bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integration Site Preference of Xenotropic Murine Leukemia Virus-Related Virus, a New Human Retrovirus Associated with Prostate Cancer
Authors: Kim Sanggu , Kim Namshin , Dong Beihua , Boren David , Lee Serena A. , Das Gupta Jaydip , Gaughan Christina , Klein Eric A. , Lee Christopher , Silverman Robert H. , Chow Samson A. 
Published: August 2008

ABSTRACT
Xenotropic murine leukemia virus-related virus (XMRV) is a new human gammaretrovirus identified in prostate cancer tissue from patients homozygous for a reduced-activity variant of the antiviral enzyme RNase L. Neither a casual relationship between XMRV infection and prostate cancer nor a mechanism of tumorigenesis has been established. To determine the integration site preferences of XMRV and the potential risk of proviral insertional mutagenesis, we carried out a genome-wide analysis of viral integration sites in the prostate cell line DU145 after an acute XMRV infection and compared the integration site pattern of XMRV with those found for murine leukemia virus and two human retroviruses, human immunodeficiency virus type 1 and human T-cell leukemia virus type 1. Among all retroviruses analyzed, XMRV has the strongest preference for transcription start sites, CpG islands, DNase-hypersensitive sites, and gene-dense regions; all are features frequently associated with structurally open transcription regulatory regions of a chromosome. Analyses of XMRV integration sites in tissues from prostate cancer patients found a similar preference for the aforementioned chromosomal features. Additionally, XMRV integration sites in cancer tissues were associated with cancer breakpoints, common fragile sites, microRNA, and cancer-related genes, suggesting a selection process that favors certain chromosomal integration sites. In both acutely infected cells and cancer tissues, no common integration site was detected within or near proto-oncogenes or tumor suppressor genes. These results are consistent with a model in which XMRV may contribute to tumorigenicity via a paracrine mechanism.
CD20, CD3, and CD40 Ligand Microclusters Segregate Three-Dimensionally In Vivo at B-Cell-T-Cell Immunological Synapses after Viral Immunity in Primate Brain
Authors: Barcia Carlos , Gomez Aurora , de Pablos Vicente , Fernández-Villalba Emiliano , Liu Chunyan , Kroeger Kurt M. , Martín Javier , Barreiro Andrés Fernández , Castro Maria G. , Lowenstein Pedro R. , Herrero Maria-Trinidad 
Published: August 2008

ABSTRACTThe clearance of virally infected cells from the brain is mediated by T cells that engage antigen-presenting cells to form supramolecular activation clusters at the immunological synapse. However, after clearance, the T cells persist at the infection site and remain activated locally. In the present work the long-term interactions of immune cells in brains of monkeys were imaged in situ 9 months after the viral inoculation. After viral immunity, the persistent infiltration of T cells and B cells was observed at the infection sites. T cells showed evidence of T-cell receptor signaling as a result of contacts with B cells. Three-dimensional analysis of B-cell-T-cell synapses showed clusters of CD3 in T cells and the segregation of CD20 in B cells, involving the recruitment of CD40 ligand at the interface. These results demonstrate that immunological synapses between B cells and T cells forming three-dimensional microclusters occur in vivo in the central nervous system and suggest that these interactions may be involved in the lymphocyte activation after viral immunity at the original infection site.
Small-Molecule Effectors of Hepatitis B Virus Capsid Assembly Give Insight into Virus Life Cycle
Authors: Bourne Christina , Lee Sejin , Venkataiah Bollu , Lee Angela , Korba Brent , Finn M. G. , Zlotnick Adam 
Published: August 2008

ABSTRACT
The relationship between the physical chemistry and biology of self-assembly is poorly understood, but it will be critical to quantitatively understand infection and for the design of antivirals that target virus genesis. Here we take advantage of heteroaryldihydropyrimidines (HAPs), which affect hepatitis B virus (HBV) assembly, to gain insight and correlate in vitro assembly with HBV replication in culture. Based on a low-resolution crystal structure of a capsid-HAP complex, a closely related series of HAPs were designed and synthesized. These differentially strengthen the association between neighboring capsid proteins, alter the kinetics of assembly, and give rise to aberrant structures incompatible with a functional capsid. The chemical nature of the HAP variants correlated well with the structure of the HAP binding pocket. The thermodynamics and kinetics of in vitro assembly had strong and predictable effects on product morphology. However, only the kinetics of in vitro assembly had a strong correlation with inhibition of HBV replication in HepG2.2.15 cells; there was at best a weak correlation between assembly thermodynamics and replication. The correlation between assembly kinetics and virus suppression implies a competition between successful assembly and misassembly, small molecule induced or otherwise. This is a predictive and testable model for the mechanism of action of assembly effectors.
Functions of Varicella-Zoster Virus ORF23 Capsid Protein in Viral Replication and the Pathogenesis of Skin Infection
Authors: Chaudhuri Vaishali , Sommer Marvin , Rajamani Jaya , Zerboni Leigh , Arvin Ann M. 
Published: August 2008

