bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA Aneuploidy in Ulcerative Colitis and in Colorectal Carcinoma – A Comparative Study
Authors: Stenling Roger , Jonsson Bernt O. , Palmqvist Richard , Rutegård Jörgen N.
Published: January 2015

DNA aneuploidy is of interest as an additive marker for carcinoma risk in ulcerative colitis. It is known that colorectal carcinomas often are aneuploid with DNA indices centered around a median value of 1.5, corresponding to triploidy, and that adenomas, if aneuploid, have DNA indices closer to 2.0, the tetraploid region. In a colonoscopic surveillance programme, colorectal mucosal biopsies from 104 patients with ulcerative colitis were examined by flow cytometry, and the DNA indices determined and compared with findings of cellular dysplasia. In 17 patients, DNA aneuploidy was diagnosed, with DNA indices ranging from 1.2 to 2.0, median 1.9. Three patients with high grade dysplasia all had DNA indices within the triploid region. These results were compared with the DNA indices from a group of 49 patients with non‐colitis‐associated aneuploid colorectal carcinomas, in which the levels ranged from 1.1 to 2.0 with a median value of 1.5. Accordingly, the DNA index in the colitis patients with aneuploidy was more often within the tetraploid region. These results, obtained in patients with ulcerative colitis, indicate a possible precancerous progress from diploidy over tetraploidy to triploidy also in patients with long‐standing ulcerative colitis. In addition, the results speak in favour of a connection between DNA indices in the triploid region and more profound premalignant alterations.
Java‐Based Coupling for Parallel Predictive‐Adaptive Domain Decomposition
Authors: Germain‐Renaud Cécile , Néri Vincent
Published: January 2015

Adaptive domain decomposition exemplifies the problem of integrating heterogeneous software components with intermediate coupling granularity. This paper describes an experiment where a data‐parallel (HPF) client interfaces with a sequential computation server through Java. We show that seamless integration of data‐parallelism is possible, but requires most of the tools from the Java palette: Java Native Interface (JNI), Remote Method Invocation (RMI), callbacks and threads.
An Evaluation of Java for Numerical Computing
Authors: Blount Brian , Chatterjee Siddhartha
Published: January 2015

This paper describes the design and implementation of high performance numerical software in Java. Our primary goals are to characterize the performance of object‐oriented numerical software written in Java and to investigate whether Java is a suitable language for such endeavors. We have implemented JLAPACK, a subset of the LAPACK library in Java. LAPACK is a high‐performance Fortran 77 library used to solve common linear algebra problems. JLAPACK is an object‐oriented library, using encapsulation, inheritance, and exception handling. It performs within a factor of four of the optimized Fortran version for certain platforms and test cases. When used with the native BLAS library, JLAPACK performs comparably with the Fortran version using the native BLAS library. We conclude that high‐performance numerical software could be written in Java if a handful of concerns about language features and compilation strategies are adequately addressed.
Hydrolysis Profiles of Formalin Fixed Paraffin‐Embedded Tumors Based on IOD (Integrated Optical Density) and Nuclear Texture Feature Measurements
Authors: Fležar Margareta , Us‐Krašovec Marija , žganec Mario , Lavrenčak Jaka , Golouh Rastko
Published: January 2015

The aim of the study was to determine optimal hydrolysis time for the Feulgen DNA staining of archival formalin fixed paraffin‐embedded surgical samples, prepared as single cell suspensions for image cytometric measurements. The nuclear texture features along with the IOD (integrated optical density) of the tumor nuclei were analysed by an automated high resolution image cytometer as a function of duration of hydrolysis treatment (in 5 N HCl at room temperature). Tissue blocks of breast carcinoma, ovarian serous carcinoma, ovarian serous tumor of borderline malignancy and leiomyosarcoma were included in the study. IOD hydrolysis profiles showed plateau between 30 and 60 min in the breast carcinoma and leiomyosarcoma, and between 40 and 60 min in the ovarian serous carcinoma and ovarian serous tumor of borderline malignancy. Most of the nuclear texture features remained stable after 20 min of hydrolysis treatment. Our results indicate that the optimal hydrolysis time for IOD and for nuclear texture feature measurements, was between 40 and 60 min in the cell preparations from tissue blocks of three epithelial and one soft tissue tumor.
Flexible IDL Compilation for Complex Communication Patterns
Authors: Eide Eric , Simister James L. , Stack Tim , Lepreau Jay
Published: January 2015

Distributed applications are complex by nature, so it is essential that there be effective software development tools to aid in the construction of these programs. Commonplace “middleware” tools, however, often impose a tradeoff between programmer productivity and application performance. For instance, many CORBA IDL compilers generate code that is too slow for high‐performance systems. More importantly, these compilers provide inadequate support for sophisticated patterns of communication. We believe that these problems can be overcome, thus making idl compilers and similar middleware tools useful for a broader range of systems. To this end we have implemented Flick, a flexible and optimizing IDL compiler, and are using it to produce specialized high‐performance code for complex distributed applications. Flick can produce specially “decomposed” stubs that encapsulate different aspects of communication in separate functions, thus providing application programmers with fine‐grain control over all messages. The design of our decomposed stubs was inspired by the requirements of a particular distributed application called Khazana, and in this paper we describe our experience to date in refitting Khazana with Flick‐generated stubs. We believe that the special idl compilation techniques developed for Khazana will be useful in other applications with similar communication requirements.
Multi‐Language Programming Environments for High Performance Java Computing
Authors: Getov Vladimir , Gray Paul , Mintchev Sava , Sunderam Vaidy
Published: January 2015

