bluuebunny/crossref_metadata_2025_split huggingface dataset:
A framework for architecture-level power, area, and thermal simulation and its application to network-on-chip design exploration
Authors: Hsieh Ming-yu , Rodrigues Arun , Riesen Rolf , Thompson Kevin , Song William 
Published: April 2011

We describe the integrated power, area and thermal modeling framework in the Structural Simulation Toolkit (SST) for large-scale high performance computer simulation. It integrates various power and thermal modeling tools and computes run-time energy dissipation for core, network on chip, memory controller and shared cache. It also has functionality to update the leakage power as temperature changes.
We illustrate the utilization of the framework by applying it to explore interconnect options in manycore systems with consideration of temperature variation and leakage feedback. We compare power, energy-delay-area product (EDAP), and energy-delay product (EDP) of four manycore configurations-1 core, 2 cores, 4 cores and 8 cores per cluster. Results from simulation with or without consideration of temperature variation both show that the 4-core per cluster configuration has the best EDAP and EDP. Even so, considering temperature variation increases total power dissipation. We demonstrate the importance of considering temperature variation in the design ow. With this power, area and thermal modeling capability, SST can be used for hardware/software co-design of future Exascale systems.
Fully decentralized computation of aggregates over data streams
Authors: Becchetti Luca , Bordino Ilaria , Leonardi Stefano , Rosen Adi 
Published: April 2011

In several emerging applications, data is collected in massive streams at several distributed points of observation. A basic and challenging task is to allow every node to monitor a neighbourhood of interest by issuing continuous aggregate queries on the streams observed in its vicinity. This class of algorithms is fully decentralized and diffusive in nature: collecting all data at few central nodes of the network is unfeasible in networks of low capability devices or in the presence of massive data sets.
The main difficulty in designing diffusive algorithms is to cope with duplicate detections. These arise both from the observation of the same event at several nodes of the network and/or receipt of the same aggregated information along multiple paths of diffusion. In this paper, we consider fully decentralized algorithms that answer locally continuous aggregate queries on the number of distinct events, total number of events and the second frequency moment in the scenario outlined above. The proposed algorithms use in the worst case or on realistic distributions sublinear space at every node. We also propose strategies that minimize the communication needed to update the aggregates when new events are observed. We experimentally evaluate for the efficiency and accuracy of our algorithms on realistic simulated scenarios.
Diagnosis of Prostate Cancer Using Differentially Expressed Genes in Stroma
Authors: Jia Zhenyu , Wang Yipeng , Sawyers Anne , Yao Huazhen , Rahmatpanah Farahnaz , Xia Xiao-Qin , Xu Qiang , Pio Rebecca , Turan Tolga , Koziol James A. , Goodison Steve , Carpenter Philip , Wang-Rodriguez Jessica , Simoneau Anne , Meyskens Frank , Sutton Manuel , Lernhardt Waldemar , Beach Thomas , Monforte Joseph , McClelland Michael , Mercola Dan 
Published: April 2011

Abstract
More than one million prostate biopsies are performed in the United States every year. A failure to find cancer is not definitive in a significant percentage of patients due to the presence of equivocal structures or continuing clinical suspicion. We have identified gene expression changes in stroma that can detect tumor nearby. We compared gene expression profiles of 13 biopsies containing stroma near tumor and 15 biopsies from volunteers without prostate cancer. About 3,800 significant expression changes were found and thereafter filtered using independent expression profiles to eliminate possible age-related genes and genes expressed at detectable levels in tumor cells. A stroma-specific classifier for nearby tumor was constructed on the basis of 114 candidate genes and tested on 364 independent samples including 243 tumor-bearing samples and 121 nontumor samples (normal biopsies, normal autopsies, remote stroma, as well as stroma within a few millimeters of tumor). The classifier predicted the tumor status of patients using tumor-free samples with an average accuracy of 97% (sensitivity = 98% and specificity = 88%) whereas classifiers trained with sets of 100 randomly generated genes had no diagnostic value. These results indicate that the prostate cancer microenvironment exhibits reproducible changes useful for categorizing the presence of tumor in patients when a prostate sample is derived from near the tumor but does not contain any recognizable tumor. Cancer Res; 71(7); 2476–87. ©2011 AACR.
Epigenetic Silencing of MicroRNA-203 Dysregulates ABL1 Expression and Drives Helicobacter-Associated Gastric Lymphomagenesis
Authors: Craig Vanessa J. , Cogliatti Sergio B. , Rehrauer Hubert , Wündisch Thomas , Müller Anne 
Published: April 2011

