Finally, the dynamic characteristics of the inerter devices are identified. It is verified experimentally that the admittance of the devices approaches the ideal inerter admittance over a useful frequency range and that friction in the devices is a major source of deviation from the ideal inerter behavior.
Iterative and Feedback Control for Hysteresis Compensation in SMA
Authors: Leang Kam K. , Ashley Seth , Tchoupo Guy
Published: December 2008

This paper investigates the design of an iteration-based controller combined with feedback control to address the positioning error caused by hysteresis in a shape memory alloy (SMA) actuator. Without compensation, the positioning error due to hysteresis can be excessively large (greater than 20%), therefore limiting the performance of SMAs in positioning applications. An iterative controller based on the Preisach hysteresis model is used to compensate for the hysteresis. However, one of the major challenges with SMA at or near the phase-transition zones, from martensite to austenite and vice versa, is the output response is shown to be sensitive to small changes in the input. In practice, an iterative controller provides limited performance due to lack of robustness. It is demonstrated that combining a simple feedback controller with an iterative controller provides the needed robustness to enable high-precision tracking. Experimental results are presented that show maximum tracking error of 0.15% of the total displacement range—this value is approximately the noise level of the sensor measurement.
Fast and Robust Synchronization of Twin-Gyro Systems
Authors: Shahruz S. M.
Published: December 2008

In this paper, design of control laws for V-gimbaled control-moment-gyro (CMG) devices is studied. Such a device has two gyros that are used to control the slewing motion of space truss arms. Control laws are designed to make the gyros of a CMG device track a desired function of time synchronously. Synchronous tracking makes the angular displacement of a truss arm track a desired function of time. Application of the synchronizing control laws to two-gyro systems in the absence and presence of parametric uncertainties and disturbances is studied. In both cases, the designed control laws achieve the desired goals.
Association of
Bacillus anthracis
Capsule with Lethal Toxin during Experimental Infection
Authors: Ezzell J. W. , Abshire T. G. , Panchal R. , Chabot D. , Bavari S. , Leffel E. K. , Purcell B. , Friedlander A. M. , Ribot W. J.
Published: December 2008

Bacillus anthracis
lethal toxin (LT) was characterized in plasma from infected African Green monkeys, rabbits, and guinea pigs. In all cases, during the terminal phase of infection only the protease-activated 63-kDa form of protective antigen (PA
63
) and the residual 20-kDa fragment (PA
20
) were detected in the plasma. No uncut PA with a molecular mass of 83 kDa was detected in plasma from toxemic animals during the terminal stage of infection. PA
63
was largely associated with lethal factor (LF), forming LT. Characterization of LT by Western blotting, capture enzyme-linked immunosorbent assay, and size exclusion chromatography revealed that the antiphagocytic poly-γ-
d
-glutamic acid (γ-DPGA) capsule released from
B. anthracis
bacilli was associated with LT in animal blood in variable amounts. While the nature of this in vivo association is not understood, we were able to determine that a portion of these LT/γ-DPGA complexes retained LF protease activity. Our findings suggest that the in vivo LT complexes differ from in vitro-produced LT and that including γ-DPGA when examining the effects of LT on specific immune cells in vitro may reveal novel and important roles for γ-DPGA in anthrax pathogenesis.
Leishmania donovani
Ornithine Decarboxylase Is Indispensable for Parasite Survival in the Mammalian Host
Authors: Boitz Jan M. , Yates Phillip A. , Kline Chelsey , Gaur Upasna , Wilson Mary E. , Ullman Buddy , Roberts Sigrid C.
Published: December 2008

Mutations within the polyamine biosynthetic pathway of
Leishmania donovani
, the etiological agent of visceral leishmaniasis, confer polyamine auxotrophy to the insect vector or promastigote form of the parasite. However, whether the infectious or amastigote form of the parasite requires an intact polyamine pathway has remained an open question. To address this issue, conditionally lethal Δ
odc
mutants lacking ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, were created by double targeted gene replacement within a virulent strain of
L. donovani
. ODC-deficient promastigotes and axenic amastigotes were auxotrophic for polyamines and capable of robust growth only when exogenous putrescine was supplied in the culture medium, confirming that polyamine biosynthesis is an essential nutritional pathway for
L. donovani
promastigotes. To assess whether the Δ
odc
lesion also affected the ability of amastigotes to sustain a robust infection, macrophage and mouse infectivity experiments were performed. Parasite loads in murine macrophages infected with each of two independent Δ
odc
knockout lines were decreased ∼80% compared to their wild-type counterpart. Furthermore, α-difluoromethylornithine, a suicide inhibitor of ODC, inhibited growth of wild-type
L. donovani
amastigotes and effectively cured macrophages of parasites, thereby preventing host cell destruction. Strikingly, however, parasitemias of both Δ
odc
null mutants were reduced by 6 and 3 orders of magnitude, respectively, in livers and spleens of BALB/c mice. The compromised infectivity phenotypes of the Δ
odc
knockouts in both macrophages and mice were rescued by episomal complementation of the genetic lesion. These genetic and pharmacological studies strongly implicate ODC as an essential cellular determinant that is necessary for the viability and growth of both
L. donovani
promastigotes and amastigotes and intimate that pharmacological inhibition of ODC is a promising therapeutic paradigm for the treatment of visceral and perhaps other forms of leishmaniasis.
Morphology and evolution of epiphytic Davalliaceae scales
Authors: Tsutsumi Chie , Kato Masahiro
Published: December 2008

