bluuebunny/crossref_metadata_2025_split huggingface dataset:
Commissioning of output factors for uniform scanning proton beams
Authors: Zheng Yuanshui , Ramirez Eric , Mascia Anthony , Ding Xiaoning , Okoth Benny , Zeidan Omar , Hsi Wen , Harris Ben , Schreuder Andries N. , Keole Sameer 
Published: April 2011

Purpose:Current commercial treatment planning systems are not able to accurately predict output factors and calculate monitor units for proton fields. Patient‐specific field output factors are thus determined by either measurements or empirical modeling based on commissioning data. The objective of this study is to commission output factors for uniform scanning beams utilized at the ProCure proton therapy centers.Methods:Using water phantoms and a plane parallel ionization chamber, the authors first measured output factors with a fixed 10 cm diameter aperture as a function of proton range and modulation width for clinically available proton beams with ranges between 4 and 31.5 cm and modulation widths between 2 and 15 cm. The authors then measured the output factor as a function of collimated field size at various calibration depths for proton beams of various ranges and modulation widths. The authors further examined the dependence of the output factor on the scanning area (i.e., uncollimated proton field), snout position, and phantom material. An empirical model was developed to calculate the output factor for patient‐specific fields and the model‐predicted output factors were compared to measurements.Results:The output factor increased with proton range and field size, and decreased with modulation width. The scanning area and snout position have a small but non‐negligible effect on the output factors. The predicted output factors based on the empirical modeling agreed within 2% of measurements for all prostate treatment fields and within 3% for 98.5% of all treatment fields.Conclusions:Comprehensive measurements at a large subset of available beam conditions are needed to commission output factors for proton therapy beams. The empirical modeling agrees well with the measured output factor data. This investigation indicates that it is possible to accurately predict output factors and thus eliminate or reduce time‐consuming patient‐specific output measurements for proton treatments.
Protective Immunity against Experimental Pulmonary Cryptococcosis in T Cell-Depleted Mice
Authors: Wozniak Karen L. , Young Mattie L. , Wormley Floyd L. 
Published: March 2011

ABSTRACTIndividuals with defects in T cell-mediated immunity (CMI) are highly susceptible to infection withCryptococcus neoformans. The purpose of these studies was to determine if protection against experimental pulmonary cryptococcosis can be generated in T cell-deficient hosts. BALB/c mice were depleted of CD4+and/or CD8+T cells or given an isotype control antibody prior to vaccination with aC. neoformansstrain, designated H99γ, previously shown to induce protection againstC. neoformansinfection in immunocompetent mice. Mice depleted of CD4+or CD8+T cells, but not both subsets, survived an acute pulmonary infection withC. neoformansstrain H99γ and a subsequent second challenge with wild-typeC. neoformansstrain H99. We observed a significant increase in the percentage of CD4+and CD8+T cells expressing the activation marker CD69 in the lungs of mice immunized withC. neoformansstrain H99γ prior to a secondary challenge with wild-type cryptococci. CD4+T cells within the lungs of immunized mice also appeared to acquire a predominantly activated effector memory cell phenotype (CD69+CD44+CCR7−CD45RB−CD62L−) following a second pulmonary challenge with wild-typeC. neoformans, compared to CD4+T cells from naïve mice. Lastly, immunization of immunocompetent mice withC. neoformansstrain H99γ prior to depletion of CD4+and/or CD8+T cells resulted in significant protection against a second challenge with wild-typeC. neoformans. Our studies demonstrate that protective immunity against pulmonary cryptococcosis can be generated in immunosuppressed hosts, thus supporting the development of cryptococcal vaccines.
Characterization of Invasive Pneumococci of Serogroup 6 from Adults in Barcelona, Spain, in 1994 to 2008
Authors: Rolo Dora , Ardanuy Carmen , Calatayud Laura , Pallares Román , Grau Immaculada , García Ernesto , Fenoll Asunción , Martín Rogelio , Liñares Josefina 
Published: March 2011

