bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual Programmed Cell Death Pathways Induced by p53 Transactivation Overcome Resistance to Oncolytic Adenovirus in Human Osteosarcoma Cells
Authors: Hasei Joe , Sasaki Tsuyoshi , Tazawa Hiroshi , Osaki Shuhei , Yamakawa Yasuaki , Kunisada Toshiyuki , Yoshida Aki , Hashimoto Yuuri , Onishi Teppei , Uno Futoshi , Kagawa Shunsuke , Urata Yasuo , Ozaki Toshifumi , Fujiwara Toshiyoshi 
Published: January 2013

Abstract
Tumor suppressor p53 is a multifunctional transcription factor that regulates diverse cell fates, including apoptosis and autophagy in tumor biology. p53 overexpression enhances the antitumor activity of oncolytic adenoviruses; however, the molecular mechanism of this occurrence remains unclear. We previously developed a tumor-specific replication-competent oncolytic adenovirus, OBP-301, that kills human osteosarcoma cells, but some human osteosarcoma cells were OBP-301–resistant. In this study, we investigated the antitumor activity of a p53-expressing oncolytic adenovirus, OBP-702, and the molecular mechanism of the p53-mediated cell death pathway in OBP-301–resistant human osteosarcoma cells. The cytopathic activity of OBP-702 was examined in OBP-301–sensitive (U2OS and HOS) and OBP-301–resistant (SaOS-2 and MNNG/HOS) human osteosarcoma cells. The molecular mechanism in the OBP-702–mediated induction of two cell death pathways, apoptosis and autophagy, was investigated in OBP-301–resistant osteosarcoma cells. The antitumor effect of OBP-702 was further assessed using an orthotopic OBP-301–resistant MNNG/HOS osteosarcoma xenograft tumor model. OBP-702 suppressed the viability of OBP-301–sensitive and -resistant osteosarcoma cells more efficiently than OBP-301 or a replication-deficient p53-expressing adenovirus (Ad-p53). OBP-702 induced more profound apoptosis and autophagy when compared with OBP-301 or Ad-p53. E1A-mediated miR-93/106b upregulation induced p21 suppression, leading to p53-mediated apoptosis and autophagy in OBP-702–infected cells. p53 overexpression enhanced adenovirus-mediated autophagy through activation of damage-regulated autophagy modulator (DRAM). Moreover, OBP-702 suppressed tumor growth in an orthotopic OBP-301–resistant MNNG/HOS xenograft tumor model. These results suggest that OBP-702–mediated p53 transactivation is a promising antitumor strategy to induce dual apoptotic and autophagic cell death pathways via regulation of miRNA and DRAM in human osteosarcoma cells. Mol Cancer Ther; 12(3); 314–25. ©2012 AACR.
Insulin-Like Growth Factors and Insulin-Like Growth Factor–Binding Proteins and Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial
Authors: Neuhouser Marian L. , Platz Elizabeth A. , Till Cathee , Tangen Catherine M. , Goodman Phyllis J. , Kristal Alan , Parnes Howard L. , Tao Yuzhen , Figg William D. , Lucia M. Scott , Hoque Ashraful , Hsing Ann W. , Thompson Ian M. , Pollak Michael 
Published: January 2013

