bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanistic Study of Broadly Neutralizing Human Monoclonal Antibodies against Dengue Virus That Target the Fusion Loop
Authors: Costin Joshua M. , Zaitseva Elena , Kahle Kristen M. , Nicholson Cindo O. , Rowe Dawne K. , Graham Amanda S. , Bazzone Lindsey E. , Hogancamp Greg , Figueroa Sierra Marielys , Fong Rachel H. , Yang Sung-Tae , Lin Li , Robinson James E. , Doranz Benjamin J. , Chernomordik Leonid V. , Michael Scott F. , Schieffelin John S. , Isern Sharon 
Published: October 2012

ABSTRACT
There are no available vaccines for dengue, the most important mosquito-transmitted viral disease. Mechanistic studies with anti-dengue virus (DENV) human monoclonal antibodies (hMAbs) provide a rational approach to identify and characterize neutralizing epitopes on DENV structural proteins that can serve to inform vaccine strategies. Here, we report a class of hMAbs that is likely to be an important determinant in the human humoral response to DENV infection. In this study, we identified and characterized three broadly neutralizing anti-DENV hMAbs: 4.8A, D11C, and 1.6D. These antibodies were isolated from three different convalescent patients with distinct histories of DENV infection yet demonstrated remarkable similarities. All three hMAbs recognized the E glycoprotein with high affinity, neutralized all four serotypes of DENV, and mediated antibody-dependent enhancement of infection in Fc receptor-bearing cells at subneutralizing concentrations. The neutralization activities of these hMAbs correlated with a strong inhibition of virus-liposome and intracellular fusion, not virus-cell binding. We mapped epitopes of these antibodies to the highly conserved fusion loop region of E domain II. Mutations at fusion loop residues W101, L107, and/or G109 significantly reduced the binding of the hMAbs to E protein. The results show that hMAbs directed against the highly conserved E protein fusion loop block viral entry downstream of virus-cell binding by inhibiting E protein-mediated fusion. Characterization of hMAbs targeting this region may provide new insights into DENV vaccine and therapeutic strategies.
Recombinant Parainfluenza Virus 5 Vaccine Encoding the Influenza Virus Hemagglutinin Protects against H5N1 Highly Pathogenic Avian Influenza Virus Infection following Intranasal or Intramuscular Vaccination of BALB/c Mice
Authors: Mooney Alaina J. , Li Zhuo , Gabbard Jon D. , He Biao , Tompkins S. Mark 
Published: October 2012

ABSTRACTNew approaches for vaccination to prevent influenza virus infection are needed. Emerging viruses, such as the H5N1 highly pathogenic avian influenza (HPAI) virus, pose not only pandemic threats but also challenges in vaccine development and production. Parainfluenza virus 5 (PIV5) is an appealing vector for vaccine development, and we have previously shown that intranasal immunization with PIV5 expressing the hemagglutinin from influenza virus was protective against influenza virus challenge (S. M. Tompkins, Y. Lin, G. P. Leser, K. A. Kramer, D. L. Haas, E. W. Howerth, J. Xu, M. J. Kennett, J. E. Durbin, R. A. Tripp, R. A. Lamb, and B. He, Virology362:139–150, 2007). While intranasal immunization is an appealing approach, PIV5 may have the potential to be utilized in other formats, prompting us to test the efficacy of rPIV5-H5, which encodes the HA from H5N1 HPAI virus, in different vaccination schemes. In the BALB/c mouse model, a single intramuscular or intranasal immunization with a live rPIV5-H5 (ZL46) rapidly induced robust neutralizing serum antibody responses and protected against HPAI challenge, although mucosal IgA responses primed by intranasal immunization more effectively controlled virus replication in the lung. The rPIV5-H5 vaccine incorporated the H5 HA into the virion, so we tested the efficacy of an inactivated form of the vaccine. Inactivated rPIV5-H5 primed neutralizing serum antibody responses and controlled H5N1 virus replication; however, similar to other H5 antigen vaccines, it required a booster immunization to prime protective immune responses. Taken together, these results suggest that rPIV5-HA vaccines and H5-specific vaccines in particular can be utilized in multiple formats and by multiple routes of administration. This could avoid potential contraindications based on intranasal administration alone and provide opportunities for broader applications with the use of a single vaccine vector.
Exceptional Simian Hemorrhagic Fever Virus Diversity in a Wild African Primate Community
Authors: Lauck Michael , Sibley Samuel D. , Hyeroba David , Tumukunde Alex , Weny Geoffrey , Chapman Colin A. , Ting Nelson , Switzer William M. , Kuhn Jens H. , Friedrich Thomas C. , O'Connor David H. , Goldberg Tony L. 
Published: October 2012

