bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrastructural Complexity of Nuclear Components During Early Apoptotic Phases in Breast Cancer Cells
Authors: Castelli Christian , Losa Gabriele A.
Published: January 2015

Fractal morphometry was used to investigate the ultrastructural features of the plasma membrane, perinuclear membrane and nuclear chromatin in SK‐BR‐3 human breast cancer cells undergoing apoptosis. Cells were incubated with 1 μM calcimycin (A23187) for 24 h. Cells in the early stage of apoptosis had fractal dimension (FD) values indicating that their plasma membranes were less rough (lower FD) than those of control cells, while their perinuclear membranes were unaffected. Changes of the chromatin texture within the entire nucleus and in selected nuclear domains were more pronounced in treated cells. This confirms that the morphological reorganization imputable to a loss of structural complexity (reduced FD) occurs in the early stage of apoptosis, is accompanied by the inhibition of distinct enzymatic events and precedes the onset of conventional cellular markers, which can only be detected during the active phases of the apoptotic process.
Application of Pfortran and Co‐Array Fortran in the Parallelization of the GROMOS96 Molecular Dynamics Module
Authors: Bała Piotr , Clark Terry , Scott L. Ridgway
Published: January 2015

After at least a decade of parallel tool development, parallelization of scientific applications remains a significant undertaking. Typically parallelization is a specialized activity supported only partially by the programming tool set, with the programmer involved with parallel issues in addition to sequential ones. The details of concern range from algorithm design down to low‐level data movement details. The aim of parallel programming tools is to automate the latter without sacrificing performance and portability, allowing the programmer to focus on algorithm specification and development. We present our use of two similar parallelization tools, Pfortran and Cray′s Co‐Array Fortran, in the parallelization of the GROMOS96 molecular dynamics module. Our parallelization started from the GROMOS96 distribution′s shared‐memory implementation of the replicated algorithm, but used little of that existing parallel structure. Consequently, our parallelization was close to starting with the sequential version. We found the intuitive extensions to Pfortran and Co‐Array Fortran helpful in the rapid parallelization of the project. We present performance figures for both the Pfortran and Co‐Array Fortran parallelizations showing linear speedup within the range expected by these parallelization methods.
Cluster Analysis of Comparative Genomic Hybridization (CGH) Data Using Self‐Organizing Maps: Application to Prostate Carcinomas
Authors: Mattfeldt Torsten , Wolter Hubertus , Kemmerling Ralf , Gottfried Hans‐Werner , Kestler Hans A.
Published: January 2015

Comparative genomic hybridization (CGH) is a modern genetic method which enables a genome‐wide survey of chromosomal imbalances. For each chromosome region, one obtains the information whether there is a loss or gain of genetic material, or whether there is no change at that region. Usually it is not possible to evaluate all 46 chromosomes of a metaphase, therefore several (up to 20 or more) metaphases are analyzed per individual, and expressed as average. Mostly one does not study one individual alone but groups of 20–30 individuals. Therefore, large amounts of data quickly accumulate which must be put into a logical order. In this paper we present the application of a self‐organizing map (Genecluster) as a tool for cluster analysis of data from pT2N0 prostate cancer cases studied by CGH. Self‐organizing maps are artificial neural networks with the capability to form clusters on the basis of an unsupervised learning rule, i.e., in our examples it gets the CGH data as only information (no clinical data). We studied a group of 40 recent cases without follow‐up, an older group of 20 cases with follow‐up, and the data set obtained by pooling both groups. In all groups good clusterings were found in the sense that clinically similar cases were placed into the same clusters on the basis of the genetic information only. The data indicate that losses on chromosome arms 6q, 8p and 13q are all frequent in pT2N0 prostatic cancer, but the loss on 8p has probably the largest prognostic importance.
Workload Decomposition Strategies for Shared Memory Parallel Systems with OpenMP
Authors: Di Martino Beniamino , Briguglio Sergio , Vlad Gregorio , Fogaccia Giuliana
Published: January 2015

A crucial issue in parallel programming (both for distributed and shared memory architectures) is work decomposition. Work decomposition task can be accomplished without large programming effort with use of high‐level parallel programming languages, such as OpenMP. Anyway particular care must still be payed on achieving performance goals. In this paper we introduce and compare two decomposition strategies, in the framework of shared memory systems, as applied to a case study particle in cell application. A number of different implementations of them, based on the OpenMP language, are discussed with regard to time efficiency, memory occupancy, and program restructuring effort.
Efficiently Building On‐line Tools for Distributed Heterogeneous Environments
Authors: Rackl Günther , Ludwig Thomas , Lindermeier Markus , Stamatakis Alexandros
Published: January 2015

Software development is getting more and more complex, especially within distributed middleware‐based environments. A major drawback during the overall software development process is the lack of on‐line tools, i.e. tools applied as soon as there is a running prototype of an application. The MIMO MIddleware MOnitor provides a solution to this problem by implementing a framework for an efficient development of on‐line tools. This paper presents a methodology for developing on‐line tools with MIMO. As an example scenario, we choose a distributed medical image reconstruction application, which represents a test case with high performance requirements. Our distributed, CORBA‐based application is instrumented for being observed with MIMO and related tools. Additionally, load balancing mechanisms are integrated for further performance improvements. As a result, we obtain an integrated tool environment for observing and steering the image reconstruction application. By using our rapid tool development process, the integration of on‐line tools shows to be very convenient and enables an efficient tool deployment.
Dynamic Load Balancing of Samr Applications on Distributed Systems
Authors: Lan Zhiling , Taylor Valerie E. , Bryan Greg
Published: January 2015

