bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative Analysis of the Bidirectional Viral G-Protein-Coupled Receptor and Lytic Latency-Associated Nuclear Antigen Promoter of Kaposi's Sarcoma-Associated Herpesvirus
Authors: Hilton Isaac B. , Dittmer Dirk P. 
Published: June 2012

ABSTRACT

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes sustained latent persistence in susceptible cells. This is dependent on the latency-associated nuclear antigen (LANA). Understanding how LANA transcription is regulated thus aids our fundamental understanding of KSHV biology. Two hundred ninety-four base pairs are sufficient to regulate LANA transcription in response to the viral RTA protein and RBPjκ. The same region controls K14/viral G-protein-coupled receptor (vGPCR) transcription in the opposite direction. We used a quantitative analysis in conjunction with specific nucleotide substitutions and defined gain-of-function and loss-of-function RTA mutants to dissect this region. We used a bidirectional reporter driving red and green luciferase to study the LANApi and K14p promoters simultaneously. This established that LANApi/K14p functions as a canonical bidirectional promoter. Both were TATA dependent. K14p was favored by ∼50-fold in this context. Eliminating the distal LANApi TATA box increased maximal output and lowered the induction threshold (
T
) of K14p even further. Two RBPjκ binding sites were independently required; however, at high concentrations of RTA, direct interactions with an RTA-responsive element (RRE) could complement the loss of one RBPjκ binding site. Intracellular Notch (ICN) was no longer able to activate RBPjκ in the viral context. This suggests a model whereby KSHV alters ICN-RBPjκ gene regulation. When the architecture of this pair of head-to-head RBPjκ binding sites is changed, the sites now respond exclusively to the viral transactivator RTA and no longer to the host mediator ICN.
Memory CD8+T Cells Specific for a Single Immunodominant or Subdominant Determinant Induced by Peptide-Dendritic Cell Immunization Protect from an Acute Lethal Viral Disease
Authors: Remakus Sanda , Rubio Daniel , Ma Xueying , Sette Alessandro , Sigal Luis J. 
Published: June 2012

ABSTRACTThe antigens recognized by individual CD8+T cells are small peptides bound to major histocompatibility complex (MHC) class I molecules. The CD8+T cell response to a virus is restricted to several peptides, and the magnitudes of the effector as well as memory phases of the response to the individual peptides are generally hierarchical. The peptide eliciting a stronger response is called immunodominant (ID), and those with smaller-magnitude responses are termed subdominant (SD). The relative importance of ID and SD determinants in protective immunity remains to be fully elucidated. We previously showed that multispecific memory CD8+T cells can protect susceptible mice from mousepox, an acute lethal viral disease. It remained unknown, however, whether CD8+T cells specific for single ID or SD peptides could be protective. Here, we demonstrate that immunization with dendritic cells pulsed with ID and some but not all SD peptides induces memory CD8+T cells that are fully capable of protecting susceptible mice from mousepox. Additionally, while natural killer (NK) cells are essential for the natural resistance of nonimmune C57BL/6 (B6) to mousepox, we show that memory CD8+T cells of single specificity also protect B6 mice depleted of NK cells. This suggests it is feasible to produce effective antiviral CD8+T cell vaccines using single CD8+T cell determinants and that NK cells are no longer essential when memory CD8+T cells are present.
Characterization and Intracellular Trafficking of Epstein-Barr Virus BBLF1, a Protein Involved in Virion Maturation
Authors: Chiu Ya-Fang , Sugden Bill , Chang Pey-Jium , Chen Lee-Wen , Lin Ying-Ju , Lan Yu-Ching , Lai Chih-Ho , Liou Jieh-Yuan , Liu Shih-Tung , Hung Chien-Hui 
Published: June 2012

ABSTRACT

Epstein-Barr virus (EBV) BBLF1 shares 13 to 15% amino acid sequence identities with the herpes simplex virus 1 UL11 and cytomegalovirus UL99 tegument proteins, which are involved in the final envelopment during viral maturation. This study demonstrates that BBLF1 is a myristoylated and palmitoylated protein, as are UL11 and UL99. Myristoylation of BBLF1 both facilitates its membrane anchoring and stabilizes it. BBLF1 is shown to localize to the
trans
-Golgi network (TGN) along with gp350/220, a site where final envelopment of EBV particles takes place. The localization of BBLF1 at the TGN requires myristoylation and two acidic clusters, which interact with PACS-1, a cytosolic protein, to mediate retrograde transport from the endosomes to the TGN. Knockdown of the expression of BBLF1 during EBV lytic replication reduces the production of virus particles, demonstrating the requirement of BBLF1 to achieve optimal production of virus particles. BBLF1 is hypothesized to facilitate the budding of tegumented capsid into glycoprotein-embedded membrane during viral maturation.
Long-term outcome of drug-eluting stenting for stenoses of the intracranial vertebrobasilar artery and vertebral ostium
Authors: Lu Haitao , Zheng Ping , Zhang Wenchuan 
Published: June 2012