ABSTRACT
The assembly of herpesvirus capsids is a complex process involving interactions of multiple proteins in the cytoplasm and in the nucleus. Based on comparative genome analyses, varicella-zoster virus (VZV) open reading frame 23 (ORF23) encodes a conserved capsid protein, referred to as VP26 (UL35) in other alphaherpesviruses. Mutagenesis using a VZV bacterial artificial chromosome system showed that ORF23 was dispensable for replication in vitro. However, the absence of ORF23 disrupted capsid assembly in a melanoma cell line. Expression of ORF23 as a red fluorescent protein (RFP) fusion protein appeared to have a dominant negative effect on replication that was rescued by ORF23 expression from a nonnative site in the VZV genome. In contrast to its VP26 homolog, ORF23 has an intrinsic nuclear localization capacity that was mapped to an SRSRVV motif at residues 229 to 234 in the extreme C terminus of ORF23. In addition, coexpression with ORF23 resulted in nuclear import of the major capsid protein, ORF40. VZV ORF33.5 also translocated ORF40, which may provide a redundant mechanism in vitro but appears insufficient to overcome the dominant negative effect of the monomeric RFP-ORF23 (mRFP23) fusion protein. ORF23 was required for VZV infection of human skin xenografts, indicating that ORF33.5 does not compensate for lack of ORF23 in vivo. These observations suggest a model of VZV capsid assembly in which nuclear transport of the major capsid protein and associated proteins requires ORF23 during VZV replication in the human host. If so, ORF23 expression could be a target for a novel antiviral drug against VZV.
The G-rich promoter and G-rich coding sequence of basic fibroblast growth factor are the targets of thalidomide in glioma
Authors: Mei Szu-Chieh , Wu Rong-Tsun 
Published: August 2008

Abstract
Thalidomide is considered to be a potent antiangiogenic and immunomodulatory drug for cancer therapy. Earlier clinical studies have found that patients responding to this drug often had high plasma levels of basic fibroblast growth factor (bFGF). This cytokine is a proangiogenic factor overexpressed in many tumors and is also a regulator of limb development; hence, it might be a target of thalidomide. Using U-87 MG cell lines, we found that thalidomide, especially when encapsulated in a liposome, down-regulated the transcription and translation of the FGF-2 gene by interacting with G-rich regions present in the promoter and the internal ribosome entry site of its transcript at concentrations much lower than therapeutic serum concentrations. Thalidomide treatment also dramatically suppressed the anchorage-independent growth of U-87 MG and other glioma cells by over a thousand fold without affecting its anchorage-dependent growth, which may be accomplished by knocking down endogenous bFGF expression in these cells. Accordingly, the addition of recombinant bFGF partially restored the anchorage-independent growth of these cells. Our data suggest that by targeting the G-rich regions of bFGF, thalidomide (at 0.1 μg/mL) can reduce cellular bFGF levels and affect tumor anchorage-independent growth, the hallmark of tumorigenicity. Our results are promising for future clinical investigations using low doses of thalidomide. [Mol Cancer Ther 2008;7(8):2405–14]
Differential response of primary tumor versus lymphatic metastasis to VEGFR-2 and VEGFR-3 kinase inhibitors cediranib and vandetanib
Authors: Padera Timothy P. , Kuo Angera H. , Hoshida Tohru , Liao Shan , Lobo Jennifer , Kozak Kevin R. , Fukumura Dai , Jain Rakesh K. 
Published: August 2008

