bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct dose to water dosimetry for pretreatment IMRT verification using a modified EPID
Authors: Gustafsson Helen , Vial Philip , Kuncic Zdenka , Baldock Clive , Denham James W. , Greer Peter B. 
Published: October 2011

Purpose:Electronic portal imaging devices (EPIDs) are high resolution systems that produce electronic dose maps with minimal time required for equipment setup, and therefore potentially present a time‐saving alternative for intensity modulated radiation therapy (IMRT) pretreatment verification. A modified commercial EPID was investigated operated with an opaque sheet blocking the optical signal produced in the phosphor layer as a precursor to a switched mode dual dosimetry‐imaging EPID system. The purpose of this study was to investigate the feasibility of using this system for direct dose to water dosimetry for pretreatment IMRT verification.Methods:A Varian amorphous silicon EPID was modified by placing an opaque sheet between the Gd2S2O:Tb phosphor layer and the photodiode array to block the optical photons. The EPID was thus converted to a direct‐detecting system (dEPID), in which the high energy radiation deposits energy directly in the photodiode array. The copper build‐up was replaced with dmax solid water. Sixty‐one IMRT beams of varying complexity were delivered to the EPID, to EDR2 dosimetric film and to a 2D ion chamber array (MapCheck). EPID data was compared to film and MapCheck data using gamma analysis with 3%, 3mm pass criteria.Results:The fraction of points that passed the gamma test was on average 98.1% and 98.6%, for the EPID versus film and EPID versus MapCheck comparisons, respectively. In the case of comparison with film, the majority of observed discrepancies were associated with problems related to film sensitivity or processing.Conclusions:The very close agreement between EPID and both film and MapCheck data demonstrates that the modified EPID is suitable for direct dose to water measurement for pretreatment IMRT verification. These results suggest a reconfigured EPID could be an efficient and accurate dosimeter. Alternatively, optical switching methods could be developed to produce a dual‐mode EPID with both dosimetry and imaging capabilities.
Virus-Like Particle Vaccine Containing Hemagglutinin Confers Protection against 2009 H1N1 Pandemic Influenza
Authors: Hossain M. Jaber , Bourgeois Melissa , Quan Fu-Shi , Lipatov Aleksandr S. , Song Jae-Min , Chen Li-Mei , Compans Richard W. , York Ian , Kang Sang-Moo , Donis Ruben O. 
Published: October 2011

ABSTRACT
Immunization of the world population before an influenza pandemic such as the 2009 H1N1 virus spreads globally is not possible with current vaccine production platforms. New influenza vaccine technologies, such as virus-like-particles (VLPs), offer a promising alternative. Here, we tested the immunogenicity and protective efficacy of a VLP vaccine containing hemagglutinin (HA) and M1 from the 2009 pandemic H1N1 influenza virus (H1N1pdm) in ferrets and compared intramuscular (i.m.) and intranasal (i.n.) routes of immunization. Vaccination of ferrets with VLPs containing the M1 and HA proteins from A/California/04/2009 (H1N1pdm) induced high antibody titers and conferred significant protection against virus challenge. VLP-vaccinated animals lost less weight, shed less virus in nasal washes, and had markedly lower virus titers in all organs tested than naïve controls. A single dose of VLPs, either i.m. or i.n., induced higher levels of antibody than did two doses of commercial split vaccine. Ferrets vaccinated with split vaccine were incompletely protected against challenge; these animals had lower virus titers in olfactory bulbs, tonsils, and intestines, but lost weight and shed virus in nasal washes to a similar extent as naïve controls. Challenge with heterologous A/Brisbane/59/07 (H1N1) virus revealed that the VLPs conferred minimal cross-protection to heterologous infection, as revealed by the lack of reduction in nasal wash and lung virus titers and slightly higher weight loss relative to controls. In summary, these experiments demonstrate the strong immunogenicity and protective efficacy of VLPs compared to the split vaccine and show that i.n. vaccination with VLPs has the potential for highly efficacious vaccination against influenza.
Performance of Nucleic Acid Amplification following Extraction of 5 Milliliters of Whole Blood for Diagnosis of Mycobacterium tuberculosis Bacteremia
Authors: Crump John A. , Tuohy Marion J. , Morrissey Anne B. , Ramadhani Habib O. , Njau Boniface N. , Maro Venance P. , Reller L. Barth , Procop Gary W. 
Published: October 2011

