bluuebunny/crossref_metadata_2025_split huggingface dataset:
First demonstration of intrafractional tumor‐tracked irradiation using 2D phantom MR images on a prototype linac‐MR
Authors: Yun Jihyun , Wachowicz Keith , Mackenzie Marc , Rathee Satyapal , Robinson Don , Fallone B. G. 
Published: May 2013

Purpose:To demonstrate intrafractional MR tumor tracking using a prototype linac‐MR by delivering radiation to a moving target undergoing simulated tumor motions.Methods:A prototype linac‐MR at the Cross Cancer Institute was used for intrafractional MR imaging and simultaneous beam delivery. A Varian 52‐leaf MK‐II multileaf collimator (MLC) was used for beam collimation. The authors used an inhouse built MR compatible motion phantom to simulate tumor motions during tracking with two different motion patterns (sine and modified cosine). Gafchromic film was inserted in the phantom to measure radiation exposure, and this film measurement was converted to dose (cGy) for further analysis. The authors demonstrated intrafractional tracking in various scenarios: [Scenario 0 (S0)] no phantom motion + no beam margin, (S1) no phantom motion + maximum beam margin, (S2) phantom motion + no beam margin, (S3) S2 + MLC tracking, and (S4) S3 + motion prediction. S0 emulates a perfect tumor tracking scenario, and its result was used as a “gold‐standard” to evaluate tracking accuracy from other scenarios. The authors compared (1) time difference in phantom and MLC motion curves in S3 and S4, and (2) dose profiles (50% beam width, 80%–20% penumbra width) from scenarios S1–S4 to S0.Results:In S4, no observable time difference exists between the phantom and MLC motion curves, indicating that MLC tracks phantom motion accurately. Comparing S4 to S0, 50% beam width reveals minimal differences of < 0.5 mm, while the increase in 80%–20% penumbra width is limited to 0.4 and 1.7 mm in the sine and modified cosine patterns, respectively.Conclusions:The authors report the first demonstration of intrafractional tumor tracking using 2D MR images. During 2 min of tracking, the authors delivered highly conformal dose to a moving target that simulates tumor motions. Compared to static target irradiation, the 50% beam width remains essentially the same (within 0.5 mm), with an increase in 80%–20% penumbra width of less than 1.7 mm in moving target irradiation. These results illustrate potential dosimetric advantages of intrafractional MR tumor tracking in treating mobile tumors as shown for the phantom case.
Lumen segmentation and stenosis quantification of atherosclerotic carotid arteries in CTA utilizing a centerline intensity prior
Authors: Tang Hui , van Walsum Theo , Hameeteman Reinhard , Shahzad Rahil , van Vliet Lucas J , Niessen Wiro J 
Published: May 2013

Purpose:The degree of stenosis is an important biomarker in assessing the severity of cardiovascular disease. The purpose of our work is to develop and evaluate a semiautomatic method for carotid lumen segmentation and subsequent carotid artery stenosis quantification in CTA images.Methods:The authors present a semiautomatic stenosis detection and quantification method following lumen segmentation. The lumen of the carotid arteries is segmented in three steps. First, centerlines of the internal and external carotid arteries are extracted with an iterative minimum cost path approach in which the costs are based on a measure of medialness and intensity similarity to lumen. Second, the lumen boundary is delineated using a level set procedure which is steered by gradient information, regional intensity information, and spatial information. Special effort is made in adding terms based on local centerline intensity prior so as to exclude all possible plaque tissues from the segmentation. Third, side branches in the segmented lumen are removed by applying a shape constraint to the envelope of the maximum inscribed spheres of the segmentation. From the segmented lumen, the authors detect and quantify the cross‐sectional area‐based and cross‐sectional diameter‐based stenosis degrees according to the North American Symptomatic Carotid En‐darterectomy Trial criterion.Results:The method is trained and tested on a publicly available database from the cls2009 challenge. For the segmentation, the authors obtain a Dice similarity coefficient of 90.2% and a mean absolute surface distance of 0.34 mm. For the stenosis quantification, the authors obtain an average error of 15.7% for cross‐sectional diameter‐based stenosis and 19.2% for cross‐sectional area‐based stenosis quantification.Conclusions:With these results, the method ranks second in terms of carotid lumen segmentation accuracy, and first in terms of carotid artery stenosis quantification.
Workload and transmission data for the installation of a digital breast tomosynthesis system
Authors: Li Xinhua , Zhang Da , Liu Bob 
Published: May 2013

