bluuebunny/crossref_metadata_2025 huggingface dataset:
SEQUESTERED UPLIFTING AND THE PATTERN OF SOFT SUPERSYMMETRY BREAKING TERMS
Authors: JEONG KWANG SIK
Published: August 2008

We examine the pattern of soft supersymmetry breaking terms in moduli stabilization, where an uplifting potential is provided by spontaneously broken supersymmetry in a generic sequestered sector. From stationary conditions, we derive the relation between moduli F-term vacuum expectation values which does not depend on the details of sequestered uplifting. This moduli F-term relation that reflects the sequestering structure is crucial for identifying the dominant source of soft terms of visible fields.
UNIVERSAL PRANDTL NUMBER IN TWO-DIMENSIONAL KRAICHNAN-BATCHELOR TURBULENCE
Authors: NANDY MALAY K.
Published: August 2008

We evaluate the universal turbulent Prandtl numbers in the energy and enstrophy régimes of the Kraichnan-Batchelor spectra of two-dimensional turbulence using a self-consistent mode-coupling formulation coming from a renormalized perturbation expansion coupled with dynamic scaling ideas. The turbulent Prandtl number is found to be exactly unity in the (logarithmic) enstrophy régime, where the theory is infrared marginal. In the energy régime, the theory being finite, we extract singularities coming from both ultraviolet and infrared ends by means of Laurent expansions about these poles. This yields the turbulent Prandtl number σ ≈ 0.9 in the energy régime.
A TWO-DIMENSIONAL STATIC DEFORMATION OF AN IRREGULAR INITIALLY STRESSED MEDIUM
Authors: SELIM M. M.
Published: August 2008

The paper discusses the problem of a two-dimensional static deformation as the result of normal line-load acting inside an irregular initially stressed isotropic half-space. The eigenvalue approach method has been used. The irregularity is expressed by a rectangle shape. Further, the results for the displacements and stresses have been derived in the closed form. The effect of initial stress and irregularity are shown graphically. It was found that the initial stresses as well as irregularity have a notable effect on this deformation.
STRUCTURE AND MAGNETIC PROPERTIES OF NANOCRYSTALLINE MnZn FERRITES BY A PHASE TRANSFORMATION METHOD
Authors: LIU YONGSHENG , ZHONG YUNBO , ZHANG JINCANG , REN ZHONGMING , CAO SHIXUN , YANG ZHENGLONG , FU XIAOMING
Published: August 2008

Nanocrystalline Mn 0.6 Zn 0.4 Fe 2 O 4 particles are synthesized by a phase transformation method. The crystal structure of these particles is that of spinel MnZn ferrite. The average particle size is about 50 nm and the grain size is about 11 nm. Magnetic measurements show that the saturation magnetization at 120 K is ~80% larger than that at 300 K, and imply that the majority of the nanoparticles are superparamagnetic from 65 to 300 K.
THE PHOTON-ASSISTED TRANSPORT AND MAXWELL POTENTIAL
Authors: ALY ARAFA H. , RYU SANG-WAN
Published: August 2008

The quantum transport in the Superconductor–Semiconductor (S–Sm) mesoscopic interface is investigated in the presence of an external electromagnetic field by suggesting a Maxwell potential at the interface. We analyze the current spectrum as a function of the frequency and the distance between the superconductor electrodes. The current displays oscillations with an amplitude that shows a strong dependence on the photon frequency, the field intensity dependence of the current can give direct information of the lead–semiconductor interface energy spectra.
MAGNETIC PROPERTIES OF ALUMINUM-SUBSTITUTED STRONTIUM HEXAFERRITE PREPARED BY CITRATE–NITRITE SOL–GEL TECHNIQUE
Authors: CHEN Q. , WANG X. Q. , GE H. L.
Published: August 2008

M-type SrFe 12-x Al x O 19(0 < x < 2.5) nanoparticles have been synthesized by citrate–nitrite sol–gel technique. The experimental results have shown that Al 3+ ions substitute Fe 3+ ions in the sublattice, and the samples remain in the hexagonal magnetoplumbite phase. The saturation magnetization Ms and remanence Mr of M-type SrFe 12-x Al x O 19(0 < x < 2.5) nanoparticles linearly decrease when x increases. x = 0, Ms = 63.5 emu/g and Ms = 23.8 emu/g at x = 2.5 when the magnets are sintered at 1100°C. Meanwhile, the coercivity Hc of the samples fluctuate as doped with Al , and reach maximum Hc = 10.59 kOe when x = 1.5. The intergranular exchange–coupling interactions between the nanoparticles, which are proved by the measurement of Henkel plots (δM), and the interactions become more intensive as the Al substitution x increases.
NONADDITIVE OPEN SYSTEMS AND THE PROBLEM OF CONSTRAINTS
Authors: BAĞCI G. B.
Published: August 2008

Klimontovich's S theorem serves as a measure of order relative to a reference state for open systems, thereby providing the correct ordering of entropy values with respect to their distance from the equilibrium state. It can also be considered as a generalization of Gibbs' theorem if one of the distributions is associated with the equilibrium state. Here, a nonadditive generalization of S theorem is obtained by the employment of Tsallis entropy. This generalized form is then illustrated by applying it to the Van der Pol oscillator. Interestingly, this generalization procedure favors the use of ordinary probability distribution instead of escort distribution.
STUDY ON THE MICROSCOPIC FIGURES OF POWER TRANSFORMER INSULATION PAPER UNDER ELECTRICAL AND THERMAL STRESSES
Authors: LIAO RUI-JIN , TANG CHAO , YANG LI-JUN
Published: August 2008