ABSTRACT

Simian hemorrhagic fever virus (SHFV) is an arterivirus that causes severe disease in captive macaques. We describe two new SHFV variants subclinically infecting wild African red-tailed guenons (
Cercopithecus ascanius
). Both variants are highly divergent from the prototype virus and variants infecting sympatric red colobus (
Procolobus rufomitratus
). All known SHFV variants are monophyletic and share three open reading frames not present in other arteriviruses. Our data suggest a need to modify the current arterivirus classification.
Herpes Simplex Virus Membrane Proteins gE/gI and US9 Act Cooperatively To Promote Transport of Capsids and Glycoproteins from Neuron Cell Bodies into Initial Axon Segments
Authors: Howard Paul W. , Howard Tiffani L. , Johnson David C. 
Published: October 2012

ABSTRACT

Herpes simplex virus (HSV) and other alphaherpesviruses must move from sites of latency in ganglia to peripheral epithelial cells. How HSV navigates in neuronal axons is not well understood. Two HSV membrane proteins, gE/gI and US9, are key to understanding the processes by which viral glycoproteins, unenveloped capsids, and enveloped virions are transported toward axon tips. Whether gE/gI and US9 function to promote the loading of viral proteins onto microtubule motors in neuron cell bodies or to tether viral proteins onto microtubule motors within axons is not clear. One impediment to understanding how HSV gE/gI and US9 function in axonal transport relates to observations that gE
−
, gI
−
, or US9
−
mutants are not absolutely blocked in axonal transport. Mutants are significantly reduced in numbers of capsids and glycoproteins in distal axons, but there are less extensive effects in proximal axons. We constructed HSV recombinants lacking both gE and US9 that transported no detectable capsids and glycoproteins to distal axons and failed to spread from axon tips to adjacent cells. Live-cell imaging of a gE
−
/US9
−
double mutant that expressed fluorescent capsids and gB demonstrated >90% diminished capsids and gB in medial axons and no evidence for decreased rates of transport, stalling, or increased retrograde transport. Instead, capsids, gB, and enveloped virions failed to enter proximal axons. We concluded that gE/gI and US9 function in neuron cell bodies, in a cooperative fashion, to promote the loading of HSV capsids and vesicles containing glycoproteins and enveloped virions onto microtubule motors or their transport into proximal axons.
The Adeno-Associated Virus Type 5 Small Rep Proteins Expressed via Internal Translation Initiation Are Functional
Authors: Fasina Olufemi , Pintel David J. 
Published: October 2012

ABSTRACT
Although precluded from using splicing to produce multiple small Rep proteins, adeno-associated virus type 5 (AAV5) generates a Rep40-like protein by alternative translation initiation at an internal AUG. A defined region upstream of the internal AUG was both required and sufficient to program internal initiation within AAV5 and may act similarly in heterologous contexts. The internally initiated AAV5 Rep40-like protein was functional and had helicase activity similar to that of AAV2 Rep40. Surprisingly, both the AAV5 Rep40-like protein and Rep52 were able to be translated from the AAV5 upstream P7-generated RNAs; however, the relative level of small to large Rep proteins was reduced compared to that of the wild type. A P19 mutant AAV5 infectious clone generated near-wild-type levels of the double-stranded monomer replicative form (mRF) replicative intermediate but reduced levels of virus, consistent with the previously defined role of Rep40-like proteins in genome encapsidation. Levels of mutant virus were dramatically reduced upon amplification.
Diagnostic accuracy of scapular physical examination tests for shoulder disorders: a systematic review
Authors: Wright Alexis A , Wassinger Craig A , Frank Mason , Michener Lori A , Hegedus Eric J 
Published: October 2012

