bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of Human Papillomavirus Type 2 Related Sequence in Oral Papilloma
Authors: Yamaguchi Taihei , Shindoh Masanobu , Amemiya Akira , Inoue Nobuo , Kawamura Masaaki , Sakaoka Hiroshi , Inoue Masakazu , Fujinaga Kei
Published: January 2015

Oral papilloma is a benign tumourous lesion. Part of this lesion is associated with human papillomavirus (HPV) infection. We analysed the genetical and histopathological evidence for HPV type 2 infection in three oral papillomas. Southern blot hybridization showed HPV 2a sequence in one lesion. Cells of the positive specimen appeared to contain high copy numbers of the viral DNA in an episomal state. In situ staining demonstrated virus capsid antigen in koilocytotic cells and surrounding cells in the hyperplastic epithelial layer. Two other specimens contained no HPV sequences by labeled probe of full length linear HPVs 2a, 6b, 11, 16, 18, 31 and 33 DNA under low stringency hybridization conditions. These results showed the possibility that HPV 2 plays a role in oral papilloma.
Flow Cytometric DNA Index and Karyotype in Childhood Lymphoblastic Leukemia
Authors: Forestier Erik , Holmgren Gösta , Roos Göran
Published: January 2015

Flow cytometric DNA‐index (DIFCM) and karyotype were analysed in 82 consecutive children with acute lymphoblastic leukemia (ALL) during a 10 year period. A statistically significant correlation existed between modal chromosome number and DIFCM (p = 0.009). DIFCM could reliably identify leukemias with >51 chromosomes, whereas only three out of 12 cases with modal chromosome numbers between 47–51 were classified as aneuploid by DIFCM. In the pseudodiploid group only one out of 20 leukemias had a DIFCM>1.0. Five leukemias with a diploid karyotype showed an aneuploid DIFCM and in three patients the flow cytometric measurement revealed biclonality undetected by karyotyping. During treatment aneuploid clones could be detected by DIFCM in a substantial number of cases where the cytogenetic analysis was normal, and the opposite was also demonstrated in one case. DIFCM gave prognostic information, showing that cases with a DI >1.12 (corresponding to 51 chromosomes) had a superior outcome with treatment protocols today in use.
Fast‐FISH Detection and Semi‐Automated Image Analysis of Numerical Chromosome Aberrations in Hematological Malignancies
Authors: Esa Arif , Trakhtenbrot Luba , Hausmann Michael , Rauch Joachim , Brok-Simoni Frida , Rechavi Gideon , Ben-Bassat Isaac , Cremer Christoph
Published: January 2015

A new fluorescence in situ hybridization (FISH) technique called Fast‐FISH in combination with semi‐automated image analysis was applied to detect numerical aberrations of chromosomes 8 and 12 in interphase nuclei of peripheral blood lymphocytes and bone marrow cells from patients with acute myelogenous leukemia (AML) and chronic lymphocytic leukemia (CLL). Commercially available α‐satellite DNA probes specific for the centromere regions of chromosome 8 and chromosome 12, respectively, were used. After application of the Fast‐FISH protocol, the microscopic images of the fluorescence‐labelled cell nuclei were recorded by the true color CCD camera Kappa CF 15 MC and evaluated quantitatively by computer analysis on a PC. These results were compared to results obtained from the same type of specimens using the same analysis system but with a standard FISH protocol. In addition, automated spot counting after both FISH techniques was compared to visual spot counting after standard FISH. A total number of about 3,000 cell nuclei was evaluated. For quantitative brightness parameters, a good correlation between standard FISH labelling and Fast‐FISH was found. Automated spot counting after Fast‐FISH coincided within a few percent to automated and visual spot counting after standard FISH. The examples shown indicate the reliability and reproducibility of Fast‐FISH and its potential for automatized interphase cell diagnostics of numerical chromosome aberrations. Since the Fast‐FISH technique requires a hybridization time as low as 1/20 of established standard FISH techniques, omitting most of the time consuming working steps in the protocol, it may contribute considerably to clinical diagnostics. This may especially be interesting in cases where an accurate result is required within a few hours.
The Effect of Primary Fixation with Standard Postfixation and the Duration of Hydrolysis on Nuclear Features in Image Cytometry
Authors: Fležar Margareta , Doudkine Alexei , Us-Krašovec Marija
Published: January 2015

The effect of three primary fixation procedures, used in the preparation of routine cytological samples: air‐drying, Delaunay, and Saccomanno fixation, with postfixation in modified Böhm–Sprenger fixative, on nuclear features as a function of hydrolysis time is reported. Three different cell types: lymphatic cells (tonsil), epithelial cells (buccal mucosa) and mesenchymal cells (uterine myometrium) were used for the study. Our findings show, that generally not all features have the same plateau times as the IOD (integrated optical density), and that many features show different values depending on cell type and fixation method. It is therefore recommended that for any primary fixative used in routine clinical work and for each cell type, the hydrolysis curve for all nuclear features to be used in sample analysis should be established.
An Automated 96‐Well‐Plate Loader for the FACScanⓇ
Authors: Illges Harald
Published: January 2015

