bluuebunny/crossref_metadata_2025 huggingface dataset:
Al
As
∕
Ga
As
micropillar cavities with quality factors exceeding 150.000
Authors: Reitzenstein S. , Hofmann C. , Gorbunov A. , Strauß M. , Kwon S. H. , Schneider C. , Löffler A. , Höfling S. , Kamp M. , Forchel A.
Published: June 2007

The authors report on AlAs∕GaAs micropillar cavities with unprecedented quality factors based on high reflectivity distributed Bragg reflectors (DBRs). Due to an increased number of mirror pairs in the DBRs and an optimized etching process record quality (Q) factors up to 165.000 are observed for micropillars with diameters of 4μm. Optical studies reveal a very small ellipticity of 5×10−4 of the pillar cross section. Because of the high Q factors, strong coupling with a vacuum Rabi splitting of 23μeV is observed for micropillars with a diameter of 3μm.
50
∕
50
beam splitter using a one-dimensional metal photonic crystal with parabolalike dispersion
Authors: Shen Linfang , Yang Tzong-Jer , Chau Yuan-Fong
Published: June 2007

The spatial dispersion properties of a one-dimensional metal photonic crystal have been analyzed and five types of dispersion curves have been shown at a normalized frequency less than 1. It is demonstrated that by exploiting a parabolalike dispersion behavior, a metal photonic crystal slab can be used to realize an exactly 50∕50 beam splitter.
Solution-processed organic thin-film phototransistors based on donor/acceptor dyad
Authors: Saragi Tobat P. I. , Fetten Michael , Salbeck Josef
Published: June 2007

The authors report on solution-processed organic thin-film phototransistors based on donor/acceptor dyad. The drain current increases significantly and the switch-on voltage is shifted toward positive bias as the incident light intensity is raised. Photoconductivity and the photovoltaic effect are assumed to be the underlying mechanism. Maximum responsivities of 0.3 and 0.03A∕W were obtained under irradiation at 370nm at an incident light intensity of 1.4μW∕cm2 and irradiation using a tungsten halogen lamp at an incident light intensity of 0.32mW∕cm2, respectively.
Huge positive magnetoresistance of GaAs∕AlGaAs high electron mobility transistor structures at high temperatures
Authors: Wang Chien-Chung , Liang C.-T. , Jiang Yu-Ting , Chen Y. F. , Cooper N. R. , Simmons M. Y. , Ritchie D. A.
Published: June 2007

The authors have performed magnetoresistivity measurements ρxx(B) on GaAs∕AlGaAs high electron mobility transistor (HEMT) structures at high temperatures T. These HEMT structures show huge positive magnetoresistance (MR). For B=±6T, the MR values are >1300% and >200% at T=20 and 80K, respectively. Since a GaAs-based HEMT structure is not susceptible to ferromagnetic noise which appears to represent a fundamental challenge to the scalability of magnetic MR devices to ultrahigh area densities, the experimental results pave the way for the integration of scalable nonmagnetic MR devices with the mature HEMT technology using the same material system.
Fabrication and characterization of Ni∕P(VDF-TrFE) nanoscaled coaxial cables
Authors: Sun Cheng-Liang , Lam Kwo Ho , Chao Chen , Lau Sien Ting , Chan Helen Lai Wa , Guo Shishang , Zhao Xingzhong
Published: June 2007

The authors have prepared poly(vinylidenefluoride-trifluoroethylene) Ni∕P(VDF-TrFE) nanoscaled coaxial cables with Ni nanowires as the cores and P(VDF-TrFE) nanotubes as the shells by a two-step process. Scanning electron microscope and x-ray diffraction measurements revealed the microstructure and crystallinity of the nanocables. Electrical measurements indicated that the nanocables possessed a large specific capacitance (∼10.84pC∕mm2) and ferroelectric remnant polarization (∼10μC∕cm2) due to the composite structure. The distribution of electrical field in the nanostructure was also analyzed.
Ion-assisted precursor dissociation and surface diffusion: Enabling rapid, low-temperature growth of carbon nanofibers
Authors: Denysenko I. , Ostrikov K.
Published: June 2007

Growth kinetics of carbon nanofibers in a hydrocarbon plasma is studied. In addition to gas-phase and surface processes common to chemical vapor deposition, the model includes (unique to plasma-exposed catalyst surfaces) ion-induced dissociation of hydrocarbons, interaction of adsorbed species with incoming hydrogen atoms, and dissociation of hydrocarbon ions. It is shown that at low, nanodevice-friendly process temperatures the nanofibers grow via surface diffusion of carbon adatoms produced on the catalyst particle via ion-induced dissociation of a hydrocarbon precursor. These results explain a lower activation energy of nanofiber growth in a plasma and can be used for the synthesis of other nanoassemblies.
Oscillation of giant tunneling magnetoresistance with respect to tunneling barrier thickness in fully epitaxial Fe∕MgO∕Fe magnetic tunnel junctions
Authors: Matsumoto Rie , Fukushima Akio , Nagahama Taro , Suzuki Yoshishige , Ando Koji , Yuasa Shinji
Published: June 2007

