bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Tumor Heterogeneity of Prostate Carcinoma by Flow‐ and Image DNA Cytometry and Histopathological Grading
Authors: Wang Naining , Wilkin Claudia , Böcking Alfred , Tribukait Bernhard
Published: January 2015

Background. Heterogeneity of prostate carcinoma is one of the reasons for pretreatment underestimation of tumor aggressiveness. We studied tumor heterogeneity and the probability of finding the highest tumor grade and DNA aneuploidy with relation to the number of biopsies. Material and methods. Specimens simulating core biopsies from five randomly selected tumor areas from each of 16 Böcking’s grade II and 23 grade III prostate carcinomas were analyzed for tumor grade and DNA ploidy by flow‐ and fluorescence image cytometry (FCM, FICM). Cell cycle composition was measured by FCM. Results. By determination of ploidy and cell cycle composition, morphologically defined tumors can further be subdivided. Heterogeneity of tumor grade and DNA ploidy (FCM) was 54% and 50%. Coexistence of diploid tumor cells in aneuploid specimens represents another form of tumor heterogeneity. The proportion of diploid tumor cells decreased significantly with tumor grade and with increase in the fraction of proliferating cell of the aneuploid tumor part. The probability of estimating the highest tumor grade or aneuploidy increased from 40% for one biopsy to 95% for 5 biopsies studied. By combining the tumor grade with DNA ploidy, the probability of detecting a highly aggressive tumor increased from 40% to 70% and 90% for one and two biopsies, respectively. Conclusion. Specimens of the size of core biopsies can be used for evaluation of DNA ploidy and cell cycle composition. Underestimation of aggressiveness of prostate carcinoma due to tumor heterogeneity is minimized by simultaneous study of the tumor grade and DNA ploidy more than by increasing the number of biopsies. The biological significance of coexistent diploid tumor cell in aneuploid lesions remains to be evaluated.
An Algebraic Programming Style for Numerical Software and Its Optimization
Authors: Dinesh T.B. , Haveraaen Magne , Heering Jan
Published: January 2015

The abstract mathematical theory of partial differential equations (PDEs) is formulated in terms of manifolds, scalar fields, tensors, and the like, but these algebraic structures are hardly recognizable in actual PDE solvers. The general aim of the Sophus programming style is to bridge the gap between theory and practice in the domain of PDE solvers. Its main ingredients are a library of abstract datatypes corresponding to the algebraic structures used in the mathematical theory and an algebraic expression style similar to the expression style used in the mathematical theory. Because of its emphasis on abstract datatypes, Sophus is most naturally combined with object‐oriented languages or other languages supporting abstract datatypes. The resulting source code patterns are beyond the scope of current compiler optimizations, but are sufficiently specific for a dedicated source‐to‐source optimizer. The limited, domain‐specific, character of Sophus is the key to success here. This kind of optimization has been tested on computationally intensive Sophus style code with promising results. The general approach may be useful for other styles and in other application domains as well.
DNA Ploidy and Chromosomal Imbalances in Invasive Ductal Breast Cancer. A Comparative Study of DNA Image Cytometry and Comparative Genomic Hybridization (CGH)
Authors: Friedrich Katrin , Scheithauer Jens , Dimmer Volker , Meyer Wolfdietrich , Theissig Franz , Haroske Gunter , Kunze Klaus Dietmar
Published: January 2015

Chromosomal imbalances were analyzed in 62 breast cancers with different DNA ploidy by CGH. The results of DNA image cytometry and CGH are consistent with peridiploid and aneuploid cases. The peritetraploid tumors harbored a high number of chromosomal imbalances, as a hint for an unfavorable prognosis. The quantitative analysis of imbalances highlighted the role of different physical constituents of the chromosome, and of chromosomal losses in different DNA ploidy groups. The peritetraploid and aneuploid tumors differed from the peridiploid tumors in losses at 8p and 18q. The peritetraploid cancers exhibited more gains at 8q, the aneuploid tumors more losses at 17p than their peridiploid counterparts. The aneuploid cases differed from the peritetraploid tumors in a higher number of losses at 11q and 14q. Combinations of imbalances provide further insights into the genetic background of DNA ploidy. Hypotheses for the progression from peridiploid to nondiploid breast cancers are given.

Figures on http://www.esacp.org/acp/2000/20-2_3/friedrich.htm.
Nuclear DNA Content and Chromatin Pattern of Rat Rhabdomyosarcoma Cell Sublines with Different Metastatic Potentials
Authors: Dufer Jean , Poupon Marie-France , Yatouji Sonia
Published: January 2015