Purpose:Digital breast tomosynthesis (DBT) differs from conventional mammography in target/filter, kVp range, and imaging geometry. The aim of this study was to assess the breast input exposure of a DBT system by completing a workload survey of DBT installations, and to determine the parameters α, β, and γ in the Archer equation for the primary radiation generated by the clinical workload distributions.Methods:The authors conducted a retrospective survey of the x‐ray breast imaging performed between September 2011 and September 2012 in three clinical DBT rooms equipped with Selenia Dimensions systems (Hologic Inc., Bedford, MA). A total of 343 examinations were analyzed to calculate the workload (mA‐minute) and the primary air kerma at 1 m from the source (K1). Transmission curves were calculated for the primary radiation generated by the workload distributions of the DBT rooms, and were fitted to the Archer equation.Results:There were large variations in patient volume and workload in the three examination rooms. In all these rooms, the average tube voltage (kVp) was about 31, the average K1 per patient was 16–21 mGy, and the average mA‐minute per patient was 1.4–2.2 times higher than that of the mammography room described in NCRP Report No. 147. Most DBT screening examinations consisted of four two‐dimensional mammographic views plus four tomosynthesis scans; the numbers of views acquired in diagnostic examinations varied widely. Tomosynthesis scans contributed about 30% of total mA‐minute and about 50% of K1. For the primary radiation generated by the clinical workload distributions, α was similar to that of 40–45 kVp W/Al (target/filter), and α + β was similar to that of 30 kVp W/Al.Conclusions:The workload (mA‐minute and K1) distributions of mammographic examinations with DBT differ from conventional mammography. A field survey of patient volume and x‐ray tube usage is important for the shielding design of DBT facilities. The clinical workloads and transmission data presented in this paper may be useful for clinical medical physicists.
Toll-Like Receptor 4 Agonistic Antibody Promotes Innate Immunity against Severe Pneumonia Induced by Coinfection with Influenza Virus and Streptococcus pneumoniae
Authors: Tanaka Akitaka , Nakamura Shigeki , Seki Masafumi , Fukudome Kenji , Iwanaga Naoki , Imamura Yoshifumi , Miyazaki Taiga , Izumikawa Koichi , Kakeya Hiroshi , Yanagihara Katsunori , Kohno Shigeru 
Published: May 2013

ABSTRACTCoinfection with bacteria is a major cause of mortality during influenza epidemics. Recently, Toll-like receptor (TLR) agonists were shown to have immunomodulatory functions. In the present study, we investigated the effectiveness and mechanisms of the new TLR4 agonistic monoclonal antibody UT12 against secondary pneumococcal pneumonia induced by coinfection with influenza virus in a mouse model. Mice were intranasally inoculated withStreptococcus pneumoniae2 days after influenza virus inoculation. UT12 was intraperitoneally administered 2 h before each inoculation. Survival rates were significantly increased and body weight loss was significantly decreased by UT12 administration. Additionally, the production of inflammatory mediators was significantly suppressed by the administration of UT12. In a histopathological study, pneumonia in UT12-treated mice was very mild compared to that in control mice. UT12 increased antimicrobial defense through the acceleration of macrophage recruitment into the lower respiratory tract induced by c-Jun N-terminal kinase (JNK) and nuclear factor kappaB (NF-κB) pathway-dependent monocyte chemoattractant protein 1 (MCP-1) production. Collectively, these findings indicate that UT12 promoted pulmonary innate immunity and may reduce the severity of severe pneumonia induced by coinfection with influenza virus andS. pneumoniae. This immunomodulatory effect of UT12 improves the prognosis of secondary pneumococcal pneumonia and makes UT12 an attractive candidate for treating severe infectious diseases.
Characterization of the Native Form of Anthrax Lethal Factor for Use in the Toxin Neutralization Assay
Authors: Lu Hang , Catania Jason , Baranji Katalin , Feng Jie , Gu Mili , Lathey Janet , Sweeny Diane , Sanford Hannah , Sapru Kavita , Patamawenu Terry , Chen June-Home , Ng Alan , Fesseha Zenbework , Kluepfel-Stahl Stefanie , Minang Jacob , Alleva David 
Published: May 2013

