bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance analysis of the OP2 framework on many-core architectures
Authors: Giles M. B. , Mudalige G. R. , Sharif Z. , Markall G. , Kelly P. H.J. 
Published: April 2011

We present a performance analysis and benchmarking study of the OP2 "active" library, which provides an abstraction framework for the solution of parallel unstructured mesh applications. OP2 aims to decouple the scientific specification of the application from its parallel implementation, achieving code longevity and near-optimal performance through re-targeting the back-end to different hardware.
Runtime performance results are presented for a representative unstructured mesh application written using OP2 on a variety of many-core processor systems, including the traditional X86 architectures from Intel (Xeon based on the older Penryn and current Nehalem micro-architectures) and GPU offerings from NVIDIA (GTX260, Tesla C2050). Our analysis demonstrates the contrasting performance between the use of CPU (OpenMP) and GPU (CUDA) parallel implementations for the solution on an industrial sized unstructured mesh consisting of about 1.5 million edges.
Results show the significance of choosing the correct partition and thread-block configuration, the factors limiting the GPU performance and insights into optimizations for improved performance.
Memory Trace Compression and Replay for SPMD Systems using Extended PRSDs?
Authors: Budanur Sandeep , Mueller Frank , Gamblin Todd 
Published: April 2011

Concurrency levels in large-scale supercomputers are rising exponentially, and shared-memory nodes with hundreds of cores and non-uniform memory access latencies are expected within the next decade. However, even current petascale systems with tens of cores per node suffer from memory bottlenecks. As core counts increase, memory issues become critical for the performance of large-scale supercomputers. Trace analysis tools are vital for diagnosing the root causes of memory problems. However, existing tools are expensive due to prohibitively large trace sizes, or they collect only statistical summaries that omit valuable information.
In this paper, we present ScalaMemTrace, a novel technique for collecting memory traces in a scalable manner. ScalaMemTrace builds on prior trace methods with aggressive compression techniques to allow lossless representation of memory traces for dense algebraic kernels, with nearconstant trace size irrespective of the problem size or the number of threads. We further introduce a replay mechanism for ScalaMemTrace traces, and discuss the results of our prototype implementation on the x86 64 architecture.
The structural simulation toolkit
Authors: Rodrigues A. F. , Hemmert K. S. , Barrett B. W. , Kersey C. , Oldfield R. , Weston M. , Risen R. , Cook J. , Rosenfeld P. , Cooper-Balis E. , Jacob B. 
Published: April 2011

As supercomputers grow, understanding their behavior and performance has become increasingly challenging. New hurdles in scalability, programmability, power consumption, reliability, cost, and cooling are emerging, along with new technologies such as 3D integration, GP-GPUs, silicon-photonics, and other "game changers". Currently, they HPC community lacks a unified toolset to evaluate these technologies and design for these challenges.
To address this problem, a number of institutions have joined together to create the Structural Simulation Toolkit (SST), an open, modular, parallel, multi-criteria, multi-scale simulation framework. The SST includes a number of processor, memory, and network models. The SST has been used in a variety of network, memory, and application studies and aims to become the standard simulation framework for designing and procuring HPC systems.
Role of Fibulin-5 in Metastatic Organ Colonization
Authors: Devitt Møller Henrik , Ralfkjær Ulrik , Cremers Natascha , Frankel Mika , Troelsgaard Pedersen Rune , Klingelhöfer Jörg , Yanagisawa Hiromi , Grigorian Mariam , Guldberg Per , Sleeman Jonathan , Lukanidin Eugene , Ambartsumian Noona 
Published: April 2011