The scales of most members of the Davalliaceae and related epiphytic, secondary-hemiepiphytic, and climbing ferns consist of a stalk and a shield, are dense, and are persistent on the long-creeping rhizomes. They differ from the sessile, mostly deciduous scales of the related terrestrial eupolypod ferns. The stalked scales first developed two-dimensionally and later produced the proximal part of the shield from near the base to comprise a peltate or pseudopeltate shield on a stalk. Anatomical observations showed variations in the cellular and histological features and the degree of stalk insertion into a rhizome concavity. A character-phylogenetic tree of scales suggested an evolutionary linkage between the stalked scale and the epiphytic life form in the lineage leading to Davalliaceae and Polypodiaceae. The elaborated scales of most species of the obligate-epiphytic Davalliaceae were similar to the sunken-stalked, peltate, absorbing, epiphyllous trichomes of some angiosperm epiphytes. These results suggest that the stalked scales may have significant roles such as protection against desiccation, external water storage, and absorption of water and nutrients.
Inland diatoms from the McMurdo Dry Valleys and James Ross Island, Antarctica
Authors: Esposito R. M.M. , Spaulding S. A. , McKnight D. M. , Van de Vijver B. , Kopalová K. , Lubinski D. , Hall B. , Whittaker T.
Published: December 2008

Diatom taxa present in the inland streams and lakes of the McMurdo Dry Valleys and James Ross Island, Antarctica, are presented in this paper. A total of nine taxa are illustrated, with descriptions of four new species ( Luticola austroatlantica sp. nov., Luticola dolia sp. nov., Luticola laeta sp. nov., Muelleria supra sp. nov.). In the perennially ice-covered lakes of the McMurdo Dry Valleys, diatoms are confined to benthic mats within the photic zone. In streams, diatoms are attached to benthic surfaces and within the microbial mat matrix. One species, L. austroatlantica, is found on James Ross Island, of the southern Atlantic archipelago, and the McMurdo Dry Valleys. The McMurdo Dry Valley populations are at the lower range of the size spectrum for the species. Streams flow for 6–10 weeks during the austral summer, when temperatures and solar radiation allow glacial ice to melt. The diatom flora of the region is characterized by species assemblages favored under harsh conditions, with naviculoid taxa as the dominant group and several major diatom groups conspicuously absent.
Magnetic properties of the ferrimagnetic spinels systems CoFe2–2xCr2xO4
Authors: Masrour R , Hamedoun M , Hourmatallah A , Bouslykhane K , Benzakour N , Benyoussef A
Published: December 2008

The magnetic properties of a diluted ferrimagnetic spinels system CoFe2–2xCr2xO4 are studied using the high-temperature series expansions method in the range 0 ≤ x ≤ 1. The inter-sublattice exchange interactions (JCo Cr or JCo–Fe) are calculated using the probability law. The high-temperature series expansions, together with the Padé-approximants method, are applied to the spinels systems CoFe2–2xCr2xO4 to determine the magnetic phase diagram, i.e., TC versus dilution x. The critical exponent associated with the magnetic susceptibility (γ) is deduced. PACS Nos.: 75.30.Et; 75.40.Cx; 74.25.Ha, 75.30.Cr
Wave properties of plasma surrounding the event horizon of a nonrotating black hole
Authors: Sharif M , Mustafa G
Published: December 2008

We study the wave properties of a cold isothermal plasma in the vicinity of a Schwarzschild black-hole event horizon. The Fourier-analyzed perturbed 3+1 general relativistic magnetohydrodynamics equations are examined such that the complex dispersion relations are obtained for nonrotating, rotating nonmagnetized, and rotating magnetized backgrounds. The propagation and attenuation vectors along with the refractive index are obtained (shown graphically) to study the dispersive properties of the medium near the event horizon. The results show that no information can be obtained from the Schwarzschild magnetosphere. Further, the pressure stops the existence of normal dispersion of waves.PACS Nos.: 95.30.Sf, 95.30.Qd, 04.30.Nk
Paramagnetic Ge–Li centres in alpha quartz revisited: The DLi([GeO4/Li]0D) centre
Authors: Claridge R F.C. , Kryliouk O M , Weil J A , Williams J A.S.
Published: December 2008