ObjectPatients with symptomatic atherosclerotic stenosis of the intracranial vertebrobasilar artery (VBA) have a poor prognosis, and those with coexistent intracranial and extracranial stenoses have worse outcomes despite medical therapy. A study was undertaken to investigate the long-term outcome and restenosis rates of patients with symptomatic atherosclerotic stenoses at the intracranial VBA and the vertebral artery ostium (VAO) after drug-eluting stent (DES) placement.MethodsFrom July 2004 to July 2008, 24 consecutive patients (mean age 65 years) with this condition underwent DES placement. Technical success was defined as stent placement of both the VAO and intracranial VBA stenoses with complete stent coverage of the lesions and residual stenosis of ≤30%. The study end point was a composite of stroke or death within 30 days and ischemic stroke in the VBA territory after 30 days.ResultsTechnical success was obtained in all patients without any stroke or death within 30 days. During a median follow-up duration of 35 months, recurrent in-stent restenosis developed in two cases (10%) at 12-month follow-up. These two patients were free from stroke recurrence. Thus, the annual stroke rate in the VBA territory (including any stroke or death within 30 days) was 0.ConclusionsThis pilot study confirms that DES placement for patients with symptomatic atherosclerotic stenoses at the intracranial VBA and VAO has an acceptable long-term outcome and may be considered as an alternative to medical therapy.
Concomitant intracranial pressure monitoring during venous sinus stenting for intracranial hypertension secondary to venous sinus stenosis
Authors: Fargen Kyle M , Velat Gregory J , Lewis Stephen B , Hoh Brian L , Mocco J , Lawson Matthew F 
Published: June 2012

BackgroundThere is a growing body of literature supporting venous sinus stenosis as a causative etiology for many patients diagnosed with idiopathic intracranial hypertension. Recent series have documented improvement in the pre- and post-stenosis venous pressure gradient as well as clinical symptoms after stenting. Concomitant real time intracranial pressure (ICP) monitoring has not been previously described during venous sinus stenting.Case reportA woman in her twenties presented with rapidly progressive visual loss and cranial neuropathies with an MRI revealing high grade right transverse sinus stenosis. Lumbar puncture demonstrated an opening pressure >55 cm H2O. Her vision and cranial neuropathies continued to worsen despite ventriculoperitoneal shunting. A parenchymal ICP monitoring wire was placed, revealing ICP persistently >70 cm H2O. She underwent venography and a pre- to post-stenosis pressure gradient of 55 mm Hg was measured. The patient underwent sinus stenting resulting in a near immediate reduction in her ICP from 70 to 20 cm H2O within 30 s after deployment. Her ICP completely normalized within 24 h of stenting.ConclusionsA case is presented of severe intracranial hypertension with rapidly progressive neurologic decline despite CSF diversion secondary to venous sinus stenosis that resolved following venous sinus stenting. This is the first report of real time ICP monitoring during venous sinus stenting.
Ecological niche modeling on the effect of climatic change and conservation of Ternstroemia lineata DC. (Ternstroemiaceae) in Mesoamerica
Authors: Luna-Vega Isolda , Alcántara-Ayala Othón , Contreras-Medina Raúl , Ríos-Muñoz César A. 
Published: June 2012

A bioclimatic modeling of the tree Ternstroemia lineata DC. (Ternstroemiaceae) was undertaken. The genus itself is considered as diagnostic or characteristic of the Mexican cloud forest. Ternstroemia lineata has the broadest distribution of all species in this family in Mexico and northern Central America. This species consists of two subspecies, T. lineata subsp. lineata and T. lineata subsp. chalicophila (Loes.) B.M. Barthol. Ecological niche models for both subspecies were generated using the genetic algorithm for rule-set production method. The ecological models for the years 2020, 2050, and 2080 were obtained under the effects of global climatic change considering two emission scenarios (A2a and B2a). When climatic change values were introduced, the ecological niche representation for both subspecies contracted in such a way that they became almost lost throughout their entire geographical range. In both cases, predictions for all years in both scenarios contracted more than 90%. This species may not be able to adapt to modifications caused by climatic change to future conditions, so it is at risk of extinction in the immediate future.
Restrained concrete shrinkage in composite trusses
Authors: Orta Luis , Bartlett F. Michael 
Published: June 2012