ABSTRACT

To investigate the performance of a nucleic acid amplification test (NAAT) for the diagnosis of
Mycobacterium tuberculosis
bacteremia, 5-ml aliquots of blood were inoculated into bioMérieux mycobacterial (MB) bottles and incubated, and 5-ml aliquots of blood were extracted and tested by real-time PCR. Of 25 samples from patients with
M. tuberculosis
bacteremia, 9 (36.0%) were positive and 1 (1.5%) of 66 control samples was positive by NAAT. The NAAT shows promise, but modifications should focus on improving sensitivity.
Modification of the Untranslated Regions of Human Enterovirus 71 Impairs Growth in a Cell-Specific Manner
Authors: Kok Chee Choy , Phuektes Patchara , Bek Emily , McMinn Peter C. 
Published: October 2011

ABSTRACT

Human enterovirus 71 (HEV71) is the causative agent of hand, foot, and mouth disease and associated acute neurological disease. At present, little is known about the genetic determinants of HEV71 neurovirulence. Studies of related enteroviruses have indicated that the untranslated regions (UTRs), which control virus-directed translation and replication, also exert significant influence on neurovirulence. We used an infectious cDNA clone of a subgenogroup B3 strain to construct and characterize chimeras with 5′- and 3′-UTR modifications. Replacement of the entire HEV71 5′ UTR with that of human rhinovirus 2 (HRV2) resulted in a small reduction in growth efficiency in cells of both nonneuronal (rhabdomyosarcoma) and neuronal (SH-SY5Y) origin due to reduced translational efficiency. However, the introduction of a 17-nucleotide deletion into the proximal region of the 3′ UTR significantly decreased the growth of HEV71-HRV2 in SH-SY5Y cells. This observation is similar to that made with stem-loop domain Z (SLD Z)-deleted coxsackievirus B3-HRV2 5′-UTR chimeras reported previously and provides the first evidence of a potentially functional SLD Z in the 3′ UTR in human enterovirus A species viruses. We further showed that the cell-specific growth impairment was caused by the synergistic effects of
cis
-acting UTR control elements on different stages of the virus life cycle. These chimeras will further improve our understanding of the control of HEV71 replication and its relationship to neurovirulence.
HIV-Specific CD4 T Cell Responses to Different Viral Proteins Have Discordant Associations with Viral Load and Clinical Outcome
Authors: Ranasinghe Srinika , Flanders Michael , Cutler Sam , Soghoian Damien Z. , Ghebremichael Musie , Davis Isaiah , Lindqvist Madelene , Pereyra Florencia , Walker Bruce D. , Heckerman David , Streeck Hendrik 
Published: October 2011

ABSTRACTA successful prophylactic vaccine is characterized by long-lived immunity, which is critically dependent on CD4 T cell-mediated helper signals. Indeed, most licensed vaccines induce antigen-specific CD4 T cell responses, in addition to high-affinity antibodies. However, despite the important role of CD4 T cells in vaccine design and natural infection, few studies have characterized HIV-specific CD4 T cells due to their preferential susceptibility to HIV infection. To establish at the population level the impact of HIV-specific CD4 T cells on viral control and define the specificity of HIV-specific CD4 T cell peptide targeting, we conducted a comprehensive analysis of these responses to the entire HIV proteome in 93 subjects at different stages of HIV infection. We show that HIV-specific CD4 T cell responses were detectable in 92% of individuals and that the breadth of these responses showed a significant inverse correlation with the viral load (P= 0.009,R= −0.31). In particular, CD4 T cell responses targeting Gag were robustly associated with lower levels of viremia (P= 0.0002,R= −0.45). Importantly, differences in the immunodominance profile of HIV-specific CD4 T cell responses distinguished HIV controllers from progressors. Furthermore, Gag/Env ratios were a potent marker of viral control, with a high frequency and magnitude of Gag responses and low proportion of Env responses associated with effective immune control. At the epitope level, targeting of three distinct Gag peptides was linked to spontaneous HIV control (P= 0.60 to 0.85). Inclusion of these immunogenic proteins and peptides in future HIV vaccines may act as a critical cornerstone for enhancing protective T cell responses.
The Effects of Host Age on the Transport of Complement-Bound Complexes to the Spleen and the Pathogenesis of Intravenous Scrapie Infection
Authors: Brown Karen L. , Gossner Anton , Mok Simon , Mabbott Neil A. 
Published: October 2011