Staining multiple samples for data acquisition with a flow cytometer is done in 96‐well plates to save time and make large data assessment in one working day possible. However, the inability of the FACScanⓇ to take up the samples from 96‐well plates is a major drawback. In order to avoid the individual transfer of samples to tubes, we have developed a system, which allows using the FACScanⓇ with 96‐well plates. The machine consists of a programmable control module and a loader which moves the 96‐well plate in 3 axis well by well along the sample collector. The machine is equipped with a wash buffer tank to avoid cross contamination of samples and a shaking option to avoid sedimentation of cells during acquisition. The machine can be further developed into a full automatic loader if connected to the FACS Station. In 24 hours about 7,000 samples with 10,000 cells each can be acquired.
Spatial Analysis of the Neuronal Density of Aminergic Brainstem Nuclei in Primary Neurodegenerative and Vascular Dementia: A Comparative Immunocytochemical and Quantitative Study Using a Graph Method
Authors: Yang Yan , Beyreuther Konrad , Schmitt Horst P.
Published: January 2015

A graph method was employed to analyse spatial neuronal patterns of pontine nuclei with ascending aminergic projections to the forebrain (nucleus centralis superior (NCS), raphes dorsalis (NRD) and locus coeruleus (LC)), in Alzheimer disease (AD), Huntington disease (HD), and vascular (VD) as well as “mixed‐type” (VA) dementia, compared with non‐demented controls (CO) and a small sample of brains from schizophrenics (“dementia praecox” (DP)). The quantitative evaluations by the “minimal spanning tree (MST)” were complemented by rough neurofibrillary tangle (NFT) counts and by semiquantitative immunohistochemical assessment of amyloid deposition, neuritic plaque formation, and cellular gliosis. The AD cases showed a significant decline of neuronal density in all nuclei examined, as compared with controls and DP. Neuronal loss was not significant in VD, while the mixed cases with both vascular and Alzheimer‐type pathology exhibited pronounced changes of neuronal density. Amyloid deposition occurred almost exclusively in AD and VA, as a rule, being of moderate degree, except for two presenile AD cases where it was marked. NFT were significantly increased in all nuclei in AD and in the VA cases, while they only occasionally appeared beyond age 55 in HD, DP and CO. The four HD cases showed in the NCS and NRD neuronal loss as severe as in AD. This neuronal loss implicates impairment of serotoninergic and noradrenergic neuromodulation as one basic mechanism promoting dementia in AD, VA and perhaps in HD.
K‐ras2 Activation and Genome Instability Increase Proliferation and Size of FAP Adenomas
Authors: Rapallo Anna , Sciutto Andrea , Geido Elio , Orecchia Roberto , Infusini Edmondo , Pujic Natalija , d’Amore Emanuele S.G. , Monaco Roberto , Risio Mauro , Rossini Francesco P. , Giaretti Walter
Published: January 2015

The possible role of K‐ras2 mutations and aneuploidy toward increase of proliferation and adenoma size in Familial Adenomatous Polyposis (FAP) adenomas is not known. The present study addresses these issues by investigating 147 colorectal adenomas obtained from four FAP patients. The majority of adenomas had size lower than or equal to 10 mm (86%), low grade dysplasia (63%), and were preferentially located in the right colon (60%). Normal mucosa samples were obtained from 19 healthy donors. Three synchronous adenocarcinomas were also investigated. K‐ras2 mutation spectrum was analysed by PCR and Sequence Specific Oligonucleotide (SSO) hybridization, while flow cytometry (FCM) was used for evaluating degree of DNA ploidy and S‐phase fraction. Overall, incidences of K‐ras2 mutations, DNA aneuploidy and high S‐phase values (>7.2%) were 6.6%, 5.4% and 10.5%, respectively. In particular, among the adenomas with size lower than 5 mm, K‐ras2 mutation and DNA aneuploidy frequencies were only slightly above 1%. Statistically significant correlations were found between K‐ras2 and size, DNA ploidy and size and K‐ras2 and S‐phase (p). In particular, among the wild type K‐ras2 adenomas, high S‐phase values were detected in 8% of the cases versus 57% among the K‐ras2 mutated adenomas (p=0.0005). The present series of FAP adenomas indicates that K‐ras2 activation and gross genomic changes play a role toward a proliferative gain and tumour growth in size.
Energy Transfer between Fluorescein Isothiocyanate and Propidium Iodide – A Problem in the Estimation of Tpot with the Bromodeoxyuridine–DNA Flow Cytometry Technique?
Authors: Johansson Maria C. , Baldetorp Bo , Oredsson Stina M.
Published: January 2015

Energy transfer in flow cytometry can occur when two fluorochromes are bound in close proximity (generally within 100 Å) and the emission spectrum of one fluorochrome overlaps significantly with the excitation spectrum of the other. The latter criterium is fullfilled for the fluorochromes fluorescein isothiocyanate and propidium iodide and also the former when they, e.g., are used in bromodeoxyuridine – DNA flow cytometry methods. In the present growth kinetic study using this method, we show that energy transfer does take place between fluorescein isothiocyanate and propidium iodide which results in a detected increase in DNA content with 2–3%. Despite the erroneous increase in the obtained DNA content values, this does not seem to have any influence on the calculation of DNA synthesis time and potential doubling time where the DNA content, based on the relative movement principle of the labelled cells, is used.
Comparative Evaluation and Case Studies of Shared‐Memory and Data‐Parallel Execution Patterns
Authors: Zhang Xiaodong , Sun Lin
Published: January 2015