A previously unreported stable paramagnetic defect centre in single-crystal alpha-quartz has been studied by quantitative X-band electron paramagnetic resonance spectroscopy at 15, 100, and 296 K, and is shown to contain a Ge3+ ion, presumably located substitutional for Si4+, with a nearby interstitial Li+ ion. The centre, called DLi herein, grows in slowly (months) after room-temperature x-irradiation and storage. Hyperfine structure arising from 73Ge, 7Li, and 29Si has been observed. The spin-Hamiltonian parameter matrices g, A(7Li), A(73Ge), and P(73Ge) are reported, also for centre CLi. A thermal dynamic process, probably involving Li+ hopping, begins to be appreciable above 100 K. Discussion of DLi, its apparent growth from another paramagnetic centre (not yet fully characterized), and comparison with other similar defects is included.PACS Nos.: 42.70.Ce, 61.72.Hh, 61.72–y, 61.72S–, 61.72uf, 61.80–x, 76.30–v, 76.30.Mi
Optical properties and microstructure of nitrogen-doped SrTiO3
Authors: Liu C M , Yuan Z L , Ju Y F , Xiang X , Zu X T , Zhou W L
Published: December 2008

Nitrogen-doped SrTiO3 samples have been successfully prepared by nitrogen-ion implantation. X-ray photoelectron spectra clearly indicate the presence of nitrogen dopants in the crystal lattice of SrTiO3. The ultraviolet–visible absorption spectra of nitrogen-doped SrTiO3 show enhanced visible light absorption in the range of 400–500 nm, which contributs to the localized N 2p state in the band gap of SrTiO3. The resistance coefficient of temperature is positive indicating metallic conducting behavior. The nonlinear dependence of voltage on current at liquid-nitrogen temperatures indicates a possible energy barrier in the grain boundary.PACS Nos.: 72.20.–i, 72.80.Ga, 78.20.–e
Parabolic band approximation of the electron energy levels in a tetrahedral-shaped quantum dot
Authors: Pengpan T , Daengngam C
Published: December 2008

In more elaborate schemes, an electron’s effective mass in a heterostructure semiconductor quantum dot (QD) depends on both its position and its energy. However, the electron’s effective mass can be simply modeled by a parabolic band approximation — the electron’s effective mass inside the QD — which is assumed to be constant and differs from the one outside the QD, which is also assumed to be constant. The governing equation to be solved for the electron’s energy levels inside the QD is the nonlinear Schrödinger equation. With the approximation, the nonlinear Schrödinger equation for a tetrahedral-shaped QD is discretized by using the finite-volume method. The discretized nonlinear Schrödinger equation is solved for the electron energy levels by a computer program. It is noted that the resulting energy levels for the parabolic mass model are nondegenerate due to the mass-gradient term at the corners, edges, and surfaces of the tetrahedral-shaped QD.PACS Nos.: 02.60.Cb, 03.65.Ge, 81.07.Ta
Exploring the utility of a new chiral phosphoramidite P,N-ligand derived from (R)-BINOL and 7-azaindole in asymmetric catalysis
Authors: Wechsler Dominik , Stradiotto Mark
Published: December 2008

Lithiation of 7-azaindole, followed by quenching with [(R)-(1,1′-binaphthalene-2,2′-diyl)]chlorophosphite afforded the new chiral phosphoramidite 1 in 92% isolated yield. Treatment of 0.5 equiv. of [(COD)MCl]2 (M = Rh, Ir; COD = η4-1,5-cyclooctadiene) with 2 equiv. of 1 afforded the corresponding [(κ1-P,N-1)(κ2-P,N-1)MCl] complexes in 68% (2a, Rh) and 72% (2b, Ir) yield, while treatment of (PPh3)3RhCl with 1 equiv. of 1 afforded [(PPh3)(κ2-P,N-1)RhCl] (3) as an analytically pure solid in 74% isolated yield. In examining the reaction of 1 with a mixture of 0.5 equiv. of [(COD)RhCl]2 and 1 equiv. of AgBF4, an inseparable mixture of [(κ2-P,N-1)2Rh]+BF4– (4a) and [(COD)(κ2-P,N-1)Rh]+BF4– (5a) was generated. Under analogous conditions employing [(COD)IrCl]2, the complex [(COD)(κ2-P,N-1)Ir]+BF4– (5b) was obtained in 86% isolated yield. Treatment of 0.5 equiv. of [(η3-allyl)PdCl]2 with 1 afforded [(η3-allyl)(κ2-P,N-1)Pd]+Cl– (6) in 86% isolated yield. The application of 1 in platinum group metal-mediated asymmetric chemical transformations, including alkene hydrogenation and hydroboration, ketone hydrosilylation, and allylic alkylation, was examined.Key words: chiral, ligand, phosphoramidite, asymmetric catalysis.
Octahedral perfluoroalkyl complexes of Ir(III) formed by oxidative addition of perfluoroalkyl iodides to Ir(acac)(CO)2
Authors: Huang Hui , Hurubeanu N Raluca , Bourgeois Cheryl J , Cheah Sue-Mei , Yuan Jian , Rheingold Arnold L , Hughes Russell P
Published: December 2008