Abstract
The tumor microenvironment is now recognized as a major factor in determining the survival and growth of disseminated tumor cells at potential metastatic sites. Tumor cells send signals to stroma cells and stimulate them to produce factors that in turn create favorable conditions for tumor cell metastasis. Activated fibroblasts constitute an important component of the tumor-associated stroma. We have previously shown that S100A4 protein produced by stromal fibroblasts in the primary tumor stimulates metastasis formation. Here we show that activated fibroblasts also stimulate the formation of metastases independently of S100A4 expression during organ colonization. To identify genes that could potentially interfere with fibroblast-driven metastasis, we used gene expression profiling of S100A4-deficient fibroblasts treated with and without tumor cell-conditioned media. Five differentially expressed genes encoding cell surface and secreted proteins with potential metastasis-modulating activity were selected. Expression of lymphocyte antigen 6 complex (Ly6c) and matrix metalloproteinase 3 (Mmp3) was upregulated in fibroblasts in response to tumor-conditioned medium, whereas expression of cadherin-16 (Cdh16), Ccn2, and fibulin-5 (Fbln5) was downregulated. Further analysis showed that Fibulin-5 is able to suppress the metastatic colonization of lungs and liver. Additional studies suggest a mechanism in which Fibulin-5 suppresses metastasis formation by inhibiting production of matrix metalloproteinase 9 (MMP9) and reducing the invasive behavior of fibroblasts. Together our data are consistent with the notion that tumors secrete factors that downregulate expression of Fbln5 in fibroblasts at sites of metastatic colonization, in turn upregulating Mmp9 expression and stimulating metastatic organ colonization. Mol Cancer Res; 9(5); 553–63. ©2011 AACR.
Adiponectin Induces Vascular Smooth Muscle Cell Differentiation via Repression of Mammalian Target of Rapamycin Complex 1 and FoxO4
Authors: Ding Min , Xie Yi , Wagner Robert J. , Jin Yu , Carrao Ana Catarina , Liu Lucinda S. , Guzman Anthony K. , Powell Richard J. , Hwa John , Rzucidlo Eva M. , Martin Kathleen A. 
Published: April 2011

Objective—
The adipocyte-secreted hormone adiponectin exerts important cardioprotective and antidiabetic effects. Little is known about its effect on vascular smooth muscle cells (VSMC), key cells in restenosis, hypertension, and atherosclerosis.

Methods and Results—
Using human coronary artery VSMC, we found that recombinant adiponectin in the high-molecular-weight or trimeric forms but not the globular form induced VSMC differentiation through a mechanism similar to the classic feedback signaling used by rapamycin, a drug known to effectively inhibit restenosis on drug-eluting stents. Using a combination of pharmacological agents, small interfering RNA, and overexpression approaches, we demonstrated that adiponectin activated 5′-AMP-activated protein kinase α2 isoform, leading to inhibition of mammalian target of rapamycin complex 1 and S6K1. This in turn stabilized insulin receptor substrate-1, driving Akt2-mediated inhibition of FoxO4 and subsequent contractile protein induction. Although adiponectin and rapamycin have similarly beneficial effects on VSMC phenotype in both cell and organ culture, a direct comparison of the effects of rapamycin versus adiponectin on endothelial cells revealed distinct differences: rapamycin inhibited Akt phosphorylation, whereas adiponectin maintained it. Importantly, Akt activity preserves endothelial function.

Conclusion—
Adiponectin promotes VSMC differentiation and preserves endothelial cell Akt signaling, suggesting that targeting the adiponectin pathway may have advantages over rapamycin in developing new drug-eluting stent therapeutics.
Hypoxia Stimulates Low-Density Lipoprotein Receptor–Related Protein-1 Expression Through Hypoxia-Inducible Factor-1α in Human Vascular Smooth Muscle Cells
Authors: Castellano Jose , Aledo Rosa , Sendra Judith , Costales Paula , Juan-Babot Oriol , Badimon Lina , Llorente-Cortés Vicenta 
Published: April 2011

Objective—
Hypoxia is considered a key factor in the progression of atherosclerotic lesions. Low-density lipoprotein receptor–related protein (LRP1) plays a pivotal role in the vasculature. The aim of this study was to investigate the effect of hypoxia on LRP1 expression and function in vascular smooth muscle cells (VSMC) and the role of hypoxia-inducible factor-α (HIF-1α).

Methods and Results—

Real-time polymerase chain reaction and Western blot analysis demonstrated that hypoxia (1% O
2
) time-dependently induced LRP1 mRNA (maximum levels at 1 to 2 hours) and protein expression (maximum levels at 12 to 24 hours). The delayed hypoxic upregulation of LRP1 protein versus mRNA may be explained by the long half-life of LRP1 protein. Luciferase assays demonstrated that hypoxia and HIF-1α overaccumulation induced LRP1 promoter activity and that 2 consensus hypoxia response element sites located at −1072/−1069 and −695/−692 participate in the induction. Chromatin immunoprecipitation showed the in vivo binding of HIF-1α to LRP1 promoter in hypoxic VSMC. Hypoxia effects on LRP1 protein expression were functionally translated into an increased cholesteryl ester (CE) accumulation from aggregated low-density lipoprotein (agLDL) uptake. The blockade of HIF-1α expression inhibited the upregulatory effect of hypoxia on LRP1 expression and agLDL-derived intracellular CE overaccumulation, suggesting that both LRP1 overexpression and CE overaccumulation in hypoxic vascular cells are dependent on HIF-1α. Immunohistochemical analysis showed the colocalization of LRP1 and HIF-1α in vascular cells of human advanced atherosclerotic plaques.