The authors fabricated fully epitaxial Fe(001)∕MgO(001)∕Fe(001) magnetic tunnel junctions (MTJs) with various MgO thicknesses (tMgO) and investigated spin-dependent transport properties. Both the tunneling resistance in the parallel magnetic state (RP) and that in the antiparallel magnetic state (RAP) exhibited short-period oscillations as functions of tMgO with the same period of 3.2Å and different phases. RAP also showed a long-period oscillation with a period of 9.9Å. As a result, tMgO dependence of magnetoresistance is expressed as a superposition of the short- and long-period oscillations. These results provide important clues for understanding the oscillatory tMgO dependence of the tunneling magnetoresistance effect.
Growth behavior of self-formed barrier at Cu–Mn∕SiO2 interface at 250–450°C
Authors: Haneda M. , Iijima J. , Koike J.
Published: June 2007

A diffusion barrier layer was self-formed at the interface between Cu–Mn alloy and tetraethylorthosilicate oxide layers at 250–450°C. No interdiffusion occurred across the self-formed barrier layer during annealing at these temperatures up to 100h. The growth of the barrier layer obeyed a logarithmic law and depended on manganese concentration. The barrier thickness could be controlled in the range of 2–8nm.
Effect of shape anisotropy on threshold current density for current-induced domain wall motion
Authors: Seo Soo-Man , Lee Kyung-Jin , Kim Woojin , Lee Taek-Dong
Published: June 2007

Using micromagnetic simulations, the authors investigate the effects of the shape anisotropy of nanowires on the threshold current density (JC) in the adiabatic limit. It is observed that the type of domain wall significantly affects the dependence of JC on the shape anisotropy. For a transverse wall, JC is proportional to the shape anisotropy, but slightly deviates from the theoretical prediction [G. Tatara and H. Kohno, Phys. Rev. Lett. 92, 086601 (2004)] possibly due to antivortex formation. For a vortex wall, JC is almost independent of the shape anisotropy, as experimentally observed [A. Yamaguchi et al., Jpn. J. Appl. Phys. Part 1 45, 3850 (2006)]. Interestingly, JC and the velocity of the vortex wall at finite temperatures are in good agreement with the experimental values even when the nonadiabatic spin torque is not considered.
Ferroelectric size effects in multiferroic BiFeO3 thin films
Authors: Chu Y. H. , Zhao T. , Cruz M. P. , Zhan Q. , Yang P. L. , Martin L. W. , Huijben M. , Yang C. H. , Zavaliche F. , Zheng H. , Ramesh R.
Published: June 2007

Ferroelectric size effects in multiferroic BiFeO3 have been studied using a host of complementary measurements. The structure of such epitaxial films has been investigated using atomic force microscopy, transmission electron microscopy, and x-ray diffraction. The crystal structure of the films has been identified as a monoclinic phase, which suggests that the polarization direction is close to ⟨111⟩. Such behavior has also been confirmed by piezoforce microscopy measurements. That also reveals that the ferroelectricity is down to at least 2nm.
Quasiparticle effect on electron confinement in Si∕SiO2 quantum-well structures
Authors: Seino K. , Wagner J.-M. , Bechstedt F.
Published: June 2007

Based on ab initio density functional theory the influence of many-body excitation effects on band structures of Si∕SiO2 multilayers with nanometer thickness is studied. The quasiparticle band structures are calculated within the GW approximation to the exchange-correlation self-energy. The resulting fundamental energy gaps are discussed and compared with experimental data.
Surface degradation of magnetic properties in manganite thin films proved with magneto-optical techniques in reflection geometry
Authors: Valencia S. , Gaupp A. , Gudat W. , Abad Ll. , Balcells Ll. , Martínez B.
Published: June 2007

Magneto-optical techniques in reflection geometry turn out to be a very efficient tool to study the surface magnetism due to their sensitivity to magnetic and chemical variations across the sample depth. The existence of a surface layer of about one to five unit cells with strongly depressed magnetic properties, when compared with the rest of the film, in La2∕3Ca1∕3MnO3 thin films is shown. These results strongly support previous theoretical predictions as well as recent findings showing the insulating nature of the topmost layers in these materials.
Structural stability of conducting oxide CaRuO3 at high temperatures
Authors: Ranjan Rajeev , Senyshyn Anatoliy , Vashook Vladimir , Niewa Rainer , Boysen Hans , Frey Friedrich
Published: June 2007

The structure of conducting oxide CaRuO3 has been studied as a function of temperature up to 1300°C by neutron powder diffraction. The structure is found to remain orthorhombic, in space group Pbnm, over the entire temperature range. The structural rigidity is evidenced by the fact that the octahedral tilt angles change by only ∼3° over the entire temperature range. The absence of any structural phase transition in this temperature range and retention of its conducting properties make CaRuO3 more useful compared to its counterpart SrRuO3 with regard to its application as metallic-interface/electrode/substrate material in epitaxial thin film devices to be used at high temperatures.
Ag
Nb
O
3
: A lead-free material with large polarization and electromechanical response
Authors: Fu Desheng , Endo Makoto , Taniguchi Hiroki , Taniyama Tomoyasu , Itoh Mitsuru
Published: June 2007

Polarization measurements reveal that AgNbO3 has an extremely large polarization, which can reach a value of 52μC∕cm2 in polycrystals. Experiments also show that the large internal atom distortion in AgNbO3 is also strongly coupled to the electric field, indicating that high piezoelectric performance can be realized in AgNbO3 system. This finding opens the way to designing a new class of lead-free, high-performance piezoelectric materials based on AgNbO3.
Effect of photoscale, interpreter bias and land type on woody crown-cover estimates from aerial photography
Authors: Fensham R. J. , Fairfax R. J.
Published: June 2007