Oxidative addition of primary, secondary, or benzylic perfluoroalkyl iodides (RF–I) to the phosphine free Ir(I) precursor Ir(acac)(CO)2 1 (acac = 2,4-pentanedionato) proceeds smoothly to afford octahedral Ir(III) products Ir(acac)(I)(RF)(CO)2, A combination of X-ray crystallographic studies and solution spectroscopy shows that these products are the result of overall trans-addition of the C–I bond to iridium, probably a result of thermodynamic control; evidence for a kinetic product resulting from net cis-addition is obtained in one case. Treatment of the Ir(III) compounds with AgOTf (Tf = CF3SO3) illustrates that the iodo ligand is replaced by triflate with retention of stereochemistry at Ir. The resulting triflate complexes are inert to displacement by H2O or H2. The Ir(III) products exhibit very high CO stretching frequencies in the IR, indicating that the CO ligands may be non-classical. A quantitative estimation of the degree of backbonding to the CO ligands in these compounds, and a comparison of the π-acceptor properties of CO and fluoroalkyl ligands, is made using an approach based on Density Functional Theory (DFT) and Natural Bond Orbital analyses.Key words: iridium, fluoroalkyl, oxidation, carbonyl, DFT.
Selaginella and 400 Million Years of Separation
Authors: Banks Jo Ann
Published: December 2008

Selaginella (spikemoss) is an enigma in the plant kingdom. Although a fascination to botanists at the turn of the twentieth century, members of this genus are unremarkable in appearance, never flower, and are of no agronomic value. However, members of this genus are relicts from ancient times, and one has to marvel at how this genus has survived virtually unchanged in appearance for hundreds of millions of years. In light of the recent completion of the Selaginella moellendorffii genome sequence, this review is intended to survey what is known about Selaginella, with a special emphasis on recent inquiries into its unique biology and importance in understanding the early evolution of vascular plants.
Levels of Tobacco-Specific Nitrosamines and Polycyclic Aromatic Hydrocarbons in Mainstream Smoke from Different Tobacco Varieties
Authors: Ding Yan S. , Zhang Liqin , Jain Ram B. , Jain Ntasha , Wang Richard Y. , Ashley David L. , Watson Clifford H.
Published: December 2008

It has been estimated that one in every five cancer deaths worldwide are related to tobacco use. According to the IARC, 10 polycyclic aromatic hydrocarbons (PAH) and 8 tobacco-specific nitrosamines (TSNA), as well as at least 45 other compounds or substances found in tobacco smoke, are potential human carcinogens. The levels of these carcinogens in contents of tobacco and smoke emissions vary between different tobacco products. We evaluated mainstream smoke emissions from cigarettes made with different types of tobacco to examine the relation between their deliveries of TSNAs and PAHs and any possible influence from tobacco nitrate content. To investigate the contribution of tobacco content to mainstream cigarette smoke deliveries without confounders such as filter design, filter ventilation, and paper porosity, we used custom-made, research-grade, unfiltered cigarettes that contained bright, burley, oriental, reconstituted, or mixtures of these tobaccos. Our findings confirm results from other researchers that tobacco type can influence the mainstream smoke delivery of nicotine, TSNAs, and PAHs. However, we found that the effect varies among individual compounds. In addition, we observed a statistically significant relationship between nitrate content and mainstream smoke 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK); nitrate level also influenced the mainstream smoke deliveries of the summed total of the 10 PAHs identified by IARC as potential human carcinogens. The influence of nitrate on mainstream smoke NNK and PAH levels were of different magnitude and direction. Our results tend to indicate an inverse relation exists between NNK and PAH deliveries when considering different tobacco blends. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3366–71)
Nicotine Metabolism in Three Ethnic/Racial Groups with Different Risks of Lung Cancer
Authors: Derby Kiersten S. , Cuthrell Kristine , Caberto Christian , Carmella Steven G. , Franke Adrian A. , Hecht Stephen S. , Murphy Sharon E. , Le Marchand Loïc
Published: December 2008