ABSTRACTInfections with variant Creutzfeldt-Jakob disease (vCJD) have almost exclusively occurred in young patients, but the reasons for this age distribution are uncertain. Our data suggest that the pathogenesis of many peripherally acquired transmissible spongiform encephalopathy (TSE) agents is less efficient in aged individuals. Four vCJD cases linked to transfusion of vCJD-contaminated blood or blood products have been described. Three cases occurred in elderly patients, implying that intravenous exposure is more efficient in aged individuals than other peripheral routes. To test this hypothesis, young (6 to 8 weeks old) and aged (600 days old) mice were injected intravenously with a TSE agent. In aged and young mice, the intravenous route was more efficient than other peripheral routes of TSE agent exposure. However, in aged mice, disease pathogenesis was significantly reduced. Although most aged mice failed to develop clinical disease during their life spans, many showed histopathological signs of TSE disease in their brains. Thus, the effects of age on intravenous TSE pathogenesis may lead to significant levels of subclinical disease in the population. After peripheral exposure, many TSE agents accumulate upon follicular dendritic cells (FDCs) in lymphoid tissues before they infect the brain. In aged spleens, PrPCexpression and TSE agent accumulation upon FDCs were reduced. Furthermore, the splenic marginal zone microarchitecture was substantially disturbed, adversely affecting the delivery of immune complexes to FDCs. This study is the first to suggest that the effects of aging on the microarchitecture and the function of the splenic marginal zone significantly influence the pathogenesis of an important pathogen.
Characterization, Mapping, and Distribution of the Two XMRV Parental Proviruses
Authors: Cingöz Oya , Paprotka Tobias , Delviks-Frankenberry Krista A. , Wildt Sheryl , Hu Wei-Shau , Pathak Vinay K. , Coffin John M. 
Published: October 2011

ABSTRACT

Xenotropic murine leukemia virus-related virus (XMRV) was previously reported to be associated with human prostate cancer and chronic fatigue syndrome. Our groups recently showed that XMRV was created through recombination between two endogenous murine retroviruses, PreXMRV-1 and PreXMRV-2, during the passaging of a prostate tumor xenograft in nude mice. Here, multiple approaches that led to the identification of PreXMRV-2, as well as the distribution of both parental proviruses among different mouse species, are described. The chromosomal loci of both proviruses were determined in the mouse genome, and integration site information was used to analyze the distribution of both proviruses in 48 laboratory mouse strains and 46 wild-derived strains. The strain distributions of PreXMRV-1 and PreXMRV-2 are quite different, the former being found predominantly in Asian mice and the latter in European mice, making it unlikely that the two XMRV ancestors could have recombined independently in the wild to generate an infectious virus. XMRV was not present in any of the mouse strains tested, and among the wild-derived mouse strains analyzed, not a single mouse carried both parental proviruses. Interestingly, PreXMRV-1 and PreXMRV-2 were found together in three laboratory strains, Hsd nude, NU/NU, and C57BR/cd, consistent with previous data that the recombination event that led to the generation of XMRV could have occurred only in the laboratory. The three laboratory strains carried the Xpr1
n
receptor variant nonpermissive to XMRV and xenotropic murine leukemia virus (X-MLV) infection, suggesting that the xenografted human tumor cells were required for the resulting XMRV recombinant to infect and propagate.
Identification of a Novel Feline Picornavirus from the Domestic Cat
Authors: Lau Susanna K. P. , Woo Patrick C. Y. , Yip Cyril C. Y. , Choi Garnet K. Y. , Wu Ying , Bai Ru , Fan Rachel Y. Y. , Lai Kenneth K. Y. , Chan Kwok-Hung , Yuen Kwok-Yung 
Published: October 2011

ABSTRACT

While picornaviruses are known to infect different animals, their existence in the domestic cat was unknown. We describe the discovery of a novel feline picornavirus (FePV) from stray cats in Hong Kong. From samples from 662 cats, FePV was detected in fecal samples from 14 cats and urine samples from 2 cats by reverse transcription-PCR (RT-PCR). Analysis of five FePV genomes revealed a distinct phylogenetic position and genomic features, with low sequence homologies to known picornaviruses especially in leader and 2A proteins. Among the viruses that belong to the closely related bat picornavirus groups 1 to 3 and the genus
Sapelovirus
, G+C content and sequence analysis of P1, P2, and P3 regions showed that FePV is most closely related to bat picornavirus group 3. However, FePV possessed other distinct features, including a putative type IV internal ribosome entry site/segment (IRES) instead of type I IRES in bat picornavirus group 3, protein cleavage sites, and H-D-C catalytic triad in 3C
pro
different from those in sapeloviruses and bat picornaviruses, and the shortest leader protein among known picornaviruses. These results suggest that FePV may belong to a new genus in the family
Picornaviridae
. Western blot analysis using recombinant FePV VP1 polypeptide showed a high seroprevalence of 33.6% for IgG among the plasma samples from 232 cats tested. IgM was also detected in three cats positive for FePV in fecal samples, supporting recent infection in these cats. Further studies are important to understand the pathogenicity, epidemiology, and genetic evolution of FePV in these common pet animals.
Effective Usage of Computational Trust Models in Rational Environments
Authors: Vu Le-Hung , Aberer Karl 
Published: October 2011