Woody vegetation cover interpreted from aerial photography requires assessment against field data as the signature of woody vegetation cover may differ between photoscales, vegetation types and photo-interpreters. Measurements of aerial woody cover taken from aerial photography of four different photoscales were compared with a field dataset from Eucalyptus- and Acacia-dominated landscapes of semi-arid Queensland. Two interpreters employed a method that utilises a stereoscope and sample-point graticule for manual quantified measurements of aerial woody cover. Both interpreters generated highly significant models accounting for 77 and 78% of deviance. Photoscale appears to have a consistent effect whereby the signature of woody cover increases as the photoscale decreases from 1 : 25 000 to 1 : 80 000, although the magnitude of this effect was different between interpreters. The results suggest no substantial differences in the shape of models predicting crown cover between Acacia- and Eucalyptus-dominated land types, although the precision of the models was greater for the Acacia (90–91% of residual deviance) than for the Eucalyptus (50–56% of residual deviance) land type. The reduced accuracy in the Eucalyptus land type probably reflects the relatively diffuse crowns of the dominant trees. The models generated for this dataset are within the range of those from other calibration studies employing photography of a range of scales and methodologies. The effect of photoscale is verified between the available studies, but there may also be variations arising from methodological differences or image properties. The present study highlights the influence of photoscale and interpreter bias for assessing woody crown cover from aerial photography. Studies that employ aerial photography should carefully consider potential biases and cater for them by calibrating assessments with field measurements.
Seed polymorphism, dormancy and germination of Salsola affinis (Chenopodiaceae), a dominant desert annual inhabiting the Junggar Basin of Xinjiang, China
Authors: Wei Yan , Dong Ming , Huang Zhen-ying
Published: June 2007

Salsola affinis C.A. Meyer, a dominant annual that primarily occurs in deserts of the Junggar Basin, China, produces three types of utricles that differ in shape, size, colour and size of wings on the fruits. Type A fruits have lignified perianths with long wings and green utricles, and they can easily be dispersed long distances from the mother plant by wind. Type B fruits have lignified perianths with short wings, or no wings, and green utricles, and they are tightly attached to the mother plant. Type C fruits have tepals without wings and yellow utricles, and are also attached tightly to the mother plant. Freshly harvested Type A and Type B seeds (utricles) can germinate at 5–30°C in light or in darkness. Rate and final percentage of germination of Type B seeds are higher than those of Type A seeds. Type C seeds have non-deep physiological dormancy; they germinate slowly and to a low percentage. Four weeks of cold stratification, scarification of covering layers (pericarp and seed coat) and treatment with KNO3 can increase the percentage and rate of seed germination. Utricle polymorphism may allow Salsola affinis to respond to spatial and temporal variations in environmental conditions, thus increasing the chances for survival of this annual species in its harsh desert habitats.
In vitro propagation of Corymbia torelliana × C. citriodora (Myrtaceae) via cytokinin-free node culture
Authors: Trueman S. J. , Richardson D. M.
Published: June 2007

Hybrids between Corymbia torelliana (F.Muell.) K.D.Hill & L.A.S.Johnson and C. citriodora subsp. variegata (F.Muell.) A.R.Bean & M.W.McDonald are used extensively to establish forestry plantations in subtropical Australia. Methods were developed for in vitro seed germination, shoot multiplication and plantlet formation that could be used to establish in vitro and ex vitro clone banks of juvenile Corymbia hybrids. Effects of sodium hypochlorite concentration and exposure time on seed contamination and germination, and effects of cytokinin and auxin concentrations on shoot multiplication and subsequent rooting, were assessed. A two-step surface sterilisation procedure, involving 70% ethanol followed by 1% sodium hypochlorite, provided almost no contamination and at least 88% germination. A novel method of cytokinin-free node culture proved most effective for in vitro propagation. Lateral bud break of primary shoots was difficult to induce by using cytokinin, but primary shoots rooted prolifically, elongated rapidly and produced multiple nodes in the absence of exogenous cytokinin. Further multiplication was obtained either by elongating lateral shoots of nodal explants in cytokinin-free medium or by inducing organogenic callus and axillary shoot proliferation with 2.2 µm benzyladenine. Plantlets were produced using an in vitro soil-less method that provided extensive rooting in sterile propagation mixture. These methods provide a means for simultaneous laboratory storage and field-testing of clones before selection and multiplication of desired genotypes.
Desiccation-induced ultrastructural and biochemical changes in the leaves of the resurrection plant Myrothamnus flabellifolia
Authors: Moore John P. , Hearshaw Meredith , Ravenscroft Neil , Lindsey George G. , Farrant Jill M. , Brandt Wolf F.
Published: June 2007

Light microscopy and low-temperature scanning electron microscopy were used to systematically compare the surface and internal ultrastructures of hydrated and desiccated leaves of the resurrection plant Myrothamnus flabellifolia (Welw.). This revealed that leaf tissue underwent considerable shrinkage and collapse on desiccation but was supported by a framework of vascular and sclerenchymous tissue, which is responsible for the fan-like shape of the leaves. In addition, the leaf ribs were covered with wax and an internal wax cuticle was observed. Biochemical analysis showed that the cyanidin 3-glucoside content increased on desiccation as did the trehalose and sucrose contents. Salt deposits were observed at the apices of desiccated leaves in the proximity of hydathode-like structures. We propose that this might regulate the leaf salt content since decreased intracellular cation concentration was observed in desiccated leaves. We believe that these unique adaptations contribute to the remarkable desiccation-tolerance properties of this plant.
The comparative study of range-wide genetic structure across related, co-distributed rainforest trees reveals contrasting evolutionary histories
Authors: Rossetto Maurizio , Crayn Darren , Ford Andrew , Ridgeway Peter , Rymer Paul
Published: June 2007

