bluuebunny/crossref_metadata_2025 huggingface dataset:
Dosimetric comparison of partial and whole breast external beam irradiation in the treatment of early stage breast cancer
Authors: Kim Yongbok , Parda David S. , Trombetta Mark G. , Colonias Athanasios , Werts E. Day , Miller Linda , Miften Moyed
Published: December 2007

A dosimetric comparison was performed on external‐beam three‐dimensional conformal partial breast irradiation (PBI) and whole breast irradiation (WBI) plans for patients enrolled in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B‐39/Radiation Therapy Oncology Group (RTOG) 0413 protocol at our institution. Twenty‐four consecutive patients were treated with either PBI (12 patients) or WBI (12 patients). In the PBI arm, the lumpectomy cavity was treated to a total dose of 38.5 Gy at 3.85 Gy per fraction twice daily using a four‐field noncoplanar beam setup. A minimum 6 h interval was required between fractions. In the WBI arm, the whole breast including the entirety of the lumpectomy cavity was treated to a total dose of 50.4 Gy at 1.8 Gy per fraction daily using opposed tangential beams. The lumpectomy cavity volume, planning target volume for evaluation (PTV_EVAL), and critical structure volumes were contoured for both the PBI and WBI patients. Dosimetric parameters, dose volume histograms (DVHs), and generalized equivalent uniform dose (gEUD) for target and critical structures were compared. Dosimetric results show the PBI plans, compared to the WBI plans, have smaller hot spots in the PTV_EVAL (maximum dose: versus ) and reduced dose to the ipsilateral breast (: versus and : versus ), contralateral breast (: versus ), ipsilateral lung (: versus ), and thyroid (maximum dose: versus ) with values . However, similar dose coverage of the PTV_EVAL ( for PBI and for WBI, on average) was observed and the dose difference for other critical structures was clinically insignificant in both arms. The gEUD data analysis showed the reduction of dose to the ipsilateral breast and lung, contralateral breast and thyroid. In addition, preliminary dermatologic adverse event assessment data suggested reduced skin toxicity for patients treated with the PBI technique.
An experimental and computational investigation of the standard temperature‐pressure correction factor for ion chambers in kilovoltage x rays
Authors: La Russa Daniel J. , McEwen Malcolm , Rogers D. W. O.
Published: December 2007

For ion chambers with cavities open to the surrounding atmosphere, the response measured at a given temperature and pressure must be corrected using the standard temperature‐pressure correction factor . A previous paper based solely on Monte Carlo simulations [D. J. La Russa and D. W. O. Rogers, Med. Phys. 33, 4590–4599 (2006)] pointed out the shortcomings of the correction factor when used to correct the response of non‐air‐equivalent chambers for low‐energy x‐ray beams. This work presents the results of several experiments that corroborate these calculations for a number of ion chambers. Monte Carlo simulations of the experimental setup revealed additional insight into the various factors affecting the extent of the breakdown of , including the effect of impurities and the sensitivity to chamber dimensions. For an unfiltered 60 kV beam, the ‐corrected response of an NE 2571 ion chamber measured at 0.7 atm was below the response measured at reference conditions. In general, Monte Carlo simulations of the experimental setup using EGSnrc were within of measured values. EGSnrc‐calculated values of air kerma calibration coefficients at low x‐ray energies are also provided as a means of estimating the level of impurities in the chambers investigated. Calculated values of normalized to the value measured for a 250 kV beam were obtained for three chambers and were within of experiment with one exception, the Exradin A12 in a 50 kV beam.
Concurrent multimodality image segmentation by active contours for radiotherapy treatment planninga)
Authors: El Naqa Issam , Yang Deshan , Apte Aditya , Khullar Divya , Mutic Sasa , Zheng Jie , Bradley Jeffrey D. , Grigsby Perry , Deasy Joseph O.
Published: December 2007

Multimodality imaging information is regularly used now in radiotherapy treatment planning for cancer patients. The authors are investigating methods to take advantage of all the imaging information available for joint target registration and segmentation, including multimodality images or multiple image sets from the same modality. In particular, the authors have developed variational methods based on multivalued level set deformable models for simultaneous 2D or 3D segmentation of multimodality images consisting of combinations of coregistered PET, CT, or MR data sets. The combined information is integrated to define the overall biophysical structure volume. The authors demonstrate the methods on three patient data sets, including a nonsmall cell lung cancer case with PET/CT, a cervix cancer case with PET/CT, and a prostate patient case with CT and MRI. CT, PET, and MR phantom data were also used for quantitative validation of the proposed multimodality segmentation approach. The corresponding Dice similarity coefficient (DSC) waswith an estimated target volume error ofvolume. Preliminary results indicate that concurrent multimodality segmentation methods can provide a feasible and accurate framework for combining imaging data from different modalities and are potentially useful tools for the delineation of biophysical structure volumes in radiotherapy treatment planning.
An algorithm for shifting MLC shapes to adjust for daily prostate movement during concurrent treatment with pelvic lymph nodesa)
Authors: Ludlum Erica , Mu Guangwei , Weinberg Vivian , Roach Mack , Verhey Lynn J. , Xia Ping
Published: December 2007

