bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparative study of a dual‐energy‐like imaging technique based on counting‐integrating readout
Authors: Roessl Ewald , Herrmann Christoph , Kraft Edgar , Proksa Roland 
Published: November 2011

Purpose:The recent introduction of a specific electronic readout chip, designed for the processing of the same signal pulses from an x‐ray sensor in one integrating and one counting channel in each pixel E. Kraftet al., [IEEE Trans. Nucl. Sci. 54, 383–390 (2007)]; E. Kraft, “Counting and integrating microelectronics development for direct conversion X‐ray imaging,” Ph.D. thesis, 2007; J. Fink, “Characterization of the imaging performance of the simultaneously counting and integrating X‐ray detector CIX,” Ph.D. thesis, 2010, enables an alternative to conventional dual‐energy imaging methods. As shown in a previous paper, the proposed alternative benefits from positively correlated noise in the raw data, inherent to the counting‐integrating readout (CIX), which results in a reduction of basis image noise after dual‐energy decomposition. In the present paper, the authors compare the new approach to dual‐energy imaging to two conventional dual‐energy techniques, the dual‐kV technique and the dual‐crystal technique and to a photon‐counting technique based on two energy windows.Methods:The study is based on x‐ray computed tomography (CT) simulations of an anthropomorphic head phantom, where the signal‐to‐noise ratios and the contrast‐to‐noise ratios in basis material images and quasi‐monochromatic images at 60 keV are compared. Moreover, a simple pictorial illustration of the relevance of input noise correlations in the noise‐propagation process during the dual‐energy basis material decomposition are presented, as well as measurement data for the correlation obtained as a function of the x‐ray flux rate.Results:Under the idealized assumptions of the absence of scatter and detector imperfections like K‐escape, crosstalk and detector noise, our comparison shows that among the dual‐energy techniques investigated, the CIX concept together with the dual‐kV technique performs best, confirming the mitigating effect of correlated measurement data on the dual‐energy basis material decomposition.Conclusions:The novel concept of simultaneous counting of photons and integrating the x‐ray energy flux has a large potential for dual‐energy applications in both projection and tomographic x‐ray imaging. Future work will have to focus on the sensitivity of the CIX dual‐energy concept to scattered radiation, detector imperfections and high x‐ray fluxes.
Uncoupling
cis
-Acting RNA Elements from Coding Sequences Revealed a Requirement of the N-Terminal Region of Dengue Virus Capsid Protein in Virus Particle Formation
Authors: Samsa Marcelo M. , Mondotte Juan A. , Caramelo Julio J. , Gamarnik Andrea V. 
Published: November 2011

ABSTRACT

Little is known about the mechanism of flavivirus genome encapsidation. Here, functional elements of the dengue virus (DENV) capsid (C) protein were investigated. Study of the N-terminal region of DENV C has been limited by the presence of overlapping
cis
-acting RNA elements within the protein-coding region. To dissociate these two functions, we used a recombinant DENV RNA with a duplication of essential RNA structures outside the C coding sequence. By the use of this system, the highly conserved amino acids FNML, which are encoded in the RNA cyclization sequence 5′CS, were found to be dispensable for C function. In contrast, deletion of the N-terminal 18 amino acids of C impaired DENV particle formation. Two clusters of basic residues (R5-K6-K7-R9 and K17-R18-R20-R22) were identified as important. A systematic mutational analysis indicated that a high density of positive charges, rather than particular residues at specific positions, was necessary. Furthermore, a differential requirement of N-terminal sequences of C for viral particle assembly was observed in mosquito and human cells. While no viral particles were observed in human cells with a virus lacking the first 18 residues of C, DENV propagation was detected in mosquito cells, although to a level about 50-fold less than that observed for a wild-type (WT) virus. We conclude that basic residues at the N terminus of C are necessary for efficient particle formation in mosquito cells but that they are crucial for propagation in human cells. This is the first report demonstrating that the N terminus of C plays a role in DENV particle formation. In addition, our results suggest that this function of C is differentially modulated in different host cells.
Durable Protection from Vaginal Simian-Human Immunodeficiency Virus Infection in Macaques by Tenofovir Gel and Its Relationship to Drug Levels in Tissue
Authors: Dobard Charles , Sharma Sunita , Martin Amy , Pau Chou-Pong , Holder Angela , Kuklenyik Zsuzsanna , Lipscomb Jonathan , Hanson Debra L. , Smith James , Novembre Francis J. , García-Lerma J. Gerardo , Heneine Walid 
Published: November 2011

