bluuebunny/crossref_metadata_2025 huggingface dataset:
Myxoma Virus Expressing Interleukin-15 Fails To Cause Lethal Myxomatosis in European Rabbits
Authors: Liu Jia , Wennier Sonia , Reinhard Mary , Roy Edward , MacNeill Amy , McFadden Grant
Published: March 2009

Myxoma virus (MYXV) is a poxvirus pathogenic only for European rabbits, but its permissiveness in human cancer cells gives it potential as an oncolytic virus. A recombinant MYXV expressing both the tdTomato red fluorescent protein and interleukin-15 (IL-15) (vMyx-IL-15-tdTr) was constructed. Cells infected with vMyx-IL-15-tdTr secreted bioactive IL-15 and had in vitro replication kinetics similar to that of wild-type MYXV. To determine the safety of this virus for future oncolytic studies, we tested its pathogenesis in European rabbits. In vivo, vMyx-IL-15-tdTr no longer causes lethal myxomatosis. Thus, ectopic IL-15 functions as an antiviral cytokine in vivo, and vMyx-IL-15-tdTr is a safe candidate for animal studies of oncolytic virotherapy.
Effect of Preexisting Immunity on an Adenovirus Vaccine Vector: In Vitro Neutralization Assays Fail To Predict Inhibition by Antiviral Antibody In Vivo
Authors: Pichla-Gollon Susan L. , Lin Shih-Wen , Hensley Scott E. , Lasaro Marcio O. , Herkenhoff-Haut Larissa , Drinker Mark , Tatsis Nia , Gao Guang-Ping , Wilson James M. , Ertl Hildegund C. J. , Bergelson Jeffrey M.
Published: March 2009

A major obstacle to the use of adenovirus vectors derived from common human serotypes, such as human adenovirus 5 (AdHu5), is the high prevalence of virus-neutralizing antibodies in the human population. We previously constructed a variant of chimpanzee adenovirus 68 (AdC68) that maintained the fundamental properties of the carrier but was serologically distinct from AdC68 and resisted neutralization by AdC68 antibodies. In the present study, we tested whether this modified vector, termed AdCDQ, could induce transgene product-specific CD8
+
T cells in mice with preexisting neutralizing antibody to wild-type AdC68. Contrary to our expectation, the data show conclusively that antibodies that fail to neutralize the AdCDQ mutant vector in vitro nevertheless impair the vector's capacity to transduce cells and to stimulate a transgene product-specific CD8
+
T-cell response in vivo. The results thus suggest that in vitro neutralization assays may not reliably predict the effects of virus-specific antibodies on adenovirus vectors in vivo.
Nonreplicating Vaccinia Virus Vectors Expressing the H5 Influenza Virus Hemagglutinin Produced in Modified Vero Cells Induce Robust Protection
Authors: Mayrhofer Josef , Coulibaly Sogue , Hessel Annett , Holzer Georg W. , Schwendinger Michael , Brühl Peter , Gerencer Marijan , Crowe Brian A. , Shuo Shen , Hong Wanjing , Tan Yee Joo , Dietrich Barbara , Sabarth Nicolas , Savidis-Dacho Helga , Kistner Otfried , Barrett P. Noel , Falkner Falko G.
Published: March 2009

The timely development of safe and effective vaccines against avian influenza virus of the H5N1 subtype will be of the utmost importance in the event of a pandemic. Our aim was first to develop a safe live vaccine which induces both humoral and cell-mediated immune responses against human H5N1 influenza viruses and second, since the supply of embryonated eggs for traditional influenza vaccine production may be endangered in a pandemic, an egg-independent production procedure based on a permanent cell line. In the present article, the generation of a complementing Vero cell line suitable for the production of safe poxviral vaccines is described. This cell line was used to produce a replication-deficient vaccinia virus vector H5N1 live vaccine, dVV-HA5, expressing the hemagglutinin of a virulent clade 1 H5N1 strain. This experimental vaccine was compared with a formalin-inactivated whole-virus vaccine based on the same clade and with different replicating poxvirus-vectored vaccines. Mice were immunized to assess protective immunity after high-dose challenge with the highly virulent A/Vietnam/1203/2004(H5N1) strain. A single dose of the defective live vaccine induced complete protection from lethal homologous virus challenge and also full cross-protection against clade 0 and 2 challenge viruses. Neutralizing antibody levels were comparable to those induced by the inactivated vaccine. Unlike the whole-virus vaccine, the dVV-HA5 vaccine induced substantial amounts of gamma interferon-secreting CD8 T cells. Thus, the nonreplicating recombinant vaccinia virus vectors are promising vaccine candidates that induce a broad immune response and can be produced in an egg-independent and adjuvant-independent manner in a proven vector system.
Differential Functions of Interferon-Upregulated Sp100 Isoforms: Herpes Simplex Virus Type 1 Promoter-Based Immediate-Early Gene Suppression and PML Protection from ICP0-Mediated Degradation
Authors: Negorev Dmitri G. , Vladimirova Olga V. , Maul Gerd G.
Published: March 2009