ObjectiveTo systematically review and critique the evidence regarding the diagnostic accuracy of physical examination tests for the scapula in patients with shoulder disorders.MethodsA systematic, computerised literature search of PubMED, EMBASE, CINAHL and the Cochrane Library databases (from database inception through January 2012) using keywords related to diagnostic accuracy of physical examination tests of the scapula. The Quality Assessment of Diagnostic Accuracy Studies tool was used to critique the quality of each paper.ResultsEight articles met the inclusion criteria; three were considered to be of high quality. Of the three high-quality studies, two were in reference to a ‘diagnosis’ of shoulder pain. Only one high-quality article referenced specific shoulder pathology of acromioclavicular dislocation with reported sensitivity of 71% and 41% for the scapular dyskinesis and SICK scapula test, respectively.ConclusionsOverall, no physical examination test of the scapula was found to be useful in differentially diagnosing pathologies of the shoulder.
SUPERLUMINAL GROUP VELOCITY OF NEUTRINOS: REVIEW, DEVELOPMENT AND PROBLEMS
Authors: FUJII KAZUYUKI 
Published: October 2012

The purpose of this paper is both to provide mathematical reinforcements to the paper [Mecozzi and Bellini, Superluminal group velocity of neutrinos, arXiv: 1110.1253 [hep-ph]] by taking decoherence into consideration and to present some important related problems. We claim that neutrinos have superluminality as a latent possibility.
The identification and management of cuttings at risk from deep-seated, delayed failure on the Highways Agency network
Authors: Parry L. N. 
Published: October 2012

Abstract
The UK trunk road network includes a considerable number of cuttings constructed through high plasticity, overconsolidated clays. These materials are prone to the process of delayed, deep-seated failure whereby instability can occur some considerable time after construction. The timescale between excavation and failure can be anywhere between 20 and 120 years. Many of the recorded deep-seated failures in the literature are from railway cuttings in the UK which are generally much older than cuttings on major highways. The bulk of trunk road construction in the UK occurred during the 1960s and 1970s and many cuttings are at, or approaching, an age when delayed, deep-seated failures might be expected to occur.
The Highways Agency (HA) has been aware of this issue and has sought to understand the causes and associated risks of these types of failure. The first phase of a study (concluded in 2007) provided a framework for assessing the likelihood of failure. The selection criteria were based on a combination of cutting height and slope angle. Mott MacDonald was commissioned to undertake the second phase of the study to focus on the application of the Phase 1 recommendations to the HA asset base. This paper describes the work undertaken during this study and conclusions reached.
Evidence for multiple ice centres during the late Palaeozoic ice age in Oman: outcrop sedimentology and provenance of the Late Carboniferous–Early Permian Al Khlata Formation
Authors: Martin Joe R. , Redfern Jonathan , Williams Brian P. J. 
Published: October 2012

Abstract
This paper proposes a model for glaciation in Oman during the late Palaeozoic ice age (LPIA) based on sedimentological and provenance analyses of the Late Carboniferous–Early Permian Al Khlata Formation, exposed in the Huqf, Oman. The results demonstrate a complex pattern of glaciation across Oman, not fully recognized in previous models. Striated glacial pavements provide evidence for two phases of ice advance: a phase of ice sheet advance towards the NE, and a second and probably younger phase where an ice centre localized on the Huqf High flowed towards the SW. The stratigraphy is constrained by previous palynological studies and is subdivided into three units, from oldest to youngest: ‘early’ AKP5, ‘late’ AKP5 and AKP5/P1. ‘Early’ AKP5 palaeogeography is characterized by ice-contact glacial lacustrine and deltaic sedimentary environments along the western margin of the Huqf High. Meltwater discharge flowed into the lake from ice margins located to the east, upon the Huqf High, recorded by progradational delta and fan complexes. ‘Late’ AKP5 palaeogeography is characterized by pro-glacial fluvial-deltaic outwash braidplains that record high-magnitude meltwater discharge from an ice margin located to the SW of the study area. The youngest undifferentiated AKP5/P1 palaeogeography is characterized by re-establishment of ice-contact glaciolacustrine conditions.
A Randomized Phase II Trial of Vismodegib versus Placebo with FOLFOX or FOLFIRI and Bevacizumab in Patients with Previously Untreated Metastatic Colorectal Cancer
Authors: Berlin Jordan , Bendell Johanna C. , Hart Lowell L. , Firdaus Irfan , Gore Ira , Hermann Robert C. , Mulcahy Mary F. , Zalupski Mark M. , Mackey Howard M. , Yauch Robert L. , Graham Richard A. , Bray Gordon L. , Low Jennifer A. 
Published: October 2012