In this paper, Atomic Force Microscope (AFM) was used to observe the microscopic figure of aged insulation paper in order to analyze the microscopic ageing mechanism of power transformer insulation paper under electrical and thermal stresses. The results indicate that there are obvious concaves and convexes on the surface of aged insulation paper, and the paper samples are punctured because of chain scission and the flow of discharge current, which destroyed the compact cellulose chains structures and the diameter of punctures is about 0.5 nm. In addition, this paper analyzed the influence to the physical chemistry characteristics of insulation paper caused by partial discharge and paper ageing.
Nuclear Activity in Nearby Galaxies
Authors: Ho Luis C.
Published: August 2008

A significant fraction of nearby galaxies show evidence of weak nuclear activity unrelated to normal stellar processes. Recent high-resolution, multiwavelength observations indicate that the bulk of this activity derives from black hole accretion with a wide range of accretion rates. The low accretion rates that typify most low-luminosity active galactic nuclei induce significant modifications to their central engine. The broad-line region and obscuring torus disappear in some of the faintest sources, and the optically thick accretion disk transforms into a three-component structure consisting of an inner radiatively inefficient accretion flow, a truncated outer thin disk, and a jet or outflow. The local census of nuclear activity supports the notion that most, perhaps all, bulges host a central supermassive black hole, although the existence of active nuclei in at least some late-type galaxies suggests that a classical bulge is not a prerequisite to seed a nuclear black hole.
Spectropolarimetry of Supernovae
Authors: Wang Lifan , Wheeler J. Craig
Published: August 2008

Overwhelming evidence has accumulated in recent years that supernova explosions are intrinsically three-dimensional phenomena with significant departures from spherical symmetry. We review the evidence derived from spectropolarimetry that has established several key results: Virtually all supernovae are significantly aspherical near maximum light; core-collapse supernovae behave differently than thermonuclear (Type Ia) supernovae; the asphericity of core-collapse supernovae is more pronounced in the inner layers, showing that the explosion process is strongly aspherical; core-collapse supernovae tend to establish a preferred direction of asymmetry; and the asphericity is stronger in the outer layers of thermonuclear supernovae, providing constraints on the burning process. We emphasize the utility of the Q/U plane as a diagnostic tool and revisit SN 1987A and SN 1993J in a contemporary context. An axially symmetric geometry can explain many basic features of core-collapse supernovae, but significant departures from axial symmetry are needed to explain most events. We introduce a spectropolarimetry type to classify the range of behavior observed in polarized supernovae. Understanding asymmetries in supernovae is important for phenomena as diverse as the origins of gamma-ray bursts and the cosmological applications of Type Ia supernovae in studies of the dynamics of the universe.
The Spitzer View of the Extragalactic Universe
Authors: Soifer Baruch T. , Helou George , Werner Michael
Published: August 2008

The Spitzer Space Telescope was launched in August 2003. Scientists from around the world have applied its orders-of-magnitude gain in imaging and spectroscopic capability to a wide array of topics in extragalactic research. Spitzer studies have found massive galaxies at redshifts greater than 6, resolved the cosmic background at 200 μm > λ > 20 μm into the dusty infrared-luminous galaxies that comprise it, directly detected dust-enshrouded star formation, and measured the star formation history of the universe to z > 3. In this review we examine a small fraction of the extragalactic studies from Spitzer that have been conducted in its first three years of operations.
The Growth Mechanisms of Macroscopic Bodies in Protoplanetary Disks
Authors: Blum Jürgen , Wurm Gerhard
Published: August 2008

The formation of planetesimals, the kilometer-sized planetary precursors, is still a puzzling process. Considerable progress has been made over the past years in the physical description of the first stages of planetesimal formation, owing to extensive laboratory work. This review examines the experimental achievements and puts them into the context of the dust processes in protoplanetary disks. It has become clear that planetesimal formation starts with the growth of fractal dust aggregates, followed by compaction processes. As the dust-aggregate sizes increase, the mean collision velocity also increases, leading to the stalling of the growth and possibly to fragmentation, once the dust aggregates have reached decimeter sizes. A multitude of hypotheses for the further growth have been proposed, such as very sticky materials, secondary collision processes, enhanced growth at the snow line, or cumulative dust effects with gravitational instability. We will also critically review these ideas.
Neutron-Capture Elements in the Early Galaxy
Authors: Sneden Christopher , Cowan John J. , Gallino Roberto
Published: August 2008

The content of neutron-capture (trans-iron-peak) elements in the low-metallicity Galactic halo varies widely from star to star. The differences are both in bulk amount of the neutron-capture elements with respect to lighter ones and in element-to-element ratios among themselves. Several well-defined abundance distributions have emerged that reveal characteristic rapid and slow neutron-capture nucleosynthesis patterns. In this review we summarize these observed metal-poor star's abundances, contrasting them with the Solar-system values, comparing them to theoretical predictions, using them to assess the types of stars responsible for their specific anomalies, and speculating on the timing and nature of early Galactic nucleosynthesis.
Dark Energy and the Accelerating Universe
Authors: Frieman Joshua A. , Turner Michael S. , Huterer Dragan
Published: August 2008