Cells have intrinsic defenses against virus infection, acting before the innate or the adaptive immune response. Preexisting antiviral proteins such as PML, Daxx, and Sp100 are stored in specific nuclear domains (ND10). In herpes simplex virus type 1 (HSV-1), the immediate-early protein ICP0 serves as a counterdefense through degradation of the detrimental protein PML. We asked whether interferon (IFN)-upregulated Sp100 is similarly antagonized by ICP0 in normal human fibroblasts by using a selective-knockdown approach. We find that of the four Sp100 isoforms, the three containing a SAND domain block the transcription of HSV-1 proteins ICP0 and ICP4 at the promoter level and that IFN changes the differential splicing of the
Sp100
transcript in favor of the inhibitor Sp100C. At the protein level, ICP0 activity does not lead to the hydrolysis of any of the Sp100 isoforms. The SAND domain-containing isoforms are not general inhibitors of viral promoters, as the activity of the major immediate-early cytomegalovirus promoter is not diminished, whereas the long terminal repeat of a retrovirus, like the ICP0 promoter, is strongly inhibited. Since we could not find a specific promoter region in the ICP0 gene that responds to the SAND domain-containing isoforms, we questioned whether Sp100 could act through other antiviral proteins such as PML. We find that all four Sp100 isoforms stabilize ND10 and protect PML from ICP0-based hydrolysis. Loss of either all PML isoforms or all Sp100 isoforms reduces the opposite constituent ND10 protein, suggesting that various interdependent mechanisms of ND10-based proteins inhibit virus infection at the immediate-early level.
NS5 of Dengue Virus Mediates STAT2 Binding and Degradation
Authors: Ashour Joseph , Laurent-Rolle Maudry , Shi Pei-Yong , García-Sastre Adolfo
Published: March 2009

The mammalian interferon (IFN) signaling pathway is a primary component of the innate antiviral response. As such, viral pathogens have devised multiple mechanisms to antagonize this pathway and thus facilitate infection. Dengue virus (DENV) encodes several proteins (NS2a, NS4a, and NS4b) that have been shown individually to inhibit the IFN response. In addition, DENV infection results in reduced levels of expression of STAT2, which is required for IFN signaling (M. Jones, A. Davidson, L. Hibbert, P. Gruenwald, J. Schlaak, S. Ball, G. R. Foster, and M. Jacobs, J. Virol. 79:5414-5420, 2005). Translation of the DENV genome results in a single polypeptide, which is processed by viral and host proteases into at least 10 separate proteins. To date, no single DENV protein has been implicated in the targeting of STAT2 for decreased levels of expression. We demonstrate here that the polymerase of the virus, NS5, binds to STAT2 and is necessary and sufficient for its reduced level of expression. The decrease in protein level observed requires ubiquitination and proteasome activity, strongly suggesting an active degradation process. Furthermore, we show that the degradation of but not binding to STAT2 is dependent on the expression of the polymerase in the context of a polyprotein that undergoes proteolytic processing for NS5 maturation. Thus, the mature form of NS5, when not expressed as a precursor, was able to bind to STAT2 but was unable to target it for degradation, establishing a unique role for viral polyprotein processing in providing an additional function to a viral polypeptide. Therefore, we have identified both a novel mechanism by which DENV evades the innate immune response and a potential target for antiviral therapeutics.
Neurodegeneration Induced by PVC-211 Murine Leukemia Virus Is Associated with Increased Levels of Vascular Endothelial Growth Factor and Macrophage Inflammatory Protein 1α and Is Inhibited by Blocking Activation of Microglia
Authors: Li Xiujie , Hanson Charlotte , Cmarik Joan L. , Ruscetti Sandra
Published: March 2009

PVC-211 murine leukemia virus (MuLV) is a neuropathogenic retrovirus that has undergone genetic changes from its nonneuropathogenic parent, Friend MuLV, that allow it to efficiently infect rat brain capillary endothelial cells (BCEC). To clarify the mechanism by which PVC-211 MuLV expression in BCEC induces neurological disease, we examined virus-infected rats at various times during neurological disease progression for vascular and inflammatory changes. As early as 2 weeks after virus infection and before any marked appearance of spongiform neurodegeneration, we detected vessel leakage and an increase in size and number of vessels in the areas of the brain that eventually become diseased. Consistent with these findings, the amount of vascular endothelial growth factor (VEGF) increased in the brain as early as 1 to 2 weeks postinfection. Also detected at this early disease stage was an increased level of macrophage inflammatory protein 1α (MIP-1α), a cytokine involved in recruitment of microglia to the brain. This was followed at 3 weeks postinfection by a marked accumulation of activated microglia in the spongiform areas of the brain accompanied by an increase in tissue plasminogen activator, a product of microglia implicated in neurodegeneration. Pathological observations at the end stage of the disease included loss of neurons, decreased myelination, and mild muscle atrophy. Treatment of PVC-211 MuLV-infected rats with clodronate-containing liposomes, which specifically kill microglia, significantly blocked neurodegeneration. Together, these results suggest that PVC-211 MuLV infection of BCEC results in the production of VEGF and MIP-1α, leading to the vascular changes and microglial activation necessary to cause neurodegeneration.
Reovirus Activates Transforming Growth Factor β and Bone Morphogenetic Protein Signaling Pathways in the Central Nervous System That Contribute to Neuronal Survival following Infection
Authors: Beckham J. David , Tuttle Kathryn , Tyler Kenneth L.
Published: March 2009