Recent developments in processor capabilities, software tools, programming languages and programming paradigms have brought about new approaches to high performance computing. A steadfast component of this dynamic evolution has been the scientific community’s reliance on established scientific packages. As a consequence, programmers of high‐performance applications are reluctant to embrace evolving languages such as Java. This paper describes the Java‐to‐C Interface (JCI) tool which provides application programmers wishing to use Java with immediate accessibility to existing scientific packages. The JCI tool also facilitates rapid development and reuse of existing code. These benefits are provided at minimal cost to the programmer. While beneficial to the programmer, the additional advantages of mixed‐language programming in terms of application performance and portability are addressed in detail within the context of this paper. In addition, we discuss how the JCI tool is complementing other ongoing projects such as IBM’s High‐Performance Compiler for Java (HPCJ) and IceT’s metacomputing environment.
Breast Carcinoma, Intratumour Heterogeneity and Histological Grading, Using Geostatistics
Authors: Sharifi‐Salamatian Vénus , de Roquancourt Anne , Rigaut Jean Paul
Published: January 2015

Tumour progression is currently believed to result from genetic instability. Chromosomal patterns specific of a type of cancer are frequent even though phenotypic spatial heterogeneity is omnipresent. The latter is the usual cause of histological grading imprecision, a well documented problem, without any fully satisfactory solution up to now. The present article addresses this problem in breast carcinoma. The assessment of a genetic marker for human tumours requires quantifiable measures of intratumoral heterogeneity. If any invariance paradigm representing a stochastic or geostatistic function could be discovered, this might help in solving the grading problem. A novel methodological approach using geostatistics to measure heterogeneity is used. Twenty tumours from the three usual (Scarff‐Bloom and Richardson) grades were obtained and paraffin sections stained by MIB‐1 (Ki‐67) and peroxidase staining. Whole two‐dimensional sections were sampled. Morphometric grids of variable sizes allowed a simple and fast recording of positions of epithelial nuclei, marked or not by MIB‐1. The geostatistical method is based here upon the asymptotic behaviour of dispersion variance. Measure of asymptotic exponent of dispersion variance shows an increase from grade 1 to grade 3. Preliminary results are encouraging: grades 1 and 3 on one hand and 2 and 3 on the other hand are totally separated. The final proof of an improved grading using this measure will of course require a confrontation with the results of survival studies.
Performance of MC2 and the ECMWF IFS Forecast Model on the Fujitsu VPP700 and NEC SX‐4M
Authors: Desgagné Michel , Thomas Stephen , Valin Michel
Published: January 2015

The NEC SX‐4M cluster and Fujitsu VPP700 supercomputers are both based on custom vector processors using low‐power CMOS technology. Their basic architectures and programming models are however somewhat different. A multi‐node SX‐4M cluster contains up to 32 processors per shared memory node, with a maximum of 16 nodes connected via the proprietary NEC IXS fibre channel crossbar network. A hybrid combination of inter‐node MPI message‐passing with intra‐node tasking or threads is possible. The Fujitsu VPP700 is a fully distributed‐memory vector machine with a crossbar interconnect which also supports MPI. The parallel performance of the MC2 model for high‐resolution mesoscale forecasting over large domains and of the IFS RAPS 4.0 benchmark are presented for several different machine configurations. These include an SX‐4/32, an SX‐4/32M cluster and up to 100 PE′s of the VPP700. Our results indicate that performance degradation for both models on a single SX‐4 node is primarily due to memory contention within the internal crossbar switch. Multinode SX‐4 performance is slightly better than single node. Longer vector lengths and SDRAM memory on the VPP700 result in lower per processor execution rates. Both models achieve close to ideal scaling on the VPP700.
Topography of Genetic Loci in Tissue Samples: Towards New Diagnostic Tool Using Interphase FISH and High‐Resolution Image Analysis Techniques
Authors: Koutná I. , Kozubek S. , Žaloudík J. , Kozubek M. , Lukášová E. , Matula P. A. , Bártová E. , Skalníková M. , Cafourková A. , Jirsová P.
Published: January 2015

