bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measuring Microarchitectural Details of Multi- and Many-Core Memory Systems through Microbenchmarking
Authors: Fang Zhenman , Mehta Sanyam , Yew Pen-Chung , Zhai Antonia , Greensky James , Beeraka Gautham , Zang Binyu 
Published: January 2015

As multicore and many-core architectures evolve, their memory systems are becoming increasingly more complex. To bridge the latency and bandwidth gap between the processor and memory, they often use a mix of multilevel private/shared caches that are either blocking or nonblocking and are connected by high-speed network-on-chip. Moreover, they also incorporate hardware and software prefetching and simultaneous multithreading (SMT) to hide memory latency. On such multi- and many-core systems, to incorporate various memory optimization schemes using compiler optimizations and performance tuning techniques, it is crucial to have microarchitectural details of the target memory system. Unfortunately, such details are often unavailable from vendors, especially for newly released processors.
In this article, we propose a novel microbenchmarking methodology based on short elapsed-time events (SETEs) to obtain comprehensive memory microarchitectural details in multi- and many-core processors. This approach requires detailed analysis of potential interfering factors that could affect the intended behavior of such memory systems. We lay out effective guidelines to control and mitigate those interfering factors. Taking the impact of SMT into consideration, our proposed methodology not only can measure traditional cache/memory latency and off-chip bandwidth but also can uncover the details of software and hardware prefetching units not attempted in previous studies. Using the newly released Intel Xeon Phi many-core processor (with in-order cores) as an example, we show how we can use a set of microbenchmarks to determine various microarchitectural features of its memory system (many are undocumented from vendors). To demonstrate the portability and validate the correctness of such a methodology, we use the well-documented Intel Sandy Bridge multicore processor (with out-of-order cores) as another example, where most data are available and can be validated. Moreover, to illustrate the usefulness of the measured data, we do a multistage coordinated data prefetching case study on both Xeon Phi and Sandy Bridge and show that by using the measured data, we can achieve 1.3X and 1.08X performance speedup, respectively, compared to the state-of-the-art Intel ICC compiler. We believe that these measurements also provide useful insights into memory optimization, analysis, and modeling of such multicore and many-core architectures.
Compiler/Runtime Framework for Dynamic Dataflow Parallelization of Tiled Programs
Authors: Kong Martin , Pop Antoniu , Pouchet Louis-Noël , Govindarajan R. , Cohen Albert , Sadayappan P. 
Published: January 2015

Task-parallel languages are increasingly popular. Many of them provide expressive mechanisms for intertask synchronization. For example, OpenMP 4.0 will integrate data-driven execution semantics derived from the StarSs research language. Compared to the more restrictive data-parallel and fork-join concurrency models, the advanced features being introduced into task-parallel models in turn enable improved scalability through load balancing, memory latency hiding, mitigation of the pressure on memory bandwidth, and, as a side effect, reduced power consumption.
In this article, we develop a systematic approach to compile loop nests into concurrent, dynamically constructed graphs of dependent tasks. We propose a simple and effective heuristic that selects the most profitable parallelization idiom for every dependence type and communication pattern. This heuristic enables the extraction of interband parallelism (cross-barrier parallelism) in a number of numerical computations that range from linear algebra to structured grids and image processing. The proposed static analysis and code generation alleviates the burden of a full-blown dependence resolver to track the readiness of tasks at runtime. We evaluate our approach and algorithms in the PPCG compiler, targeting OpenStream, a representative dataflow task-parallel language with explicit intertask dependences and a lightweight runtime. Experimental results demonstrate the effectiveness of the approach.
Expression of Three Cell Adhesion Molecules in Bladder Carcinomas: Correlation with Pathological Features
Authors: Mialhe Agnès , Louis Josette , Pasquier Dominique , Rambeaud Jean‐Jacques , Seigneurin Daniel 
Published: January 2015