Australia’s rainforests exhibit high taxonomic diversity and endemism, yet relatively little is known about patterns of genetic diversity across the flora. Habitat contractions caused by the aridification of the continent and the recent glacial cycles have left discrete genetic signatures on modern-day populations, with the nature of between-population differentiation likely to be influenced by a range of ecological and environmental factors. We used microsatellites to examine range-wide population genetic structure in two congeneric rainforest trees, Elaeocarpus angustifolius and E. largiflorens (Elaeocarpaceae), with similar habitat preference and dispersal potential. The aim was to investigate the relationships between genetic structure, geographic disjunction and morphological differentiation and attempt to clarify the likely evolutionary processes responsible for the observed patterns. We found substantial differences in the amount and type of genetic differentiation within the two co-distributed species. While Elaeocarpus largiflorens revealed an abrupt genetic disjunction front between two subspecies separated by a recognised biogeographic barrier (the Black Mountain Corridor), E. angustifolius showed lower genetic differentiation across a much wider geographic area. Our findings suggest that biogeographic features have different impacts on related species, and that generalisations on evolutionary patterns can be untenable without considering a range of factors. Also, on the basis of the available molecular data, a likely hypothesis is of pre-Pleistocene differentiation followed by reinforcement of differentiation patterns during recent glacial cycles (further studies are needed to conclusively date divergence).
Identification ofMycobacterium aviumpathogenicity island important for macrophage and amoeba infection
Authors: Danelishvili Lia , Wu Martin , Stang Bernadette , Harriff Melanie , Cirillo Stuart , Cirillo Jeffrey , Bildfell Robert , Arbogast Brian , Bermudez Luiz E.
Published: June 2007

The ability to infect macrophages is a common characteristic shared among many mycobacterial species.Mycobacterium avium,Mycobacterium tuberculosis, andMycobacterium kansasiienter macrophages, using the complement receptors CR1, CR3, CR4, and the mannose receptor. To identifyM. aviumgenes and host cell pathways involved in the bacterial uptake by macrophages, we screened aM. aviumtransposon mutant library for the inability to enter macrophages. Uptake-impaired clones were selected. Sequence of sixM. aviumclones identified one gene involved in glycopeptidolipid biosynthesis, one gene encoding the conserved membrane protein homologue to theM. aviumsubsp.paratuberculosis MAP2446cgene and four others belonging to the same region of the chromosome. Analysis of the chromosome region revealed a pathogenicity island inserted between two tRNA sequences with 58% of G+C content versus 69% in theM. aviumgenome. The region is unique forM. aviumand is not present inM. tuberculosisorM. paratuberculosis. Although the mutants did not differ from the WT bacterium regarding the binding to macrophage cell membrane, analysis of macrophage proteins after 1 h infection revealed a deficiency in the mutant to phosphorylate certain proteins on uptake. To understandM. aviuminteraction with two evolutionarily distinct hosts, the mutants were evaluated forAcanthamoeba castellaniiinvasion. The defect in the ability of the mutants to invade both cells was highly similar, suggesting thatM. aviummight have evolved mechanisms that are used to enter amoebas and human macrophages.
Preferential attachment in sexual networks
Authors: de Blasio Birgitte Freiesleben , Svensson Åke , Liljeros Fredrik
Published: June 2007

Many social networks are characterized by a highly uneven distribution of links. The observed skewed distributions have in several cases been attributed to preferential attachment (PA), a tendency among nodes in a growing network to form new links preferentially to nodes with high numbers of links. We test the PA conjecture in sexual contact networks. A maximum likelihood estimation-based expectation–maximization fitting technique is used to model new partners over a 1-year period based on the number of partners in foregoing periods of 2 years, 4 years, and lifetime. The PA model is modified to account for individual heterogeneity in the inclination to find new partners and fitted to Norwegian survey data on heterosexual men and women. Results show evidence of nonrandom, sublinear PA when comparing the growth in 3- to 5-year periods. The potential implications of these findings are discussed.
Interleukin-18 controls energy homeostasis by suppressing appetite and feed efficiency
Authors: Zorrilla Eric P. , Sanchez-Alavez Manuel , Sugama Shuei , Brennan Molly , Fernandez Rosette , Bartfai Tamas , Conti Bruno
Published: June 2007

Circulating levels of the cytokine interleukin 18 (IL-18) are elevated in obesity. Here, we show that administration of IL-18 suppresses appetite, feed efficiency, and weight regain in food-deprived male and female C57BL/6J mice. Intraperitoneal vs. intracerebroventricular routes of IL-18 administration had similar potency and did not promote formation of a conditioned taste aversion (malaise-like behavior). Mice partially (
Il18
+/−
) or totally (
Il18
−/−
) deficient in IL-18 were hyperphagic by young adulthood, with null mutants then becoming overweight by the fifth month of life. Adult
Il18
−/−
mice gained 2- to 3-fold more weight than WT mice per unit energy consumed of low- or high-fat diet. Indirect calorimetry revealed reduced energy expenditure in female
Il18
−/−
mice and increased respiratory exchange ratios [volume of carbon dioxide production (VCO
2
)/volume of oxygen consumption (VO
2
)] in mutants of both sexes. Hyperphagia continued in maturity, with overeating greatest during the mid- to late-dark cycle. Relative white fat-pad mass of
Il18
−/−
mice was ≈2- to 3-fold greater than that of WT, with gonadal, mesenteric, and inguinal depots growing most. The data suggest that endogenous IL-18 signaling modulates food intake, metabolism, and adiposity during adulthood and might be a central or peripheral pharmacological target for controlling energy homeostasis.
Epigenome scans and cancer genome sequencing converge on
WNK2
, a kinase-independent suppressor of cell growth
Authors: Hong Chibo , Moorefield K. Scott , Jun Peter , Aldape Kenneth D. , Kharbanda Samir , Phillips Heidi S. , Costello Joseph F.
Published: June 2007

