bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of the phase transition and charge ordering in single-crystalline Nd1/2Sr1/2MnO3 using x-ray scattering
Authors: Du C.-H. , Ghazi M. E. , Hatton P. D. , Collins S. P. , Murphy B. M. , Kim B. G. , Cheong S-W.
Published: July 2008

We report a sequent phase transition using high-resolution synchrotron x-ray scattering in a single crystal Nd1/2Sr1/2MnO3. By measuring the peak profile of Bragg reflections, upon cooling, we observed an increase in the width of the Bragg reflections around the Curie temperature (252 K) corresponding to the transition from a paramagnetic to a ferromagnetic state. Below approximately 200 K, dramatic changes in the width and integrated intensity were observed. Changes continued until the formation of charge ordering with q=(12,0,0) at TCO=152 K. This charge ordering was observed to be the first order transition with a large hysteresis width of 10 K. This sequent transition is understood by the formation of different magnetic domains at different temperature ranges as that observed by neutron powder diffraction.
Improved insight in charge trapping of high-k ZrO2/SiO2 stacks by use of tunneling atomic force microscopy
Authors: Paskaleva A. , Yanev V. , Rommel M. , Lemberger M. , Bauer A. J.
Published: July 2008

In this work, tunneling atomic force microscopy (TUNA) is used to describe the charge trapping in high-k ZrO2 dielectric stacks at nanoscale dimensions by analyzing the alteration of the I-V curves and the I-V hysteresis phenomena with repeated measurements (up to 100 curves) at a single spot of only several nm2 in area. TUNA is also suggested as a powerful technique to correlate the electrical characteristics to the physical properties of the stacks. In particular, the influence of the thin SiO2 interfacial layer thickness and its modification with annealing conditions on the electrical properties is demonstrated. Furthermore, the appearance of an I-V hysteresis and its relation to degradation mechanisms in high-k dielectric stacks are explained. Trapping at pre-existing traps is evidenced.
Phase transitional behavior, microstructure, and electrical properties in Ta-modified [(K0.458Na0.542)0.96Li0.04] NbO3 lead-free piezoelectric ceramics
Authors: Chang Yunfei , Yang Zu-pei , Ma Difei , Liu Zonghuai , Wang Zenglin
Published: July 2008

Lead-free [(K0.458Na0.542)0.96Li0.04] (Nb1−xTax)O3 ceramics were prepared by ordinary sintering technique. The effects of Ta content on the phase transitional behavior, Raman spectrum, microstructure, and dielectric, piezoelectric, and ferroelectric properties of the ceramics were investigated. X-ray diffraction results indicate that the phase structure undergoes a transition from orthorhombic to tetragonal phase with the increase in x. The small and large peaks observed in the Raman spectra can all be attributed to the internal modes of the NbO6 octahedron, and both ν5 and ν1 modes slightly shift to lower frequency numbers by increasing x. Ta substitution for Nb leads to the disappearance of the abnormal grain growth behavior, inhibits the grain growth, and improves the density of the ceramics. Increasing x leads to the different variations of dielectric constants before and after poling and makes the ceramics more relaxorlike. The proper substitution of Ta shifts the polymorphic phase transition (at To-T) to near room temperature, and a coexistence of orthorhombic and tetragonal phases is formed, which leads to significant enhancements of the electrical properties. For the ceramics with x=0.15, the electrical properties become optimum, which are as follows: piezoelectric coefficient d33=298 pC/N, electromechanical coupling coefficient kp=0.52, dielectric constant εr=1195, dielectric loss tan δ=0.016, To-T=35 °C, Curie temperature TC=366 °C, remanent polarization Pr=28.68 μC/cm2, and coercive field Ec=7.14 kV/cm. These properties are much higher than those of previously reported (K,Na,Li)(Nb,Ta)O3 systems with K:Na=1:1.
Estimating threshold reduction for spin-injected semiconductor lasers
Authors: Vurgaftman I. , Holub M. , Jonker B. T. , Meyer J. R.
Published: July 2008

The magnitude of threshold reduction in a semiconductor laser with electron spin injection is shown to depend on such intrinsic properties of the active region as the dominant recombination mechanism, the ratio of hole-to-electron densities of states, the active-region doping, and the available material gain as well as cavity properties such as the optical loss. The threshold reduction is expected to be greatest when the laser’s active region is undoped, the recombination is strongly dominated by Auger processes, and the threshold gain is low. It can approach a factor of 3.5 for fully spin-polarized electrons in the active region.
Heteroperovskite phase formation and magnetotransport properties of YBa2Cu3O7−x/SrRuO3 quasimultilayers
Authors: Cai Chuanbing , Liu Jinlei , Liu Zhiyong , Ying Liliang , Gao Bo , Peng Lin , Chen Changzhao
Published: July 2008

A series of quasimultilayers consisting of YBa2Cu3O7−δ (YBCO) and SrRuO3 (SRO), namely, p×(YBCO(m)/SRO(n)) (p: repetition periods; m: YBCO pulse number; n: SRO pulse number), is prepared on single crystal SrTiO3 by pulsed laser deposition. X-ray diffraction measurements reveal that a heterogeneous phase of Ba2YRuO6 is formed due to the chemical reaction, while both the in-plane and out-of-plane textures of the present quasimultilayers are as good as in the pure YBCO films. The content of Ba2YRuO6 increases as the pulse number of SRO increases, leading to the decrease in superconducting transition temperature (Tc). There is no obvious difference in Tc between the samples with the different deposition sequence orders of YBCO and SRO. The magnetic field dependence of critical current density (Jc) shows an enhanced flux pinning at relatively high fields for all the present quasimultilayers, which occurs at different ranges of fields depending on the applied temperatures. The Jc of the quasimultilayers can reach two times higher than that of pure YBCO films in a wide range of magnetic fields, which shows the promising application for coated conductors.
Exchange bias in the layered cobaltite Sr1.5Pr0.5CoO4
Authors: Ang R. , Sun Y. P. , Luo X. , Hao C. Y. , Zhu X. B. , Song W. H.
Published: July 2008