Ten years ago, the discovery that the expansion of the universe is accelerating put in place the last major building block of the present cosmological model, in which the universe is composed of 4% baryons, 20% dark matter, and 76% dark energy. At the same time, it posed one of the most profound mysteries in all of science, with deep connections to both astrophysics and particle physics. Cosmic acceleration could arise from the repulsive gravity of dark energy—for example, the quantum energy of the vacuum—or it may signal that general relativity (GR) breaks down on cosmological scales and must be replaced. We review the present observational evidence for cosmic acceleration and what it has revealed about dark energy, discuss the various theoretical ideas that have been proposed to explain acceleration, and describe the key observational probes that will shed light on this enigma in the coming years.
The Double Pulsar
Authors: Kramer M. , Stairs I.H.
Published: August 2008

A landmark discovery was made in 2003 when the first binary system containing two active radio pulsars was observed. Not only is this system, PSR J0737-3039A/B, the most relativistic binary system ever found, but it also exhibits eclipses and magnetospheric interactions. The observational and theoretical insights provided by this first double pulsar go far beyond applications in pulsar astrophysics alone. Timing observations of the two pulsars provide the best test of general relativity (GR) in strong gravitational fields. Studies of the system's evolution suggest the possibility of an unusual neutron star formation process. The discovery of this system has a significant impact on the expected coalescence rate of galactic double neutron stars and the detection of merging systems in Earth-bound gravitational-wave detectors. Moreover, observations and modeling of the eclipses provide evidence for relativistic spin precession and dipolar magnetic fields in pulsar magnetospheres. This paper reviews the double pulsar's properties and what they mean for fundamental physics and astrophysics.
CaSR stimulates secretion of Wnt5a from colonic myofibroblasts to stimulate CDX2 and sucrase-isomaltase using Ror2 on intestinal epithelia
Authors: Pacheco Ivan I. , MacLeod R. John
Published: August 2008

To understand whether extracellular calcium-sensing receptor (CaSR) expression on colonic myofibroblast cells (18Co) contributed to epithelial homeostasis, we activated the CaSR with 5 mM Ca2+, screened by RT-PCR Wnt family members, and measured their secretion. Transcripts for Wnt 1, 2, 2b, 3a, 4, and 7a were either absent or unchanged whereas Wnt3 decreased and Wnt5a increased. We assessed Wnt5a secretion by Western blot. High Ca2+ (5 mM) substantially increased Wnt5a secretion; small interfering RNA (siRNA) against the CaSR reduced this to constitutive amounts. Expression of Wnt5a plasmid but not Wnt1 or Wnt3a increased caudal homeodomain factor CDX2 transcripts and protein in HT-29 adenocarcinoma cells. Wnt5a increased activity of a sucrase-isomaltase (SI) promoter in Caco-2BBE cells. Wnt5a protein stimulation of CDX2 transcripts and protein and SI reporter were increased by overexpression of wild-type Ror2, a Wnt5a receptor, and reduced with siRNA against Ror2. CaSR activation of HT-29 cells increased Ror2 protein expression. Ror2 protein was expressed in mouse jejunum from crypt base to villus tip and in the colon on surface epithelia. Our results show that activation of a G protein-coupled receptor, the CaSR, stimulates secretion of Wnt5a from myofibroblasts. Stimulation of epithelia by the CaSR increased the expression of a receptor for Wnt5a, the tyrosine kinase Ror2, suggesting existence of a unique paracrine relationship for CDX2 homoeostasis in the intestine and revealing new contributions of CaSR-activated myofibroblasts to intestinal stem cell niche microenvironments.
High dietary inorganic phosphate enhances cap-dependent protein translation, cell-cycle progression, and angiogenesis in the livers of young mice
Authors: Xu Cheng-Xiong , Jin Hua , Lim Hwang-Tae , Kim Ji-Eun , Shin Ji-Young , Lee Eun-Sun , Chung Youn-Sun , Lee Yeon-Sook , Beck George , Lee Kee Ho , Cho Myung-Haing
Published: August 2008

Inorganic phosphate (Pi) plays a key role in diverse physiological functions. Recent studies have indicated that Piaffects Akt signaling through the sodium-dependent phosphate cotransporter. Akt signaling, in turn, plays an important role in liver development; however, the effects of high dietary Pion the liver have not been investigated. Here, we examined the effects of high dietary phosphate on the liver in developing mice. We found that high dietary Piincreased liver mass through enhancing Akt-related cap-dependent protein translation, cell cycle progression, and angiogenesis. Thus careful regulation of Piconsumption may be important in maintaining normal development of the liver.
Sphingosine-1-phosphate enhances IL-1β-induced COX-2 expression in mouse intestinal subepithelial myofibroblasts
Authors: Ohama Takashi , Okada Muneyoshi , Murata Takahisa , Brautigan David L. , Hori Masatoshi , Ozaki Hiroshi
Published: August 2008