ABSTRACTA vaginal gel containing 1% tenofovir (TFV) was found to be safe and effective in reducing HIV infection in women when used pericoitally. Because of the long intracellular half-life of TFV and high drug exposure in vaginal tissues, we hypothesized that a vaginal gel containing TFV may provide long-lasting protection. Here, we performed delayed-challenge experiments and showed that vaginal 1% TFV gel protected 4/6 macaques against vaginal simian-human immunodeficiency virus (SHIV) exposures occurring 3 days after gel application, demonstrating long-lasting protection. Despite continued gel dosing postinfection, neither breakthrough infection had evidence of drug resistance by ultrasensitive testing of SHIV in plasma and vaginal lavage. Analysis of the active intracellular tenofovir diphosphate (TFV-DP) in vaginal lymphocytes collected 4 h to 3 days after gel dosing persistently showed high TFV-DP levels (median, 1,810 fmol/106cells) between 4 and 24 h that exceed the 95% inhibitory concentration (IC95), reflecting rapid accumulation and long persistence. In contrast to those in peripheral blood mononuclear cells (PBMCs) following oral dosing, TFV-DP levels in vaginal lymphocytes decreased approximately 7-fold by 3 days, exhibiting a much higher rate of decay. We observed a strong correlation between intracellular TFV-DP in vaginal lymphocytes,in vitroantiviral activity, andin vivoprotection, suggesting that TFV-DP above thein vitroIC95in vaginal lymphocytes is a good predictor of high efficacy. Data from this model reveal an extended window of protection by TFV gel that supports coitus-independent use. The identification of protective TFV-DP concentrations in vaginal lymphocytes may facilitate the evaluation of improved delivery methods of topical TFV and inform clinical studies.
Measles Virus C Protein Interferes with Beta Interferon Transcription in the Nucleus
Authors: Sparrer Konstantin M. J. , Pfaller Christian K. , Conzelmann Karl-Klaus 
Published: November 2011

ABSTRACT

Transcriptional induction of beta interferon (IFN-β) through pattern recognition receptors is a key event in the host defense against invading viruses. Infection of cells by paramyxoviruses, like measles virus (MV) (genus
Morbillivirus
), is sensed predominantly by the ubiquitous cytoplasmic helicase RIG-I, recognizing viral 5′-triphosphate RNAs, and to some degree by MDA5. While MDA5 activation is effectively prevented by the MV V protein, the viral mechanisms for inhibition of MDA5-independent induction of IFN-β remained obscure. Here, we identify the 186-amino-acid MV C protein, which shuttles between the nucleus and the cytoplasm, as a major viral inhibitor of IFN-β transcription in human cells. Activation of the transcription factor IRF3 by upstream kinases and nuclear import of activated IRF3 were not affected in the presence of C protein, suggesting a nuclear target. Notably, C proteins of wild-type MV isolates, which are poor IFN-β inducers, were found to comprise a canonical nuclear localization signal (NLS), whereas the NLSs of all vaccine strains, irrespective of their origins, were mutated. Site-directed mutagenesis of the C proteins from an MV wild-type isolate and from the vaccine virus strain Schwarz confirmed a correlation of nuclear localization and inhibition of IFN-β transcription. A functional NLS and efficient nuclear accumulation are therefore critical for MV C to retain its potential to downregulate IFN-β induction. We suggest that a defect in efficient nuclear import of C protein contributes to attenuation of MV vaccine strains.
Adenovirus Serotype 5-Specific Neutralizing Antibodies Target Multiple Hexon Hypervariable Regions
Authors: Bradley Ritu R. , Maxfield Lori F. , Lynch Diana M. , Iampietro Mark J. , Borducchi Erica N. , Barouch Dan H. 
Published: November 2011