Abstract
The role of the insulin-like growth factor (IGF) axis and whether IGFs interact with androgen-suppressing agents in relation to prostate carcinogenesis is unclear. This nested case–control study (n = 1,652 cases/1,543 controls) examined whether serum IGF1, IGF2, IGFBP2, IGFBP3, and the IGF1:IGFBP3 ratio were associated with prostate cancer in the Prostate Cancer Prevention Trial (PCPT), a randomized, placebo-controlled trial of finasteride for prostate cancer prevention. Presence or absence of cancer was determined by prostate biopsy. Baseline serum was assayed for IGF-axis analytes using ELISA. Logistic regression estimated ORs and 95% confidence intervals for risk of total, low-grade (Gleason 2–6) and high-grade (Gleason 7–10) cancers. Results were stratified by intervention assignment. In both the placebo and finasteride arms, serum IGF1, IGF2, IGFBP3, and the IGF1:IGFBP3 ratio were not associated with prostate cancer. However, men in the highest versus lowest quartile of serum IGFBP2 had a 48% (Ptrend = 0.02) and 55% (Ptrend = 0.01) increased risk for total and low-grade cancers, respectively. These IGFBP2 associations were attenuated and no longer statistically significant in the finasteride arm. Our results suggest that in general, serum IGF-axis analytes were not associated with prostate cancer risk in the PCPT in which presence or absence of all cancers was biopsy-determined. The exception was the finding that high serum IGFBP2 is a risk factor for low-grade disease, which was attenuated for men on finasteride. Further research is needed to understand better the risk incurred by high IGFBP2 and whether androgen-suppressing agents such as finasteride influence aspects of IGFBP2 physiology relevant to prostate carcinogenesis. Cancer Prev Res; 6(2); 91–9. ©2013 AACR.
Resequencing and Clinical Associations of the 9p21.3 Region
Authors: Johnson Andrew D. , Hwang Shih-Jen , Voorman Arend , Morrison Alanna , Peloso Gina M. , Hsu Yi-Hsiang , Thanassoulis George , Newton-Cheh Christopher , Rogers Ian S. , Hoffmann Udo , Freedman Jane E. , Fox Caroline S. , Psaty Bruce M. , Boerwinkle Eric , Cupples L. Adrienne , O’Donnell Christopher J. 
Published: January 2013

Background—
9p21.3 is among the most strongly replicated regions for cardiovascular disease. There are few reports of sequencing the associated 9p21.3 interval. We set out to sequence the 9p21.3 region followed by a comprehensive study of genetic associations with clinical and subclinical cardiovascular disease and its risk factors, as well as with copy number variation and gene expression, in the Framingham Heart Study (FHS).

Methods and Results—

We sequenced 281 individuals (94 with myocardial infarction, 94 with high coronary artery calcium levels, and 93 control subjects free of elevated coronary artery calcium or myocardial infarction), followed by genotyping and association in >7000 additional FHS individuals. We assessed genetic associations with clinical and subclinical cardiovascular disease, risk factor phenotypes, and gene expression levels of the protein-coding genes
CDKN2A
and
CDKN2B
and the noncoding gene
ANRIL
in freshly harvested leukocytes and platelets. Within this large sample, we found strong associations of 9p21.3 variants with increased risk for myocardial infarction, higher coronary artery calcium levels, and larger abdominal aorta diameters and no evidence for association with traditional cardiovascular disease risk factors. No common protein-coding variation, variants in splice donor or acceptor sites, or copy number variation events were observed. By contrast, strong associations were observed between genetic variants and gene expression, particularly for a short isoform of
ANRIL
and for
CDKN2B
.

Conclusions—

Our thorough genomic characterization of 9p21.3 suggests common variants likely account for observed disease associations and provides further support for the hypothesis that complex regulatory variation affecting
ANRIL
and
CDKN2B
gene expression may contribute to increased risk for clinically apparent and subclinical coronary artery disease and aortic disease.
Prospective, Multicenter Study of Ventricular Assist Device Infections
Authors: Gordon Rachel J. , Weinberg Alan D. , Pagani Francis D. , Slaughter Mark S. , Pappas Pat S. , Naka Yoshifumi , Goldstein Daniel J. , Dembitsky Walter P. , Giacalone Julie C. , Ferrante Jennifer , Ascheim Deborah D. , Moskowitz Alan J. , Rose Eric A. , Gelijns Annetine C. , Lowy Franklin D. ,   Authors in the VAD Infection Study Group include:, Fox Sarah , Leventhal Christina L. , Gallagher Colleen , Idrissi Katharine , Flannery Margaret , Te-Frey Rosie , Swayze Roger , Adamson Robert M. , Jaski Brian E. , Gravitt Gina , Kohlmyer Chris , Chillcott Suzanne , Stahovich Marcia , Icenogle Timothy B. , Puhlman Mark , Tector Alfred , Miller Maggie , Edwards Niloo M. , Yakey Jan , Long Jim , Acker Michael , Donnelly Joseph P. , Dougherty Deb , Dowling Robert , Adkisson Pam 
Published: January 2013

Background—
Ventricular assist devices (VADs) improve survival and quality of life in patients with advanced heart failure, but their use is frequently complicated by infection. There are limited data on the microbiology and epidemiology of these infections.