Computational reputation-based trust models using statistical learning have been intensively studied for distributed systems where peers behave maliciously. However practical applications of such models in environments with both malicious and rational behaviors are still very little understood. In this article, we study the relation between their accuracy measures and their ability to enforce cooperation among participants and discourage selfish behaviors. We provide theoretical results that show the conditions under which cooperation emerges when using computational trust models with a given accuracy, and how cooperation can still be sustained while reducing the cost and accuracy of those models.
Specifically, we propose a peer selection protocol that uses a computational trust model as a dishonesty detector to filter out unfair ratings. We prove that such a model with reasonable misclassification error bound in identifying malicious ratings can effectively build trust and cooperation in the system, considering rationality of participants. These results reveal two interesting observations. First, the key to the success of a reputation system in a rational environment is not a sophisticated trust-learning mechanism, but an effective identity-management scheme to prevent whitewashing behaviors. Second, given an appropriate identity-management mechanism, a reputation-based trust model with a moderate accuracy bound can be used to effectively enforce cooperation in systems with both rational and malicious participants. As a result, in heterogeneous environments where peers use different algorithms to detect misbehavior of potential partners, cooperation may still emerge. We verify and extend these theoretical results to a variety of settings involving honest, malicious, and strategic players through extensive simulation. These results will enable a much more targeted, cost-effective and realistic design for decentralized trust management systems, such as needed for peer-to-peer, electronic commerce, or community systems.
In Vivo Implantation of Tissue‐Engineered Human Nasal Septal Neocartilage Constructs
Authors: Chang Angela A. , Reuther Marsha S. , Briggs Kristen K. , Schumacher Barbara L. , Williams Gregory M. , Corr Maripat , Sah Robert L. , Watson Deborah 
Published: October 2011

ObjectiveTo determine the in vivo biocompatibility of septal neocartilage constructs developed in vitro by an alginate intermediate step.Study DesignProspective, animal model.SettingResearch laboratory.Subjects and MethodsA murine model was used to examine the maturation of neocartilage constructs in vivo. Chondrocytes collected from patients undergoing septoplasty were expanded in monolayer and suspended in alginate beads for 3‐dimensional culture in media containing human serum and growth factors. After in vitro incubation for 5 weeks, the constructs were implanted in the dorsum of athymic mice for 30 and 60 days (n = 9). After the mice were sacrificed, the constructs were recovered for assessment of their morphological, histochemical, biochemical, and biomechanical properties.ResultsThe mice survived and tolerated the implants well. Infection and extrusion were not observed. Neocartilage constructs maintained their general shape and size and demonstrated cell viability after implantation. The implanted constructs were firm and opaque, sharing closer semblance to native septal tissue relative to the gelatinous, translucent preimplant constructs. Histochemical staining with hematoxylin and eosin (H&E) revealed that the constructs exhibited distinct morphologies characteristic of native tissue, which were not observed in preimplant constructs. DNA and type II collagen increased with duration of implantation, whereas type I collagen and glycoaminoglycans (GAG) decreased. Mechanical testing of a 60‐day implanted construct demonstrated characteristics similar to native human septal cartilage.ConclusionsNeocartilage constructs are viable in an in vivo murine model. The histologic, biochemical, and biomechanical features of implanted constructs closely resemble native septal tissue when compared with preimplant constructs.
A novel type of congenital hypochromic anemia associated with a nonsense mutation in the STEAP3/TSAP6 gene
Authors: Grandchamp Bernard , Hetet Gilles , Kannengiesser Caroline , Oudin Claire , Beaumont Carole , Rodrigues-Ferreira Sylvie , Amson Robert , Telerman Adam , Nielsen Peter , Kohne Elisabeth , Balser Christina , Heimpel Hermann 
Published: October 2011