There is a constant need of features able to characterize potentially metastatic cells among the heterogeneous cell subpopulations which constitute a tumor. Image cytometry of metastatic tumor cells give rise to variable results, partly because of a heterogeneous origin of cells, or potential drug effects. The aim of this work was to characterize nuclear changes observed in metastatic cell clones issued in vitro from the same parental cell population The nuclear phenotypes of 6 cell sublines isolated from a rat rhabdomyosarcoma cell line and differing in their metastatic ability were evaluated by image cytometry on Feulgen‐stained preparations. Densitometric [5], geometric [3] and textural [9] features were computed from each nuclear image. For each cell subline, a metastatic score, ranging from 0 to 10, was calculated on the basis of in vitro invasivity data, by measuring the number of pulmonary metastases observed after s.c. graft of tumor cells in rats. Data obtained were compared to karyotype, growth characteristics, and oncogene expressions of cell lines. The nuclear DNA content, the chromosome numbers, the cell sublines doubling times, and the distribution of cells within the cell cycle appear unrelated with this score. On the contrary, increase in metastatic ability is accompanied by changes in chromatin pattern as assessed by textural features. Progressive increase in chromatin condensation can be observed in cell sublines with increasing metastatic score. These results were confirmed by an unsupervised multivariate partitioning of rhabdomyosarcoma cells which identified two separate subsets whose distributions within the analyzed cell lines correlate with their metastatic ability. These data suggest that, in rat rhabdomyosarcoma cell sublines, metastatic ability could be associated with nuclear morphological changes at the level of chromatin texture.
A Scalable Version of the Navy Operational Global Atmospheric Prediction System Spectral Forecast Model
Authors: Rosmond Thomas E.
Published: January 2015

The Navy Operational Global Atmospheric Prediction System (NOGAPS) includes a state‐of‐the‐art spectral forecast model similar to models run at several major operational numerical weather prediction (NWP) centers around the world. The model, developed by the Naval Research Laboratory (NRL) in Monterey, California, has run operational at the Fleet Numerical Meteorological and Oceanographic Center (FNMOC) since 1982, and most recently is being run on a Cray C90 in a multi‐tasked configuration. Typically the multi‐tasked code runs on 10 to 15 processors with overall parallel efficiency of about 90%. resolution is T159L30, but other operational and research applications run at significantly lower resolutions. A scalable NOGAPS forecast model has been developed by NRL in anticipation of a FNMOC C90 replacement in about 2001, as well as for current NOGAPS research requirements to run on DOD High‐Performance Computing (HPC) scalable systems. The model is designed to run with message passing (MPI). Model design criteria include bit reproducibility for different processor numbers and reasonably efficient performance on fully shared memory, distributed memory, and distributed shared memory systems for a wide range of model resolutions. Results for a wide range of processor numbers, model resolutions, and different vendor architectures are presented. Single node performance has been disappointing on RISC based systems, at least compared to vector processor performance. This is a common complaint, and will require careful re‐examination of traditional numerical weather prediction (NWP) model software design and data organization to fully exploit future scalable architectures.
New Approaches to Molecular Profiling of Tissue Samples
Authors: Best Carolyn J. M. , Gillespie John W. , Englert Chad R. , Swalwell Jennifer I. , Pfeifer John , Krizman David B. , Petricoin Emanuel F. , Liotta Lance A. , Emmert-Buck Michael R.
Published: January 2015

Figures on http://www.esacp.org/acp/2000/20-1/best.htm.
The Same‐Source Parallel MM5
Authors: Michalakes John
Published: January 2015

Beginning with the March 1998 release of the Penn State University/NCAR Mesoscale Model (MM5), and continuing through eight subsequent releases up to the present, the official version has run on distributed ‐memory (DM) parallel computers. Source translation and runtime library support minimize the impact of parallelization on the original model source code, with the result that the majority of code is line‐for‐line identical with the original version. Parallel performance and scaling are equivalent to earlier, hand‐parallelized versions; the modifications have no effect when the code is compiled and run without the DM option. Supported computers include the IBM SP, Cray T3E, Fujitsu VPP, Compaq Alpha clusters, and clusters of PCs (so‐called Beowulf clusters). The approach also is compatible with shared‐memory parallel directives, allowing distributed‐memory/shared‐memory hybrid parallelization on distributed‐memory clusters of symmetric multiprocessors.
Immunohistochemical Assessment of the Tumour‐Associated Epitopes CD44v6 and E48 in Tumour‐Free Lymph Nodes from Patients with Squamous Cell Carcinoma in the Head‐Neck Region
Authors: Fabricius Eva-Maria , Guschmann Michael , Langford Angelika , Hell Berthold , Bier Jürgen
Published: January 2015

We examined immunohistochemically 370 tumour‐free lymph nodes from 41 patients with a head and neck squamous cell carcinoma (HNSCC) to clarify whether the tumour‐associated epitopes CD44v6 and E48 are suitable for adjuvant postoperative immunotherapy. All the positively immunostained cells found were single cells.

CD44v6+ cells were found in 55% of the lymph nodes, with their numbers increasing in pN>0‐patients (62%). Only pN>0‐patients had abundant to massive CD44v6+ cells. A comparison with mononuclear cells in lymphatic tissue from control patients suggested a similarity with activated T‐cells. In the 41 cancer patients there were significantly fewer lymph nodes with E48+ cells (11%), but the number of E48+ cells increased in pN>1‐patients (29%) with predominantly abundant E48+ cells. We conclude from the comparison with the epithelial marker EMA that the E48+ single cells are epithelial in origin. Only a specific E48 peptide sequence appears suitable for adjuvant immunotherapy in patients with head‐neck tumours.
Intratumor Heterogeneity of K‐Ras and p53 Mutations among Human Colorectal Adenomas Containing Early Cancer
Authors: Giaretti Walter , Macciocu Barbara , Geido Elio , Hermsen Mario , Postma Cindy , Baak Jan , Williams Richard , Meijer Gerrit
Published: January 2015

