bluuebunny/crossref_metadata_2025 huggingface dataset:
Iustitia in Caritate: Miscellanea Di Studi in Onore di Velasio de Paolis
Authors: Ombres OP Robert
Published: February 2007

Aspects of Anglican Identity COLIN PODMORE
Church House Publishing, London, 2005, 208 pp (paperback £14.99)
ISBN 0715140744
Identity and Adornment in the Third-millennium bc Mesopotamian ‘Royal Cemetery’ at Ur
Authors: Gansell Amy Rebecca
Published: February 2007

This article presents a study of the deposition of jewellery on bodies in the third-millennium bc Mesopotamian ‘Royal Cemetery’ at Ur. Four assemblages of adornments are identified and evaluated in relation to burial type, gender, age, privilege, and behavioural role. Aspects of the social and ritual identities of the dead are then interpreted through adornment. While the historic definition of the interred community and the precise nature of their practices are open to speculation, this study begins to clarify dynamics of group and individual identity at this site of human sacrifice.
Serious Mortality: the Date of the Fussell's Lodge Long Barrow
Authors: Wysocki Michael , Bayliss Alex , Whittle Alasdair
Published: February 2007

Twenty-seven radiocarbon results are now available from the Fussell's Lodge long barrow, and are presented within an interpretive Bayesian statistical framework. Three alternative archaeological interpretations of the sequence are given, each with a separate Bayesian model. It is hard to decide between these, though we prefer the third. In the first (following the excavator), the construction is a unitary one, and the human remains included are by definition already old. In the second, the primary mortuary structure is seen as having two phases, and is set within a timber enclosure; these are later closed by the construction of a long barrow. In that model of the sequence, deposition began in the thirty-eighth century cal. bc and the mortuary structure was extended probably in the 3660s–3650s cal. bc; the long barrow was probably built in the 3630s–3620s cal. bc; ancestral remains are not in question; and the use of the primary structure may have lasted for a century or so. In the third, preferred model, a variant of the second, we envisage the inclusion of some ancestral remains in the primary mortuary structure alongside fresh remains. This provides different estimates of the date of initial construction (probably in the last quarter of the thirty-eighth century cal. bc or the first half of the thirty-seventh century cal. bc) and the duration of primary use, but agrees in setting the date of the long barrow probably in the 3630s–3620s cal. bc. These results are discussed in relation to the development and meanings of long barrows at both national and local scales.
Fertilizability and chromosomal integrity of frozen-thawed Bryde's whale (Balaenoptera edeni) spermatozoa intracytoplasmically injected into mouse oocytes
Authors: Watanabe H. , Tateno H. , Kusakabe H. , Matsuoka T. , Kamiguchi Y. , Fujise Y. , Ishikawa H. , Ohsumi S. , Fukui Y.
Published: February 2007

Prior to attempting thein vitroproduction of embryos in the Bryde's whale (Balaenoputera edeni), we investigated whether spermatozoa can retain the capacity for oocyte activation and pronucleus formation as well as chromosomal integrity under cryopreservation by using intracytoplasmic sperm injection (ICSI) into mouse oocytes. Regardless of motility and viability, whale spermatozoa efficiently led to the activation of mouse oocytes (90.3–97.4%), and sperm nuclei successfully transformed into male pronucleus within activated ooplasm (87.2–93.6%). Chromosome analysis at the first cleavage metaphase (M) of the hybrid zygotes revealed that a majority (95.2%) of motile spermatozoa had the normal chromosome complement, while the percentage of chromosomal normality was significantly reduced to 63.5% in immotile spermatozoa and 50.0% in dead spermatozoa due to the increase in structural chromosome aberrations. This is the first report showing that motile Bryde's whale spermatozoa are competent to support embryonic development.
Ovine (Ovis aries) blastula from an in vitro production system and isolation of primary embryonic stem cells
Authors: Zhu S-X. , Sun Z. , Zhang J-P.
Published: February 2007

Livestock embryo production in in vitro systems has been highlighted due to the emergence of interest in embryo stem cells (ESC). ESC potency and their wide potential applications have been recognized in medicine, fundamental research fields and commercial markets due to ESC totipotency or pluripotency and self-renewal. Ovine ESC probably is a useful technical platform for transgenic livestock and animal cloning, but ESC lines have not yet been founded because of difficulties in ESC isolation and the lack of blastula materials. We have established an IVP (in vitro production) system in our laboratory, including in vitro maturation, in vitro fertilization and in vitro culture, to produce sheep blastula using fresh ovaries and testes collected from livestock production. This system can achieve rates of mature eggs and blastulas of 65 and 50% respectively, and can provide enough blastulas for ICM (inner cell mass) isolation. Furthermore, ESC-like clones were isolated from the ICM on ovine embryonic fibroblast (OEF) feeder cells and in ES-DMEM supplemented with the cell factors LIF and SCF, and these survived to the third passage, which was primarily identified by AKP staining and morphology. This work provides a basis for ovine ESC isolation and foundation of ESC lines.
A finite-state morphological grammar of Hebrew
Authors: YONA S. , WINTNER S.
Published: February 2007