Previously, we documented that smoking-associated lung cancer risk is greater in Hawaiians and lower in Japanese compared with Whites. Nicotine metabolism by cytochrome P450 2A6 (CYP2A6) varies across ethnicity/race and is hypothesized to affect smoking behavior. We investigated whether higher CYP2A6 activity results in the smoker extracting more nicotine (adjusting for cigarettes per day) and being exposed to higher levels of tobacco-specific nitrosamine [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)] and pyrene, a representative polycyclic aromatic hydrocarbon. We conducted a cross-sectional study of 585 smokers among the three main ethnic/racial groups in Hawaii and examined whether differences in CYP2A6 activity correlate with the ethnic/racial differences in lung cancer risk. We assessed CYP2A6 activity by nicotine metabolite ratio (total trans-3-hydroxycotinine/total cotinine) and caffeine metabolite ratio (1,7-dimethyl uric acid/1,7-dimethylxanthine) in 12 h urine. We also measured urinary nicotine equivalents (sum of nicotine, cotinine, and trans-3-hydroxycotinine and their respective glucuronides), a marker of nicotine dose, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronide, markers of NNK exposure, and 1-hydroxypyrene, a marker of pyrene exposure. The nicotine metabolite ratio was higher in Whites than in Japanese and intermediate in Hawaiians (P values < 0.05). Cigarettes per day-adjusted nicotine equivalents were lower in Japanese compared with Hawaiians or Whites (P = 0.005 and P < 0.0001, respectively) and greater in men than women (P < 0.0001). Nicotine equivalents and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol increased with CYP2A6 activity, indicating that smokers with greater nicotine metabolism smoke more extensively and have a higher internal NNK dose. The particularly low nicotine metabolism of Japanese smokers may contribute to their previously described decreased lung cancer risk. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3526–35)
Correlates of Human Papillomavirus Viral Load with Infection Site in Asymptomatic Men
Authors: Flores Roberto , Beibei Lu , Nielson Carrie , Abrahamsen Martha , Wolf Kyle , Lee Ji-Hyun , Harris Robin B. , Giuliano Anna R.
Published: December 2008

Numerous studies have evaluated human papillomavirus (HPV) DNA load in women, especially HPV-16 viral load, and its role in cervical carcinogenicity. Few studies have examined HPV viral load in men, none among asymptomatic men. The aim of the current study is to quantify HPV-16 viral load in male anogenital specimens and to explore its correlates with anatomic sites. Two-hundred and ninety-four specimens from 42 men who tested positive for HPV-16 at one or more anatomic sites were evaluated. HPV DNA was detected with PGMY 09/11 primer and genotyped with reverse line blot assay followed by HPV-16 viral quantification using type-specific real-time PCR assay (TaqMan). The quantitative PCR assay showed a higher sensitivity in HPV-16 viral DNA detection compared with the reverse line blot assay. Viral load varied significantly by anatomic site (P = 0.019). Penile shaft specimens had significantly higher viral load than any other anatomic site evaluated except for the anal canal. HPV-16 viral load was positively correlated between proximal anatomic sites: perianal and anal canal (P = 0.003), perianal and scrotum (P = 0.011), scrotum and glans/corona (P = 0.045), and scrotum and penile shaft (P = 0.037). In conclusion, the penile shaft seemed to be the preferred site for HPV-16 viral replication. Viral load correlation between proximal sites suggested a possible autoinoculation in male HPV transmission. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3573–6)
Methylation of the TWIST1 Promoter, TWIST1 mRNA Levels, and Immunohistochemical Expression of TWIST1 in Breast Cancer
Authors: Gort Eelke H. , Suijkerbuijk Karijn P.M. , Roothaan Suzan M. , Raman Venu , Vooijs Marc , van der Wall Elsken , van Diest Paul J.
Published: December 2008

TWIST1, an antiapoptotic and prometastatic transcription factor, is overexpressed in many epithelial cancers including breast. Only little is known regarding the regulation of TWIST1 in these cancers. Recently, an increase in the TWIST1 promoter methylation has been shown in breast cancers. To correlate the percentage of TWIST1 promoter methylation to the protein levels, we analyzed simultaneously the methylation status as well as the mRNA and the percentage of cells expressing TWIST1 in normal breast tissue and 76 invasive breast cancers. We found that TWIST1 promoter methylation is significantly more prevalent in malignant compared with healthy breast tissue. Furthermore, the percentage of cells expressing TWIST1 was greater in breast malignancy compared with matched healthy tissue from the same patients. There was no correlation, however, between TWIST1 promoter methylation and TWIST1 protein or RNA expression. This indicates that although TWIST1 CpG methylation is useful as a biomarker in breast cancer diagnosis, there is no direct correlation with TWIST1 expression. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3325–30)
Physical Activity and Postmenopausal Breast Cancer: Effect Modification by Breast Cancer Subtypes and Effective Periods in Life
Authors: Schmidt Martina E. , Steindorf Karen , Mutschelknauss Elke , Slanger Tracy , Kropp Silke , Obi Nadia , Flesch-Janys Dieter , Chang-Claude Jenny
Published: December 2008