Concurrent treatment of the prostate and the pelvic lymph nodes encounters the problem of the prostate gland moving independently from the pelvic lymph nodes on a daily basis. The purpose of this study is to develop a leaf‐tracking algorithm for adjustment of IMRT portals without requirement of online dose calculation to account for daily prostate position during concurrent treatment with pelvic lymph nodes. A leaf‐shifting algorithm was developed and programmed to adjust the positions of selected MLC leaf pairs according to prostate movement in the plane perpendicular to each beam angle. IMRT plans from five patients with concurrent treatment of the prostate and pelvic lymph nodes were selected to test the feasibility of this algorithm by comparison with isocenter‐shifted plans, using defined dose endpoints. When the prostate moved 0.5, 1.0, and 1.5 cm along the anterior/posterior direction, the average doses to of the prostate for the iso‐shift plans were similar to the MLC‐shift plans, (54.7, 54.4, and 54.1 Gy versus 54.5, 54.3, and 53.9 Gy, respectively). The corresponding averages to the pelvic lymph nodes were reduced from the prescription dose of 45 Gy to 42.7, 38.3, and 34.0 Gy for iso‐shift plans ( for each comparison), while the averages for the MLC‐shift plans did not significantly differ from the prescription dose, at 45.0, 44.8, and 44.5 Gy. Compensation for prostate movement along the superior/inferior direction was more complicated due to a limiting MLC leaf width of 1.0 cm. In order to concurrently treat the prostate and pelvic lymph nodes with the prostate moving independently, shifting selected MLC leaf pairs may be a more practical adaptive solution than shifting the patient.
Joint model of motion and anatomy for PET image reconstruction
Authors: Qiao Feng , Clark John W. , Pan Tinsu , Mawlawi Osama
Published: December 2007

Anatomy‐based positron emission tomography (PET) image enhancement techniques have been shown to have the potential for improving PET image quality. However, these techniques assume an accurate alignment between the anatomical and the functional images, which is not always valid when imaging the chest due to respiratory motion. In this article, we present a joint model of both motion and anatomical information by integrating a motion‐incorporated PET imaging system model with an anatomy‐based maximum a posteriori image reconstruction algorithm. The mismatched anatomical information due to motion can thus be effectively utilized through this joint model. A computer simulation and a phantom study were conducted to assess the efficacy of the joint model, whereby motion and anatomical information were either modeled separately or combined. The reconstructed images in each case were compared to corresponding reference images obtained using a quadratic image prior based maximum a posteriori reconstruction algorithm for quantitative accuracy. Results of these studies indicated that while modeling anatomical information or motion alone improved the PET image quantitation accuracy, a larger improvement in accuracy was achieved when using the joint model. In the computer simulation study and using similar image noise levels, the improvement in quantitation accuracy compared to the reference images was 5.3% and 19.8% when using anatomical or motion information alone, respectively, and 35.5% when using the joint model. In the phantom study, these results were 5.6%, 5.8%, and 19.8%, respectively. These results suggest that motion compensation is important in order to effectively utilize anatomical information in chest imaging using PET. The joint motion‐anatomy model presented in this paper provides a promising solution to this problem.
A new fixation aid for the radiotherapy of eye tumors
Authors: Buchgeister Markus , Grisanti Salvatore , Süsskind Daniela , Bamberg Michael , Paulsen Frank
Published: December 2007

A modified swim goggle holding a light spot as an optical guide for actively aligning the eye in a reproducible orientation has been constructed to perform radiotherapy of ocular tumors. This device is compatible with computed tomography (CT) and magnetic resonance imaging systems. Image fusion of these data sets yielded clinically acceptable results. The reproducibility of the eye's positioning is tested by repeated CT. The eye's alignment during radiotherapy is monitored by an infrared TV camera with individual markings of the eye's position on the TV‐monitor screen. From 2003–2006, 50 patients were treated with this fixation aid by radiosurgery with good patient compliance.
Treatment planning for a small animal using Monte Carlo simulation
Authors: Chow James C. L. , Leung Michael K. K.
Published: December 2007

The development of a small animal model for radiotherapy research requires a complete setup of customized imaging equipment, irradiators, and planning software that matches the sizes of the subjects. The purpose of this study is to develop and demonstrate the use of a flexible in‐house research environment for treatment planning on small animals. The software package, calledDOSCTP, provides a user‐friendly platform for DICOM computed tomography‐based Monte Carlo dose calculation using the EGSnrcMP‐based DOSXYZnrc code. Validation of the treatment planning was performed by comparing the dose distributions for simple photon beam geometries calculated through the Pinnacle3treatment planning system and measurements. A treatment plan for a mouse based on a CT image set by a 360‐deg photon arc is demonstrated. It is shown that it is possible to create 3D conformal treatment plans for small animals with consideration of inhomogeneities using small photon beam field sizes in the diameter range of 0.5–5 cm, with conformal dose covering the target volume while sparing the surrounding critical tissue. It is also found that Monte Carlo simulation is suitable to carry out treatment planning dose calculation for small animal anatomy with voxel size about one order of magnitude smaller than that of the human.
Small-Scale Jetlike Features in Penumbral Chromospheres
Authors: Katsukawa Y. , Berger T. E. , Ichimoto K. , Lites B. W. , Nagata S. , Shimizu T. , Shine R. A. , Suematsu Y. , Tarbell T. D. , Title A. M. , Tsuneta S.
Published: December 2007

We observed fine-scale jetlike features, referred to as penumbral microjets, in chromospheres of sunspot penumbrae. The microjets were identified in image sequences of a sunspot taken through a Ca II H-line filter on the Solar Optical Telescope on board the Japanese solar physics satellite Hinode. The microjets' small width of 400 kilometers and short duration of less than 1 minute make them difficult to identify in existing observations. The microjets are possibly caused by magnetic reconnection in the complex magnetic configuration in penumbrae and have the potential to heat the corona above a sunspot.
Twisting Motions of Sunspot Penumbral Filaments
Authors: Ichimoto K. , Suematsu Y. , Tsuneta S. , Katsukawa Y. , Shimizu T. , Shine R. A. , Tarbell T. D. , Title A. M. , Lites B. W. , Kubo M. , Nagata S.
Published: December 2007