Dynamic load balancing(DLB) for parallel systems has been studied extensively; however, DLB for distributed systems is relatively new. To efficiently utilize computing resources provided by distributed systems, an underlying DLB scheme must address both heterogeneous and dynamic features of distributed systems. In this paper, we propose a DLB scheme for Structured Adaptive Mesh Refinement(SAMR) applications on distributed systems. While the proposed scheme can take into consideration (1) the heterogeneity of processors and (2) the heterogeneity and dynamic load of the networks, the focus of this paper is on the latter. The load‐balancing processes are divided into two phases: global load balancing and local load balancing. We also provide a heuristic method to evaluate the computational gain and redistribution cost for global redistribution. Experiments show that by using our distributed DLB scheme, the execution time can be reduced by 9%‐ to using parallel DLB scheme which does not consider the heterogeneous and dynamic features of distributed systems.
Evaluation of Prognostic Factors Following Flow‐Cytometric DNA Analysis after Cytokeratin Labelling: II. Cervical and Endometrial Cancer
Authors: Wimberger Pauline , Hillemanns Peter , Kapsner Thomas , Hepp Hermann , Kimmig Rainer
Published: January 2015

In gynecologic oncology valid prognostic factors are necessary to define biologically similar subgroups for analysis of therapeutic efficacy. This study is the first published prospective study concerning prognostic significance of DNA ploidy and S‐phase fraction in cervical and endometrial cancer following enrichment of tumor cells by cytokeratin labelling. Epithelial cells were labeled by FITC‐conjugated cytokeratin antibody (CK 5, 6, 8, and CK 17) prior to flow cytometric cell cycle analysis in 91 specimens of cervical cancer and 73 samples of endometrial cancer. In cervical cancer neither DNA‐ploidy nor S‐phase fraction were relevant prognostic parameters. But CV of the G0G1‐peak showed prognostic relevance in cervical cancer cells, even in multivariate analysis. This interesting observation, however, seems to have no therapeutic consequence due to the small discrimination capacity of CV. In endometrial carcinoma, gross DNA‐aneuploidy (DNA‐index > 1.3) and a high percentage of proliferating cells (>75th percentile) were univariate and multivariate highly significant prognostic factors for recurrence‐free survival. Especially DNA‐aneuploidy (DI>1.3) is one of the most important independent molecular biological prognostic factors. While diagnostic curettage we could identify risk patients even preoperatively by determination of the prognostic factors like histologic tumor type, grading, cervical involvement and DNA‐ploidy. Thereby these patients could be treated primarily in an oncologic center. In conclusion, our investigations showed that the determination of DNA‐ploidy should be done in endometrial carcinoma. In cervical cancer no clinical significance for determination of DNA‐parameters was found.
Telomerase Activity Levels in the Surgical Margin and Tumour Distant Tissue of the Squamous Cell Carcinoma of the Head‐And‐Neck
Authors: Fabricius Eva‐Maria , Gurr Ulrike , Wildner Gustav‐Paul
Published: January 2015

The survival of patients with a head‐and‐neck squamous cell carcinoma is determined by loco‐regional recurrence and second primary carcinomas. As a complement to histopathology, molecular changes of tumour marginal and tumour distant tissue may confirm curative surgical tumour extirpation. We tested telomerase activity with PCR‐ELISA kits. 20 tumour margin biopsies were chosen by the surgeon from 20 patients. In addition, 3 tissue samples were taken from each of 20 additional patients, one from the carcinoma centre, the tumour margin and one distant from the tumour. 50% of the carcinoma centres were telomerase‐positive. Thirteen of the 40 tumour margin samples showed increased telomerase levels, and in 3 of these residual carcinoma was histopathologically detected. Six of the 20 tumour distant tissues revealed increased telomerase levels. Telomerase positivity in carcinoma‐free tumour margins correlated with a good prognosis. Confirmation of the results in a larger patient group is needed.
The UNICORE Grid Infrastructure
Authors: Romberg Mathilde
Published: January 2015

UNICORE (Uniform Interface to Computer Resources) is a software infrastructure supporting seamless and secure access to distributed resources. UNICORE allows uniform access to different hardware and software platforms as well as different organizational environments. Based on the abstract job model it offers services for security, translation of abstract jobs into real batch jobs for different target systems, and a public key infrastructure. This paper describes the UNICORE architecture and the services provided.
OpenMP Programming for a Global Inverse Model
Authors: Wang Ping , Wu Xiaoping
Published: January 2015