Physical activity (PA) has been inversely associated with postmenopausal breast cancer risk. However, it is unclear how and in which life periods PA may be effective to reduce breast cancer risk. Moreover, the evidence is still not judged as ‘convincing’ as there is some heterogeneity among study results. Most studies regarded breast cancer as a single disease, at best separated by menopausal status. Yet, breast cancers are heterogeneous and likely have different etiologies. Therefore, we analyzed the association of PA with different breast cancer subtypes in 3,414 postmenopausal cases and 6,569 controls from a case-control study on breast cancer conducted 2002-2005 in Germany (MARIE study). PA in the age periods 30-49 and 50+ years was assessed, including leisure-time PA (sports, cycling, walking) and non-recreational PA (occupational and household activities). There was a significant protective effect of leisure-time PA for ER+/PR+ carcinomas (adjusted odds ratio = 0.71, 95% confidence interval: 0.60, 0.85; trend P = 0.0001), but no effect for ER-/PR- carcinomas. Moreover, looking at physical activity pattern over time, the effect of PA after menopause on reducing breast cancer risk was more pronounced than the effect of PA before menopause. Overall, effects of PA were independent from adult weight gain, body mass index, and energy intake. These findings suggest that leisure-time PA after menopause may reduce postmenopausal breast cancer risk at least in part via hormonal pathways and not solely by changing body composition. Inactive postmenopausal women should be encouraged to become physically active even later in life. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3402–10)
Genetic Variation inCYP19A1and Risk of Breast Cancer and Fibrocystic Breast Conditions among Women in Shanghai, China
Authors: Chen Chu , Sakoda Lori C. , Doherty Jennifer A. , Loomis Melissa M. , Fish Sherianne , Ray Roberta M. , Lin Ming Gang , Fan Wenhong , Zhao Lue Ping , Gao Dao Li , Stalsberg Helge , Feng Ziding , Thomas David B.
Published: December 2008

CYP19A1 encodes for aromatase, which irreversibly converts androgens to estrogens; variation in this gene may affect individual susceptibility to breast cancer and other sex hormone-dependent outcomes. In a case-control study nested within a breast self-examination trial conducted in China, we examined whether CYP19A1 polymorphisms (rs1870049, rs1004982, rs28566535, rs936306, rs11636639, rs767199, rs4775936, rs11575899, rs10046, and rs4646) were associated with risk of breast cancer and fibrocystic breast conditions. Cases were diagnosed with breast cancer (n = 614) or fibrocystic breast conditions (n = 465) during 1989 to 2000. Controls were free of breast disease during the same period (n = 879). Presence of proliferative changes within the extratumoral tissue of women with breast cancer and the lesions of women with fibrocystic conditions only was assessed. None of the polymorphisms were associated with overall risk of breast cancer or fibrocystic breast conditions. Differences in breast cancer risk, however, were observed by proliferation status. The risk of breast cancer with (but not without) proliferative fibrocystic conditions was increased among women homozygous for the minor allele of rs1004982 (C), rs28566535 (C), rs936306 (T), and rs4775936 (C) relative to those homozygous for the major allele [age-adjusted odds ratios (95% confidence intervals), 2.19 (1.24-3.85), 2.20 (1.27-3.82), 1.94 (1.13-3.30), and 1.95 (1.07-3.58), respectively]. Also, haplotypes inferred using all polymorphisms were not associated with overall risk of either outcome, although some block-specific haplotypes were associated with an increased risk of breast cancer with concurrent proliferative fibrocystic conditions. Our findings suggest that CYP19A1 variation may enhance breast cancer development in some women, but further confirmation is warranted. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3457–66)
Genetic and Epigenetic Alterations of Familial Pancreatic Cancers
Authors: Brune Kieran , Hong Seung-Mo , Li Ang , Yachida Shinichi , Abe Tadayoshi , Griffith Margaret , Yang Dawei , Omura Noriyuki , Eshleman James , Canto Marcia , Schulick Rich , Klein Alison P. , Hruban Ralph H. , Iacobuzio-Donohue Christine , Goggins Michael
Published: December 2008

Background: Little is known about the genetic and epigenetic changes that contribute to familial pancreatic cancers. The aim of this study was to compare the prevalence of common genetic and epigenetic alterations in sporadic and familial pancreatic ductal adenocarcinomas.

Methods: DNA was isolated from the microdissected cancers of 39 patients with familial and 36 patients with sporadic pancreatic adenocarcinoma. KRAS2 mutations were detected by BstN1 digestion and/or cycle sequencing. TP53 and SMAD4 status were determined by immunohistochemistry on tissue microarrays of 23 archival familial pancreatic adenocarcinomas and in selected cases by cycle sequencing to identify TP53 gene mutations. Methylation-specific PCR analysis of seven genes (FoxE1, NPTX2, CLDN5, P16, TFPI-2, SPARC, ppENK) was done on a subset of fresh-frozen familial pancreatic adenocarcinomas.

Results: KRAS2 mutations were identified in 31 of 39 (80%) of the familial versus 28 of 36 (78%) of the sporadic pancreatic cancers. Positive immunolabeling for p53 was observed in 57% of the familial pancreatic cancers and loss of SMAD4 labeling was observed in 61% of the familial pancreatic cancers, rates similar to those observed in sporadic pancreatic cancers. The mean prevalence of aberrant methylation in the familial pancreatic cancers was 68.4%, which was not significantly different from that observed in sporadic pancreatic cancers.