The molecular pathways and the timing of genetic events during human colorectal carcinogenesis are still not fully understood. We have addressed the intratumor heterogeneity of the mutational status of the k‐ras oncogene and of the p53 oncosuppressor gene during the adenoma–carcinoma sequence by investigating 26 human colorectal adenomas containing early cancer. An intratumor comparative analysis was obtained among the adenomatous and carcinomatous component pairs. Additionally, we have analyzed 17 adenomas having cancer in the near vicinity.
The adenomatous components of the adenomas containing early cancer and the adenomas having cancer in the near vicinity had comparable frequencies for k‐ras mutations (28 and 47%) but different for p53 mutations (52 and 7%, p‐value = 0.01). Interestingly, the adenomatous and carcinomatous components of the adenomas containing early cancer were rarely heterogeneous for the k‐ras mutational status (only in 13% of the cases) but were characterized by heterogeneity of the p53 status in 59% of the cases (p‐value < 0.01). In addition, the mutations of p53 for the adenomatous components of the adenomas containing early cancer were statistically significantly associated with severe dysplasia (p‐value = 0.01).
Intratumor homogeneity of k‐ras status during the human colorectal adenoma–carcinoma sequence suggests that the role of k‐ras is more related to tumor initiation than to tumor progression. On the contrary, intratumor heterogeneity of p53 mutations indicates that the type of the p53 mutations may also be relevant for selection and expansion of new subclones leading to tumor progression.

Erratum to “Intratumor Heterogeneity of k-ras and p53 Mutations Among Human Colorectal Adenomas Containing Early Cancer”dx.doi.org/10.1155/2001/905923
Current Experiences with Internet Telepathology and Possible Evolution in the Next Generation of Internet Services
Authors: Della Mea V. , Beltrami C. A.
Published: January 2015

The last five years experience has definitely demonstrated the possible applications of the Internet for telepathology. They may be listed as follows: (a) teleconsultation via multimedia e‐mail; (b) teleconsultation via web‐based tools; (c) distant education by means of World Wide Web; (d) virtual microscope management through Web and Java interfaces; (e) real‐time consultations through Internet‐based videoconferencing. Such applications have led to the recognition of some important limits of the Internet, when dealing with telemedicine: (i) no guarantees on the quality of service (QoS); (ii) inadequate security and privacy; (iii) for some countries, low bandwidth and thus low responsiveness for real‐time applications. Currently, there are several innovations in the world of the Internet. Different initiatives have been aimed at an amelioration of the Internet protocols, in order to have quality of service, multimedia support, security and other advanced services, together with greater bandwidth.

The forthcoming Internet improvements, although induced by electronic commerce, video on demand, and other commercial needs, are of real interest also for telemedicine, because they solve the limits currently slowing down the use of Internet. When such new services will be available, telepathology applications may switch from research to daily practice in a fast way.
Technical Aspects of Telepathology with Emphasis on Future Development
Authors: Schwarzmann P. , Binder B. , Klose R.
Published: January 2015

Pathology undergoes presently changes due to new developments in diagnostic opportunities and cost saving efforts in health care. Out of the wide field of telepathology the paper selects three prototype applications: telepathology in teleeducation, expert advice for preselected details of a slide and finally telepathology for remote diagnosis. The most challenging field for remote diagnosis is the application in the frozen section scenario. The paper starts with the mental experiment to map conventional procedures to counterparts in telepathology.

Technical opportunities and economical restrictions of telepathology equipment are discussed with respect to the components: electronic camera, display devices, haptic sensors and displays, available telecommunication channels and telepathology software.

As an example and for illustration of the state of the art for an advanced telemicroscopy system able to perform remote frozen section diagnosis, the HISTKOM equipment is presented in more details.

The section concerning future developments regards the aspects of the acceptance by tentative users, legal aspects, costs and affordability of equipment, the market for equipment components and the adequate telecommunication services. Further is regarded the mutual influence of properties of existing systems and application experiences gained with them on the next generation of equipment and application software. Conclusions and references close the paper.
Different Proliferation Patterns in Breast Cancer: AgNOR Measurements in ER‐Negative and ER‐Positive Tumor Cells
Authors: Günther Lukas , Hufnagl Peter , Winzer Klaus‐Jürgen , Guski Hans
Published: January 2015

The relation between estrogen receptors (ER) and argyrophilic nucleolar organizer regions (AgNORs) in situ within human breast cancer cells was analyzed. For AgNOR measurements in 49 invasive breast carcinomas, a new reproducible staining method for dual demonstration of ER and AgNORs was applied. Quantitative AgNOR variables were determined in ER‐positive and ER‐negative tumor cells by digital image analysis. The relationships between AgNOR parameters of ER‐positive and ER‐negative cells and other prognostic factors of breast cancer [Bloom–Richardson‐Grading and growth fraction (Ki‐67 index)] were investigated. A higher AgNOR content in ER‐negative cells and a special clustering phenomenon in ER‐positive tumor cells were found. Correlation with other criteria of malignant potential could be exclusively demonstrated for ER‐negative cells. ER‐negative cells of breast cancer can be characterized as the more malignant and possibly prognosis‐dictating cell fraction. Thus, ER‐negative cells probably contribute more to the progression of the tumor disease and furthermore to the prognosis than ER‐positive cells. We recommend measurement AgNORs exclusively in ER‐negative cells of breast cancer.
Heterogeneous Chromosomal Aberrations in Intraductal Breast Lesions Adjacent to Invasive Carcinoma
Authors: Aubele Michaela , Cummings Margaret , Walch Axel , Zitzelsberger Horst , Nährig Jörg , Höfler Heinz , Werner Martin
Published: January 2015