Intestinal subepithelial myofibroblasts (SEMFs) is a specific population of cells involved in intestinal inflammation and carcinogenesis via an elaborate network of cytokines, chemokines and other inflammatory factors, including PGE2. Sphingosine-1-phosphate (S1P) has been implicated as an important mediator of inflammation and cancer and in certain cell types increases cyclooxygenase-2 (COX-2) expression. In the present study, we aimed to assess involvement of S1P in COX-2 expression by SEMFs. Primary SEMFs were obtained from C57BL/6J mouse and their identity was verified by fluorescent staining of specific marker proteins. Expression of S1P receptors 1, 2, 3 and sphingosine kinases 1 and 2 in SEMFs were determined by RT-PCR analysis. COX-2 expression and PGE2production were assayed by Western blotting and ELISA, respectively. COX-2 mRNA stability was assayed by Northern blotting. S1P produced dose-dependent increase in COX-2 expression, resulting in increased PGE2release from SEMFs. Using specific inhibitors, we show that actions of p38, ERK, IKK, and PKC were involved in S1P-induced COX-2 expression. On the other hand, p38 and PKC had lesser roles in IL-1β-induced COX-2 expression. Inhibition of sphingosine kinase to block S1P production did not affect IL-1β-induced COX-2 expression, but S1P amplified IL-1β-induced p38 activation and COX-2 expression. PKC inhibition blocked S1P amplified COX-2 expression. S1P addition increased COX-2 mRNA stability. In SEMFs, S1P amplifies IL-1β-induced COX-2 expression through increased mRNA stability. These observations point to involvement of S1P in activation of SEMFs that may contribute to intestinal inflammation and carcinogenesis.
Mitigation of chlorine-induced lung injury by low-molecular-weight antioxidants
Authors: Leustik Martin , Doran Stephen , Bracher Andreas , Williams Shawn , Squadrito Giuseppe L. , Schoeb Trenton R. , Postlethwait Edward , Matalon Sadis
Published: August 2008

Chlorine (Cl2) is a highly reactive oxidant gas used extensively in a number of industrial processes. Exposure to high concentrations of Cl2 results in acute lung injury that may either resolve spontaneously or progress to acute respiratory failure. Presently, the pathophysiological sequelae associated with Cl2-induced acute lung injury in conscious animals, as well as the cellular and biochemical mechanisms involved, have not been elucidated. We exposed conscious Sprague-Dawley rats to Cl2 gas (184 or 400 ppm) for 30 min in environmental chambers and then returned them to room air. At 1 h after exposure, rats showed evidence of arterial hypoxemia, respiratory acidosis, increased levels of albumin, IgG, and IgM in bronchoalveolar lavage fluid (BALF), increased BALF surfactant surface tension, and significant histological injury to airway and alveolar epithelia. These changes were more pronounced in the 400-ppm-exposed rats. Concomitant decreases of ascorbate (AA) and reduced glutathione (GSH) were also detected in both BALF and lung tissues. In contrast, heart tissue AA and GSH content remained unchanged. These abnormalities persisted 24 h after exposure in rats exposed to 400 ppm Cl2. Rats injected systemically with a mixture of AA, deferoxamine, and N-acetyl-l-cysteine before exposure to 184 ppm Cl2 had normal levels of AA, lower levels of BALF albumin and normal arterial Po2 and Pco2 values. These findings suggest that Cl2 inhalation damages both airway and alveolar epithelial tissues and that resulting effects were ameliorated by prophylactic administration of low-molecular-weight antioxidants.
No effect of metformin on the innate airway hyperresponsiveness and increased responses to ozone observed in obese mice
Authors: Shore Stephanie A. , Williams Erin S. , Zhu Ming
Published: August 2008

We have previously reported that obese db/db mice exhibit innate airway hyperresponsiveness. These mice also have enhanced inflammatory responses to ozone, a common air pollutant that exacerbates asthma. Since db/db mice are diabetic as well as obese, the purpose of the present study was to determine whether metformin, an antihyperglycemic agent, alters the pulmonary phenotype of db/db mice. Lean wild-type (C57BL/6J) and obese db/db mice were treated by gavage with water or metformin (300 μg/g) once a day for 2 wk. Twenty-four hours after the last treatment, in mice of both genotypes, we either measured airway responsiveness to methacholine by forced oscillation, or we exposed the mice to ozone (2 parts per million for 3 h) and examined the ensuing inflammatory response. Compared with water, treatment with metformin caused a significant decrease in fasting blood glucose in obese mice. Airway responsiveness was increased in db/db versus wild-type mice, but metformin did not affect responsiveness in either group. Four hours after exposure to ozone, there was a significant increase in bronchoalveolar lavage fluid neutrophils and chemokines in mice of both genotypes, but the magnitude of these changes was greater in db/db than wild-type mice. Metformin did not affect ozone-induced inflammation in mice of either genotype. The results indicate that hyperglycemia is unlikely to account for the pulmonary phenotype of obese mice.
Differential attenuation of AMPK activation during acute exercise following exercise training or AICAR treatment
Authors: McConell G. K. , Manimmanakorn A. , Lee-Young R. S. , Kemp B. E. , Linden K. C. , Wadley G. D.
Published: August 2008

Short-term exercise training in humans attenuates AMP-activated protein kinase (AMPK) activation during subsequent exercise conducted at the same absolute workload. Short-term 5-aminoimidazole-4-carboxyamide- ribonucleoside (AICAR) administration in rats mimics exercise training on skeletal muscle in terms of increasing insulin sensitivity, mitochondrial enzymes, and GLUT4 content, but it is not known whether these adaptations are accompanied by reduced AMPK activation during subsequent exercise. We compared the effect of 10 days of treadmill training (60 min/day) with 10 days of AICAR administration (0.5 mg/g body weight ip) on subsequent AMPK activation during 45 min of treadmill exercise in male Sprague-Dawley rats. Compared with nonexercised control rats, acute exercise significantly ( P < 0.05) increased AMPKα Thr172 phosphorylation (p-AMPKα; 1.6-fold) and ACCβ Ser218 phosphorylation (p-ACCβ; 4.9-fold) in the soleus and p-ACCβ 2.2-fold in the extensor digitorum longus. Ten days of exercise training abolished the increase in soleus p-AMPKα and attenuated the increase in p-ACCβ (nonsignificant 2-fold increase). Ten days of AICAR administration also attenuated the exercise-induced increases in AMPK signaling in the soleus although not as effectively as 10 days of exercise training (nonsignificant 1.3-fold increase in p-AMPKα; significant 3-fold increase in p-ACCβ). The increase in skeletal muscle 2-deoxyglucose uptake during exercise was greater after either 10 days of exercise training or AICAR administration. In conclusion, 10 days of AICAR administration substantially mimics the effect of 10 days training on attenuating skeletal muscle AMPK activation in response to subsequent exercise.
Phase-contrast MRI reveals mechanical behavior of superficial and deep aponeuroses in human medial gastrocnemius during isometric contraction
Authors: Kinugasa Ryuta , Shin Dongsuk , Yamauchi Junichiro , Mishra Chandan , Hodgson John A. , Edgerton V. Reggie , Sinha Shantanu
Published: August 2008

