bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation and evaluation of a communication intensive application on the EARTH multithreaded system
Authors: Theobald Kevin B. , Kumar Rishi , Agrawal Gagan , Heber Gerd , Thulasiram Ruppa K. , Gao Guang R.
Published: August 2002

This paper reports a study of sparse Matrix Vector Multiplication (MVM) on a parallel computing platform based on a fine‐grained multithreaded program execution model. Such sparse MVM computations, when parallelized without performing graph partitioning, suffers a very high communication to computation ratio, and is well known to have a very limited scalability on traditional distributed‐memory machines. The particular multithreaded system we use is the Efficient Architecture for Running THreads (EARTH) model, which can be implemented from off‐the‐shelf processors.

With the Class B input sparse matrix from the NAS CG benchmark (75 000 rows), we attain an absolute speedup of 90 on 120 nodes of a distributed memory configuration. This is achieved without using inspector/executor or graph partitioning, or any communication minimization phase, which means that similar results can be expected for adaptive problems as well. High scalability is achieved because of a number of characteristics of the EARTH architecture: local synchronizations, low communication overheads, ability to overlap communication and computation, and low context‐switching costs. Copyright © 2002 John Wiley & Sons, Ltd.
A flexible framework for consistency management
Authors: Weber S. , Nixon P. A. , Tangney B.
Published: August 2002

Recent distributed shared memory (DSM) systems provide increasingly more support for the sharing of objects rather than portions of memory. However, like earlier DSM systems these distributed shared object systems (DSO) still force developers to use a single protocol, or a small set of given protocols, for the sharing of application objects. This limitation prevents the applications from optimizing their communication behaviour and results in unnecessary overhead.

A current general trend in software systems development is towards customizable systems, for example frameworks, reflection, and aspect‐oriented programming all aim to give the developer greater flexibility and control over the functionality and performance of their code. This paper describes a novel object‐oriented framework that defines a DSM system in terms of aconsistency modeland an underlyingcoherency protocol. Different consistency models and coherency protocols can be used within a single application because they can be customized, by the application programmer, on a per‐object basis. This allows application specific semantics to be exploited at a very fine level of granularity and with a resulting improvement in performance.

The framework is implemented in JAVA and the speed‐up obtained by a number of applications that use the framework is reported. Copyright © 2002 John Wiley & Sons, Ltd.
An analysis of VI Architecture primitives in support of parallel and distributed communication
Authors: Begel Andrew , Buonadonna Philip , Culler David E. , Gay David
Published: August 2002

We present the results of a detailed study of the Virtual Interface (VI) paradigm as a communication foundation for a distributed computing environment. Using Active Messages and the Split‐C global memory model, we analyze the inherent costs of using VI primitives to implement these high‐level communication abstractions. We demonstrate a minimum mapping cost (i.e. the host processing required to map one abstraction to a lower abstraction) of 5.4 μs for both Active Messages and Split‐C using four‐way 550 MHz Pentium III SMPs and the Myrinet network. We break down this cost to the use of individual VI primitives in supporting flow control, buffer management and event processing and identify the completion queue as the source of the highest overhead. Bulk transfer performance plateaus at 44 Mbytes/s for both implementations are due to the addition of fragmentation requirements. Based on this analysis, we present the implications for the VI successor, Infiniband. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of predistorted reflection‐mode hybrid prototype networks with symmetrical and asymmetrical characteristics
Authors: Fathelbab W. M. , Hunter I. C. , Rhodes J. D.
Published: August 2002

A new technique for predistorting filter transfer functions to compensate for the dissipative losses present in the resonator elements is introduced. The method is based on the formation of two admittances from lossless transfer functions. Each admittance is then individually predistorted and connected to a 3‐dB hybrid coupler. A simulated numerical example demonstrates that the method is capable of designing network prototypes with a combined predistorted reflection and transmission functions. Tables of prototype element values for elliptic lowpass/highpass functions are also provided. Copyright © 2001 John Wiley & Sons, Ltd.
An approximation for the input conductivity function of the non‐linear resistive grid
Authors: Gluskin Emanuel
Published: August 2002

The 2‐term approximations for the input conductivity functions, iin=fin(vin), of a grid of similar weakly non‐linear (parabolic) conductors, and the grid's symmetric cuts, measured between two close nodes, are derived, using a semi‐empirical method; the results of a relevant PSpice simulation are presented. The functions fin(vin) of the grid's symmetric cuts possess a common analytical feature. Simulation results show that the error in the calculation of the non‐linear terms in the input functions is less than 1 per cent. Copyright © 2001 John Wiley & Sons, Ltd.
A study on WTA cellular neural networks
Authors: Forti Mauro
Published: August 2002

This paper addresses a number of basic issues concerning the dynamics of a class of winner‐take‐all cellular neural networks (WTA CNNs) proposed by Seiler and Nossek. The main result is an analytical estimate for the settling time, which shows from a theoretical point of view that such CNNs are well suited for on‐line applications requiring a large number of units, fast processing speed and a relatively high resolution. Other results are the determination of the largest parameter set that guarantee a correct WTA functionality for all initial conditions and the solution of a conjecture made by Seiler and Nossek. These results are proved by means of a new Lyapunov function to analyse the global dynamical behaviour of the WTA CNNs. Copyright © 2001 John Wiley & Sons, Ltd.
Improved design of FIR notch filter by using Bernstein polynomial
Authors: Tseng Chien‐Cheng
Published: August 2002