Abstract
Gastric B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) develops in the chronically inflamed mucosa of patients infected with the bacterial pathogen Helicobacter pylori. Here we use patient material, primary gastric lymphoma cell cultures, and a preclinical model of the disease to examine the role of microRNA (miRNA)-mediated posttranscriptional regulation—focusing in particular on miR-203 and its target ABL1—in gastric MALT lymphomagenesis. Microarray-based miRNA expression profiling revealed a strong downregulation of the putative tumor suppressor miRNA miR-203 in human MALT lymphoma samples, which resulted from extensive promoter hypermethylation of the miR-203 locus and coincided with the dysregulation of the miR-203 target ABL1 in lymphoma biopsies compared with matched adjacent normal material from the same patients. Treatment of lymphoma B cells with demethylating agents led to increased miR-203 expression and the concomitant downregulation of ABL1, confirming the epigenetic regulation of this miRNA. Ectopic reexpression of miR-203 by transfection of a human lymphoma cell line or lentiviral transduction of explanted primary MALT lymphoma cells was sufficient to prevent tumor cell proliferation in vitro. Similarly, the treatment of primary MALT lymphoma cells with the ABL inhibitors imatinib and dasatinib prevented tumor cell growth. Finally, we show that the treatment of tumor-bearing mice with imatinib induces MALT lymphoma regression in a preclinical model of the disease, implicating ABL1 in MALT lymphoma progression. In summary, our results show that the transformation from gastritis to MALT lymphoma is epigenetically regulated by miR-203 promoter methylation and identify ABL1 as a novel target for the treatment of this malignancy. Cancer Res; 71(10); 3616–24. ©2011 AACR.
Increased Thrombin Generation Is Associated With Acute Ischemic Stroke but Not With Coronary Heart Disease in the Elderly
Authors: Carcaillon Laure , Alhenc-Gelas Martine , Bejot Yannick , Spaft Christian , Ducimetière Pierre , Ritchie Karen , Dartigues Jean-François , Scarabin Pierre-Yves 
Published: April 2011

Objective—
A high thrombin generation level has been associated with the risk of venous thrombosis. Whether changes in this biomarker are relevant to arterial disease remains unknown. We investigated the association of thrombin generation with coronary heart disease (CHD) and acute ischemic stroke (AIS) in the elderly.

Methods and Results—

We used data from the Three-City study, a prospective cohort including 9294 subjects aged >65 years. After 4 years of follow-up, a case-cohort study was established. Using the calibrated automated thrombography method, endogenous thrombin potential and peak height were measured in plasma samples of all CHD and AIS cases and a random sample of 1177 controls. We did not find any significant association between thrombin generation and CHD. In multivariate analyses, high levels of endogenous thrombin potential and peak height were associated with an increased risk of AIS (hazard ratio=1.16 [95% CI, 0.90 to 1.50] and 1.31 [95% CI, 1.01 to 1.69] for a 1 SD increase, respectively). Data also suggested that these associations might be more important in women (hazard ratio=1.55 [95% CI, 1.05 to 2.33] and 1.71 [95% CI, 1.11 to 2.63], respectively) than in men (
P
for interaction=0.04 and 0.08, respectively).

Conclusion—
Thrombin generation emerges as an independent predictor of AIS, particularly in women. Hypercoagulability may have an important role in the pathogenesis of AIS.
Helper-Dependent Adenovirus Is Superior to First-Generation Adenovirus for Expressing Transgenes in Atherosclerosis-Prone Arteries
Authors: Jiang Bo , Qian Kun , Du Liang , Luttrell Ian , Chitaley Kanchan , Dichek David A. 
Published: April 2011

Objective—
Vascular gene transfer is a powerful tool for investigating and treating vascular diseases; however, its utility is limited by brevity of transgene expression and vector-associated inflammation. Helper-dependent adenovirus (HDAd), an advanced-generation adenovirus that lacks all viral genes, is superior to first-generation adenovirus (FGAd) in normal rabbit arteries. We compared HDAd to FGAd in arteries of cholesterol-fed rabbits, a model of early atherogenesis in which transgene expression might be decreased, and inflammation increased.