ABSTRACT

A total of 91 of 1,480 invasive isolates (6.1%) collected from adults in Barcelona, Spain, in the period of 1994 to 2008 were of serogroup 6 (6B, 47 isolates; 6A, 28; and 6C, 16). Throughout this period, serotype 6B (Spain
6B
-ST90) decreased, and serotype 6A remained stable. An increase in serotype 6C (ST224) in the 2004-2008 period was observed.
Web-Accessible Database of
hsp65
Sequences from Mycobacterium Reference Strains
Authors: Dai Jianli , Chen Yuansha , Lauzardo Michael 
Published: March 2011

ABSTRACT

Mycobacteria include a large number of pathogens. Identification to species level is important for diagnoses and treatments. Here, we report the development of a Web-accessible database of the
hsp65
locus sequences (
http://msis.mycobacteria.info
) from 149 out of 150
Mycobacterium
species/subspecies. This database can serve as a reference for identifying
Mycobacterium
species.
Antibody-Dependent Cell-Mediated Viral Inhibition Emerges after Simian Immunodeficiency Virus SIVmac251 Infection of Rhesus Monkeys Coincident with gp140-Binding Antibodies and Is Effective against Neutralization-Resistant Viruses
Authors: Asmal Mohammed , Sun Yue , Lane Sophie , Yeh Wendy , Schmidt Stephen D. , Mascola John R. , Letvin Norman L. 
Published: March 2011

ABSTRACTAntibody-dependent cell-mediated viral inhibition (ADCVI) is an attractive target for vaccination because it takes advantage of both the anamnestic properties of an adaptive immune response and the rapid early response characteristics of an innate immune response. Effective utilization of ADCVI in vaccine strategies will depend on an understanding of the natural history of ADCVI during acute and chronic human immunodeficiency virus type 1 (HIV-1) infection. We used the simian immunodeficiency virus (SIV)-infected rhesus monkey as a model to study the kinetics of ADCVI in early infection, the durability of ADCVI through the course of infection, and the effectiveness of ADCVI against viruses with envelope mutations that are known to confer escape from antibody neutralization. We demonstrate the development of ADCVI, capable of inhibiting viral replication 100-fold, within 3 weeks of infection, preceding the development of a comparable-titer neutralizing antibody response by weeks to months. The emergence of ADCVI was temporally associated with the emergence of gp140-binding antibodies, and in most animals, ADCVI persisted through the course of infection. Highly evolved viral envelopes from viruses isolated at late time points following infection that were resistant to plasma neutralization remained susceptible to ADCVI, suggesting that the epitope determinants of neutralization escape are not shared by antibodies that mediate ADCVI. These findings suggest that despite the ability of SIV to mutate and adapt to multiple immunologic pressures during the course of infection, SIV envelope may not escape the binding of autologous antibodies that mediate ADCVI.
The Cellular Factors Vps18 and Mon2 Are Required for Efficient Production of Infectious HIV-1 Particles
Authors: Tomita Yuriko , Noda Takeshi , Fujii Ken , Watanabe Tokiko , Morikawa Yuko , Kawaoka Yoshihiro 
Published: March 2011

ABSTRACT

Like all viruses, HIV-1 requires cellular host factors for replication. The mechanisms for production of progeny virions involving these host factors, however, are not fully understood. To better understand these mechanisms, we used a yeast (
Saccharomyces cerevisiae
) genetic screen to identify mutant strains in which HIV-1 Gag targeting to the plasma membrane was aberrant. Of the 917 mutants identified, we selected 14 mutants whose missing genes had single orthologous counterparts in human and tested them for Gag-induced viruslike particle (VLP) release in yeast cells. We found that the Vps18 and Mon2 proteins were important for HIV-1 Gag-induced VLP release in yeast. In eukaryote cells, these host proteins are highly conserved and function in protein trafficking. Depletion of hVps18 or hMon2 reduced the efficient production of infectious HIV-1 virions in human cells. Our data suggest that these cellular factors play an important role in the efficient production of infectious HIV-1 virion particles.
Adaptation of an ICAM-1-Tropic Enterovirus to the Mouse Respiratory Tract
Authors: Wang Eric S. , Dobrikova Elena , Goetz Christian , Dufresne Andrew T. , Gromeier Matthias 
Published: March 2011