Human cancer genome and epigenome projects aim to identify new cancer genes and targets for therapy that have been overlooked by conventional approaches. Here we integrated large-scale genomics and epigenomics of 31 human infiltrative gliomas and identified low-frequency deletion and highly recurrent epigenetic silencing of
WNK2
, encoding a putative serine/threonine kinase. Prior cancer genome sequencing projects also identified point mutations in
WNK1–4
, suggesting that
WNK
family genes may have a role in cancers. We observed consistent gene silencing in tumors with dense aberrant methylation across 1.3 kb of the CpG island but more variable expression when the 5′-most region remained unmethylated. This primary tumor data fit well with
WNK2
promoter analysis, which showed strong promoter activity in the 5′-most region, equivalent to the simian virus 40 promoter, but no activity in the 3′ region. WT WNK2 exhibited autophosphorylation and protein kinase activity that was enhanced in cells exposed to hypertonic conditions, similar to WNK1. WNK2 inhibited up to 78% of colony formation by glioma cells but in an unexpectedly kinase-independent manner. The
WNK2
silencing by epigenetic mechanisms was significantly associated (
P
< 0.01) with a known genetic signature of chemosensitive oligodendroglial tumors, 1p and 19q deletion, in two small but independent tumor sets. Taken together, the epigenetic silencing, occasional deletion and point mutation, and functional assessment suggest that aberrations of
WNK2
may contribute to unregulated tumor cell growth. Thus, our integrated genetic and epigenetic approach might be useful to identify genes that are widely relevant to cancer, even when genetic alterations of the locus are infrequent.
An empirical test of the concomitantly variable codon hypothesis
Authors: Merlo Lauren M. F. , Lunzer Mark , Dean Antony M.
Published: June 2007

A central assumption of models of molecular evolution, that each site in a sequence evolves independently of all other sites, lacks empirical support. We investigated the extent to which sites evolve codependently in triosephosphate isomerase (TIM), a ubiquitous glycolytic enzyme conserved in both structure and function. Codependencies among sites, or concomitantly variable codons (covarions), are evident from the reduced function and misfolding of hybrid TIM proteins. Although they exist, we find covarions are relatively rare, and closely related proteins are unlikely to have developed them. However, the potential for covarions increases with genetic distance so that highly divergent proteins may have evolved codependencies between many sites. The evolution of covarions undermines a key assumption in phylogenetics and calls into question our ability to disentangle ancient relationships among major taxonomic groups.
Monomeric G protein-coupled receptor rhodopsin in solution activates its G protein transducin at the diffusion limit
Authors: Ernst Oliver P. , Gramse Verena , Kolbe Michael , Hofmann Klaus Peter , Heck Martin
Published: June 2007

G protein-coupled receptors mediate biological signals by stimulating nucleotide exchange in heterotrimeric G proteins (Gαβγ). Receptor dimers have been proposed as the functional unit responsible for catalytic interaction with Gαβγ. To investigate whether a G protein-coupled receptor monomer can activate Gαβγ, we used the retinal photoreceptor rhodopsin and its cognate G protein transducin (G
t
) to determine the stoichiometry of rhodopsin/G
t
binding and the rate of catalyzed nucleotide exchange in G
t
. Purified rhodopsin was prepared in dodecyl maltoside detergent solution. Rhodopsin was monomeric as concluded from fluorescence resonance energy transfer, copurification studies with fluorescent labeled and unlabeled rhodopsin, size exclusion chromatography, and multiangle laser light scattering. A 1:1 complex between light-activated rhodopsin and G
t
was found in the elution profiles, and one molecule of GDP was released upon complex formation. Analysis of the speed of catalytic rhodopsin/G
t
interaction yielded a maximum of ≈50 G
t
molecules per second and molecule of activated rhodopsin. The bimolecular rate constant is close to the diffusion limit in the diluted system. The results show that the interaction of G
t
with an activated rhodopsin monomer is sufficient for fully functional G
t
activation. Although the activation rate in solution is at the physically possible limit, the rate in the native membrane is still 10-fold higher. This is likely attributable to the precise orientation of the G protein to the membrane surface, which enables a fast docking process preceding the actual activation step. Whether docking in membranes involves the formation of rhodopsin dimers or oligomers remains to be elucidated.
Placebo effects on human μ-opioid activity during pain
Authors: Wager Tor D. , Scott David J. , Zubieta Jon-Kar
Published: June 2007