ABSTRACTThe cell-based anthrax toxin neutralization assay (TNA) is used to determine functional antibody titers of sera from animals and humans immunized with anthrax vaccines. The anthrax lethal toxin is a critical reagent of the TNA composed of protective antigen (PA) and lethal factor (LF), which are neutralization targets of serum antibodies. Cytotoxic potency of recombinant LF (rLF) lots can vary substantially, causing a challenge in producing a renewable supply of this reagent for validated TNAs. To address this issue, we characterized a more potent rLF variant (rLF-A) with the exact native LF amino acid sequence that lacks the additional N-terminal histidine and methionine residues present on the commonly used form of rLF (rLF-HMA) as a consequence of the expression vector. rLF-A can be used at 4 to 6 ng/ml (in contrast to 40 ng/ml rLF-HMA) with 50 ng/ml recombinant PA (rPA) to achieve 95 to 99% cytotoxicity. In the presence of 50 ng/ml rPA, both rLF-A and rLF-HMA allowed for similar potencies (50% effective dilution) among immune sera in the TNA. rPA, but not rLF, was the dominant factor in determining potency of serum samples containing anti-PA antibodies only or an excess of anti-PA relative to anti-rLF antibodies. Such anti-PA content is reflected in immune sera derived from most anthrax vaccines in development. These results support that 7- to 10-fold less rLF-A can be used in place of rLF-HMA without changing TNA serum dilution curve parameters, thus extending the use of a single rLF lot and a consistent, renewable supply.
Complete Genome Sequence of Glaciecola psychrophila Strain 170
T
Authors: Yin Jinlong , Chen Jing , Liu Guiming , Yu Yong , Song Lai , Wang Xumin , Qu Xiaobo 
Published: May 2013

ABSTRACT

Here, we report the complete genome sequence of
Glaciecola psychrophila
strain 170
T
, a novel species of the genus
Glaciecola
, isolated from sea ice at high-latitude Arctic locations. The genome consists of a single chromosome (5,413,691 bp) and 5,363 genes. The genomics information will facilitate the study of the physiology, cold adaptation, and evolution of this genus.
Whole-Genome Sequences of Streptococcus tigurinus Type Strain AZ_3a and
S
.
tigurinus
1366, a Strain Causing Prosthetic Joint Infection
Authors: Gizard Yann , Zbinden Andrea , Schrenzel Jacques , François Patrice 
Published: May 2013

ABSTRACT

Streptococcus tigurinus
, a novel member of the
Streptococcus mitis
group, was recently identified as a causative agent of invasive infections. We report the complete genome sequences of the
S. tigurinus
type strain AZ_3a and
S. tigurinus
strain 1366. The genome sequences assist in the characterization of virulence determinants of
S. tigurinus.
Structural and Functional Characterization of the Mumps Virus Phosphoprotein
Authors: Cox Robert , Green Todd J. , Purushotham Sangeetha , Deivanayagam Champion , Bedwell Gregory J. , Prevelige Peter E. , Luo Ming 
Published: May 2013

ABSTRACT

The phosphoprotein (P) is virally encoded by the
Rhabdoviridae
and
Paramyxoviridae
in the order
Mononegavirales
. P is a self-associated oligomer and forms complexes with the large viral polymerase protein (L), the nucleocapsid protein (N), and the assembled nucleocapsid. P from different viruses has shown structural diversities even though their essential functions are the same. We systematically mapped the domains in mumps virus (MuV) P and investigated their interactions with nucleocapsid-like particles (NLPs). Similar to other P proteins, MuV P contains N-terminal, central, and C-terminal domains with flexible linkers between neighboring domains. By pulldown assays, we discovered that in addition to the previously proposed nucleocapsid binding domain (residues 343 to 391), the N-terminal region of MuV P (residues 1 to 194) could also bind NLPs. Further analysis of binding kinetics was conducted using surface plasmon resonance. This is the first observation that both the N- and C-terminal regions of a negative-strand RNA virus P are involved in binding the nucleocapsid. In addition, we defined the oligomerization domain (P
OD
) of MuV P as residues 213 to 277 and determined its crystal structure. The tetrameric MuV P
OD
is formed by one pair of long parallel α-helices with another pair in opposite orientation. Unlike the parallel orientation of each α-helix in the tetramer of Sendai virus P
OD
, this represents a novel orientation of a P
OD
where both the N- and the C-terminal domains are at either end of the tetramer. This is consistent with the observation that both the N- and the C-terminal domains are involved in binding the nucleocapsid.
Hypervariable Domain of Nonstructural Protein nsP3 of Venezuelan Equine Encephalitis Virus Determines Cell-Specific Mode of Virus Replication
Authors: Foy Niall J. , Akhrymuk Maryna , Shustov Alexander V. , Frolova Elena I. , Frolov Ilya 
Published: May 2013