ABSTRACT

Respiratory tract (RT) infections by members of the enterovirus (EV) genus of the
Picornaviridae
family are the most frequent cause for the common cold and a major factor in the exacerbation of chronic pulmonary diseases. The lack of a practical small-animal model for these infections has obstructed insight into pathogenic mechanisms of the common cold and their role in chronic RT illness and has hampered preclinical evaluation of antiviral strategies. Despite significant efforts, it has been difficult to devise rodent models that exhibit viral replication in the RT. This is due mainly to well-known intracellular host restrictions of EVs with RT tropism in rodent cells. We report the evolution of variants of the common-cold-causing coxsackievirus A21, an EV with tropism for the human intercellular adhesion molecule 1 (hICAM-1), through serial passage in the lungs of mice transgenic for the
hICAM-1
gene. This process was accompanied by multiple changes in the viral genome, suggesting exquisite adaptation of hICAM-1-tropic enteroviruses to the specific growth conditions within the RT.
In vivo
mouse RT-adapted, variant coxsackievirus A21 exhibited replication competence in the lungs of
hICAM-1
transgenic mice, providing a basis for unraveling EV-host interactions in the mouse RT.
Three Amino Acid Mutations (F51L, T59A, and S390L) in the Capsid Protein of the Hepatitis E Virus Collectively Contribute to Virus Attenuation
Authors: Córdoba Laura , Huang Yao-Wei , Opriessnig Tanja , Harral Kylie K. , Beach Nathan M. , Finkielstein Carla V. , Emerson Suzanne U. , Meng Xiang-Jin 
Published: March 2011

ABSTRACT

Hepatitis E virus (HEV) is an important but extremely understudied human pathogen, and the mechanisms of HEV replication and pathogenesis are largely unknown. We previously identified an attenuated genotype 3 HEV mutant (pSHEV-1) containing three unique amino acid mutations (F51L, T59A, and S390L) in the capsid protein. To determine the role of each of these mutations, we constructed three HEV single mutants (rF51L, rT59A, and rS390L) which were all found to be replication competent in Huh7 liver cells. To determine the pathogenicities of the mutants, we utilized the specific-pathogen-free (SPF) pig model for HEV and a unique inoculation procedure that bypasses the need for propagating infectious HEV
in vitro
. A total of 60 pigs were intrahepatically inoculated, via an ultrasound-guided technique, with
in vitro
-transcribed full-length capped RNA transcripts from the infectious clones of each single mutant, the pSHEV-1 triple mutant, wild-type pSHEV-3, or phosphate-buffered saline (PBS) buffer (
n
= 10). The results showed that the F51L mutation partially contributed to virus attenuation, whereas the T59A and S390L mutations resulted in more drastic attenuation of HEV in pigs, as evidenced by a significantly lower incidence of viremia, a delayed appearance and shorter duration of fecal virus shedding and viremia, and lower viral loads in liver, bile, and intestinal content collected at three different necropsy times. The results indicate that the three mutations in the capsid protein collectively contribute to HEV attenuation. This study has important implications for developing a modified live-attenuated vaccine against HEV.
Oncolytic Vesicular Stomatitis Virus Induces Apoptosis in U87 Glioblastoma Cells by a Type II Death Receptor Mechanism and Induces Cell Death and Tumor Clearance In Vivo
Authors: Cary Zachary D. , Willingham Mark C. , Lyles Douglas S. 
Published: March 2011