Conclusion: The prevalence of mutant KRAS2, inactivation of TP53 and SMAD4, and aberrant DNA methylation of a seven-gene panel is similar in familial pancreatic adenocarcinomas as in sporadic pancreatic adenocarcinomas. These findings support the use of markers of sporadic pancreatic adenocarcinomas to detect familial pancreatic adenocarcinomas. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3536–42)
Reproductive Factors, Age at Maximum Height, and Risk of Three Histologic Types of Breast Cancer
Authors: Beaber Elisabeth F. , Holt Victoria L. , Malone Kathleen E. , Porter Peggy L. , Daling Janet R. , Li Christopher I.
Published: December 2008

Numerous studies have evaluated the association between factors related to maturation and reproduction and breast cancer risk, but few have assessed how these factors are related to different histologic types of breast cancer among postmenopausal women. We used polytomous logistic regression to assess the effect of age at maximum height and reproductive factors on risk of invasive breast cancer by histologic type in three case groups (524 ductal, 324 lobular, and 196 ductal-lobular) and 469 controls enrolled in a population-based case-control study of women ages 55 to 74 years residing in the Seattle-Puget Sound region of Washington State (2000-2004). Histologic type was determined by a centralized tissue review for 83% of cases. Age at menarche and age at maximum height were inversely associated with risk of ductal-lobular carcinoma (Ptrend = 0.04 for both exposures) but not ductal or lobular carcinoma. Relative to nulliparous women, parous women had a 50% reduced risk of all histologic types of breast cancer. We observed similar increases in risk across histologic types associated with having a first live birth at ages ≥30 years compared with ages ≤19 years. Compared with parous women who never breast-fed, those who breast-fed had a reduced risk of ductal carcinoma (odds ratio, 0.7; 95% confidence interval, 0.5-0.9) but not lobular or ductal-lobular carcinoma. Further exploration of breast cancer risk by histology is merited to understand differences in the etiology of ductal, lobular, and ductal-lobular carcinoma. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3427–34)
Repeated Measurements of Urinary Methylated/Oxidative DNA Lesions, Acute Toxicity, and Mutagenicity in Coke Oven Workers
Authors: Chao Mu-Rong , Wang Chien-Jen , Wu Ming-Tsang , Pan Chih-Hong , Kuo Chung-Yih , Yang Hao-Jan , Chang Louis W. , Hu Chiung-Wen
Published: December 2008

We conducted a repeated-measures cohort study of coke oven workers to evaluate the relationships between the traditional exposure biomarker, urinary 1-hydroxypyrene (1-OHP), and a series of biomarkers, including urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), N7-methylguanine (N7-MeG), acute toxicity, and mutagenicity. A total of eight spot urine samples were collected from each high-exposed (at topside oven area) and low-exposed workers (at side oven area) during the whole working cycle, which consisted of 6 consecutive days of working followed by 2 days off. Our results showed that the high-exposed workers had significantly higher urinary levels of 1-OHP, 8-oxodG, and N7-MeG compared with the low-exposed workers. Acute toxicity and mutagenicity of urine were also found to be markedly increased in the high-exposed workers, as determined by Microtox assay and Ames test, respectively. Multivariate regressions analysis revealed that the urinary 8-oxodG, N7-MeG, or acute toxicity was significantly correlated with 1-OHP concentrations. Overall, the present study showed that exposure to coke oven emissions increased oxidatively damaged DNA products and mutagenicity of urine, and for the very first time, such exposure was also found to increase DNA methylation and urinary acute toxicity. The potential source of methylating agents in coke oven emissions warrants further investigation. Additionally, with repeated measurements, the pattern of time course for urinary 1-OHP was found to be different from those of 8-oxodG and N7-MeG, as well as acute toxicity and mutagenicity. This finding implies that the single measurement that was often conducted in occupational healthy investigations should be used with certain precautions, because single measurement may fail to provide the proper information of interest. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3381–9)
Identification of Common Variants in the SHBG Gene Affecting Sex Hormone-Binding Globulin Levels and Breast Cancer Risk in Postmenopausal Women
Authors: Thompson Deborah J. , Healey Catherine S. , Baynes Caroline , Kalmyrzaev Bolot , Ahmed Shahana , Dowsett Mitch , Folkerd Elizabeth , Luben Robert N. , Cox David , Ballinger Dennis , Pharoah Paul D.P. , Ponder Bruce A.J. , Dunning Alison M. , Easton Douglas F. ,   The Studies in Epidemiology and Risks of Cancer Heredity Team
Published: December 2008

Background: Circulating levels of sex hormone-binding globulin (SHBG) are inversely associated with breast cancer risk in postmenopausal women. Three polymorphisms within the SHBG gene have been reported to affect SHBG levels, but there has been no systematic attempt to identify other such variants.

Methods: We looked for associations between SHBG levels in 1,134 healthy, postmenopausal women and 11 tagging single nucleotide polymorphisms (SNP) in or around the SHBG gene. Associations between SHBG SNPs and breast cancer were tested in up to 6,622 postmenopausal breast cancer cases and 6,784 controls.