The penumbra of a sunspot is composed of numerous thin, radially extended, bright and dark filaments carrying outward gas flows (the Evershed flow). Using high-resolution images obtained by the Solar Optical Telescope aboard the solar physics satellite Hinode, we discovered a number of penumbral bright filaments revealing twisting motions about their axes. These twisting motions are observed only in penumbrae located in the direction perpendicular to the symmetry line connecting the sunspot center and the solar disk center, and the direction of the twist (that is, lateral motions of intensity fluctuation across filaments) is always from limb side to disk-center side. Thus, the twisting feature is not an actual twist or turn of filaments but a manifestation of dynamics of penumbral filaments with three-dimensional radiative transfer effects.
Chromospheric Anemone Jets as Evidence of Ubiquitous Reconnection
Authors: Shibata Kazunari , Nakamura Tahei , Matsumoto Takuma , Otsuji Kenichi , Okamoto Takenori J. , Nishizuka Naoto , Kawate Tomoko , Watanabe Hiroko , Nagata Shin'ichi , UeNo Satoru , Kitai Reizaburo , Nozawa Satoshi , Tsuneta Saku , Suematsu Yoshinori , Ichimoto Kiyoshi , Shimizu Toshifumi , Katsukawa Yukio , Tarbell Theodore D. , Berger Thomas E. , Lites Bruce W. , Shine Richard A. , Title Alan M.
Published: December 2007

The heating of the solar chromosphere and corona is a long-standing puzzle in solar physics. Hinode observations show the ubiquitous presence of chromospheric anemone jets outside sunspots in active regions. They are typically 3 to 7 arc seconds = 2000 to 5000 kilometers long and 0.2 to 0.4 arc second = 150 to 300 kilometers wide, and their velocity is 10 to 20 kilometers per second. These small jets have an inverted Y-shape, similar to the shape of x-ray anemone jets in the corona. These features imply that magnetic reconnection similar to that in the corona is occurring at a much smaller spatial scale throughout the chromosphere and suggest that the heating of the solar chromosphere and corona may be related to small-scale ubiquitous reconnection.
Response to Comment on "Synthesis of Ultra-Incompressible Superhard Rhenium Diboride at Ambient Pressure"
Authors: Chung Hsiu-Ying , Weinberger Michelle B. , Levine Jonathan B. , Cumberland Robert W. , Kavner Abby , Yang Jenn-Ming , Tolbert Sarah H. , Kaner Richard B.
Published: December 2007

Dubrovinskaia
et al
. question our demonstration that rhenium diboride (ReB
2
) is hard enough to scratch diamond. Here, we provide conclusive evidence of a scratch through atomic force microscopy depth profiling and elemental mapping. With high hardness, high-bulk modulus, and the ability to withstand extreme differential stress, ReB
2
and related materials should be investigated regardless of their cost, which is not prohibitive.
Ketamine-Induced Loss of Phenotype of Fast-Spiking Interneurons Is Mediated by NADPH-Oxidase
Authors: Behrens M. Margarita , Ali Sameh S. , Dao Diep N. , Lucero Jacinta , Shekhtman Grigoriy , Quick Kevin L. , Dugan Laura L.
Published: December 2007

Abuse of the dissociative anesthetic ketamine can lead to a syndrome indistinguishable from schizophrenia. In animals, repetitive exposure to this
N
-methyl-
d
-aspartate–receptor antagonist induces the dysfunction of a subset of cortical fast-spiking inhibitory interneurons, with loss of expression of parvalbumin and the γ-aminobutyric acid–producing enzyme GAD67. We show here that exposure of mice to ketamine induced a persistent increase in brain superoxide due to activation in neurons of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Decreasing superoxide production prevented the effects of ketamine on inhibitory interneurons in the prefrontal cortex. These results suggest that NADPH oxidase may represent a novel target for the treatment of ketamine-induced psychosis.
Designing Superoleophobic Surfaces
Authors: Tuteja Anish , Choi Wonjae , Ma Minglin , Mabry Joseph M. , Mazzella Sarah A. , Rutledge Gregory C. , McKinley Gareth H. , Cohen Robert E.
Published: December 2007

Understanding the complementary roles of surface energy and roughness on natural nonwetting surfaces has led to the development of a number of biomimetic superhydrophobic surfaces, which exhibit apparent contact angles with water greater than 150 degrees and low contact angle hysteresis. However, superoleophobic surfaces—those that display contact angles greater than 150 degrees with organic liquids having appreciably lower surface tensions than that of water—are extremely rare. Calculations suggest that creating such a surface would require a surface energy lower than that of any known material. We show how a third factor, re-entrant surface curvature, in conjunction with chemical composition and roughened texture, can be used to design surfaces that display extreme resistance to wetting from a number of liquids with low surface tension, including alkanes such as decane and octane.
Chromospheric Alfvénic Waves Strong Enough to Power the Solar Wind
Authors: De Pontieu B. , McIntosh S. W. , Carlsson M. , Hansteen V. H. , Tarbell T. D. , Schrijver C. J. , Title A. M. , Shine R. A. , Tsuneta S. , Katsukawa Y. , Ichimoto K. , Suematsu Y. , Shimizu T. , Nagata S.
Published: December 2007