Recently, independent studies have shown that the expression of two integrin chains, β4 and α2, plus the epithelial cadherin are related to tumour progression in human bladder carcinomas. For the first time, we compare the expression of these three cell adhesion molecules using immunohistochemical analysis of consecutive cryosections from a series of 50 bladder tumours. E‐cadherin, β4, and α2 were strongly expressed in normal urothelium. A majority of non‐invasive bladder cancers stained positively for E‐cadherin (62%), whereas only 29% expressed normal positivity for α2, and only 35% for β4. However, most invasive tumours presented an aberrant expression of α2 (81%), β4 (100%), and E‐cadherin (75%). We studied the correlation of immunoreactivity with histological grade and stage. The α2 pattern was not correlated with stage and grade. In contrast, loss of normal β4 expression was significantly related to increasing tumour grade and deep invasion with a higher correlation for grade. Finally, E‐cadherin expression was highly correlated with stage, but not with grade. Thus our results indicate that, although many invasive bladder tumours presented a disorder in expression of the two integrins α2 and β4, E‐cadherin appeared to be a better marker of invasiveness in bladder carcinomas.Erratum of
“Expression of Three Cell Adhesion Molecules in Bladder Carcinomas: Correlation with Pathological Features”dx.doi.org/10.1155/1997/585174
Comparative Intracellular Cytokine Production by In Vitro Stimulated T Lymphocytes from Human Umbilical Cord Blood (HUCB) and Adult Peripheral Blood (APB)
Authors: García Vela J. A. , Delgado I. , Bornstein R. , Alvarez B. , Auray M. C. , Martin I. , Oña F. , Gilsanz F. 
Published: January 2015

To date over 400 HUCB transplants have been reported from different centers. It has been suggested that there is a reduced graft‐versus‐host‐disease (GVHD) with HUCB compared to bone marrow transplantation. Since cytokine production by a cell is an indication of the cells function it is important to determinate the differences between APB and HUCB with respect to production of these soluble factors. Our aim was to analyse the intracellular cytokine production by HUCB and APB T lymphocytes with and emphasize on their possible role in GVHD.Heparinized HUCB samples from 8 normal full‐term deliveries and 10 normal blood donors were stimulated 4 hours at 37&compfn;C and 5% CO2 with phorbol 12‐myristate 13‐acetate (PMA) and Ionomycin in the presence of brefeldine. Afterwards cells were stained with CD3, CD4 or CD8 in different combinations. Finally, after cell permeabilization, cells were stained with Il‐2, Il‐4 or IFN‐γ. Data acquisition was performed on a FACScan flow cytometer.Compared to APB, HUCB T lymphocytes produced less Il‐2, Il‐4 and IFN‐γ. In HUCB, Il‐2, Il‐4 and IFN‐γ were produced predominantly by CD4+ T cells. In APB, Il‐2 and Il‐4 were also produced predominantly by CD4+ cells compared with CD8+ T lymphocytes, however, IFN‐γ was produced by both CD4+ and CD8+ T cells.
These results indicate that there are clear differences in the cytokine profile between T cells in APB and HUCB.
Acceptance of Telepathology in Daily Practice
Authors: Mairinger Thomas 
Published: January 2015

The availability of pathology services differs greatly in our environment. Although pathology would be especially suitable for being practised at a distance by transporting digital image information, the spread of telepathology into everyday work still is relatively slow.The article describes the situation of diffusion of this innovative technology by reviewing the literature and discussing this in context to data based on questionnaires dealing with the acceptance of telepathology. The current situation of telepathology can be discussed by five items for innovation spead: (1) communication and influence; (2) economic costs and benefits; (3) knowledge barriers and learning; (4) feasibility of techniques offered for the demands of the users; (5) clarification of the legal status and other factors concerning international collaboration. All these head lines do not represent realistic obstacles for the more widespread use of telepathology. The real drawbacks may therefore be found behind certain professional habits of pathologists. The most important causes may be that (a) telediagnosis is not as easy as it may seem at the first glance; (b) telepathology is seen as a potential highway to a world‐wide competition of pathology service providers. As soon as these mostly unjustified prejudices are corrected and telepathology is percepted as additional technique in pathology, it will become a diagnostic tool as common and as useful as the telephone.
Increased Cell Proliferation in Chronic Helicobacter pylori Positive Gastritis and Gastric Carcinoma – Correlation between Immuno‐Histochemistry and Tv Image Cytometry
Authors: Szaleczky Erika , Prónai László , Molnár Béla , Berczi Lajos , Fehér János , Tulassay Zsolt 
Published: January 2015