Abstract
Blood vessels are required for a tumor to grow and functional lymphatic vessels are required for it to disseminate to lymph nodes. In an attempt to eradicate both the primary tumor and its lymphatic metastasis, we targeted both blood and lymphatic vessels using two different tyrosine kinase inhibitors (TKIs): cediranib and vandetanib, which block vascular endothelial growth factor receptor (VEGFR)-2 and -3 in enzymatic assays. We found that although both cediranib and vandetanib slowed the growth rate of primary tumors and reduced blood vessel density, neither agent was able to prevent lymphatic metastasis when given after tumor cells had seeded the lymph node. However, when given during tumor growth, cediranib reduced the diameters of the draining lymphatic vessels, the number of tumor cells arriving in the draining lymph node, and the incidence of lymphatic metastasis. On the other hand, vandetanib had minimal effect on any of these variables, suggesting that vandetanib did not effectively block VEGFR-3 on lymphatic endothelial cells in our animal model. Collectively, these data indicate that the response of lymphatic vessels to a TKI can determine the incidence of lymphatic metastasis, independent of the effect of the TKI on blood vessels. [Mol Cancer Ther 2008;7(8):2272–9]
An Energy-Constrained Parameterization of Eddy Buoyancy Flux
Authors: Cessi Paola 
Published: August 2008

Abstract
A parameterization for eddy buoyancy fluxes for use in coarse-grid models is developed and tested against eddy-resolving simulations. The development is based on the assumption that the eddies are adiabatic (except near the surface) and the observation that the flux of buoyancy is affected by barotropic, depth-independent eddies. Like the previous parameterizations of Gent and McWilliams (GM) and Visbeck et al. (VMHS), the horizontal flux of a tracer is proportional to the local large-scale horizontal gradient of the tracer through a transfer coefficient assumed to be given by the product of a typical eddy velocity scale and a typical mixing length. The proposed parameterization differs from GM and VMHS in the selection of the eddy velocity scale, which is based on the kinetic energy balance of baroclinic eddies. The three parameterizations are compared to eddy-resolving computations in a variety of forcing configurations and for several sets of parameters. The VMHS and the energy balance parameterizations perform best in the tests considered here.
Western Arctic Shelfbreak Eddies: Formation and Transport
Authors: Spall Michael A. , Pickart Robert S. , Fratantoni Paula S. , Plueddemann Albert J. 
Published: August 2008

Abstract
The mean structure and time-dependent behavior of the shelfbreak jet along the southern Beaufort Sea, and its ability to transport properties into the basin interior via eddies are explored using high-resolution mooring data and an idealized numerical model. The analysis focuses on springtime, when weakly stratified winter-transformed Pacific water is being advected out of the Chukchi Sea. When winds are weak, the observed jet is bottom trapped with a low potential vorticity core and has maximum mean velocities of O(25 cm s−1) and an eastward transport of 0.42 Sv (1 Sv ≡ 106 m3 s−1). Despite the absence of winds, the current is highly time dependent, with relative vorticity and twisting vorticity often important components of the Ertel potential vorticity. An idealized primitive equation model forced by dense, weakly stratified waters flowing off a shelf produces a mean middepth boundary current similar in structure to that observed at the mooring site. The model boundary current is also highly variable, and produces numerous strong, small anticyclonic eddies that transport the shelf water into the basin interior. Analysis of the energy conversion terms in both the mooring data and the numerical model indicates that the eddies are formed via baroclinic instability of the boundary current. The structure of the eddies in the basin interior compares well with observations from drifting ice platforms. The results suggest that eddies shed from the shelfbreak jet contribute significantly to the offshore flux of heat, salt, and other properties, and are likely important for the ventilation of the halocline in the western Arctic Ocean. Interaction with an anticyclonic basin-scale circulation, meant to represent the Beaufort gyre, enhances the offshore transport of shelf water and results in a loss of mass transport from the shelfbreak jet.
Physics of “Saturation-Based” Dissipation Functions Proposed for Wave Forecast Models
Authors: Babanin Alexander V. , van der Westhuysen AndréJ. 
Published: August 2008

Abstract
The dissipation term is one of the three most important source functions of the radiative transfer equation employed by all spectral wave models to predict the wave spectrum. In this paper, the issue of physics of such dissipation functions is discussed. It is argued that the physics presently utilized in the models do not adequately describe currently known features of the wave dissipation process, and the dissipation functions, to a great extent, remain a residual tuning term in spite of important experimental progress in wave breaking studies. A recently suggested “saturation-based” dissipation function and its connections with the experimental physics are analyzed in detail.
Observations of the Dispersion Characteristics and Meridional Sea Level Structure of Equatorial Waves in the Pacific Ocean
Authors: Farrar J. Thomas 
Published: August 2008