The objective of our investigation is to establish robust inverse algorithms to convert GRACE gravity and ICESat altimetry mission data into global current and past surface mass variations. To assess separation of global sources of change and to evaluate spatio‐temporal resolution and accuracy statistically from full posterior covariance matrices, a high performance version of a global simultaneous grid inverse algorithm is essential. One means to accomplish this is to implement a general, well‐optimized, parallel global model on massively parallel supercomputers. In our present work, an efficient parallel version of a global inverse program has been implemented on the Origin 2000 using the OpenMP programming model. In this paper, porting a sequential global code to a shared‐memory computing system is discussed; several efficient strategies to optimize the code are reported; well‐optimized scientific libraries are used; detailed parallel implementation of the global model is reported; performance data of the code are analyzed. Scaling performance on a shared‐memory system is also discussed. The parallel version software gives good speedup and dramatically reduces total data processing time.
On Determining the Order of Markov Dependence of an Observed Process Governed by a Hidden Markov Model
Authors: Boys R.J. , Henderson D.A.
Published: January 2015

This paper describes a Bayesian approach to determining the order of a finite state Markov chain whose transition probabilities are themselves governed by a homogeneous finite state Markov chain. It extends previous work on homogeneous Markov chains to more general and applicable hidden Markov models. The method we describe uses a Markov chain Monte Carlo algorithm to obtain samples from the (posterior) distribution for both the order of Markov dependence in the observed sequence and the other governing model parameters. These samples allow coherent inferences to be made straightforwardly in contrast to those which use information criteria. The methods are illustrated by their application to both simulated and real data sets.
Grids: The Top Ten Questions
Authors: Schopf Jennifer M. , Nitzberg Bill
Published: January 2015

The design and implementation of a national computing system and data grid has become a reachable goal from both the computer science and computational science point of view. A distributed infrastructure capable of sophisticated computational functions can bring many benefits to scientific work, but poses many challenges, both technical and socio‐political. Technical challenges include having basic software tools, higher‐level services, functioning and pervasive security, and standards, while socio‐political issues include building a user community, adding incentives for sites to be part of a user‐centric environment, and educating funding sources about the needs of this community. This paper details the areas relating to Grid research that we feel still need to be addressed to fully leverage the advantages of the Grid.
CD10 Expression in Non‐Small Cell Lung Cancer
Authors: Kristiansen Glen , Schlüns Karsten , Yongwei Yu , Dietel Manfred , Petersen Iver
Published: January 2015

CD10 is a cell surface endopeptidase that inactivates various potentially growth stimulatory peptides. In lung cancer cell lines this downregulation has been associated with increased proliferation. Downregulation of CD10 in lung cancer tissue is described, suggesting a potential role in carcinogenesis and a possible use of CD10 as a prognostic marker. We aimed to determine the rate of CD10 expression in our non‐small cell lung cancer (NSCLC) collection and to clarify its correlation with clinicopathological parameters and patient survival. 114 NSCLC were analysed immunohistochemically using a monoclonal CD10 antibody (clone NCL‐CD10‐270) on an NSCLC tissue micro array. The staining was semiquantitatively scored. CD10 expression was observed in 19% of cases, without any significant association with tumour type, ‐size, ‐grading, nodal status, clinical stage, and patient survival time. We conclude that a diagnostic use of CD10 immunostaining in NSCLC is unlikely.
An Integrated System for Feature Evaluation of 3D Images of a Tissue Specimen
Authors: Umesh Adiga P.S.
Published: January 2015

In this article we have proposed an integrated system for measurement of important features from 3D tissue images. We propose a segmentation technique, where we combine several methods to achieve a good degree of automation. Important histological and cytological three‐dimensional features and strategies to measure them are described. Figures can be viewed in colour on http://www.esacp.org/acp/2002/24‐23/adiga.htm
Fitting Hidden Markov Models to Psychological Data
Authors: Visser Ingmar , Raijmakers Maartje E.J. , Molenaar Peter C.M.
Published: January 2015

Markov models have been used extensively in psychology of learning. Applications of hidden Markov models are rare however. This is partially due to the fact that comprehensive statistics for model selection and model assessment are lacking in the psychological literature. We present model selection and model assessment statistics that are particularly useful in applying hidden Markov models in psychology. These statistics are presented and evaluated by simulation studies for a toy example. We compare AIC, BIC and related criteria and introduce a prediction error measure for assessing goodness‐of‐fit. In a simulation study, two methods of fitting equality constraints are compared. In two illustrative examples with experimental data we apply selection criteria, fit models with constraints and assess goodness‐of‐fit. First, data from a concept identification task is analyzed. Hidden Markov models provide a flexible approach to analyzing such data when compared to other modeling methods. Second, a novel application of hidden Markov models in implicit learning is presented. Hidden Markov models are used in this context to quantify knowledge that subjects express in an implicit learning task. This method of analyzing implicit learning data provides a comprehensive approach for addressing important theoretical issues in the field.
Chromosomal Regions in Prostatic Carcinomas Studied by Comparative Genomic Hybridization, Hierarchical Cluster Analysis and Self‐Organizing Feature Maps
Authors: Mattfeldt Torsten , Wolter Hubertus , Trijic Danilo , Gottfried Hans‐Werner , Kestler Hans A.
Published: January 2015