ABSTRACT

Venezuelan equine encephalitis virus (VEEV) is one of the most pathogenic members of the
Alphavirus
genus in the
Togaviridae
family. This genus is divided into the Old World and New World alphaviruses, which demonstrate profound differences in pathogenesis, replication, and virus-host interactions. VEEV is a representative member of the New World alphaviruses. The biology of this virus is still insufficiently understood, particularly the function of its nonstructural proteins in RNA replication and modification of the intracellular environment. One of these nonstructural proteins, nsP3, contains a hypervariable domain (HVD), which demonstrates very low overall similarity between different alphaviruses, suggesting the possibility of its function in virus adaptation to different hosts and vectors. The results of our study demonstrate the following. (i) Phosphorylation of the VEEV nsP3-specific HVD does not play a critical role in virus replication in cells of vertebrate origin but is important for virus replication in mosquito cells. (ii) The VEEV HVD is not required for viral RNA replication in the highly permissive BHK-21 cell line. In fact, it can be either completely deleted or replaced by a heterologous protein sequence. These variants require only one or two additional adaptive mutations in nsP3 and/or nsP2 proteins to achieve an efficiently replicating phenotype. (iii) However, the carboxy-terminal repeat in the VEEV HVD is indispensable for VEEV replication in the cell lines other than BHK-21 and plays a critical role in formation of VEEV-specific cytoplasmic protein complexes. Natural VEEV variants retain at least one of the repeated elements in their nsP3 HVDs.
The Interaction of the Cellular Export Adaptor Protein Aly/REF with ICP27 Contributes to the Efficiency of Herpes Simplex Virus 1 mRNA Export
Authors: Tian Xiaochen , Devi-Rao Gayathri , Golovanov Alexander P. , Sandri-Goldin Rozanne M. 
Published: May 2013

ABSTRACT
Herpes simplex virus 1 (HSV-1) protein ICP27 enables viral mRNA export by accessing the cellular mRNA export receptor TAP/NXF, which guides mRNA through the nuclear pore complex. ICP27 binds viral mRNAs and interacts with TAP/NXF, providing a link to the cellular mRNA export pathway. ICP27 also interacts with the mRNA export adaptor protein Aly/REF, which binds cellular mRNAs and also interacts with TAP/NXF. Studies using small interfering RNA (siRNA) knockdown indicated that Aly/REF is not required for cellular mRNA export, and similar knockdown studies during HSV-1 infection led us to conclude that Aly/REF may be dispensable for viral RNA export. Recently, the structural basis of the interaction of ICP27 with Aly/REF was elucidated at atomic resolution, and it was shown that three ICP27 residues, W105, R107, and L108, interface with the RNA recognition motif (RRM) domain of Aly/REF. Here, to determine the role the interaction of ICP27 and Aly/REF plays during infection, these residues were mutated to alanine, and a recombinant virus, WRL-A, was constructed. Virus production was reduced about 10-fold during WRL-A infection, and export of ICP27 protein and most viral mRNAs was less efficient. We conclude that interaction of ICP27 with Aly/REF contributes to efficient viral mRNA export.
Response of Hepatitis C Virus to Long-Term Passage in the Presence of Alpha Interferon: Multiple Mutations and a Common Phenotype
Authors: Perales Celia , Beach Nathan M. , Gallego Isabel , Soria Maria Eugenia , Quer Josep , Esteban Juan Ignacio , Rice Charles , Domingo Esteban , Sheldon Julie 
Published: May 2013