Methods and Results—

One hundred fifty patients scheduled for VAD implantation were enrolled (2006–2008) at 11 US cardiac centers and followed prospectively until transplantation, explantation for recovery, death, or for 1 year. Eighty-six patients (57%) received HeartMate II devices. Data were collected on potential preoperative, intraoperative, and postoperative risk factors for infection. Clinical, laboratory, and microbiological data were collected for suspected infections and evaluated by an infectious diseases specialist. Thirty-three patients (22%) developed 34 VAD-related infections with an incidence rate of 0.10 per 100 person-days (95% confidence interval, 0.073–0.142). The median time to infection was 68 days. The driveline was the most commonly infected site (n=28); 18 (64%) were associated with invasive disease. Staphylococci were the most common pathogen (47%), but pseudomonas or other Gram-negative bacteria caused 32% of infections. A history of depression and elevated baseline serum creatinine were independent predictors of VAD infection (adjusted hazard ratio=2.8 [
P
=0.007] and 1.7 [
P
=0.023], respectively). The HeartMate II was not associated with a decreased risk of infection. VAD infection increased 1-year mortality (adjusted hazard ratio=5.6;
P
<0.0001).

Conclusions—
This prospective, multicenter study demonstrates that infection frequently complicates VAD placement and is a continuing problem despite the use of newer, smaller devices. Depression and renal dysfunction may increase the risk of VAD infection. VAD infection is a serious consequence because it adversely affects patient survival.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01471795.
Small Cloud Particle Shapes in Mixed-Phase Clouds
Authors: McFarquhar Greg M. , Um Junshik , Jackson Robert 
Published: January 2013

AbstractThe shapes of cloud particles with maximum dimensions Dmax between 35 and 60 μm in mixed-phase clouds were studied using high-resolution particle images collected by a cloud particle imager (CPI) during the Mixed-Phase Arctic Cloud Experiment (M-PACE) and the Indirect and Semi-Direct Aerosol Campaign (ISDAC). The area ratio α, the projected area of a particle divided by the area of a circle with diameter Dmax, quantified particle shape. The differing optical characteristics of CPIs used in M-PACE and ISDAC had no effect on derived α provided that Dmax > 35 μm and CPI focus > 45. The fraction of particles with 35 < Dmax < 60 μm with α > 0.8 increased with the ratio of liquid water content (LWC) to total water content (TWC). The average αmean of small particles in each 10-s interval in mixed-phase clouds was correlated with LWC/TWC with a correlation coefficient of 0.60 for M-PACE and 0.43 for ISDAC. The stronger correlation seen during M-PACE was most likely associated with the presence of more liquid droplets that were larger than the CPI detection threshold contributing to αmean; the modal effective radius was larger (11 vs 6 μm), and drops with D > 35 μm had concentrations during M-PACE that were 6 times as large as those of ISDAC. This study hence suggests that area ratio can be used to identify the phase of particles with 35 < Dmax < 60 μm and questions the assumption used in previous studies that all particles in this size range are supercooled droplets.
A Nonparametric Approach to the Removal of Documented Inhomogeneities in Climate Time Series
Authors: Ambrosino Chiara , Chandler Richard E. 
Published: January 2013

AbstractClimate data often suffer from artificial inhomogeneities, resulting from documented or undocumented events. For a time series to be used with confidence in climate analysis, it should only be characterized by variations intrinsic to the climate system. Many methods (e.g., direct or indirect) have been proposed according to the data characteristics (e.g., location, variable, or data completeness). This paper is focused on the abrupt-changes problem (when the properties of a time series change abruptly), when their timing is known, and suggests that a nonparametric regression framework provides an appealing way to correct for discontinuities in such a way as to recognize and allow for the existence of other structures such as seasonality and long-term smooth trends. The approach is illustrated by using reanalysis data for southern Africa, for which discontinuities are present because of the introduction of satellite technology in 1979.
Analysis of Tornado-Induced Tree Fall Using Aerial Photography from the Joplin, Missouri, and Tuscaloosa–Birmingham, Alabama, Tornadoes of 2011
Authors: Karstens Christopher D. , Gallus William A. , Lee Bruce D. , Finley Catherine A. 
Published: January 2013

