bluuebunny/crossref_metadata_2025 huggingface dataset:
Stanislavsky and Ramacharaka: The Influence of Yoga and Turn-of-the-Century Occultism on the System
Authors: White R. Andrew
Published: April 2006

Fin-de-siècle Russia was a culture replete with interest in the occult, spiritualism, and the religions of the Far East. Curiosity about the mystical infused all tiers of society. Among those influenced by the spiritual was none other than Konstantin Stanislavsky himself, who experienced a personal crisis in which he began to doubt his own ability as an actor. In 1906, he took his now-famous trip to Finland, where he sequestered himself for the summer, examined his artistic life, and began to reconsider seriously his process as an actor. While reflecting on his past artistic work, he began to organize years of notes on acting; and several notions drawn from Eastern mysticism in general and Yoga in particular found their way into his “system.” Although a handful of articles that examine Stanislavsky's use of Yoga have been published in the West, over the past century scholars and teachers have paid little attention to the spiritual facets of Stanislavsky's thinking, focusing instead on the psychological aspects of his work. Given, however, the presence of important Yogic elements in the system at its very inception, a full understanding of Stanislavsky's technique is impossible without knowledge of the intersections between his system and Yoga. Borrowing from Yoga, Stanislavsky offers actors much more than theories about how to be more believable or psychologically realistic in their roles. He adapts specific Yogic exercises in order to help actors transcend the limitations of the physical senses and tap into higher levels of creative consciousness.
Post-Imperial Brecht: Politics and Performance, East and South
Authors: Cole Catherine M.
Published: April 2006

Loren Kruger's Post-Imperial Brecht: Politics and Performance, East and South is an impressive transnational study of Brechtian theatre that is notable for its simultaneous breadth and depth. Kruger takes us far beyond nationalist frameworks, which have long dominated theatre studies. She also avoids the common pitfalls of “global” and comparative studies: sweeping generalizations that flatten historical specificity are not to be found in this book's 400 richly footnoted pages. Post-Imperial Brecht provides a precise and detailed study of the transnational flow of Brecht's ideas and plays between West and East Germany, and between Germany and South Africa, from the 1930s to the present.
Performing Medieval Narrative
Authors: Gertsman Elina
Published: April 2006

The subject of medieval performance has recently come under the scrutiny of scholars from several disciplines—history, art history, religious studies, anthropology, and literature, to name but a few. In the process, “performance” has come to be used rather loosely to signify a number of different concepts. Evelyn Birge Vitz, Nancy Freeman Regalado, and Marilyn Lawrence—the editors of Performing Medieval Narrative—attend to a particular aspect of performance that they define as the confluence of four essential characteristics: the presence of a performer; the action of telling or enacting; a story being told or enacted; and, finally, and most important for the book, the presence of an audience. The volume is broken into four parts, each addressing different aspects of the performance traditions that form an integral part of medieval narratives.
Le mémoire de Mahelot: Mémoire pour la décoration des pièces qui se représentent par les Comédiens du Roi
Authors: Muller David G.
Published: April 2006

The previously available edition of this important source of evidence that documents scenic practice in the public theatres of seventeenth-century France was prepared by Henry Carrington Lancaster in 1920 as Le Mémoire de Mahelot, Laurent et d'autres décorateurs de l'Hôtel de Bourgogne et de la Comédie Française au XVIIesiècle. If only for supplanting Lancaster's with one that will be more widely available for purchase and consultation, Pierre Pasquier's new critical edition would be an excellent resource for theatre scholarship, continuing the transmission of documentary evidence and disciplinary knowledge to future generations. However, in the eighty-six years since Lancaster's edition, the discoveries, methods, and aims of theatre scholarship have changed dramatically, and Pasquier's significant introduction, which encompasses more pages than the presentation of the Mémoire itself, is also an excellent contextual synthesis of historical work that relies on this vital manuscript (BNF, ms. 24330).
The Victorian Marionette Theatre
Authors: Donohue Joseph
Published: April 2006

John McCormick's delightful book The Victorian Marionette Theatre is at once a labor of love, a comprehensive history of a popular art form, an insider's description of the craft by a longtime practitioner, and a nostalgic reminiscence of a nearly forgotten aspect of the Victorian theatre. For all that, the book has an authoritative point of view and a cohesive unity establishing it as one of the most important sources of its kind, complementing George Speaight's more wide-ranging, classic treatment of the subject, The History of the English Puppet Theatre (London: G. G. Harrap, 1955; 2d ed., Carbondale: Southern Illinois University Press, 1990) and McCormick's own companion study, coauthored with Bennie Pratasik, Popular Puppet Theatre in Europe, 1800–1914 (Cambridge: Cambridge University Press, 1998). Those three works anchor a shelf of studies of a major cultural phenomenon.
The Theatre of Suzuki Tadashi
Authors: Iezzi Julie A.
Published: April 2006

Suzuki Tadashi is arguably Japan's best known and most influential contemporary director, and this long-awaited comprehensive study presents a complete picture of his work to date. An eleven-page detailed production chronology at the beginning of the book lists everything from Suzuki's first production at the Waseda Free Stage (Jiyū Butai) Drama Society in 1959, through his opera Vision of Lear for the Third International Theatre Olympics in Moscow in 2001. This who-what-when-where chronological reference allows one to map quickly the arc of Suzuki's career, from his work as a director in Japan and his rise to international recognition in the 1970s, through his roles as International Festival coordinator and actor trainer, to his artistic directorships at the Acting Company Mito (ACM) and later Shizuoka Performing Arts Center (SPAC) in the 1990s.
Submarine hydrothermal venting related to volcanism in the Lesser Antilles: Evidence from ferromanganese precipitates
Authors: Frank M. , Marbler H. , Koschinsky A. , van de Flierdt T. , Klemm V. , Gutjahr M. , Halliday A. N. , Kubik P. W. , Halbach P.
Published: April 2006

