bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct Renin Inhibition With Aliskiren Protects Against Myocardial Ischemia/Reperfusion Injury by Activating Nitric Oxide Synthase Signaling in Spontaneously Hypertensive Rats
Authors: Zhang Wen , Han Yi , Meng Guoliang , Bai Wenli , Xie Liping , Lu Hui , Shao Yongfeng , Wei Lei , Pan Shiyang , Zhou Suming , Chen Qi , Ferro Albert , Ji Yong 
Published: January 2014

Background

We tested the hypothesis that direct renin inhibition with aliskiren protects against myocardial ischemia/reperfusion (I/R) injury in spontaneously hypertensive rats (
SHR
), and examined the mechanism by which this occurs.

Methods and Results

Male
SHR
were treated (orally, 4 weeks) with saline or aliskiren (30 or 60 mg kg
−1
day
−1
) and subjected to 30 minutes of left anterior descending coronary artery occlusion followed by 6 or 24 hours of reperfusion. Only the higher dose significantly lowered systolic blood pressure, the lower dose causing a smaller apparent lowering that was nonsignificant. Despite this difference in blood pressure‐lowering effect, both doses increased the ejection fraction and fractional shortening and reduced myocardial infarct size equally. I/R decreased cardiac expression of phosphatidylinositol 3‐kinase (PI3K), phospho‐Akt and phospho‐endothelial nitric oxide synthase (phospho‐
eNOS
), but increased expression of inducible nitric oxide synthase (
iNOS
); these changes were all abrogated by aliskiren. Moreover, aliskiren decreased superoxide anion generation and increased cyclic guanosine‐3′,5′‐monophosphate, an index of bioactive nitric oxide, in myocardium. It also decreased the expression of myocardial matrix metalloproteinase‐2, matrix metalloproteinase‐9, and tissue inhibitor of metalloproteinases‐1 (
TIMP
‐1) following I/R. In a
L
angendorff heart preparation, the detrimental cardiac effects of I/R were abrogated by aliskiren, and these protective effects were abolished by
NOS
or PI3K inhibition. In a parallel study, although specific
iNOS
inhibition reduced plasma malondialdehyde and myocardial superoxide anion generation, it did not affect the deleterious effects of I/R on myocardial structure and function.

Conclusions

Direct renin inhibition protects against myocardial I/R injury through activation of the PI3K‐Akt‐
eNOS
pathway.
Sildenafil Mediates Blood-Flow Redistribution and Neuroprotection After Neonatal Hypoxia-Ischemia
Authors: Charriaut-Marlangue Christiane , Nguyen Thao , Bonnin Philippe , Duy An Phan , Leger Pierre-Louis , Csaba Zsolt , Pansiot Julien , Bourgeois Thomas , Renolleau Sylvain , Baud Olivier 
Published: January 2014

Background and Purpose—
The best conceivable treatment for hypoxia-ischemia (HI) is the restoration of blood flow to the hypoxic-ischemic region(s). Our objective was to examine whether boosting NO-cGMP signaling using sildenafil citrate, a phosphodiesterase-type 5 inhibitor, could modify cerebral blood flow and reduce lesions in the developing brain.

Methods—
HI was induced in P7 Sprague–Dawley rats by unilateral carotid artery occlusion and hypoxia, and followed by either PBS or sildenafil. Blood-flow velocities were measured by ultrasound imaging with sequential Doppler recordings to evaluate collateral recruitment. Cell death, blood–brain barrier integrity, and glial activation were analyzed by immunohistochemistry. Motor behavior was evaluated using an open-field device adapted to neonatal animals.

Results—
Sildenafil citrate (10 mg/kg) induced collateral patency, reduced terminal dUTP nick-end labeling–positive cells, reactive astrogliosis, and macrophage/microglial activation at 72 hours and 7 days post-HI. Sildenafil also reduced the number of terminal dUTP nick-end labeling–positive endothelial cells within lesion site. Seven days after HI and sildenafil treatment, tissue loss was significantly reduced, and animals recovered motor coordination.