Viral infections of the central nervous system (CNS) are important causes of worldwide morbidity and mortality, and understanding how viruses perturb host cell signaling pathways will facilitate identification of novel antiviral therapies. We now show that reovirus infection activates transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signaling in a murine model of encephalitis in vivo. TGF-β receptor I (TGF-βRI) expression is increased and its downstream signaling factor, SMAD3, is activated in the brains of reovirus-infected mice. TGF-β signaling is neuroprotective, as inhibition with a TGF-βRI inhibitor increases death of infected neurons. Similarly, BMP receptor I expression is increased and its downstream signaling factor, SMAD1, is activated in reovirus-infected neurons in the brains of infected mice in vivo. Activated SMAD1 and SMAD3 were both detected in regions of brain infected by reovirus, but activated SMAD1 was found predominantly in uninfected neurons in close proximity to infected neurons. Treatment of reovirus-infected primary mouse cortical neurons with a BMP agonist reduced apoptosis. These data provide the first evidence for the activation of TGF-β and BMP signaling pathways following neurotropic viral infection and suggest that these signaling pathways normally function as part of the host's protective innate immune response against CNS viral infection.
Nyamanini and Midway Viruses Define a Novel Taxon of RNA Viruses in the Order
Mononegavirales
Authors: Mihindukulasuriya Kathie A. , Nguyen Nang L. , Wu Guang , Huang Henry V. , Travassos da Rosa Amelia P. A. , Popov Vsevolod L. , Tesh Robert B. , Wang David
Published: March 2009

Here, we report the sequencing and classification of Nyamanini virus (NYMV) and Midway virus (MIDWV), two antigenically related viruses that were first isolated in 1957 and 1966, respectively. Although these viruses have been cultured multiple times from cattle egrets, seabirds, and their ticks, efforts to classify them taxonomically using conventional serological and electron microscopic approaches have failed completely. We used a random shotgun sequencing strategy to define the genomes of NYMV and MIDWV. Contigs of 11,631 and 11,752 nucleotides, representing the complete genome of NYMV and the near-complete genome of MIDWV, respectively, were assembled. Each virus genome was predicted to carry six open reading frames (ORFs). BLAST analysis indicated that only two of the ORF proteins of each virus, the putative nucleocapsid and polymerase, had detectable sequence similarity to known viral proteins. Phylogenetic analysis of these ORF proteins demonstrated that the closest relatives of NYNV and MIDWV are negative-stranded-RNA viruses in the order
Mononegavirales
. On the basis of their very limited sequence similarity to known viruses, we propose that NYMV and MIDWV define a novel genus,
Nyavirus
, in this order.
STUDY OF LASER BEAT-WAVE INTERFEROMETRY FOR LASER TRACKING OF MOVING BODY
Authors: XIE CHI , ZHOU ZHAO-FEI , CAI PENG , ZHANG TAO
Published: March 2009

In order to increase more greatly the measurement accuracy for the laser tracking system in measuring the moving body, a laser beat-wave interferometry method is approached based on the absolute measuring distance. The He – Ne laser with the two hot steady frequency modes is used as the light source for the laser tracking system. The light source developed by us not only has the advantages of steady frequency, high precision and strongly anti-interference capability, but also it mainly has the same character in the shoot stability degrees and laser frequency stability degrees. By using the laser beat-wave interferometry method, we can realize the absolute distance measurement of the moving body, and the laser tracking system has very high measurement precision, fast tracking speed and anti-interference capability.
DECONVOLUTION METHOD ON OSL CURVES FROM ZrO2 IRRADIATED BY BETA AND UV RADIATIONS
Authors: RIVERA T. , KITIS G. , AZORÍN J. , FURETTA C.
Published: March 2009

This paper reports the optically stimulated luminescent (OSL) response of ZrO 2 to beta and ultraviolet radiations in order to investigate the potential use of this material as a radiation dosimeter. The experimentally obtained OSL decay curves were analyzed using the computerized curve de-convolution (CCD) method. It was found that the OSL curve structure, for the short (practical) illumination time used, consists of three first order components. The individual OSL dose response behavior of each component was found. The values of the time at the OSL peak maximum and the decay constant of each component were also estimated.
A SOLITON HIERARCHY FROM THE LEVI SPECTRAL PROBLEM AND ITS TWO INTEGRABLE COUPLINGS, HAMILTONIAN STRUCTURE
Authors: ZHANG YONGQING , LI YAN
Published: March 2009

A soliton-equation hierarchy from the D. Levi spectral problem is obtained under the framework of zero curvature equation. By employing two various multi-component Lie algebras and the loop algebras, we enlarge the Levi spectral problem and the corresponding time-part isospectral problems so that two different integrable couplings are produced. Using the quadratic-form identity yields the Hamiltonian structure of one of the two integrable couplings.
DYNAMICAL BEHAVIORS OF THE WIGNER FUNCTION OF EXCITED BINOMIAL STATES IN THERMAL CHANNEL
Authors: MEI SHAN-HAI , LI SHANG-BIN
Published: March 2009

In this paper, we investigate the non-classicality of excited binomial states by analyzing the partial negativity of the Wigner function. The volume of the negative part of the Wigner function is numerically calculated for some single-photon-excited binomial states. The dynamical behaviors of the Wigner distribution of excited binomial states in the thermal channel are investigated.
SPECTRAL LINE NARROWING IN ELECTROMAGNETICALLY INDUCED TRANSPARENCY
Authors: XIAO YANHONG
Published: March 2009