Comparative genomic hybridization (CGH) is an established genetic method which enables a genome‐wide survey of chromosomal imbalances. For each chromosome region, one obtains the information whether there is a loss or gain of genetic material, or whether there is no change at that place. Therefore, large amounts of data quickly accumulate which must be put into a logical order. Cluster analysis can be used to assign individual cases (samples) to different clusters of cases, which are similar and where each cluster may be related to a different tumour biology. Another approach consists in a clustering of chromosomal regions by rewriting the original data matrix, where the cases are written as rows and the chromosomal regions as columns, in a transposed form. In this paper we applied hierarchical cluster analysis as well as two implementations of self‐organizing feature maps as classical and neuronal tools for cluster analysis of CGH data from prostatic carcinomas to such transposed data sets. Self‐organizing maps are artificial neural networks with the capability to form clusters on the basis of an unsupervised learning rule. We studied a group of 48 cases of incidental carcinomas, a tumour category which has not been evaluated by CGH before. In addition we studied a group of 50 cases of pT2N0‐tumours and a group of 20 pT3N0‐carcinomas. The results show in all case groups three clusters of chromosomal regions, which are (i) normal or minimally affected by losses and gains, (ii) regions with many losses and few gains and (iii) regions with many gains and few losses. Moreover, for the pT2N0‐ and pT3N0‐groups, it could be shown that the regions 6q, 8p and 13q lay all on the same cluster (associated with losses), and that the regions 9q and 20q belonged to the same cluster (associated with gains). For the incidental cancers such clear correlations could not be demonstrated.
Flow Cytometric Bivariate Analysis of DNA and Cytokeratin in Colorectal Cancer
Authors: Post Carolin , Christensen Ib Jarle , Flyger Henrik , Christiansen Jette , Larsen Jørgen K.
Published: January 2015

Different opinions about flow cytometric estimates of DNA aneuploidy and/or S‐phase fraction (SPF) as supplementary prognostic markers in colorectal cancer are to some degree associated with methodology. Using univariate DNA analysis, we have previously investigated the DNA ploidy in colorectal cancer, its heterogeneity within and between tumors and its relation to survival. To improve detection of DNA aneuploid subpopulations and particularly estimation of their SPF′s we investigated a method for bivariate DNA/cytokeratin analysis on fine‐needle aspirates of 728 frozen biopsies from 157 colorectal tumors. Unfixed aspirates were stained with propidium iodide and FITC‐conjugated anti‐cytokeratin antibody in a saponin‐buffer. A significant association between SPF and debris was observed. There were no substantial difference in DNA ploidy patterns between univariate and bivariate measurements (concordance was 92–95%). No new DNA aneuploid subpopulations were detected in cytokeratin‐gated compared to ungated or univariate histograms. Debris‐adjusted SPF′s of cytokeratin‐gated histograms were significantly higher than of ungated histograms, also for subpopulations with DI>1.4 (p < 0.0001). There was no significant
association between SPF and survival.
ARMS: An Agent‐Based Resource Management System for Grid Computing
Authors: Cao Junwei , Jarvis Stephen A. , Saini Subhash , Kerbyson Darren J. , Nudd Graham R.
Published: January 2015

Resource management is an important component of a grid computing infrastructure. The scalability and adaptability of such systems are two key challenges that must be addressed. In this work an agent‐based resource management system, ARMS, is implemented for grid computing. ARMS utilises the performance prediction techniques of the PACE toolkit to provide quantitative data regarding the performance of complex applications running on a local grid resource. At the meta‐level, a hierarchy of homogeneous agents are used to provide a scalable and adaptable abstraction of the system architecture. Each agent is able to cooperate with other agents and thereby provide service advertisement and discovery for the scheduling of applications that need to utilise grid resources. A case study with corresponding experimental results is included to demonstrate the efficiency of the resource management and scheduling system.
How Good is OpenMP
Authors: Mattson Timothy G.
Published: January 2015

The OpenMP standard defines an Application Programming Interface (API) for shared memory computers. Since its introduction in 1997, it has grown to become one of the most commonly used API′s for parallel programming. But success in the market doesn′t necessarily imply successful computer science. Is OpenMP a "good" programming environment? What does it even mean to call a programming environment good? And finally, once we understand how good or bad OpenMP is; what can we do to make it even better? In this paper, we will address these questions.
Interprocedural Definition‐Use Chains of Dynamic Pointer‐Linked Data Structures
Authors: Hwang Yuan-Shin , Saltz Joel
Published: January 2015

This paper presents a flow‐sensitive algorithm to compute interprocedural definition‐use chains of dynamic pointer‐linked data structures. The goal is to relate the statements that construct links of dynamic pointer‐linked data structures (i.e. definitions) to the statements that might traverse the structures through the links (i.e. uses). Specifically, for each statement S that defines links of pointer‐linked data structures, the algorithm finds the set of statements that traverse the links which are defined by S. This algorithm solves the definition‐use chaining problem by performing backward iterative data flow analysis to compute the set of upward exposed uses at each statement. The results of this algorithm can be used to identify parallelism in programs even with cyclic pointer‐linked data structures.
Implementing a High Performance Tensor Library
Authors: Landry Walter
Published: January 2015

Template methods have opened up a new way of building C++ libraries. These methods allow the libraries to combine the seemingly contradictory qualities of ease of use and uncompromising efficiency. However, libraries that use these methods are notoriously difficult to develop. This article examines the benefits reaped and the difficulties encountered in using these methods to create a friendly, high performance, tensor library. We find that template methods mostly deliver on this promise, though requiring moderate compromises in usability and efficiency.
In Vitro Model for Studying Malignancy Associated Changes
Authors: Sun Xiao Rong , Zheng Yonghong , MacAulay Calum , Lam Stephen , Doudkine Alexei , Palcic Branko
Published: January 2015