Shared‐memory and data‐parallel programming models are two important paradigms for scientific applications. Both models provide high‐level program abstractions, and simple and uniform views of network structures. The common features of the two models significantly simplify program coding and debugging for scientific applications. However, the underlining execution and overhead patterns are significantly different between the two models due to their programming constraints, and due to different and complex structures of interconnection networks and systems which support the two models. We performed this experimental study to present implications and comparisons of execution patterns on two commercial architectures. We implemented a standard electromagnetic simulation program (EM) and a linear system solver using the shared‐memory model on the KSR‐1 and the data‐parallel model on the CM‐5. Our objectives are to examine the execution pattern changes required for an implementation transformation between the two models; to study memory access patterns; to address scalability issues; and to investigate relative costs and advantages/disadvantages of using the two models for scientific computations. Our results indicate that the EM program tends to become computation‐intensive in the KSR‐1 shared‐memory system, and memory‐demanding in the CM‐5 data‐parallel system when the systems and the problems are scaled. The EM program, a highly data‐parallel program performed extremely well, and the linear system solver, a highly control‐structured program suffered significantly in the data‐parallel model on the CM‐5. Our study provides further evidence that matching execution patterns of algorithms to parallel architectures would achieve better performance.
Transient Variable Caching in Java’s Stack‐Based Intermediate Representation
Authors: Týma Paul
Published: January 2015

Java’s stack‐based intermediate representation (IR) is typically coerced to execute on register‐based architectures. Unoptimized compiled code dutifully replicates transient variable usage designated by the programmer and common optimization practices tend to introduce further usage (i.e., CSE, Loop‐invariant Code Motion, etc.). On register based machines, often transient variables are cached within registers (when available) saving the expense of actually accessing memory. Unfortunately, in stack‐based environments because of the need to push and pop the transient values, further performance improvement is possible. This paper presents Transient Variable Caching (TVC), a technique for eliminating transient variable overhead whenever possible. This optimization would find a likely home in optimizers attached to the back of popular Java compilers. Side effects of the algorithm include significant instruction reordering and introduction of many stack‐manipulation operations. This combination has proven to greatly impede the ability to decompile stack‐based IR code sequences. The code that results from the transform is faster, smaller, and greatly impedes decompilation.
The AgNOR Quantity as Prognostic Parameter in Choroidal Melanomas: A Standardised Analysis
Authors: Tuccari G. , Giménez‐Mas J. A. , Fedele F. , Del‐Agua C. , Melcon B. , Trombetta C. J. , Giuffrè G.
Published: January 2015

In order to assess the prognostic significance of silver‐stained nucleolar organizer region (AgNOR) proteins, a standardised analysis has been performed on 34 ocular globes with choroidal melanomas. On formalin‐fixed paraffin‐embedded sections, the visualisation and quantification of AgNORs were achieved according to the guidelines of the Committee on AgNOR Quantification (1995); statistical analysis was performed on the mean AgNOR area values (NORA). We have encountered significantly higher NORA values in non‐spindle shaped elements, in tumours of larger dimensions as well as in those with worse clinical course; no correlations were achieved when the AgNOR quantity was compared with age, sex and amount of pigment. The comparison of Kaplan–Meier survival curves revealed that patients affected by melanomas with higher NORA values (>3.327 μm2), non‐spindle cell histotype and increased size of tumour had a worse prognosis; finally, by Cox multivariate analysis, the AgNOR quantity appeared the only independent prognostic variable to predict the final outcome of patients.
Automatic Morphological Sieving: Comparison between Different Methods, Application to DNA Ploidy Measurements
Authors: Boudry Christophe , Herlin Paulette , Plancoulaine Benoit , Masson Eric , Elmoataz Abderrahim , Cardot Hubert , Coster Michel , Bloyet Daniel , Chermant Jean‐Louis
Published: January 2015

The aim of the present study is to propose alternative automatic methods to time consuming interactive sorting of elements for DNA ploidy measurements. One archival brain tumour and two archival breast carcinoma were studied, corresponding to 7120 elements (3764 nuclei, 3356 debris and aggregates). Three automatic classification methods were tested to eliminate debris and aggregates from DNA ploidy measurements (mathematical morphology (MM), multiparametric analysis (MA) and neural network (NN)). Performances were evaluated by reference to interactive sorting. The results obtained for the three methods concerning the percentage of debris and aggregates automatically removed reach 63, 75 and 85% for MM, MA and NN methods, respectively, with false positive rates of 6, 21 and 25%. Information about DNA ploidy abnormalities were globally preserved after automatic elimination of debris and aggregates by MM and MA methods as opposed to NN method, showing that automatic classification methods can offer alternatives to tedious interactive elimination of debris and aggregates, for DNA ploidy measurements of archival tumours.
Proliferation Index and Karyometric Features of Pancreatic Intraductal Proliferative Lesions
Authors: Tomaszewska Romana , Okoń Krzysztof , Nowak Krystyna , Stachura Jerzy
Published: January 2015