Alfvén waves have been invoked as a possible mechanism for the heating of the Sun's outer atmosphere, or corona, to millions of degrees and for the acceleration of the solar wind to hundreds of kilometers per second. However, Alfvén waves of sufficient strength have not been unambiguously observed in the solar atmosphere. We used images of high temporal and spatial resolution obtained with the Solar Optical Telescope onboard the Japanese Hinode satellite to reveal that the chromosphere, the region sandwiched between the solar surface and the corona, is permeated by Alfvén waves with strong amplitudes on the order of 10 to 25 kilometers per second and periods of 100 to 500 seconds. Estimates of the energy flux carried by these waves and comparisons with advanced radiative magnetohydrodynamic simulations indicate that such Alfvén waves are energetic enough to accelerate the solar wind and possibly to heat the quiet corona.
Serological Evaluation of Specific-Antibody Levels in Patients Treated for Chronic Chagas' Disease
Authors: Sánchez Negrette Olga , Sánchez Valdéz Fernando J. , Lacunza Carlos D. , García Bustos María Fernanda , Mora María Celia , Uncos Alejandro D. , Basombrío Miguel Ángel
Published: December 2007

Serological tests are the main laboratory procedures used for diagnosis during the indeterminate and chronic stages of Chagas' disease. A serological regression to negativity is the main criterion used to define parasitological cure in treated patients. The aim of this work was to monitor the individual specificities of antibody levels for 3 years posttreatment in 18 adult patients. Conventional serological techniques (hemagglutination assays and enzyme-linked immunosorbent assay [ELISA]) were modified by using recombinant antigens to detect early markers of treatment effectiveness. For this purpose, serum samples were taken before and during treatment and every 6 months after treatment for at least 3 years. When hemagglutination assays were used, a decrease in antibody levels was observed in only one patient. When ELISA with serum dilutions was used, antibody clearance became much more apparent: in 77.7% (14/18) of the patients, antibody titers became negative with time. This was observed at serum dilutions of 1/320 and occurred between the 6th and the 30th months posttreatment. The immune response and the interval for a serological regression to negativity were different for each patient. For some of the recombinant antigens, only 50% (9/18) of the patients reached the serological regression to negativity. Recombinant antigen 13 might be a good marker of treatment effectiveness, since 66.6% (six of nine) of the patients presented with an early regression to negativity for specific antibodies to this antigen (
P
= 0.002).
Prevalence, Types, and RNA Concentrations of Human Parechoviruses, Including a Sixth Parechovirus Type, in Stool Samples from Patients with Acute Enteritis
Authors: Baumgarte Sigrid , de Souza Luna Luciano Kleber , Grywna Klaus , Panning Marcus , Drexler Jan Felix , Karsten Claudia , Huppertz Hans Iko , Drosten Christian
Published: December 2007

Parechovirus epidemiology and disease association are not fully understood. Real-time reverse transcriptase PCR (RT-PCR) for all human parechoviruses (HPeV) was applied on stool samples from two groups of patients. Both groups contained patients with acute enteritis of all age groups, seen during one full year. Patients with norovirus, adenovirus, enterovirus, astrovirus, or rotavirus infections were excluded. In 118 patients from outbreak and hospital settings, no HPeV was detected. In a prospective study group of 499 nonhospitalized patients, the detection rate was 1.6%. One virus-positive patient was detected from 39 control patients. Positive samples occurred only in summer and autumn. Only one patient had accompanying respiratory symptoms. An association with travel or animal contact was not found. All positive patients except one were <2 years of age, with a neutral gender ratio. In children <2 years of age, the detection rate was 11.6% (7 of 60 children). The range of viral loads was 3,170 to 503,377,290 copies per gram or milliliter of stool. One of the highest viral loads occurred in a control child without symptoms at the time of testing. Phylogenetic analysis showed mainly contemporary HPeV1 strains in our patients but also showed a separate new lineage of HPeV1 in evolutionary transition from the historical prototype strain. Moreover, a novel sixth HPeV type was identified. Full genome analysis of the two viruses revealed recombination between HPeV1 and -3 in one and HPeV6 and -1 in another. HPeV seems relevant in children <2 years and specific RT-PCR for HPeV should be included in enteritis screening.
Real-Time Reverse Transcription-PCR Assay for Comprehensive Detection of Human Rhinoviruses
Authors: Lu Xiaoyan , Holloway Brian , Dare Ryan K. , Kuypers Jane , Yagi Shigeo , Williams John V. , Hall Caroline B. , Erdman Dean D.
Published: December 2007

Human rhinoviruses (HRVs) are important contributors to respiratory disease, but their healthcare burden remains unclear, primarily because of the lack of sensitive, accurate, and convenient means of determining their causal role. To address this, we developed and clinically validated the sensitivity and specificity of a real-time reverse transcription-PCR (RT-PCR) assay targeting the viral 5′ noncoding region defined by sequences obtained from all 100 currently recognized HRV prototype strains and 85 recently circulating field isolates. The assay successfully amplified all HRVs tested and could reproducibly detect 50 HRV RNA transcript copies, with a dynamic range of over 7 logs. In contrast, a quantified RNA transcript of human enterovirus 68 (HEV68) that showed the greatest sequence homology to the HRV primers and probe set was not detected below a concentration of 5 × 10
5
copies per reaction. Nucleic acid extracts of 111 coded respiratory specimens that were culture positive for HRV or HEV were tested with the HRV real-time RT-PCR assay and by two independent laboratories that used different in-house HRV/HEV RT-PCR assays. Eighty-seven HRV-culture-positive specimens were correctly identified by the real-time RT-PCR assay, and 4 of the 24 HEV-positive samples were positive for HRV. HRV-specific sequences subsequently were identified in these four specimens, suggesting HRV/HEV coinfection in these patients. The assay was successfully applied in an investigation of a coincidental outbreak of HRV respiratory illness among laboratory staff.
A Premature Termination Codon Mutation at the C Terminus of Foamy Virus Gag Downregulates the Levels of Spliced
pol
mRNA
Authors: Lee Eun-Gyung , Kuppers Daniel , Horn Megan , Roy Jacqueline , May Cynthia , Linial Maxine L.
Published: December 2007