Using single and dual colour fluorescence in situ hybridisation (FISH) combined with image analysis techniques the topographic characteristics of genes and centromeres in nuclei of human colon tissue cells were investigated. The distributions of distances from the centre‐of‐nucleus to genes (centromeres) and from genes to genes (centromeres to centromeres) were studied in normal colon tissue cells found in the neighbourhood of tumour samples, in tumour cell line HT‐29 and in promyelocytic HL‐60 cell line for comparison. Our results show that the topography of genetic loci determined in 3D‐fixed cell tissue corresponds to that obtained for 2D‐fixed cells separated from the tissue. The distributions of the centre‐of‐nucleus to gene (centromere) distances and gene to gene (centromere to centromere) distances and their average values are different for various genetic loci but similar for normal colon tissue cells, HT‐29 colon tumour cell line and HL‐60 promyelocytic cell line. It suggests that the arrangement of genetic loci in cell nucleus is conserved in different types of human cells. The investigations of trisomic loci in HT‐29 cells revealed that the location of the third genetic element is not different from the location of two homologues in diploid cells. We have shown that the topographic parameters used in our experiments for different genetic elements are not tissue or tumour specific. In order to validate high‐resolution cytometry for oncology, further investigations should include more precise parameters reflecting the state of chromatin in the neighbourhood of critical oncogenes or tumour suppresser genes.
Design and Performance Analysis of a Massively Parallel Atmospheric General Circulation Model
Authors: Schaffer Daniel S. , J. Suárez Max
Published: January 2015

In the 1990′s, computer manufacturers are increasingly turning to the development of parallel processor machines to meet the high performance needs of their customers. Simultaneously, atmospheric scientists studying weather and climate phenomena ranging from hurricanes to El Niño to global warming require increasingly fine resolution models. Here, implementation of a parallel atmospheric general circulation model (GCM) which exploits the power of massively parallel machines is described. Using the horizontal data domain decomposition methodology, this FORTRAN 90 model is able to integrate a 0.6° longitude by 0.5° latitude problem at a rate of 19 Gigaflops on 512 processors of a Cray T3E 600; corresponding to 280 seconds of wall‐clock time per simulated model day. At this resolution, the model has 64 times as many degrees of freedom and performs 400 times as many floating point operations per simulated day as the model it replaces.
A Transparent Runtime Data Distribution Engine for OpenMP
Authors: Nikolopoulos Dimitrios S. , Papatheodorou Theodore S. , Polychronopoulos Constantine D. , Labarta Jesús , Ayguadé Eduard
Published: January 2015

This paper makes two important contributions. First, the paper investigates the performance implications of data placement in OpenMP programs running on modern NUMA multiprocessors. Data locality and minimization of the rate of remote memory accesses are critical for sustaining high performance on these systems. We show that due to the low remote‐to‐local memory access latency ratio of contemporary NUMA architectures, reasonably balanced page placement schemes, such as round‐robin or random distribution, incur modest performance losses. Second, the paper presents a transparent, user‐level page migration engine with an ability to gain back any performance loss that stems from suboptimal placement of pages in iterative OpenMP programs. The main body of the paper describes how our OpenMP runtime environment uses page migration for implementing implicit data distribution and redistribution schemes without programmer intervention. Our experimental results verify the effectiveness of the proposed framework and provide a proof of concept that it is not necessary to introduce data distribution directives in OpenMP and warrant the simplicity or the portability of the programming model.
Extending OpenMP for NUMA Machines
Authors: Bircsak John , Craig Peter , Crowell RaeLyn , Cvetanovic Zarka , Harris Jonathan , Nelson C. Alexander , Offner Carl D.
Published: January 2015

This paper describes extensions to OpenMP that implement data placement features needed for NUMA architectures. OpenMP is a collection of compiler directives and library routines used to write portable parallel programs for shared‐memory architectures. Writing efficient parallel programs for NUMA architectures, which have characteristics of both shared‐memory and distributed‐memory architectures, requires that a programmer control the placement of data in memory and the placement of computations that operate on that data. Optimal performance is obtained when computations occur on processors that have fast access to the data needed by those computations. OpenMP ‐‐ designed for shared‐memory architectures ‐‐ does not by itself address these issues. The extensions to OpenMP Fortran presented here have been mainly taken from High Performance Fortran. The paper describes some of the techniques that the Compaq Fortran compiler uses to generate efficient code based on these extensions. It also describes some additional compiler optimizations, and concludes with some preliminary results.
The MicroGrid: A Scientific Tool for Modeling Computational Grids
Authors: Song H.J. , Liu X. , Jakobsen D. , Bhagwan R. , Zhang X. , Taura K. , Chien A.
Published: January 2015

The complexity and dynamic nature of the Internet (and the emerging Computational Grid) demand that middleware and applications adapt to the changes in configuration and availability of resources. However, to the best of our knowledge there are no simulation tools which support systematic exploration of dynamic Grid software (or Grid resource) behavior. We describe our vision and initial efforts to build tools to meet these needs. Our MicroGrid simulation tools enable Globus applications to be run in arbitrary virtual grid resource environments, enabling broad experimentation. We describe the design of these tools, and their validation on micro‐benchmarks, the NAS parallel benchmarks, and an entire Grid application. These validation experiments show that the MicroGrid can match actual experiments within a few percent (2% to 4%).
Machine and Collection Abstractions for User‐Implemented Data‐Parallel Programming
Authors: Haveraaen Magne
Published: January 2015