Conclusions—
Our findings strongly indicate that sildenafil citrate treatment, associated with a significant increase in cerebral blood flow, reduces HI damage and improves motor locomotion in neonatal rats. Sildenafil may represent an interesting therapeutic strategy for neonatal neuroprotection.
Collaterals at Angiography and Outcomes in the Interventional Management of Stroke (IMS) III Trial
Authors: Liebeskind David S. , Tomsick Thomas A. , Foster Lydia D. , Yeatts Sharon D. , Carrozzella Janice , Demchuk Andrew M. , Jovin Tudor G. , Khatri Pooja , von Kummer Ruediger , Sugg Rebecca M. , Zaidat Osama O. , Hussain Syed I. , Goyal Mayank , Menon Bijoy K. , Al Ali Firas , Yan Bernard , Palesch Yuko Y. , Broderick Joseph P. 
Published: January 2014

Background and Purpose—
Endovascular strategies provide unique opportunity to correlate angiographic measures of collateral circulation at the time of endovascular therapy. We conducted systematic analyses of collaterals at conventional angiography on recanalization, reperfusion, and clinical outcomes in the endovascular treatment arm of the Interventional Management of Stroke (IMS) III trial.

Methods—
Prospective evaluation of angiographic collaterals was conducted via central review of subjects treated with endovascular therapy in IMS III (n=331). Collateral grade before endovascular therapy was assessed with the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology scale, blinded to all other data. Statistical analyses investigated the association between collaterals with baseline clinical variables, angiographic measures of recanalization, reperfusion and clinical outcomes.

Results—

Adequate views of collateral circulation to the ischemic territory were available in 276 of 331 (83%) subjects. Collateral grade was strongly related to both recanalization of the occluded arterial segment (
P
=0.0016) and downstream reperfusion (
P
<0.0001). Multivariable analyses confirmed that robust angiographic collateral grade was a significant predictor of good clinical outcome (modified Rankin Scale score ≤2) at 90 days (
P
=0.0353), adjusted for age, history of diabetes mellitus, National Institutes of Health Stroke Scale strata, and Alberta Stroke Program Early CT Score. The relationship between collateral flow and clinical outcome may depend on the degree of reperfusion.

Conclusions—
More robust collateral grade was associated with better recanalization, reperfusion, and subsequent better clinical outcomes. These data, from the largest endovascular trial to date, suggest that collaterals are an important consideration in future trial design.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00359424.
Direct Thrombin Inhibitor Argatroban Reduces Stroke Damage in 2 Different Models
Authors: Lyden Patrick , Pereira Benedict , Chen Bo , Zhao Lifu , Lamb Jessica , Lei I-farn , Rajput Padmesh 
Published: January 2014

Background and Purpose—
We showed previously robust neuroprotection with the thrombin inhibitor argatroban and now sought additional support for its neuroprotective potential.

Methods—
We used behavioral and histological end points; rigorously blinded the study groups; extended the treatment window to 3 hours after ischemia onset; and used 2 separate models. First, 2-hour filament middle cerebral artery occlusion in 64 male Sprague-Dawley rats was followed by learning and memory testing and quantitative histomorphometry. Randomly assigned treatment was 0.45 mg argatroban, saline, or 0.4 U thrombin. Second, we used the quantal bioassay (n=272) after 2-hour middle cerebral artery occlusion to detect the longest time delay after which therapy failed.

Results—

Argatroban powerfully and significantly reversed learning and memory deficits because of focal ischemia compared with saline or thrombin (
P
<0.03; ANOVA). Argatroban was significantly (
P
<0.05;
t
test with Bonferroni) protective when given immediately or after 1, 2, 3, but not 4 hours delay.

Conclusions—
We obtained supportive evidence for argatroban protection of the neurovascular unit using behavioral and histological measurements at realistic therapeutic time windows.
CMIP5 Model Intercomparison of Freshwater Budget and Circulation in the North Atlantic
Authors: Deshayes Julie , Curry Ruth , Msadek Rym 
Published: January 2014

Abstract
The subpolar North Atlantic is a center of variability of ocean properties, wind stress curl, and air–sea exchanges. Observations and hindcast simulations suggest that from the early 1970s to the mid-1990s the subpolar gyre became fresher while the gyre and meridional circulations intensified. This is opposite to the relationship of freshening causing a weakened circulation, most often reproduced by climate models. The authors hypothesize that both these configurations exist but dominate on different time scales: a fresher subpolar gyre when the circulation is more intense, at interannual frequencies (configuration A), and a saltier subpolar gyre when the circulation is more intense, at longer periods (configuration B). Rather than going into the detail of the mechanisms sustaining each configuration, the authors’ objective is to identify which configuration dominates and to test whether this depends on frequency, in preindustrial control runs of five climate models from phase 5 of the Coupled Model Intercomparison Project (CMIP5). To this end, the authors have developed a novel intercomparison method that enables analysis of freshwater budget and circulation changes in a physical perspective that overcomes model specificities. Lag correlations and a cross-spectral analysis between freshwater content changes and circulation indices validate the authors’ hypothesis, as configuration A is only visible at interannual frequencies while configuration B is mostly visible at decadal and longer periods, suggesting that the driving role of salinity on the circulation depends on frequency. Overall, this analysis underscores the large differences among state-of-the-art climate models in their representations of the North Atlantic freshwater budget.
Northern Eurasian Heat Waves and Droughts
Authors: Schubert Siegfried D. , Wang Hailan , Koster Randal D. , Suarez Max J. , Groisman Pavel Ya. 
Published: January 2014