Radiogenic isotope compositions (Sr, Nd, Pb, Hf, and Os) of sediment‐hosted seafloor ferromanganese crusts and sediments incrusted with ferromanganese oxyhydroxides from the Lesser Antilles island arc were measured to distinguish between hydrogenous (seawater‐derived) and hydrothermal metal sources. The ages of the precipitates range between recent (last few thousand years) and a few 100 kyr as deduced from 10Be and Co concentrations. Evidence from the presence of bladed todorokite and nontronite, together with the major element and REE composition, suggests that a significant proportion of these sediment‐hosted precipitates formed at relatively low temperatures from a mixture of seawater and hydrothermal fluids associated with island arc volcanism. The radiogenic isotope compositions of all metals mentioned above, except Pb, show large differences in hydrothermal versus hydrogenous contributions over space and time. In contrast to precipitates of high‐temperature fluids which mainly scavenge their REE contents from seawater the crusts of this study show 143Nd/144Nd of up to 0.512817 (ɛNd = +3.5). This is close to the signature of the nearby island arc rocks and far above the expected local seawater ratio of ∼0.51209 (ɛNd = −10.7). These crusts also show high 176Hf/177Hf (up to 0.283102), low 87Sr/86Sr (up to 0.7069), and low 187Os/188Os (up to 0.16) compared with local seawater, as expected from hydrothermal, island‐arc‐derived metal contributions. In contrast, the Pb isotope signatures of the crusts cannot be explained by mixing between seawater and hydrothermal sources. It is suggested that Pb was either removed from the ascending fluids within the sediment column before they reached seawater or the temperatures were too low to leach significant amounts of Pb from the rocks or sediments. External sources such as Saharan dust, particulate inputs from the Orinoco River, or even incongruent release of Pb isotopes from the island arc rock‐derived particles must have contributed to the observed Pb isotope variability. Our results suggest that submarine hydrothermalism originating from intraoceanic island arc volcanism creates distinct geochemical environments for the dispersion of hydrothermal fluids and may be an important mechanism to supply metals of hydrothermal origin to seawater.
Geometrical impact of the San Andreas Fault on stress and seismicity in California
Authors: Li Qingsong , Liu Mian
Published: April 2006

Most large earthquakes in northern and central California clustered along the main trace of the San Andreas Fault (SAF), the North American‐Pacific plate boundary. However, in southern California earthquakes were rather scattered. Here we suggest that such along‐strike variation of seismicity may largely reflect the geometrical impact of the SAF. Using a dynamic finite element model that includes the first‐order geometric features of the SAF, we show that strain partitioning and crustal deformation in California are closely related to the geometry of the SAF. In particular, the Big Bend is shown to reduce slip rate on southern SAF and cause high shear stress and strain energy over a broad region in southern California, and a belt of high strain energy in the Eastern California Shear Zone.
Modeling the permeability evolution of microcracked rocks from elastic wave velocity inversion at elevated isostatic pressure
Authors: Benson Philip , Schubnel Alexandre , Vinciguerra Sergio , Trovato Concetta , Meredith Philip , Young R. Paul
Published: April 2006

A key consequence of the presence of microcracks within rock is their significant influence upon elastic anisotropy and transport properties. Here two rock types (a basalt and a granite) with contrasting microstructures, dominated by microcracks, have been investigated using an advanced experimental arrangement capable of measuring porosity, P wave velocity, S wave velocity, and permeability contemporaneously at effective pressures up to 100 MPa. Using the Kachanov (1994) noninteractive effective medium theory, the measured elastic wave velocities are inverted using a least squares fit, permitting the recovery of the evolution of crack density and aspect ratio with increasing isostatic pressure. Overall, the agreement between measured and predicted velocities is good, with average error less than 0.05 km/s. At larger scales and above the percolation threshold, macroscopic fluid flow also depends on the crack density and aspect ratio. Using the permeability model of Guéguen and Dienes (1989) and the crack density and aspect ratio recovered from the elastic wave velocity inversion, we successfully predict the evolution of permeability with pressure for direct comparison with the laboratory measurements. We also calculate the evolution of the crack porosity with increasing isostatic pressure, on the basis of the calculated crack density, and compare this directly with the experimentally measured porosity. These combined experimental and modeling results illustrate the importance of understanding the details of how rock microstructures change in response to an external stimulus when predicting the simultaneous evolution of rock physical properties.
Continuous tree distribution in China: A comparison of two estimates from Moderate‐Resolution Imaging Spectroradiometer and Landsat data
Authors: Liu Ronggao , Liang Shunlin , Liu Jiyuan , Zhuang Dafang
Published: April 2006