The increasing frequency and poor prognosis in pancreatic cancer prompt us to search for morphological lesions being a substrate for its development. Studies of autopsy and surgically resected material as well as recent molecular studies have proved that one of the possible pathways of pancreatic neoplasia is the intraepithelial proliferation – dysplasia – cancer sequence. In the present paper we studied the proliferative activity (Ki‐67 index) in pancreatic intraepithelial proliferative lesions and its correlation with geometric features of cell nuclei as signs of increasing dysplasia. The studies were carried out in a group of 35 patients operated on for pancreatic cancer, chronic pancreatitis and other conditions not associated with the pancreas. We used immunohistochemical methods and basic morphometric parameters. The results of our studies indicate that the cell proliferative activity depends both on the type of epithelial proliferation and underlying pancreatic disease. The values of Ki‐67 index are significantly different in low‐grade proliferation (flat and papillary hyperplasia) and high‐grade proliferation (atypical papillary hyperplasia and carcinoma in situ). A set of karyometric features correlates with Ki‐67 index but there is no single feature which would have a diagnostic value.
Recent Developments and Present Status of Telepathology
Authors: Kayser K. , Beyer M. , Blum S. , Kayser G.
Published: January 2015

Telepathology which is the diagnostic work of a pathologist at a distance has been developed to routine application within the last ten years. It can be classified in relation to application, technical solutions, or performance conditions. Diagnostic pathology performance distinguishes primary diagnosis (for example, frozen section statement) from secondary diagnosis (for example, expert consultation) and quality assurance (diagnostic accuracy, continuous education and training). Applications comprise (a) frozen section service; (b) expert consultations; (c) remote control measurements; and (d) education and training. The technical solutions distinguish active (remote control, live imaging) systems from passive (conventional microscope handling, static imaging), and the performance systems with interactive (on‐line, live imaging) use from those with passive (off‐line, static imaging) practice. Intra‐operative frozen section service is mainly performed with remote control systems; whereas expert consultations and education/training are commonly based upon Internet connections with static imaging in an off‐line mode. The image quality, transfer rates, and screen resolution of active and passive telepathology systems are sufficient for an additional or primary judgment of histological slides and cytological smears. From the technical point of view, remote control telepathology requires a fast transfer and at least near on‐line judgement of images, i.e., image acquisition, transfer and presentation can be considered one performance function. Thus, image size, line transfer rate and screen resolution define the practicability of the system. In expert consultation, the pixel resolution of images and natural color presentation are the main factors for diagnostic support, whereas the line transfer rate is of minor importance. These conditions define the technical compartments, especially size and resolution of camera and screen. The performance of commercially available systems has reached a high quality standard. Pathologists can be trained in a short time and use the systems in a routine manner. Several telepathology systems have been implemented in large Institutes of Pathology which serve for frozen section diagnosis in small hospitals located in the local area. In contrast, expert consultation is mainly performed with international connections. There is a remarkable increase of expert consultations by telepathology according to the experiences of the Armed Forces Institute of Pathology or the Department of Pathology, Thoraxklinik, Heidelberg. In expansion of these experiences, a “globalization” of telepathology can be expected. Telepathology can be used to shrink the period necessary for final diagnosis by request for diagnostic assistance to colleagues working in appropriate related time zones. Telepathology is, therefore, not a substitute of conventional diagnostic procedures but a real improvement in the world of pathology.
Reconstruction of Axial Tomographic High Resolution Data from Confocal Fluorescence Microscopy: A Method for Improving 3D FISH Images
Authors: Heintzmann R. , Kreth G. , Cremer C.
Published: January 2015

Fluorescent confocal laser scanning microscopy allows an improved imaging of microscopic objects in three dimensions. However, the resolution along the axial direction is three times worse than the resolution in lateral directions. A method to overcome this axial limitation is tilting the object under the microscope, in a way that the direction of the optical axis points into different directions relative to the sample. A new technique for a simultaneous reconstruction from a number of such axial tomographic confocal data sets was developed and used for high resolution reconstruction of 3D‐data both from experimental and virtual microscopic data sets. The reconstructed images have a highly improved 3D resolution, which is comparable to the lateral resolution of a single deconvolved data set. Axial tomographic imaging in combination with simultaneous data reconstruction also opens the possibility for a more precise quantification of 3D data. The color images of this publication can be accessed from http://www.esacp.org/acp/2000/20‐1/heintzmann.htm. At this web address an interactive 3D viewer is additionally provided for browsing the 3D data. This java applet displays three orthogonal slices of the data set which are dynamically updated by user mouse clicks or keystrokes.
A Telepathology Based Virtual Reference and Certification Centre for DNA Image Cytometry
Authors: Haroske G. , Giroud Francoise , Kunze K. D. , Meyer W.
Published: January 2015

An increasing need for flexible consultation between pathologists, including the application of fast evolving supplementary technologies, has been identified during the last years. Although pathology is already one of the most advanced application of telemedicine there is more to come from the fast evolution towards computerized microscope image analysis: A reproducible quantification of measurable descriptors of the lesions in cells and tissues (so‐called biological markers) is an indispensable adjunct to routine diagnostic application. Among such quantitative methods DNA image cytometry is increasingly applied by pathologists for assistance in diagnostics.