Data parallelism has appeared as a fruitful approach to the parallelisation of compute‐intensive programs. Data parallelism has the advantage of mimicking the sequential (and deterministic) structure of programs as opposed to task parallelism, where the explicit interaction of processes has to be programmed. In data parallelism data structures, typically collection classes in the form of large arrays, are distributed on the processors of the target parallel machine. Trying to extract distribution aspects from conventional code often runs into problems with a lack of uniformity in the use of the data structures and in the expression of data dependency patterns within the code. Here we propose a framework with two conceptual classes, Machine and Collection. The Machine class abstracts hardware communication and distribution properties. This gives a programmer high‐level access to the important parts of the low‐level architecture. The Machine class may readily be used in the implementation of a Collection class, giving the programmer full control of the parallel distribution of data, as well as allowing normal sequential implementation of this class. Any program using such a collection class will be parallelisable, without requiring any modification, by choosing between sequential and parallel versions at link time. Experiments with a commercial application, built using the Sophus library which uses this approach to parallelisation, show good parallel speed‐ups, without any adaptation of the application program being needed.
Technique and Feasibility of a Dual Staining Method for Estrogen Receptors and AgNORs
Authors: Günther Lukas , Hufnagl Peter
Published: January 2015

A new staining method for dual demonstration of Estrogen receptors (ER) and argyrophilc Nucleolus‐Organizer Regions (AgNORs) was developed. To rule out possible reciprocal effects, serial slides of 10 invasive ductale breast cancers were stained with either the single staining method or the simultaneous ER/AgNOR‐staining method and investigated comparatively. By measuring the slides with the image analysis system AMBA, reciprocal effects could be excluded. It was proven that dual staining of both markers results in a reproducible and specific staining result. We concluded that it is justified to measure AgNORs in immunohistochemically stained cells.
Comparative Intracellular Cytokine Production by In Vitro Stimulated T Lymphocytes from Human Umbilical Cord Blood (HUCB) and Adult Peripheral Blood (APB)
Authors: García Vela J. A. , Delgado I. , Bornstein R. , Alvarez B. , Auray M. C. , Martin I. , Oña F. , Gilsanz F.
Published: January 2015

To date over 400 HUCB transplants have been reported from different centers. It has been suggested that there is a reduced graft‐versus‐host‐disease (GVHD) with HUCB compared to bone marrow transplantation. Since cytokine production by a cell is an indication of the cells function it is important to determinate the differences between APB and HUCB with respect to production of these soluble factors. Our aim was to analyse the intracellular cytokine production by HUCB and APB T lymphocytes with and emphasize on their possible role in GVHD.

Heparinized HUCB samples from 8 normal full‐term deliveries and 10 normal blood donors were stimulated 4 hours at 37∘C and 5% CO2 with phorbol 12‐myristate 13‐acetate (PMA) and Ionomycin in the presence of brefeldine. Afterwards cells were stained with CD3, CD4 or CD8 in different combinations. Finally, after cell permeabilization, cells were stained with Il‐2, Il‐4 or IFN‐γ. Data acquisition was performed on a FACScan flow cytometer.

Compared to APB, HUCB T lymphocytes produced less Il‐2, Il‐4 and IFN‐γ. In HUCB, Il‐2, Il‐4 and IFN‐γ were produced predominantly by CD4+ T cells. In APB, Il‐2 and Il‐4 were also produced predominantly by CD4+ cells compared with CD8+ T lymphocytes, however, IFN‐γ was produced by both CD4+ and CD8+ T cells.
These results indicate that there are clear differences in the cytokine profile between T cells in APB and HUCB.
Acceptance of Telepathology in Daily Practice
Authors: Mairinger Thomas
Published: January 2015

The availability of pathology services differs greatly in our environment. Although pathology would be especially suitable for being practised at a distance by transporting digital image information, the spread of telepathology into everyday work still is relatively slow.

The article describes the situation of diffusion of this innovative technology by reviewing the literature and discussing this in context to data based on questionnaires dealing with the acceptance of telepathology. The current situation of telepathology can be discussed by five items for innovation spead: (1) communication and influence; (2) economic costs and benefits; (3) knowledge barriers and learning; (4) feasibility of techniques offered for the demands of the users; (5) clarification of the legal status and other factors concerning international collaboration. All these head lines do not represent realistic obstacles for the more widespread use of telepathology. The real drawbacks may therefore be found behind certain professional habits of pathologists. The most important causes may be that (a) telediagnosis is not as easy as it may seem at the first glance; (b) telepathology is seen as a potential highway to a world‐wide competition of pathology service providers. As soon as these mostly unjustified prejudices are corrected and telepathology is percepted as additional technique in pathology, it will become a diagnostic tool as common and as useful as the telephone.
The Telepathology and Teleradiology Network in Croatia
Authors: Seiwerth S. , Danilovic Z.
Published: January 2015

Telepathology as a demanding branch of telemedicine poses a real challenge to experts. The introduction of telepathology in underprivileged countries with poor infrastructure and low health‐care budget is a difficult task. On the other hand these countries would mostly benefit by introducing telemedicine/telepathology. In our experience it is possible to build an efficient telepathology/teleradiology network using analogue telephone links and still image transmission, and a store and forward mode of operation. This experience is based on the application of telepathology in Croatia for seven years leading to a national teleradiology network. In this paper the ideas, development and software solutions in the process of establishing a national telepathology and teleradiology network are highlighted.
Requirements and Problems in Parallel Model Development at DWD
Authors: Schäattler Ulrich , Doms Güunther , Steppeler Jüurgen
Published: January 2015