AbstractIn this study, aerial imagery of tornado damage is used to digitize the falling direction of trees (i.e., tree fall) along the 22 May 2011 Joplin, Missouri, and 27 April 2011 Tuscaloosa–Birmingham, Alabama, tornado tracks. Normalized mean patterns of observed tree fall from each tornado’s peak-intensity period are subjectively compared with results from analytical vortex simulations of idealized tornado-induced tree fall to characterize mean properties of the near-surface flow as depicted by the model. A computationally efficient method of simulating tree fall is applied that uses a Gumbel distribution of critical tree-falling wind speeds on the basis of the enhanced Fujita scale. Results from these simulations suggest that both tornadoes had strong radial near-surface winds. A few distinct tree-fall patterns are identified at various locations along the Tuscaloosa–Birmingham tornado track. Concentrated bands of intense tree fall, collocated with and aligned parallel to the axis of underlying valley channels, extend well beyond the primary damage path. These damage patterns are hypothesized to be the result of flow acceleration caused by channeling within valleys. Another distinct pattern of tree fall, likely not linked to the underlying topography, may have been associated with a rear-flank downdraft (RFD) internal surge during the tornado’s intensification stage. Here, the wind field was strong enough to produce tornado-strength damage well beyond the visible funnel cloud. This made it difficult to distinguish between tornado- and RFD-related damage and thus illustrates an ambiguity in ascertaining tornado-damage-path width in some locations.
A Formulation of Unified Three-Dimensional Wave Activity Flux of Inertia–Gravity Waves and Rossby Waves
Authors: Kinoshita Takenari , Sato Kaoru 
Published: January 2013

Abstract
A companion paper formulates the three-dimensional wave activity flux (3D-flux-M) whose divergence corresponds to the wave forcing on the primitive equations. However, unlike the two-dimensional wave activity flux, 3D-flux-M does not accurately describe the magnitude and direction of wave propagation. In this study, the authors formulate a modification of 3D-flux-M (3D-flux-W) to describe this propagation using small-amplitude theory for a slowly varying time-mean flow. A unified dispersion relation for inertia–gravity waves and Rossby waves is also derived and used to relate 3D-flux-W to the group velocity. It is shown that 3D-flux-W and the modified wave activity density agree with those for inertia–gravity waves under the constant Coriolis parameter assumption and those for Rossby waves under the small Rossby number assumption.
To compare 3D-flux-M with 3D-flux-W, an analysis of the European Centre for Medium-Range Weather Forecasts (ECMWF) Interim Re-Analysis (ERA-Interim) data is performed focusing on wave disturbances in the storm tracks during April. While the divergence of 3D-flux-M is in good agreement with the meridional component of the 3D residual mean flow associated with disturbances, the 3D-flux-W divergence shows slight differences in the upstream and downstream regions of the storm tracks. Further, the 3D-flux-W magnitude and direction are in good agreement with those derived by R. A. Plumb, who describes Rossby wave propagation. However, 3D-flux-M is different from Plumb’s flux in the vicinity of the storm tracks. These results suggest that different fluxes (both 3D-flux-W and 3D-flux-M) are needed to describe wave propagation and wave–mean flow interaction in the 3D formulation.
How Does the Eye Warm? Part II: Sensitivity to Vertical Wind Shear and a Trajectory Analysis
Authors: Stern Daniel P. , Zhang Fuqing 
Published: January 2013

Abstract
In Part II of this study, idealized simulations of tropical cyclones are used to investigate the influence of vertical wind shear on the structure of warming and descent in the eye; results are compared with the no-shear simulation that was analyzed in Part I. During intensification of a tropical cyclone in a quiescent environment, time-averaged eye descent is maximized at 12–13-km height. Warming is not generally maximized at these levels, however, because the static stability is at a minimum. Consequently, the perturbation temperature is maximized at midlevels. Each of the above results remains valid for sheared tropical cyclones, and therefore shear does not systematically alter the height of the warm core.
An analysis of over 90 000 parcel trajectories yields further insight into the mechanisms of eye warming and addresses several outstanding questions regarding the character of eye descent. The rate at which parcels are stirred from the eye into the eyewall is a strong function of intensity. While stirring is large at the beginning of rapid intensification (RI), once a sufficient intensity is achieved, most parcels originating near the storm center can remain inside the eye for at least several days. Many parcels in the upper troposphere are able to descend within the eye by 5–10 km. The above results are relatively insensitive to the presence of up to 10 m s−1 of shear. In contrast, stirring in the eye–eyewall interface region is substantially enhanced by shear.
The Major Floods in the Amazonas River and Tributaries (Western Amazon Basin) during the 1970–2012 Period: A Focus on the 2012 Flood*
Authors: Espinoza Jhan Carlo , Ronchail Josyane , Frappart Frédéric , Lavado Waldo , Santini William , Guyot Jean Loup 
Published: January 2013