Electromagnetically induced transparency (EIT) can make an otherwise opaque medium transparent by utilizing quantum coherence. EIT has attracted great interest since the 1990s for its wide applications in metrology, nonlinear and quantum optics, and quantum information science. We present a review on spectral line narrowing mechanisms in EIT-related systems, accounting for linewidths much narrower than expected from the standard mechanisms of Doppler broadening, transit time broadening, magnetic field inhomogeneity and power broadening. Topics covered include Dicke narrowing, atomic-motion-induced Ramsey narrowing, motional narrowing, density narrowing, laser induced narrowing and power-broadening-free resonance. Intuitive pictures are provided to describe the essential physics of each mechanism.
LOW ENERGY QUANTUM GRAVITY, THE COSMOLOGICAL CONSTANT AND GAUGE COUPLING CONSTANTS
Authors: TOMS DAVID J.
Published: March 2009

Robinson and Wilczek have suggested that loop corrections in quantum gravity can alter the running gauge coupling constants from the behaviour found in the absence of gravity. Although their original calculation is not correct, the basic idea behind their paper has been re-examined recently for quantized Einstein–Maxwell theory with a cosmological constant. In this essay I discuss some of the issues surrounding the calculation and mention some of the implications. I argue that it is possible for a theory that is not conventionally asymptotically free to become so in the presence of gravity, and for gravity to lead to a new ultraviolet fixed point. This establishes a provocative link between the microscopic and macroscopic realms.
COSMOLOGICAL PARTICLE CREATION: FLUCTUATIONS AND AN ENSEMBLE PICTURE
Authors: KAYA ALI
Published: March 2009

We point out that in the context of quantum fields in time-dependent classical backgrounds, the number of created particles with a given momentum largely deviates about its mean value. Since the corresponding Fourier modes are nonlocal, this deviation shows that the expectation value of the number operator can make sense only in an ensemble of space–times. Using a complete orthonormal family of localized wave packets, we show how an ensemble interpretation can be given to cosmological particle creation in local terms. The reheating process following inflation is re-examined in the light of this construction.
SUBTLETIES IN THE QUASI-CLASSICAL CALCULATION OF HAWKING RADIATION
Authors: AKHMEDOV EMIL T. , PILLING TERRY , SINGLETON DOUGLAS
Published: March 2009

The quasi-classical method of deriving Hawking radiation is investigated. In order to recover the original Hawking temperature one must take into account a previously ignored contribution coming from the temporal part of the action. This contribution plus a contribution coming from the spatial part of the action gives the correct temperature.
IS PHYSICS ASKING FOR A NEW KINEMATICS?
Authors: ALDROVANDI R. , PEREIRA J. G.
Published: March 2009

It is discussed whether some of the consistency problems of present day physics could be solved by replacing special relativity, whose underlying kinematics is ruled by the Poincaré group, with de Sitter relativity, whose underlying kinematics is ruled by the de Sitter group. In contrast to ordinary special relativity, which seems to fail at the Planck scale, this new relativity is "universal," in the sense that it holds at all energy scales.
LATE TIME DECAY OF THE FALSE VACUUM, MEASUREMENT, AND QUANTUM COSMOLOGY
Authors: KRAUSS LAWRENCE M. , STARKMAN GLENN D. , DENT JAMES
Published: March 2009

The recent suggestion that late time quantum dynamics may be important for resolving cosmological issues associated with our observed universe requires a consideration of several subtle issues associated with quantum cosmology, as we describe here. The resolution of these issues will be important if we are to be able to properly ascribe probability measures associated with eternal inflation, and a string landscape.
WHY SUPERSYMMETRY SHOULD BE RESTORED AT THE TeV SCALE
Authors: GASPERINI M.
Published: March 2009

It is explained why the curvature associated with the vacuum energy density arising from SUSY breaking cannot be completely transferred to the extra spatial dimensions of a bulk space–time manifold, and it is shown — without using hierarchy arguments but only the results of current large-scale observations — why the TeV scale should correspond to the maximal allowed SUSY-breaking scale.
COSMOLOGY WITH DECAYING DARK ENERGY AND COSMOLOGICAL "CONSTANT"
Authors: WESSON P. S. , MASHHOON B. , OVERDUIN J. M.
Published: March 2009

We outline an improved cosmology which uses a higher-dimensional space of the type implied by unification, where the cosmological "constant" decays from an unbounded value at the big bang to an acceptable value today. This model leads to a better understanding of inflation and is in good agreement with observations of galaxies.
HALOS OF MODIFIED GRAVITY
Authors: KRASNOV KIRILL , SHTANOV YURI
Published: March 2009

We describe how a certain simple modification of general relativity, in which the local cosmological constant is allowed to depend on the space–time curvature, predicts the existence of halos of modified gravity surrounding spherically symmetric objects. We show that the gravitational mass of an object weighed together with its halo can be much larger than its gravitational mass as seen from inside the halo. This effect could provide an alternative explanation of the dark-matter phenomenon in galaxies. In this case, the local cosmological constant in the solar system must be some six orders of magnitude larger than its cosmic value obtained in the supernova type Ia experiments. This is well within the current experimental bounds, but may be directly observable in future high-precision experiments.
QUANTUM FIELD THEORY IN CURVED SPACE–TIME, THE OPERATOR PRODUCT EXPANSION, AND DARK ENERGY
Authors: HOLLANDS STEFAN , WALD ROBERT M.
Published: March 2009