Malignancy associated changes (MAC) can be defined as subtle morphological and physiologic changes that are found in ostensibly normal cells of patients harboring malignant disease. It has been postulated that MAC have a potential to become a useful tool in detection, diagnosis and prognosis of malignant diseases. An in vitro cell culture model system was designed to study interactions between non‐small cell lung cancer (NSCLC) and the normal bronchial epithelium of the human respiratory tract in vivo to see if the MAC‐like phenomenon can be detected in such a system. In this study we examined changes in nuclear features of normal human bronchial epithelial cells (NHBE) when they were co‐cultured with cells derived from a lung cancer cell line NCI‐H460. Using discriminant function analysis, nuclear features were determined which allow maximal discrimination between normal cells incubated with or without cancerous cells. Our results demonstrate that MAC appear to be specific to changes induced by malignancy, and that these changes differ from those induced by growth factors in the serum. This study provides evidence in support to the hypothesis that MAC are induced by a soluble factor(s) released by malignant cells. Colour figure can be viewed on http://www.esacp.org/acp/2003/25‐2/sun.htm.
OpenMP Issues Arising in the Development of Parallel BLAS and LAPACK Libraries
Authors: Addison C. , Ren Y. , van Waveren M.
Published: January 2015

Dense linear algebra libraries need to cope efficiently with a range of input problem sizes and shapes. Inherently this means that parallel implementations have to exploit parallelism wherever it is present. While OpenMP allows relatively fine grain parallelism to be exploited in a shared memory environment it currently lacks features to make it easy to partition computation over multiple array indices or to overlap sequential and parallel computations. The inherent flexible nature of shared memory paradigms such as OpenMP poses other difficulties when it becomes necessary to optimise performance across successive parallel library calls. Notions borrowed from distributed memory paradigms, such as explicit data distributions help address some of these problems, but the focus on data rather than work distribution appears misplaced in an SMP context.
Earliest Detection of Oral Cancer Using Non‐Invasive Brush Biopsy Including DNA‐Image‐Cytometry: Report on Four Cases
Authors: Remmerbach Torsten W. , Weidenbach Horst , Hemprich Alexander , Böcking Alfred
Published: January 2015

Objective: We describe four patients presenting early oral cancers, detected cytologically on non‐invasive brush biopsies including DNA‐image cytometry as an adjunctive method before histology on scalpel biopsies confirmed the evidence of malignancy. Methods: Brush biopsies were performed and smears thereof investigated cytologically. After Feulgen restaining, DNA‐measurements were performed using a DNA‐Image‐Cytometer. Case reports: Oral squamous cell carcinomas were diagnosed cytologically in macroscopically suspicious lesions and malignancy confirmed by DNA‐cytometry. The initially performed scalpel biopsies did neither supply evidence of oral cancer nor of severe dysplasia. After at least one to 15 months the occurrence of cancer was finally proven histologically on a second scalpel biopsy each (three microinvasive and one in situ carcinoma). Conclusion: Non‐invasive brush biopsies are a suitable instrument for early cytologic detection of cancer of the mouth. DNA‐image‐cytometry, as an adjunctive method, can be used to confirm the cytologic diagnosis or suspicion of cancer in patients with doubtful lesions (dysplasias). DNA‐aneuploidy is a marker for (prospective) malignancy in smears of the oral cavity, which may detect malignancy months prior to histology. In future this method could be used as a mass screening tool in dentists practise. Colour figures can be viewed on http://www.esacp.org/acp/2003/25‐4/remmerbach.htm.
DNA Extraction from Bronchial Aspirates for Molecular Cytology: Which Method to Take?
Authors: Grote Hans Jürgen , Schmiemann Viola , Sarbia Mario , Böcking Alfred
Published: January 2015

Objective: To date, there are only few systematic reports on the quality of DNA extracted from routine diagnostic cytologic specimens. It was the aim of the present study to evaluate the ability of 50% ethanol/2% carbowax (Saccomanno fixative) to preserve bronchial secretions with high quality genomic DNA as well as to compare different DNA extraction methods. Methods: DNA was extracted from 45 bronchial aspirates by four different extraction protocols. Beside DNA yield, DNA quality with regard to purity, integrity, and PCR success rate were investigated. Results: No fragmentation of sample DNA due to the fixative was detected. It was preserved as high molecular weight DNA. DNA yield, purity, and integrity were dependent on the DNA extraction method to some extend. Irrespective of the DNA extraction method the PCR success rate for amplification of β‐globin gene fragments (268, 536, and 989 bp) was 100%. Conclusions: A fixative containing 50% ethanol/2% carbowax preserves high quality DNA which is well suited for PCR‐based assays regardless of the extraction protocol used. The selection of the DNA extraction protocol has to be adjusted to the circumstances of application.
An Original Approach for Quantification of Blood Vessels on the Whole Tumour Section
Authors: Kim Nga Tran , Elie Nicolas , Plancoulaine Benoît , Herlin Paulette , Coster Michel
Published: January 2015