We investigate the exchange bias phenomenon in the layered cobaltite Sr1.5Pr0.5CoO4 by using magnetometry. The exchange bias is strongly dependent on the cooling magnetic field as well as the measuring field. These results suggest that the exchange coupling at the interfaces between the ferromagnetic (FM) regions and the spin-glass (SG) regions may induce an exchange anisotropy. The observed exchange bias effect is suggested to originate from the pinning to FM moments by frozen spins in the SG regions along the cooling field direction. Our results also expand the concept of the magnetically tunable exchange bias, which can contribute to the potential applications for spintronic devices.
Infrared emission from the substrate of GaAs-based semiconductor lasers
Authors: Ziegler Mathias , Pomraenke Robert , Felger Max , Tomm Jens W. , Vasa Parinda , Lienau Christoph , Sanayeh Marwan Bou , Gomez-Iglesias Alvaro , Reufer Martin , Bugge Frank , Erbert Götz
Published: July 2008

We report on the origin of three additional low-energy spontaneously emitted bands in GaAs-based broad-area laser diodes. Spectrally and spatially resolved scanning optical microscopy and Fourier-transform infrared spectroscopy assign the different contributions to bandtail-related luminescence from the gain region as well as interband and deep-level-related luminescences from the GaAs substrate. The latter processes are photoexcited due to spontaneous emission from the active region followed by a cascaded photon-recycling process within the substrate.
Fabrication of one-dimensional programmable-height nanostructures via dynamic stencil deposition
Authors: Wasserman J. L. , Lucas K. , Lee S. H. , Ashton A. , Crowl C. T. , Marković N.
Published: July 2008

Dynamic stencil deposition (DSD) techniques offer a variety of fabrication advantages not possible with traditional lithographic processing, such as the ability to directly deposit nanostructures with programmable-height profiles. However, DSD systems have not enjoyed widespread usage due to their complexity. We demonstrate a simple, low-profile, portable, one-dimensional nanotranslation system that facilitates access to nanoscale DSD abilities. Furthermore we show a variety of fabricated programmable-height nanostructures, including parallel arrays of such structures, and suggest other applications that exploit the unique capabilities of DSD fabrication methods.
Piezoelectric disks used as metamaterial inclusions
Authors: Acher O. , Ledieu M. , Bardaine A. , Levassort F.
Published: July 2008

The permeability of inclusions consisting of commercially available piezoelectric disks was investigated, leading to the observation of several resonances in the 100MHz–3GHz range. This could be described through a simple analytical relation, and the inclusions were deemed attractive for manufacturing metamaterials with negative permeabilities over a significant frequency range. Moreover, they can be used as reference permeability samples.
Effect of waveguide sidewall roughness on the threshold current density and slope efficiency of quantum cascade lasers
Authors: Toor Fatima , Sivco Deborah L. , Liu Hao E. , Gmachl Claire F.
Published: July 2008

We report on a study to determine the effect of waveguide sidewall roughness on quantum cascade (QC) laser performance using two two-wavelength heterogeneous QC laser structures, one with emission wavelengths of 7.0μm∕11.2μm, and the other with 8.7μm∕12.0μm. For the range of roughness standard deviation values from about 0.4to1.0μm, for which all four QC lasers were operating, the threshold current density increases by 12%–15% and the slope efficiency decreases by 30%–70% with stronger performance degradation for the shorter wavelength lasers, which is in agreement with a model based on Rayleigh scattering.
Wide-range characterization of current conduction in high-Tc coated conductors
Authors: Thompson J. R. , Polat Ö. , Christen D. K. , Kumar D. , Martin P. M. , Sinclair J. W.
Published: July 2008

The conduction of supercurrents in a short-segment state-of-the-art coated conductor prototype has been studied over ∼8 decades of dissipation. A combination of conventional transport methods, magnetometry in a swept magnetic field, and “flux creep” measurements was used to obtain current density J versus electric field E characteristics over a span E∼10−5–10−13V∕cm. The inductive measurements allow facile exploration of current conduction over a wide range of temperatures, magnetic fields, and dissipation levels where future applications are envisioned.
Growth and structural characterization of (0.2)Bi(Zn1∕2Ti1∕2)O3–(0.8)PbTiO3 epitaxial thin films by off-axis rf sputtering
Authors: Kwon Daeyoung , Kim Bongju , Tong P. , Kim Bog G.
Published: July 2008

We report the epitaxial growth of ferroelectric (0.2)Bi(Zn1∕2Ti1∕2)O3–(0.8)PbTiO3 thin films. Despite its high c∕a ratio, the off-axis rf magnetron sputtering yields the epitaxial growth of high-quality thin films on (001) SrTiO3 substrates. The structural development of the film with increasing film thickness has been examined by using the synchrotron x-ray diffraction and x-ray reflectivity. The experimental results can be explained in terms of the strain relaxation process associated with the misfit dislocations between the thin film and the substrate.
In-plane anisotropic strain in a-ZnO films grown on r-sapphire substrates
Authors: Saraf G. , Lu Y. , Siegrist T.
Published: July 2008