Morphological analysis is a crucial component of several natural language processing tasks, especially for languages with a highly productive morphology, where stipulating a full lexicon of surface forms is not feasible. This paper describes HAMSAH (HAifa Morphological System for Analyzing Hebrew), a morphological processor for Modern Hebrew, based on finite-state linguistically motivated rules and a broad coverage lexicon. The set of rules comprehensively covers the morphological, morpho-phonological and orthographic phenomena that are observable in contemporary Hebrew texts. Reliance on finite-state technology facilitates the construction of a highly efficient, completely bidirectional system for analysis and generation.
1D hybrid simulations of planetary ion‐pickup: Energy partition
Authors: Cowee M. M. , Winske D. , Russell C. T. , Strangeway R. J.
Published: February 2007

Ion pickup in planetary environments results in unstable newborn ion populations with sufficient free energy to generate electromagnetic plasma waves. Estimates of the SO2+ pickup rates near the Jovian moon, Io, based on ion cyclotron wave observations assumed that the newborn pickup ions lose 50% of their energy to wave growth. Using one‐dimensional initial‐value hybrid simulation, we test this assumption and predict that at most ∼25% of the energy of the newborn ion population is lost to wave growth for conditions at Io. This energy is lost over >1400 SO2+ gyroperiods (∼1 hour), with the majority lost after saturation of the instability. Thus the saturation wave energy is low, at <3% of the newborn ion population's energy. In contrast, newborn ions in cometary environments saturate at substantially higher wave energies (∼30% of the newborn ion population's energy), but do not continue to lose energy afterwards.
Investigation of the immunosuppressive activity of artemether on T‐cell activation and proliferation
Authors: Wang J‐X , Tang W , Shi L‐P , Wan J , Zhou R , Ni J , Fu Y‐F , Yang Y‐F , Li Y , Zuo J‐P
Published: February 2007

Background and purpose:

Artemisinin and its derivatives exhibit potent immunosuppressive activity. The purpose of the current study was to examine the immunosuppressive activity of artemether directly on T lymphocytes and to explore its potential mode of action.

Experimental approach:

In vitro, T‐cell proliferation was measured using [3H]‐thymidine incorporation assay in cells stimulated with ConA, alloantigen and anti‐CD3 antibody. CFSE‐labeled cell division and cell cycle distribution were monitored by flow cytometry. In vivo, the effects of artemether were evaluated in delayed‐type hypersensitivity (DTH) and purified T‐cell responses to ovalbumin in ovalbumin‐immunized mice. The activation of extracellular signal‐regulated kinase1/2 (ERK1/2) and Raf1 were assessed by Western blot analysis and the activation of Ras was tested in pull‐down assays.

Key results:

We show that, in vitro, artemether suppressed ConA‐ or alloantigen‐induced splenocyte proliferation, influenced production of the cytokines IL‐2 and IFN‐γ and inhibited cell cycle progression through the G0/G1 transition. In vivo, administration of artemether attenuated CD4 T‐cell‐mediated DTH reaction, and suppressed antigen‐specific T‐cell response in immunized mice. Further experiments showed that, treatment with artemether impaired both antigen‐ and anti‐CD3‐induced phosphorylation of ERK. In primary T cells, artemether profoundly inhibited anti‐CD3‐induced phosphorylation of Raf1 and activation of Ras.

Conclusions and implications:

This study provided experimental evidence of the immunosuppressive effects of artemether directly on T cells both in vitro and in vivo. Its immunosuppressive mechanism involved inhibition of the activation of the Ras‐Raf1‐ERK1/2 protein kinase cascade in T cells.

British Journal of Pharmacology (2007) 150, 652–661. doi:10.1038/sj.bjp.0707137
Magnetic structures in Pr6Ni2Si3 and Pr5Ni2Si3
Authors: Jiles D. C. , Song S. H.
Published: February 2007

The temperature dependence of magnetization in Pr6Ni2Si3 and Pr5Ni2Si3 compounds has been studied with the objective of providing a theoretical understanding of the behavior of the magnetic properties of the material. The ternary Pr–Ni–Si system contains the homologous series of compounds R(n+2)(n+1)Nin(n−1)+2Sin(n+1), where R is a rare earth element which provides a range of materials with different but related structures. The crystal structures and unit cells of Pr6Ni2Si3 (n=2) and Pr5Ni2Si3 (n=3) compounds are closely related consisting of an overall hexagonal structure comprising trigonal columns of atoms, in which the only difference is in the size of the triangular base of the column which depends directly on the chemical composition, specifically the index n. The calculations were based on a nearest neighbor exchange interaction approximation under two kinds of conditions: collinear and noncollinear magnetic structures. The results of these calculations show the Curie temperature, but do not yet predict quantitatively the spin reorientation transition at lower temperatures.
Free energy landscape of receptor-mediated cell adhesion
Authors: Yang Tianyi , Zaman Muhammad H.
Published: February 2007

Receptor-mediated cell adhesion plays a critical role in cell migration, proliferation, signaling, and survival. A number of diseases, including cancer, show a strong correlation between integrin activation and metastasis. A better understanding of cell adhesion is highly desirable for not only therapeutic but also a number of tissue engineering applications. While a number of computational models and experimental studies have addressed the issue of cell adhesion to surfaces, no model or theory has adequately addressed cell adhesion at the molecular level. In this paper, the authors present a thermodynamic model that addresses receptor-mediated cell adhesion at the molecular level. By incorporating the entropic, conformational, solvation, and long- and short-range interactive components of receptors and the extracellular matrix molecules, they are able to predict adhesive free energy as a function of a number of key variables such as surface coverage, interaction distance, molecule size, and solvent conditions. Their method allows them to compute the free energy of adhesion in a multicomponent system where they can simultaneously study adhesion receptors and ligands of different sizes, chemical identities, and conformational properties. The authors’ results not only provide a fundamental understanding of adhesion at the molecular level but also suggest possible strategies for designing novel biomaterials.
A retractable electron emitter for the creation of unperturbed pure electron plasmas
Authors: Berkery John W. , Pedersen Thomas Sunn , Sampedro Luis
Published: February 2007