Methods and Results—
Carotid arteries of chow- and cholesterol-fed rabbits were infused with FGAd, HDAd, or medium. HDAd expressed a transgene at least as well in arteries of cholesterol-fed rabbits as in arteries of chow-fed rabbits and expressed more durably than FGAd. In arteries of cholesterol-fed rabbits, HDAd stimulated less intimal growth, lipid deposition, and inflammation than FGAd. Neither vector affected phenylephrine-induced contraction or nitroprusside-mediated relaxation; however, both vectors decreased maximal acetylcholine-stimulated vasorelaxation. The relative absence of intimal growth in HDAd arteries could interfere with the utility of this model for testing atheroprotective genes; however, both coinfusion of FGAd and extension of cholesterol feeding yielded larger intimal lesions, on which atheroprotective genes could be tested.

Conclusion—
HDAd is superior to FGAd for expression of transgenes in atherosclerosis-prone arteries.
Matrix Metalloproteinases Are Associated With Increased Blood–Brain Barrier Opening in Vascular Cognitive Impairment
Authors: Candelario-Jalil Eduardo , Thompson Jeffrey , Taheri Saeid , Grossetete Mark , Adair John C. , Edmonds Elaine , Prestopnik Jillian , Wills John , Rosenberg Gary A. 
Published: April 2011

Background and Purpose—
Subcortical ischemic vascular disease (SIVD) is a major form of vascular cognitive impairment (VCI) due to small vessel disease. Matrix metalloproteinases (MMPs) are neutral proteases that disrupt the blood–brain barrier and degrade myelin basic protein under conditions of neuroinflammation. Brain tissues and cerebrospinal fluid (CSF) of patients with VCI have increased levels of MMPs. We hypothesized that patients with SIVD have increased MMPs in the CSF, which are associated with increased CSF albumin.

Methods—
We studied 60 patients with suspected VCI. Twenty-five were classified as SIVD, whereas other groups included mixed Alzheimer disease and VCI, multiple strokes, and leukoaraiosis when white matter lesions were present and the diagnosis of VCI was uncertain. MMP-2 and MMP-9 in CSF and plasma were measured by gel zymography and indexed to CSF and plasma albumin. MMP-3 activity was measured by fluorescent assay.

Results—

We found reduced MMP-2 index (
P
<0.001) in the CSF for the full group of patients (SIVD, multiple strokes, mixed Alzheimer disease and VCI, and leukoaraiosis) compared with control subjects, whose CSF was obtained during spinal anesthesia. MMP-3 activity was increased in VCI compared with control subjects (
P
<0.01). In SIVD, MMP-2 index showed a negative correlation with albumin index, which was absent with the MMP-9 index. Combining MMP-2 index and MMP-3 activity separated the patients with SIVD from the control subjects with high specificity (
P
<0.0005).

Conclusions—
Our results support the hypothesis that MMPs are associated with increased CSF albumin and suggest that they may contribute to the pathophysiology of SIVD.
Preexisting Statin Use Is Associated With Greater Reperfusion in Hyperacute Ischemic Stroke
Authors: Ford Andria L. , An Hongyu , D'Angelo Gina , Ponisio Rosana , Bushard Patrick , Vo Katie D. , Powers William J. , Lin Weili , Lee Jin-Moo 
Published: April 2011

Background and Purpose—
Statin pretreatment has been associated with improved outcomes in patients with ischemic stroke. Although several mechanisms have been examined in animal models, few have been examined in patients. We hypothesized that patients using statins before stroke onset may have greater reperfusion than patients not using statins.

Methods—
Acute ischemic stroke patients underwent 2 MR scans: within 4.5 (tp1) and at 6 hours (tp2) after stroke onset. Regions of reperfusion were defined by prolonged mean transit time (MTT) at tp1, which normalized at tp2. Four MTT thresholds were assessed to ensure that results were not spuriously based on an arbitrary threshold. Baseline characteristics, relative reperfusion, and change in NIHSS between tp1 and 1-month follow-up (ΔNIHSS) were compared between patients who were using statins at stroke onset and those who were not.

Results—

Thirty-one stroke patients were prospectively enrolled; 12 were using statins and 19 were not. Baseline characteristics did not differ between the 2 groups except the statin group had greater coronary artery disease (
P
=0.03). Patients using statins showed significantly greater reperfusion compared to untreated patients across all MTT thresholds. For MTT of 4 seconds, median relative reperfusion was 50% (interquartile range, 30%–56%) in the preexisting statin group versus 13% (interquartile range, 5%–36%) in the untreated group (
P
=0.014). The statin group had greater ΔNIHSS (8.8±4.0 points) compared to the untreated group (4.4±5.7 points;
P
=0.028).