To make sense of quantum field theory in an arbitrary (globally hyperbolic) curved space–time, the theory must be formulated in a local and covariant manner in terms of locally measureable field observables. Since a generic curved space–time does not possess symmetries or a unique notion of a vacuum state, the theory also must be formulated in a manner that does not require symmetries or a preferred notion of a "vacuum state" and "particles". We propose such a formulation of quantum field theory, wherein the operator product expansion (OPE) of the quantum fields is elevated to a fundamental status, and the quantum field theory is viewed as being defined by its OPE. Since the OPE coefficients may be better behaved than any quantities having to do with states, we suggest that it may be possible to perturbatively construct the OPE coefficients — and, thus, the quantum field theory. By contrast, ground/vacuum states — in space–times, such as Minkowski space–time, where they may be defined — cannot vary analytically with the parameters of the theory. We argue that this implies that composite fields may acquire nonvanishing vacuum state expectation values due to nonperturbative effects. We speculate that this could account for the existence of a nonvanishing vacuum expectation value of the stress-energy tensor of a quantum field occurring at a scale much smaller than the natural scales of the theory.
THE DELOCALIZED EFFECTIVE DEGREES OF FREEDOM OF A BLACK HOLE AT LOW FREQUENCIES
Authors: KOL BARAK
Published: March 2009

Identifying the fundamental degrees of freedom of a black hole poses a long-standing puzzle. Recently Goldberger and Rothstein forwarded a theory of the low frequency degrees of freedom within the effective field theory approach, where they are relevancy-ordered but of unclear physical origin. Here these degrees of freedom are identified with near-horizon but non-compact gravitational perturbations which are decomposed into delocalized multipoles. Their world-line (kinetic) action is determined within the classical effective field theory (CLEFT) approach and their interactions are discussed. The case of the long-wavelength scattering of a scalar wave off a Schwarzschild black hole is treated in some detail, interpreting within the CLEFT approach the equality of the leading absorption cross section with the horizon area.
A COVARIANT ENTROPY BOUND CONJECTURE ON THE DYNAMICAL HORIZON
Authors: HE SONG , ZHANG HONGBAO
Published: March 2009

We propose, as a compelling pattern for the holographic principle, a covariant entropy bound conjecture for more general dynamical horizons. Then we apply our conjecture to ΛCDM cosmological models, where we find that it imposes a novel upper bound, 10-90, on the cosmological constant for our own universe by taking into account the dominant entropy contribution from supermassive black holes, which thus provides an alternative macroscopic perspective for understanding the long-standing cosmological constant problem. As an intriguing implication of this conjecture, we also discuss the possible profound relation between the present cosmological constant, the origin of mass, and the anthropic principle.
ENTANGLEMENT AND THERMODYNAMICS OF BLACK HOLE ENTROPY
Authors: BROUT R.
Published: March 2009

Using simple conditions drawn from the stability of the cosmos in terms of vacuum energy density, the cutoff momentum of entanglement is related to the Planckian mass. In so doing the black hole entropy is shown to be independent of the number of field species that contribute to vacuum fluctuations. And this is in spite of the fact that the number of field species is a linear multiplicand of the entanglement entropy when the latter is expressed in terms of the fundamental momentum cutoff of all fields.
A NOTE ON DARK ENERGY INDUCED BY D-BRANE MOTION
Authors: CHINGANGBAM R. , DESHAMUKHYA A.
Published: March 2009

In this note we study the possibility of obtaining a dark energy solution in a D-brane scenario against a warped background that includes brane-position-dependent corrections for the nonperturbative superpotential. The volume modulus is stabilized at instantaneous minima of the potential. Though the model can account for the existence of dark energy within the present observational bound, fine-tuning of the model parameters becomes unavoidable. Moreover, the model does not possess a tracker solution.
BLACK HOLES WITHOUT BOUNDARIES
Authors: NIELSEN ALEX B.
Published: March 2009

We discuss some of the drawbacks of using event horizons to define black holes and suggest ways in which black holes can be described without event horizons, using trapping horizons. We show that these trapping horizons give rise to thermodynamic behavior and possibly Hawking radiation too. This raises the issue of whether the event horizon or the trapping horizon should be seen as the true boundary of a black hole. This difference is important if we believe that quantum gravity will resolve the central singularity of the black hole and clarifies several of the issues associated with black hole thermodynamics and information loss.
STRING THEORY, THE CRISIS IN PARTICLE PHYSICS AND THE ASCENT OF METAPHORIC ARGUMENTS
Authors: SCHROER BERT
Published: March 2009

This essay presents a critical evaluation of the concepts of string theory and its impact on particle physics. The point of departure is a historical review of four decades of string theory within the broader context of six decades of failed attempts at an autonomous S matrix approach to particle theory.

The central message, contained in Secs. 5 and 6, is that string theory is not what its name suggests, namely a theory of objects in space–time whose localization is string-instead of pointlike. Contrary to popular opinion, the oscillators corresponding to the Fourier models of a quantum-mechanical string do not become embedded in space–time and neither does the "range space" of a chiral conformal QFT acquire the interpretation of stringlike-localized quantum matter.

Rather, string theory represents a solution to a problem which enjoyed some popularity in the 1960s: find a principle which, similar to the SO (4,2) group in the case of the hydrogen spectrum, determines an infinite component wave function with a (realistic) mass/spin spectrum. Instead of the group theory used in the old failed attempts, it creates this mass/spin spectrum by combining an internal oscillator quantum mechanics with a pointlike-localized quantum-field-theoretic object, i.e. the mass/spin tower "sits" over one point and does not arise from a wiggling string in space–time.