Foamy viruses (FV) comprise a subfamily of retroviruses. Orthoretroviruses, such as human immunodeficiency virus type 1, synthesize Gag and Pol from unspliced genomic RNA. However, FV Pol is expressed from a spliced mRNA independently of Gag. FV
pol
splicing uses a 3′ splice site located at the 3′ end of
gag
, resulting in a shared exon between
gag
and
pol
. Previously, our laboratory showed that C-terminal Gag premature termination codon (PTC) mutations in the 3′ shared exon led to greatly decreased levels of Pol protein (C. R. Stenbak and M. L. Linial, J. Virol.
78
:9423-9430, 2004). To further characterize these mutants, we quantitated the levels of unspliced
gag
and spliced
pol
mRNAs using a real-time PCR assay. In some of the PTC mutants, the levels of spliced
pol
mRNA were reduced as much as 30-fold, whereas levels of unspliced
gag
RNA were not affected. Substitutions of a missense codon in place of a PTC restored normal levels of spliced
pol
mRNA. Disrupting Upf proteins involved in nonsense-mediated mRNA decay (NMD) did not affect Pol protein expression. Introduction of an exonic splicing enhancer downstream of the PTC mutation restored
pol
splicing to the wild-type level. Taken together, our results show that the PTC mutation itself is responsible for decreased levels of
pol
mRNA but that mechanisms other than NMD might be involved in downregulating Pol expression. The results also suggest that normal
pol
splicing utilizes a suboptimal splice site seen for other spliced mRNAs in most retroviruses, in that introduced exonic enhancer elements can increase splicing efficiency.
Independent and Cooperative Antiviral Actions of Beta Interferon and Gamma Interferon against Herpes Simplex Virus Replication in Primary Human Fibroblasts
Authors: Peng Tao , Zhu Jia , Hwangbo Yon , Corey Lawrence , Bumgarner Roger E.
Published: December 2007

Type I and type II interferons (IFNs) act in synergy to inhibit the replication of a variety of viruses, including herpes simplex virus (HSV). To understand the mechanism of this effect, we have analyzed the transcriptional profiles of primary human fibroblast cells that were first treated with IFN-β1, IFN-γ, or a combination of both and then subsequently infected with HSV-1. We have identified two types of synergistic activities in the gene expression patterns induced by IFN-β1 and IFN-γ that may contribute to inhibition of HSV-1 replication. The first is defined as “synergy by independent action,” in which IFN-β1 and IFN-γ induce distinct gene categories. The second, “synergy by cooperative action,” is a term that describes the positive interaction between IFN-β1 and IFN-γ as defined by a two-way analysis of variance. This form of synergy leads to a much higher level of expression for a subset of genes than is seen with either interferon alone. The cooperatively induced genes by IFN-β1 and IFN-γ include those involved in apoptosis, RNA degradation, and the inflammatory response. Furthermore, the combination of IFN-β1 and IFN-γ induces significantly more apoptosis and inhibits HSV-1 gene expression and DNA replication significantly more than treatment with either interferon alone. Taken together, these data suggest that IFN-β1 and IFN-γ work both independently and cooperatively to create an antiviral state that synergistically inhibits HSV-1 replication in primary human fibroblasts and that cooperatively induced apoptosis may play a role in the synergistic effect on viral replication.
Negative Feedback Regulation of RIG-I-Mediated Antiviral Signaling by Interferon-Induced ISG15 Conjugation
Authors: Kim Min-Jung , Hwang Sun-Young , Imaizumi Tadaatsu , Yoo Joo-Yeon
Published: December 2007

RIG-I senses intracellular virus-specific nucleic acid structures and initiates an antiviral response that induces interferon (IFN) production, which, in turn, activates the transcription of RIG-I to increase RIG-I protein levels. Upon intracellular poly(I:C) stimulation, however, the levels of RIG-I protein did not correlate with the expression patterns of
RIG-I
transcripts. When the ISG15 conjugation system was overexpressed, ISG15 was conjugated to RIG-I and cellular levels of the unconjugated form of RIG-I decreased. The ISGylation of RIG-I reduced levels of both basal and virus-induced IFN promoter activity. Levels of unconjugated RIG-I also decreased when 26S proteasome activity was blocked by treatment with MG132, ALLN, or Lactacystin. In the presence of MG132, ISG15 conjugation to RIG-I increased, and hence, the unconjugated form of RIG-I was reduced. In Ube1L
−/−
cells, which lack the ability to conjugate ISG15, basal levels of both RIG-I protein and transcripts were increased compared to those in wild-type cells. As a result, enhanced production of ISGs and enhanced IFN promoter activity in Ube1L
−/−
cells were observed, and the phenotype was restored to that of wild-type cells by the overexpression of Ube1L. Based on these results, we propose a novel negative feedback loop which adjusts the strength of the RIG-I-mediated antiviral response and IFN production through the regulation of RIG-I protein by IFN-induced ISG15 conjugation.
Replication of Coxsackievirus B3 in Primary Cell Cultures Generates Novel Viral Genome Deletions
Authors: Kim K.-S. , Chapman N. M. , Tracy S.
Published: December 2007