An analytical approach to compute restrained shrinkage effects on composite concrete deck – steel truss members is presented and validated using strains and deflections obtained by Brattland and Kennedy, who in 1986 tested two full-scale (11.8 m × 2.35 m in plan) composite trusses and companion drying specimens for approximately 90 d. The test-to-predicted ratios for these quantities are excellent, with a mean value of 0.89 and a coefficient of variation of 0.11. It is also demonstrated that (1) single test specimens with a single drying face exhibit a large gradient of free shrinkage strain across the depth of the specimen that must be properly considered in the analysis; (2) shrinkage parameters estimated using generic rules based on the concrete mixture composition are not realistic for the particular mix used by Brattland and Kennedy; and (3) history-independent analysis methods, as described in Annex H of CSA S16-09, do not accurately predict the slab strains and truss deflections observed by Brattland and Kennedy unless the variation of the free shrinkage strain with slab depth, tensile creep, and concrete modulus of elasticity are properly accounted for.
An algorithm for 3D simulation of branchwork karst networks using Horton parameters and 𝒜★ Application to a synthetic case
Authors: Collon-Drouaillet Pauline , Henrion Vincent , Pellerin Jeanne 
Published: June 2012

Abstract
This paper presents a method to stochastically simulate 3D karstic networks and more specifically branchwork pattern cave systems. Considering that they can be compared with 3D fluvial networks, the topological classification of Strahler and the corresponding ratios of Horton are used to define three morphometric parameters. These parameters are integrated in an algorithm that computes branches hierarchically to obtain a final network organized around the main observed inlet and outlet with a branching complexity controlled by the user. Each branch corresponds to a low-cost path between two points calculated with the 𝒜★ graph search algorithm. Speleogenetic information on inception horizons, palaeo-water tables and fractures is accounted for by adapted definitions of the searching functions of 𝒜★. The method is demonstrated on a 3D synthetic case with discrete fractures networks, inception horizons and a palaeo-water table. The simulated karsts have a realistic geometry and are geologically consistent.
Reservoir properties and petrophysical modelling of carbonate sand bodies: outcrop analogue study in an epicontinental basin (Triassic, Germany)
Authors: Palermo Denis , Aigner Thomas , Seyfang Bjoern , Nardon Sergio 
Published: June 2012

Abstract

This paper represents the second part of an integrated study that is focussed on the development and distribution of reservoir bodies and properties in epeiric carbonate systems. It is based on outcrop analogue data from Triassic ‘layer-cake’ carbonates in the South German Basin, which were deposited along an epicontinental, very gently inclined carbonate ramp. The reservoir facies consists of skeletal and oolitic carbonate grainstones (Φ
max
23%,
K
max
700 mD), which are organized in a pronounced hierarchy of stratigraphic cycles. Based on outcrops, cores, gamma ray (GR) logs and thin sections, a high-resolution, geocellular 3D facies model was generated, which covers the area of a Middle East giant gas field (25×36 km). The spatial distribution of reservoir properties was systematically investigated on different scales. The lateral distribution of reservoir properties remains in the same order of magnitude for hundreds of metres, within in the same stratigraphic position. However, on a kilometre scale, facies bodies, diagenetic trends and thus reservoir properties show gradual lateral changes. Vertically, in contrast, properties change commonly on a decimetre scale and are largely controlled by stratigraphic cycles. Petrophysical modelling enhanced the understanding of key factors and processes controlling both reservoir quality and quantity.
Magnetic characterization of oil sands at Osmington Mills and Mupe Bay, Wessex Basin, UK
Authors: Emmerton Stacey , Muxworthy Adrian R. , Sephton Mark A 
Published: June 2012

Abstract

This study combines magnetic experimentation and geochemical analysis on oil sands from Osmington Mills and Mupe Bay, Wessex Basin, UK to investigate the possibility of a relationship between hydrocarbons and magnetic mineralogy. Removal of hydrocarbons by chemical extraction was conducted to allow comparison of (1) oil sands and (2) cleaned sands. Detailed magnetic analysis including low-temperature and high-temperature experimentation revealed that all but one sample was dominated by siderite, identified by the Néel transition at 37–38 K as well as containing large grains of multidomain magnetite (Verwey transition 110 K) and hematite (Morin transition 250 K). Scanning electron microscopy and energy dispersive x-ray analysis confirmed the presence of iron oxides, in particular framboids 500 nm–45 µm in diameter, probably magnetite. Hysteresis parameters showed distinct grouping of oil sands compared to their clean counterparts and a negative linear regression in log space was observed (
R
2
=0.7) between the percentage of extractable organic matter and magnetic susceptibility. These results suggest a relationship exists between magnetic minerals and the alteration of oil due to biodegradation, which is not yet fully understood. Possible mechanisms are suggested to be due to anaerobic bacteria or the transportation of the oil as it migrates through the host rock.
Tankyrase and the Canonical Wnt Pathway Protect Lung Cancer Cells from EGFR Inhibition
Authors: Casás-Selves Matias , Kim Jihye , Zhang Zhiyong , Helfrich Barbara A. , Gao Dexiang , Porter Christopher C. , Scarborough Hannah A. , Bunn Paul A. , Chan Daniel C. , Tan Aik Choon , DeGregori James 
Published: June 2012