We deposited (112¯0) nonpolar a-plane ZnO (a-ZnO) films on (011¯2) r-sapphire substrates using metalorganic chemical vapor deposition. Unit cell deformation due to interfacial strain in films was determined by triple-axis x-ray diffraction. Due to low symmetry of a-plane, anisotropic strain is observed along the [0001] (c-axis) and [11¯00] (m-axis) in-plane axes. Out-of-plane strain along [112¯0] (a-axis) is tensile and relaxes for film thickness ⩾2μm. The in-plane m-axis is under tensile strain and c-axis is under compressive strain. Increase in film thickness increases in-plane strain anisotropy due to faster relaxation along the m-axis. Thermal and lattice mismatch strains are separated by curve fitting.
Space and Protest Policing at International Summits
Authors: Zajko Mike , Béland Daniel
Published: July 2008

Since the 1970s a growing body of literature has taken a ‘geographic turn’ and sought to incorporate the study of spatial factors into the social sciences. Building on this theoretical literature, this study undertakes a spatial analysis of the contentious politics that have become so closely and regularly linked to international summit diplomacy. The paper examines and compares the protests surrounding two international summits held in Canada: the Vancouver Asia-Pacific Economic Cooperation summit (1997) and the Kananaskis G8 summit (2002). These two cases serve to demonstrate many of the important ways in which space is controlled and contested by both protesters and state actors such as the police.
The Work of Policy: Actor Networks, Governmentality, and Local Action on Climate Change in Portland, Oregon
Authors: Rutland Ted , Aylett Alex
Published: July 2008

To develop and implement public policy requires work. In this paper, we examine some of the work involved in a pathbreaking climate change policy adopted in Portland, Oregon. Seeking to address shortcomings in existing studies of local environmental governance, we focus particular attention on how climate change became a political priority in Portland, how a particular representation of local carbon dioxide emissions was developed in the process of public consultations, and how the local state attempted to achieve its adopted policy objectives by enlisting the self-governing capacities of its residents. To carry out such an analysis, we draw on both actor-network theory (ANT) and governmentality. The first approach offers an understanding of how collective priorities emerge as different actants learn how to move toward their goals by working together, and also suggests how subjects and objects are reshaped by their enrolment in such configurations. The second approach offers a more precise understanding of how the state attempts to achieve its objectives—once they are established—by conducting the conduct of its citizens. Brought together, we argue, ANT and governmentality provide an incisive approach to questions of local environmental governance, and to broader political concerns as well. As each approach addresses well-cited shortcomings of the other, the combined approach developed in this paper could be deployed in many studies that examine the emergence of political priorities and the capacity to achieve them.
Crystal structure of the cell wall anchor domain of MotB, a stator component of the bacterial flagellar motor: Implications for peptidoglycan recognition
Authors: Roujeinikova Anna
Published: July 2008

The stator ring of the bacterial flagellar motor is composed of the MotA and MotB proteins that act together to generate a turning force (torque) acting on the FliG ring of the rotor. The C-terminal domain of MotB (MotB-C) is believed to anchor the MotA/MotB complex to peptidoglycan (PG) of the cell wall. The first crystal structures of MotB-C and its complex with
N
-acetylmuramic acid (NAM) have been determined to 1.6- and 2.3-Å resolution, respectively. MotB-C is a dimer, both in solution and in the crystal. The two glycan chains of the PG ligand can be modeled as semirigid helices and docked into the grooves harboring the NAM molecules on the opposite faces of the dimer. The model suggests that a concave hydrophilic surface created upon edge-to-edge β-sheet dimerization and centered around the 2-fold axis of the dimer can accommodate the peptide cross-bridge linking the two sugar chains. Significant structural similarities were found between MotB-C and the PG-binding domains of reduction-modifiable protein M and peptidoglycan-associated lipoprotein exclude, suggesting that PG recognition by different outer membrane protein A-like proteins may be governed by very similar molecular mechanisms that evidently involve protein dimerization.
Mechanism for alternating access in neurotransmitter transporters
Authors: Forrest Lucy R. , Zhang Yuan-Wei , Jacobs Miriam T. , Gesmonde Joan , Xie Li , Honig Barry H. , Rudnick Gary
Published: July 2008

Crystal structures of LeuT, a bacterial homologue of mammalian neurotransmitter transporters, show a molecule of bound substrate that is essentially exposed to the extracellular space but occluded from the cytoplasm. Thus, there must exist an alternate conformation for LeuT in which the substrate is accessible to the cytoplasm and a corresponding mechanism that switches accessibility from one side of the membrane to the other. Here, we identify the cytoplasmic accessibility pathway of the alternate conformation in a mammalian serotonin transporter (SERT) (a member of the same transporter family as LeuT). We also propose a model for the cytoplasmic-facing state that exploits the internal pseudosymmetry observed in the crystal structure. LeuT contains two structurally similar repeats (TMs1–5 and TMs 6–10) that are inverted with respect to the plane of the membrane. The conformational differences between them result in the formation of the extracellular pathway. Our model for the cytoplasm-facing state exchanges the conformations of the two repeats and thus exposes the substrate and ion-binding sites to the cytoplasm. The conformational change that connects the two states primarily involves the tilting of a 4-helix bundle composed of transmembrane helices 1, 2, 6, and 7. Switching the tilt angle of this bundle is essentially equivalent to switching the conformation of the two repeats. Extensive mutagenesis of SERT and accessibility measurements, using cysteine reagents, are accommodated by our model. These observations may be of relevance to other transporter families, many of which contain internal inverted repeats.
Correlation Between In Vivo and In Vitro Pulmonary Responses to Jet Propulsion Fuel-8 Using Precision-Cut Lung Slices and a Dynamic Organ Culture System
Authors: Hays Allison M. , Lantz R. Clark , Witten Mark L.
Published: July 2008