ABSTRACT
The immunogenicity of adenovirus serotype 5 (Ad5) vectors has been shown to be suppressed by neutralizing antibodies (NAbs) directed primarily against the hexon hypervariable regions (HVRs). We previously reported that replacing all seven HVRs with those from the rare serotype virus Ad48 resulted in a chimeric Ad5HVR48(1-7) vector that largely evaded preexisting Ad5 immunity in mice and rhesus monkeys. In this study, we evaluated the extent to which Ad5-specific NAbs are directed against various HVRs. We constructed partial HVR-chimeric Ad5 vectors with only a subset of HVRs exchanged, and we utilized these vectors in both NAb assays and murine immunogenicity studies with and without baseline Ad5 immunity. Our results demonstrate that Ad5-specific NAbs target multiple HVRs, suggesting that replacing all HVRs is required to optimize evasion of anti-Ad5 immunity. These data have important implications for the development of novel vectors for both vaccines and gene therapy.
Evidence against Extracellular Exposure of a Highly Immunogenic Region in the C-Terminal Domain of the Simian Immunodeficiency Virus gp41 Transmembrane Protein
Authors: Postler Thomas S. , Martinez-Navio José M. , Yuste Eloísa , Desrosiers Ronald C. 
Published: November 2011

ABSTRACTThe generally accepted model for human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein topology includes a single membrane-spanning domain. An alternate model has been proposed which features multiple membrane-spanning domains. Consistent with the alternate model, a high percentage of HIV-1-infected individuals produce unusually robust antibody responses to a region of envelope, the so-called “Kennedy epitope,” that in the conventional model should be in the cytoplasm. Here we show analogous, robust antibody responses in simian immunodeficiency virus SIVmac239-infected rhesus macaques to a region of SIVmac239 envelope located in the C-terminal domain, which in the conventional model should be inside the cell. Sera from SIV-infected rhesus macaques consistently reacted with overlapping oligopeptides corresponding to a region located within the cytoplasmic domain of gp41 by the generally accepted model, at intensities comparable to those observed for immunodominant areas of the surface component gp120. Rabbit serum raised against this highly immunogenic region (HIR) reacted with SIV envelope in cell surface-staining experiments, as did monoclonal anti-HIR antibodies isolated from an SIVmac239-infected rhesus macaque. However, control experiments demonstrated that this surface staining could be explained in whole or in part by the release of envelope protein from expressing cells into the supernatant and the subsequent attachment to the surfaces of cells in the culture. Serum and monoclonal antibodies directed against the HIR failed to neutralize even the highly neutralization-sensitive strain SIVmac316. Furthermore, a potential N-linked glycosylation site located close to the HIR and postulated to be outside the cell in the alternate model was not glycosylated. An artificially introduced glycosylation site within the HIR was also not utilized for glycosylation. Together, these data support the conventional model of SIV envelope as a type Ia transmembrane protein with a single membrane-spanning domain and without any extracellular loops.
p53 Promotes Cardiac Dysfunction in Diabetic Mellitus Caused by Excessive Mitochondrial Respiration-Mediated Reactive Oxygen Species Generation and Lipid Accumulation
Authors: Nakamura Hideo , Matoba Satoaki , Iwai-Kanai Eri , Kimata Masaki , Hoshino Atsushi , Nakaoka Mikihiko , Katamura Maki , Okawa Yoshifumi , Ariyoshi Makoto , Mita Yuichiro , Ikeda Koji , Okigaki Mitsuhiko , Adachi Souichi , Tanaka Hideo , Takamatsu Tetsuro , Matsubara Hiroaki 
Published: November 2011

Background—
Diabetic cardiomyopathy is characterized by energetic dysregulation caused by glucotoxicity, lipotoxicity, and mitochondrial alterations. p53 and its downstream mitochondrial assembly protein, synthesis of cytochrome c oxidase 2 (SCO2), are important regulators of mitochondrial respiration, whereas the involvement in diabetic cardiomyopathy remains to be determined.

Methods and Results—

The role of p53 and SCO2 in energy metabolism was examined in both type I (streptozotocin [STZ] administration) and type II diabetic (
db/db
) mice. Cardiac expressions of p53 and SCO2 in 4-week STZ diabetic mice were upregulated (185% and 152% versus controls, respectively,
P
<0.01), with a marked decrease in cardiac performance. Mitochondrial oxygen consumption was increased (136% versus control,
P
<0.01) in parallel with augmentation of mitochondrial cytochrome c oxidase (complex IV) activity. Reactive oxygen species (ROS)-damaged myocytes and lipid accumulation were increased in association with membrane-localization of fatty acid translocase protein FAT/CD36. Antioxidant tempol reduced the increased expressions of p53 and SCO2 in STZ-diabetic hearts and normalized alterations in mitochondrial oxygen consumption, lipid accumulation, and cardiac dysfunction. Similar results were observed in
db/db
mice, whereas in p53-deficient or SCO2-deficient diabetic mice, the cardiac and metabolic abnormalities were prevented. Overexpression of SCO2 in cardiac myocytes increased mitochondrial ROS and fatty acid accumulation, whereas knockdown of SCO2 ameliorated them.