Abstract
Spectral techniques applied to altimetry data are used to examine the dispersion relation and meridional sea level structure of wavelike variability with periods of about 20 to 200 days in the equatorial Pacific Ocean. Zonal wavenumber–frequency power spectra of sea surface height, when averaged over about 7°S–7°N, exhibit spectral peaks near the theoretical dispersion curves of first baroclinic-mode equatorial Kelvin and Rossby waves. There are distinct, statistically significant ridges of power near the first and second meridional-mode Rossby wave dispersion curves. Sea level variability near the theoretical Kelvin wave and first meridional-mode Rossby wave dispersion curves is dominantly (but not perfectly) symmetric about the equator, while variability near the theoretical second meridional-mode Rossby wave dispersion curve is dominantly antisymmetric. These results are qualitatively consistent with expectations from classical or shear-modified theories of equatorial waves.
The meridional structures of these modes resemble the meridional modes of equatorial wave theory, but there are some robust features of the meridional profiles that were not anticipated. The meridional sea level structure in the intraseasonal Kelvin wave band closely resembles the theoretically expected Gaussian profile, but sea level variability coherent with that at the equator is detected as far away as 11.75°S, possibly as a result of the forced nature of these Kelvin waves. Both first and second meridional-mode Rossby waves have larger amplitude in the Northern Hemisphere. The meridional sea level structure of tropical instability waves closely resembles that predicted by Lyman et al. using a model linearized about a realistic equatorial zonal current system.
Interannual Variability of Sea Surface Height over the Black Sea: Relation to Climatic Patterns
Authors: Kara A. Birol , Barron Charlie N. , Wallcraft Alan J. , Oguz Temel 
Published: August 2008

Abstract
Sea surface height (SSH) variability is presented over the Black Sea during 1993–2005. The 1/4° × 1/4° resolution daily SSH fields are formed using optimal interpolation of available altimeter data. SSH variability reveals distinct maxima in the eastern and western basins, reflecting variations in the corresponding gyres. A joint examination of SSH and sea surface temperature (SST) indicates strong relationship between the two only in winter, with correlations as high as 0.6 or more. This would reflect a steric change in sea surface height due to thermal expansion averaged over a relatively deep winter mixed layer. Newly developed SSH fields also demonstrate a switch to the positive mode of SSH starting from the end of 1996 lasting ≈4 yr. Such a climatic shift is found to be strongly related to large-scale teleconnection patterns. Finally, the daily SSH and SST anomaly fields presented in this paper can supplement various applications in the Black Sea, such as examination of biological production and mesoscale eddy dynamics.
Evaluation of a Satellite Multispectral VIS–IR Daytime Statistical Rain-Rate Classifier and Comparison with Passive Microwave Rainfall Estimates
Authors: Capacci Davide , Porcù Federico 
Published: August 2008

Abstract
A daytime surface rain-rate classifier, based on artificial neural networks (ANNs), is proposed for the Spinning Enhanced Visible and Infrared Imager (SEVIRI) on board the Meteosat-8 geostationary satellite. It is developed over the British Isles and surrounding waters, where the Met Office radar network provided the “ground precipitation truth” for training and validation. The algorithm classifies rain rate in five classes at 15 min and 5 km of time and spatial resolution, and is applied on daytime hours in a summer and winter database. A further ANN application is restricted to hours between 1200 and 1400 UTC for which the Advanced Microwave Scanning Radiometer for Earth Observing System (AMSR-E) on board the Aqua polar-orbiting satellite scans the U.K. area: ANN-classifier algorithms for the SEVIRI and AMSR-E data have been developed and the results have been compared. A reliable validation procedure is adopted to quantify the performance in view of the operational application of the daytime classifier and to investigate the relative skills of passive microwave and visible–infrared radiances in sensing precipitation if processed with equivalent algorithms. The key statistical parameters used are the equitable threat score (ETS) and the bias for rain–no rain classes and the Heidke skill score (HSS) for rain-rate classes. The SEVIRI daytime classifier shows, for mean seasonal conditions, the best performance in summer, with ETS = 47% and HSS = 22%, and in winter ETS = 36% and HSS = 17% were found. The comparison between AMSR-E and SEVIRI noon classifiers reveals a similar overall skill: in detecting rain areas, SEVIRI is slightly better than AMSR-E, while the opposite is true for rain-rate classification.
The Association of the Evolution of Intraseasonal Oscillations to ENSO Phase
Authors: Roundy Paul E. , Kravitz Joseph R. 
Published: August 2008