In tissue slice models, interactions between the heterogeneous cell types comprising the lung parenchyma are maintained thus providing a controlled system for the study of pulmonary toxicology in vitro. However, validation of the model in vitro system must be affirmed. Previous reports, in in vivo systems, have demonstrated that Clara cells and alveolar type II cells are the targets following inhalation of JP-8 jet fuel. We have utilized the lung slice model to determine if cellular targets are similar following in vitro exposure to JP-8. Agar-filled adult rat lung explants were cored and precision cut, using the Brendel/Vitron tissue slicer. Slices were cultured on titanium screens located as half-cylinders in cylindrical Teflon cradles that were loaded into standard scintillation vials and incubated at 37°C. Slices were exposed to JP-8 jet fuel (0.5 mg/ml, 1.0 mg/ml, and 1.5 mg/ml in medium) for up to 24 hours. We determined ATP content using a luciferin-luciferase bioluminescent assay. No significant difference was found between the JP-8 jet fuel doses or time points, when compared to controls. Results were correlated with structural alterations following aerosol inhalation of JP-8. As a general observation, ultrastructural evaluation of alveolar type II cells revealed an apparent increase in the number and size of surfactant secreting lamellar bodies that was JP-8 jet fuel-dose dependent. These results are similar to those observed following aerosol inhalation exposure. Thus, the lung tissue slice model appears to mimic in vivo effects of JP-8 and therefore is a useful model system for studying the mechanisms of lung injury following JP-8 exposure.
Recommended Tissue List for Histopathologic Examination in Repeat-Dose Toxicity and Carcinogenicity Studies: A Proposal of the Society of Toxicologic Pathology (STP)
Authors: Bregman Carla L. , Adler Rick R. , Morton Daniel G. , Regan Karen S. , Yano Barry L.
Published: July 2008

The Executive Committee of the Society of Toxicologic Pathology (STP) appointed an ad hoc task force to devise and recommend a standard list of tissues to be evaluated histopathologically in repeat-dose toxicity and carcinogenicity studies that are used to support the registration of new pharmaceutical products. The recommended tissue list is intended to be a minimum core list that can be used for all types of repeat-dose toxicity and carcinogenicity studies, regardless of route of administration, species or strain of mammalian laboratory animal, duration, or class of drug to be tested. The resulting recommendations of the task force, presented here, were subsequently reviewed by the STP membership and endorsed by the STP Executive Committee.
Methimazole-Induced Damage in the Olfactory Mucosa: Effects on Ultrastructure and Glutathione Levels
Authors: Bergström Ulrika , Giovanetti Anna , Piras Elena , Brittebo Eva B.
Published: July 2008

Methimazole is an antithyroid drug that can induce loss of smell and taste in humans. It is also an olfactory toxicant in rodents. The aim of the present study was to examine involvement of glutathione in methimazole-induced damage of the olfactory mucosa (OM) of mice, and to study early onset of this damage using transmission electron microscopy (TEM). We found that an intraperitoneal dose of methimazole induced a dose-dependent decrease of nonprotein sulfhydryl groups (NP-SH; mainly glutathione) in the OM. Hepatic NP-SH was not decreased. One hour after administration (50 mg/kg), TEM demonstrated an extensive damage to acinar and intraepithelial excretory duct cells of Bowman's glands (BG) including dilatation of the endoplasmic reticulum and mitochondrial swelling. Furthermore, large vacuoles were noted in basal intraepithelial duct cells. After 2 hours there were ruptures of secretory granule membranes in BG and mitochondrial swelling and degeneration of sustentacular cells. The basal cells were less damaged. After four hours the neuroepithelium was disorganized although the columnar organization of neurons was largely intact. The acinar organization of the BG was frequently lost. The subsequent detachment of the neuroepithelium is suggested to be secondary to extensive damage of BG excretory ducts and sustentacular cells.
Involvement of Toxicity as an Early Event in Urinary Bladder Carcinogenesis Induced by Phenethyl Isothiocyanate, Benzyl Isothiocyanate, and Analogues in F344 Rats
Authors: Akagi Keisuke , Sano Masashi , Ogawa Kumiko , Hirose Masao , Goshima Hideo , Shirai Tomoyuki
Published: July 2008