Nearly 30 years after introducing the first computer model for weather forecasting, the Deutscher Wetterdienst (DWD) is developing the 4th generation of its numerical weather prediction (NWP) system. It consists of a global grid point model (GME) based on a triangular grid and a non‐hydrostatic Lokal Modell (LM). The operational demand for running this new system is immense and can only be met by parallel computers. From the experience gained in developing earlier NWP models, several new problems had to be taken into account during the design phase of the system. Most important were portability (including efficieny of the programs on several computer architectures) and ease of code maintainability. Also the organization and administration of the work done by developers from different teams and institutions is more complex than it used to be. This paper describes the models and gives some performance results. The modular approach used for the design of the LM is explained and the effects on the development are discussed.
Biological Characterisation of Superficial Bladder Cancer by Bivariate Cytokeratin 7/DNA Analysis, Flow Cytometric Assessment of MIB‐1, and an Immunohistochemical Study
Authors: Leonardi Elena , Palma Paolo Dalla , Reich Alessandro , Caffo Orazio , Luciani Lucio
Published: January 2015

A total of 238 cases of bladder carcinoma stages Ta, Tis, T1 were submitted prospectively to multiparameter flow cytometry and immunohistochemical study in order to determine the biological aggressiveness of the tumour. DNA index (DI), S‐phase fraction (SPF) obtained by bivariate cytokeratin 7=DNA analyses, and the immunohistochemical evaluation of p53 and MIB‐1 were studied in relation to the traditional prognostic factors in bladder cancer (stage and grade). The variance analysis results showed that DNA aneuploidy was significantly associated with high stage (p = 0:0001), high grade (p = 0:0001), high SPF value ≥5.5% (p = 0:0001), MIB‐1 positivity ≥31% (p = 0:0001) and high expression of p53 (staining involving >50% of cells, p = 0:0001). Even if there was no statistical significance the hypotetraploid class (1.70<DI<1.89) showed poor prognostic biomarkers more frequently than the other aneuploid classes. Out of 238 cases, 101 were also submitted to flow cytometric measurement ofMIB‐1 (fMIB‐1) to study the correlation between cell proliferation and DNA content. Data obtained from fresh, 3 : 1 methanol=acetone fixed samples were compared with values obtained from both cell cycle analysis methods and routine application of the MIB‐1 immunostaining in histological sections. fMIB‐1 values were positively correlated with SPF values (r = 0:801, p < 0:01) and S+G2M fraction (percentage of cells in S and in G2M phases) (r = 0:763, p < 0:01) but no correlation with paraffin sections was found. A fMIB‐1 value >7% was strongly associated with aneuploidy (p = 0:0001). The determination of DNA content coupled with the study of the epithelial (cytokeratin 7) and proliferative (MIB‐1) markers could be useful in providing important information on the biological behaviour of superficial bladder tumours.
Telepathology: Design of a Modular System
Authors: Brauchli K. , Christen H. , Meyer P. , Haroske G. , Meyer W. , Kunze K. D. , Otto R. , Oberholzer M.
Published: January 2015

Although telepathology systems have been developed for more than a decade, they are still not a widespread tool for routine diagnostic applications. Lacking interoperability, software that is not satisfying user needs as well as high costs have been identified as reasons. In this paper we would like to demonstrate that with a clear separation of the tasks required for a telepathology application, telepathology systems can be built in a modular way, where many modules can be implemented using standard software components. With such a modular design, systems can be easily adapted to changing user needs and new technological developments and it is easier to integrate modular systems into existing environments.
Scalable Molecular Dynamics for Large Biomolecular Systems
Authors: Brunner Robert K. , Phillips James C. , Kalé Laxmikant V.
Published: January 2015

We present an optimized parallelization scheme for molecular dynamics simulations of large biomolecular systems, implemented in the production‐quality molecular dynamics program NAMD. With an object‐based hybrid force and spatial decomposition scheme, and an aggressive measurement‐based predictive load balancing framework, we have attained speeds and speedups that are much higher than any reported in literature so far. The paper first summarizes the broad methodology we are pursuing, and the basic parallelization scheme we used. It then describes the optimizations that were instrumental in increasing performance, and presents performance results on benchmark simulations.
Key Elements of the User‐Friendly, GFDL SKYHI General Circulation Model
Authors: Hemler Richard S.
Published: January 2015

Over the past seven years, the portability of the GFDL SKYHI general circulation model has greatly increased. Modifications to the source code have allowed SKYHI to be run on the GFDL Cray Research PVP machines, the TMC CM‐5 machine at Los Alamos National Laboratory, and more recently on the GFDL 40‐processor Cray Research T3E system. At the same time, changes have been made to the model to make it more usable and flexible. Because of the reduction of the human resources available to manage and analyze scientific experiments, it is no longer acceptable to consider only the optimization of computer resources when producing a research code; one must also consider the availability and cost of the people necessary to maintain, modify and use the model as an investigative tool, and include these factors in defining the form of the model code. The new SKYHI model attempts to strike a balance between the optimization of the use of machine resources (CPU time, memory, disc) and the optimal use of human resources (ability to understand code, ability to modify code, ability to perturb code to do experiments, ability to run code on different platforms). Two of the key features that make the new SKYHI code more usable and flexible are the archiving package and the user variable block. The archiving package is used to manage the writing of all archive files, which contain data for later analysis. The model‐supplied user variable block allows the easy inclusion of any new variables needed for particular experiments.
Increased Cell Proliferation in Chronic Helicobacter pylori Positive Gastritis and Gastric Carcinoma – Correlation between Immuno‐Histochemistry and Tv Image Cytometry
Authors: Szaleczky Erika , Prónai László , Molnár Béla , Berczi Lajos , Fehér János , Tulassay Zsolt
Published: January 2015