There is evidence that breast cancer is a heterogeneous disease phenotypically as well as molecular biologically. So far, heterogeneity on the molecular biological level has not been investigated in potential precursor lesions, such as ductal hyperplasia (DH) and ductal carcinoma in situ (DCIS). In this study we applied comparative genomic hybridization (CGH) to formalin‐fixed, paraffin‐embedded breast tissue with DH and DCIS, adjacent to invasive ductal carcinoma (IDC), to screen these potential precursor lesions for whole genomic chromosomal imbalances. Laser‐microdissection was used to select pure cell populations from the sections. Isolated DNA was amplified by degenerate oligonucleotide primed PCR (DOP‐PCR) and further processed for CGH analysis.

Investigating multiple samples (n=25) from four patients we found an average of 5.6 ± 0.9 (mean ± SEM) chromosomal imbalances already present in DH. In the twelve DCIS lesions an average of 10.8 (±0.9) aberrations was identified with 14.8 (±0.8) aberrations in the four adjacent IDC lesions. The increasing number of chromosomal changes in parallel with the histopathological sequence corroborate the hypothesis, that the carcinomas may have developed through a sequential progression from normal to proliferative epithelium and eventually into carcinoma. However, heterogeneous results were identified in the multiple samples per entity from the same patient, demonstrated mainly in the DCIS samples in the chromosomal regions 6p, 9p, 11q, 16p and 17q, in the DH samples by 3p, 16p and 17q. This heterogeneous findings were most pronounced within the DH and was less in the DCIS and IDC samples. The only aberration consistently found in all samples – even in all DH samples – was amplification of the 20q13 region.

Our results demonstrate, that the applied combination of laser‐microdissection, DOP‐PCR and CGH, may serve to analyse breast carcinogenesis pathways in suitable histological material. However, so far, it is unclear how to handle heterogeneous results and these make identification of relevant changes more difficult. Setting a threshold and valuating only those chromosomal changes which are present in a majority of samples may be one possibility. This involves however, the risk that infrequent but possibly significant aberrations may be missed.

Figures on http://www.esacp.org/acp/2000/20‐1/aubele.htm.
A Debugging Standard for High‐Performance Computing
Authors: Francioni Joan M. , Pancake Cherri M.
Published: January 2015

Throughout 1998, the High Performance Debugging Forum worked on defining a base level standard for high performance debuggers. The standard had to meet the sometimes conflicting constraints of being useful to users, realistically implementable by developers, and architecturally independent across multiple platforms. To meet criteria for timeliness, the standard had to be defined in one year and in such a way that it could be implemented within an additional year. The Forum was successful, and in November 1998 released Version 1 of the HPD Standard. Implementations of the standard are currently underway. This paper presents an overview of Version 1 of the standard and an analysis of the process by which the standard was developed. The status of implementation efforts and plans for follow‐on efforts are discussed as well.
Genetic Instability Promotes the Acquisition of Chromosomal Imbalances in T1b and T1c Breast Adenocarcinomas
Authors: Blegen Harald , Ghadimi B. Michael , Jauho Annukka , Zetterberg Anders , Eriksson Elina , Auer Gert , Ried Thomas
Published: January 2015

In order to evaluate biological and genetic properties of early breast carcinomas we analyzed microdissected tissue from 33 primary breast carcinomas stage T1b and T1c with respect to the nuclear DNA content, the expression pattern of Ki‐67, cyclin A, p27KIP1, p53 and p21WAF1, and chromosomal gains and losses. The results show that T1b carcinomas (6–10 mm, n=17) were frequently near‐diploid (53%) with low proliferative activity and staining patterns of p53 and p21WAF1 that suggest the presence of wild type protein. The majority (12/16) of the T1c tumors (11–20 mm), however, was aneuploid, and proliferative activity and p53 expression were increased. Larger tumor size correlated with an increasing number of chromosomal copy number changes and in particular with regional amplifications. High level copy number increases (amplifications), however, were found exclusively in the aneuploid tumors. Amplification events correlated with elevated cyclin A and reduced p27 expression, respectively. Our results suggest that the sequential acquisition of genomic imbalances during tumor progression is accelerated in aneuploid tumors, and may contribute to the increased malignancy potential.
Laminin‐5 γ2 Chain Expression Correlates with Unfavorable Prognosis in Colon Carcinomas
Authors: Lenander C. , Habermann J. K. , Öst Å. , Nilsson B. , Schimmelpenning H. , Tryggvason K. , Auer G.
Published: January 2015