Forest change is a major contributor to changes in carbon stocks and trace gas fluxes between terrestrial and atmospheric layers. This study compares two satellite estimates of percent tree distribution data sets over China. One estimate is from the Chinese National Land Cover Data Set (NLCD) generated by a multiyear national land cover project in China through visual interpretation of Landsat thematic mapper (TM) and the Enhanced Thematic Mapper Plus (ETM+) images primarily acquired in the year 2000. The other estimate is the Moderate‐Resolution Imaging Spectroradiometer (MODIS) standard product (MOD44B) from the same year. The two products reveal some common features, but significant discrepancies exist. Detailed analyses are carried out with different land cover types and over different regions. Comparison results show that the difference of the total tree canopy area for the whole country is 159,000 km2. The pixel counts in the NLCD data set for dense forest are ∼4 times those in the MODIS data set with the reverse holding for sparse forest. Generally, the percent tree canopy area of the NLCD data set is larger in eastern China and lower in the Tibetan plateau margin region. For different land cover types the percentage of tree canopy areas shows a good agreement for evergreen forests but a large discrepancy for deciduous forests. The largest variations are associated with grassland and nonvegetation classes. Regarding the spatial distributions of their differences, Inner Mongolia is the place where both data sets show a diverse result, but Guizhou and Fujian present the least divergence among those provinces with the tree canopy area being more than 20,000 km2.
Evidence for Pacific‐modulated precipitation variability during the late Holocene from the southwestern USA
Authors: Rasmussen Jessica B. T. , Polyak Victor J. , Asmerom Yemane
Published: April 2006

The mechanisms driving late Holocene drought cycles in the western United States are not well known due to the general scarcity of long‐term, high‐resolution, absolutely dateable proxies for precipitation in continental interiors. Here we show that late Holocene precipitation variability in the southwestern United States has been caused by changes in the Pacific Ocean. We present a stalagmite‐based, annually resolved moisture record that indicates large shifts from pluvial to drought conditions alternating with periods of dampened, near‐average precipitation over the last 3000 years. Significant spectral peaks at decadal‐scale (∼20–50, 70–80 year) frequencies likely correspond to modern frequencies of the Pacific Decadal Oscillation or a low‐frequency component of the El Niño‐Southern Oscillation, and are dominant during episodes of large precipitation shifts. Overall pluvial conditions punctuated by severe droughts may have challenged the adaptive capacities of emerging agrarian communities of ancestral Americans.
340 years of atmospheric circulation characteristics reconstructed from an eastern Antarctic Peninsula ice core
Authors: Russell A. , McGregor G. R. , Marshall G. J.
Published: April 2006

Precipitation delivery mechanisms for Dolleman Island (DI), located off the east coast of the Antarctic Peninsula, are investigated using reanalysis and back trajectory data. The Southern Annular Mode (SAM) and ENSO are both shown to influence precipitation delivery and event size. Precipitation delivery variability is compared against the interannual variation of chemical data from two DI ice cores. Nitrate concentration in the cores is strongly linked with the ratio of easterly to westerly back trajectories arriving at DI, as described by a Cross‐Peninsula Index (CPI) defined in this paper. This CPI is used subsequently to reconstruct the atmospheric circulation characteristics for the 340‐year ice core record. The analysis highlights a period of increased easterlies during 1720–1780 and an increase in westerlies for 1950–1980, the latter concomitant with a positive SAM trend and western Peninsula warming. The reconstruction also reveals periods when polynyas may have been present in the Weddell Sea.
Nocturnal odd‐oxygen budget and its implications for ozone loss in the lower troposphere
Authors: Brown S. S. , Neuman J. A. , Ryerson T. B. , Trainer M. , Dubé W. P. , Holloway J. S. , Warneke C. , de Gouw J. A. , Donnelly S. G. , Atlas E. , Matthew B. , Middlebrook A. M. , Peltier R. , Weber R. J. , Stohl A. , Meagher J. F. , Fehsenfeld F. C. , Ravishankara A. R.
Published: April 2006

Nitrogen oxides are important to the regulation of ozone throughout the Earth's atmosphere. Of particular interest for regional air quality is photochemical production and nocturnal destruction of O3 in the lower troposphere in high NOx(=NO + NO2) environments. Nocturnal tropospheric odd oxygen (Ox), defined as O3 + NO2 + 2NO3 + 3N2O5, is used to assess the impact of NOx emissions on nocturnal O3 loss. Recent aircraft measurements of the components of Ox and HNO3 yield a detailed accounting of the nocturnal Ox budget in a regionally polluted environment. The analysis demonstrates the role of NO3 and N2O5 reactions in nocturnal O3 destruction and shows that multiple factors, including timing of NOx emissions, hydrocarbon and aerosol loading, seasonality and atmospheric mixing, govern the impact of NOx emissions on regional‐scale air quality.
Effects of ionization on N-glycylglycine peptide: Influence of intramolecular hydrogen bonds
Authors: Gil Adrià , Bertran Joan , Sodupe Mariona
Published: April 2006

The ionization effects on 28 conformations of N-glycylglycine are analyzed by means of the hybrid B3LYP and the hybrid meta-MPWB1K density functionals and by single-point calculations at the CCSD(T) level of theory. The most favorable process observed corresponds to the ionization of the only neutral conformation that presents a OH⋯NH2 intramolecular hydrogen bond, which leads to CO2 elimination after a spontaneous proton transfer from –COOH to NH2. The remaining neutral structures evolve to 20 different conformations of N-glycylglycine radical cation, which lie about 25–40kcal∕mol higher than the decarboxylated [NH3CH2CONHCH2]+̇⋯[CO2] complex. Structural changes induced by ionization depend on the intramolecular hydrogen bonds of the initial conformation, since they determine the nature of the electron hole formed. In most cases, ionization takes place at the terminal –NH2 and –CO of the amide bond, which produces a strengthening of the peptide bond and the formation of new –NH2⋯OCamide and –NH2⋯OCOH hydrogen bonds. However, if –NH2 and –COamide simultaneously act as proton acceptor in the neutral conformation, ionization is mainly localized at the carboxylic group, which produces a strengthening of the –COOH⋯OCamide bond. Both functionals lead to similar trends and compare well with CCSD(T) results except for a few cases for which B3LYP provides a too delocalized picture of the electron hole and consequently leads to artificial geometry reorganization.
Analysis of metallic impurity density profiles in low collisionality Joint European Torus H-mode and L-mode plasmas
Authors: Puiatti M. E. , Valisa M. , Angioni C. , Garzotti L. , Mantica P. , Mattioli M. , Carraro L. , Coffey I. , Sozzi C. ,   JET-EFDA contributors
Published: April 2006