A retractable electron emitter has been constructed for the creation of unperturbed pure electron plasmas on magnetic surfaces in the Columbia Non-neutral Torus stellarator. The previous method of electron emission using emitters mounted on stationary rods limited the confinement time to 20 ms. A pneumatically driven system that can retract from the magnetic axis to the last closed flux surface in less than 20 ms while filling the surfaces with electrons was designed. The motion of the retractable emitter was modeled with a system of dynamical equations. The measured position versus time of the emitter agrees well with the model and the fastest axis-to-edge retraction was measured to be 20 ms with 40 psig helium gas driving the pneumatic piston.
Probing irradiation induced DNA damage mechanisms using excited state Car-Parrinello molecular dynamics
Authors: Markwick Phineus R. L. , Doltsinis Nikos L. , Schlitter Jürgen
Published: February 2007

Photoinduced proton transfer in the Watson-Crick guanine (G)-cytosine (C) base pair has been studied using Car-Parrinello molecular dynamics (CP-MD). A flexible mechanical constraint acting on all three hydrogen bonds in an unbiased fashion has been devised to explore the free energy profile along the proton transfer coordinate. The lowest barrier has been found for proton transfer from G to C along the central hydrogen bond. The resulting charge transfer excited state lies energetically close to the electronic ground state suggesting the possibility of efficient radiationless decay. It is found that dynamic, finite temperature fluctuations significantly reduce the energy gap between the ground and excited states for this charge transfer product, promoting the internal conversion process. A detailed analysis of the internal degrees of freedom reveals that the energy gap is considerably reduced by out-of-plane molecular vibrations, in particular. Consequently, it appears that considering only the minimum energy path provides an upper-bound estimate of the associated energy gap compared to the full-dimension dynamical reaction coordinate. Furthermore, the first CP-MD simulations of the G-C base pair in liquid water are presented, and the effects of solvation on its electronic structure are analyzed.
Resistance random access memory switching mechanism
Authors: Hsu Sheng T. , Li Tingkai , Awaya Nobuyoshi
Published: February 2007

The properties of Pr0.7Ca0.3MnO3 resistance random access memory devices have been studied in terms of electrical pulse width, pulse polarity, film thickness, resistivity distribution, temperature dependence, device impedance, and dynamics property. Based on the experimental data it is concluded that the resistance increase is due to localization of valence electrons. Voltage pulse induced high density of excessive nonequilibrium electrons near the cathode of the device caused the free valence electrons in transition metal oxide to be localized, the well known Jahn-Teller effect. The voltage pulse induced reduction of resistance is due to delocalization of localized valence electrons by high electric fields.
Passivation effect on the liquid crystal alignment on a-C:H films: A two-step treatment by argon and hydrogen plasma beam scanning
Authors: Wu K. Y. , Chang S. J. , Hwang J. , Lee C.-Y. , Tang H.-C. , Chen C.-W. , Liu C. H. , Wei H. K. , Kou C. S. , Lee C.-D.
Published: February 2007

A two-step treatment by argon (Ar) and hydrogen plasma beam scanning was developed to modify the surface bonds of a hydrogenated amorphous carbon (a-C:H) film on indium tin oxide glass. The modified a-C:H film is an excellent layer for liquid crystal alignment, on which the pretilt angle of a nematic liquid crystal (ZLI-2293) can be adjusted by the two-step scanning treatment. The chemical bonding characteristics of the as-scanned a-C:H films were measured using micro-Raman and x-ray photoemission spectroscopies. The antiparallel cells were filled with the nematic liquid crystal on the as-scanned a-C:H film to measure the pretilt angle. Experimental results indicate that the carbon dangling bonds are generated through a bond-breaking process during the Ar plasma beam scanning step (first step). The hydrogen plasma beam scanning step (second step) can passivate some of the carbon dangling bonds that are generated in the first step. The pretilt angle decreases as the hydrogen plasma beam scanning time increases. The decrease of pretilt angle is due to the formation of C–H bonds that passivate the a-C:H film and limit the formation of C–O bonds in air.
One by one control of the exact number of carbon nanotubes formed by chemical vapor deposition growth: A digital growth process
Authors: Maeda Masatoshi , Kamimura Takafumi , Matsumoto Kazuhiko
Published: February 2007

The authors have succeeded in precisely controlling the exact number of individual bridging carbon nanotubes (CNTs) between two electrodes during thermal chemical vapor deposition (CVD) by counting the number of steps in a monitoring current. A direct current bias was applied between electrodes and the resulting current was monitored during the CVD process. The monitoring current showed several steplike increases, each of which corresponded to bridging by a single CNT. After thermal CVD, the number of bridging CNTs was confirmed by scanning electron microscopy observation and by the electrical breakdown process: the results coincided exactly with the number of current steps monitored during the CVD growth.
Hydrophilic polymer assisted synthesis of room-temperature ferromagnetic Fe3O4 nanochains
Authors: Geng B. Y. , Ma J. Z. , Liu X. W. , Du Q. B. , Kong M. G. , Zhang L. D.
Published: February 2007