Coxsackievirus B3 (CVB3) generates 5′-terminally deleted genomes (TDs) during replication in murine hearts. We show here that CVB3 populations with TDs can also be generated within two to three passages of CVB3 in primary, but not immortalized, cell cultures. Deletions of less than 49 nucleotides increase in size during passage, while 5′ TDs of 49 nucleotides appear to be the maximum deletion size. The cellular environment of contact-inhibited primary cell cultures or the myocardium in vivo is sufficient for the selection of 5′ TDs over undeleted genomes.
Evidence of the Recombinant Origin of a Bat Severe Acute Respiratory Syndrome (SARS)-Like Coronavirus and Its Implications on the Direct Ancestor of SARS Coronavirus
Authors: Hon Chung-Chau , Lam Tsan-Yuk , Shi Zheng-Li , Drummond Alexei J. , Yip Chi-Wai , Zeng Fanya , Lam Pui-Yi , Leung Frederick Chi-Ching
Published: December 2007

Bats have been identified as the natural reservoir of severe acute respiratory syndrome (SARS)-like and SARS coronaviruses (SLCoV and SCoV). However, previous studies suggested that none of the currently sampled bat SLCoVs is the descendant of the direct ancestor of SCoV, based on their relatively distant phylogenetic relationship. In this study, evidence of the recombinant origin of the genome of a bat SLCoV is demonstrated. We identified a potential recombination breakpoint immediately after the consensus intergenic sequence between open reading frame 1 and the S coding region, suggesting the replication intermediates may participate in the recombination event, as previously speculated for other CoVs. Phylogenetic analysis of its parental regions suggests the presence of an uncharacterized SLCoV lineage that is phylogenetically closer to SCoVs than any of the currently sampled bat SLCoVs. Using various Bayesian molecular-clock models, interspecies transfer of this SLCoV lineage from bats to the amplifying host (e.g., civets) was estimated to have happened a median of 4.08 years before the SARS outbreak. Based on this relatively short window period, we speculate that this uncharacterized SLCoV lineage may contain the direct ancestor of SCoV. This study sheds light on the possible host bat species of the direct ancestor of SCoV, providing valuable information on the scope and focus of surveillance for the origin of SCoV.
Complete In Vitro Reconstitution of Adeno-Associated Virus DNA Replication Requires the Minichromosome Maintenance Complex Proteins
Authors: Nash Kevin , Chen Weijun , Muzyczka Nicholas
Published: December 2007

Adeno-associated virus (AAV) replicates its DNA exclusively by a leading-strand DNA replication mechanism and requires coinfection with a helper virus, such as adenovirus, to achieve a productive infection. In previous work, we described an in vitro AAV replication assay that required the AAV terminal repeats (the origins for DNA replication), the AAV Rep protein (the origin binding protein), and an adenovirus-infected crude extract. Fractionation of these crude extracts identified replication factor C (RFC), proliferating cell nuclear antigen (PCNA), and polymerase δ as cellular enzymes that were essential for AAV DNA replication in vitro. Here we identify the remaining factor that is necessary as the minichromosome maintenance (MCM) complex, a cellular helicase complex that is believed to be the replicative helicase for eukaryotic chromosomes. Thus, polymerase δ, RFC, PCNA, and the MCM complex, along with the virally encoded Rep protein, constitute the minimal protein complexes required to reconstitute efficient AAV DNA replication in vitro. Interfering RNAs targeted to MCM and polymerase δ inhibited AAV DNA replication in vivo, suggesting that one or more components of the MCM complex and polymerase δ play an essential role in AAV DNA replication in vivo as well as in vitro. Our reconstituted in vitro DNA replication system is consistent with the current genetic information about AAV DNA replication. The use of highly conserved cellular replication enzymes may explain why AAV is capable of productive infection in a wide variety of species with several different families of helper viruses.
Epstein-Barr Virus Latent Membrane Protein 1 Induces Cellular MicroRNA miR-146a, a Modulator of Lymphocyte Signaling Pathways
Authors: Cameron Jennifer E. , Yin Qinyan , Fewell Claire , Lacey Michelle , McBride Jane , Wang Xia , Lin Zhen , Schaefer Brian C. , Flemington Erik K.
Published: December 2007

The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is a functional homologue of the tumor necrosis factor receptor family and contributes substantially to the oncogenic potential of EBV through activation of nuclear factor κB (NF-κB). MicroRNAs (miRNAs) are a class of small RNA molecules that are involved in the regulation of cellular processes such as growth, development, and apoptosis and have recently been linked to cancer phenotypes. Through miRNA microarray analysis, we demonstrate that LMP1 dysregulates the expression of several cellular miRNAs, including the most highly regulated of these, miR-146a. Quantitative reverse transcription-PCR analysis confirmed induced expression of miR-146a by LMP1. Analysis of miR-146a expression in EBV latency type III and type I cell lines revealed substantial expression of miR-146a in type III (which express LMP1) but not in type I cell lines. Reporter studies demonstrated that LMP1 induces miR-146a predominantly through two NF-κB binding sites in the miR-146a promoter and identified a role for an Oct-1 site in conferring basal and induced expression. Array analysis of cellular mRNAs expressed in Akata cells transduced with an miR-146a-expressing retrovirus identified genes that are directly or indirectly regulated by miR-146a, including a group of interferon-responsive genes that are inhibited by miR-146a. Since miR-146a is known to be induced by agents that activate the interferon response pathway (including LMP1), these results suggest that miR-146a functions in a negative feedback loop to modulate the intensity and/or duration of the interferon response.
Manipulation of Rab GTPase Function by Intracellular Bacterial Pathogens
Authors: Brumell John H. , Scidmore Marci A.
Published: December 2007