This paper describes the behavior of nickel in low confinement (L-mode) and high confinement (H-mode) Joint European Torus (JET) discharges [P. J. Lomas, Plasma Phys. Control. Fusion 31, 1481 (1989)] characterized by the application of radio-frequency (rf) power heating and featuring ITER (International Thermonuclear Experimental Reactor) relevant collisionality. The impurity transport is analyzed on the basis of perturbative experiments (laser blow off injection) and is compared with electron heat and deuterium transport. In the JET plasmas analyzed here, ion cyclotron resonance heating (ICRH) is applied either in mode conversion (MC) to heat the electrons or in minority heating (MH) to heat the ions. The two heating schemes have systematically different effects on nickel transport, yielding flat or slightly hollow nickel density profiles in the case of ICRH in MC and peaked nickel density profiles in the case of rf applied in MH. Accordingly, both diffusion coefficients and pinch velocities of nickel are found to be systematically different. Linear gyrokinetic calculations by means of the code GS2 [M. Kotschenreuther, G. Rewoldt, and W.M. Tang, Comput. Phys. Commun. 88, 128 (1995)] provide a possible explanation of such different behavior by exploring the effects produced by the different microinstabilities present in these plasmas. In particular, trapped electron modes driven by the stronger electron temperature gradients measured in the MC cases, although subdominant, produce a contribution to the impurity pinch directed outwards that is qualitatively in agreement with the pinch reversal found in the experiment. Particle and heat diffusivities appear to be decoupled in MH shots, with χe and DD≫DNi, and are instead quite similar in the MC ones. In the latter case, nickel transport appears to be driven by the same turbulence that drives the electron heat transport and is sensitive to the value of the electron temperature gradient length. These findings give ground to the idea that in ITER it should be possible to find conditions in which the risk of accumulation of metals such as nickel can be contained.
On the existence of ion-acoustic double layers in two-electron temperature plasmas
Authors: Verheest Frank , Cattaert Tom , Hellberg Manfred A. , Mace Richard L.
Published: April 2006

Earlier Sagdeev pseudopotential treatments of ion-acoustic double layers in plasmas with two electron populations were based on a model in which both electron densities were described by isothermal Boltzmann distributions. Using a more recent fluid-dynamical approach, with polytropic equations of state indices γj, one finds analytically that no double layers can be formed for γj⩾3∕2, due to total rarefaction of the cooler electrons or infinite compression of the ions. For γj<3∕2, rarefactive double layers occur, but, just below 3/2, at unrealistically small cool electron densities or large Mach numbers. As γj decreases towards 1, these constraints become less restrictive and go over smoothly to those known from Boltzmann studies. Contrary to what appears in the literature, very weak compressive double layers can also be found for Boltzmann electrons, but only for soliton conditions barely above the existence threshold; i.e., marginally super-ion-acoustic. Any slight increase in the critical Mach number destroys the possibility of having positive double layers, and, within the limits of numerical accuracy, no window could be found for γj≠1, where compressive double layers exist.
Isochronous and partially isochronous Hamiltonian systems are not rare
Authors: Calogero F. , Leyvraz F.
Published: April 2006

A technique is provided that allows to associate to a Hamiltonian another, ω-modified, Hamiltonian, which reduces to the original one when the parameter ω vanishes, and for ω>0 features an open, hence fully dimensional, region in its phase space where all its solutions are isochronous, i.e., completely periodic with the same period. The class of Hamiltonians to which this technique is applicable is large: it includes for instance the Hamiltonian characterizing the classical many-body problem with potentials that are translation-invariant but otherwise completely arbitrary, which is largely used in this paper to illustrate these findings. We also discuss variants of this technique that yield partially isochronous Hamiltonians, which also feature a region in their phase space where all solutions are isochronous, that region having however a bit less than full dimensionality (for instance codimension one or two) in phase space.
Asymmetric radiation-induced toroidal flow and improved confinement in tokamaks
Authors: Singh R. , Kaw P. K. , Rogister A. L. , Tangri V.
Published: April 2006

The role of impurity radiation in influencing the toroidal flow and radial electric fields (parameters critical for determining turbulent transport) has been studied on the edge of a tokamak plasma. It is demonstrated for the first time that the impurities distributed in an asymmetric (poloidally) manner may lead to significant density and temperature perturbations on magnetic surfaces. These, in turn, interact with the θ dependent toroidal field variations and yield a mean divergence of the stress tensor driving strong neoclassical toroidal flows. A self-consistent theory of interplay of equilibrium, fluctuations, neoclassical flows, and E⃗×B⃗ shear rotation in a tokamak is also presented. It is shown that the resulting enhanced toroidal velocity shear on the outer radiative layers produces a stabilizing effect on the well known instabilities (which determine edge transport) such as the drift resistive ballooning mode, the drift trapped electron mode, and the ion temperature gradient mode. For various values of the radiation asymmetry parameter, investigation of the turbulent particle flux as a function of the density gradient shows that the plasma can undergo a bifurcation into a better-confined state with a peaked density.
Nonlinear equation method for band structure calculations of photonic crystal slabs
Authors: Gao Dingshan , Zhou Zhiping
Published: April 2006