Conclusion—
Hypoxia upregulates LRP1 expression and agLDL-derived intracellular CE accumulation in human VSMC through HIF-1α induction.
Recurrent Hypoglycemia Exacerbates Cerebral Ischemic Damage in Streptozotocin-Induced Diabetic Rats
Authors: Dave Kunjan R. , Tamariz John , Desai Kushal M. , Brand Frank J. , Liu Annie , Saul Isabel , Bhattacharya Sanjoy K. , Pileggi Antonello 
Published: April 2011

Background and Purpose—
Stroke and heart disease are the most serious complications of diabetes accounting for >65% of mortality among diabetics. Although intensive insulin therapy has significantly improved the prognosis of diabetes and its complications, it is associated with an elevated risk of recurrent hypoglycemia (RH). We tested the hypothesis that RH exacerbates cerebral ischemic damage in a rodent model of diabetes.

Method—
We determined the extent of neuronal death in CA1 hippocampus after global cerebral ischemia in control and streptozotocin-induced diabetic rats. Diabetic animals included an insulin-treated streptozotocin-diabetic (ITD) group and a group of ITD rats exposed also to 10 episodes of hypoglycemia (ITD+recurrent hypoglycemia: RH). Hypoglycemia (55 to 65 mg/dL blood glucose) was induced twice daily for 5 consecutive days.

Results—
As expected, uncontrolled diabetes (streptozotocin-diabetes, untreated animals) resulted in a 70% increase in ischemic damage as compared with the control group. Insulin treatment was able to lower ischemic damage by 64% as compared with the diabetic group. However, ITD+RH rats had 44% more damage when compared with the ITD group. We also observed that free radical release from mitochondria is increased in ITD+RH rats.

Conclusions—
This is the first report on the impact of RH in exacerbating cerebral ischemic damage in diabetic animals. Our results suggest that increased free radical release from mitochondria may be responsible for observed increased ischemic damage in ITD+RH rats. RH thus may be an unexplored but important factor responsible for increased ischemic damage in diabetes.
Prevalence and Calcification of Intracranial Arterial Stenotic Lesions as Assessed With Multidetector Computed Tomography Angiography
Authors: Homburg Philip J. , Plas Gerben J.J. , Rozie Sietske , van der Lugt Aad , Dippel Diederik W.J. 
Published: April 2011

Background and Purpose—
Intracranial arterial stenosis (ICAS) in patients with recent ischemic stroke is associated with a high risk of recurrent stroke. More insight into the pathophysiology of ICAS could help identify patients at high risk requiring more aggressive secondary prevention. We evaluated the prevalence, distribution, calcification, and the risk factors predisposing ICAS in a European stroke population.

Methods—
Consecutive patients with a transient ischemic attack or ischemic stroke (n=786) were evaluated for the presence and distribution of ICAS (≥30% luminal narrowing) by CT angiography. ICAS were categorized as symptomatic or asymptomatic, and the presence of calcification was assessed. The association of traditional cerebrovascular risk factors and the erythrocyte sedimentation rate with ICAS was analyzed.

Results—
In 178 of 786 patients (23%), 288 ICAS were observed. Most stenoses (n=194/288; 67%) were located in the posterior circulation arteries. In 59 of 786 patients (8%), ICAS were considered symptomatic. ICAS in the basilar artery and arteries beyond the circle of Willis were mainly noncalcified. In addition to age, gender, and several traditional cerebrovascular risk factors, erythrocyte sedimentation rate was independently associated with the presence of ICAS (OR, 1.20; 95% CI, 1.06–1.36) and with the presence of noncalcified ICAS in particular (OR, 1.20; 95% CI, 1.05–1.37).

Conclusions—
ICAS was observed in a noteworthy number of European stroke patients. Particularly, the majority of ICAS was observed in the posterior circulation, possibly conferring worse prognosis. ICAS in distal arteries were mainly noncalcified. Association of noncalcified ICAS and erythrocyte sedimentation rate may indicate a prominent role for inflammatory factors in intracranial atherosclerotic disease.
Risk and Cumulative Risk of Stroke Recurrence
Authors: Mohan Keerthi M. , Wolfe Charles D.A. , Rudd Anthony G. , Heuschmann Peter U. , Kolominsky-Rabas Peter L. , Grieve Andrew P. 
Published: April 2011

Background and Purpose—
Estimates of risk of stroke recurrence are widely variable and focused on the short- term. A systematic review and meta-analysis was conducted to estimate the pooled cumulative risk of stroke recurrence.