ABSTRACT

Vesicular stomatitis virus (VSV) is a potential oncolytic virus for treating glioblastoma multiforme (GBM), an aggressive brain tumor. Matrix (M) protein mutants of VSV have shown greater selectivity for killing GBM cells versus normal brain cells than VSV with wild-type M protein. The goal of this research was to determine the contribution of death receptor and mitochondrial pathways to apoptosis induced by an M protein mutant (M51R) VSV in U87 human GBM tumor cells. Compared to controls, U87 cells expressing a dominant negative form of Fas (dnFas) or overexpressing Bcl-X
L
had reduced caspase-3 activation following infection with M51R VSV, indicating that both the death receptor pathway and mitochondrial pathways are important for M51R VSV-induced apoptosis. Death receptor signaling has been classified as type I or type II, depending on whether signaling is independent (type I) or dependent on the mitochondrial pathway (type II). Bcl-X
L
overexpression inhibited caspase activation in response to a Fas-inducing antibody, similar to the inhibition in response to M51R VSV infection, indicating that U87 cells behave as type II cells. Inhibition of apoptosis
in vitro
delayed, but did not prevent, virus-induced cell death. Murine xenografts of U87 cells that overexpress Bcl-X
L
regressed with a time course similar to that of control cells following treatment with M51R VSV, and tumors were not detectable at 21 days postinoculation. Immunohistochemical analysis demonstrated similar levels of viral antigen expression but reduced activation of caspase-3 following virus treatment of Bcl-X
L
-overexpressing tumors compared to controls. Further, the pathological changes in tumors following treatment with virus were quite different in the presence versus the absence of Bcl-X
L
overexpression. These results demonstrate that M51R VSV efficiently induces oncolysis in GBM tumor cells despite deregulation of apoptotic pathways, underscoring its potential use as a treatment for GBM.
Pivotal Role of Antibody and Subsidiary Contribution of CD8+T Cells to Recovery from Infection in a Murine Model of Japanese Encephalitis
Authors: Larena Maximilian , Regner Matthias , Lee Eva , Lobigs Mario 
Published: March 2011

ABSTRACTThe immunological correlates for recovery from primary Japanese encephalitis virus (JEV) infection in humans and experimental animals remain poorly defined. To investigate the relative importance of the adaptive immune responses, we have established a mouse model for Japanese encephalitis in which a low-dose virus inoculum was administered into the footpads of adult C57BL/6 mice. In this model, ∼60% of the mice developed a fatal encephalitis and a virus burden in the central nervous system (CNS). Using mice lacking B cells (μMT−/−mice) and immune B cell transfer to wild-type mice, we show a critically important role for humoral immunity in preventing virus spread to the CNS. T cell help played an essential part in the maintenance of an effective antibody response necessary to combat the infection, since mice lacking major histocompatibility complex class II showed truncated IgM and blunted IgG responses and uniformly high lethality. JEV infection resulted in extensive CD8+T cell activation, judged by upregulation of surface markers CD69 and CD25 and cytokine production after stimulation with a JEV NS4B protein-derived H-2Db-binding peptide and trafficking of virus-immune CD8+T cells into the CNS. However, no significant effect of CD8+T cells on the survival phenotype was found, which was corroborated in knockout mice lacking key effector molecules (Fas receptor, perforin, or granzymes) of cytolytic pathways triggered by T lymphocytes. Accordingly, CD8+T cells are mostly dispensable for recovery from infection with JEV. This finding highlights the conflicting role that CD8+T cells play in the pathogenesis of JEV and closely related encephalitic flaviviruses such as West Nile virus.
Missing opportunities for preventing unwanted pregnancy: a qualitative study of emergency contraception
Authors: Maharaj Pranitha , Rogan Michael 
Published: March 2011

Background and methodologyHigh levels of unplanned pregnancy among young people are a huge public health problem in South Africa. However, use of emergency contraception (EC) remains low. Studies suggest that providers constitute an important link to increasing access to EC use. The aim of the study was to provide greater insights into the attitudes of providers towards EC in order to better understand factors influencing uptake. The study drew upon 30 in-depth interviews with providers at private and public health facilities in Durban, South Africa.ResultsThe results of the study highlight several barriers to the provision of EC in both public and private health facilities. The cost of EC products in commercial pharmacies is likely to be a major barrier to use for many women. In addition, providers in both public and private facilities are often reluctant to provide EC over the counter because they feel that the use of EC is likely to discourage regular use of contraception and increase the risk of unprotected sexual intercourse and, as a result, contribute to the spread of HIV/AIDS in South Africa. In addition, they reported that they do not have an opportunity to counsel women about EC because of time constraints. Providers in both the public and private sectors also demonstrated a level of uncertainty about the clinical effects of EC pills and on the regulations surrounding their provision.Discussion and conclusionsDespite relatively progressive legislation on EC provision and the widespread availability of EC products in South Africa, providers in pharmacies, family planning clinics and public health clinics need more training on EC provision. Interventions should aim to educate health providers on both the clinical and social aspects of EC provision.
Teenage pregnancies that end in abortion: what can they tell us about contraceptive risk-taking?
Authors: Hoggart Lesley , Phillips Joan 
Published: March 2011