Expression of the γ2 chain at the invasive front of different tumors has indicated an important role for laminin‐5 in cell migration during tumor invasion and tissue remodeling. As there is considerable need for reliable invasion and prognostic markers we evaluated the correlation of laminin‐5 γ2 chain expression with clinicopathologic parameters and patient survival in 93 primary colon carcinomas. Epithelial cells of normal mucosa were consistently negative for staining. In contrast, positive cytoplasmic staining was observed in 89 tumors (96%). Twenty‐four (26%) cases were scored as sparse, 34 (37%) as moderate, and 31 (33%) as frequent γ2 chain expression. There was a significant association of laminin‐5 γ2 chain expression and local invasiveness of colon carcinomas according to Dukes stage (A‐C) (p = 0.001) and tumor budding (p < 0.001). A statistical significance could also be noted in decreasing tumor differentiation (p < 0.001) and correlation to tumor size (p = 0.032). No correlation was observed to tumor site. Univariate analysis identified laminin‐5 (p = 0.010), tumor differentiation (p = 0.006) and Dukes grade (p < 0.001) as significant variables in predicting prognosis. However, by multivariate analyses, this study could not demonstrate that laminin‐5 γ2 chain expression is an independent predictive factor for survival. The results indicate that laminin‐5 γ2 chain expression is up‐regulated during the progression of human colon cancer and that it plays a role in the aggressiveness of these tumors. Demonstration of laminin‐5 γ2 chain positivity also facilitates detection of individual cells or minor cell clusters invading the surrounding stroma.
Amplification at 9p in Cervical Carcinoma by Comparative Genomic Hybridization
Authors: Jee Kowan J. , Kim Young Tak , Kim Kyu Rae , Aalto Yan , Knuutila Sakari
Published: January 2015

DNA copy number changes were studied by comparative genomic hybridization on 10 tumor specimens of squamous cell carcinoma of cervix obtained from Korean patients. DNA was extracted from paraffin‐embedded sections after removal of non‐malignant cells by microdissection technique. Copy number changes were found in 8/10 tumors. The most frequent changes were chromosome 19 gains (n=6) and losses on chromosomes 4 (n=4), 5 (n=3), and 3p (n=3). A novel finding was amplification in chromosome arm 9p21‐pter in 2 cases. Gains in 1, 3q, 5p, 6p, 8q, 16p, 17, and 20q and losses at 2q, 6q, 8p, 9q, 10p, 11, 13, 16q, and 18q were observed in at least one of the cases.
Compiler Optimization Techniques for OpenMP Programs
Authors: Satoh Shigehisa , Kusano Kazuhiro , Sato Mitsuhisa
Published: January 2015

We have developed compiler optimization techniques for explicit parallel programs using the OpenMP API. To enable optimization across threads, we designed dataflow analysis techniques in which interactions between threads are effectively modeled. Structured description of parallelism and relaxed memory consistency in OpenMP make the analyses effective and efficient. We developed algorithms for reaching definitions analysis, memory synchronization analysis, and cross‐loop data dependence analysis for parallel loops. Our primary target is compiler‐directed software distributed shared memory systems in which aggressive compiler optimizations for software‐implemented coherence schemes are crucial to obtaining good performance. We also developed optimizations applicable to general OpenMP implementations, namely redundant barrier removal and privatization of dynamically allocated objects. Experimental results for the coherency optimization show that aggressive compiler optimizations are quite effective for a shared‐write intensive program because the coherence‐induced communication volume in such a program is much larger than that in shared‐read intensive programs.
High Resolution Comparative Genomic Hybridization Detects 7–8 Megabasepair Deletion in PCR Amplified DNA1
Authors: Larsen Jacob , Ottesen Anne Marie , Kirchhoff Maria , Lundsteen Claes , Larsen Jørgen K.
Published: January 2015

We investigated if any change in spatial resolution of comparative genomic hybridization analysis could be detected when using DNA amplified by degenerate oligonucleotide primed PCR (DOP‐PCR) as opposed to the use of unamplified DNA. Five DNA samples from B‐cell leukemias with small 11q deletions were amplified by DOP‐PCR and analysed by means of high resolution comparative genomic hybridization (HR‐CGH) for the evaluation of aberration size detection limit. By means of HR‐CGH, we found the detection limit of DOP‐PCR CGH for deletions to be between 3 Mbp and 7–8 Mbp.
Ovarian Carcinoma and Serous Effusions. Changing Views Regarding Tumor Progression and Review of Current Literature1
Authors: Davidson Ben
Published: January 2015

Carcinoma of the ovary is the leading cause of death from gynecological cancer in western countries. Ovarian carcinoma is commonly associated with the accumulation of fluid containing malignant cells in the peritoneal, and not infrequently in the pleural cavity. The differentiation of these cells from reactive mesothelial cells is at times difficult. In addition, tumor progression in ovarian carcinoma and the biological characteristics of carcinoma cells in effusions compared to their counterparts in solid tumors are poorly understood. This review details the current knowledge regarding diagnostic and biologic aspects of effusion cytology, with emphasis on ovarian carcinoma. Results from our first studies of effusions are subsequently presented. These attempt to address several issues. First, to improve the diagnostic ability to detect cancer cells in effusions using antibodies designed for the differentiation of epithelial cells from mesothelial cells. Secondly, to study genotypic and phenotypic differences between ovarian carcinoma cells in effusions, solid primary tumors and metastatic lesions, as well as to compare malignant cells in peritoneal and pleural effusions. These studies of carbohydrate antigens, E‐cadherin complex and matrix metalloproteinases (MMP) attempted to evaluate whether ovarian carcinoma cells in effusions possess true metastatic properties, or are similar to the cells in primary tumors, thereby merely representing the result of a shedding process. Finally, the prognostic role of these molecules was studied in solid tumors from a patient cohort consisting of long‐ and short‐term survivors, followed for up to 20 years. Figure 1 on http://www.esacp.org/acp/2001/23‐3,4/davidson.htm.
An Iterative Solver Benchmark
Authors: Dongarra Jack , Eijkhout Victor , Vorst Henk van der
Published: January 2015