Relative abundance of tumour angiogenesis has been shown to be of clinical relevance in cancers of various locations such as the ovary. Nevertheless, several problems are encountered when quantifying tumour microvessels: (i) as many other tumour markers, vascularity pattern is often heterogeneous within the tumour mass and even within the same histological section. As a consequence, an adequate acquisition method must be developed for accurate field sampling. (ii) Manual microvessel counting is long, tedious and subject to poor reproducibility. Introduction in routine practice requires a fast, reproducible and reliable automatic image processing. In this study we present an original procedure combining a slide scanner image acquisition and a fully automatic image analysis sequence. The slide scanner offers the advantage of recording an image of the whole histological section for subsequent automatic blood vessel detection and hot spot area location. Microvessel density and surface fraction were measured for the whole section as well as within hot spots. Different immunostaining methods were tested in order to optimise the procedure. Moreover, the method proposed was submitted to a quality control procedure, with reference to interactive identification of microvessels at scanner level. This experiment showed that 93 to 97% of blood vessels were detected, according to the staining protocol used. Colour figures can be viewed on http://www.esacp.org/acp/2003/25‐2/kim.htm.
Application of Multilevel Models to Morphometric Data. Part 1. Linear Models and Hypothesis Testing
Authors: Tsybrovskyy O. , Berghold A.
Published: January 2015

Morphometric data usually have a hierarchical structure (i.e., cells are nested within patients), which should be taken into consideration in the analysis. In the recent years, special methods of handling hierarchical data, called multilevel models (MM), as well as corresponding software have received considerable development. However, there has been no application of these methods to morphometric data yet. In this paper we report our first experience of analyzing karyometric data by means of MLwiN – a dedicated program for multilevel modeling. Our data were obtained from 34 follicular adenomas and 44 follicular carcinomas of the thyroid. We show examples of fitting and interpreting MM of different complexity, and draw a number of interesting conclusions about the differences in nuclear morphology between follicular thyroid adenomas and carcinomas. We also demonstrate substantial advantages of multilevel models over conventional, single‐level statistics, which have been adopted previously to analyze karyometric data. In addition, some theoretical issues related to MM as well as major statistical software for MM are briefly reviewed.
A Feature Set for Cytometry on Digitized Microscopic Images
Authors: Rodenacker Karsten , Bengtsson Ewert
Published: January 2015

Feature extraction is a crucial step in most cytometry studies. In this paper a systematic approach to feature extraction is presented. The feature sets that have been developed and used for quantitative cytology at the Laboratory for Biomedical Image Analysis of the GSF as well as at the Center for Image Analysis in Uppsala over the last 25 years are described and illustrated. The feature sets described are divided into morphometric, densitometric, textural and structural features. The latter group is used to describe the eu‐ and hetero‐chromatin in a way complementing the textural methods. The main goal of the paper is to bring attention to the need of a common and well defined description of features used in cyto‐ and histometrical studies. The application of the sets of features is shown in an overview of projects from different fields. Finally some rules of thumb for the design of studies in this field are proposed. Colour figures can be viewed on http://www.esacp.org/acp/2003/25‐1/rodenacker.htm.
Expression of the Cell Adhesion Molecule CD146/MCAM in Non‐Small Cell Lung Cancer
Authors: Kristiansen Glen , Yu Yongwei , Schlüns Karsten , Sers Christine , Dietel Manfred , Petersen Iver
Published: January 2015

Expression of MCAM is observed in a variety of human malignancies. We aimed to determine the rate of MCAM expression in our non‐small cell lung cancer (NSCLC) collection and to clarify its correlation with clinicopathological parameters and patient survival. 85 NSCLC were analysed immunohistochemically using a monoclonal MCAM antibody (clone N1238) on an NSCLC tissue micro array. The staining was semiquantitatively scored. We found MCAM expression in 51% of NSCLC, preferentially squamous cell carcinomas (p=0.004). No other correlations to tumour size, grade, or stage were found. Univariate survival analysis showed no significant differences of MCAM positive and negative tumours. In adenocarcinomas however, MCAM positivity was significantly associated with shorter patient survival (p=0.016). We conclude, that MCAM is expressed in a high proportion of NSCLC and might be predictive of shortened patient survival in adenocarcinomas of the lung. Colour figure can be viewed on http://www.esacp.org/acp/2003/25-2/kristiansen.htm.
Automated Detection of Working Area of Peripheral Blood Smears Using Mathematical Morphology
Authors: Angulo Jesús , Flandrin Georges
Published: January 2015

The paper presents a technique to automatically detect the working area of peripheral blood smears stained with May‐Grünwuald Giemsa. The optimal area is defined as the well spread part of the smear. This zone starts when the erythrocytes stop overlapping (on the body film side) and finishes when the erythrocytes start losing their clear central zone (on the feather edge side). The approach yields a quick detection of this area in images scanned under low magnifying power (immersion objective ×25 or ×16). The algorithm consists of two stages. First, an image analysis procedure using mathematical morphology is applied for extracting the erythrocytes, the centers of erythrocytes and the erythrocytes with center. Second, the number of connected components from the three kinds of particles is counted and the coefficient of spreading ρs and the coefficient of overlapping ρo are calculated. The data from fourteen smears illustrate how the technique is used and its performance. Colour figures can be viewed on http://www.esacp.org/acp/2003/25‐1/angulo.htm.
Diagnostic Value of Nucleolar Organizer Regions (AgNORs) in Brush Biopsies of Suspicious Lesions of the Oral Cavity
Authors: Remmerbach Torsten W. , Weidenbach Horst , Müller Conrad , Hemprich Alexander , Pomjanski Natalja , Buckstegge Birgit , Böcking Alfred
Published: January 2015