Intracellular bacterial pathogens have evolved highly specialized mechanisms to enter and survive within their eukaryotic hosts. In order to do this, bacterial pathogens need to avoid host cell degradation and obtain nutrients and biosynthetic precursors, as well as evade detection by the host immune system. To create an intracellular niche that is favorable for replication, some intracellular pathogens inhibit the maturation of the phagosome or exit the endocytic pathway by modifying the identity of their phagosome through the exploitation of host cell trafficking pathways. In eukaryotic cells, organelle identity is determined, in part, by the composition of active Rab GTPases on the membranes of each organelle. This review describes our current understanding of how selected bacterial pathogens regulate host trafficking pathways by the selective inclusion or retention of Rab GTPases on membranes of the vacuoles that they occupy in host cells during infection.
Interspecies Interactions within Oral Microbial Communities
Authors: Kuramitsu Howard K. , He Xuesong , Lux Renate , Anderson Maxwell H. , Shi Wenyuan
Published: December 2007

While reductionism has greatly advanced microbiology in the past 400 years, assembly of smaller pieces just could not explain the whole! Modern microbiologists are learning “system thinking” and “holism.” Such an approach is changing our understanding of microbial physiology and our ability to diagnose/treat microbial infections. This review uses oral microbial communities as a focal point to describe this new trend. With the common name “dental plaque,” oral microbial communities are some of the most complex microbial floras in the human body, consisting of more than 700 different bacterial species. For a very long time, oral microbiologists endeavored to use reductionism to identify the key genes or key pathogens responsible for oral microbial pathogenesis. The limitations of reductionism forced scientists to begin adopting new strategies using emerging concepts such as interspecies interaction, microbial community, biofilms, polymicrobial disease, etc. These new research directions indicate that the whole is much more than the simple sum of its parts, since the interactions between different parts resulted in many new physiological functions which cannot be observed with individual components. This review describes some of these interesting interspecies-interaction scenarios.
THE MODIFIED ELECTRODES FOR THE APPLICATION OF POLAR MOLECULE DOMINATED ELECTRORHEOLOGICAL (PM-ER) FLUIDS
Authors: WANG XUEZHAO , SHEN RONG , SUN GANG , WEN WEIJIA , LU KUNQUAN
Published: December 2007

For polar molecule dominated electrorheological (PM-ER) fluids [1], the surfaces of ordinary metallic electrodes cannot satisfy the condition of polar molecules' aligning and interaction. Slide must occur at the interface between PM-ER fluids and electrodes so that the measured shear stress is much lower than the true value. Several modified electrodes are developed and tested for increasing the adhesion of PM-ER fluids to the electrodes and weakening the slide in shearing. The modified electrodes can not only improve the measured shear stress to approach the intrinsic one, but also greatly reduce the current density of PM-ER fluids. Using the modified electrodes is certainly necessary for measuring and applying the PM-ER fluids.
INFLUENCE OF PARTICLE SHAPE ON THE PROPERTIES OF MAGNETORHEOLOGICAL FLUIDS
Authors: BELL R. C. , MILLER E. D. , KARLI J. O. , VAVRECK A. N. , ZIMMERMAN D. T.
Published: December 2007

We present studies of the rheological properties and dispersion stability of MR fluids as a function of particle shape by comparing fluids made with uniform nickel spheres to those employing nickel microwires suspended in silicone oil. The wires were fabricated using template-based electrodeposition having diameters in the range 300 ± 30 nm and lengths in the range of 5 – 25 μm . The properties of these wires were compared to commercial nickel carbonyl spheres (1–10 μm dia.). Qualitatively, the off-state (field off) viscosity of fluids containing only wires was found to be substantially greater than those fluids that contain only spherical particles. Rheological measurements of the on-state viscosities were conducted using a custom rheometer equipped with an electromagnet capable of magnetic fields up to 0.6 T. Placed in this field, we observed yield stresses of 1.88 ± 0.23 and 1.86 ± 0.26 kPa for 7.6 volume percent of pure nickel spheres and microwires, respectively. The fluids containing spherical nickel particles tended to settle rather quickly (< 20 minutes), while those containing only wires remained suspended even after several months.
COMBINATORIC AND DIAGRAMMATIC STUDY IN KNOT THEORY
Authors: HSIEH CHUN-CHUNG
Published: December 2007

Motivated by Massey–Milnor linking and Chern–Simon–Witten perturbative quantum field theory, we developed some combinatorial and diagrammatic study in this paper, aiming at knot theory in the combinatoric aspect.
n-DIMENSIONAL GEOMETRIES AND EINSTEIN EQUATIONS FROM SYSTEMS OF PDE'S
Authors: GALLO EMANUEL , MARCIANO-MELCHOR MAGDALENA , SILVA-ORTIGOZA GILBERTO
Published: December 2007

The aim of this work is twofold: first, we show how all the n-dimensional Riemannian and Lorentzian metrics can be constructed from a certain class of systems of second-order PDE's which are in duality to the Hamilton–Jacobi equation; second, we impose the Einstein equations on these PDE's.
MEASUREMENT OF FLICKER NOISE AS A DIAGNOSTIC TOOL FOR HOT-ELECTRON DEGRADATION IN GaN-BASED LEDS
Authors: FONG W. K. , LEUNG K. K. , LUI H. F. , WAI P. K. A. , SURYA C. , CHEN Z. , CAO C. B.
Published: December 2007