Phenethyl isothiocyanate (PEITC)1 and benzyl isothiocyanate (BITC), naturally occurring constituents of cruciferous vegetables, have been reported to exert inhibitory effects against development of tobacco-specific carcinogen-induced lung tumors and are regarded as promising chemopreventive agents for lung cancer. However, tumor promoting and carcinogenic activities in the rat urinary bladder have been detected in several animal models. The purpose of the present study was to investigate early changes in rat urinary bladder epithelium induced by PEITC and BITC and to explore promotion/carcinogenic mechanisms. In the first experiment, in order to assess acute toxic effects, PEITC or BITC at 0.1% each in the diet were administered to 6-week-old F344 rats for 1, 2, 3, and 7 days and sequential histopathological assessment and urinalysis were performed. In the second and third experiments, structure-activity relationships of PEITC, BITC and 8 other analogues, benzyl isocyanate and benzyl thiocyanate, and phenyl-, α-naphthyl-, tert-butyl-, butyl-, methyl-, and ethyl isothiocyanates (ITCs) were explored in a 14-day experiment. In the first experiment, the urinary pH was significantly lowered on day 1 by both PEITC and BITC. Striking features of toxicity, such as marked inflammatory changes characterized by cellular infiltration, apoptosis/single cell necrosis, cytoplasmic vacuolation, erosion, and hemorrhage in the urinary bladder were caused, with peaks apparent on days 2 or 3, respectively. Sequential change in 5-bromo-2'-deoxyuridine (BrdU) labeling indices was in line with the inflammatory response, but the thickness of the urinary bladder epithelium continued to gradually increase up to day 7. In the second and third experiments, simple and papillary or nodular (PN) hyperplasias were observed after 14-days treatment with PEITC, BITC, and phenyl- and butyl ITCs. These results suggest that continuous urinary epithelial cell proliferation due to cytotoxicity may play an important role in the early stage of rat urinary bladder carcinogenesis due to oral administration of ITCs. In addition, hydrophobic activity of ITCs, dependent on the alkyl carbon chain length, might strongly influence the induction of bladder lesions in rats.
Transcription Profiling Distinguishes Dose-Dependent Effects in the Livers of Rats Treated with Clofibrate
Authors: Kramer Jeffrey A. , Blomme Eric A.G. , Bunch Roderick T. , Davila Julio C. , Jackson Carmen J. , Jones Patrick F. , Kolaja Kyle L. , Curtiss Sandra W.
Published: July 2008

Peroxisome proliferators such as the fibrates act via the peroxisome proliferator activated receptor (PPAR)- α as hypolipidemic agents. Many peroxisome proliferators are also nongenotoxic hepatic carcinogens and hepatotoxicants in rodents. We performed transcription profiling using cDNA microarrays on livers of rats treated for 5 days with 3 doses of the peroxisome proliferator clofibrate. All 3 doses had hepatic effects as assessed by liver to body weight ratio, alanine aminotransferase (ALT) increases and histopathology examination. Analysis of the transcription profiling data identified changes in the expression of many genes within several mechanistic pathways that support existing hypotheses regarding peroxisome proliferator mediated carcinogenicity. Additionally, the transcription profiling, histopathology, and clinical chemistry results suggested a biphasic response to clofibrate. These findings provide insight into the pathogenesis of toxic and carcinogenic effects of clofibrate in rodents and demonstrate the ability of cDNA microarrays to provide information regarding mechanisms of toxicity identified during the drug development process.
Main Vascular Changes Seen in the Saline Controls of Continuous Infusion Studies in the Cynomolgus Monkey over an Eight-Year Period
Authors: Lilbert Juliette , Burnett Roger
Published: July 2008

The aim of this study was to characterize the main vascular lesions seen in the saline controls in continuous infusion studies in monkeys. Data were collected from 17 studies over an 8-year period (ie, around 50 males and 50 females). The study was restricted to lesions at the injection site, in lungs and at the entry point. It showed that the level of the most severe procedure-related lesions (ie, necrosis with abscess formation at the injection site and at the entry point, thromboemboli and probable infarcts in lungs) was low ( <10%). Minor changes such as endothelial hyperplasia and intimal thickening at the injection site, and low-graded interstitial pneumonitis in lungs were the most frequent changes (40 to 50% of the animals). Thrombi at the injection site were present in around 30% in males and 40% in females. The slightly higher incidence of thrombi in females was not explained by a difference of vessel size or by hematological differences. This study permitted an opportunity to harmonise terminology among pathologists and to define the main procedure-related changes and their incidence, which could help pathologists better interpret changes in future infusion studies.
Development of Sperm Granulomas in the Epididymides of L-Cysteine-Treated Rats
Authors: Sawamoto Osamu , Yamate Jyoji , Kuwamura Mitsuru , Kotani Takao , Kurisu Kazunobu
Published: July 2008

We investigated the histopathological effects of excess L-cysteine on the male rat reproductive tract during sexual maturation. Male 6-week-old Sprague—Dawley rats were injected intraperitoneally daily with L-cysteine, 1,000 mg/kg body weight, for 1, 2, 3, and 4 weeks. L-Cysteine-treated rats developed sperm granulomas in the epididymides at an incidence of 0% (0/6), 50% (3/6), 83% (5/6), and 100% (6/6) in rats examined at study weeks 1, 2, 3, and 4, respectively. These sperm granulomas were unilateral or bilateral, and most frequently involved the proximal cauda region of the epididymides. Interestingly, small ducts, indicative of immaturity, were seen frequently in L-cysteine-treated rats. These findings suggest that the maturation of epididymides in L-cysteine-treated rats might be delayed. Additionally, dilated ducts and interstitial edema, suggestive of an increase in intraluminal pressure, were seen often in the epididymides of L-cysteine-treated rats. Labeling spermatozoa and epithelial cells with monobromobimane indicated no influence of the thiol—disulfide status of L-cysteine to the epididymides. The testes and prostate glands also showed no effects, suggesting that inhibited epididymis maturation was not a result of hormonal deficiencies. We speculate that defective development of the ducts might result in aberrant fluid flow, leading to ductal rupture in the epididymides. In that case, sperm granulomas might form around leaked spermatozoa.
Development of Methodology for the Three-Dimensional Modelling of the Metabolic Capacity of the Rat Nasal Cavity using Glutathione S-Transferase M1 as an Example
Authors: Robinson Darren A. , Foster John R. , Nash John A. , Reed Celia J.
Published: July 2008