The widespread acceptance of a theory whose interpretation has been based on metaphoric reasoning had a corroding influence on particle theory, a point which will be illustrated in the last section with some remarks of a more sociological nature. These remarks also lend additional support to observations on connections between the discourse in particle physics and the present Zeitgeist of the post–Cold War period that are made in the introduction.
A MEDICAL KNOWLEDGE SERVICE SYSTEM FOR CROSS-ORGANIZATIONAL HEALTHCARE COLLABORATION
Authors: CHEN YUH-JEN
Published: March 2009

Collaboration among healthcare organizations depends on coordination, communication and control among healthcare organizations and effective sharing of medical information and knowledge.

Medical services are knowledge-intensive activities. All information, knowledge, techniques and experience should be integrated, managed and shared using the Internet and information technology. Overall medical service quality and efficiency would be improved markedly if medical professionals and staff at different healthcare organizations could use and share medical knowledge resources. Therefore, a collaborative medical knowledge service would promote medical service quality.

This study presents a novel medical knowledge service system for cross-organizational healthcare collaboration such that all medical professionals and staff at different healthcare organizations could capture, store, manage, integrate and share medical knowledge. This system should improve medical service quality and efficiency, and promote competition in the healthcare industry. Thus, this study (i) proposes a collaborative medical knowledge service model, (ii) designs a collaborative medical knowledge service system framework, (iii) develops this proposed system, and (iv) evaluates the developed system based on user satisfaction.
APPLICATIONS ARITHMÉTIQUES DE L'INTERPOLATION LAGRANGIENNE
Authors: RIVOAL TANGUY
Published: March 2009

Newton's polynomial interpolation was applied in many situations in number theory, for example, to prove Polya's famous theorem on the growth of arithmetic entire function or the transcendency of eπ by Gel'fond. In this paper, we study certain arithmetic applications of the rational interpolation defined by René Lagrange in 1935, which was never done before. More precisely, we obtain new proofs of the irrationality of the numbers log(2) and ζ(3). Furthermore, we provide a simultaneous generalization of Newton and Lagrange's interpolations, which enables us to get the irrationality of ζ(2).

L'interpolation polynomiale de Newton a eu de très nombreuses applications arithmétiques en théorie des nombres, comme le célèbre théorème de Polya sur la croissance des fonctions entières arithmétiques ou encore la transcendance de eπ par Gel'fond. Dans ce papier, on présente certaines applications arithmétiques de l'interpolation rationnelle définie par René Lagrange en 1935, ce qui n'avait jamais été fait auparavant. On retrouve ainsi l'irrationalité des nombres log(2) et ζ(3). On montre ensuite comment généraliser simultanément l'interpolation de Newton et celle de Lagrange, ce qui nous permet de retrouver l'irrationalité de ζ(2).
INDIVISIBILITY OF ORDERS OF SELMER GROUPS FOR MODULAR FORMS
Authors: CHIDA MASATAKA
Published: March 2009

In this paper, we consider indivisibility of orders of Selmer groups for modular forms under quadratic twists. Then, we will give a generalization of a theorem of James–Ono and Kohnen–Ono.
ON q-SERIES IDENTITIES ARISING FROM LECTURE HALL PARTITIONS
Authors: ANDREWS GEORGE E. , CORTEEL SYLVIE , SAVAGE CARLA D.
Published: March 2009

In this paper, we highlight two q-series identities arising from the "five guidelines" approach to enumerating lecture hall partitions and give direct, q-series proofs. This requires two new finite corollaries of a q-analog of Gauss's second theorem. In fact, the method reveals stronger results about lecture hall partitions and anti-lecture hall compositions that are only partially explained combinatorially.
ENTIRE FUNCTIONS SHARING ARGUMENTS OF INTEGRALITY, I
Authors: PILA JONATHAN
Published: March 2009

Let f be an entire function that is real and strictly increasing for all sufficiently large real arguments, and that satisfies certain additional conditions, and let Xfbe the set of non-negative real numbers at which f is integer valued. Suppose g is an entire function that takes integer values on Xf. We find growth conditions under which f,g must be algebraically dependent (over ℤ) on X. The result generalizes a weak form of a theorem of Pólya.
THE INFLUENCE OF SUBSTRATE TEMPERATURE ON THE ELECTRICAL PROPERTIES OF ZnO FILMS PREPARED BY THE RF MAGNETRON SPUTTERING TECHNIQUE
Authors: SARAVANAKUMAR K. , SENTHILKUMAR V. , SANJEEVIRAJA C. , JAYACHANDRAN M. , GANESAN V. , KOIZHAIGANOVA RAUSHAN B. , VASUDEVAN T. , LEE MU SANG
Published: March 2009

ZnO thin films were grown by the RF magnetron sputtering technique at different substrate temperatures, from RT to 300°C. The crystallite size was calculated from XRD and the grain size was measured from AFM for different substrate temperatures. The influence of the substrate temperature on the electrical properties of the films was investigated through the Hall effect, and conductivity studies were performed under UV light illumination. The conductivity and the carrier mobility of the films were found to increase with increasing substrate temperature, which can be due to the grain-boundary-dominated conduction mechanism. The thermal activation energy and photosensitivity of the films were calculated, and the results are presented in this paper.
UNUSUAL ELECTROCHEMICAL RESPONSE OF ELECTROCHEMICAL ETCHING ON MULTIWALLED CARBON NANOTUBES
Authors: YE JIAN-SHAN , MO GUANGQUAN , ZHANG WEI DE , LIU XIAO , SHEU FWU-SHAN
Published: March 2009