Placebo-induced expectancies have been shown to decrease pain in a manner reversible by opioid antagonists, but little is known about the central brain mechanisms of opioid release during placebo treatment. This study examined placebo effects in pain by using positron-emission tomography with [
11
C]carfentanil, which measures regional μ-opioid receptor availability
in vivo
. Noxious thermal stimulation was applied at the same temperature for placebo and control conditions. Placebo treatment affected endogenous opioid activity in a number of predicted μ-opioid receptor-rich regions that play central roles in pain and affect, including periaqueductal gray and nearby dorsal raphe and nucleus cuneiformis, amygdala, orbitofrontal cortex, insula, rostral anterior cingulate, and lateral prefrontal cortex. These regions appeared to be subdivided into two sets, one showing placebo-induced opioid activation specific to noxious heat and the other showing placebo-induced opioid reduction during warm stimulation in anticipation of pain. These findings suggest that a mechanism of placebo analgesia is the potentiation of endogenous opioid responses to noxious stimuli. Opioid activity in many of these regions was correlated with placebo effects in reported pain. Connectivity analyses on individual differences in endogenous opioid system activity revealed that placebo treatment increased functional connectivity between the periaqueductal gray and rostral anterior cingulate, as hypothesized
a priori
, and also increased connectivity among a number of limbic and prefrontal regions, suggesting increased functional integration of opioid responses. Overall, the results suggest that endogenous opioid release in core affective brain regions is an integral part of the mechanism whereby expectancies regulate affective and nociceptive circuits.
The lipofuscin fluorophore A2E perturbs cholesterol metabolism in retinal pigment epithelial cells
Authors: Lakkaraju Aparna , Finnemann Silvia C. , Rodriguez-Boulan Enrique
Published: June 2007

Proteins involved in cholesterol trafficking are known to contribute to the pathogenesis of atherosclerosis and Alzheimer's disease. Allelic variants in the cholesterol transporters apolipoprotein E and ATP-binding cassette protein A1 (ABCA1) have recently been associated with susceptibility to age-related macular degeneration (AMD). Histopathological analyses of eyes with AMD demonstrate the presence of cholesterol and cholesteryl ester deposits beneath the retinal pigment epithelium (RPE), implicating abnormal cholesterol trafficking in disease progression. Here, we show that A2E, a quaternary amine and retinoid by-product of the visual cycle, causes the accumulation of free and esterified cholesterol in RPE cells. The mechanism involves neither generalized alterations in late endosomal/lysosomal pH nor a direct inhibition of acid lipase activity. Rather, A2E prevents cholesterol efflux from these organelles, which in turn indirectly inhibits acid lipase, leading to a subsequent accumulation of cholesteryl esters. Transcriptional activation of the ABCA1 cholesterol transporter by agonists of the liver X receptor/peroxisome proliferator-activated receptor pathway relieves the A2E-induced block on cholesterol efflux and restores cholesterol homeostasis in RPE cells. Our data also demonstrate that A2E, which is a cone-shaped lipid, increases the chemical activity and displacement of cholesterol from model membranes, providing a biophysical mechanism for cholesterol sequestration in A2E-loaded cells. Although endogenously produced A2E in the RPE has been associated with macular degeneration, the precise mechanisms are unclear. Our results provide direct evidence that A2E causes aberrant cholesterol metabolism in RPE cells which could likely contribute to AMD progression.
Carbon nanotube-based synthetic gecko tapes
Authors: Ge Liehui , Sethi Sunny , Ci Lijie , Ajayan Pulickel M. , Dhinojwala Ali
Published: June 2007

We have developed a synthetic gecko tape by transferring micropatterned carbon nanotube arrays onto flexible polymer tape based on the hierarchical structure found on the foot of a gecko lizard. The gecko tape can support a shear stress (36 N/cm2) nearly four times higher than the gecko foot and sticks to a variety of surfaces, including Teflon. Both the micrometer-size setae (replicated by nanotube bundles) and nanometer-size spatulas (individual nanotubes) are necessary to achieve macroscopic shear adhesion and to translate the weak van der Waals interactions into high shear forces. We have demonstrated for the first time a macroscopic flexible patch that can be used repeatedly with peeling and adhesive properties better than the natural gecko foot. The carbon nanotube-based tape offers an excellent synthetic option as a dry conductive reversible adhesive in microelectronics, robotics, and space applications.
Roles of DNA topoisomerase II isozymes in chemotherapy and secondary malignancies
Authors: Azarova Anna M. , Lyu Yi Lisa , Lin Chao-Po , Tsai Yuan-Chin , Lau Johnson Yiu-Nam , Wang James C. , Liu Leroy F.
Published: June 2007

Drugs that target DNA topoisomerase II (Top2), including etoposide (VP-16), doxorubicin, and mitoxantrone, are among the most effective anticancer drugs in clinical use. However, Top2-based chemotherapy has been associated with higher incidences of secondary malignancies, notably the development of acute myeloid leukemia in VP-16-treated patients. This association is suggestive of a link between carcinogenesis and Top2-mediated DNA damage. We show here that VP-16-induced carcinogenesis involves mainly the β rather than the α isozyme of Top2. In a mouse skin carcinogenesis model, the incidence of VP-16-induced melanomas in the skin of 7,12-dimethylbenz[
a
]anthracene-treated mice is found to be significantly higher in TOP2β
+
than in skin-specific
top2
β-knockout mice. Furthermore, VP-16-induced DNA sequence rearrangements and double-strand breaks (DSBs) are found to be Top2β-dependent and preventable by cotreatment with a proteasome inhibitor, suggesting the importance of proteasomal degradation of the Top2β-DNA cleavage complexes in VP-16-induced DNA sequence rearrangements. VP-16 cytotoxicity in transformed cells expressing both Top2 isozymes is, however, found to be primarily Top2α-dependent. These results point to the importance of developing Top2α-specific anticancer drugs for effective chemotherapy without the development of treatment-related secondary malignancies.
The coactivator host cell factor-1 mediates Set1 and MLL1 H3K4 trimethylation at herpesvirus immediate early promoters for initiation of infection
Authors: Narayanan Aarthi , Ruyechan William T. , Kristie Thomas M.
Published: June 2007