Background and methodologyIn 1999, the Government set the ambitious target of halving the number of under-18 conceptions by 2010. It is now clear that this target will not be met. Much media and policy attention has been paid to teenage mothers, and yet approximately 50% of teenage conceptions end in abortion not motherhood. In London, where the present research was based, the percentage is significantly higher. The research into teenage abortion and repeat abortion, though based in London, generated insights that could potentially help different areas reduce the number of under-18 conceptions ending in abortion. A qualitative research methodology was adopted and a wide range of interviews were conducted with young women, and professionals, in 10 London primary care trusts.ResultsOur analysis adds to a substantial body of qualitative research that points to the complexity of sexual decision-making for young women. Contraceptive risk-taking was evident as some young women spoke of the difficulties they experienced with user-dependent methods (primarily the condom and the pill) in often unplanned, sexual encounters. They were also generally poorly informed about different contraceptive methods. Misunderstandings about fertility also emerged as an important issue that can lead young women to draw the wrong conclusions if they do not become pregnant following unprotected sex.ConclusionsYoung people need improved access to, and informed understanding of, the full range of contraceptive methods available to them. In addition, efforts should be made to enable young women to have a better understanding of their own likely fertility.
Load Balancing and Range Queries in P2P Systems Using P-Ring
Authors: Crainiceanu Adina , Linga Prakash , Machanavajjhala Ashwin , Gehrke Johannes , Shanmugasundaram Jayavel 
Published: April 2011

In peer-to-peer (P2P) systems, computers from around the globe share data and can participate in distributed computation. P2P became famous, and infamous, due to file-sharing systems like Napster. However, the scalability and robustness of these systems make them appealing to a wide range of applications.
This article introduces P-Ring, a new peer-to-peer index structure. P-Ring is fully distributed, fault tolerant, and provides load balancing and logarithmic search performance while supporting both equality and range queries. Our theoretical analysis as well as experimental results, obtained both in a simulated environment and on PlanetLab, show the performance of our system.
Performance analysis of a hybrid MPI/CUDA implementation of the NASLU benchmark
Authors: Pennycook S. J. , Hammond S. D. , Jarvis S. A. , Mudalige G. R. 
Published: April 2011

We present the performance analysis of a port of the LU benchmark from the NAS Parallel Benchmark (NPB) suite to NVIDIA's Compute Unified Device Architecture (CUDA), and report on the optimisation efforts employed to take advantage of this platform. Execution times are reported for several different GPUs, ranging from low-end consumergrade products to high-end HPC-grade devices, including the Tesla C2050 built on NVIDIA's Fermi processor.
We also utilise recently developed performance models of LU to facilitate a comparison between future large-scale distributed clusters of GPU devices and existing clusters built on traditional CPU architectures, including a quad-socket, quad-core AMD Opteron cluster and an IBM BlueGene/P.
A framework for mining interesting pattern sets
Authors: De Bie Tijl , Kontonasios Kleanthis-Nikolaos , Spyropoulou Eirini 
Published: April 2011

This paper suggests a framework for mining subjectively interesting pattern sets that is based on two components: (1) the encoding of prior information in a model for the data miner's state of mind; (2) the search for a pattern set that is maximally informative while efficient to convey to the data miner.
We illustrate the framework with an instantiation for tile patterns in binary databases where prior information on the row and column marginals is available. This approach implements step (1) above by constructing the MaxEnt model with respect to the prior information [2, 3], and step (2) by relying on concepts from information and coding theory. We provide a brief overview of a number of possible extensions and future research challenges, including a key challenge related to the design of empirical evaluations for subjective interestingness measures.