Multiwalled carbon nanotubes (MWNTs) can be etched at potentials more positive than 1.7 V versus Ag / AgCl (3 M KCl ) in 0.2 M HNO 3. The electrochemically etched MWNTs show an increase in electrochemical impedance and sluggish electron transfer kinetics, and lose the electrocatalytic effects toward the oxidation of glucose, H 2 O 2, uric acid (UA) and L-ascorbic acid (L-AA). Transmission electron microscope (TEM) images reveal that the nanotube tips are cut off by electrochemical oxidation. This may lead to the degradation of electrocatalytic ability in the MWNTs. Furthermore, the current response after different electrochemically etched cycles shows that the electrocatalytic ability of the MWNTs toward different molecules can be tuned by etched cycles. For example, five etched cycles leads to the total disappearance of the oxidative response to L-AA, with the remaining over 50% of the UA current response in the L-AA and UA mixture. Thus, electrochemical etching is a simple yet novel way to tune the electrocatalytic reactivity and improve the selectivity of the MWNTs.
GROWTH OF HIGH QUALITY ZINC OXIDE NANOWIRES BY SIMPLE OXIDATION OF ZINC POWDER IN AIR
Authors: KOO TAE-WOONG , WHANG DONGMOK
Published: March 2009

Single-crystal ZnO nanowires are synthesized by direct oxidation of zinc particles in air at a temperature much lower than the melting temperature of zinc solids. This simple and low-cost technique produces dense and high-quality ZnO nanowires. SEM and TEM studies revealed that as-grown ZnO nanowires have a uniform diameter and defect-free single-crystal structure. The growth direction of ZnO nanowires is the a axis, which is different from the common growth direction of one-dimensional ZnO structure. Room temperature PL spectra of ZnO nanowires grown with different oxygen pressures indicated that the quality of ZnO nanowires grown in air is much better than that of wires grown at reduced oxygen pressure. The excellent property of ZnO nanowires grown in air was confirmed by electrical transport measurements of individual ZnO nanowire field effect transistors.
LOX-1-dependent transcriptional regulation in response to oxidized LDL treatment of human aortic endothelial cells
Authors: Mattaliano Mark D. , Huard Christine , Cao Wei , Hill Andrew A. , Zhong Wenyan , Martinez Robert V. , Harnish Doug C. , Paulsen Janet E. , Shih Heather H.
Published: March 2009

Oxidized low-density lipoprotein (OxLDL) has been implicated as a proatherogenic factor with a pathological role in the induction of endothelial dysfunction. Endothelial cells bind and uptake OxLDL primarily through the scavenger receptor lectin-like oxidized-low-density lipoprotein receptor-1 (LOX-1), which is believed to mediate critical effects of OxLDL in endothelial cells. To examine the biological events following LOX-1 activation by OxLDL, we used cDNA microarray analysis to globally analyze gene expression changes induced by OxLDL treatment of human aortic endothelial cell line (HAECT) cells overexpressing LOX-1. Consistent with reported functions of OxLDL, in control HAECT cells, OxLDL elicited gene changes in the oxidative stress pathway and other signaling pathways related to OxLDL. With OxLDL treatment, LOX-1-dependent gene expression changes associated with inflammation, cell adhesion, and signal transduction were observed. The transcripts of a number of cytokines and chemokines were induced, which included interleukin-8, CXCL2, CXCL3, and colony-stimulating factor-3. The secretion of these cytokines was confirmed by enzyme-linked immunosorbent assay analysis. In addition, our data revealed a novel link between LOX-1 and a number of genes, including Delta/notch-like epidermal growth factor repeat containing, stanniocalcin-1, cAMP response element modulator, and dual specificity phosphatase 1. Promoter analysis on the genes that changed as a result of LOX-1 activation by OxLDL allowed us to identify early growth response 1 and cAMP response element-binding protein as potential novel transcription factors that function downstream of LOX-1. Our study has enabled us to elucidate the gene expression changes following OxLDL activation of LOX-1 in endothelial cells and discover novel downstream targets for LOX-1.
Ischemia-reperfusion-inducible protein modulates cell sensitivity to anticancer drugs by regulating activity of efflux transporter
Authors: Prokopenko Olga , Mirochnitchenko Oleg
Published: March 2009

Human ischemia-reperfusion-inducible protein (hIRIP) or hYrdC belongs to the SUA5/YrdC/YciO protein family and affects activity of a variety of cellular transporters. We observed that overexpression of wild-type or dominant-negative mutant of hIRIP protein affects the cellular sensitivity to anticancer drugs with different mechanisms of toxicity. Here we investigated in detail the effect of hIRIP on cell sensitivity to doxorubicin and show that hIRIP inhibits the drug efflux. Multidrug-resistant P-glycoprotein was identified as one of the target transporters. IRIP does not influence P-glycoprotein biosynthesis but affects its processing and promotes degradation. We also show that P-glycoprotein is associated with COP-α, one of the proteins of the COPI complex. This interaction is sensitive to the level of hIRIP expression. These findings suggest that hIRIP expression can regulate cargo assembly and function of efflux transporters, including P-glycoprotein, which mediates one of the most common mechanisms of the multidrug resistance.
Role of basic fibroblast growth factor (FGF-2) in diabetic nephropathy and mechanisms of its induction by hyperglycemia in human renal fibroblasts
Authors: Vasko Radovan , Koziolek Michael , Ikehata Masami , Rastaldi Maria Pia , Jung Klaus , Schmid Holger , Kretzler Matthias , Müller Gerhard Anton , Strutz Frank
Published: March 2009