Objective: The aim of this retrospective study was to report on the diagnostic accuracy of AgNOR‐analysis as an adjunctive diagnostic tool of conventional oral exfoliative cytology taken from suspicious lesions in our clinic. Study design: Cytological diagnoses obtained from brush biopsies of macroscopically suspicious lesions of the oral mucosa from 75 patients (final diagnoses: 53 histologically proven squamous cell carcinomas, 11 leukoplakias and other inflammatory oral lesions) and from 11 patients with normal mucosa as a negative control group were compared with histological and/or clinical follow‐ups. Five smears were doubtful and seven suspicious for tumor cells in the cytologic report. Number of AgNOR′s were counted in 100 squamous epithelial cell‐nuclei per slide after silver‐restaining. Results: Sensitivity of our cytological diagnosis alone on oral smears for the detection of squamous carcinomas was 92.5%, specificity 100%, positive predictive value was 100% and negative 84.6%. The best cut‐off value of the mean number of AgNOR dots per nucleus distinguishing benign from malignant cells was 4.8. The percentage of nuclei with more than three AgNORs had a cut‐off level of 70%. Applying these methods to twelve doubtful or suspicious cytological diagnoses we were able to correctly establish the diagnosis of malignancy in ten cases of histologically proven cancers and to reveal benignity in two histologically proven cases. Thus we achieved a positive and negative predictive value of 100% each. Conclusions: Smears from brushings of visible oral lesions, if clinically considered as suspicious for cancer, are an easily practicable, non‐invasive, painless, safe and accurate screening method for detection of oral cancerous lesions. We conclude that AgNOR‐analysis may be a useful adjunct to other methods in routine cytological diagnosis of oral cancer that can help to solve cytologically suspicious or doubtful cases. Colour figures can be viewed on http://www.esacp.org/acp/2003/25‐3/remmerbach.htm.
A Tool for Performance Modeling of Parallel Programs
Authors: González J.A. , Rodríguez C. , Rodríguez G. , de Sande F. , Printista M.
Published: January 2015

Current performance prediction analytical models try to characterize the performance behavior of actual machines through a small set of parameters. In practice, substantial deviations are observed. These differences are due to factors as memory hierarchies or network latency. A natural approach is to associate a different proportionality constant with each basic block, and analogously, to associate different latencies and bandwidths with each "communication block". Unfortunately, to use this approach implies that the evaluation of parameters must be done for each algorithm. This is a heavy task, implying experiment design, timing, statistics, pattern recognition and multi‐parameter fitting algorithms. Software support is required. We present a compiler that takes as source a C program annotated with complexity formulas and produces as output an instrumented code. The trace files obtained from the execution of the resulting code are analyzed with an interactive interpreter, giving us, among other information, the values of those parameters.
Gain in 1q is a Common Abnormality in Phyllodes Tumours of the Breast
Authors: Jee Kowan J. , Gong Gyungyub , Ahn Sei Hyun , Park Jeong Mi , Knuutila Sakari
Published: January 2015

We studied DNA copy number changes by CGH and allelic imbalance (AI) on 3p by LOH analysis on 22 phyllodes tumours (PT) of the breast in order to gain insight into the genetic basis of tumour progression in PT. Copy number changes were observed in 14 cases (63%). Gain in 1q with 1q21–23 as the minimal overlapping area was seen in 12 cases (55%). The gain was observed both in benign and malignant tumours. Our study did not reveal any DNA copy number changes or allelic loss on 3p. The results suggest that DNA copy number changes are not associated with the histological grade or clinical behaviour of PT and the chromosomal changes on 3p appear to be rare. Colour figure can be viewed on http://www.esacp.org/acp/2003/25‐2/jee.htm.
A Multiprogramming Aware OpenMP Implementation
Authors: Barekas Vasileios K. , Hadjidoukas Panagiotis E. , Polychronopoulos Eleftherios D. , Papatheodorou Theodore S.
Published: January 2015

In this work, we present an OpenMP implementation suitable for multiprogrammed environments on Intel‐based SMP systems. This implementation consists of a runtime system and a resource manager, while we use the NanosCompiler to transform OpenMP‐coded applications into code with calls to our runtime system. The resource manager acts as the operating system scheduler for the applications built with our runtime system. It executes a custom made scheduling policy to distribute the available physical processors to the active applications. The runtime system cooperates with the resource manager in order to adapt each application′s generated parallelism to the number of processors allocated to it, according to the resource manager scheduling policy. We use the OpenMP version of the NAS Parallel Benchmark suite in order to evaluate the performance of our implementation. In our experiments we compare the performance of our implementation with that of a commercial OpenMP implementation. The comparison proves that our approach performs better both on a dedicated and on a heavily multiprogrammed environment.
Quantitation of Monoclonal Plasma Cells in Bone Marrow Biopsies in Plasma Cell Dyscrasia
Authors: Markey G. M. , Kettle P. , Morris T. C. M. , Connolly N. , Foster H.
Published: January 2015