A variety of chemicals induce site-specific lesions in the rodent nasal cavity. In order to explore the reasons for this site-selectivity, methodology for (a) creation of a 3-dimensional (3D) model of a rat nasal cavity, and (b) mapping of semiquantitative data onto the model has been developed. The head of a rat was fixed, decalcified, step-sectioned (every 100 μm) and stained with hematoxylin and eosin. Digital images of the sections were optically captured, and a KS400 image analysis system (Imaging Associates, Thame, Oxford, UK), attached to a standard personal computer, was used to align adjacent images and reconstruct the series in 3D. The final model was anatomically correct, and could be rotated in any plane and manipulated to display individual internal structures. The spatial localization of a glutathione S-transferase (rGSTM1, previously known as GST 3-3) within this model was investigated using immunohistochemistry. Step sections (every 400 μm) were stained, analyzed by imaging densitometry, and the results for the stained regions within the nasal cavity divided into 4 grades representing high to low expression of rGSTM1. The data was mapped onto the 3D model and showed that the highest expression of this enzyme was in the central regions of the nasal cavity at the transition between respiratory and olfactory epithelia. This methodology will allow investigation of the relationship between the in situ localization of bioactivating and detoxifying enzyme systems and the site-specificity of nasal lesions.
Spontaneous Acute Tumor Lysis Syndrome in a DBA/1J Mouse: A Case Report and Review
Authors: Lovelace Karen , Vangessel Yvonne , Asher Ludmila V. , Vogel Peter
Published: July 2008

Spontaneous acute tumor lysis syndrome (ATLS) was diagnosed in a 10-month-old female DBA/1J sentinel mouse with leukemic lymphoma. The mouse was unable to maintain balance and died shortly after being observed rolling around in its cage. Disseminated neoplastic disease, including a large cranial mediastinal mass, enlarged lymph nodes and splenomegaly, was present at necropsy. Histopathologic examination revealed widespread massive necrosis of lymphoblastic tumor cells, and widely disseminated microemboli composed of nuclear and cytoplasmic cell debris. Although ATLS is widely recognized as an oncologic emergency in humans, acute lesions of ATLS have not been described. The mechanical obstruction of capillary beds by microemboli originating from disintegrating necrotic tumor cells was the likely cause of clinical signs and death in this mouse. We propose that similar microemboli may contribute to the pathogenesis of the acute renal failure and other clinical signs associated with ATLS in humans. Recognition of spontaneous ATLS in laboratory animals is especially important in studies that assess the efficacy and/or toxicity of anticancer treatments, where early deaths due to ATLS might mistakenly be attributed to a direct test article effect.
Differences in Immunohistochemical Expression of Xenobiotic-Metabolizing Enzymes Between Normal Pancreas, Chronic Pancreatitis and Pancreatic Cancer
Authors: Standop Jens , Schneider Matthias , Ulrich Alexis , Büchler Markus W. , Pour Parviz M.
Published: July 2008

Metabolic activation of many toxins, carcinogens, drugs, and anti-cancer agents is governed by the cytochrome P450 (CYP) drug-metabolizing enzyme system. To help elucidate the role of this enzyme system in the pathogenesis of chronic inflammatory and malignant pancreatic diseases, we compared the immunohistochemical expression pattern of 8 CYP-enzymes in 24 normal, 20 chronic pancreatitis, and 21 pancreatic cancer specimens using antibodies to CYP 1A1, 1A2, 2B6, 2C8/9/19, 2D6, 2E1, and 3A4, and the NADPH cytochrome P450 oxido-reductase (NA-OR). Compared to the normal pancreas, a higher frequency of immunopositivity for CYP 1A2, 2B6, 2C8/9/19, 2D6, and NA-OR was found in chronic pancreatitis, and of all CYPs but 1A2 in pancreatic cancer. On the other hand, CYP 1A1 and 2E1 antibody staining was less frequently observed in chronic pancreatitis. In all specimens with pancreatic polypeptide (PP)-rich regions (pancreas head), more islet cells than ductal and acinar cells were immunopositive. Moreover, the immunoreactivity of islet cells from PP-rich specimens with anti-CYP antibodies was consistently more frequent and intense than in islet cells from PP-poor areas (body and tail). Immunoreactivity for xenobiotic-metabolizing enzymes was frequently observed in the normal pancreas, chronic pancreatitis, and pancreatic cancer, and displayed differences of its frequency and intensity between the 3 groups. Considering immunohistochemical evidence of enzyme expression and pancreatic blood supply together, islet cells appear to be an important and possible early site of CYP-enzyme induction in pancreatic diseases.
Stage-Dependent Expression of an Angiogenic Agent and Vascular Organization in Experimental Skin Tumor Development
Authors: Näyhä Veera , Laitakari Jaakko , Stenbäck Frej
Published: July 2008

Increased angiogenesis and expression of antibodies to vascular endothelial growth factor (VEGF), an angiogenic agent, have been shown in the tumor development of many tissues. Areas of skin expressing VEGF and total volume of vessels expressing laminin in the wall were measured in chemical carcinogen-exposed mice using CAS-200 morphometry apparatus having a sensitivity exceeding 99% and reproducibility exceeding 99%. The area of VEGF expression was increased in carcinogen-exposed skin, dysplasia and in well-differentiated squamous cell carcinomas, but decreased in squamous cell carcinomas with decreased degree of differentiation. The vessel volume increased prior to the formation of tumors in carcinogen-exposed skin as well as in highly malignant neoplasms. In well-differentiated squamous cell carcinomas with an expansive growth pattern, the vessels were parallel to the basal membrane, in moderately differentiated tumors the vessels were in the direction of tumor invasion, and in poorly differentiated tumors, active angiogenesis consisted of numerous, enlarged vessels within the tumor. This study showed increased VEGF expression and number of vessels occurring in early stages of skin tumor development, pointing to a role of angiogenesis in chemical risk assessment and in cancer prevention. Altered vessel structure and vessel arrangement were distinct in later stages of tumor growth and in malignant neoplasms, pointing to the utility of detailed vessel analysis in neoplasm characterization.
An Alternative Perspective: A Critical Evaluation of the Waddell Threshold Extrapolation Model in Chemical Carcinogenesis
Authors: Haseman J.K.
Published: July 2008