As for other pathological issues, too, a reference center for the clinical application of DNA image cytometry might be therefore of utmost value for pathologists using that method.

Based on advanced telematic technologies, a Virtual Reference and Certification Center (VRCC) could be installed for certifying the cytometry hardware and software, the analytical procedures, and the basic interpretation of the results. It will be designed to be operated as a non‐attended service, based on quantification servers accessible via Internet round the clock. The VRCC will supply appropriate standardization and normalization materials and run a GroupWare platform for consensus making by experts.
Analysis of Erythrocyte Glycophorin‐A Variants by Flow Cytometry in Lung Disease Patients Detects the Effect of Tobacco Smoke
Authors: Neri Monica , Geido Elio , Filiberti Rosangela , Orecchia Roberto , Di Vinci Angela , Cafferata Mara , Tassara Elisabetta , Puntoni Riccardo , Giaretti Walter
Published: January 2015

The glycophoryn A (GPA) assay evaluates somatic in vivo mutations. It is considered a cumulative biodosimeter for genotoxic exposures and is under evaluation in cancer risk assessment.

GPA, a polymorphic membrane protein of the erythrocytes, determines the MN blood groups. The N0 and NN variant frequencies (VF) may be detected in MN subjects (about 50% of the population) by flow cytometry using two differently labelled antibodies.

We explored if GPA N0 and NN VF might be relevant to the assessment of individual lung cancer risk and susceptibility, in a small population with a high prevalence of heavy tobacco smokers: 8 lung cancer patients and 16 subjects with non‐malignant lung diseases associated with increased risk of lung cancer.

There was a wide interindividual variability and complete overlap between non‐neoplastic and neoplastic patients. A significant positive correlation was seen with smoking duration in N0 VF (p=0.04, age‐adjusted). Current smokers (n=12) displayed higher N0 values than never (n=1) or ex‐smokers (n=11), 36.3±18.2 and 21.0±13.2, respectively (p < 0:01). No association was shown with occupational exposure.

The present exploratory study suggests that assessment of individual lung cancer risk and susceptibility by the GPA assay does not seem to be feasible. The assay appears to provide a biomarker of longterm exposure to tobacco smoke.
Combining Dynamic and Static Robotic Telepathology: A Report on 184 Consecutive Cases of Frozen Sections, Histology and Cytology
Authors: Della Mea Vincenzo , Cataldi Palmina , Pertoldi Barbara , Beltrami Carlo A.
Published: January 2015

The aim of this paper is to describe the experiments carried out to evaluate the diagnostic efficacy of a dynamic‐robotic telepathology system for the delivery of pathology services to distant hospitals. The system provides static/dynamic features and the remote control of a robotized microscope over 4 ISDN lines. For evaluation purposes, 184 consecutive cases of frozen sections (60), gastrointestinal pathology (64), and urinary cytology (60) have been diagnosed at a distance using the system, and the telediagnosis obtained in this way has been compared with the traditional microscopic diagnosis. Diagnostic agreement ranged from 90% in urinary cytology to 100% in frozen sections. The results obtained suggest that such a system can be considered a useful tool for supporting the pathology practice in isolated hospitals.
Diagnosis of Congenital Heart Malformations – Possibilities for the Employment of Telepathology
Authors: Tennstedt Cornelia , Sunkel-Wehrstedt Kathrin , Vogel Martin , Hufnagl Peter
Published: January 2015

Goal: In a study of 10 autopsy cases with congenital cardiac malformations we investigated whether obtaining a second opinion by means of telepathology could satisfy quality standards for the diagnosis of cardiac malformations and what the advantages and disadvantages of such a procedure might be. Material: The investigatory samples were 10 formalin‐fixed hearts with complex malformations from 9 fetuses and one newborn on which autopsies had been performed at the Pathological Institute of the Charité Hospital. The requests for a second opinion, which included text and image data, were sent in the form of Microsoft PowerPoint presentations to 5 experts in 4 countries. Per case the number of images that were sent was between 3 and 7. The size of the files was between 439 and 942 kb. The time required for preparation of the cases for sending them to the specialists was between 1 and 2 hours: this encompassed the time for putting the notation on the images, compressing them, creating a file that included both the images and the clinical data and then sending the case file. Results: All 10 cardiac malformations were correctly identified. In 8 of the 10 cases at least one expert had questions. After these questions had been answered and further images had been sent final correct diagnoses were made in all cases. All experts said that the quality of the images was very good. Use of a standardized findings questionnaire, which also included the marking of anatomic structures and of pathological findings in the images, proved useful. Standardized findings forms facilitate orientation during interpretation of the cases and should be used generally to avoid misunderstandings in telepathological communication. Conclusions: In general it is possible to obtain an effective and reliable diagnosis of congenital heart malformations by means of telepathology. It is far quicker to get a second opinion by this means than by conventional means.
How Could Static Telepathology Improve Diagnosis in Neuropathology?
Authors: Remmelinck Myriam , Lopes M. Beatriz S. , Nagy Nathalie , Rorive Sandrine , Rombaut Katja , Decaestecker Christine , Kiss Robert , Salmon Isabelle
Published: January 2015

The present paper reports our experience with, and our opinion of static telepathology as applied to neuropathology by means of the PHAROS acquisition system and conventional telephone data transmission (modem). The classical procedure of expert consultation based on surface mailing of histological slides is routinely performed, especially in highly specialized fields of pathology. Telepathology is an easy means of sharing scientific expertise at international level and could thus improve diagnosis particularly in neuropathology, where certain tumor types are very rare and complex to diagnose. Dynamic telepathology allows the referring pathologist to capture by himself images supporting their diagnosis. Using static telepathology the pathologist could be limited in diagnosis by problems in fields selection.