Methods—
Studies reporting cumulative risk of recurrence after first-ever stroke were identified using electronic databases and by manually searching relevant journals and conference abstracts. Overall cumulative risks of stroke recurrence at 30 days and 1, 5, and 10 years after first stroke were calculated, and analyses for heterogeneity were conducted. A Weibull model was fitted to the risk of stroke recurrence of the individual studies and pooled estimates were calculated with 95% CI.

Results—
Sixteen studies were identified, of which 13 studies reported cumulative risk of stroke recurrence in 9115 survivors. The pooled cumulative risk was 3.1% (95% CI, 1.7–4.4) at 30 days, 11.1% (95% CI, 9.0–13.3) at 1 year, 26.4% (95% CI, 20.1–32.8) at 5 years, and 39.2% (95% CI, 27.2–51.2) at 10 years after initial stroke. Substantial heterogeneity was found at all time points. This study also demonstrates a temporal reduction in 5-year risk of stroke recurrence from 32% to 16.2% across the studies.

Conclusions—
The cumulative risk of recurrence varies greatly up to 10 years. This may be explained by differences in case mix and changes in secondary prevention over time However, methodological differences are likely to play an important role and consensus on definitions would improve future comparability of estimates and characterization of groups of stroke survivors at increased risk of recurrence.
Different Regulation of Connexin26 and ZO-1 in Cochleas of Developing Rats and of Guinea Pigs with Endolymphatic Hydrops
Authors: Suzuki Toshihiro , Masahito Oyamada , Takamatsu Tetsuro 
Published: April 2011

Using confocal microscopy and morphometry, we analyzed the expression of connexin26 (Cx26) and ZO-1 in rat cochlea during the postnatal period to elucidate spatiotemporal changes in gap junctions and tight junctions during auditory development. We also studied changes in these junctions in experimental endolymphatic hydrops in the guinea pig. In the adult rat cochlear lateral wall, Cx26 was detected in fibrocytes in the spiral ligament and in the basal cell layer of the stria vascularis, whereas ZO-1 was detected in the apical surfaces of marginal cells and in the basal cell layer. During postnatal development, Cx26 expression increased mainly in the spiral ligament, whereas ZO-1 expression increased in the basal cell layer. The morphometry of Cx26 showed a sigmoid time course with a rapid increase on postnatal day (PND) 14, whereas that of ZO-1 showed a marked increase on PND 7. In experimental endolymphatic hydrops, the expression of Cx26 significantly decreased, whereas there were no obvious changes in the expression of ZO-1. These results indicate that gap junctions and tight junctions in the cochlea increase in a different spatiotemporal manner during the development of auditory function and that gap junctions and tight junctions in the cochlea are differentially regulated in experimental endolymphatic hydrops. (J Histochem Cytochem 49:573–586, 2001)
Single-copy Gene Detection Using Branched DNA (bDNA) In Situ Hybridization
Authors: Player Audrey N. , Shen Lu-Ping , Kenny Daryn , Antao Vincent P. , Kolberg Janice A. 
Published: April 2011

We have developed a branched DNA in situ hybridization (bDNA ISH) method for detection of human papillomavirus (HPV) DNA in whole cells. Using human cervical cancer cell lines with known copies of HPV DNA, we show that the bDNA ISH method is highly sensitive, detecting as few as one or two copies of HPV DNA per cell. By modifying sample pretreatment, viral mRNA or DNA sequences can be detected using the same set of oligonucleotide probes. In experiments performed on mixed populations of cells, the bDNA ISH method is highly specific and can distinguish cells with HPV-16 from cells with HPV-18 DNA. Furthermore, we demonstrate that the bDNA ISH method provides precise localization, yielding positive signals retained within the subcellular compartments in which the target nucleic acid sequences are localized. As an effective and convenient means for nucleic acid detection, the bDNA ISH method is applicable to the detection of cancers and infectious agents. (J Histochem Cytochem 49:603–611, 2001)
Quantitative Immunohistochemistry of Glucose Transport Protein (Glut3) Expression in the Rat Hippocampus During Aging
Authors: Fattoretti Patrizia , Bertoni-Freddari Carlo , Stefano Giuseppina Di , Casoli Tiziana , Gracciotti Natascia , Solazzi Moreno , Pompei Pierluigi 
Published: April 2011