In this letter a nonlinear equation method based on effective-medium approximation is presented to calculate the band structure of photonic crystal slabs. At a definite wave vector, the normalized frequency is inversely proportional to the effective refractive index of the photonic crystals. Effective-medium approximation is used to calculate the effective refractive indices of the two dimensional photonic crystals and photonic crystal slab. The corresponding relation between the band structure of the photonic crystal slab and that of two dimensional photonic crystals is given by a nonlinear equation. Through the nonlinear equation, the three dimensional photonic crystal slabs problems are simplified as two dimensional simulations. The results by this method agree very well with those of three dimensional finite-difference time-domain method and the calculation is much faster.
Epitaxial nanolayers of quaterrylene: Influence of the substrate on the growth of the first and second monolayers
Authors: Franke R. , Franke S. , Wagner C. , Dienel T. , Fritz T. , Mannsfeld S. C. B.
Published: April 2006

We present a combined low energy electron diffraction and scanning tunneling microscopy study on the growth of the first and second monolayers (MLs) of quaterrylene on single crystalline Au(111). For the first ML, we observe a point-on-line coincident growth of flat lying molecules which agrees well with our potential energy calculations. In contrast, we observe alternating upstanding and flat lying molecules in the second layer. This behavior nicely demonstrates that the substrate has a very strong influence on the structure of the first layer, whereas the second layer is much weakly affected and exhibits properties comparable to the bulk.
Mapping the local nanostructure inside a specimen by tomographic small-angle x-ray scattering
Authors: Schroer C. G. , Kuhlmann M. , Roth S. V. , Gehrke R. , Stribeck N. , Almendarez-Camarillo A. , Lengeler B.
Published: April 2006

Small-angle x-ray scattering is combined with scanning microtomography to reconstruct the small-angle diffraction pattern in the direction of the tomographic rotation axis at each location on a virtual section through a specimen. These data yield information about the local nanoscale structure of the sample. With rotational symmetry present in the diffraction patterns, e.g., for isotropic or fiber-textured scatterers, the full reciprocal space information in the small-angle scattering regime can be reconstructed at each location inside the specimen. The method is illustrated investigating a polymer rod made by injection molding.
Enhanced transmission of optically thick metallic films at infrared wavelengths
Authors: Han Dezhuan , Li Xin , Wu Fengqin , Liu Xiaohan , Zi Jian
Published: April 2006

For an optically thick metallic film, the transmission for both s- and p-polarized waves is extremely low. If the metallic film is coated on both sides with a finite dielectric layer, light transmission for p-polarized waves can be enhanced considerably. This enhancement is not related to surface plasmon-polaritions. Instead, it is due to the interplay between Fabry-Perot interference in the coated dielectric layer and the existence of the Brewster angle at the dielectric/metallic interface. It is shown that the coated metallic films can act as excellent polarizers at infrared wavelengths.
Second-harmonic generation in optical superlattices at the oblique incidence of light
Authors: Zhao Li-Ming , Gu Ben-Yuan
Published: April 2006

We investigate second-harmonic generation (SHG) when light obliquely launches upon optical superlattices, which is optimally devised with the use of a simulated annealing method and can achieve simultaneously a multiple wavelength SHG with a high conversion efficiency. We find that the conversion efficiency at the oblique incidence of light can be increased significantly, compared to that at the normal incidence of light.
Patient-to-Patient Transmission of Hepatitis C Virus Through the Use of Multidose Vials During General Anesthesia
Authors: Germain Jeanne-Marie , Carbonne Anne , Thiers Valérie , Gros Hélène , Chastan Sylvie , Bouvet Elisabeth , Astagneau Pascal
Published: April 2006

A duster of four patients with hepatitis C virus (HCV) infection was identified in a surgery clinic. Molecular characterization revealed close homology between viruses. This cluster was related to unsafe injection practices through multidose vials and reused materials. Among 796 patients potentially exposed to and screened for HCV, no other cluster was identified.
Repression of Flt3 by Pax5 is crucial for B-cell lineage commitment
Authors: Holmes Melissa L. , Carotta Sebastian , Corcoran Lynn M. , Nutt Stephen L.
Published: April 2006

Early B-lymphopoiesis requires the growth-factor receptors, IL-7R and Flt3, and the activity of a number of transcription factors. One factor, Pax5, is required for commitment to the B-cell lineage, although the molecular mechanism by which this occurs is unknown. We demonstrate here that an important function of Pax5 is to repress Flt3 transcription in B-cell progenitors, as Pax5-deficient pro-B cells express abundant Flt3 that is rapidly silenced upon the reintroduction of Pax5, whereas enforced expression of Flt3 in wild-type progenitors significantly impairs B-cell development. These findings demonstrate that the repression of Flt3 by Pax5 is essential for normal B-lymphopoiesis.
Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation
Authors: Nguyen Bach-Cuc , Lefort Karine , Mandinova Anna , Antonini Dario , Devgan Vikram , Della Gatta Giusy , Koster Maranke I. , Zhang Zhuo , Wang Jian , di Vignano Alice Tommasi , Kitajewski Jan , Chiorino Giovanna , Roop Dennis R. , Missero Caterina , Dotto G. Paolo
Published: April 2006