The behavior of the entire medial gastrocnemius (MG) superficial and deep aponeurosis structure was investigated with velocity-encoded phase-contrast, spin-tag, and three-dimensional morphometric magnetic resonance imaging. The displacements and strain of both these aponeuroses, muscle length, and the cross-sectional segment length of the deep aponeurosis were measured during isometric plantarflexion at 20% and 40% of maximal voluntary contraction (MVC). The length of the entire MG shortened during 20% and 40% MVC. All regions of interest in both aponeuroses moved proximally. Positive strain (lengthening) occurred in both ends of the deep aponeurosis and in the proximal region of the superficial aponeurosis. In contrast, negative strain (shortening) was observed in the middle region of the deep aponeurosis and in the distal region of the superficial aponeurosis. Consistent with this shortening of the deep aponeurosis length along the proximal-distal axis was expansion of the aponeuroses in the medial-lateral and anterior-posterior directions in the cross-sectional plane. It is concluded that at low to moderate force levels of isometric contraction, regional differences in strain occur along the proximal-distal axis of both aponeuroses, and some regions of both aponeuroses shorten.
Mechanisms of active laryngeal closure during noninvasive intermittent positive pressure ventilation in nonsedated lambs
Authors: Roy Bianca , Samson Nathalie , Moreau-Bussière François , Ouimet Alain , Dorion Dominique , Mayer Sandeep , Praud Jean-Paul
Published: August 2008

The present study stems from our recent demonstration (Moreau-Bussiere F, Samson N, St-Hilaire M, Reix P, Lafond JR, Nsegbe E, Praud JP. J Appl Physiol 102: 2149–2157, 2007) that a progressive increase in nasal intermittent positive pressure ventilation (nIPPV) leads to active glottal closure in nonsedated, newborn lambs. The aim of the study was to determine whether the mechanisms involved in this glottal narrowing during nIPPV originate from upper airway receptors and/or from bronchopulmonary receptors. Two groups of newborn lambs were chronically instrumented for polysomnographic recording: the first group of five lambs underwent a two-step bilateral thoracic vagotomy using video-assisted thoracoscopic surgery (bilateral vagotomy group), while the second group, composed of six lambs, underwent chronic laryngotracheal separation (isolated upper airway group). A few days later, polysomnographic recordings were performed to assess glottal muscle electromyography during step increases in nIPPV (volume control mode). Results show that active glottal narrowing does not develop when nIPPV is applied on the upper airways only, and that this narrowing is prevented by bilateral vagotomy when nIPPV is applied on intact airways. In conclusion, active glottal narrowing in response to increasing nIPPV originates from bronchopulmonary receptors.
Cyclooxygenase-2 Inhibitors in Colorectal Cancer Prevention: Counterpoint
Authors: Jankowski Janusz , Hunt Richard
Published: August 2008

Aspirin is the best chemoprevention agent for colorectal cancer risk reduction despite the fact that the evidence for a decrease in mortality is weak. The cyclooxygenase-2 selective agents (COXIBS) have an efficacy similar to that of aspirin for most gastrointestinal (GI) lesions but not esophagus. Specifically, there are beneficial short term effects of COXIBs on the risk of colorectal adenoma as shown in the Approve, PreSAP, and APC studies. However, there is still an increased risk of upper GI complications with COXIBs when compared with placebo, and this risk may increase further in some people when aspirin is also consumed. Whereas aspirin reduces the risk of cardiovascular events, COXIBs and most traditional nonsteroidal anti-inflammatory drugs (but not all) are both associated with an increased risk of thrombotic cardiovascular events compared with placebo.

In conclusion, COXIBs have a niche role for patients with familial adenomatous polyposis. The value of aspirin remains with respect for efficacy, mainly in the esophagus, and the side effect profile, especially in the elderly if given with acid suppression therapy. COXIBs should be used in younger populations, but if they are considered in the elderly because of increased GI risks, and the cardiovascular risk is also increased, then combination treatment with aspirin and a proton-pump inhibitor should also be considered instead, such as in the ASPECT trial. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1858–61)
ESR1 Promoter Hypermethylation Does Not Predict Atypia in RPFNA nor Persistent Atypia after 12 Months Tamoxifen Chemoprevention
Authors: Baker Joseph C. , Ostrander Julie H. , Lem Siya , Broadwater Gloria , Bean Gregory R. , D'Amato Nicholas C. , Goldenberg Vanessa K. , Rowell Craig , Ibarra-Drendall Catherine , Grant Tracey , Pilie Patrick G. , Vasilatos Shauna N. , Troch Michelle M. , Scott Victoria , Wilke Lee G. , Paisie Carolyn , Rabiner Sarah M. , Torres-Hernandez Alejandro , Zalles Carola M. , Seewaldt Victoria L.
Published: August 2008

Purpose: Currently, we lack biomarkers to predict whether high-risk women with mammary atypia will respond to tamoxifen chemoprevention.