Abstract
This article reviews the understanding of the characteristics and causes of northern Eurasian summertime heat waves and droughts. Additional insights into the nature of temperature and precipitation variability in Eurasia on monthly to decadal time scales and into the causes and predictability of the most extreme events are gained from the latest generation of reanalyses and from supplemental simulations with the NASA Goddard Earth Observing System model, version 5 (GEOS-5). Key new results are 1) the identification of the important role of summertime stationary Rossby waves in the development of the leading patterns of monthly Eurasian surface temperature and precipitation variability (including the development of extreme events such as the 2010 Russian heat wave); 2) an assessment of the mean temperature and precipitation changes that have occurred over northern Eurasia in the last three decades and their connections to decadal variability and global trends in SST; and 3) the quantification (via a case study) of the predictability of the most extreme simulated heat wave/drought events, with some focus on the role of soil moisture in the development and maintenance of such events. A literature survey indicates a general consensus that the future holds an enhanced probability of heat waves across northern Eurasia, while there is less agreement regarding future drought, reflecting a greater uncertainty in soil moisture and precipitation projections. Substantial uncertainties remain in the understanding of heat waves and drought, including the nature of the interactions between the short-term atmospheric variability associated with such extremes and the longer-term variability and trends associated with soil moisture feedbacks, SST anomalies, and an overall warming world.
Improving WSR-88D Radar QPE for Orographic Precipitation Using Profiler Observations
Authors: Qi Youcun , Zhang Jian , Kaney Brian , Langston Carrie , Howard Kenneth 
Published: January 2014

Abstract
Quantitative precipitation estimation (QPE) in the West Coast region of the United States has been a big challenge for Weather Surveillance Radar-1988 Doppler (WSR-88D) because of severe blockages caused by the complex terrain. The majority of the heavy precipitation in the West Coast region is associated with strong moisture flux from the Pacific that interacts with the coastal mountains. Such orographic enhancement of precipitation occurs at low levels and cannot be observed well by WSR-88D because of severe blockages. Specifically, the radar beam either samples too high above the ground or misses the orographic enhancement at lower levels, or the beam broadens with range and cannot adequately resolve vertical variations of the reflectivity structure. The current study developed an algorithm that uses S-band Precipitation Profiler (S-PROF) radar observations in northern California to improve WSR-88D QPEs in the area. The profiler data are used to calculate two sets of reference vertical profiles of reflectivity (RVPRs), one for the coastal mountains and another for the Sierra Nevada. The RVPRs are then used to correct the WSR-88D QPEs in the corresponding areas. The S-PROF–based VPR correction methodology (S-PROF-VPR) has taken into account orographic processes and radar beam broadenings with range. It is tested using three heavy rain events and is found to provide significant improvements over the operational radar QPE.
Unfiltering Earth Radiation Budget Experiment (ERBE) Scanner Radiances Using the CERES Algorithm and Its Evaluation with Nonscanner Observations
Authors: Shrestha Alok K. , Kato Seiji , Wong Takmeng , Rutan David A. , Miller Walter F. , Rose Fred G. , Smith G. Louis , Bedka Kristopher M. , Minnis Patrick , Fernandez Jose R. 
Published: January 2014