One-dimensional chains consisting of crystalline Fe3O4 nanoparticles have been synthesized by using a polyacrylic acid template method. The characterizations of composition, structure, and magnetic property of the chains are performed. The formation mechanism of Fe3O4 nanocrystal chains is proposed to be a polymer template and magnetostatic interaction. In a weak magnetic field, the synthesized nanochains can be reorganized. The as-synthesized nanochains are ferromagnetic at room temperature with lower saturation magnetization and higher coercivity value than those of bulk Fe3O4, which could have potential applications in nanosensors for rapid and sensitive detection of biologic or chemical molecules.
Anchoring gold nanoparticles onto a mica surface by oxygen plasma ashing for sequential nanocomponent assembly
Authors: Takagi Akihiko , Ojima Kaoru , Mikamo Eriko , Matsumoto Takuya , Kawai Tomoji
Published: February 2007

Water-soluble gold nanoparticles were immobilized in both polar (water) and nonpolar (chloroform) liquids on hydrophilic mica surface by oxygen plasma ashing. It is then demonstrated that a DNA with a thiol at an extremity is attached to the immobilized nanoparticles due to the gold-thiol coupling and stretched in the flow direction of the following water rinse. This technique allows a sequential integration of nanoparticles and molecules for various solutions, since the nanoparticles remain on a solid surface rather than dissolve into the solution.
In situ growth regime characterization of cubic GaN using reflection high energy electron diffraction
Authors: Schörmann J. , Potthast S. , As D. J. , Lischka K.
Published: February 2007

Cubic GaN layers were grown by plasma-assisted molecular beam epitaxy on 3C-SiC (001) substrates. In situ reflection high energy electron diffraction was used to quantitatively determine the Ga coverage of the GaN surface during growth. Using the intensity of the electron beam as a probe, optimum growth conditions of c-GaN were found when a 1 ML Ga coverage is formed at the surface. 1μm thick c-GaN layers had a minimum surface roughness of 2.5nm when a Ga coverage of 1 ML was established during growth. These samples revealed also a minimum full width at half maximum of the (002) rocking curve.
Metallic phase transition investigated via terahertz time-domain spectroscopy
Authors: Chau K. J. , Rieckmann K. M. , Elezzabi A. Y.
Published: February 2007

Terahertz time-domain spectroscopy is applied to noninvasively investigate the solid-liquid phase transition of metallic gallium (Ga) microparticles over the temperature range from 21.2to38.2°C. Fourier and correlation analyses of the transmitted radiation reveal solid-liquid phase transformation at the melting transition temperature Tm and particle conglomeration at a temperature Tc>Tm.
Shock front instability associated with reflected ions at the perpendicular shock
Authors: Burgess D. , Scholer M.
Published: February 2007

Two-dimensional hybrid simulations of perpendicular, supercritical collisionless shocks are carried out in a geometry with the magnetic field perpendicular to the simulation plane so that parallel propagating fluctuations, such as Alfvén ion cyclotron waves, are suppressed. In terms of average profile and large downstream ion temperature anisotropy, the results resemble those from earlier one-dimensional hybrid simulations, and differ markedly from the results of two-dimensional simulations in which field-parallel propagating fluctuations are included. In addition, we find an instability at the shock front, in which a pattern of magnetic field and density enhancements propagates along the shock surface in the direction of gyration and at the average speed of the ions reflected at the shock. The instability mechanism depends on a spatio-temporal modulation of the fraction of reflected ions over the shock surface. The instability has a threshold that depends on the Mach number and the upstream ion plasma beta, being stabilized by an increased beta and decreased Mach number. In a realistic three-dimensional planar shock, this instability will be only one of several mechanisms contributing to shock front nonstationarity. However, at a three-dimensional curved shock, there is a region where the instability mechanism described may dominate.
Enhanced exchange bias coupling in Fe∕FexMn1−x bilayer by reducing vertical lattice constants
Authors: Lin Wen-Chin , Wang Bo-Yao , Chen Te-Yu , Lin Ling-Chih , Liao Yu-Wen , Pan Wei , Jih Nai-Yeou , Song Ker-Jar , Lin Minn-Tsong
Published: February 2007

The modification of crystalline structure by epitaxial growth on different single crystals induces crucial effects on the exchange bias coupling. Due to the larger lattice constant (a0) of Cu3Au(100) (a0=3.75Å), the vertical lattice constants of Fe∕FexMn1−x films on Cu3Au(100) are much smaller than those of the Fe∕FexMn1−x∕Cu(100) system (Cu: a0=3.61Å). By reducing the vertical lattice constants, the interface exchange bias coupling energy of Fe∕FexMn1−x∕Cu3Au(100) is enhanced to be 0.12–0.18erg∕cm2, which is approximately four times that of the Cu(100) system.
Thermoelectric properties and a device based on n-InSb and p-InAs
Authors: Kaiwa Nakaba , Yamazaki Jun , Matsumoto Takayuki , Saito Masataka , Yamaguchi Shigeo , Yamamoto Atsushi
Published: February 2007

The authors measured the temperature dependence of thermoelectric properties and fabricated a device based on n-InSb and p-InAs bulk crystals. The temperature was ranged from 300to600K. The power factor of n-InSb was over 10−3W∕mK2 over the entire temperature range, and that of p-InAs was nearly 10−3W∕mK2 between 300 and 500K. The open output voltage and the maximum output power of the device were 323mV and 186.0μW, respectively, when the temperature difference was 160K. The authors proposed a device with impedance matching and a capacitor, and found that in the time-averaged region, the output power became a maximum, even when the internal resistance of the device was not equal to the load resistance.
High thermal stability of cross-linked aromatic self-assembled monolayers: Nanopatterning via selective thermal desorption
Authors: Turchanin A. , El-Desawy M. , Gölzhäuser A.
Published: February 2007