Experimental Design: Thirty-four women with cytologic mammary atypia from the Duke University High-Risk clinic were offered tamoxifen chemoprevention. We tested whether ESR1 promoter hypermethylation and/or estrogen receptor (ER) protein expression by immunohistochemistry predicted persistent atypia in 18 women who were treated with tamoxifen for 12 months and in 16 untreated controls.

Results: We observed a statistically significant decrease in the Masood score of women on tamoxifen chemoprevention for 12 months compared with control women. This was a significant interaction effect of time (0, 6, and 12 months) and treatment group (tamoxifen versus control) P = 0.0007. However, neither ESR1 promoter hypermethylation nor low ER expression predicted persistent atypia in Random Periareolar Fine Needle Aspiration after 12 months tamoxifen prevention.

Conclusions: Results from this single institution pilot study provide evidence that, unlike for invasive breast cancer, ESR1 promoter hypermethylation and/or low ER expression is not a reliable marker of tamoxifen-resistant atypia. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1884–90)
Effects of Socioeconomic Status and Treatment Disparities in Colorectal Cancer Survival
Authors: Le Hoa , Ziogas Argyrios , Lipkin Steven M. , Zell Jason A.
Published: August 2008

Background: Poor survival among colorectal cancer (CRC) cases has been associated with African-American race and low socioeconomic status (SES). However, it is not known whether the observed poor survival of African-American CRC cases is due to SES itself and/or treatment disparities. We set out to determine this using data from the large, population-based California Cancer Registry database.

Methods: A case-only analysis of CRC was conducted including all age groups using California Cancer Registry data from 1994 to 2003, including descriptive analysis of relevant clinical variables, race, and SES. CRC-specific survival univariate analyses were conducted using the Kaplan-Meier method. Multivariate survival analyses were done using Cox proportional hazards ratios (HR).

Results: Incident cases of colon (90,273) and rectal (37,532) cancer were analyzed, including 91,739 (71.8%) non-Hispanic Whites, 8,535 (6.7%) African-Americans, 14,943 (11.7%) Hispanics, 3,564 (2.8%) Chinese, and 7,950 (6.2%) non-Chinese Asians. African-Americans had a greater proportion of metastatic stage at presentation (P < 0.0001) and decreased CRC-specific survival (P < 0.0001 for colon and rectal cancer). After adjustment for age, sex, histology, site within the colon, and stage, African-Americans [colon: HR, 1.19; 95% confidence interval (95% CI), 1.14-1.25; rectum: HR, 1.27; 95% CI, 1.17-1.38] had an increased risk of death compared with Caucasians. However, after further adjustment for SES and treatment, the risk of death for African-Americans compared with Caucasians was substantially diminished (colon: HR, 1.08; 95% CI, 1.03-1.13; rectum: HR, 1.11; 95% CI, 1.02-1.20).

Conclusion: Among CRC cases, disparities in treatment and SES largely explain the observed decreased survival of African-Americans, underscoring the importance of health disparity research in this disease. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1950–62)
Disparities in the Receipt of Fecal Occult Blood Test versus Endoscopy among Filipino American Immigrants
Authors: Maxwell Annette E. , Danao Leda L. , Crespi Catherine M. , Antonio Cynthia , Garcia Gabriel M. , Bastani Roshan
Published: August 2008

Background: This report examines disparities associated with the type of colorectal screening test, fecal occult blood test versus endoscopy, within a particular racial/ethnic group, Filipino American immigrants.

Methods: Between July 2005 and October 2006, Filipino Americans aged 50 to 75 years from 31 community organizations in Los Angeles completed a 15-minute survey in English (65%) or Filipino (35%).

Results: Of the 487 respondents included in this analysis, 257 (53%) had never received any type of colorectal cancer screening. Among the 230 subjects who had ever received a routine screening test, 78 had fecal occult blood test only (16% of the total sample), and 152 had endoscopy with or without fecal occult blood test (31% of the total sample). After controlling for access to care and key demographic variables in a multivariate analysis, only two characteristics distinguished between respondents who had fecal occult blood test only versus those who had endoscopy: acculturation, assessed by percent lifetime in the United States and language of interview, and income.

Conclusions: Our data suggest a two-tier system, fecal occult blood test for less acculturated Filipino Americans with lower income versus endoscopy for Filipino immigrants with higher levels of acculturation and income. The disparity persists after adjusting for access to care. Instead of treating minority groups as monolithic, differences within groups need to be examined so that interventions can be appropriately targeted. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1963–7)
Increased Childhood Liver Cancer Mortality and Arsenic in Drinking Water in Northern Chile
Authors: Liaw Jane , Marshall Guillermo , Yuan Yan , Ferreccio Catterina , Steinmaus Craig , Smith Allan H.
Published: August 2008