Abstract
The NOAA-9 Earth Radiation Budget Experiment (ERBE) scanner measured broadband shortwave, longwave, and total radiances from February 1985 through January 1987. These scanner radiances are reprocessed using the more recent Clouds and the Earth’s Radiant Energy System (CERES) unfiltering algorithm. The scene information, including cloud properties, required for reprocessing is derived using Advanced Very High Resolution Radiometer (AVHRR) data on board NOAA-9, while no imager data were used in the original ERBE unfiltering. The reprocessing increases the NOAA-9 ERBE scanner unfiltered longwave radiances by 1.4%–2.0% during daytime and 0.2%–0.3% during nighttime relative to those derived from the ERBE unfiltering algorithm. Similarly, the scanner unfiltered shortwave radiances increase by ~1% for clear ocean and land and decrease for all-sky ocean, land, and snow/ice by ~1%. The resulting NOAA-9 ERBE scanner unfiltered radiances are then compared with NOAA-9 nonscanner irradiances by integrating the ERBE scanner radiance over the nonscanner field of view. The comparison indicates that the integrated scanner radiances are larger by 0.9% for shortwave and 0.7% smaller for longwave. A sensitivity study shows that the one-standard-deviation uncertainties in the agreement are ±2.5%, ±1.2%, and ±1.8% for the shortwave, nighttime longwave, and daytime longwave irradiances, respectively. The NOAA-9 and ERBS nonscanner irradiances are also compared using 2 years of data. The comparison indicates that the NOAA-9 nonscanner shortwave, nighttime longwave, and daytime longwave irradiances are 0.3% larger, 0.6% smaller, and 0.4% larger, respectively. The longer observational record provided by the ERBS nonscanner plays a critical role in tying the CERES-like NOAA-9 ERBE scanner dataset from the mid-1980s to the present-day CERES scanner data record.
Particle-based modeling of the compaction of fiber yarns and woven textiles
Authors: Samadi Reza , Robitaille François 
Published: January 2014

This paper proposes a particle-based modeling method for predicting the constitutive behavior of textiles when subjected to various compressive loading conditions. The method, which is demonstrated for stacked layers of plain woven textiles, utilizes discrete mechanics as an alternative to traditional continuum mechanics. Fibers are modeled as a series of conjoined points, and their configurations are determined mechanistically using a modified Metropolis algorithm and inter-particle strain energy terms. The implementation presented in this paper enables intricate geometric modeling of textiles at microscopic, mesoscopic and macroscopic scales. It also enables extensive mechanical modeling of the textiles, from first principles, as they are loaded upon manufacturing of typical technical textile structures. While this paper focuses on the compaction behavior of weaves, the modeling method is readily adaptable to the analysis of shear, bending, buckling, punching, relaxation and other loading scenarios applied on a wide array of different textile types. These scenarios will be demonstrated in forthcoming publications. Comparative data from in silico and in situ testing shows excellent agreement. Results demonstrate an improvement in simulation accuracy over prior comparable modeling techniques. The method presented here successfully predicts the actual behavior of yarns, single-layer and double-layer textile stacks in compaction.
Plasma CD147 reflects histological features in patients with lupus nephritis
Authors: Maeda-Hori M , Kosugi T , Kojima H , Sato W , Inaba S , Maeda K , Nagaya H , Sato Y , Ishimoto T , Ozaki T , Tsuboi N , Muro Y , Yuzawa Y , Imai E , Johnson RJ , Matsuo S , Kadomatsu K , Maruyama S 
Published: January 2014

Objective A glycosylated transmembrane protein, CD147, has been implicated in regulating lymphocyte responsiveness and leukocyte recruitment. As lupus nephritis (LN) often follows a relapsing-remitting disease course, accurate understanding of the disease activity would be extremely helpful in improving prognosis. Unfortunately, neither clinical nor serological data can accurately reflect the histological features of LN. The present study investigated whether CD147 can accurately predict pathological features of LN. Methods Plasma and spot urine samples were collected from 64 patients who underwent renal biopsy between 2008 and 2011. Disease activity for LN tissues was evaluated using the biopsy activity index, and compared to levels of biomarkers including CD147. Results In LN tissues, CD147 induction was striking in injured glomeruli and infiltrating inflammatory cells, but not in damaged tubules representing atrophy. Plasma CD147 levels accurately reflected the histological disease activity. However, prediction using a single molecule would be quite difficult because of the complex pathogenesis of LN. The diagnostic accuracy of multiplex parameters indicated that the combination including plasma CD147 might yield excellent diagnostic abilities for guiding ideal LN therapy. Conclusion Plasma CD147 levels might offer useful insights into disease activity as a crucial biomarker in patients with LN.
A comprehensive look at transcription factor gene expression changes in colorectal adenomas
Authors: Vonlanthen Janine , Okoniewski Michal J , Menigatti Mirco , Cattaneo Elisa , Pellegrini-Ochsner Daniela , Haider Ritva , Jiricny Josef , Staiano Teresa , Buffoli Federico , Marra Giancarlo 
Published: January 2014