Originally identified as an essential component of the herpes simplex virus immediate early (IE) gene enhancer complex, the transcriptional coactivator host cell factor-1 (HCF-1) has been implicated in a broad range of cellular regulatory circuits. The protein mediates activation through multiple interactions with transcriptional activators, coactivators, and chromatin remodeling complexes. However, the mechanisms involved in HCF-1-dependent transcriptional stimulation were undefined. By using a minimal HCF-1-dependent promoter and a model activator, the varicella zoster IE62 protein, it was determined that HCF-1 was not required for the assembly of the RNAPII basal complex, which depended solely on IE62 in conjunction with the cellular factor Sp1. In contrast, HCF-1 was required for recruitment of the histone methyltransferases Set1 and MLL1 (mixed-lineage leukemia 1), leading to histone H3K4 trimethylation and transcriptional activation. Similarly, in a varicella zoster virus lytic infection, HCF-1, Set1, and MLL1 were recruited to the viral genomic IE promoter, suggesting an essential role for HCF-1 in chromatin modification and remodeling during initiation of lytic infection. The results indicate that one biological rationale for the incorporation of the viral IE activators in the viral particle is to recruit HCF-1/histone methyltransferase complexes and promote assembly of the viral IE gene promoters into transcriptionally active chromatin. These studies also contribute to the model whereby the induced nuclear transport of HCF-1 in sensory neurons may be critical to the reactivation of latent herpesviruses by promoting the activation of chromatin modifications.
Wayward Modeling: Population Genetics and Natural Selection
Authors: Glymour Bruce
Published: June 2007

Since the introduction of mathematical population genetics, its machinery has shaped our fundamental understanding of natural selection. Selection is taken to occur when differential fitnesses produce differential rates of reproductive success, where fitnesses are understood as parameters in a population genetics model. To understand selection is to understand what these parameter values measure and how differences in them lead to frequency changes. I argue that this traditional view is mistaken. The descriptions of natural selection rendered by population genetics models are in general neither predictive nor explanatory and introduce avoidable conceptual confusions. I conclude that a correct understanding of natural selection requires explicitly causal models of reproductive success.
Discussion: Malament on Time Reversal
Authors: Leeds Stephen
Published: June 2007

David Malament has recently responded to David Albert's argument that classical electrodynamics is not time-reversal invariant by introducing a novel conception of time reversal, which supports the conventional view that under time reversal the magnetic field changes sign but the electric field remains unchanged. I will argue here that Malament's transformation has both passive and active versions. I will claim that the passive version is not relevant to Albert's argument, and the active version does not lead to the conventional transformation.
Realism versus Instrumentalism in a New Statistical Framework
Authors: Mikkelson Gregory M.
Published: June 2007

In this paper, I offer a new defense of scientific realism, tailored for the Akaikean paradigm of statistical hypothesis testing. After proposing definitions of verisimilitude and predictive success, I use computer simulations to show how the latter depends on the former, even in the kind of case featured in a recent argument for instrumentalism.
Unpacking “For Reasons of Symmetry”: Two Categories of Symmetry Arguments
Authors: Hon Giora , Goldstein Bernard R.
Published: June 2007

Hermann Weyl succeeded in presenting a consistent overarching analysis that accounts for symmetry in (1) material artifacts, (2) natural phenomena, and (3) physical theories. Weyl showed that group theory is the underlying mathematical structure for symmetry in all three domains. But in this study Weyl did not include appeals to symmetry arguments which, for example, Einstein expressed as “for reasons of symmetry” (wegen der Symmetrie; aus Symmetriegründen). An argument typically takes the form of a set of premises and rules of inference that lead to a conclusion. Symmetry may enter an argument both in the premises and the rules of inference, and the resulting conclusion may also exhibit symmetrical properties. Taking our cue from Pierre Curie, we distinguish two categories of symmetry arguments, axiomatic and heuristic; they will be defined and then illustrated by historical cases.
How to Split Concepts: A Reply to Piccinini and Scott
Authors: Machery Edouard
Published: June 2007

In “Concepts Are Not a Natural Kind” (2005), I argued that the notion of concept in psychology and in neuropsychology fails to pick out a natural kind. Piccinini and Scott (2006, in this issue) have criticized the argument I used to support this conclusion. They also proposed two alternative arguments for a similar conclusion. In this reply, I rebut Piccinini and Scott's main objection against the argument proposed in “Concepts Are Not a Natural Kind.” Moreover, I show that the two alternative arguments developed by Piccinini and Scott are not promising for supporting the conclusion that concepts are not a natural kind.
Open access and accuracy: author‐archived manuscripts vs. published articles
Authors: GOODMAN David , DOWSON Sarah , YAREMCHUK Jean
Published: June 2007