Backgound: Epithelial cell proliferation activity has been reported both to be unaltered and increased in Helicobacter pylori (H. pylori) associated chronic gastritis. The proliferation rate decreased following H. pylori eradication, but results are controversial whether this change is dependent on the success of eradication. We compared the cell proliferation activity of H. pylori positive and negative gastric epithelial biopsies in chronic gastritis with and without intestinal metaplasia (IM) and gastric cancer by the expression of proliferation cell nuclear antigen (PCNA) and Tv image cytometry, and assessed the effect of H. pylori eradication on the cell proliferation rate in the gastric epithelium.Methods: Brush smears and antral biopsies were taken from 70 patients (42 men, 28 women, mean age 58 ± 15 y.o.) on routine endoscopy. Patients were divided into four groups according to the histology; normal epithelia (n=10), chronic gastritis without IM (n=24), chronic gastritis with IM (n=20), and gastric carcinoma (n=16). Thirty‐three patients were H. pylori positive, and success of eradication was controlled in 24 cases. Cell proliferation was measured by immunohistochemistry using PCNA labeling index (LI) and by Tv image cytometry evaluating 12 morpho‐ and densitometric parameters of each nuclei and 6 additional parameters of each smear.Results: PCNA LI, DNA index and S + G2 ratio were all higher in chronic gastritis than in the normal epithelium, and were further increased in carcinoma. The lower PCNA LI observed in chronic gastritis with IM corresponds to the lower S phase ratio determined by Tv image analysis. In H. pylori positive cases, the proliferation activity was 69.3 ± 13.05% prior to the eradication and it decreased to 55.8 ± 23.31% after the successful eradication therapy. When immunohistochemistry was compared with Tv image cytometry, PCNA LI significantly correlated with the percentage of cells in G1 phase (r=−0.415) and S phase (r=0.385), Integrated Optical Density mean (r=0.598), density maximum (r=0.608), surface (r=0.670), layers (r=0.638), diameter minimum (r=0.619), diameter maximum (r=0.730) and perimeter (r=0.501), respectively (p < 0.05).Conclusions: Epithelial cell turnover is increased in chronic gastritis with or without IM, and in gastric carcinoma. The lower PCNA LI observed in chronic gastritis with IM corresponds to the lower S phase ratio determined by Tv image analysis. Cell proliferation decreases after successful H. pylori eradication. Both methods proved to be reliable for the determination of epithelial cell proliferation.
Evaluation of C‐ErbB‐2 Overexpression and Her‐2/neu Gene Copy Number Heterogeneity in Barrett’s Adenocarcinoma
Authors: Walch Axel , Bink Karin , Gais Peter , Stangl Stefan , Hutzler Peter , Aubele Michaela , Mueller James , Höfler Heinz , Werner Martin 
Published: January 2015

Amplifiction of the Her‐2/neu gene is accompanied by overexpression of its cell surface receptor product, c‐erbB‐2 protein. To investigate the degree of intratumoural heterogeneity we applied immunohistochemistry in primary Barrett’s adenocarcinoma (BCA) (n = 6) and dysplasia adjacent to the carcinoma (n = 4). In addition, fluorescence in situ hybridisation (FISH) was performed in primary BCA (n=5) and dysplastic areas (n=4). For an objective evaluation digital image analysis and laser scanning microscopy were used. Five of six BCA showed a marked intratumoural heterogeneous staining pattern ranging from areas in which the tumour cells were negative or faintly positive to tumour areas with a strong staining of the entire membrane. Among the two dysplastic areas also a heterogenous staining pattern was observed. FISH analysis revealed marked heterogeneity of intratumoural gene copy number changes in all BCA showing populations with different fractions of cells with polysomy, low level amplification and high level amplification. One dysplasia showed a minor population with Her‐2/neu signal clusters. In conclusion, we observed marked intratumoural heterogeneity of c‐erbB‐2 protein overexpression and Her‐2/neu gene copy number in the majority of the primary BCA analyzed. Digital image analysis and laser scanning microscopy were helpful in quantifying the variations in protein expression and DNA copy number in individual tumour cells. The observed heterogeneity could hamper the exact diagnostic determination of the c‐erbB‐2 status in small biopsies and possibly influence the effectiveness of a potential c‐erbB‐2 targeting therapy.Figures on http://www.esacp.org/acp/2000/20‐1/walch.htm.
Malignancy‐Associated Changes in Breast Tissue Detected by Image Cytometry
Authors: Mommers Ellen C. M. , Poulin Neal , Meijer Chris J. L. M. , Baak Jan P. A. , van Diest Paul J. 
Published: January 2015