Conclusions—
Statin use before ischemic stroke onset was associated with greater early reperfusion and NIHSS improvement. Further studies in larger populations are required to confirm our preliminary findings.
Dissociation of Vasospasm and Secondary Effects of Experimental Subarachnoid Hemorrhage by Clazosentan
Authors: Sabri Mohammed , Ai Jinglu , Macdonald R. Loch 
Published: April 2011

Background and Purpose—
Endothelin receptor antagonists such as clazosentan decrease large-artery vasospasm after experimental and clinical subarachnoid hemorrhage. We used clazosentan to gain insight into the pathophysiology of subarachnoid hemorrhage by determining if decreasing vasospasm is associated with alleviation of other secondary complications of subarachnoid hemorrhage such as oxidative stress, endothelial nitric oxide synthase dysfunction, microthromboembolism, and neuronal injury.

Methods—
Mice were subjected to subarachnoid hemorrhage by injection of blood into the chiasmatic cistern. They were treated with clazosentan or vehicle by continuous intraperitoneal infusion for 48 hours. Middle cerebral artery vasospasm, superoxide anion radical, peroxynitrite, microthromboemboli, endothelial nitric oxide synthase uncoupling, cerebral blood flow, neuronal injury, and mortality were assessed.

Results—
Clazosentan preserved cerebral blood flow, alleviated vasospasm, and decreased mortality but did not affect superoxide anion radical, peroxynitrite, or microthromboemboli in the brain. Endothelial nitric oxide synthase uncoupling and neuronal injury also were not reduced by clazosentan.

Conclusions—
This study shows large-artery vasospasm is pathophysiologically independent of some other effects of subarachnoid hemorrhage. The findings have implications for development of treatments for this disease.
The Cortactin-binding Postsynaptic Density Protein ProSAP1 in Non-neuronal Cells
Authors: Redecker Peter , Gundelfinger Eckart D. , Boeckers Tobias M. 
Published: April 2011

Proline-rich synapse-associated protein-1 (ProSAP1) is a neuronal PDZ domain-containing protein that has recently been identified as an essential element of the postsynaptic density. Via its interaction with the actin-binding protein cortactin and its integrative function in the organization of neurotransmitter receptors, ProSAP1 is believed to be involved in the linkage of the postsynaptic signaling machinery to the actin-based cytoskeleton, and may play a role in the cytoskeletal rearrangements that underlie synaptic plasticity. As a result of our ongoing studies on the distribution and function of this novel PDZ domain protein, we now report that the expression of ProSAP1 is restricted neither to neurons and interneuronal junctions nor to the nervous system. Using immunohistochemical techniques in conjunction with specific antibodies, we found that, in the CNS, ProSAP1 can be detected in certain glial cells, such as ependymal cells, tanycytes, subpial/radial astrocytes, and in the choroid plexus epithelium. Moreover, our immunohistochemical analyses revealed the presence of ProSAP1 in endocrine cells of the adenohypophysis and of the pancreas, as well as in non-neuronal cell types of other organs. In the pancreas, ProSAP1 immunoreactivity was also localized in the duct system of the exocrine parenchyma. Our findings demonstrate that, in addition to neurons, ProSAP1 is present in various non-neuronal cells, in which it may play a crucial role in the dynamics of the actin-based cytoskeleton. (J Histochem Cytochem 49:639–648, 2001)
Changes of AT2 Receptor Levels in the Rat Adrenal Cortex and Medulla Induced by Bilateral Nephrectomy and Its Modulation by Circulating ANG II
Authors: Peters Barbara , Clausmeyer Susanne , Teubner Philipp , Obermüller Nicholas , Kränzlin Bettina , Gretz Norbert , Inagami Tadashi , Peters Jörg 
Published: April 2011