In a recent Perspective article ( Toxicologic Pathology 31: 260—262, 2003) Waddell asserts that he has developed a log linear extrapolation model that can demonstrate a threshold and resolve for once and for all the uncertainies associated with low dose cancer risk extrapolation. However, his method essentially forces, rather than demonstrates, a threshold, and has many serious flaws that result in significant under-estimation of low dose risk. It would be a serious mistake for the scientific community to adopt Waddell's log linear extrapolation model for chemical carcinogenesis risk assessment.
Sequential Alteration of Apoptosis, p53 Expression, and Cell Proliferation in the Rat Pancreas Treated with 4-Hydroxyaminoquinoline 1-Oxide
Authors: Imazawa Takayoshi , Nishikawa Akiyoshi , Toyoda Kazuhiro , Furukawa Fumio , Mitsui Masayuki , Hirose Masao
Published: July 2008

Changes in p53 expression, apoptosis and cell proliferation after treatment with 4-hydroxyaminoquinoline 1-oxide (4HAQO) were investigated in the rat pancreas and liver, target and nontarget organs for tumorigenesis, respectively. Male rats were given a single intravenous injection of 4HAQO at a dose of 20 mg/kg body weight and control rats received vehicle alone and were euthanized after 2—72 hours. Pancreata and livers were removed for histopathological examination, immunohistochemistry for p53 protein, PCNA and Ki-67, and TUNEL labeling and electron microscopic observation for detecting apoptosis. In the pancreas, p53 expression and apoptosis were significantly increased first at 4 and 6 hours, respectively, while no change was evident in the liver. The rates peaked at 24 hours, consistent with the peak for PCNA-labeling, while Ki-67-labeling rates peaked at 72 hours. Electron microscopically, apoptotic changes in pancreatic acinar cells were observed after 2 hours. No significant apoptosis, p53 expression or cell proliferation were noted in the pancreatic tissues of the control rats nor in liver cells regardless of 4HAQO treatment. Taken together with our previous data, the results suggest that apoptosis, p53 expression, and enhanced cell replication are closely related phenomena involved in the carcinogenesis of 4HAQO following DNA adduct formation.
Iron Lactate-Induced Osteomalacia in Association with Osteoblast Dynamics
Authors: Matsushima Shuuichi , Tor Mikinori , Ozaki Kiyokazu , Narama Isao
Published: July 2008

Osteomalacia was induced in rats fed a diet containing 50,000 ppm (5%) iron lactate for 13 weeks. The histopathology and histomorphometrical dynamics of osteoblasts under this condition were examined. Bone histomorphometry of the proximal tibial metaphysis revealed that the osteoblast surface, osteoid volume, osteoid surface and labeled surface ratio, which are the parameters of bone formation had increased. The blood chemistry revealed the greatest elevation in the osteocalcin level; however, the parathyroid hormone (PTH) secretion and inorganic phosphorus level were very low. From the serum biochemical, histopathological and histomorphometrical findings, the bone lesion in iron lactate-overloaded rats was considered to be similar to low turnover osteomalacia showing decreased trabeculae in secondary spongiosa and increased lamellar osteoid. Furthermore, an iron-positive reaction was detected at the interface between osteoid and mineralized bone. In the bone lesions induced by chronic iron overload, osteoblast recruitment exceeded that of mineralization or, alternatively, the iron within osteoblasts along the trabecular bone suppressed the remodeling and led to an increase in osteoid thickness.
Effects of Exogenous Melatonin—A Review
Authors: Anisimov Vladimir N.
Published: July 2008

The results of studies on the effect of pineal indole hormone melatonin on the life span of mice, rats, fruit flies, and worms are critically reviewed. In mice, long-term administration of melatonin was followed by an increase in their life span in 12 experiments and had no effect in 8 of 20 different experiments. In D. melanogaster , the supplementation of melatonin to the nutrient medium during developmental stages gave contradictory results, but when melatonin was added to food throughout the life span, an increase in the longevity of fruit flies has been observed. Melatonin decreased the survival of C. elegans but increased the clonal life span of planaria Paramecium tertaurelia. Available data suggest antioxidant and atherogenic effects of melatonin. Melatonin alone turned out to be neither toxic nor mutagenic in the Ames test and revealed clastogenic activity in high concentration in the COMET assay. Melatonin inhibits mutagenesis induced by irradiation and by indirect chemical mutagens and inhibits the development of spontaneous and chemical-induced tumors in mice and rats. Further studies and clinical trials are needed to verify that melatonin is both safe and has geroprotector efficacy for humans.
Integrated fluorine-18 fluorodeoxyglucose (18f-fdg) pet/ct compared to standard contrast-enhanced CT for characterization and staging of pulmonary tumors eligible for surgical resection
Authors: Quaia E. , Tona G. , Gelain F. , Lubin E. , Pizzolato R. , Boscolo E. , Bussoli L.
Published: July 2008

Background: Accurate staging is necessary to determine the appropriate therapy in patients with lung cancer. Few studies have compared integrated fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and contrast-enhanced CT in the characterization and staging of pulmonary tumors considered eligible for surgical resection.