We devoted a whole year to collecting all the technical parameters characterizing the use of digitized neuropathological data files in order to investigate the feasibility of telepathology and the extent to which its use could improve diagnoses. Our results on a series of 38 histological brain examinations illustrate how we successfully established an international connection between two departments of pathology in Belgium and the USA. The referring pathologists gave diagnoses in 35 cases and deferred only 3. Despite a time‐consuming procedure for the telepathology session of a few cases, this tool provides easy access to expert diagnosis and real‐time discussion, both of which are of considerable interest and offer significant improvements in neuropathology.
Reliability of Telepathology for Frozen Section Service
Authors: Wellnitz Uwe , Binder Bernd , Fritz Peter , Friedel Godehard , Schwarzmann Peter
Published: January 2015

One of the most promising applications of telepathology (pathology at a distance by electronic transmission of images in pathology) is frozen section diagnosis, especially because by means of this tool operations requiring an intraoperative histopathological diagnosis are feasible at hospitals without a pathologist on‐site. For the introduction of this diagnostic tool into pathologist′s daily practice the evidence of its diagnostic accuracy comparable to that of the conventional frozen section diagnosis is crucial.

For this purpose the literature on the diagnostic accuracy of telepathological frozen section diagnosis was reviewed. In a metaanalysis these studies and reports, in which a total of more than 1290 cases had been examined, showed a slightly lower overall diagnostic accuracy (of the telepathological frozen section diagnosis) of about 0.91 than the conventional frozen section diagnosis with an average accuracy of about 0.98 found in an analysis of several studies (on frozen section diagnosis of different organs). This difference is at least predominantly caused by a higher rate of deferred and false negative frozen section diagnoses in the telepathological method, while the specificity of both methods, each more than 0.99 was not significantly different.

In conclusion, the introduction of a telepathological frozen section diagnosis for hospitals without an acceptable access to a pathologist is justifiable already at the current state of the technological development especially when considering the advantages (time saving, reduction in costs) compared to the alternative of surgical interventions without access to an intraoperative diagnosis.
The Biological Safety of Condom Material Can Be Determined Using an In Vitro Cell Culture System
Authors: Motsoane N. A. , Pretorius E. , Bester M. J. , Becker P. J.
Published: January 2015

Latex products have long been recognized as a cause of latex protein allergy. The increased usage of latex gloves, with the consequent increased occurrence of latex allergies appears to have escalated with increasing awareness of the transmission of HIV–AIDS and other infections. The use of condoms as a means to prevent the transmission of STD′s (sexually transmitted diseases) and HIV–AIDS has been widely promoted. Although extensive testing is done to evaluate the physical quality of condoms, no information is available regarding the biological safety of condoms. This study was undertaken to determine the effects of short‐term exposure to physiological levels of condom surface material on cell viability (MTT assay) and cell growth (crystal violet assay). A direct contact cell culture testing method (FDA test method F813‐83 used to evaluate the cytotoxic potential of medical materials and devices) was used. The modified test method was found to be a sensitive test system for the evaluation of the biological safety of condoms. This study reveals the importance of evaluating the biological safety of all condoms that are commercially available, because of the potential health risk that may be associated with prolonged use of certain types of condoms.
Intratumoral Variations in DNA Ploidy and S‐Phase Fraction in Human Breast Cancer
Authors: Arnerlöv Conny , Emdin Stefan O. , Cajander Stefan , Bengtsson Nils‐Olof , Tavelin Björn , Roos Göran
Published: January 2015

To study intratumoral DNA ploidy heterogeneity and S‐phase fraction (SPF) variability, we prospectively collected five different samples from 48 breast carcinomas and each sample was analysed separately by flow cytometry. Aneuploidy rate was 89.6% after analysis of four or five samples. DNA ploidy heterogeneity, i.e., different samples classified as either DNA euploid or DNA aneuploid in the same tumor was seen in 17%, and DNA index heterogeneity, i.e., tumor populations with different DNA indices (DIs) seen in different samples was 44%. A statistical model defining SPF heterogeneity is proposed. SPF heterogeneity as defined by us was 71%, and as expected the SPF heterogeneity rate increased significantly with increasing number of analysed samples. Four or more samples are needed to detect the most deviant (highest) SPF values. An unrecognized intratumor heterogeneity of DNA ploidy and SPF may partly explain the conflicting results reported in the literature on the above prognostic indicators.
Rapid Stereology Based Quantitative Immunohistochemistry of Dendritic Cells in Lymph Nodes: A Methodological Study
Authors: van Hensbergen Yvette , Luykx‐de Bakker Sylvia A. , Heideman Daniëlle A. M. , Meijer Gerrit A. , Pinedo Herbert M. , van Diest Paul J.
Published: January 2015