We studied regulation of the AT2 receptor by investigating the effect of bilateral nephrectomy (bNX) in Sprague–Dawley rats. The expression of aldosterone synthase (CYP11B2) and AT2 receptor mRNA was detected by nonradioactive in situ hybridization. AT2 receptor mRNA was detected in cells of the first two or three subcapsular cell layers of the zona glomerulosa (ZG) and in the medulla of sham-operated animals. After bNX, the number and area of distribution of AT2 receptor-positive cells increased in the ZG. This was associated with an enlargement of the steroidogenic active ZG and with reduced proliferation rate (sham 5.9 ± 0.9%; bNX 2.4 ± 0.2%; p > 0.02). Infusion of angiotensin II (ANG II; 200 ng/kg/min SC for 56 hr) to bNX rats did not reverse the effect of nephrectomy on the distribution of AT2 receptor expression, although mRNA levels per cell were reduced compared to NX alone. ANG II infusion decreased proliferation rate further (0.4 ± 0.07%; p > 0.001). In the adrenal medulla after bNX, decreased expression of the AT2 receptor was associated with increased proliferation (2.6 ± 0.2% vs 6.6 ± 0.5%). These results demonstrate differential regulation of the AT2 receptor in the adrenal gland and suggest that expression of the AT2 receptor is involved in regulating proliferation and differentiation in the ZG and medulla. (J Histochem Cytochem 49:649–656, 2001)
Secretion of Carbonic Anhydrase Isoenzyme VI (CA VI) from Human and Rat Lingual Serous von Ebner's Glands
Authors: Leinonen Jukka , Parkkila Seppo , Kaunisto Kari , Koivunen Petri , Rajaniemi Hannu 
Published: April 2011

Salivary carbonic anhydrase VI (CA VI) appears to contribute to taste function by protecting taste receptor cells (TRCs) from apoptosis. The serous von Ebner's glands locating in the posterior tongue deliver their saliva into the bottom of the trenches surrounding the TRC-rich circumvallate and foliate papillae. Because these glands deliver their saliva directly into the immediate vicinity of TRCs, we investigated whether CA VI is secreted by the von Ebner's glands, using immunochemical techniques. The immunohistochemical results showed that CA VI is present in the serous acinar cells, ductal cells, and ductal content of von Ebner's glands and in the demilune and ductal cells plus ductal content of rat lingual mucous glands. More importantly, CA VI was also detected in taste buds and in the taste pores. Western blotting of saliva collected from the orifices of human von Ebner's glands and CAs purified from rat von Ebner's glands confirmed that CA VI is expressed in these glands and secreted to the bottom of the trenches surrounding the circumvallate and foliate papillae. These findings are consistent with the hypothesis that locally secreted CA VI is implicated in the paracrine modulation of taste function and TRC apoptosis. (J Histochem Cytochem 49:657–662, 2001)
The Use of Counterflow Centrifugation to Enrich Gonadotropes and Somatotropes
Authors: Childs Gwen V. , Unabia Geda 
Published: April 2011

Counterflow centrifugation produces populations of gonadotropes or growth hormone (GH) cells enriched to 90% in a Beckman elutriator. The pituitary populations are first separated by size into three fractions applying different flow rates, stimulated with either gonadotropin-releasing hormone (GnRH) to enlarge the gonadotropes or growth hormone-releasing hormone (GHRH) to enlarge the somatotropes for 3 hr. The fractions are re-eluted, first at the original flow rates and then at higher flow rates to separate enlarged gonadotropes or somatotropes. Most other cell types are reduced to less than 5%. However, co-storage of GH and gonadotropin antigens is seen in either population. Enriched gonadotropes or somatotropes can be used in studies of proliferation, autocrine or paracrine regulation, or ion channel functions. (J Histochem Cytochem 49:663–664, 2001)
Intracellular Accumulation of Rhodamine 110 in Single Living Cells
Authors: Jeannot Valérie , Salmon Jean-Marie , Deumié Michel , Viallet Pierre 
Published: April 2011

To gain a better understanding of the internalization of rhodamines, vital staining of living cells in situ by two different rhodamines, R110 and R123, was studied by microfluorometry. These dyes differ strongly in their lipophilic properties because of differences in charge distribution. Microspectrofluorometry was used to study the fluorescence emission spectra of R110-loaded cells to determine reliable loading conditions. Cell uptake and cell efflux studies of R110 were performed by numerical microfluorescence imaging. A slower uptake was observed for R110 (14 hr) vs R123 (2 hr), but the R110 efflux was much more rapid (30 min) than that of R123 (<24 hr). Although it appeared in the R110 and R123 co-localization study that R110 was able to accumulate in mitochondria, labeling with R110 was lower than with R123. Our results indicate that, rhodamine 110 in its acid cationic form is able to cross the plasma and mitochondrial membrane and to accumulate in cell compartments as does the cationic rhodamine 123. However, because of its acido-basic properties, R110 should be able to decrease the pH of cell compartments, depending on their ability to regulate pH. In such a model, mitochondrial pH should be more greatly decreased than cytosolic pH, leading to a lower mitochondrial accumulation of R110 than of R123. Surprisingly, these effects, which should affect the energetic state of mitochondria, do not influence cell growth, because no cytotoxic effect was observed. (J Histochem Cytochem 45:403–412, 1997)