In several tissues, nuclear differences have been described in normal‐appearing cells from patients with invasive carcinomas compared to cases without invasive carcinoma, a phenomenon known as malignancy‐associated changes (MACs). The aim of this study was to determine the presence of malignancy‐associated changes in breast tissue.Image cytometry was performed on Feulgen stained tissue sections of patients with usual ductal hyperplasia with (n=30) or without (n=41) adjacent invasive breast carcinoma. Nuclear features of normal‐appearing cells as well as of usual ductal hyperplastic cells were separately compared between the two groups.Many features of normal‐appearing epithelial cells were significantly different between cases with and without invasive cancer. Significant differences were also found by measuring ductal hyperplastic nuclei instead of normal‐appearing nuclei. Cases with or without cancer could be distinguished with a classification accuracy of 80% by discriminant analysis using 2 nuclear features derived from ductal hyperplastic cells.In conclusion, image cytometry on breast tissue sections shows that malignancy‐associated changes can be found in normal as well as in usual ductal hyperplastic breast cells. This could be clinically relevant for the detection of occult breast cancer, for the prediction of risk in these lesions, and to monitor the effect of chemopreventive agents.
Deletion of Chromosome 4q Predicts Outcome in Stage II Colon Cancer Patients
Authors: Brosens R. P. M. , Belt E. J. T. H. , Haan J. C. , Buffart T. E. , Carvalho B. , Grabsch H. , Quirke P. , Cuesta M. A. , Engel A. F. , Ylstra B. , Meijer G. A. 
Published: January 2015

Background: Around 30% of all stage II colon cancer patients will relapse and die of their disease. At present no objective parameters to identify high-risk stage II colon cancer patients, who will benefit from adjuvant chemotherapy, have been established. With traditional histopathological features definition of high-risk stage II colon cancer patients is inaccurate. Therefore more objective and robust markers for prediction of relapse are needed. DNA copy number aberrations have proven to be robust prognostic markers, but have not yet been investigated for this specific group of patients. The aim of the present study was to identify chromosomal aberrations that can predict relapse of tumor in patients with stage II colon cancer.Materials and Methods: DNA was isolated from 40 formaldehyde fixed paraffin embedded stage II colon cancer samples with extensive clinicopathological data. Samples were hybridized using Comparative Genomic Hybridization (CGH) arrays to determine DNA copy number changes and microsatellite stability was determined by PCR. To analyze differences between stage II colon cancer patients with and without relapse of tumor a Wilcoxon rank-sum test was implemented with multiple testing correction.Results: Stage II colon cancers of patients who had relapse of disease showed significantly more losses on chromosomes 4, 5, 15q, 17q and 18q. In the microsatellite stable (MSS) subgroup (n=28), only loss of chromosome 4q22.1–4q35.2 was significantly associated with disease relapse (p < 0.05, FDR < 0.15). No differences in clinicopathological characteristics between patients with and without relapse were observed.Conclusion: In the present series of MSS stage II colon cancer patients losses on 4q22.1–4q35.2 were associated with worse outcome and these genomic alterations may aid in selecting patients for adjuvant therapy.
Comparison of Different Promoter Methylation Assays in Breast Cancer
Authors: Suijkerbuijk Karijn P. M. , Pan Xiaojuan , van der Wall Elsken , van Diest Paul J. , Vooijs Marc 
Published: January 2015