This study was done to arrive at a fast and reliable protocol for assessment of fractional volumes of immunohistochemically stained dendritic cells in lymph nodes. Twenty axillary lymph nodes of patients with locally advanced breast cancer were immuno‐histochemically stained with an S100 antibody. Fractional volumes of dendritic cells were assessed by stereology based quantitative immunohistochemistry using an interactive video overlay system including an automated microscope. The gold standard percentage of dendritic cells was the fractional volume of S100 stained cells in 500 fields systematically spread over the whole lymph node. Then, in a computer simulation, different sample sizes (1–200 fields of vision) were tested and the coefficient of variation (CV) for each sample size was calculated. The CV dropped with increasing sample size. A sample size of 100 fields of vision appeared to be optimal. Intra‐ and interobserver reproducibility appeared to be good (correlation coefficients of 0.95 and 0.86, respectively) when re‐analyzing the cases with the established protocol. In conclusion, a fast and reliable assessment of the fractional volume of dendritic cells in lymph nodes is possible with semi‐automated quantitative immuno‐histochemistry. This method will form the base for further clinical studies into the immunological response in lymph nodes of patients with locally advanced breast cancer.
SKaMPI: A Comprehensive Benchmark for Public Benchmarking of MPI
Authors: Reussner Ralf , Sanders Peter , Träff Jesper Larsson
Published: January 2015

The main objective of the MPI communication library is to enable portable parallel programming with high performance within the message‐passing paradigm. Since the MPI standard has no associated performance model, and makes no performance guarantees, comprehensive, detailed and accurate performance figures for different hardware platforms and MPI implementations are important for the application programmer, both for understanding and possibly improving the behavior of a given program on a given platform, as well as for assuring a degree of predictable behavior when switching to another hardware platform and/or MPI implementation. We term this latter goal performance portability, and address the problem of attaining performance portability by benchmarking. We describe the SKaMPI benchmark which covers a large fraction of MPI, and incorporates well‐accepted mechanisms for ensuring accuracy and reliability. SKaMPI is distinguished among other MPI benchmarks by an effort to maintain a public performance database with performance data from different hardware platforms and MPI implementations.
Dependence of DNA‐Histograms on The Sampling Techniques in Fine Needle Aspirates of the Breast
Authors: Elzagheid A. , Collan Y.
Published: January 2015

48 fine needle aspiration biopsy (FNAB) samples from 25 breast cancer cases, originally used for cytodiagnosis were subjected to DNA cytometry. There were air dried smears stained with the MGG method, and samples stained with HE or PAP stain after 50% ethanol fixation and cytocentrifugation. Different sampling strategies were applied. Four methods were tested: method 1: cell groups measured, method 2: all cells measured, method 3: free cells measured, and method 4: atypical free cells measured. Method 4 showed most often DNA aneuploid histogram patterns, sampling method 1 had the highest number of DNA diploid histogram patterns. Diagnostic approaches may benefit from a sampling method detecting the hiding aneuploid cell population. Grading of neoplasm could potentially benefit from other approaches.
Chromosomal Imbalances are Associated with Metastasis‐Free Survival in Breast Cancer Patients
Authors: Aubele Michaela , Auer Gert , Braselmann Herbert , Nährig Jörg , Zitzelsberger Horst , Quintanilla‐Martinez Leticia , Smida Jan , Walch Axel , Höfler Heinz , Werner Martin
Published: January 2015

Multiple chromosomal imbalances have been identified in breast cancer using comparative genomic hybridization (CGH). Their association with the primary tumors′ potential for building distant metastases is unknown. In this study we have investigated 39 invasive breast carcinomas with a mean follow‐up period of 99 months (max. 193 months) by CGH to determine the prognostic value of chromosomal gains and losses. The mean number of chromosomal imbalances per tumor was 6.5±0.7 (range 2 to 18). The most frequent alterations identified in more than 1/3 of cases were gains on chromosomes 11q13, 12q24, 16, 17, and 20q, and losses on 2q and 13q. A significantly different frequency of chromosomal aberrations (p≤0.05) was found between DNA‐diploid and non‐diploid tumors (gain on chromosome 17). Differences were also noted between tumors progressing to distant metastases within the period of follow‐up and those which do not (gains on 11q13 and 12q24; loss on 12q). Significant univariate correlations (p≤0.05) with the metastasis‐free survival of patients were found for lymph node status, the cytometrical determined DNA ploidy (diploid/non‐diploid) and anisokaryosis, and for DNA gains on 11q13, 12q24, 17, and 18p. An unexpected inverse correlation was found between clinical outcome and gains on 11q13 and 12q24. In multivariate analysis independent prognostic value, in addition to lymph node status, was found for chromosomal gains on 11q13, 12q24, 17 and 18p. Amplification on 20q, which did not correlate with metastasis‐free survival in a univariate analysis, showed weak prognostic significance in combination with the nodal status. The prognostic value of chromosomal alterations – some of them by inverse correlation – suggests an interaction and/or compensation of the involved amplified genes and their effects on the occurrence of distant metastases in breast cancer patients.
Expression of Multidrug Resistance‐Associated Markers, Their Relation to Quantitative Pathologic Tumour Characteristics and Prognosis in Advanced Ovarian Cancer
Authors: Brinkhuis Mariël , Izquierdo Miguel A. , Baak Jan P. A. , van Diest Paul J. , Kenemans Peter , Scheffer George L. , Scheper Rik J.
Published: January 2015