Basic fibroblast growth factor (FGF-2) plays a role in renal fibrogenesis, although its potential implications for tubulointerstitial involvement in diabetic nephropathy are unknown. We evaluated the expression of FGF-2 in kidney biopsies from patients with diabetic nephropathy and studied the mechanisms of its induction in human renal fibroblasts under hyperglycemia. Tubulointerstitial expression of FGF-2 was significantly upregulated in diabetic nephropathy compared with control kidneys with a good correlation to the degree of the injury. Fibroblasts cultivated in high glucose displayed increased FGF-2 mRNA as well as protein synthesis and secretion compared with normal glucose. Proliferation rates under hyperglycemia were significantly higher and could be almost completely inhibited by addition of a neutralizing FGF-2 antibody. Alterations in proliferation were associated with changes in p27kip1expression. Hyperglycemia induced the expression of PKC-β1 and PKC-β2; however, only inhibition of PKC-β1 but not PKC-β2 led to a significant decrease of FGF-2 levels. Relevance of the culture findings and functional association was corroborated by colocalization of FGF-2 and PKC-β in human diabetic kidneys in vivo. High glucose stimulated fibronectin synthesis and secretion, which could be substantially prevented by inhibition of PKC-β1 and to a lesser extent by inhibiting the FGF-2. Expression of active phosphorylated form of p38 mitogen-activated protein kinase was upregulated under hyperglycemia; however, its inhibition had no effects on FGF-2 synthesis. Our results implicate a role of FGF-2 in high glucose-altered molecular signaling in pathogenesis of diabetic renal disease.
Nitrogen excretion in developing zebrafish (Danio rerio): a role for Rh proteins and urea transporters
Authors: Braun M. H. , Steele S. L. , Ekker M. , Perry S. F.
Published: March 2009

Injection of antisense oligonucleotide morpholinos to elicit selective gene knockdown of ammonia (Rhag, Rhbg, and Rhcg1) or urea transporters (UT) was used as a tool to assess the relative importance of each transporter to nitrogen excretion in developing zebrafish ( Danio rerio). Knockdown of UT caused urea excretion to decrease by ∼90%, whereas each of the Rh protein knockdowns resulted in an ∼50% reduction in ammonia excretion. Contrary to what has been hypothesized previously for adult fish, each of the Rh proteins appeared to have a similar effect on total ammonia excretion, and thus all are required to facilitate normal ammonia excretion in the zebrafish larva. As demonstrated in other teleosts, zebrafish embryos utilized urea to a much greater extent than adults and were effectively ureotelic until hatching. At that point, ammonia excretion rapidly increased and appeared to be triggered by a large increase in the mRNA expression of Rhag, Rhbg, and Rhcg1. Unlike the situation in the adult pufferfish ( 35 ), the various transporters are not specifically localized to the gills of the developing zebrafish, but each protein has a unique expression pattern along the skin, gills, and yolk sac. This disparate pattern of expression would appear to preclude interaction between the Rh proteins in zebrafish embryos. However, this may be a developmental feature of the delayed maturation of the gills, because as the embryos matured, expression of the transporters in and around the gills increased.
Urinary endothelin-1 in chronic kidney disease and as a marker of disease activity in lupus nephritis
Authors: Dhaun Neeraj , Lilitkarntakul Pajaree , MacIntyre Iain M. , Muilwijk Eline , Johnston Neil R. , Kluth David C. , Webb David J. , Goddard Jane
Published: March 2009

Chronic inflammation contributes to the development and progression of chronic kidney disease (CKD). Identifying renal inflammation early is important. There are currently no specific markers of renal inflammation. Endothelin-1 (ET-1) is implicated in the pathogenesis of CKD. Thus, we investigated the impact of progressive renal dysfunction and renal inflammation on plasma and urinary ET-1 concentrations. In a prospective study, plasma and urinary ET-1 were measured in 132 subjects with CKD stages 1 to 5, and fractional excretion of ET-1 (FeET-1) was calculated. FeET-1, serum C-reactive protein (CRP), urinary ET-1:creatinine ratio, and urinary albumin:creatinine ratio were also measured in 29 healthy volunteers, 85 subjects with different degrees of inflammatory renal disease but normal renal function, and in 10 subjects with rheumatoid arthritis without renal involvement (RA). In subjects with nephritis associated with systemic lupus erythematosus (SLE), measurements were done before and after 6 mo of treatment. In subjects with CKD, plasma ET-1 increased linearly as renal function declined, whereas FeET-1 rose exponentially. In subjects with normal renal function, FeET-1 and urinary ET-1:creatinine ratio were higher in SLE subjects than in other groups (7.7 ± 2.7%, 10.0 ± 3.0 pg/μmol, both P < 0.001), and correlated with CRP, and significantly higher than in RA subjects (both P < 0.01) with similar CRP concentrations. In SLE patients, following treatment, FeET-1 fell to 3.6 ± 1.4% ( P < 0.01). Renal ET-1 production increases as renal function declines. In subjects with SLE, urinary ET-1 may be a useful measure of renal inflammatory disease activity while measured renal function is still normal.
Reconfiguration of the Spinal Interneuronal Network During Locomotion in Vertebrates
Authors: Frigon Alain
Published: March 2009

Within the spinal cord, the vast network of excitatory and inhibitory interneurons must be functionally reconfigured on an ongoing basis during locomotion to adapt to the environment and meet particular demands of the task. It is clear that different rhythmic motor behaviors are generated by shared and specialized circuitry and that reconfiguration is governed by multiple inputs that dynamically interact at the spinal level.