Notch signaling promotes commitment of keratinocytes to differentiation and suppresses tumorigenesis. p63, a p53 family member, has been implicated in establishment of the keratinocyte cell fate and/or maintenance of epithelial self-renewal. Here we show that p63 expression is suppressed by Notch1 activation in both mouse and human keratinocytes through a mechanism independent of cell cycle withdrawal and requiring down-modulation of selected interferon-responsive genes, including IRF7 and/or IRF3. In turn, elevated p63 expression counteracts the ability of Notch1 to restrict growth and promote differentiation. p63 functions as a selective modulator of Notch1-dependent transcription and function, with the Hes-1 gene as one of its direct negative targets. Thus, a complex cross-talk between Notch and p63 is involved in the balance between keratinocyte self-renewal and differentiation.
Id1 Transcription Inhibitor–Matrix Metalloproteinase 9 Axis Enhances Invasiveness of the Breakpoint Cluster Region/Abelson Tyrosine Kinase–Transformed Leukemia Cells
Authors: Nieborowska-Skorska Margaret , Hoser Grazyna , Rink Lori , Malecki Maciej , Kossev Plamen , Wasik Mariusz A. , Skorski Tomasz
Published: April 2006

Breakpoint cluster region/Abelson (BCR/ABL) tyrosine kinase enhances the ability of leukemia cells to infiltrate various organs. We show here that expression of the helix-loop-helix transcription factor Id1 is enhanced by BCR/ABL in a signal transducer and activator of transcription 5 (STAT5)–dependent manner. Enhanced expression of Id1 plays a key role in BCR/ABL–mediated cell invasion. Down-regulation of Id1 in BCR/ABL leukemia cells by the antisense cDNA significantly reduced their invasive capability through the Matrigel membrane and their ability to infiltrate hematopoietic and nonhematopoietic organs resulting in delayed leukemogenesis in mice. The Id1-promoted cell invasiveness was seemingly mediated by matrix metalloproteinase 9 (MMP9). Transactivation of MMP9 promoter in BCR/ABL cells was dependent on Id1 and abrogation of the MMP9 catalytic activity by a metalloproteinase inhibitor or blocking antibody decreased invasive capacity of leukemia cells. These data suggest that BCR/ABL-STAT5-Id1-MMP9 pathway may play a critical role in BCR/ABL–mediated leukemogenesis by enhancing invasiveness of leukemia cells. (Cancer Res 2006; 66(8): 4108-16)
Retinoic Acid Induces p27Kip1 Nuclear Accumulation by Modulating Its Phosphorylation
Authors: Borriello Adriana , Cucciolla Valeria , Criscuolo Maria , Indaco Stefania , Oliva Adriana , Giovane Alfonso , Bencivenga Debora , Iolascon Achille , Zappia Vincenzo , Della Ragione Fulvio
Published: April 2006

All-trans-retinoic acid (ATRA), the most biologically active metabolite of vitamin A, controls cell proliferation, apoptosis, and differentiation depending on the cellular context. These activities point to ATRA as a candidate for cancer therapy. A pivotal effect of the molecule is the modulation of p27Kip1, a cyclin-dependent kinase (CDK) inhibitor (CDKI). Here, we investigate the mechanisms by which ATRA regulates p27Kip1 level in LAN-5, a neuroblastoma cell line. When added to the cells, ATRA causes a rapid nuclear increase of p27Kip1, which clearly precedes growth arrest. The early buildup is not due to impairment of the CDKI degradation, in contrast to previous observations. Particularly, we did not detect the down-regulation of Skp2 and Cks1, two proteins involved in the nuclear ubiquitin-dependent p27Kip1 removal. Moreover, the morphogen does not impair the CDKI nuclear export and does not cause CDK2 relocalization. The characterization of CDKI isoforms by two-dimensional PAGE/immunoblotting showed that ATRA induces an early nuclear up-regulation of monophosphorylated p27Kip1. Immunologic studies established that this isoform corresponds to p27Kip1 phosphorylated on S10. The buildup of phospho(S10)p27Kip1 precedes the CDKI accumulation and increases its half-life. Finally, ATRA-treated nuclear LAN-5 extracts showed an enhanced capability of phosphorylating p27Kip1 on S10, thus explaining the nuclear up-regulation of the isoform. In conclusion, our data suggest a novel mechanism of ATRA antiproliferative activity, in which the morphogen rapidly up-regulates a nuclear kinase activity that phosphorylates p27Kip1 on S10. In turn, this event causes the stabilization of p27Kip1 and its accumulation in the nuclear compartment. (Cancer Res 2006; 66(8): 4240-8)
The Requirement for and Changing Composition of the Activating Protein-1 Transcription Factor during Differentiation of Human Leukemia HL60 Cells Induced by 1,25-Dihydroxyvitamin D3
Authors: Wang Xuening , Studzinski George P.
Published: April 2006