Some approaches to open access (OA) use authors' manuscript copies for the OA version, in the form accepted after peer review but prior to full editing. Advocates of such approaches are certain that these versions differ only trivially from the publishers' versions; many of those who oppose them are equally certain that there can be major discrepancies. In a pilot study, we have examined the actual differences in a small number of such article pairs in the social sciences and in biology. Using an operational classification of the extent of error, we have determined that neither pronouncement is likely to be correct. We found numerous small differences that affect readability; we also found a low frequency of potentially confusing errors, but sometimes it was the publisher's and sometimes the manuscript version that was more accurate. In two cases errors introduced by the publisher omit technical details that are necessary to evaluate the validity of the conclusions. However, we found no error that actually affected the validity of the data or results. Interestingly, we did find problems with the stability of the document locations on authors' sites, and, in some cases, with their disappearance from PubMed Central after initial placement there.
A medical journal's beta site: experimentation at NEJM
Authors: ANDERSON Kent R. , NUGENT Jean
Published: June 2007

When continuous development becomes the norm on the social web, finding a way to put forward new development ideas to your audience and get their feedback at an early stage is the natural result. This article discusses how one major medical journal created a ‘beta’ site to support new online development and gather user feedback, speeding development initiatives and creating intrinsic value in the experimental environment. The goals of the site, organization of the teams, and practical and brand benefits are discussed.
Improving peer review with CARMA
Authors: CARMI Ran , KOCH Christof
Published: June 2007

We propose to test and improve the quality of peer review through CARMA (Community‐based Assessment of Review Materials): an online repository of review materials that will include all intermediate versions of published manuscripts, associated reviews, and author replies to reviewer comments. CARMA would add the content of reviews to the public scientific record without compromising the anonymity of reviewers. The benefits to the relevant stakeholders are as follows:

• For readers, CARMA would reveal the actual impact of peer review on scholarly manuscripts;

• CARMA would encourage reviewers to provide thorough evaluations without jeopardizing their candor;

• Editors could utilize CARMA for quality assurance by soliciting ratings of reviews from their readership;

• For publishers, implementing CARMA would incur minimal costs, and could increase revenues.

Whatever the present quality of peer review, making this process more transparent would be in the best interest of meritocratic scholars and society at large.
Bulleyaconitine A Isolated from Aconitum Plant Displays Long-acting Local Anesthetic Properties In Vitro and In Vivo
Authors: Wang Chi-Fei , Gerner Peter , Wang Sho-Ya , Wang Ging Kuo
Published: June 2007

Background:

Bulleyaconitine A (BLA) is an active ingredient of Aconitum bulleyanum plants. BLA has been approved for the treatment of chronic pain and rheumatoid arthritis in China, but its underlying mechanism remains unclear.

Methods:

The authors examined (1) the effects of BLA on neuronal voltage-gated Na+ channels in vitro under the whole cell patch clamp configuration and (2) the sensory and motor functions of rat sciatic nerve after single BLA injections in vivo.

Results:

BLA at 10 μm did not affect neuronal Na+ currents in clonal GH3 cells when stimulated infrequently to +50 mV. When stimulated at 2 Hz for 1,000 pulses (+50 mV for 4 ms), BLA reduced the peak Na+ currents by more than 90%. This use-dependent reduction of Na+ currents by BLA reversed little after washing. Single injections of BLA (0.2 ml at 0.375 mm) into the rat sciatic notch not only blocked sensory and motor functions of the sciatic nerve but also induced hyperexcitability, followed by sedation, arrhythmia, and respiratory distress. When BLA at 0.375 mm was coinjected with 2% lidocaine (approximately 80 mm) or epinephrine (1:100,000) to reduce drug absorption by the bloodstream, the sensory and motor functions of the sciatic nerve remained fully blocked for approximately 4 h and regressed completely after approximately 7 h, with minimal systemic effects.

Conclusions:

BLA reduces neuronal Na+ currents strongly at +50 mV in a use-dependent manner. When coinjected with lidocaine or epinephrine, BLA elicits prolonged block of both motor and sensory functions in rats with minimal adverse effects.
Contribution of Calcium Channel Subtypes to the Intracellular Calcium Signal in Sensory Neurons
Authors: Fuchs Andreas , Rigaud Marcel , Sarantopoulos Constantine D. , Filip Patrick , Hogan Quinn H.
Published: June 2007

Background:

Although the activation-induced intracellular Ca2+ signal is disrupted by sensory neuron injury, the contribution of specific Ca2+ channel subtypes is unknown.

Methods:

Transients in dissociated rat dorsal root ganglion neurons were recorded using fura-2 microfluorometry. Neurons from control rats and from neuropathic animals after spinal nerve ligation were activated either by elevated bath K+ or by field stimulation. Transients were compared before and after application of selective blockers of voltage-activated Ca2+ channel subtypes.

Results:

Transient amplitude and area were decreased by blockade of the L-type channel, particularly during sustained K+ stimulation. Significant contributions to the Ca2+ transient are attributable to the N-, P/Q-, and R-type channels, especially in small neurons. Results for T-type blockade varied widely between cells. After injury, transients lost sensitivity to N-type and R-type blockers in axotomized small neurons, whereas adjacent small neurons showed decreased responses to blockers of R-type channels. Axotomized large neurons were less sensitive to blockade of N- and P/Q-type channels. After injury, neurons adjacent to axotomy show decreased sensitivity of K+-induced transients to L-type blockade but increased sensitivity during field stimulation.

Conclusions:

All high-voltage–activated Ca2+ current subtypes contribute to Ca2+ transients in sensory neurons, although the L-type channel contributes predominantly during prolonged activation. Injury shifts the relative contribution of various Ca2+ channel subtypes to the intracellular Ca2+ transient induced by neuronal activation. Because this effect is cell-size specific, selective therapies might potentially be devised to differentially alter excitability of nociceptive and low-threshold sensory neurons.