Background: Promoter hypermethylation has emerged as a promising cancer biomarker. Currently, a large variety of quantitative and non-quantitative techniques is used to measure methylation in clinical specimens. Here we directly compared three commonly used methylation assays and assessed the influence of tissue fixation, target sequence location and the amount of DNA on their performance.Methods: We used Methylation-Specific PCR (MSP), Quantitative Multiplex MSP (QM-MSP) and Methylation-Specific Multiplex Ligation-dependent Probe Amplification (MS-MLPA) to compare methylation of CCND2, SCGB3A1, RARB and RASSF1 on DNA from 40 breast carcinomas.Results: A comparison between MSP and QM-MSP on the same samples showed a high discrepancy: 20% of tumors that showed no methylation in MSP gave >10% methylation in QM-MSP. In contrast, QM-MSP correlated strongly with MS-MLPA when targeting the same sequence in DNA from paraffin embedded as well as fresh frozen tissue. This correlation declined when target sequences were non-overlapping. In titration experiments, MSP and MS-MLPA performed robust with 10 ng of DNA, while QM-MSP was at least ten-fold more sensitive.Conclusion: Despite the difference in molecular basis, QM-MSP and MS-MLPA showed moderate to strong correlations. In contrast, there was a poor concordance between either of these techniques and non-quantitative MSP. For biological samples with scarce DNA, QM-MSP is the method of choice.
Gene Expression in Oligodendroglial Tumors
Authors: Shaw Elisabeth J. , Haylock Brian , Husband David , du Plessis Daniel , Sibson D. Ross , Warnke Peter C. , Walker Carol 
Published: January 2015

Background: Oligodendroglial tumors with 1p/19q loss are more likely to be chemosensitive and have longer survival than those with intact 1p/19q, but not all respond to chemotherapy, warranting investigation of the biological basis of chemosensitivity.Methods: Gene expression profiling was performed using amplified antisense RNA from 28 oligodendroglial tumors treated with chemotherapy (26 serial stereotactic biopsy, 2 resection). Expression of differentially expressed genes was validated by real-time PCR.Results: Unsupervised hierarchical clustering showed clustering of multiple samples from the same case in 14/17 cases and identified subgroups associated with tumor grade and 1p/19q status. 176 genes were differentially expressed, 164 being associated with 1p/19q loss (86% not on 1p or 19q). 94 genes differed between responders and non-responders to chemotherapy; 12 were not associated with 1p/19q loss. Significant differential expression was confirmed in 11/13 selected genes. Novel genes associated with response to therapy includedSSBP2,GFRA1,FAPandRASD1.IQGAP1,INA,TGIF1,NR2F2andMYCBPwere differentially expressed in oligodendroglial tumors with 1p/19q loss.Conclusion: Gene expression profiling using serial stereotactic biopsies indicated greater homogeneity within tumors than between tumors. Genes associated with 1p/19q status or response were identified warranting further elucidation of their role in oligodendroglial tumors.
TS Gene Polymorphisms Are Not Good Markers of Response to 5-FU Therapy in Stage III Colon Cancer Patients
Authors: Fariña-Sarasqueta A. , Gosens M. J. E. M. , Moerland E. , van Lijnschoten I. , Lemmens V. E. P. P. , Slooter G. D. , Rutten H. J. T. , van den Brule A. J. C. 
Published: January 2015

Aim: Although the predictive and prognostic value of thymidylate synthase (TS) expression and gene polymorphism in colon cancer has been widely studied, the results are inconclusive probably because of methodological differences. With this study, we aimed to elucidate the role of TS gene polymorphisms genotyping in therapy response in stage III colon carcinoma patients treated with 5-FU adjuvant chemotherapy.Patients and Methods: 251 patients diagnosed with stage III colon carcinoma treated with surgery followed by 5-FU based adjuvant therapy were selected. The variable number of tandem repeats (VNTR) and the single nucleotide polymorphism (SNP) in the 5′-untranslated region of the TS gene were genotyped.Results: There was a positive association between tumor T stage and the VNTR genotypes (p=0.05). In both univariate and multivariate survival analysis no effects of the studied polymorphisms on survival were found. However, there was an association between both polymorphisms and age. Among patients younger than 60 years, the patients homozygous for 2R seemed to have a better overall survival, whereas among the patients older than 67 this longer survival was seen by the carriers of other genotypes.Conclusion: We conclude that the TS VNTR and SNP do not predict response to 5-FU therapy in patients with stage III colon carcinoma. However, age appears to modify the effects of TS polymorphisms on survival.