Abstract
Lung cancer is the leading cause of death worldwide. Adenocarcinomas, the most common histologic subtype of non-small cell lung cancer (NSCLC), are frequently associated with activating mutations in the epidermal growth factor receptor (EGFR) gene. Although these patients often respond clinically to the EGFR tyrosine kinase inhibitors erlotinib and gefitinib, relapse inevitably occurs, suggesting the development of escape mechanisms that promote cell survival. Using a loss-of-function, whole genome short hairpin RNA (shRNA) screen, we identified that the canonical Wnt pathway contributes to the maintenance of NSCLC cells during EGFR inhibition, particularly the poly-ADP-ribosylating enzymes tankyrase 1 and 2 that positively regulate canonical Wnt signaling. Inhibition of tankyrase and various other components of the Wnt pathway with shRNAs or small molecules significantly increased the efficacy of EGFR inhibitors both in vitro and in vivo. Our findings therefore reveal a critical role for tankyrase and the canonical Wnt pathway in maintaining lung cancer cells during EGFR inhibition. Targeting the Wnt-tankyrase-β-catenin pathway together with EGFR inhibition may improve clinical outcome in patients with NSCLC. Cancer Res; 72(16); 4154–64. ©2012 AACR.
Neuropilin-1 Stimulates Tumor Growth by Increasing Fibronectin Fibril Assembly in the Tumor Microenvironment
Authors: Yaqoob Usman , Cao Sheng , Shergill Uday , Jagavelu Kumaravelu , Geng Zhimin , Yin Meng , de Assuncao Thiago M. , Cao Ying , Szabolcs Anna , Thorgeirsson Snorri , Schwartz Martin , Yang Ju Dong , Ehman Richard , Roberts Lewis , Mukhopadhyay Debabrata , Shah Vijay H. 
Published: June 2012

Abstract
The tumor microenvironment, including stromal myofibroblasts and associated matrix proteins, regulates cancer cell invasion and proliferation. Here, we report that neuropilin-1 (NRP-1) orchestrates communications between myofibroblasts and soluble fibronectin that promote α5β1 integrin–dependent fibronectin fibril assembly, matrix stiffness, and tumor growth. Tumor growth and fibronectin fibril assembly were reduced by genetic depletion or antibody neutralization of NRP-1 from stromal myofibroblasts in vivo. Mechanistically, the increase in fibronectin fibril assembly required glycosylation of serine 612 of the extracellular domain of NRP-1, an intact intracellular NRP-1 SEA domain, and intracellular associations between NRP-1, the scaffold protein GIPC, and the nonreceptor tyrosine kinase c-Abl that augmented α5β1 fibronectin fibril assembly activity. Analysis of human cancer specimens established an association between tumoral NRP-1 levels and clinical outcome. Our findings indicate that NRP-1 activates the tumor microenvironment, thereby promoting tumor growth. These results not only identify new molecular mechanisms of fibronectin fibril assembly but also have important implications for therapeutic targeting of the myofibroblast in the tumor microenvironment. Cancer Res; 72(16); 4047–59. ©2012 AACR.
Cell Death via DR5, but not DR4, Is Regulated by p53 in Myeloma Cells
Authors: Surget Sylvanie , Chiron David , Gomez-Bougie Patricia , Descamps Géraldine , Ménoret Emmanuelle , Bataille Régis , Moreau Philippe , Le Gouill Steven , Amiot Martine , Pellat-Deceunynck Catherine 
Published: June 2012