Direct measurement of monoclonal plasma cell mass in bone marrow biopsies may be a useful parameter to establish in plasma cell dyscrasia. In this study monoclonal plasma cells/mm2 in light chain immunoglobulin immunostained archival bone marrow sections from 22 patients in whom a diagnosis of multiple myeloma (MM) had been excluded but who had monoclonal proteins were counted by two observers at light microscopic level. There was good correlation between the counts of the two observers. The levels of monoclonal plasma cells/mm2 in biopsies were not related to the % counts in the aspirates taken at the same time as the biopsies. Three of seven patients with biopsy levels in excess of the polyclonal levels in patients without plasma cell dyscrasia developed progressive MM within the observation time. Monoclonal plasma cell levels/mm2 of bone marrow biopsies can be measured and they provide a useful parameter for the assessment of patients with low volume plasma cell dyscrasia. Colour figure can be viewed on http://www.esacp.org/acp/2003/25‐4/markey.htm.
An Interactive Environment for Supporting the Transition from Simulation to Optimization
Authors: Bischof Christian H. , Bücker H. Martin , Lang Bruno , Rasch Arno
Published: January 2015

Numerical simulation is a powerful tool in science and engineering, and it is also used for optimizing the design of products and experiments rather than only for reproducing the behavior of scientific and engineering systems. In order to reduce the number of simulation runs, the traditional "trial and error" approach for finding near‐to‐optimum design parameters is more and more replaced with efficient numerical optimization algorithms. Done by hand, the coupling of simulation and optimization software is tedious and error‐prone. In this note we introduce a software environment called EFCOSS (Environment For Combining Optimization and Simulation Software) that facilitates and speeds up this task by doing much of the required work automatically. Our framework includes support for automatic differentiation providing the derivatives required by many optimization algorithms. We describe the process of integrating the widely used computational fluid dynamics package FLUENT and a MINPACK‐1 least squares optimizer into EFCOSS and follow a sample session solving a data assimilation problem.
Mixed‐Language High‐Performance Computing for Plasma Simulations
Authors: Lu Quanming , Getov Vladimir
Published: January 2015

Java is receiving increasing attention as the most popular platform for distributed computing. However, programmers are still reluctant to embrace Java as a tool for writing scientific and engineering applications due to its still noticeable performance drawbacks compared with other programming languages such as Fortran or C. In this paper, we present a hybrid Java/Fortran implementation of a parallel particle‐in‐cell (PIC) algorithm for plasma simulations. In our approach, the time‐consuming components of this application are designed and implemented as Fortran subroutines, while less calculation‐intensive components usually involved in building the user interface are written in Java. The two types of software modules have been glued together using the Java native interface (JNI). Our mixed‐language PIC code was tested and its performance compared with pure Java and Fortran versions of the same algorithm on a Sun E6500 SMP system and a Linux cluster of Pentium~III machines.
Pattern Operators for Grid Environments
Authors: Gomes Maria Cecília , Rana Omer F. , Cunha José C.
Published: January 2015

A pattern based approach for developing applications in a Grid computing environment is presented, and is based on the ability to manage components and their interactions. The approach provides a formal way of combining recurrent themes in Grid applications, and provides a set of operators that may be used to manipulate the patterns. The operators may be applied to individual patterns or groups, and may be managed as an independent library. The patterns distinguish between service providers and users, and may be used to also analyse the properties of a collection of components, or to vary these properties subject to a set of predefined constraints. Patterns are expressed in the Unified Modelling Language (UML), and operators correspond to manipulation of components within each pattern.
Analysis of Ploidy in Hypopharyngeal Cancer by Laser Scanning Cytometry on Fine Needle Aspirate Biopsies
Authors: Gerstner Andreas O.H. , Machlitt Julia , Welkoborsky Hans‐Jürgen , Bootz Friedrich , Tárnok Attila
Published: January 2015

Aim To test laser scanning cytometry (LSC) for the analysis of ploidy in squamous cell carcinoma of the hypopharynx (SCCH) and to develop a routine application for minimal samples such as fine needle aspirate biopsies (FNABs). Methods: From 11 individuals 30 FNABs of primary tumors (n=11) and lymphatic metastases of SCCH (n=11) and non‐metastatic lymph nodes (n=8) are analyzed by LSC. This microscope based instrument scans the cells after immobilization on a glass slide and after double staining of cytokeratin and DNA. The location of each cell is stored with the fluorescence data. Therefore the morphology of every cell can be documented by re‐staining with H&E and re‐localization on the slide. Additionally, aliquots are Feulgen‐stained for image cytometry in 8 specimens. Results: The diploid reference peak is identified taking leukocytes as internal standard. The DNA‐index of the carcinoma cells ranges from 0.4 to 3.8. Comparison with image cytometry shows good correlation (r=0.89). Conclusion: LSC provides a reliable and objective way to determine the ploidy of SCCH pre‐operatively. Colour figures can be viewed on http://www.esacp.org/acp/2003/25‐2/gerstner.htm.