Results: Ten SNPs within or close to the SHBG gene were significantly associated with SHBG levels as was the (TAAAA)n polymorphism. The best-fitting combination of rs6259, rs858521, and rs727428 and body mass index, waist, hip, age, and smoking status accounted for 24% of the variance in SHBG levels (natural logarithm transformed). Haplotype analysis suggested that rs858518, rs727428, or a variant in linkage disequilibrium with them acts to decrease SHBG levels but that this effect is neutralized by rs6259 (D356N). rs1799941 increases SHBG levels, but the previously reported association with (TAAAA)n repeat length appears to be a consequence of linkage disequilibrium with these SNPs. One further SHBG SNP was significantly associated with breast cancer (rs6257, per-allele odds ratio, 0.88; 95% confidence interval, 0.82-0.95; P = 0.002).

Conclusion: At least 3 SNPs showed associations with SHBG levels that were highly significant but relatively small in magnitude. rs6257 is a potential breast cancer susceptibility variant, but relationships between the genetic determinants of SHBG levels and breast cancer are complex. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3490–8)
Lack of Association between the Functional Polymorphisms in the Estrogen-Metabolizing Genes and Risk for Hepatocellular Carcinoma
Authors: Yuan Xiaoyan , Zhou Gangqiao , Zhai Yun , Xie Weimin , Cui Ying , Cao Jia , Zhi Lianteng , Zhang Hongxing , Yang Hao , Zhang Xiaoai , Qiu Wei , Peng Yong , Zhang Xiumei , Yu Ling , Xia Xia , He Fuchu
Published: December 2008

Estrogens have been proposed to act as tumor promoters and induce hepatocarcinogenesis. Recently, we observed a significant association between the risk for hepatocellular carcinoma and the polymorphisms of the estrogen receptor (ESR) α (ESR1) gene, supporting the hypothesis of involvement for the estrogen-ESR axis in the estrogen-induced hepatocarcinogenesis. In this study, based on another hypothesis in which estrogen metabolites can directly cause DNA damage and affect tumor initiation, we examined whether the polymorphisms of the estrogen-metabolizing enzymes (EME), which are involved in biogenesis (CYP17, CYP19), bioavailability (CYP1A1, CYP1B1), and degradation (catechol-O-methyltransferase) of the estrogens, have any bearing on the risk for hepatocellular carcinoma. Seven functional polymorphisms in five EMEs (CYP17 MspAI site, CYP19 Trp39Arg, Ile462Val and MspI site in CYP1A1, CYP1B1 Val432Leu, and Ala72Ser and Val158Met in catechol-O-methyltransferase) were genotyped in 434 patients with hepatocellular carcinoma and 480 controls by PCR-RFLP analysis. The associations between the polymorphisms and hepatocellular carcinoma risk were evaluated while controlling for confounding factors. No significant association with the risk for hepatocellular carcinoma was observed with the seven polymorphisms in hepatitis B virus carriers and non–hepatitis B virus carriers after correction for multiple comparisons. After stratification by common confounding factors of hepatocellular carcinoma, the EME polymorphism remained no significant association with the hepatocellular carcinoma risk. Furthermore, no signs of gene-gene interactions were observed for each combination of the seven polymorphisms. Our findings suggest that the polymorphisms of EMEs may not contribute significantly to the risk for hepatocellular carcinoma. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3621–7)
Tamoxifen Prevents Premalignant Changes of Breast, but not Ovarian, Cancer in Rats at High Risk for Both Diseases
Authors: Ting Alison Y. , Kimler Bruce F. , Fabian Carol J. , Petroff Brian K.
Published: December 2008

Women at increased risk for breast cancer are at increased risk for ovarian cancer as well, reflecting common risk factors and intertwined etiology of the two diseases. We previously developed a rat model of elevated breast and ovarian cancer risk, allowing evaluation of dual-target cancer prevention strategies. Tamoxifen, a Food and Drug Administration–approved breast cancer chemoprevention drug, has been shown to promote ovarian cysts in premenopausal women; however, the effect of tamoxifen on ovarian cancer risk is still controversial. In the current experiment, Fischer 344 rats (n = 8 per treatment group) received tamoxifen (TAM) or vehicle (control) in factorial combination with combined breast and ovarian carcinogen (17β-estradiol and 7,12 dimethylbenza[a]anthracene, respectively). Mammary and ovarian morphologies were normal in the control and TAM groups. Carcinogen (CARC) treatment induced mammary dysplasia with elevated cell proliferation and reduced estrogen receptor-α expression and promoted preneoplastic changes in the ovary. In the CARC + TAM group, tamoxifen reduced preneoplastic changes and proliferation rate in the mammary gland, but not in the ovary, compared with rats treated with carcinogen alone. Putative stem cell markers (Oct-4 and aldehyde dehydrogenase 1) were also elevated in the mammary tissue by carcinogen and this expansion of the stem cell population was not reversed by tamoxifen. Our study suggests that tamoxifen prevents early progression to mammary cancer but has no effect on ovarian cancer progression in this rat model.