Conclusions—
Myocardial p53/SCO2 signal is activated by diabetes-mediated ROS generation to increase mitochondrial oxygen consumption, resulting in excessive generation of mitochondria-derived ROS and lipid accumulation in association with cardiac dysfunction.
Loop Current Mixed Layer Energy Response to Hurricane Lili (2002). Part I: Observations
Authors: Uhlhorn Eric W. , Shay Lynn K. 
Published: November 2011

Abstract
The ocean mixed layer response to a tropical cyclone within and immediately adjacent to the Gulf of Mexico Loop Current is examined. In the first of a two-part study, a comprehensive set of temperature, salinity, and current profiles acquired from aircraft-deployed expendable probes is utilized to analyze the three-dimensional oceanic energy evolution in response to Hurricane Lili’s (2002) passage. Mixed layer temperature analyses show that the Loop Current cooled &lt;1°C in response to the storm, in contrast to typically observed larger decreases of 3°–5°C. Correspondingly, vertical current shear associated with mixed layer currents, which is responsible for entrainment mixing of cooler water, was found to be up to 50% weaker, on average, than observed in previous studies within the directly forced region. The Loop Current, which separates the warmer, lighter Caribbean Subtropical Water from the cooler, heavier Gulf Common Water, was found to decrease in intensity by −0.18 ± 0.25 m s−1 over an approximately 10-day period within the mixed layer. Contrary to previous ocean response studies, which have assumed approximately horizontally homogeneous ocean structure prior to storm passage, a kinetic energy loss of 5.8 ± 6.4 kJ m−2, or approximately −1 wind stress-scaled energy unit, was observed. By examining near-surface currents derived from satellite altimetry data, the Loop Current is found to vary similarly in magnitude over such time scales, suggesting storm-generated energy is rapidly removed by the preexisting Loop Current. In a future study, the simulated mixed layer evolution to a Hurricane Lili–like storm within an idealized preexisting baroclinic current is analyzed to help understand the complex air–sea interaction and resulting energetic response.
Diabetes and Femoral Neck Strength: Findings from The Hip Strength Across the Menopausal Transition Study
Authors: Ishii Shinya , Cauley Jane A. , Crandall Carolyn J. , Srikanthan Preethi , Greendale Gail A. , Huang Mei-Hua , Danielson Michelle E. , Karlamangla Arun S. 
Published: November 2011

Context:
Diabetes mellitus is associated with increased hip fracture risk, despite being associated with higher bone mineral density in the femoral neck.

Objective:
The objective of the study was to test the hypothesis that composite indices of femoral neck strength, which integrate dual-energy x-ray absorptiometry derived femoral neck size, femoral neck areal bone mineral density, and body size and are inversely associated with hip fracture risk, would be lower in diabetics than in nondiabetics and be inversely related to insulin resistance, the primary pathology in type 2 diabetes.

Design:
This was a cross-sectional analysis.

Setting and Participants:
The study consisted of a multisite, multiethnic, community-dwelling sample of 1887 women in pre- or early perimenopause.

Outcome Measurements:
Composite indices for femoral neck strength in different failure modes (axial compression, bending, and impact) were measured.

Results:
Adjusted for age, race/ethnicity, menopausal stage, body mass index, smoking, physical activity, calcium and vitamin D supplementation, and study site, diabetic women had higher femoral neck areal bone mineral density [+0.25 sd, 95% confidence interval (CI) (+0.06, +0.44) sd] but lower composite strength indices [−0.20 sd, 95% CI (−0.38, −0.03) sd for compression, −0.19 sd, 95% CI (−0.38, −0.003) sd for bending, −0.19 sd, 95% CI (−0.37, −0.02) sd for impact] than nondiabetic women. There were graded inverse relationships between homeostasis model-assessed insulin resistance and all three strength indices, adjusted for the same covariates.