We present a benchmark of iterative solvers for sparse matrices. The benchmark contains several common methods and data structures, chosen to be representative of the performance of a large class of methods in current use. We give results on some high performance processors that show that performance is largely determined by memory bandwidth.
Prognostic Significance of DNA Cytometry in Carcinoma of the Uterine Cervix FIGO Stage IB and II
Authors: Grote Hans Jürgen , Friedrichs Nicolaus , Pomjanski Natalia , Guhde Helen Friderike , Reich Olaf , Böcking Alfred
Published: January 2015

Objective: To assess the prognostic value of DNA‐image cytometry in cervical carcinoma of the uterus and its relation to other established prognostic factors. Study design: The study included 116 cases of cervical carcinoma FIGO stages IB and II which were treated with radical abdominal hysterectomy. The median follow‐up was 55 months (range 1–162 months). DNA image cytometry was performed on cytologic specimens prepared by enzymatic cell separation from formalin‐fixed, paraffin‐embedded tissues. DNA stemline ploidy, DNA stemline aneuploidy, 5c exceeding rate, 9c exceeding rate, 2c deviation index, and DNA malignancy grade were computed. DNA‐variables as well as various clinical and histological variables were related to survival rates. Results: In multivariate statistical analysis DNA stemline ploidy using 2.2c as a cut‐off value and FIGO stage showed to be statistically significant available presurgery predictors of survival, whereas the postsurgical parameters lymphonodal status, tumor size and parametrial involvement were significantly correlated with survival. The synopsis of all parameters in a multivariate Cox model indicated that – with declining relevance – the number of positive pelvic lymph nodes, DNA stemline ploidy using a cut‐off level at a modal value of 2.2c, largest pelvic lymph node, 5c exceeding rate, and ratio of carcinoma area to cervix area, were of predictive value for survival. Conclusions: Our results suggest that prognostic information deducted from classical staging parameters is successfully complemented by DNA image cytometry which can be applied pretherapeutically.
Automated Detection of Connective Tissue by Tissue Counter Analysis and Classification and Regression Trees
Authors: Smolle Josef , Kahofer Peter
Published: January 2015

Objective: To evaluate the feasibility of the CART (Classification and Regression Tree) procedure for the recognition of microscopic structures in tissue counter analysis. Methods: Digital microscopic images of H&E stained slides of normal human skin and of primary malignant melanoma were overlayed with regularly distributed square measuring masks (elements) and grey value, texture and colour features within each mask were recorded. In the learning set, elements were interactively labeled as representing either connective tissue of the reticular dermis, other tissue components or background. Subsequently, CART models were based on these data sets. Results: Implementation of the CART classification rules into the image analysis program showed that in an independent test set 94.1% of elements classified as connective tissue of the reticular dermis were correctly labeled. Automated measurements of the total amount of tissue and of the amount of connective tissue within a slide showed high reproducibility (r=0.97 and r=0.94, respectively; p < 0.001). Conclusions: CART procedure in tissue counter analysis yields simple and reproducible classification rules for tissue elements.
Telomerase Activity in Cervical Smears
Authors: Saretzki G. , Fischer H. , Kaufmann I.-G. , Schewe C. , Nadjari B. , Blohmer J. , Hauptmann St.
Published: January 2015

It is well known that almost all carcinoma cells including those of the uterine cervix have re‐established their telomerase activity. However, until now there is no conclusive picture on the telomerase activity in cervical dysplasias and about their relationship to HPV infection. To investigate this question, material from 34 patients (15 with normal epithelium, 11 with LGSIL, 8 with HGSIL) obtained by conventional cervical brushing was used and subjected to non‐radioactive TRAP‐ELISA (Boehringer Mannheim). The HPV analysis was performed by PCR on formalin‐fixed, paraffin‐embedded biopsy material obtained after cytological investigation. We could show that telomerase activity is detectable in normal cervical epithelium, and that an gradual increase exists for both telomerase activity and HPV positivity from normal epithelium to HGSIL. However, HPV infection and telomerase activity appear to be independent of each other. The high frequency of telomerase positivity in patients with normal cervical epithelium indicates that telomerase activity is not a useful differential diagnostic aid. Whether patients with telomerase‐positive dysplasias have a higher probability to progress into an invasive carcinoma remains to be clarified by follow‐up studies.
In Situ Reverse Transcriptase‐Nested Polymerase Chain Reaction to Identify Intracellular Nucleic Acids without the Necessity of Dnase Pretreatment and Hybridisation
Authors: Menschikowski Mario , Vogel Margot , Eckey Rolf , Dinnebier Gerd , Jaross Werner
Published: January 2015