Abstract
Purpose: Vismodegib, a Hedgehog pathway inhibitor, has preclinical activity in colorectal cancer (CRC) models. This trial assessed the efficacy, safety, and pharmacokinetics of adding vismodegib to first-line treatment for metastatic CRC (mCRC).
Experimental design: Patients were randomized to receive vismodegib (150 mg/day orally) or placebo, in combination with FOLFOX or FOLFIRI chemotherapy plus bevacizumab (5 mg/kg) every 2 weeks until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Key secondary objectives included evaluation of predictive biomarkers and pharmacokinetic drug interactions.
Results: A total of 199 patients with mCRC were treated on protocol (124 FOLFOX, 75 FOLFIRI). The median PFS hazard ratio (HR) for vismodegib treatment compared with placebo was 1.25 (90% CI: 0.89–1.76; P = 0.28). The overall response rates for placebo-treated and vismodegib-treated patients were 51% (90% CI: 43–60) and 46% (90% CI: 37–55), respectively. No vismodegib-associated benefit was observed in combination with either FOLFOX or FOLFIRI. Increased tumor tissue Hedgehog expression did not predict clinical benefit. Grade 3 to 5 adverse events reported for more than 5% of patients that occurred more frequently in the vismodegib-treated group were fatigue, nausea, asthenia, mucositis, peripheral sensory neuropathy, weight loss, decreased appetite, and dehydration. Vismodegib did not alter the pharmacokinetics of FOLFOX, FOLFIRI, or bevacizumab.
Conclusions: Vismodegib does not add to the efficacy of standard therapy for mCRC. Compared with placebo, treatment intensity was lower for all regimen components in vismodegib-treated patients, suggesting that combined toxicity may have contributed to lack of efficacy. Clin Cancer Res; 19(1); 258–67. ©2012 AACR.
Comparison of Two Different Cloud Climatologies Derived from CALIOP-Attenuated Backscattered Measurements (Level 1): The CALIPSO-ST and the CALIPSO-GOCCP
Authors: Chepfer H. , Cesana G. , Winker D. , Getzewich B. , Vaughan M. , Liu Z. 
Published: October 2012

Abstract
Two different cloud climatologies have been derived from the same NASA–Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP)-measured attenuated backscattered profile (level 1, version 3 dataset). The first climatology, named Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations–Science Team (CALIPSO-ST), is based on the standard CALIOP cloud mask (level 2 product, version 3), with the aim to document clouds with the highest possible spatiotemporal resolution, taking full advantage of the CALIOP capabilities and sensitivity for a wide range of cloud scientific studies. The second climatology, named GCM-Oriented CALIPSO Cloud Product (CALIPSO-GOCCP), is aimed at a single goal: evaluating GCM prediction of cloudiness. For this specific purpose, it has been designed to be fully consistent with the CALIPSO simulator included in the Cloud Feedback Model Intercomparison Project (CFMIP) Observation Simulator Package (COSP) used within version 2 of the CFMIP (CFMIP-2) experiment and phase 5 of the Coupled Model Intercomparison Project (CMIP5).
The differences between the two datasets in the global cloud cover maps—total, low level (P &gt; 680 hPa), midlevel (680 &lt; P &lt; 440 hPa), and high level (P &lt; 440 hPa)—are frequently larger than 10% and vary with region.
The two climatologies show significant differences in the zonal cloud fraction profile (which differ by a factor of almost 2 in some regions), which are due to the differences in the horizontal and vertical averaging of the measured attenuated backscattered profile CALIOP profile before the cloud detection and to the threshold used to detect clouds (this threshold depends on the resolution and the signal-to-noise ratio).
Technical issues that affect the use of retrofit panel thermal shutters in commercial buildings
Authors: Hashemi A , Gage S 
Published: October 2012

Retrofit insulated window shutters are examined. An initial investigation reveals that internal shutters are more viable in this context. Condensation is identified as a potential risk. Extensive investigations using modelling software as well as site and laboratory experiments are described which demonstrate that this risk is low. The thermal effectiveness of internal shutters is modelled and laboratory tested. Practical application: This article results from research into the possibility of creating a retrofit thermal shutter system for existing commercial buildings. Building on earlier research, the paper examines whether this type of shutter is best fixed externally or internally to existing brick clad buildings and concludes that the latter is the best strategy. It then examines whether condensation between existing glazing and the outer shutter face is a problem and finds that this is not a significant issue. The way is clear for the development of this type of system as an alternative to costly triple glazing solutions.
Telomere length is associated with ACE I/D polymorphism in hypertensive patients with left ventricular hypertrophy
Authors: Fyhrquist Frej , Eriksson Anders , Saijonmaa Outi , Nordestgaard Børge G , Kontula Kimmo , de Faire Ulf , Ibsen Hans , Kjeldsen Sverre , Os Ingrid , Dahlöf Björn 
Published: October 2012