AbstractIn this work, the authors analyze the origin of the extreme floods in the Peruvian Amazonas River during the 1970–2012 period, focusing on the recent April 2012 flooding (55 400 m3 s−1). Several hydrological variables, such as rainfall, terrestrial water storage, and discharge, point out that the unprecedented 2012 flood is mainly related to an early and abundant wet season over the north of the basin. Thus, the peak of the Marañón River, the northern contributor of the Amazonas, occurred sooner than usual (in April instead of May), coinciding with the peak of the Ucayali River, the southern contributor. This concomitance caused a dramatic flood downstream in the Peruvian Amazonas. These results are compared to the amplitude and timing of the three most severe extreme floods (1970–2011). The analysis of the climatic features related to the most important floods (1986, 1993, 1999, and 2012) suggests that they are characterized by a La Niña event, which originates a geopotential height wave train near the ground, with positive anomalies over the subtropical South and North Pacific and Atlantic and over southeastern South America. These patterns contribute to 1) the origin of an abundant humidity transport flux from the tropical North Atlantic and the Caribbean Sea toward the northwestern Amazon and 2) the maintenance of the monsoon flux over this region. They both favor a strong convergence of humidity in the northern Amazonas basin. Finally, the authors suggest that the intensity of floods is more likely related to an early La Niña event (as observed during the 2011/12 season), early rainfall, and simultaneous peaks of both tributaries of the Amazonas River.
Correction of Reflectivity in the Presence of Partial Beam Blockage over a Mountainous Region Using X-Band Dual Polarization Radar
Authors: P. C., Shakti , Maki M. , Shimizu S. , Maesaka T. , Kim D.-S. , Lee D.-I. , Iida H. 
Published: January 2013

AbstractTwo approaches to correcting the partial beam blockage of radar reflectivity in mountainous areas were evaluated using X-band dual polarization radar data from the Hakone mountain region, Kanto, Japan. The comparatively simple digital elevation model (DEM) method calculates the power loss in the received signal based on the geometrical relationship between radar beams and a DEM. The second approach, the modified DEM method, attempts to account for unknown power losses related to ground clutter, hardware calibration errors, etc. Comparison between ground data and reflectivity data corrected by both methods suggests that the DEM method alone was insufficient to correct beam blockage problems but that the modified DEM data were in generally good agreement with the ground data. The authors also estimated 10-min rainfall amounts using reflectivity corrected by the modified DEM method and compared these with data from a network of rain gauges in the mountainous region. In general, the results show good agreement between radar estimates and rain gauge measurements. On the basis of their results, the authors conclude that the modified DEM method offers a suitable solution to the problem of beam blockage in mountainous regions, provided that the beam blockage rate is less than 80%.
Effect of Sitting or Standing on Touch Screen Performance and Touch Characteristics
Authors: Chourasia Amrish O. , Wiegmann Douglas A. , Chen Karen B. , Irwin Curtis B. , Sesto Mary E. 
Published: January 2013

Objective: The aim of this study was to evaluate the effect of sitting and standing on performance and touch characteristics during a digit entry touch screen task in individuals with and without motor-control disabilities. Background: Previously, researchers of touch screen design have not considered the effect of posture (sitting vs. standing) on touch screen performance (accuracy and timing) and touch characteristics (force and impulse). Method: Participants with motor-control disabilities ( n = 15) and without ( n = 15) completed a four-digit touch screen number entry task in both sitting and standing postures. Button sizes varied from 10 mm to 30 mm (5-mm increments), and button gap was 3 mm or 5 mm. Results: Participants had more misses and took longer to complete the task during standing for smaller button sizes (<20 mm). At larger button sizes, performance was similar for both sitting and standing. In general, misses, time to complete task, and touch characteristics were increased for standing. Although disability affected performance (misses and timing), similar trends were observed for both groups across posture and button size. Conclusion: Standing affects performance at smaller button sizes (<20 mm). For participants with and without motor-control disabilities, standing led to greater exerted force and impulse. Application: Along with interface design considerations, environmental conditions should also be considered to improve touch screen accessibility and usability.