AbstractBackgroundBiological processes are controlled by transcription networks. Expression changes of transcription factor (TF) genes in precancerous lesions are therefore crucial events in tumorigenesis. Our aim was to obtain a comprehensive picture of these changes in colorectal adenomas.MethodsUsing a 3-pronged selection procedure, we analyzed transcriptomic data on 34 human tissue samples (17 adenomas and paired samples of normal mucosa, all collected with ethics committee approval and written, informed patient consent) to identify TFs with highly significant tumor-associated gene expression changes whose potential roles in colorectal tumorigenesis have been under-researched. Microarray data were subjected to stringent statistical analysis of TF expression in tumor vs. normal tissues, MetaCore-mediated identification of TF networks displaying enrichment for genes that were differentially expressed in tumors, and a novel quantitative analysis of the publications examining the TF genes’ roles in colorectal tumorigenesis.ResultsThe 261 TF genes identified with this procedure includedDACH1,which plays essential roles in the proper proliferation and differentiation of retinal and leg precursor cell populations inDrosophila melanogaster.Its possible roles in colorectal tumorigenesis are completely unknown, but it was found to be markedly overexpressed (mRNA and protein) in all colorectal adenomas and in most colorectal carcinomas. However, DACH1 expression was absent in some carcinomas, most of which were DNA mismatch-repair deficient. When networks were built using the set of TF genes identified by all three selection procedures, as well as the entire set of transcriptomic changes in adenomas, five hub genes (TGFB1,BIRC5, MYB,NR3C1, andTERT) where identified as putatively crucial components of the adenomatous transformation process.ConclusionThe transcription-regulating network of colorectal adenomas (compared with that of normal colorectal mucosa) is characterized by significantly altered expression of over 250 TF genes, many of which have never been investigated in relation to colorectal tumorigenesis.
RETRACTED ARTICLE: Cellular immunotherapy using irradiated lung cancer cell vaccine co-expressing GM-CSF and IL-18 can induce significant antitumor effects
Authors: Tian Hongwei , Shi Gang , Yang Guoyou , Zhang Junfeng , Li Yiming , Du Tao , Wang Jianzhou , Xu Fen , Cheng Lin , Zhang Xiaomei , Dai Lei , Chen Xiaolei , Zhang Shuang , Yang Yang , Yu Dechao , Wei Yuquan , Deng Hongxin 
Published: January 2014

Abstract
Background
Although the whole tumor cell vaccine can provide the best source of immunizing antigens, there is still a limitation that most tumors are not naturally immunogenic. Tumor cells genetically modified to secrete immune activating cytokines have been proved to be more immunogenic. IL-18 could augment proliferation of T cells and cytotoxicity of NK cells. GM-CSF could stimulate dendritic cells, macrophages and enhance presentation of tumor antigens. In our study, we used mouse GM-CSF combined with IL-18 to modify Lewis lung cancer LL/2, then investigated whether vaccination could suppress tumor growth and promote survival.

Methods
The Lewis lung cancer LL/2 was transfected with co-expressing mouse GM-CSF and IL-18 plasmid by cationic liposome, then irradiated with a sublethal dose X ray (100 Gy) to prepare vaccines. Mice were subcutaneously immunized with this inactivated vaccine and then inoculated with autologous LL/2 to estimate the antitumor efficacy.

Results
The studies reported here showed that LL/2 tumor cell vaccine modified by a co-expressing mouse GM-CSF and IL-18 plasmid could significantly inhibit tumor growth and increased survival of the mice bearing LL/2 tumor whether prophylactic or adoptive immunotherapy in vivo. A significant reduction of proliferation and increase of apoptosis were also observed in the tumor treated with vaccine of co-expressing GM-CSF and IL-18. The potent antitumor effect correlated with higher secretion levels of pro-inflammatory cytokines such as IL-18, GM-CSF, interferon-γ in serum, the proliferation of CD4+ IFN-γ+, CD8+ IFN-γ+ T lymphocytes in spleen and the infiltration of CD4+, CD8+ T in tumor. Furthermore, the mechanism of tumor-specific immune response was further proved by 51Cr cytotoxicity assay in vitro and depletion of CD4, CD8, NK immune cell subsets in vivo. The results suggested that the antitumor mechanism was mainly depended on CD4+, CD8+ T lymphocytes.

Conclusions
These results provide a new insight into therapeutic mechanisms of IL-18 plus GM-CSF modified tumor cell vaccine and provide a potential clinical cancer immunotherapeutic agent for improved antitumor immunity.