Immunohistochemistry of Glut3 (45 kD), an integral membrane peptide mediating the transport of glucose in neurons, was carried out in the hippocampus of 3- and 28-month-old rats to assess the effect of age on energy metabolism. Free-floating sections of fixed-frozen hippocampi were processed for quantitative immunohistochemistry of Glut3. A rabbit affinity-purified antibody identified Glut3 immunoreactivity. Glut3 staining was intense in neuropil, axons, and dendrites, whereas nerve cell bodies were unstained. With aging, Glut3 reactivity was significantly decreased in the inner molecular layer of the hip-pocampal dentate gyrus (–46%) and the mossy fibers of the CA3 sector (–34%), whereas the stratum radiatum of CA1 did not show any difference due to age. These data document an age-dependent decrease in Glut3 expression in discrete areas of rat hippocampus. Glut3 constitutes the predominant glucose transporter in neurons and is found abundantly in regions with high synaptic density characterized by frequent bursts of function-adequate metabolic activity. Our findings therefore lend further support to the critical role of an impaired metabolism in age-related brain dysfunctions and disease. (J Histochem Cytochem 49:671–672, 2001)
The ELF-97 Alkaline Phosphatase Substrate Provides a Bright, Photostable, Fluorescent Signal Amplification Method for FISH
Authors: Paragas Violette B. , Zhang Yu-Zhong , Haugland Richard P. , Singer Victoria L. 
Published: April 2011

We used the ELF-97 (Enzyme-Labeled Fluorescence) phosphatase substrate, 2-(5'-chloro-2-phosphoryloxyphenyl)-6-chloro-4(3H)-quinazolinone, with alkaline phosphatase conjugates of streptavidin and appropriate antibodies to amplify signals from biotinylated and haptenylated hybridization probes. The dephosphorylated product, ELF-97 alcohol, is a bright yellow-green fluorescent precipitate optimally excited at ∼360 nm, with emission centered at ∼530 nm. This large Stokes shift allows ELF-97 signals to be easily distinguished from sample autofluorescence and signals arising from counterstains or other fluorophores. The ELF-97 precipitate was extremely photostable compared to fluorescein, allowing multiple photographic exposures of samples without significant signal intensity loss. For RNA in situ hybridization, labeling was specific and localized well to targets in cultured cells, tissue sections, and whole-mount zebrafish embryos. ELF-97 signals developed in seconds to minutes and were easily distinguished from pigmented tissues or cells, unlike those obtained using colorimetric substrates. We used the substrate with singly biotinylated short oligonucleotides to detect actin mRNA in MDCK cells and actin and β-galactosidase mRNA in LacZ+ mouse fibroblasts. We also used a biotinylated cDNA, complementary to the mRNA encoded by the constant region of the T-cell receptor β-chain, to specifically identify T-cells in mouse lymph node tissue sections. With digoxigenin-labeled probes, we detected several developmentally expressed mRNAs in whole-mount zebrafish embryos. Hybridization to centromere repeat regions in human metaphase and interphase chromosomes was also detected; ELF-97 signals were manyfold brighter than signals obtained with fluorescein conjugates. Finally, Southern blot hybridization using singly labeled oligonucleotide probes yielded a sensitivity similar to that obtained with radioactivity. (J Histochem Cytochem 45:345–357, 1997)
Tissue Distribution of Human gp330/Megalin, a Putative Ca2+-sensing Protein
Authors: Lundgren Stefan , Carling Tobias , Hjälm Göran , Juhlin Claes , Rastad Jonas , Pihlgren Ulla , Rask Lars , Åkerström Göran , Hellman Per 
Published: April 2011

We used riboprobes and monoclonal antibodies to characterize tissue distribution of the human 550-kD homologue to gp330/megalin, primarily identified in the rat kidney. Human gp330/megalin mRNA and protein are readily identified in human parathyroid cells, placental cytotrophoblasts, kidney proximal tubule cells, and epididymal epithelial cells. The immunoreactivity is found on the surface of the cells and is heterogeneously downregulated in parathyroid hyperplasia and adenomas. Cells of the proximal kidney tubule and epididymis express the protein on their luminal aspect. Moreover, the protein is expressed in Type II pneumocytes, mammary epithelial and thyroid follicular cells, and the ciliary body of the eye. Sequence analysis of cDNA fragments, obtained by RT-PCR, revealed identical nucleotide sequences in parathyroid, kidney, placenta, epididymis, and lung. Immunohistochemistry for parathyroid hormone-related protein (PTHrP) revealed partial co-expression with human gp330/megalin in parathyroid, placenta, and mammary gland. The findings substantiate human gp330/megalin expression in a variety of human tissues expected to possess calcium-sensing functions. It may constitute a protein of utmost importance to adult and fetal calcium homeostasis, although other important functions may also be coupled to this exceptionally large protein with highly restricted tissue distribution. (J Histochem Cytochem 45:383–392, 1997)