The activating protein-1 (AP-1) transcription factor complex is a heterogeneous entity, composed in mammalian cells of dimers chosen from a group of at least eight proteins belonging to three families: jun, fos, and activating transcription factor (ATF). The AP-1 complexes participate in diverse biological processes that include cell proliferation, survival, and differentiation. These seemingly contrasting functions have been attributed to the intensity and duration of the signals provided by AP-1, but the biological consequences of changing composition of the AP-1 complex have not been fully explored. Here, we show that functional AP-1 is required for 1,25-dihydroxyvitamin D3 (1,25D)-induced monocytic differentiation, and that the composition of the AP-1 protein complex that binds TRE, its cognate DNA element, changes as cells differentiate. In HL60 cells in an early stage of differentiation, the principal AP-1 components detected by gel shift analysis include c-jun, ATF-2, fos-B, fra-1, and fra-2. In cells with a more established monocytic phenotype, the demonstrable AP-1 components are c-jun, ATF-2, jun-B, and fos-B. Following the addition of 1 nmol/L of 1,25D, the cellular content of each of these four proteins markedly increased in a sustained manner, whereas the increases in c-fos, fra-1, fra-2, and jun-D were minimal, if any. Small increases in mRNA levels encoding all AP-1 component proteins, except c-fos, were also noted. These findings provide a basis for the previously found participation of the c-Jun N-terminal kinase pathway in 1,25D-induced differentiation of myeloid leukemia cells, and direct attention to jun-B and fos-B as new cellular therapeutic targets, that may promote replicative quiescence associated with differentiation of malignant cells. (Cancer Res 2006; 66(8): 4202-9)
Noninvasive Magnetic Resonance Imaging of Transport and Interstitial Fluid Pressure in Ectopic Human Lung Tumors
Authors: Hassid Yaron , Furman-Haran Edna , Margalit Raanan , Eilam Raya , Degani Hadassa
Published: April 2006

Tumor response to blood borne drugs is critically dependent on the efficiency of vascular delivery and transcapillary transfer. However, increased tumor interstitial fluid pressure (IFP) forms a barrier to transcapillary transfer, leading to resistance to drug delivery. We present here a new, noninvasive method which estimates IFP and its spatial distribution in vivo using contrast-enhanced magnetic resonance imaging (MRI). This method was tested in ectopic human non–small-cell lung cancer which exhibited a high IFP of ∼28 mm Hg and, for comparison, in orthotopic MCF7 human breast tumors which exhibited a lower IFP of ∼14 mm Hg, both implanted in nude mice. The MRI protocol consisted of slow infusion of the contrast agent [gadolinium-diethylenetriaminepentaacetic acid (GdDTPA)] into the blood for ∼2 hours, sequential acquisition of images before and during the infusion, and measurements of T1 relaxation rates before infusion and after blood and tumor GdDTPA concentration reached a steady state. Image analysis yielded parametric images of steady-state tissue GdDTPA concentration with high values of this concentration outside the tumor boundaries, ∼1 mmol/L, declining in the tumor periphery to ∼0.5 mmol/L, and then steeply decreasing to low or null values. The distribution of steady-state tissue GdDTPA concentration reflected the distribution of IFP, showing an increase from the rim inward, with a high IFP plateau inside the tumor. The changes outside the borders of the tumors with high IFP were indicative of convective transport through the interstitium. This work presents a noninvasive method for assessing the spatial distribution of tumor IFP and mapping barriers to drug delivery and transport. (Cancer Res 2006; 66(8): 4159-66)
Phospholipase C-δ1 Is a Critical Target for Tumor Necrosis Factor Receptor–Mediated Protection against Adriamycin-Induced Cardiac Injury
Authors: Lien Yu-Chin , Noel Teresa , Liu Hua , Stromberg Arnold J. , Chen Kuey-Chu , St. Clair Daret K.
Published: April 2006

The clinical application of adriamycin, an exceptionally good chemotherapeutic agent, is limited by its dose-related cardiomyopathy. Our recent study showed that tumor necrosis factor-α (TNF-α) receptors mediated cytoprotective signaling against adriamycin-induced mitochondrial injury and cardiomyocyte apoptosis. In the present study, we investigated the potential targets of TNF receptor–mediated cytoprotective signaling by global genome microarray analysis using wild-type and TNF receptor–deficient mice. Microarray analysis revealed that adriamycin treatment induced the down-regulation of several mitochondrial functions and energy production–related genes in double TNF receptor–deficient mice, notably, phospholipase C-δ1, a protein involved in fatty acid metabolism and calcium regulation. The role of phospholipase C-δ1 in TNF receptor–mediated cardioprotection against adriamycin-induced injury was evaluated by measuring changes in cardiac function using high-frequency ultrasound biomicroscopy. Selective inhibition of phospholipase C activity in wild-type mice by its inhibitor, U73122, exacerbated adriamycin-induced cardiac dysfunction. Inhibition of phospholipase C-δ1 resulted in the significant decrease of left ventricular ejection fraction and fractional shortening, and the decreased levels were similar to those observed in adriamycin-treated double TNF receptor–deficient mice. The data derived from the global genome analysis identified phospholipase C-δ1 as an important target for TNF receptors and revealed the critical role of TNF receptor signaling in the protection against adriamycin-induced cardiotoxicity. (Cancer Res 2006; 66(8): 4329-38)
Hemangioblastomas Share Protein Expression with Embryonal Hemangioblast Progenitor Cell
Authors: Gläsker Sven , Li Jie , Xia John B. , Okamoto Hiroaki , Zeng Weifen , Lonser Russell R. , Zhuang Zhengping , Oldfield Edward H. , Vortmeyer Alexander O.
Published: April 2006