Hot-electron stressing on GaN -based light emitting diodes (LEDs) has been performed using a dc stressing current. Detailed characterizations on the degradations in the optoelectronic and low-frequency noise properties of the devices have been conducted. Experimental results on I-V, electroluminescence (EL) and the integrated light output of the devices exhibit significant degradations with the stress time. Investigations on the low-frequency excess noise of the devices show that the degradations of the device properties arise from the generation of interface states at the InGaN / GaN heterointerface due to hot-electron stressing. Over two orders of magnitude increase in the current noise power spectral density, SI(f), is typically observed prior to the failure of the devices. Furthermore, it is shown that the initial rate of increase in SI(f) resulting from a dc current stress time of 48 hours is strongly correlated to the lifetimes of the devices demonstrating that flicker noise measurement can be used as a diagnostic tool for hot-electron hardness of the device.
THREE-DIMENSIONAL PENETRATION SIMULATION USING SMOOTHED PARTICLE HYDRODYNAMICS
Authors: ZHOU C. E. , LIU G. R. , LOU K. Y.
Published: December 2007

This paper presents three-dimensional computational simulations of the hypervelocity impact (HVI) using standard smoothed particle hydrodynamics (SPH). The classic Taylor-Bar-Impact test is revisited with the focus on the variation of results corresponding to the different model parameters in the SPH implementation. The second example involves both normal and oblique HVIs of a sphere on the thin plate, producing large deformation of structures. Based on original experimental results and some numerical results reported previously, some comparisons are also made, in the hope of providing informative data on appropriate SPH implementation options for the software being developed. The results obtained show that the current SPH procedure is well suited for the HVI problems.
PROCESS OPTIMIZATION AND SENSITIVITY INVESTIGATION IN LASER FORMING WITH FINITE ELEMENT ANALYSIS
Authors: JUNG H. C. , KRUMDIECK S.
Published: December 2007

Laser forming is a flexible sheet metal manufacturing technique capable of producing various shapes, without hard tools and external forces, by irradiation across the surface of the metal piece. A three-dimensional thermal-elasto-plastic (TEP) finite element model for a straight line laser forming process has been developed during the course of this study, which simulates bend angles and temperature distributions. Laser forming process optimization and material sensitivity are investigated. In order to seek the optimal process conditions to generate a desired bend angle in the multi-scan laser bending process, an optimization algorithm based on the approximation of objective function and state variables is integrated into the numerical model. An optimal set of process parameters such as laser power, scan speed, beam diameter and the number of scans are obtained with optimization procedure. In order to assess process sensitivity to material roperties, associations between bend angle and material properties are statistically determined using the Pearson product-moment correlation coefficient via Monte Carlo simulations, for which a large number of the finite element simulations are carried out. The material properties of interest include the coefficient of thermal expansion, thermal conductivity, specific heat, modulus of elasticity, and Poisson's ratio. Results show that the process optimization coupled with finite element analysis can be used to determine processing parameters, and that the material properties of primary importance are the coefficient of thermal expansion, thermal conductivity and specific heat.
Cenozoic behind-arc volcanism in the Bolivian Andes, South America: implications for mantle melt generation and lithospheric structure
Authors: Hoke Leonore , Lamb Simon
Published: December 2007

We develop a model of arc and behind-arc volcanism, as well as constraining the evolution of the lithospheric mantle structure beneath the Bolivian Andes during the last 25 Ma, using new geochronological and geochemical data on behind-arc mafic volcanic rocks, together with a regional isotopic study of geothermal helium emissions, and a comparison with seismic tomographic images of the same region. Helium isotopes measured in natural gas emissions in geothermal and mineral-water springs suggest recent mantle melting in a wide zone extending at
c
. 20°S from a few tens of kilometres west of the volcanic arc to over 300 km behind the arc, where the subducted slab is at depths increasing from
c
. 100 to
c
. 250 km. During the Neogene, there has been behind-arc mafic–felsic magmatism right across the high Andes between 17° and 22°S, in the Altiplano and western margin of the Eastern Cordillera. Modelling of Plio-Pleistocene basalts and basaltic andesites (<5.2 Ma), using REE, suggests that the main melt source region is in spinel and spinel–garnet peridotite, at depths <100 km. In detail, the best-fit REE inversions suggest two spatially distinct melt zones: (1) a
c
. 15% depleted mid-ocean ridge basalt (MORB) source at depths between
c
. 75 km and
c
. 110 km for mafic volcanic rocks that crop out <75 km behind the arc; (2) a slightly enriched MORB source at depths between
c
. 65 km and
c
. 90 km for those that crop out >100 km behind the arc. REE inversions for Oligo-Miocene shoshonites and basalts (
c
. 25–21 Ma) suggest that they originated at significantly shallower depths (
c
. 45 km to
c
. 100 km) from a slightly enriched MORB source. Eruption of shoshonitic lavas also occurred in the Altiplano between 13 and 11 Ma, and widespread behind-arc intermediate–felsic volcanism has been more or less continuous since the early Miocene. All this suggests that since
c
. 25 Ma there has been a thin (<100 km) lithosphere beneath the high part of the Bolivian Andes. Long-lived mantle melting is best explained by wet adiabatic decompression in the upwelling part of the corner flow in the mantle wedge, controlled by the lithospheric thickness variations, with depleted melt advected into the melt zone beneath the arc. Widespread arc and behind-arc magmatism may have been triggered at
c
. 25 Ma by the opening up of a mantle wedge and inflow of hot asthenosphere, as a consequence of the steepening of the subducted slab and detachment of hydrated and weakened mantle lithosphere and possibly mafic lower crust.