Arsenic in drinking water is an established cause of lung, bladder, and skin cancers in adults and may also cause adult kidney and liver cancers. Some evidence for these effects originated from region II of Chile, which had a period of elevated arsenic levels in drinking water, in particular from 1958 to 1970. This unique exposure scenario provides a rare opportunity to investigate the effects of early-life arsenic exposure on childhood mortality; to our knowledge, this is the first study of childhood cancer mortality and high concentrations of arsenic in drinking water. In this article, we compare cancer mortality rates under the age of 20 in region II during 1950 to 2000 with those of unexposed region V, dividing subjects into those born before, during, or after the peak exposure period. Mortality from the most common childhood cancers, leukemia and brain cancer, was not increased in the exposed population. However, we found that childhood liver cancer mortality occurred at higher rates than expected. For those exposed as young children, liver cancer mortality between ages 0 and 19 was especially high: the relative risk (RR) for males born during this period was 8.9 [95% confidence interval (95% CI), 1.7-45.8; P = 0.009]; for females, the corresponding RR was 14.1 (95% CI, 1.6-126; P = 0.018); and for males and females pooled, the RR was 10.6 (95% CI, 2.9-39.2; P < 0.001). These findings suggest that exposure to arsenic in drinking water during early childhood may result in an increase in childhood liver cancer mortality. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1982–7)
p16 Promoter Methylation Is a Potential Predictor of Malignant Transformation in Oral Epithelial Dysplasia
Authors: Hall Gillian L. , Shaw Richard J. , Field E. Anne , Rogers Simon N. , Sutton David N. , Woolgar Julia A. , Lowe Derek , Liloglou Triantafillos , Field John K. , Risk Janet M.
Published: August 2008

Management of the patient with oral epithelial dysplasia depends on the ability to predict malignant transformation. Histologic grading of this condition fails in this regard and is also subject to interpathologist and intrapathologist variability. This study uses longitudinal clinical samples to explore the prognostic value of a previously validated panel of methylation biomarkers in a cohort of patients with histologically proven oral dysplasia. Methylation enrichment pyrosequencing assays were used to provide the sensitivity of traditional methylation-specific PCR with the additional specificity advantages of a subsequent confirmatory sequencing reaction. In 57% (8 of 14) patients with a lesion that transformed to oral squamous cell carcinoma, 26% (26 of 100) of longitudinal samples collected over ≥3 years showed p16 methylation. Only 1% (2 of 184) of samples from 8% of patients (2 of 24) not undergoing malignant transformation within 3 years had p16 methylation. Both of these samples with p16 promoter methylation were the most recently collected and the patients remain under continuing clinical review. Promoter methylation of MGMT, CYGB, and CCNA1 did not correlate with malignant progression. We thus conclude that methylation of the p16 gene promoter shows promise as a predictor for malignant transformation (Fisher's exact, P = 0.002) in a subset of patients. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2174–9)
Studying Genetic Research Participants: Lessons from the “Learning About Research in North Carolina” Study
Authors: Corbie-Smith Giselle , Blumenthal Connie , Henderson Gail , Garrett Joanne , Bussey-Jones Jada , Moloney Mairead , Sandler Robert S. , Lloyd Stacey W. , Dorrance Jessica , Darter Jane
Published: August 2008

Given the prohibitive cost of recruiting large and diverse populations for genetic explorations in cancer research, there has been a call for genetic studies to engage existing cohorts of research participants. This strategy could lead to more efficient recruitment and potentially result in significant advances in the understanding of cancer etiology and treatment. The Learning About Research in North Carolina (LeARN) study responded to the National Human Genome Research Institute interest in research on how study participants from diverse populations who had participated in genetic research perceived the risks and benefits of participating in combined epidemiologic-genetic research, how well they understand the purpose of the research and the uses to which the research results may be put, and how involvement in such research affects perceptions of disease causality. In this article, we give an overview of the LeARN study, summarizing the methods we used, challenges we encountered, and lessons learned about recruiting participants who have previously participated in genetic research. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2019–24)
Gene Expression Profiling Identifies Genes Predictive of Oral Squamous Cell Carcinoma
Authors: Chen Chu , Méndez Eduardo , Houck John , Fan Wenhong , Lohavanichbutr Pawadee , Doody Dave , Yueh Bevan , Futran Neal D. , Upton Melissa , Farwell D. Gregory , Schwartz Stephen M. , Zhao Lue Ping
Published: August 2008

Oral squamous cell carcinoma (OSCC) is associated with substantial mortality and morbidity. To identify potential biomarkers for the early detection of invasive OSCC, we compared the gene expressions of incident primary OSCC, oral dysplasia, and clinically normal oral tissue from surgical patients without head and neck cancer or preneoplastic oral lesions (controls), using Affymetrix U133 2.0 Plus arrays. We identified 131 differentially expressed probe sets using a training set of 119 OSCC patients and 35 controls. Forward and stepwise logistic regression analyses identified 10 successive combinations of genes which expression differentiated OSCC from controls. The best model included LAMC2, encoding laminin-γ2 chain, and COL4A1, encoding collagen, type IV α1 chain. Subsequent modeling without these two markers showed that COL1A1, encoding collagen, type I α1 chain, and PADI1, encoding peptidyl arginine deiminase, type 1, could also distinguish OSCC from controls. We validated these two models using an internal independent testing set of 48 invasive OSCC and 10 controls and an external testing set of 42 head and neck squamous cell carcinoma cases and 14 controls (GEO GSE6791), with sensitivity and specificity above 95%. These two models were also able to distinguish dysplasia (n = 17) from control (n = 35) tissue. Differential expression of these four genes was confirmed by quantitative reverse transcription-PCR. If confirmed in larger studies, the proposed models may hold promise for monitoring local recurrence at surgical margins and the development of second primary oral cancer in patients with OSCC. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2152–62)
Circulating Human Interleukin-8 as an Indicator of Cancer Progression in a Nude Rat Orthotopic Human Non–Small Cell Lung Carcinoma Model
Authors: Millar Hillary J. , Nemeth Jeffrey A. , McCabe Francis L. , Pikounis Bill , Wickstrom Eric
Published: August 2008