An extremely high thermal stability of electron cross-linked biphenyl self-assembled monolayers (SAMs) is reported. The authors found that pristine biphenylthiol SAMs desorb at ∼400K from gold surfaces, which is induced by a breaking of C–S bonds. Despite of a similar bond cleavage in cross-linked SAMs, these remain on the surface up to 1000K, which is the highest temperature reported for a SAM. When patterns of pristine and cross-linked SAMs are heated, the pristine regions desorb, and the cross-linked regions remain on the surface. The authors show that this thermal desorption lithography can be utilized for the fabrication of molecular surface nanostructures.
Process optimization of organic thin-film transistor by ink-jet printing of DH4T on plastic
Authors: Song Dae Ho , Choi Min Hee , Kim June Young , Jang Jin , Kirchmeyer S.
Published: February 2007

The authors studied the organic thin-film transistor (OTFT) with a solution based dihexylquaterthiophene (DH4T) by ink-jet printing. The DH4T with 1.0wt% solution in dichlorobenzene was used for printing of an active layer of OTFTs. In order to obtain a smooth and uniform film of DH4T, the substrate temperature was elevated to 60°C and the printing was performed by an overlapping method. The OTFT on plastic exhibited an on/off current ratio of ∼107, a threshold voltage of −0.25V, a gate voltage swing of 0.45V/decade, and a field-effect mobility of 0.043cm2∕Vs in the saturation region.
Size-induced symmetric enhancement and its relevance to photoluminescence of scheelite CaWO4 nanocrystals
Authors: Li Liping , Su Yiguo , Li Guangshe
Published: February 2007

This work explores size-induced lattice modification and its relevance to photoluminescence properties of scheelite nanostructures. CaWO4 nanocrystals, a prototype scheelite compound, exhibited a lattice expansion and an increased symmetry of structural units with physical dimension reduction, which is in contradiction to the trend previously reported in bulk CaWO4 at high pressures or high temperatures. Lattice variations in CaWO4 nanocrystals are probably due to the “negative pressures” that originated from strong defect dipole interactions on surfaces. The increased structural symmetry along with surface citric modifications produced a significant enhancement in photoluminescence of CaWO4 nanocrystals, indicating a quantitatively structural control over the electronic properties.
Substrate interactions with human ferrochelatase
Authors: Medlock Amy , Swartz Larkin , Dailey Tamara A. , Dailey Harry A. , Lanzilotta William N.
Published: February 2007

Ferrochelatase, the terminal enzyme in heme biosynthesis, catalyzes the insertion of ferrous iron into protoporphyrin IX to form protoheme IX. Human ferrochelatase is a homodimeric, inner mitochondrial membrane-associated enzyme that possesses an essential [2Fe-2S] cluster. In this work, we report the crystal structure of human ferrochelatase with the substrate protoporphyrin IX bound as well as a higher resolution structure of the R115L variant without bound substrate. The data presented reveal that the porphyrin substrate is bound deep within an enclosed pocket. When compared with the location of
N
-methylmesoporphyrin in the
Bacillus subtilis
ferrochelatase, the porphyrin is rotated by ≈100° and is buried an additional 4.5 Å deeper within the active site. The propionate groups of the substrate do not protrude into solvent and are bound in a manner similar to what has been observed in uroporphyrinogen decarboxylase. Furthermore, in the substrate-bound form, the jaws of the active site mouth are closed so that the porphyrin substrate is completely engulfed in the pocket. These data provide insights that will aid in the determination of the mechanism for ferrochelatase.
Transcutaneous β-amyloid immunization reduces cerebral β-amyloid deposits without T cell infiltration and microhemorrhage
Authors: Nikolic William V. , Bai Yun , Obregon Demian , Hou Huayan , Mori Takashi , Zeng Jin , Ehrhart Jared , Shytle R. Douglas , Giunta Brian , Morgan Dave , Town Terrence , Tan Jun
Published: February 2007

Alzheimer's disease (AD) immunotherapy accomplished by vaccination with β-amyloid (Aβ) peptide has proved efficacious in AD mouse models. However, “active” Aβ vaccination strategies for the treatment of cerebral amyloidosis without concurrent induction of detrimental side effects are lacking. We have developed a transcutaneous (t.c.) Aβ vaccination approach and evaluated efficacy and monitored for deleterious side effects, including meningoencephalitis and microhemorrhage, in WT mice and a transgenic mouse model of AD. We demonstrate that t.c. immunization of WT mice with aggregated Aβ
1–42
plus the adjuvant cholera toxin (CT) results in high-titer Aβ antibodies (mainly of the Ig G1 class) and Aβ
1–42
-specific splenocyte immune responses. Confocal microscopy of the t.c. immunization site revealed Langerhans cells in areas of the skin containing the Aβ
1–42
immunogen, suggesting that these unique innate immune cells participate in Aβ
1–42
antigen processing. To evaluate the efficacy of t.c. immunization in reducing cerebral amyloidosis, transgenic PSAPP (APPsw, PSEN1dE9) mice were immunized with aggregated Aβ
1–42
peptide plus CT. Similar to WT mice, PSAPP mice showed high Aβ antibody titers. Most importantly, t.c. immunization with Aβ
1–42
plus CT resulted in significant decreases in cerebral Aβ
1–40,42
levels coincident with increased circulating levels of Aβ
1–40,42
, suggesting brain-to-blood efflux of Aβ. Reduction in cerebral amyloidosis was not associated with deleterious side effects, including brain T cell infiltration or cerebral microhemorrhage. Together, these data suggest that t.c. immunization constitutes an effective and potentially safe treatment strategy for AD.
Potentiation of mammary cancer inhibition by combination of antagonists of growth hormone-releasing hormone with docetaxel
Authors: Buchholz Stefan , Schally Andrew V. , Engel Jörg B. , Hohla Florian , Heinrich Elmar , Koester Frank , Varga Jozsef L. , Halmos Gabor
Published: February 2007