Purpose: To compare 18F-FDG PET/CT with standard contrast-enhanced CT for the diagnosis and staging of lung neoplasms eligible for surgical resection.

Material and Methods: Seventy-six consecutive patients (56 male, 20 female; mean age±SD, 63.4±20 years) with 84 pulmonary tumors suspected for malignancy and considered eligible for surgical resection were prospectively enrolled. Seventy-three malignant (65 non-small-cell lung carcinomas, one small-cell lung cancer, two carcinoids, and five metastases) and 11 benign lung tumors (three hamartomas, two sarcoidosis, one amyloidosis, one Wegener granulomatosis, one tuberculosis, and three areas of scarring) were finally diagnosed by histology. Tumor staging was based on the revised American Joint Committee on Cancer.

Results: In lesion characterization, the sensitivity and specificity of 18F-FDG PET/CT versus contrast-enhanced CT were 90% vs. 83% and 18% vs. 63% ( P<0.05, McNemar test), respectively. In nodal staging, the sensitivity and specificity of 18F-FDG PET/CT versus contrast-enhanced CT were 78% vs. 46% and 80% vs. 93% ( P<0.05), respectively.

Conclusion: In patients with lung neoplasms considered eligible for surgical resection, 18F-FDG PET/CT versus contrast-enhanced CT revealed higher sensitivity in nodal staging, but lower specificity both in lesion characterization and nodal staging.
Computed tomography-guided core-needle biopsy specimens demonstrate epidermal growth factor receptor mutations in patients with non-small-cell lung cancer
Authors: Chen C.-M. , Chang J. W.-C. , Cheung Y.-C. , Lin G. , Hsieh J.-J. , Hsu T. , Huang S.-F.
Published: July 2008

Background: Target therapy with a new class of epidermal growth factor receptor (EGFR) inhibitors shows improved clinical response in EGFR gene-mutated lung cancers.

Purpose: To evaluate the use of computed tomography (CT)-guided core-needle biopsy specimens for the assessment of EGFR gene mutation in non-small-cell lung cancer (NSCLC).

Material and Methods: Seventeen (nine males, eight females) patients with advanced NSCLC were enrolled in this study. All patients underwent CT-guided core-needle biopsy of the lung tumor prior to treatment with the EGFR inhibitor gefitinib. There were no life-threatening complications of biopsy. The specimens were sent fresh-frozen for EGFR mutation analysis and histopathological study.

Results: There were 12 (70.6%) EGFR gene mutants and five (29.4%) nonmutants. The objective response rate to gefitinib therapy was 73.3% (11 of 15 patients), with 91.7% (11 of 12 mutants) for the mutant group and 0% for the nonmutant group.

Conclusion: CT-guided core-needle biopsy of advanced NSCLC enables the acquisition of sufficient tissue for EGFR gene mutation analysis.
Sociodemographic determinants of multiple unhealthy behaviours
Authors: Laaksonen Mikko , Prättälä Ritva , Lahelma Eero
Published: July 2008

Background: Although behaviours regarded as unhealthy are widespread, behaving in an unhealthy manner in several respects is relatively uncommon. However, people with multiple unhealthy behaviours exist and their number is larger than expected if the behaviours were not related to each other. The aim of this study was to examine sociodemographic determinants of multiple unhealthy behaviours, with special reference to independent and combined effects of the determinants. Methods : Data on unhealthy behaviours were derived from nationwide surveys among Finnish adults. The mean number of unhealthy behaviours practised on a daily basis and the probability of reporting three or four of these behaviours was examined across sociodemographic groups.

Results: Age, educational level and marital status predicted reporting of three or four unhealthy behaviours. Interactions were observed between education and age in both genders as well as between marital status and age in men and educational level and living area in women. Mean numbers of unhealthy behaviours showed similar patterns to having three or four unhealthy behaviours but few differences between the means were statistically significant and there were no interactions. Conclusion: The influence of each sociodemographic determinant on multiple unhealthy behaviours was relatively independent from the other sociodemographic determinants. As the effect of these determinants tends to be cumulative, engaging in multiple unhealthy behaviours is common in population subgroups with several unfavourable characteristics. In health promotion initiatives special attention should be paid to such population groups and their social circumstances.
Activation of Gαi3 triggers cell migration via regulation of GIV
Authors: Ghosh Pradipta , Garcia-Marcos Mikel , Bornheimer Scott J. , Farquhar Marilyn G.
Published: July 2008

During migration, cells must couple direction sensing to signal transduction and actin remodeling. We previously identified GIV/Girdin as a Gαi3 binding partner. We demonstrate that in mammalian cells Gαi3 controls the functions of GIV during cell migration. We find that Gαi3 preferentially localizes to the leading edge and that cells lacking Gαi3 fail to polarize or migrate. A conformational change induced by association of GIV with Gαi3 promotes Akt-mediated phosphorylation of GIV, resulting in its redistribution to the plasma membrane. Activation of Gαi3 serves as a molecular switch that triggers dissociation of Gβγ and GIV from the Gi3–GIV complex, thereby promoting cell migration by enhancing Akt signaling and actin remodeling. Gαi3–GIV coupling is essential for cell migration during wound healing, macrophage chemotaxis, and tumor cell migration, indicating that the Gαi3–GIV switch serves to link direction sensing from different families of chemotactic receptors to formation of the leading edge during cell migration.