Abstract
The Pacific Ocean intraseasonal Kelvin wave is a leading oceanic mode that links intraseasonal tropical atmospheric variations with interannual variations in the coupled ocean–atmosphere system. This study considers the premise that these waves may evolve differently with their associated weather patterns during different phases of El Niño–Southern Oscillation (ENSO). If atmospheric and oceanic intraseasonal modes interact and evolve differently during various stages of ENSO, this result may provide useful information with regard to the role of these intraseasonal processes in ENSO evolution. This work utilizes signals of the oceanic Kelvin wave as a statistical basis for a simple composite averaging technique that is applied during different phases of ENSO to objectively analyze the evolution of oceanic and the associated portions of atmospheric intraseasonal oscillations. Results confirm the above premise and suggest that coupling between Kelvin waves and atmospheric convection evolves differently during different stages of ENSO. Further, intraseasonal zonal wind anomalies across the east Pacific timed with oceanic Kelvin waves are stronger during adjustment toward El Niño than during adjustment away from El Niño. These and other patterns in the composites suggest the possibility that systematic changes in the evolution of intraseasonal variations over the course of ENSO might feed back upon this interannual mode to influence the evolution of ENSO itself.
Indian Ocean Capacitor Effect on Indo–Western Pacific Climate during the Summer following El Niño
Authors: Xie Shang-Ping , Hu Kaiming , Hafner Jan , Tokinaga Hiroki , Du Yan , Huang Gang , Sampe Takeaki 
Published: August 2008

Abstract
Significant climate anomalies persist through the summer (June–August) after El Niño dissipates in spring over the equatorial Pacific. They include the tropical Indian Ocean (TIO) sea surface temperature (SST) warming, increased tropical tropospheric temperature, an anomalous anticyclone over the subtropical northwest Pacific, and increased mei-yu–baiu rainfall over East Asia. The cause of these lingering El Niño effects during summer is investigated using observations and an atmospheric general circulation model (GCM). The results herein indicate that the TIO warming acts like a capacitor anchoring atmospheric anomalies over the Indo–western Pacific Oceans. It causes tropospheric temperature to increase by a moist-adiabatic adjustment in deep convection, emanating a baroclinic Kelvin wave into the Pacific. In the northwest Pacific, this equatorial Kelvin wave induces northeasterly surface wind anomalies, and the resultant divergence in the subtropics triggers suppressed convection and the anomalous anticyclone. The GCM results support this Kelvin wave–induced Ekman divergence mechanism. In response to a prescribed SST increase over the TIO, the model simulates the Kelvin wave with low pressure on the equator as well as suppressed convection and the anomalous anticyclone over the subtropical northwest Pacific. An additional experiment further indicates that the north Indian Ocean warming is most important for the Kelvin wave and northwest Pacific anticyclone, a result corroborated by observations.
These results have important implications for the predictability of Indo–western Pacific summer climate: the spatial distribution and magnitude of the TIO warming, rather than simply whether there is an El Niño in the preceding winter, affect summer climate anomalies over the Indo–western Pacific and East Asia.
An Analysis of the Performance of the UFAM Pulsed Doppler Lidar for Observing the Boundary Layer
Authors: Pearson Guy , Davies Fay , Collier Chris 
Published: August 2008

Abstract
The performance of the 1.5-μm pulsed Doppler lidar, operated by the U.K. Universities Facility for Atmospheric Measurement (UFAM) over a 51-day continuous and unattended field deployment in southern England, is described and analyzed with a view to demonstrating the capabilities of the system for remote measurements of aerosols and velocities in the boundary layer. A statistical assessment of the vertical pointing mode in terms of the availability and errors in the data versus range is presented. Examples of lidar data are compared to theoretical predictions, radiosondes, the UFAM radar wind profiler, and an ultrasonic anemometer.