AbstractMyeloma cells are sensitive to TRAIL through the two death receptors DR4 and DR5. Because p53 directly modulates expression of death receptors, we investigated here whether p53 can modulate myeloma sensitivity to TRAIL. We found that p53 affects the sensitivity of myeloma cells to the DR5 agonistic human antibody lexatumumab but not the DR4 antibody mapatumumab. TP53 wild-type myeloma cells overexpressed DR5 in correlation with sensitivity to lexatumumab. Both nongenotoxic (nutlin-3a) and genotoxic (melphalan) p53-inducing stresses increased DR5 expression only in TP53 wild-type cells and synergistically increased lexatumumab efficiency yet did not increase DR4 expression, nor sensitivity to mapatumumab. Silencing of p53 strongly decreased DR5 expression and induced resistance to nutlin-3a and lexatumumab but did not modulate DR4 expression or sensitivity to mapatumumab. Increase of lexatumumab efficiency induced by nutlin-3a was related to a p53-dependent increase of DR5 expression. In primary myeloma cells, nutlin-3a increased DR5 expression and lexatumumab efficiency but did not increase mapatumumab efficiency. Taken together, our findings indicate that p53 controls the sensitivity of myeloma through DR5 but not DR4 and suggest that a subset of patients with multiple myeloma may benefit from DR5 therapy. Cancer Res; 72(17); 4562–73. ©2012 AACR.
The Signal Peptide of Mouse Mammary Tumor Virus-Env: A Phosphoprotein Tumor Modulator
Authors: Feldman Dafna , Roniger Maayan , Bar-Sinai Allan , Braitbard Ori , Natan Carmit , Love Dona C. , Hanover John A. , Hochman Jacob 
Published: June 2012

Abstract
Mouse mammary tumor virus (MMTV) is associated primarily with mammary carcinomas and lymphomas. The signal peptide of the MMTV envelope precursor is uniquely targeted to nucleoli of cells that harbor the virus, where it can function as a nuclear export factor for intron-containing transcripts. Antibodies to this signal peptide, which we refer to as p14, were previously shown to label nucleoli in a subset of human breast cancers. To look for additional cellular functions of p14, different mutants were ectopically expressed in the MCF-7 human breast cancer cell line. This approach identified motifs responsible for its nucleolar targeting, nucleocytoplasmic shuttling, target protein (B23, nucleophosmin) binding, and phosphorylation at serine 18 and 65 both in situ and in vitro. To test the role of these phosphorylation sites, we carried out in vivo tumorigenesis studies in severe combined immunodeficient mice. The findings show that the p14-Ser65Ala mutation is associated with impaired tumorigenicity, whereas the p14-Ser18Ala mutation is associated with enhanced tumorigenicity. Microarray analysis suggests that phosphorylation at serine 18 or at serine 65 is associated with transcriptional regulation of the L5 nucleolar ribosomal protein (a p14 target) and the Erb-B signal transduction pathway. Taken together, these results show that the phosphorylation status of p14 determines whether it functions as a pro-oncogenic or antioncogenic modulator. Mol Cancer Res; 10(8); 1077–86. ©2012 AACR.
Automated volumetric analysis of four cardiac chambers in pulmonary embolism
Authors: Sirota-Cohen Chen , Steinvil Arie , Keren Gad , Banai Shmuel , Sosna Jacob , Berliner Shlomo , Rogowski Ori , Aviram Galit 
Published: June 2012

SummaryIdentification of patients with acute pulmonary embolism (PE) who might be at risk of circulatory collapse by using a fast, automated system is highly desired. It was our objective to investigate whether automated cardiac volumetric analysis following computerised tomographic pulmonary angiography (CTPA) is useful to identify increased clot load and adverse prognosis in patients with acute PE. We retrospectively analysed a consecutive series of non-gated CTPA studies of 124 patients with acute PE and 43 controls. Right and left ventricular diameters (RV/LV) were measured on four-chamber view, while each cardiac chamber underwent automatic volumetric measurements. Findings were correlated to the pulmonary arterial obstruction index (PAOI). Outcome was expressed by admission to an intensive care unit (ICU) or mortality within 30 days. There was a significant positive correlation between the PAOI and the volumes of the right side cavities (r=0.25 for the atrium and r=0.49 for the ventricle), and between the right-to-left atrial and ventricular volume ratios (r=0.49 and r=0.57, respectively). Results for the combined outcome of mortality or ICU admission that fell in the upper tertile of the right atrial and right ventricular volumes yielded hazard ratios of 3.9 and 3.3, respectively, compared to those in the lower tertile. RV/LV diameter ratio did not correlate with outcome. In conclusion, adverse outcome and significant pulmonary clot load in patients with acute PE are associated with a volume shift towards right heart cavities, which correlates to prognosis better than the CT-measured RV/LV diameter ratio, suggesting the advantage of using fast fully automatic volumetric analysis to identify patients at risk.