In the present study a protocol of in situ reverse transcriptase‐nested polymerase chain reaction (in situ RT‐nested PCR) was examined based on the following modifications. (i) To exclude false positive signals caused by “DNA repair mechanisms” and “endogenous priming”, a two‐step PCR was applied after reverse transcription. The first step was performed in the presence of extrinsic primers and unlabeled nucleotides with a maximum of PCR cycles possible without destroying the cell morphology. The second step consisted of only one annealing/elongation reaction, the target sequence marked by addition of digoxigenin‐labeled nucleotides and intrinsic primers. (ii) In order to prevent amplifications of genomic DNA nested primer pairs were applied crossing intron sequences. (iii) To minimize the diffusion of PCR products in cells, the extrinsic primers were extended with complementary 5′‐tails. This approach results in the generation of high molecular weight concatamers during PCR cycles. By applying this protocol, immunostainings specific for phospholipase A2 of type IIA mRNA were exclusively detectable in the cytoplasm of HepG2 hepatoma cells, which were used as a model system, whereas the nuclei were unstained. Multiple control experiments yielded completely negative results. These data suggest that the in situ RT‐nested PCR, which in comparison to the method of in situ RT‐PCR‐in situ‐hybridisation is simpler and less time‐consuming, can be used as an alternative approach to identify intracellular nucleic acids.
AgNOR Count in Resting Cells (Resting NOR) Is a New Prognostic Marker in Invasive Bladder Tumor
Authors: Tomobe Mitsuro , Shimazui Toru , Uchida Katsunori , Akaza Hideyuki
Published: January 2015

Purpose: We have previously demonstrated that the AgNOR count in proliferating cells is a predictor of tumor recurrence in superficial bladder tumor (J. Urol. 162 (1999), 63–68). In the present study, we evaluate the type of AgNOR associated with cell cycles as a prognostic factor in invasive bladder tumor using a double staining technique employing both AgNOR and MIB‐1 labelling. Materials and methods: Forty‐four paraffin sections of invasive bladder tumors were stained simultaneously with AgNOR and MIB‐1. The number of AgNORs in proliferating (MIB‐1 positive) or resting (MIB‐1 negative) cells were counted from a total of 100 nuclei. Correlations between MIB‐1 associated AgNOR count and clinicopathological parameters were statistically analyzed. Results: The AgNOR count in proliferating cells (proliferating NOR) was significantly higher than that in resting cells (resting NOR) (p < 0.01). The resting NOR in tumors with distant metastases was significantly higher than that in tumors without metastases (p < 0.05). Patients with a low resting NOR tumor had a better prognosis than those with a high resting NOR tumor, whereas the proliferating NOR was not associated with survival. Survival analysis revealed that the resting NOR was the most powerful prognostic marker in patients with invasive bladder tumor (p < 0.05). Conclusions: Resting NOR had a predictive value in the prognosis of patients with invasive bladder tumor. Keywords: Transitional cell carcinoma, invasive, resting cell, AgNORs, MIB‐1
Overlapping Communication and Computation with OpenMP and MPI
Authors: Kaiser Timothy H. , Baden Scott B.
Published: January 2015

Machines comprised of a distributed collection of shared memory or SMP nodes are becoming common for parallel computing. OpenMP can be combined with MPI on many such machines. Motivations for combing OpenMP and MPI are discussed. While OpenMP is typically used for exploiting loop‐level parallelism it can also be used to enable coarse grain parallelism, potentially leading to less overhead. We show how coarse grain OpenMP parallelism can also be used to facilitate overlapping MPI communication and computation for stencil‐based grid programs such as a program performing Gauss‐Seidel iteration with red‐black ordering. Spatial subdivision or domain decomposition is used to assign a portion of the grid to each thread. One thread is assigned a null calculation region so it was free to perform communication. Example calculations were run on an IBM SP using both the Kuck & Associates and IBM compilers.
Application of OpenMP to Weather, Wave and Ocean Codes
Authors: Malfetti Paolo
Published: January 2015

Weather forecast limited area models, wave models and ocean models run commonly on vector machines or on MPP systems. Recently shared memory multiprocessor systems with ccNUMA architecture (SMP‐ccNUMA) have been shown to deliver very good performances on many applications. It is important to know that the SMP‐ccNUMA systems perform and scale well even for the above mentioned models and that a relatively simple effort is needed to parallelize the codes on these systems due to the availability of OpenMP as standard shared memory paradigm. This paper will deal with the implementation on a SGI Origin 2000 of a weather forecast model (LAMBO — Limited Area Model Bologna, the NCEP ETA model adapted to the Italian territory), a wave model (WA.M. — Wave Model, on the Mediterranean Sea and on the Adriatic Sea) and an ocean model (M.O.M. — Modular Ocean Model, used with data assimilation). These three models were written for vector machines, so the paper will describe the technique used to port a vector code to a SMP‐ccNUMA architecture. Another aspect covered by this paper are the performances that these models have on these systems.
Flow Cytometric DNA Analysis Using Cytokeratin Labeling for Identification of Tumor Cells in Carcinomas of the Breast and the Female Genital Tract
Authors: Kimmig Rainer , Wimberger Pauline , Kapsner Thomas , Hillemanns Peter
Published: January 2015