Antagonists of growth hormone-releasing hormone (GHRH) are being developed for the treatment of various cancers. In this study, we investigated the effectiveness of treatment with GHRH antagonist JMR-132 alone and in combination with docetaxel chemotherapy in nude mice bearing MX-1 human breast cancers. Specific high-affinity binding sites for GHRH were found on MX-1 tumor membranes using ligand competition assays with
125
I-labeled GHRH antagonist JV-1-42. JMR-132 displaced radiolabeled JV-1-42 with an IC
50
of 0.14 nM, indicating a high affinity of JMR-132 to GHRH receptors. Treatment of nude mice bearing xenografts of MX-1 with JMR-132 at 10 μg per day s.c. for 22 days significantly (
P
< 0.05) inhibited tumor volume by 62.9% and tumor weight by 47.8%. Docetaxel given twice at a dose of 20 mg/kg i.p. significantly reduced tumor volume and weight by 74.1% and 58.6%, respectively. Combination treatment with JMR-132 (10 μg/day) and docetaxel (20 mg/kg i.p.) led to growth arrest of most tumors as shown by an inhibition of tumor volume and weight by 97.7% and 95.6%, respectively (
P
< 0.001). Because no vital cancer cells were detected in some of the excised tumors, a total regression of the tumors was achieved in some cases. Treatment with JMR-132 also strongly reduced the concentration of EGF receptors in MX-1 tumors. Our results demonstrate that GHRH antagonists might provide a therapy for breast cancer and could be combined with docetaxel chemotherapy to enhance the efficacy of treatment.
Peroxisome proliferator–activated receptor (PPAR)α expression in T cells mediates gender differences in development of T cell–mediated autoimmunity
Authors: Dunn Shannon E. , Ousman Shalina S. , Sobel Raymond A. , Zuniga Luis , Baranzini Sergio E. , Youssef Sawsan , Crowell Andrea , Loh John , Oksenberg Jorge , Steinman Lawrence
Published: February 2007

Peroxisome proliferator–activated receptor (PPAR)α is a nuclear receptor that mediates gender differences in lipid metabolism. PPARα also functions to control inflammatory responses by repressing the activity of nuclear factor κB (NF-κB) and c-jun in immune cells. Because PPARα is situated at the crossroads of gender and immune regulation, we hypothesized that this gene may mediate sex differences in the development of T cell–mediated autoimmune disease. We show that PPARα is more abundant in male as compared with female CD4+ cells and that its expression is sensitive to androgen levels. Genetic ablation of this gene selectively removed the brake on NF-κB and c-jun activity in male T lymphocytes, resulting in higher production of interferon γ and tumor necrosis factor (but not interleukin 17), and lower production of T helper (Th)2 cytokines. Upon induction of experimental autoimmune encephalomyelitis, male but not female PPARα−/− mice developed more severe clinical signs that were restricted to the acute phase of disease. These results suggest that males are less prone to develop Th1-mediated autoimmunity because they have higher T cell expression of PPARα.
Local expression of IGF‐1 accelerates muscle regeneration by rapidly modulating inflammatory cytokines and chemokines
Authors: Pelosi Laura , Giacinti Cristina , Nardis Chiara , Borsellino Giovanna , Rizzuto Emanuele , Nicoletti Carmine , Wannenes Francesca , Battistini Luca , Rosenthal Nadia , Molinaro Mario , Musar Antoniò
Published: February 2007

Muscle regeneration following injury is characterized by myonecrosis accompanied by local inflammation, activation of satellite cells, and repair of injured fibers. The resolution of the inflammatory response is necessary to proceed toward muscle repair, since persistence of inflammation often renders the damaged muscle incapable of sustaining efficient muscle regeneration. Here, we show that local expression of a muscle‐restricted insulin‐like growth factor (IGF)‐1 (mIGF‐1) transgene accelerates the regenerative process of injured skeletal muscle, modulating the inflammatory response, and limiting fibrosis. At the molecular level, mIGF‐1 expression significantly down‐regulated proinflammatory cytokines, such as tumor necrosis factor (TNF)‐alpha and interleukin (IL)‐1beta, and modulated the expression of CC chemokines involved in the recruitment of monocytes/macrophages. Analysis of the underlying molecular mechanisms revealed that mIGF‐1 expression modulated key players of inflammatory response, such as macrophage migration inhibitory factor (MIF), high mobility group protein‐1 (HMGB1), and transcription NF‐KB. The rapid restoration of injured mIGF‐1 transgenic muscle was also associated with connective tissue remodeling and a rapid recovery of functional properties. By modulating the inflammatory response and reducing fibrosis, supplemental mIGF‐1 creates a qualitatively different environment for sustaining more efficient muscle regeneration and repair.—Pelosi, L., Giacinti, C., Nardis, C., Borsellino, G., Rizzuto, E., Nicoletti, C., Wannenes, F., Battistini, L., Rosenthal, N., Molinaro, M., Musaro, A. Local expression of IGF‐1 accelerates muscle regeneration by rapidly modulating inflammatory cytokines and chemokines. FASEB J. 21, 1393–1402 (2007)
Spaced Out in Cyberspace? Evaluations of Computer‐Based Information1
Authors: Stephan John , Brockner Joel
Published: February 2007