Backgound: Epithelial cell proliferation activity has been reported both to be unaltered and increased in Helicobacter pylori (H. pylori) associated chronic gastritis. The proliferation rate decreased following H. pylori eradication, but results are controversial whether this change is dependent on the success of eradication. We compared the cell proliferation activity of H. pylori positive and negative gastric epithelial biopsies in chronic gastritis with and without intestinal metaplasia (IM) and gastric cancer by the expression of proliferation cell nuclear antigen (PCNA) and Tv image cytometry, and assessed the effect of H. pylori eradication on the cell proliferation rate in the gastric epithelium.

Methods: Brush smears and antral biopsies were taken from 70 patients (42 men, 28 women, mean age 58 ± 15 y.o.) on routine endoscopy. Patients were divided into four groups according to the histology; normal epithelia (n=10), chronic gastritis without IM (n=24), chronic gastritis with IM (n=20), and gastric carcinoma (n=16). Thirty‐three patients were H. pylori positive, and success of eradication was controlled in 24 cases. Cell proliferation was measured by immunohistochemistry using PCNA labeling index (LI) and by Tv image cytometry evaluating 12 morpho‐ and densitometric parameters of each nuclei and 6 additional parameters of each smear.

Results: PCNA LI, DNA index and S + G2 ratio were all higher in chronic gastritis than in the normal epithelium, and were further increased in carcinoma. The lower PCNA LI observed in chronic gastritis with IM corresponds to the lower S phase ratio determined by Tv image analysis. In H. pylori positive cases, the proliferation activity was 69.3 ± 13.05% prior to the eradication and it decreased to 55.8 ± 23.31% after the successful eradication therapy. When immunohistochemistry was compared with Tv image cytometry, PCNA LI significantly correlated with the percentage of cells in G1 phase (r=−0.415) and S phase (r=0.385), Integrated Optical Density mean (r=0.598), density maximum (r=0.608), surface (r=0.670), layers (r=0.638), diameter minimum (r=0.619), diameter maximum (r=0.730) and perimeter (r=0.501), respectively (p < 0.05).

Conclusions: Epithelial cell turnover is increased in chronic gastritis with or without IM, and in gastric carcinoma. The lower PCNA LI observed in chronic gastritis with IM corresponds to the lower S phase ratio determined by Tv image analysis. Cell proliferation decreases after successful H. pylori eradication. Both methods proved to be reliable for the determination of epithelial cell proliferation.
Experience with a Dynamic Inexpensive Video‐Conferencing System for Frozen Section Telepathology
Authors: Baak J. P. A. , van Diest P. J. , Meijer G. A.
Published: January 2015

Aim: To evaluate the feasibility of an inexpensive, generally applicable video‐conferencing system for frozen section telepathology (TP). Methods: A commercially widely available PC‐based dynamic video‐conferencing system (PictureTel LIVE, model PCS 100) has been evaluated, using two, four and six ISDN channels (128–384 kilobits per second (kbs)) bandwidths. 129 frozen sections have been analyzed which were classified by TP as benign, uncertain (the remark probably benign, or probably malignant was allowed), malignant, or not acceptable image quality. The TP results were compared with the original frozen section diagnosis and final paraffin diagnosis. Results: Only 384 kbs (3 ISDN‐2 lines) resulted in acceptable speed and quality of microscope images, and synchronous image/speech transfer. In one of the frozen section cases (0.7%), TP image quality was classified as not acceptable, leaving 128 frozen sections for the analysis. Five of these cases were uncertain by TP, and also deferred by frozen section procedure (FS). One more benign and three malignant FS cases were classified as uncertain by TP. Three additional cases were uncertain by FS, but benign according to TP (in agreement with the final diagnosis). In one case, FS diagnosis was uncertain but TP was malignant (in agreement with the final diagnosis). Thus, test efficiency (i.e., cases with complete agreement) was 120/128 (93.8%, Kappa = 0.88) between FS and TP. Sensitivity was 93.5%, specificity 98.6%, positive and negative predictive values were 97.7% and 96.0%. Between TP and final diagnosis agreement was even higher. More importantly, there was not a single discrepancy as to benign‐malignant. Moreover, there was a clear learning effect: 5 of the 8 FS/TP discrepancies occurred in the first 42 cases (5/42=11.9%), the remaining 3 in the following 86 cases (3/86=3.5%). Discussion: The results are encouraging. However, TP evaluation is time‐consuming (5–15 min for one case instead of 2–4 min although speed went up with more experience) and is more tiring. The system has the following technical drawbacks: no possibility to point at objects or areas of interest in the life image at the other end, resolution (rarely) may become suboptimal (blocky), storage of images evaluated (which is essential for legal reasons) is not easy and no direct control of a remote motorized microscope. Yet, all users were positive about the system both for telepathology and personal contact by video‐conferencing. Conclusion: With a relatively simple videoconferencing system, accurate dynamic telepathology frozen section diagnosis can be obtained without false positive or negative results, although a limited number of uncertain cases will have to be accepted.
Evaluation of C‐ErbB‐2 Overexpression and Her‐2/neu Gene Copy Number Heterogeneity in Barrett’s Adenocarcinoma
Authors: Walch Axel , Bink Karin , Gais Peter , Stangl Stefan , Hutzler Peter , Aubele Michaela , Mueller James , Höfler Heinz , Werner Martin
Published: January 2015