Mean nuclear area has been consistently shown by different researchers to be a strong and independent prognostic factor in advanced ovarian carcinoma. However, the biological background of the prognostic value of nuclear area remains unclear. Others have found that the multidrug‐resistance (MDR) related protein LRP has strong prognostic value. In the present study we have analysed whether the mean nuclear area and LRP are related in tumour tissue of the ovary obtained at the debulking operation before the administration of chemotherapy in 40 patients. The mitotic activity index, volume percentage epithelium, standard deviation of nuclear area and the other MDR‐related proteins P‐glycoprotein (JSB‐1, MRK‐16) and MRP have been investigated additionally for correlations and prognostic value. No correlations were found between the morphometrical features and MDR‐related proteins. Mean nuclear area tended to be larger in LRP positive tumours, but the correlation was not significant. In multivariate analysis LRP‐protein expression and mean nuclear area had independent prognostic value. Further studies are required to elucidate the biological background of the strong prognostic value of mean nuclear area in advanced ovarian cancer.
Towards a Protocol for the Attachment of Metadata to Grid Service Descriptions and Its Use in Semantic Discovery
Authors: Miles Simon , Papay Juri , Payne Terry , Luck Michael , Moreau Luc
Published: January 2015

Service discovery in large scale, open distributed systems is difficult because of the need to filter out services suitable to the task at hand from a potentially huge pool of possibilities. Semantic descriptions have been advocated as the key to expressive service discovery, but the most commonly used service descriptions and registry protocols do not support such descriptions in a general manner. In this paper, we present a protocol, its implementation and an api for registering semantic service descriptions and other task/user‐specific metadata, and for discovering services according to these. Our approach is based on a mechanism for attaching structured and unstructured metadata, which we show to be applicable to multiple registry technologies. The result is an extremely flexible service registry that can be the basis of a sophisticated semantically‐enhanced service discovery engine, an essential component of a Semantic Grid.
Individual‐Based Simulation of the Clustering Behaviour of Epidermal Growth Factor Receptors
Authors: Goldman Jacki P. , Gullick William J. , Johnson Colin G.
Published: January 2015

This paper describes ongoing work on a project to simulate the behaviour of epidermal growth factor receptors. These are structures which can be found on the surface of cells in the body, which receive and process chemical signals concerned with cell growth. The implementation of a program which simulates the stimulation and clustering behaviour of these structures is described, then the paper discusses how the simulation can be scaled up so that a whole cell can be simulated on a tractable timescale. Finally some early results are given which show the effect of changing parameters in the system, and discuss ongoing work on calibrating the simulation against results from experiments.
SCALEA‐G: A Unified Monitoring and Performance Analysis System for the Grid
Authors: Truong Hong-Linh , Fahringer Thomas
Published: January 2015

This paper describes SCALEA‐G, a unified monitoring and performance analysis system for the Grid. SCALEA‐G is implemented as a set of grid services based on the Open Grid Services Architecture (OGSA). SCALEA‐G provides an infrastructure for conducting online monitoring and performance analysis of a variety of Grid services including computational and network resources, and Grid applications. Both push and pull models are supported, providing flexible and scalable monitoring and performance analysis. Source code and dynamic instrumentation are implemented to perform profiling and monitoring of Grid applications. A novel instrumentation request language for dynamic instrumentation and a standardized intermediate representation for binary code have been developed to facilitate the interaction between client and instrumentation services.
Dynamic Grid Scheduling with Job Migration and Rescheduling in the GridLab Resource Management System
Authors: Kurowski K. , Ludwiczak B. , Nabrzyski J. , Oleksiak A. , Pukacki J.
Published: January 2015

Grid computing has become one of the most important research topics that appeared in the field of computing in the last years. Simultaneously, we have noticed the growing popularity of new Web‐based technologies which allow us to create application‐oriented Grid middleware services providing capabilities required for dynamic resource and job management, monitoring, security, etc. Consequently, end users are able to get easier access to geographically distributed resources. In this paper we present the results of our experiments with the Grid(Lab) Resource Management System (GRMS), which acts on behalf of end users and controls their computations efficiently using distributed heterogeneous resources. We show how resource matching techniques used within GRMS can be improved by the use of a job migration based rescheduling policy. The main aim of this policy is to shorten job pending times and reduce machine overloads. The influence of this method on application performance and resource utilization is studied in detail and compared with two other simple policies.
XMatch: A Language for Satisfaction‐Based Selection of Grid Services
Authors: Andreozzi Sergio , Montesi Danilo , Moretti Rocco
Published: January 2015

Grid systems enable the sharing of a large number of geographically‐dispersed resources among different communities of users. They require a mapping functionality for the association of users requests expressed in terms of requirements and preferences to actual resources. This functionality should deal with a potentially high number of similar resources and with the diversity of the perceived satisfactions of users. We propose XMatch, a query language enabling the expression of the user request in terms of the expected satisfaction over XML‐based representation of available resources. This language offers a compact way for users to express their preferences for Grid resources and enable the maximization of the global preference.