This study draws on cognitive elaboration theory to examine when and why people evaluate computer‐based information more favorably than information from a less automated source. Half of participants received information from a computer, while half received the identical information from a less automated source. Moreover, participants were induced to be more vs. less involved in the information‐acquisition process. As predicted, participants in the low‐involvement condition evaluated the information more favorably when it came from a computer than from a less automated source. This difference was eliminated in the high‐involvement condition. Further supporting our reasoning, the interaction effect between information source and level of involvement was more pronounced for participants low, rather than high, in need for cognition.
Participation in an Older Adult Heart Health Program Affects Lifestyle Behavior
Authors: Pescatello Linda S. , Delaney Katherine E. , Brennan Patrick , Marschke Lisa , Coble Denis , Belyea Monica , Hasson Scott
Published: February 2007

The Older Adult Heart Health Program (HHP) was a university‐based outreach health screen and education program. The purpose of this study was to determine whether the HHP was associated with lifestyle behavior change among participants. HHP volunteers (n=136) were mostly white (98.5%) women (79.4%) with a mean (± SEM) age of 75.1±0.6 years. A follow‐up survey was sent to the participants' homes 4 months after the HHP inquiring about physician office visitation and adoption of healthy lifestyle behaviors since the HHP. A majority (n=60, 64.5%) of those who completed the survey (n=93, 68.4% response rate) indicated they visited their physician after the HHP. A greater percentage of survey respondents who visited their physician made lifestyle behavior changes than those who did not, 71.1% vs. 45.4%, respectively (p=0.032). These findings suggest participating in programs such as the HHP prompt physician visitation and behavior change among older adults residing in the community.
Risk Factors for Childhood Obesity in Elementary School‐Age Taiwanese Children
Authors: Chen Jyu‐Lin , Kennedy Christine , Yeh Chao‐Hsing , Kools Susan
Published: February 2007

A cross‐sectional study design was used to examine factors that contribute to high relative weight in children in Taiwan. A total sample of 331 Chinese children (ages 7 and 8) and their parents participated in the study. Parents completed questionnaires regarding demographic information, family functioning, parenting styles, physical activity, and dietary intake. Children completed physical fitness tests and questionnaires regarding physical activity, dietary intake, coping strategies, and self‐esteem. The weight‐for‐length index was used to measure children's relative weight. The findings revealed that four variables contributed to higher weight‐for‐length index in boys compared with girls and explained 37.7% of the variance: high maternal body mass index, poor aerobic capacity, healthy family role functioning, and poor family affective responsiveness. Two variables were found to contribute to higher weight‐for‐length index in girls and explained 12.8% of the variance: high household income and high maternal body mass index. Taken together, the results indicate the importance of assessment of children's weight status, maternal weight status, and family functioning as part of routine child health care and the need for developmentally appropriate and gender‐specific approaches to prevent childhood obesity.
Pheochromocytoma Presenting as Heart Failure
Authors: Farroni Jennifer A.
Published: February 2007

Pheochromocytoma is a rare neuroendocrine tumor that secretes high levels of catecholamines and usually causes paroxysmal or sustained hypertension. Various forms of myocardial damage have also been reported, including cardiomyopathy, myocardial infarction, arrhythmias, and angina. When patients present with severe unexplained heart failure, exploring all causes for the source of cardiomyopathy is essential, especially if the cause is reversible. The authors describe the case of a young man who presented to the hospital with acute heart failure who was later diagnosed with a pheochromocytoma.
Immunohistochemical diagnosis of the cagA‐gene genotype of Helicobacter pylori with anti‐East Asian CagA‐specific antibody
Authors: Uchida Tomohisa , Kanada Ryoko , Tsukamoto Yoshiyuki , Hijiya Naoki , Matsuura Keiko , Yano Shinji , Yokoyama Shigeo , Kishida Tetsuko , Kodama Masaaki , Murakami Kazunari , Fujioka Toshio , Moriyama Masatsugu
Published: February 2007

Cytotoxin‐associated antigen A (CagA) protein produced by Helicobacter pylori is proposed to be associated with the pathogenesis of gastric cancer as well as gastritis and gastroduodenal ulcer. It has been reported that the CagA of H. pylori widespread in East Asian countries, where the mortality rate due to gastric cancer is high, is structurally different from that in Western countries, where the gastric cancer mortality rate is relatively low. In this study, we generated an antibody, East Asian CagA‐specific antibody (α‐EAS Ab), which is specifically immunoreactive with East Asian CagA but not with Western CagA. The CagA was immunohistochemically detected at the surface of the gastric mucosa. Interestingly, positive immunoreactivity was also detected in the nucleus and cytoplasm of the infected gastric epithelium, suggesting that CagA may play some pathogenic role in both the nucleus and cytoplasm. Immunohistochemistry of 47 gastric biopsy specimens detected East Asian CagA‐positive H. pylori in 43 cases. In 46 of the 47 cases examined, the data obtained by immunohistochemistry were completely consistent with those obtained by sequencing of the cagA gene of the isolated strain, suggesting that our immunohistochemical method is reliable and useful for diagnosis of the cagA genotype. (Cancer Sci 2007; 98: 521–528)
Tumor‐specific antivascular effect of TZT‐1027 (Soblidotin) elucidated by magnetic resonance imaging and confocal laser scanning microscopy
Authors: Natsume Tsugitaka , Watanabe Junichi , Ogawa Kenji , Yasumura Kazuhiko , Kobayashi Motohiro
Published: February 2007