Flow cytometric assessment of DNA‐ploidy and S‐phase fraction in malignant tumors is compromised by the heterogeneity of cell subpopulations derived from the malignant and surrounding connective tissue, e.g., tumor, stromal and inflammatory cells. To evaluate the effect on quality of DNA cell cycle analysis and determination of DNA ploidy, cytokeratin labeling of epithelial cells was used for tumor cell enrichment in breast, ovarian, cervical and endometrial cancer prior to DNA analysis. In a prospective study, tumor cell subpopulations of 620 malignant tumors were labeled by a FITC‐conjugated cytokeratin antibody (CK 5, 6, CK18 and CK 5, 6, 8 and CK 17, respectively) prior to flow cytometric cell cycle analysis. Compared to total cell analysis, detection rate of DNA‐aneuploid tumors following cytokeratin labeling was increased from 62% to 76.5% in breast cancer, from 68% to 77% in ovarian cancer, from 60% to 80% in cervical cancer and from 30% to 53% in endometrial cancer. Predominantly in DNA‐diploid tumors, a significantly improved detection of S‐phase fraction of the tumor cells was shown due to the elimination of contaminating nonproliferating “normal cells”. S‐phase fraction following tumor cell enrichment was increased by 10% (mean) following cytokeratin staining in ovarian and endometrial cancer, by 30% in breast cancer and even by 70% in cervical cancer compared to total cell analysis. Thus, diagnostic accuracy of DNA‐analysis was enhanced by cytokeratin labeling of tumor cells for all tumor entities investigated.
Quantification of Tumour Vascularity in Squamous Cell Carcinoma of the Tongue Using CARD Amplification, a Systematic Sampling Technique, and True Colour Image Analysis
Authors: Hannen Egied J. M. , van der Laak Jeroen A. W. M. , Kerstens Harold M. J. , Cuijpers Vincent M. J. I. , Hanselaar Antonius G. J. M. , Manni Johannes J. , de Wilde Peter C. M.
Published: January 2015

The aims of this study of head and neck tissue samples were to develop an immunohistochemical protocol based on the catalysed reporter deposition (CARD) technique to enhance staining results for use in automated true colour image analysis, to assess the reproducibility of systematic tissue sampling in the angiogenic hot spot selection, and quantification of microvessel density (MVD) and other vessel characteristics. The latter data were compared between six metastasised tongue squamous cell carcinomas, vs. four non‐metastasised. In comparison to the standard immunohistochemical protocol with anti‐CD34 antibodies, CARD amplification resulted in both more intensely stained and larger numbers of vessels. Averaging the 10 most vascularised fields of the 40 to 60 systematically sampled fields in a tissue section resulted in an overall acceptable interobserver reproducibility for most assessed vessel parameters (r ≧ 0.76 and p ≦ 0.01). The percentage vessels with diameter <5 μm was significantly higher in the non‐metastasised tongue carcinomas (p = 0.02). However, for a number of tumours the effect of tissue sampling was significant. We conclude that CARD amplification is needed for reliable segmentation of vessels by image analysis systems, and that tumour heterogeneity is a limiting factor for all procedures in which tumour vascularity is assessed in a single tissue section.
New OpenMP Directives for Irregular Data Access Loops
Authors: Labarta J. , Ayguadé E. , Oliver J. , Henty D.S.
Published: January 2015

Many scientific applications involve array operations that are sparse in nature, ie array elements depend on the values of relatively few elements of the same or another array. When parallelised in the shared‐memory model, there are often inter‐thread dependencies which require that the individual array updates are protected in some way. Possible strategies include protecting all the updates, or having each thread compute local temporary results which are then combined globally across threads. However, for the extremely common situation of sparse array access, neither of these approaches is particularly efficient. The key point is that data access patterns usually remain constant for a long time, so it is possible to use an inspector/executor approach. When the sparse operation is first encountered, the access pattern is inspected to identify those updates which have potential inter‐thread dependencies. Whenever the code is actually executed, only these selected updates are protected. We propose a new OpenMP clause, indirect, for parallel loops that have irregular data access patterns. This is trivial to implement in a conforming way by protecting every array update, but also allows for an inspector/executor compiler implementation which will be more efficient in sparse cases. We describe efficient compiler implementation strategies for the new directive. We also present timings from the kernels of a Discrete Element Modelling application and a Finite Element code where the inspector/executor approach is used. The results demonstrate that the method can be extremely efficient in practice.
Nested Parallelism: Allocation of Threads to Tasks and OpenMP Implementation
Authors: Blikberg Ragnhild , Sørevik Tor
Published: January 2015

In this paper we discuss the use of nested parallelism. Our claim is that if the problem naturally possesses multiple levels of parallelism, then applying parallelism to all levels may significantly enhance the scalability of your algorithm. This claim is sustained by numerical experiments. We also discuss how to implement multi‐level parallelism using OpenMP. We find current OpenMP implementation, based on version 1.0, to have severe limitation for implementing nested parallelization. We then show how this can be circumvented by explicitly assign task to threads. Load balancing issues become more complicated with two (or more) levels of parallelism. To handle this problem, we have designed a distribution algorithm which groups threads into teams, each team being responsible for one course grain outer‐level task. This algorithm is proven to produce the optimal load balance, under given assumptions.
Development and Implementation of a Distributed‐Object Job‐Execution Environment
Authors: Fatoohi Rod , Smith Lance
Published: January 2015

This paper describes the development and implementation of a distributed job execution environment for highly iterative jobs. An iterative job is defined here as a binary code that is run multiple times with incremental changes in the input values for each run. An execution environment is a set of resources on a computing platform that can be made available to run the job and hold the output until it is collected. The goal is to design a complete, object‐oriented execution system that runs a variety of jobs with minimal changes. Areas of code that are unique to a specific type of job are decoupled from the rest. The system allows for fine‐grained job control, timely status notification and dynamic registration and deregistration of execution platforms depending on resources available. Several objected‐oriented technologies are employed: Java, CORBA, UML, and software design patterns. The environment has been tested using a simulation code, INS2D.