Introduction: Short telomeres are often associated with cardiovascular risk factors and age-related diseases, while the angiotensin converting enzyme (ACE) gene insertion/deletion polymorphism (DD, ID, II) has shown such associations less consistently. We hypothesized that telomere length and association of telomere length with cardiovascular risk is affected by ACE (I/D) genotype. Methods: We measured leucocyte telomere length (LTL) by Southern blot and analysed ACE I/D genotypes in 1249 subjects with hypertension and left ventricular hypertrophy (LVH). We examined interactions of ACE I/D genotype with LTL and cardiovascular risk. Results: Mean LTL in DD or ID genotype was shorter (8.15 and 8.14 kb, respectively), than in II genotype (8.27 kb, p=0.0005). This difference was significant in the younger subjects (55–64 years, p=0.02) but not in the older group (65–80 years, p=0.56 ). In DD but not I/D or II genotype, proportion of short telomeres (<5 kb) was related to Framingham risk score. Conclusions: Shorter LTL in genotypes DD or ID suggests a negative effect of the D allele on telomere length. Homozygocity for the D allele appears to strengthen the association of telomere length with increased cardiovascular risk in elderly hypertensive subjects with LVH.
In aggressive forms of mastocytosis, TET2 loss cooperates with c-KITD816V to transform mast cells
Authors: Soucie Erinn , Hanssens Katia , Mercher Thomas , Georgin-Lavialle Sophie , Damaj Gandhi , Livideanu Cristina , Chandesris Maria Olivia , Acin Yolène , Létard Sebastien , de Sepulveda Paulo , Hermine Olivier , Bernard Olivier A. , Dubreuil Patrice 
Published: October 2012

Abstract
Although a role for oncogenic KIT in driving mast cell disease is clear, the mechanisms driving the multiple phenotypic and clinical manifestations of this disorder are not well elucidated. We now show, using a large cohort of mastocytosis patients, including an almost equal number of aggressive and nonaggressive cases of systemic mastocytosis, that in contrast to the oncogenic KITD816V, TET2 mutation statistically associates with aggressive forms of the disease. By infecting primary murine bone marrow–derived mast cells with KITD816V, we also observe a significant and competitive growth advantage for KITD816V in Tet2-nullizygous compared with wild-type cells. TET2-deficient cells display increased proliferation and can survive in the absence of cytokines. Taken together, these data demonstrate a oncogenic cooperation in mast cells and reveal TET2 mutation as a potential marker to diagnose and predict severe forms of mastocytosis.
Humans with chronic granulomatous disease maintain humoral immunologic memory despite low frequencies of circulating memory B cells
Authors: Moir Susan , De Ravin Suk See , Santich Brian H. , Kim Jin Young , Posada Jacqueline G. , Ho Jason , Buckner Clarisa M. , Wang Wei , Kardava Lela , Garofalo Mary , Marciano Beatriz E. , Manischewitz Jody , King Lisa R. , Khurana Surender , Chun Tae-Wook , Golding Hana , Fauci Anthony S. , Malech Harry L. 
Published: October 2012

Abstract
CD27+ memory B cells are reduced in the blood of patients with chronic granulomatous disease (CGD) for reasons and consequences that remain unclear. Here we confirm not only decreased CD27+ but also IgG+ B cells in the blood of CGD patients compared with healthy donors (HDs). However, among IgG+ B cells, the ratio of CD27− to CD27+ was significantly higher in CGD patients compared with HDs. Similar to conventional memory B cells, CD27−IgG+ B cells of CGD patients expressed activation markers and had undergone somatic hypermutation, albeit at levels lower than their CD27+ counterparts. Functional analyses revealed slight reductions in frequencies of total IgG but not influenza-specific memory B-cell responses, as measured by Elispot in CGD patients compared with HDs. Serum IgG levels and influenza-specific antibodies were also normal in these CGD patients. Finally, we provide evidence that influenza-specific memory B cells can be present within the CD27−IgG+ B-cell compartment. Together, these findings show that, despite reduced circulating CD27+ memory B cells, CGD patients maintain an intact humoral immunologic memory, with potential contribution from CD27− B cells.