Amplifiction of the Her‐2/neu gene is accompanied by overexpression of its cell surface receptor product, c‐erbB‐2 protein. To investigate the degree of intratumoural heterogeneity we applied immunohistochemistry in primary Barrett’s adenocarcinoma (BCA) (n = 6) and dysplasia adjacent to the carcinoma (n = 4). In addition, fluorescence in situ hybridisation (FISH) was performed in primary BCA (n=5) and dysplastic areas (n=4). For an objective evaluation digital image analysis and laser scanning microscopy were used. Five of six BCA showed a marked intratumoural heterogeneous staining pattern ranging from areas in which the tumour cells were negative or faintly positive to tumour areas with a strong staining of the entire membrane. Among the two dysplastic areas also a heterogenous staining pattern was observed. FISH analysis revealed marked heterogeneity of intratumoural gene copy number changes in all BCA showing populations with different fractions of cells with polysomy, low level amplification and high level amplification. One dysplasia showed a minor population with Her‐2/neu signal clusters. In conclusion, we observed marked intratumoural heterogeneity of c‐erbB‐2 protein overexpression and Her‐2/neu gene copy number in the majority of the primary BCA analyzed. Digital image analysis and laser scanning microscopy were helpful in quantifying the variations in protein expression and DNA copy number in individual tumour cells. The observed heterogeneity could hamper the exact diagnostic determination of the c‐erbB‐2 status in small biopsies and possibly influence the effectiveness of a potential c‐erbB‐2 targeting therapy.

Figures on http://www.esacp.org/acp/2000/20‐1/walch.htm.
Malignancy‐Associated Changes in Breast Tissue Detected by Image Cytometry
Authors: Mommers Ellen C. M. , Poulin Neal , Meijer Chris J. L. M. , Baak Jan P. A. , van Diest Paul J.
Published: January 2015

In several tissues, nuclear differences have been described in normal‐appearing cells from patients with invasive carcinomas compared to cases without invasive carcinoma, a phenomenon known as malignancy‐associated changes (MACs). The aim of this study was to determine the presence of malignancy‐associated changes in breast tissue.

Image cytometry was performed on Feulgen stained tissue sections of patients with usual ductal hyperplasia with (n=30) or without (n=41) adjacent invasive breast carcinoma. Nuclear features of normal‐appearing cells as well as of usual ductal hyperplastic cells were separately compared between the two groups.

Many features of normal‐appearing epithelial cells were significantly different between cases with and without invasive cancer. Significant differences were also found by measuring ductal hyperplastic nuclei instead of normal‐appearing nuclei. Cases with or without cancer could be distinguished with a classification accuracy of 80% by discriminant analysis using 2 nuclear features derived from ductal hyperplastic cells.

In conclusion, image cytometry on breast tissue sections shows that malignancy‐associated changes can be found in normal as well as in usual ductal hyperplastic breast cells. This could be clinically relevant for the detection of occult breast cancer, for the prediction of risk in these lesions, and to monitor the effect of chemopreventive agents.
Informational Aspects of Telepathology in Routine Surgical Pathology
Authors: Gombas Peter
Published: January 2015

Application of computer and telecommunication technology calls serious challenges in routine diagnostic pathology. Complete data integration, fast access patients′ data to usage of diagnosis thesaurus labeled with standardized codes and free text supplements, complex inquiry of the data contents, data exchange via teleconsultation and multilevel data protection are required functions of an integrated information system. Increasing requirement for teleconsultation transferring a large amount of multimedia data among different pathology information systems raises new questions in telepathology. Creation of complex telematic systems in pathology requires efficient methods of software engineering and implementation. Information technology of object‐oriented modeling, usage of client server architecture and relational database management systems enables more compatible systems in field of telepathology. The aim of this paper is to present a practical example how to unify text based database, image archive and teleconsultation in a frame of an integrated telematic system and to discuss the main conceptual questions of information technology of telepathology.
Enabling Technologies for Improved Data Management: Hardware
Authors: Dam-Kleese Kerstin van , Hopewell Michael
Published: January 2015