ABSTRACTCell culture-produced hepatitis C virus (HCV) has been subjected to up to 100 serial passages in human hepatoma cells in the absence or presence of different doses of alpha interferon (IFN-α). Virus survival, genetic changes, fitness levels, and phenotypic traits have been examined. While high initial IFN-α doses (increasing from 1 to 4 IU/ml) did not allow HCV survival beyond passage 40, a gradual exposure (from 0.25 to 10 IU/ml) allowed the virus to survive for at least 100 passages. The virus passaged in the presence of IFN-α acquired IFN-α resistance as evidenced by enhanced progeny production and viral protein expression in an IFN-α environment. A partial IFN-α resistance was also noted in populations passaged in the absence of IFN-α. All lineages acquired adaptative mutations, and multiple, nonsynonymous mutations scattered throughout the genome were present in IFN-α-selected populations. Comparison of consensus sequences indicates a dominance of synonymous versus nonsynonymous substitutions. IFN-α-resistant populations displayed decreased sensitivity to a combination of IFN-α and ribavirin. A phenotypic trait common to all assayed viral populations is the ability to increase shutoff host cell protein synthesis, accentuated in infections with IFN-α-selected populations carried out in the presence of IFN-α. The trait was associated with enhanced phosphorylation of protein kinase R (PKR) and eIF2α, although other contributing factors are likely. The results suggest that multiple, independent mutational pathways can confer IFN-α resistance to HCV and might explain why no unified picture has been obtained regarding IFN-α resistancein vivo.
Cellular Chaperonin CCTγ Contributes to Rabies Virus Replication during Infection
Authors: Zhang Jinyang , Wu Xiaopeng , Zan Jie , Wu Yongping , Ye Chengjin , Ruan Xizhen , Zhou Jiyong 
Published: May 2013

ABSTRACT
Rabies, as the oldest known infectious disease, remains a serious threat to public health worldwide. The eukaryotic cytosolic chaperonin TRiC/CCT complex facilitates the folding of proteins through ATP hydrolysis. Here, we investigated the expression, cellular localization, and function of neuronal CCTγ during neurotropic rabies virus (RABV) infection using mouse N2a cells as a model. Following RABV infection, 24 altered proteins were identified by using two-dimensional electrophoresis and mass spectrometry, including 20 upregulated proteins and 4 downregulated proteins. In mouse N2a cells infected with RABV or cotransfected with RABV genes encoding nucleoprotein (N) and phosphoprotein (P), confocal microscopy demonstrated that upregulated cellular CCTγ was colocalized with viral proteins N and P, which formed a hollow cricoid inclusion within the region around the nucleus. These inclusions, which correspond to Negri bodies (NBs), did not form in mouse N2a cells only expressing the viral protein N or P. Knockdown of CCTγ by lentivirus-mediated RNA interference led to significant inhibition of RABV replication. These results demonstrate that the complex consisting of viral proteins N and P recruits CCTγ to NBs and identify the chaperonin CCTγ as a host factor that facilitates intracellular RABV replication. This work illustrates how viruses can utilize cellular chaperonins and compartmentalization for their own benefit.
Simulating liquids and solid-liquid interactions with lagrangian meshes
Authors: Clausen Pascal , Wicke Martin , Shewchuk Jonathan R. , O'Brien James F. 
Published: May 2013

This article describes a Lagrangian finite element method that simulates the behavior of liquids and solids in a unified framework. Local mesh improvement operations maintain a high-quality tetrahedral discretization even as the mesh is advected by fluid flow. We conserve volume and momentum, locally and globally, by assigning to each element an independent rest volume and adjusting it to correct for deviations during remeshing and collisions. Incompressibility is enforced with per-node pressure values, and extra degrees of freedom are selectively inserted to prevent pressure locking. Topological changes in the domain are explicitly treated with local mesh splitting and merging. Our method models surface tension with an implicit formulation based on surface energies computed on the boundary of the volume mesh.
With this method we can model elastic, plastic, and liquid materials in a single mesh, with no need for explicit coupling. We also model heat diffusion and thermoelastic effects, which allow us to simulate phase changes. We demonstrate these capabilities in several fluid simulations at scales from millimeters to meters, including simulations of melting caused by external or thermoelastic heating.