Conclusions:
Despite having higher bone density, diabetic women have lower indices of femoral neck strength relative to load, consistent with their documented higher fracture risk. Insulin resistance appears to play an important role in bone strength reduction in diabetes.
“Et le moyen plain de paine et tristesse”: Solution, Symbology, and Context in Ockeghem's “Prenez sur moi”
Authors: Lee-De Amici Beth Anne 
Published: November 2011

For five hundred years, scholars, theorists, and performers have searched for solutions to the puzzles encoded in Ockeghem's “Prenez sur moi.” Most of the literature to date has concentrated on the opening pitches and matters of mode. Much less attention has been paid either to the text or to the illumination found in the sole surviving contemporary source, the Copenhagen Chansonnier.
This article explores connections among text, music, and illumination in an attempt to go beyond prescriptions for performance and instead to explain what the canon might have meant to Ockeghem and his contemporaries. In particular, Ockeghem seems to have drawn on the line “et le moyen plain de paine et tristesse” (and the middle full of pain and sorrow) as inspiration for a series of complex references to center, symmetry, and mirror image in the canon’s musical structure and solmization. The illumination in the Copenhagen Chansonnier also appears to participate in these references, as well as to demonstrate connections to other aspects of medieval French court culture, in particular the Roman de la rose and astrology/astronomy. Further, Ockeghem's explorations of center, symmetry, and mirror image allow us to posit that “Prenez sur moi” may be construed as a musical labyrinth.
On the Scenic Route to Irving Berlin's Holiday Inn (1942)
Authors: Decker Todd 
Published: November 2011

This study of Irving Berlin's Holiday Inn (Paramount, 1942) considers the collaboration of the film's four primary creative figures: Irving Berlin, Mark Sandrich, Bing Crosby, and Fred Astaire. Extracted from a wide array of production materials, the story of the making of Holiday Inn demonstrates how archival research can address questions of broad scholarly interest, such as large-scale form, star personas, musical style, musical-dramatic integration, the representation of blackness and African American characters, and political meaning in popular-culture products.
Examining details of the film's production history sheds particular light upon the function of songs and musical routines as quasi-autonomous parts of the whole.
Piloting a Novel Algorithm for Glucose Control in the Coronary Care Unit
Authors: Nerenberg Kara A. , Goyal Abhinav , Xavier Denis , Sigamani Alben , Ng Jennifer , Mehta Shamir R. , Díaz Rafael , Kosiborod Mikhail , Yusuf Salim , Gerstein Hertzel C. ,   for the RECREATE Investigators
Published: November 2011

OBJECTIVE
Elevated glucose levels are common after an acute myocardial infarction (AMI) and increase the risk of death. Prior trials of glucose control after AMI have been inconsistent in their ability to lower glucose levels and have reported mixed effects on mortality. We developed a paper-based glucose-lowering algorithm and assessed its feasibility and safety in the setting of AMI.

RESEARCH DESIGN AND METHODS
A total of 287 participants with an acute ST segment elevation myocardial infarction (STEMI) and a capillary glucose level ≥8.0 mmol/L were randomly allocated to glucose management with intravenous glulisine insulin using this algorithm in the coronary care unit (CCU), followed by once-daily subcutaneous insulin glargine for 30 days versus standard glycemic approaches. The primary outcome was a difference in mean glucose levels at 24 h. Participants were followed for clinical outcomes through 90 days.

RESULTS
At 24 h, the mean glucose level was 1.41 mmol/L (95% CI 0.69–2.13) lower in the insulin (6.53 vs. 7.94 mmol/L). Differences in glucose levels were maintained at 72 h and 30 days. A total of 22.7% of the insulin group versus 4.4% of the standard group had biochemical hypoglycemia (with neither signs nor symptoms) in the CCU because of lower glycemic goals. However, there were no differences in symptomatic hypoglycemia or clinical outcomes between the groups.

CONCLUSIONS
A paper-based insulin algorithm targeting glucose levels of 5.0–6.5 mmol/L (90–117 mg/dL) can be feasibly implemented in the CCU. A cardiovascular outcomes trial using this approach can determine whether targeted glucose lowering improves patient outcomes.
Decentralized H
∞ control for damping power system oscillations
Authors: Li Guo-Jie , Lie Tek 
Published: November 2011

Abstract
Inter-area oscillations are serious problems to large-scale power systems. A decentralized H
∞ generator excitation controller of a power system is proposed to damp the inter-area oscillations and to enhance power system stability. The design procedure for a linear composite system is presented in terms of positive semi-definite solutions to modified algebraic inequalities. The resulting controller guarantees closed-loop stability, robustness and an H
∞-norm bound on disturbance attenuation even under uncertainties such as high frequency noise. The control is decentralized in the sense that the control of each generator depends on local information only. The effectiveness of the H
∞ controller is demonstrated through digital simulation studies on a two-machine power system.