TZT‐1027 (soblidotin), an antimicrotubule agent, has previously been evaluated in terms of its antivascular effects. In this study, Evans blue perfusion, magnetic resonance imaging (MRI), and confocal laser scanning microscopy (CLSM) were utilized to further elucidate the antivascular effect of TZT‐1027 in female nude mice and rats bearing human breast tumor MX‐1, as well as in female Sprague‐Dawley rats that developed breast tumors induced by dimethylbenz(a)anthracene (DMBA). Therapeutic doses of TZT‐1027 caused nearly complete regression of implanted MX‐1 tumors in nude mice and rats as well as DMBA‐induced tumors in rats. The perfusion in MX‐1 tumor implanted in nude mice was drastically reduced within 30 min after TZT‐1027 administration and was completely inhibited after 6 h or more, although not reduced in normal tissue of kidney. The study using MRI demonstrated that rich blood flow within tumors was remarkably reduced 1–3 h after TZT‐1027 administration both in nude rats bearing MX‐1 tumors and in rats with DMBA‐induced tumors. Furthermore, the study with CLSM in nude mice bearing MX‐1 tumors revealed a disruption of tumor microvessels at 1 h and a destruction of tumor microvessel network at 3 h after TZT‐1027 administration. In contrast, these types of vascular disorders were not observed in heart and kidney. These results suggest that TZT‐1027 specifically damages tumor vasculatures, leading to extensive tumor necrosis within tolerable dose range, and confirms earlier observations that TZT‐1027 exerts a considerable antivascular effect in addition to an excellent cytotoxic effect. (Cancer Sci 2007; 98: 598–604)
Overexpression of caveolin‐1 in a human melanoma cell line results in dispersion of ganglioside GD3 from lipid rafts and alteration of leading edges, leading to attenuation of malignant properties
Authors: Nakashima Hideyuki , Hamamura Kazunori , Houjou Toshiaki , Taguchi Ryo , Yamamoto Noriyuki , Mitsudo Kenji , Tohnai Iwai , Ueda Minoru , Urano Takeshi , Furukawa Keiko , Furukawa Koichi
Published: February 2007

Caveolin‐1 is a component of lipid rafts, and is considered to be a tumor suppressor molecule. However, the mechanisms by which caveolin‐1 functions in cancer cells are not well understood. We generated caveolin‐1 transfectant cells (Cav‐1+ cells) using a human melanoma cell line (SK‐MEL‐28) and investigated the effects of caveolin‐1 overexpression on the GD3‐mediated malignant properties of melanomas. Cav‐1+ cells had decreased cell growth and motility, and reduced phosphorylation levels of p130Cas and paxillin relative to controls. In floatation analysis, although GD3 was mainly localized in glycolipid‐enriched microdomain (GEM)/rafts in control cells, it was dispersed from GEM/rafts in Cav‐1+ cells. Correspondingly, GD3 in Cav‐1+ cells stained uniformly throughout the membrane, whereas control cells showed partial staining of the membrane, probably at the leading edge. p130Cas and paxillin were stained in the leading edges and colocalized with GD3 in the control cells. In contrast, these molecules were diffusely stained and no definite leading edges were detected in Cav‐1+ cells. These results suggest that caveolin‐1 regulates GD3‐mediated malignant signals by altering GD3 distribution and leading edge formation. These results reveal one of the mechanisms by which caveolin‐1 curtails the malignant properties of tumor cells. (Cancer Sci 2007; 98: 512–520)
Do threatened hosts have fewer parasites? A comparative study in primates
Authors: ALTIZER SONIA , NUNN CHARLES L. , LINDENFORS PATRIK
Published: February 2007

Parasites and infectious diseases have become a major concern in conservation biology, in part because they can trigger or accelerate species or population declines. Focusing on primates as a well‐studied host clade, we tested whether the species richness and prevalence of parasites differed between threatened and non‐threatened host species.

We collated data on 386 species of parasites (including viruses, bacteria, protozoa, helminths and arthropods) reported to infect wild populations of 36 threatened and 81 non‐threatened primate species. Analyses controlled for uneven sampling effort and host phylogeny.

Results showed that total parasite species richness was lower among threatened primates, supporting the prediction that small, isolated host populations harbour fewer parasite species. This trend was consistent across three major parasite groups found in primates (helminths, protozoa and viruses). Counter to our predictions, patterns of parasite species richness were independent of parasite transmission mode and the degree of host specificity.

We also examined the prevalence of selected parasite genera among primate sister‐taxa that differed in their ranked threat categories, but found no significant differences in prevalence between threatened and non‐threatened hosts.

This study is the first to demonstrate differences in parasite richness relative to host threat status. Results indicate that human activities and host characteristics that increase the extinction risk of wild animal species may lead simultaneously to the loss of parasites. Lower average parasite richness in threatened host taxa also points to the need for a better understanding of the cascading effects of host biodiversity loss for affiliated parasite species.