Abstract
STEAP3/TSAP6 encodes a ferrireductase that is involved in the acquisition of iron by developing erythroblasts and steap3/tsap6 null-mice display severe microcytic anemia. We report a family in which 3 siblings born to healthy parents display transfusion-dependent hypochromic anemia. A nonsense STEAP3/TSAP6 was identified in the siblings at the heterozygous state. This mutation was inherited from their father while no mutation was found in their mother. A large variability of expression was found between normal alleles in a control population, confirming a previous report that STEAP3/TSAPS6 is an expressed quantitative trait locus (e-QTL). Determination of the relative allele expression showed that the “normal” allele was expressed at a significantly higher level in the father than in the affected siblings relative to the shared mutated allele. The blood level of STEAP3/TSAP6 mRNA was severely reduced in the siblings, while both parents were in the lower range of normal controls. The STEAP3/TSAP6 protein was also reduced in lymphocytic cell lines from the patients. Collectively, our data support the hypothesis that STEAP3/TSAP6 deficiency leads to severe anemia in the affected siblings and results from the combination of a mutated allele inherited from their father and a weakly expressed allele inherited from their mother.
Paracrine inhibition of GM-CSF signaling by human cytomegalovirus in monocytes differentiating to dendritic cells
Authors: Carlier Jérome , Martin Hélène , Mariamé Bernard , Rauwel Benjamin , Mengelle Catherine , Weclawiak Hugo , Coaquette Alain , Vauchy Charline , Rohrlich Pierre , Kamar Nassim , Rostaing Lionel , Herbein Georges , Davrinche Christian 
Published: October 2011

AbstractA primary HCMV infection or virus reactivation may cause severe disease in hosts with a deficient immune system. The virus can disturb both innate and adaptive immunity by targeting dendritic cell (DC) functions. Monocytes, the precursors of DCs in vivo (MoDCs), are the primary targets of HCMV; they can also harbor latent virus. The DCs generated from infected monocytes (CMV-MoDCs) have an altered phenotype and functional defects. We have shown that CMV-MoDCs do not secrete IL-12 in response to lipopolysaccharide stimulation, cannot ingest dead cells, induce TH1 differentiation, or the proliferation of naive allogeneic CD4+ T cells. We found that the GM-CSF signaling in an entire population of CMV-MoDCs was impaired, although only half of the cells were productively infected, and that IL-6 secretion and suppressors of cytokine signaling 3 induction contributed to this bystander effect. We also showed that MoDCs derived ex vivo from monocytes of viremic patients had the same altered phenotype as CMV-MoDCs, including decreased STAT5 phosphorylation, indicating defective GM-CSF signaling. We have thus described a new mechanism of HCMV-induced immunosupression, indicated how infection may disturb both GM-CSF–dependent physiologic processes and proposed GM-CSF–based therapeutic approaches.
Secreted-frizzled related protein 1 is a transcriptional repression target of the t(8;21) fusion protein in acute myeloid leukemia
Authors: Cheng Chi Keung , Li Libby , Cheng Suk Hang , Ng Kitty , Chan Natalie P. H. , Ip Rosalina K. L. , Wong Raymond S. M. , Shing Matthew M. K. , Li Chi Kong , Ng Margaret H. L. 
Published: October 2011

AbstractSecreted-frizzled related proteins (SFRPs) are modulators of the Wnt signaling pathway that is closely involved in normal and malignant hematopoiesis. Epigenetic deregulation of Wnt modulators leading to aberrant signaling has been reported in adult patients with acute myeloid leukemia (AML), but its occurrence in childhood patients with AML and the role of individual modulators are unclear. In this study, we examined SFRP1, SFRP2, SFRP4, and SFRP5 promoter methylation in 83 patients with AML (59 children and 24 adults) and found preferential SFRP1 methylation and mRNA down-regulation in the prognostically favorable subgroup of AML with t(8;21) translocation. Among the 4 genes, SFRP1 methylation independently predicted prolonged event-free and relapse-free survivals in childhood patients with nonacute promyelocytic leukemia with nonadverse cytogenetics. Mechanistically, we further demonstrated that RUNX1-ETO, the t(8;21) fusion product, specifically bound the SFRP1 promoter and repressed its transcription via a consensus RUNX binding site. In t(8;21)–leukemia cells, SFRP1 selectively inhibited canonical Wnt signaling and cellular proliferation that were associated with concomitant down-regulation of Wnt/β-catenin target genes, including CCND1 and MYC. Taken together, we identified SFRP1 as a transcriptional repression target of the t(8;21) fusion protein and demonstrated a novel mechanism of Wnt activation in a specific subtype of AML.