Hemangioblastomas are central nervous system (CNS) tumors of unknown histogenesis, which can occur sporadically or in von Hippel-Lindau disease. Hemangioblastomas are composed of neoplastic “stromal” cells of unknown origin, accompanied by intensive reactive angiogenesis. Failure to specify the cytologic origin of the stromal cell has precluded the development of nonsurgical therapies and limits understanding of its basic biology. We report that the stromal cells express proteins (Scl, brachyury, Csf-1R, Gata-1, Flk-1, and Tie-2) that characterize embryonic progenitor cells with hemangioblastic differentiation potential and conclude that embryonic progenitors with hemangioblast potential represent a possible cytologic equivalent of the stromal cell. We also identified a new autocrine/paracrine stimulatory loop between the receptor Tie-2 and the hypoxia-inducible factor target Ang-1, which, combined with previous observations, suggests that a variety of autocrine loops may be initiated in hemangioblastomas, depending on the differentiation status of the tumor cells and the extent of HIF downstream activation. Finally, the consistent identification of Scl in the stromal cells may help explain the unique and characteristic topographical distribution of hemangioblastomas within the CNS. (Cancer Res 2006; 66(8):4167-72)
Tumor Imaging Using a Picomolar Affinity HER2 Binding Affibody Molecule
Authors: Orlova Anna , Magnusson Mikaela , Eriksson Tove L.J. , Nilsson Martin , Larsson Barbro , Höidén-Guthenberg Ingmarie , Widström Charles , Carlsson Jörgen , Tolmachev Vladimir , Ståhl Stefan , Nilsson Fredrik Y.
Published: April 2006

The detection of cell-bound proteins that are produced due to aberrant gene expression in malignant tumors can provide important diagnostic information influencing patient management. The use of small radiolabeled targeting proteins would enable high-contrast radionuclide imaging of cancers expressing such antigens if adequate binding affinity and specificity could be provided. Here, we describe a HER2-specific 6 kDa Affibody molecule (hereinafter denoted Affibody molecule) with 22 pmol/L affinity that can be used for the visualization of HER2 expression in tumors in vivo using gamma camera. A library for affinity maturation was constructed by re-randomization of relevant positions identified after the alignment of first-generation variants of nanomolar affinity (50 nmol/L). One selected Affibody molecule, ZHER2:342 showed a >2,200-fold increase in affinity achieved through a single-library affinity maturation step. When radioiodinated, the affinity-matured Affibody molecule showed clear, high-contrast visualization of HER2-expressing xenografts in mice as early as 6 hours post-injection. The tumor uptake at 4 hours post-injection was improved 4-fold (due to increased affinity) with 9% of the injected dose per gram of tissue in the tumor. Affibody molecules represent a new class of affinity molecules that can provide small sized, high affinity cancer-specific ligands, which may be well suited for tumor imaging. (Cancer Res 2006; 66(8): 4339-48)
Stat1 Deficiency in the Host Enhances Interleukin-12–Mediated Tumor Regression
Authors: Torrero Marina N. , Xia Xueqing , Henk Williams , Yu Shry , Li Shulin
Published: April 2006

Signal transducer and activator of transcription 1 (Stat1) is considered a key transcription factor that inhibits tumorigenesis, and Stat1 activation in the host is required for interleukin-12 (IL-12)–mediated generation of CTL activity. Using syngeneic Stat1−/− C3H mice bearing SCCVII tumors in this study, we discovered opposite results. Stat1 deficiency in the host significantly enhances IL-12–mediated tumor regression, resulting in tumor eradication from 60% of SCCVII tumor–bearing mice and significant inhibition of tumor growth when compared with control treatment (P < 0.01). This effect is independent of both Stat1-activating cytokine IFN-γ and Stat1-downstream effector molecule FasL because neither neutralization of IFN-γ nor knocking out of FasL enhances or inhibits IL-12–mediated tumor regression. IL-12 induces a high intensity of tumor-specific CTL activity in Stat1-deficient mice (P < 0.01), increases the CD8 T-cell density in tumor bearing Stat1−/− mice, and induces a T-cell–dependent tumor regression. The increased CTL activity and the high-intensity infiltration of T cells into the tumors in IL-12–treated Stat1−/− mice are likely due to the longer survival than the same cells from wild-type mice. Together, the data show that inhibition of Stat1 expression in the host enhances tumor-local IL-12 gene therapy for regressing tumors. This conclusion provides a new concept for designing an effective treatment strategy. (Cancer Res 2006; 66(8): 4461-7)
Notch1 Signaling Promotes Primary Melanoma Progression by Activating Mitogen-Activated Protein Kinase/Phosphatidylinositol 3-Kinase-Akt Pathways and Up-regulating N-Cadherin Expression
Authors: Liu Zhao-Jun , Xiao Min , Balint Klara , Smalley Keiran S.M. , Brafford Patricia , Qiu Ruihua , Pinnix Chelsea C. , Li Xueli , Herlyn Meenhard
Published: April 2006

Cellular signaling mediated by Notch receptors results in coordinated regulation of cell growth, survival, and differentiation. Aberrant Notch activation has been linked to a variety of human neoplasms. Here, we show that Notch1 signaling drives the vertical growth phase (VGP) of primary melanoma toward a more aggressive phenotype. Constitutive activation of Notch1 by ectopic expression of the Notch1 intracellular domain enables VGP primary melanoma cell lines to proliferate in a serum-independent and growth factor–independent manner in vitro and to grow more aggressively with metastatic activity in vivo. Notch1 activation also enhances tumor cell survival when cultured as three-dimensional spheroids. Such effects of Notch signaling are mediated by activation of the mitogen-activated protein kinase (MAPK) and Akt pathways. Both pathways are activated in melanoma cells following Notch1 pathway activation. Inhibition of either the MAPK or the phosphatidylinositol 3-kinase (PI3K)-Akt pathway reverses the Notch1 signaling-induced tumor cell growth. Moreover, the growth-promoting effect of Notch1 depends on mastermind-like 1. We further showed that Notch1 activation increases tumor cell adhesion and up-regulates N-cadherin expression. Our data show regulation of MAPK/PI3K-Akt pathway activities and expression of N-cadherin by the Notch pathway and provide a mechanistic basis for Notch signaling in the promotion of primary melanoma progression. (Cancer Res 2006; 66(8): 4182-90)