The most valuable assets in every scientific community are the expert work force and the research results/data produced. The last decade has seen new experimental and computational techniques developing at an ever‐faster pace, encouraging the production of ever‐larger quantities of data in ever‐shorter time spans. Concurrently the traditional scientific working environment has changed beyond recognition. Today scientists can use a wide spectrum of experimental, computational and analytical facilities, often widely distributed over the UK and Europe. In this environment new challenges are posed for the Management of Data every day, but are we ready to tackle them? Do we know exactly what the challenges are? Is the right technology available and is it applied where necessary? This part of enabling technologies investigates current hardware techniques and their functionalities and provides a comparison between various products.
Parallel Programming Environment for OpenMP
Authors: Park Insung , Voss Michael J. , Kim Seon Wook , Eigenmann Rudolf
Published: January 2015

We present our effort to provide a comprehensive parallel programming environment for the OpenMP parallel directive language. This environment includes a parallel programming methodology for the OpenMP programming model and a set of tools (Ursa Minor and InterPol) that support this methodology. Our toolset provides automated and interactive assistance to parallel programmers in time‐consuming tasks of the proposed methodology. The features provided by our tools include performance and program structure visualization, interactive optimization, support for performance modeling, and performance advising for finding and correcting performance problems. The presented evaluation demonstrates that our environment offers significant support in general parallel tuning efforts and that the toolset facilitates many common tasks in OpenMP parallel programming in an efficient manner.
The Semi‐Automatic Parallelisation of Scientific Application Codes Using a Computer Aided Parallelisation Toolkit
Authors: Ierotheou C.S. , Johnson S.P. , Leggett P.F. , Cross M. , Evans E.W. , Jin H. , Frumkin M. , Yan J.
Published: January 2015

The shared‐memory programming model can be an effective way to achieve parallelism on shared memory parallel computers. Historically however, the lack of a programming standard using directives and the limited scalability have affected its take‐up. Recent advances in hardware and software technologies have resulted in improvements to both the performance of parallel programs with compiler directives and the issue of portability with the introduction of OpenMP. In this study, the Computer Aided Parallelisation Toolkit has been extended to automatically generate OpenMP‐based parallel programs with nominal user assistance. We categorize the different loop types and show how efficient directives can be placed using the toolkit′s in‐depth interprocedural analysis. Examples are taken from the NAS parallel benchmarks and a number of real‐world application codes. This demonstrates the great potential of using the toolkit to quickly parallelise serial programs as well as the good performance achievable on up to 300 processors for hybrid message passing‐directive parallelisations.
Towards a Genetic‐Based Classification of Human Lung Cancer
Authors: Petersen Iver , Petersen Simone
Published: January 2015

Lung cancer is a highly aggressive neoplasm which is reflected by a multitude of genetic aberrations being detectable on the chromosomal and molecular level. In order to understand this seemingly genetic chaos, we performed Comparative Genomic Hybridisation (CGH) in a large collective of human lung carcinomas investigating different tumor entities as well as multiple individual tumour specimens of single patients. Despite the considerable genetic instability being reflected by the well known morphological heterogeneity of lung cancer the comparison of different tumour groups using custom made computer software revealed recurrent aberration patterns and highlighted chromosomal imbalances that were significantly associated with morphological histotypes and biological phenotypes. Specifically we identified imbalances in NSCLC being associated with metastasis formation which are typically present in SCLC thus explaining why the latter is such an aggressive neoplasm characterized by widespread tumor dissemination. Based on the genetic data a new model for the development of SCLC is presented. It suggests that SCLC evolving from the same stem cell as NSCLC should be differentiated into primary and secondary tumors. Primary SCLC corresponding to the classical type evolved directly from an epithelial precursor cell. In contrast, secondary SCLC correlating with the combined SCLC develops via an NSCLC intermediate. In addition, we established libraries of differentially expressed genes from different human lung cancer types to identify new candidate genes for several of the chromosomal subregions identified by CGH. In this review, we summarise the status of our results aiming at a refined classification of lung cancer based on the pattern of genetic aberrations.
Comparing Global Strategies for Coding Adjoints
Authors: Faure Christèle , Charpentier Isabelle
Published: January 2015

From a computational point of view, sensitivity analysis, calibration of a model, or variational data assimilation may be tackled after the differentiation of the numerical code representing the model into an adjoint code. This paper presents and compares methodologies to generate discrete adjoint codes. These methods can be implemented when hand writing adjoint codes, or within Automatic Differentiation (AD) tools. AD has been successfully applied to industrial codes that were large and general enough to fully validate this new technology. We compare these methodologies in terms of execution time and memory requirement on a one dimensional thermal‐hydraulic module for two‐phase flow modeling. With regard to this experiment, some development axes for AD tools are extracted as well as methods for AD tool users to get efficient adjoint codes semi‐automatically. The next objective is to generate automatically adjoint codes as efficient as hand written ones.
Recursive Approach in Sparse Matrix LU Factorization
Authors: Dongarra Jack , Eijkhout Victor , Łuszczek Piotr
Published: January 2015

This paper describes a recursive method for the LU factorization of sparse matrices. The recursive formulation of common linear algebra codes has been proven very successful in dense matrix computations. An extension of the recursive technique for sparse matrices is presented. Performance results given here show that the recursive approach may perform comparable to leading software packages for sparse matrix factorization in terms of execution time, memory usage, and error estimates of the solution.