Clinically relevant animal models of human cancer are necessary for the evaluation of putative therapeutics. We hypothesized that circulating human lung cancer–associated proteins would correlate with physiologic measurements from an orthotopic H460 human non–small cell lung carcinoma model that we developed in immunodeficient rats. Physiologic measurements and serum samples were collected over time. Serum interleukin-8 (IL-8), p53, vascular endothelial growth factor, and matrix metalloproteinase-9 were quantitated for correlation with physiologic measurements. Matrix metalloproteinase-9 and p53 were not significantly detectable. Circulating vascular endothelial growth factor was detected at high levels in some tumor-bearing animals. Human IL-8 was detectable in all tumor-bearing animals and correlated positively with markers of respiratory acidosis (pH, P = 0.012; TCO2, P = 0.024; pCO2, P = 0.007; and HCO3−, P = 0.029) and with surface body temperature (P = 0.001) beginning on day 16 after implantation. IL-8 levels negatively correlated with survival (P < 0.001), indicating an association with tumor burden. Circulating human IL-8 might be a useful, clinically relevant circulating tumor protein marker due to its positive correlation with multiple physiologic variables associated with lung cancer progression. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2180–7)
Pharmacokinetics of 6-Gingerol, 8-Gingerol, 10-Gingerol, and 6-Shogaol and Conjugate Metabolites in Healthy Human Subjects
Authors: Zick Suzanna M. , Djuric Zora , Ruffin Mack T. , Litzinger Amie J. , Normolle Daniel P. , Alrawi Sara , Feng Meihua Rose , Brenner Dean E.
Published: August 2008

Background: Ginger shows promising anticancer properties. No research has examined the pharmacokinetics of the ginger constituents 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol in humans. We conducted a clinical trial with 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol, examining the pharmacokinetics and tolerability of these analytes and their conjugate metabolites.

Methods: Human volunteers were given ginger at doses from 100 mg to 2.0 g (N = 27), and blood samples were obtained at 15 minutes to 72 hours after a single p.o. dose. The participants were allocated in a dose-escalation manner starting with 100 mg. There was a total of three participants at each dose except for 1.0 g (N = 6) and 2.0 g (N = 9).

Results: No participant had detectable free 6-gingerol, 8-gingerol, 10-gingerol, or 6-shogaol, but 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol glucuronides were detected. The 6-gingerol sulfate conjugate was detected above the 1.0-g dose, but there were no detectable 10-gingerol or 6-shogaol sulfates except for one participant with detectable 8-gingerol sulfate. The Cmax and area under the curve values (mean ± SE) estimated for the 2.0-g dose are 0.85 ± 0.43, 0.23 ± 0.16, 0.53 ± 0.40, and 0.15 ± 0.12 μg/mL; and 65.6.33 ± 44.4, 18.1 ± 20.3, 50.1 ± 49.3, and 10.9 ± 13.0 μg·hr/mL for 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol. The corresponding tmax values are 65.6 ± 44.4, 73.1 ± 29.4, 75.0 ± 27.8, and 65.6 ± 22.6 minutes, and the analytes had elimination half-lives <2 hours. The 8-gingerol, 10-gingerol, and 6-shogaol conjugates were present as either glucuronide or sulfate conjugates, not as mixed conjugates, although 6-gingerol and 10-gingerol were an exception.

Conclusion: Six-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol are absorbed after p.o. dosing and can be detected as glucuronide and sulfate conjugates. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1930–6)
Perceived Medical Discrimination and Cancer Screening Behaviors of Racial and Ethnic Minority Adults
Authors: Crawley LaVera M. , Ahn David K. , Winkleby Marilyn A.
Published: August 2008

Background: Discrimination has been shown as a major causal factor in health disparities, yet little is known about the relationship between perceived medical discrimination (versus general discrimination outside of medical settings) and cancer screening behaviors. We examined whether perceived medical discrimination is associated with lower screening rates for colorectal and breast cancers among racial and ethnic minority adult Californians.

Methods: Pooled cross-sectional data from 2003 and 2005 California Health Interview Survey were examined for cancer screening trends among African American, American Indian/Alaskan Native, Asian, and Latino adult respondents reporting perceived medical discrimination compared with those not reporting discrimination (n = 11,245). Outcome measures were dichotomous screening variables for colorectal cancer among respondents ages 50 to 75 years and breast cancer among women ages 40 to 75 years.

Results: Women perceiving medical discrimination were less likely to be screened for colorectal [odds ratio (OR), 0.66; 95% confidence interval (95% CI), 0.64-0.69] or breast cancer (OR, 0.52; 95% CI, 0.51-0.54) compared with women not perceiving discrimination. Although men who perceived medical discrimination were no less likely to be screened for colorectal cancer than those who did not (OR, 1.02; 95% CI, 0.97-1.07), significantly lower screening rates were found among men who perceived discrimination and reported having a usual source of health care (OR, 0.30; 95% CI, 0.28-0.32).

Conclusions: These findings of a significant association between perceived racial or ethnic-based medical discrimination and cancer screening behaviors have serious implications for cancer health disparities. Gender differences in patterns for screening and perceived medical discrimination warrant further investigation. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1937–44)