Bernstein polynomial has been used to design maximally flat FIR notch filters. However, the designed magnitude response is not exactly zero valued at notch frequency. In order to eliminate this undesired distortion, a novel method is presented to improve notch filter design in this paper. The designed notch filter is not only exactly zero valued at notch frequency but also has unity gain at ω=0 and π. Copyright © 2001 John Wiley & Sons, Ltd.
A behavioural modelling technique for visual microprocessor mixed‐signal VLSI chips
Authors: Földesy P. , Rodríguez‐Vázquez A.
Published: August 2002

This paper describes procedures to build custom‐tailored behavioural models of cellular neural networks (CNNs), and acompanion tool to run these models. The main property of the CNNs is the emerging behaviour, i.e. new phenomena arise from the interactions of thousands of identical cells. The existence of these phenomena need is to be checked during the design phase, which requires a full network simulation and therefore constitutes a very time‐consuming step of circuit verification. To solve this task as a modelling problem, we introduce a new behavioural model optimization technique. Starting from a user‐defined set of block models, the proposed framework produces an optimized selection which is used to build up a full‐chip model. The optimization goal is the minimization of the simulation CPU time and the maximization of the time domain precision. A dedicated environment has been developed for efficient numerical simulation; this environment is briefly described in the paper. Two case studies are also presented to demonstrate the effectivity of the technique. Copyright © 2002 John Wiley & Sons, Ltd.
Robustness oriented design tool for multilayer DTCNN applications
Authors: López P. , Vilariño D. L. , Brea V. M. , Cabello D.
Published: August 2002

In this work, we present a design automation tool for the synthesis of multilayer discrete time cellular neural network (DTCNN) structures that takes into account hardware implementation constraints. In so doing, the possible implementation on a VLSI CNN chip of the solutions found is guaranteed. The algorithm is based on stochastic optimization strategies, particularly genetic algorithms. In order to guarantee correct operation of analog VLSI chips the robustness of the templates and the network complexity have been considered during the optimization process by means of the introduction of penalty functions. This strategy has the side effect of reducing the computational cost of the optimization process since it focuses on those areas of the search space that meet the implementation requirements. As a difference from previous approaches to robust template design, the problem of robustness in greyscale input applications is also considered under the assumption of an appropriate selection of the training set, that must not only define the task but also contain relevant information about the images to be processed. Copyright © 2002 John Wiley & Sons, Ltd.
Telomere length measurement by fluorescence in situ hybridization and flow cytometry: Tips and pitfalls
Authors: Baerlocher Gabriela M. , Mak Jennifer , Tien Teri , Lansdorp Peter M.
Published: August 2002

Background

Telomeres containing noncoding DNA repeats at the end of the chromosomes are essential for chromosomal stability and are implicated in regulating the replication and senescence of cells. The gradual loss of telomere repeats in cells has been linked to aging and tumor development and methods to measure telomere length are of increasing interest. At least three methods for measuring the length of telomere repeats have been described: Southern blot analysis and quantitative fluorescence in situ hybridization using either digital fluorescence microscopy (Q‐FISH) or flow cytometry (flow‐FISH). Both Southern blot analysis and Q‐FISH have specific limitations and are time‐consuming, whereas the flow‐FISH technique requires relatively few cells (105) and can be completed in a single day. A further advantage of the flow‐FISH method is that data on the telomere length from individual cells and subsets of cells (lymphocytes and granulocytes) can be acquired from the same sample. In order to obtain accurate and reproducible results using the flow‐FISH technique, we systematically explored the influence of various steps in the protocol on telomere length values and established an acceptable range for the most critical parameters.

Methods

Isolated leukocytes from whole blood are denatured by heat and 70%/75% formamide, then hybridized with or without a telomere‐specific fluorescein isothiocyante (FITC)‐conjugated peptide nucleic acid probe (PNA). Unbound telomere PNA is washed away, the DNA is counterstained, and telomere fluorescence is measured on a flow cytometer using an argon ion laser (488 nm) to excite FITC. For each sample, duplicates of telomere PNA‐stained and unstained tubes are analyzed.

Results

Cell counts and flow‐FISH telomere length measurements were performed on leukocytes and thymocytes of humans and other species. Leukocyte suspensions were prepared by two red blood cell lysis steps with ammonium chloride. Optimal denaturation of DNA was achieved by heating at 85–87°C for 15 min in a solution containing 70%/75% formamide. Hybridization was performed at room temperature with a 0.3 μg/ml telomere‐PNA probe for at least 60–90 min. Unbound telomere‐PNA probe was diluted at least 4,000–40,000 times with wash steps containing 70%/75% formamide at room temperature. LDS 751 and DAPI were suitable as DNA counterstains as they did not show significant interference with telomere length measurement.

Conclusions

The use of flow‐FISH for telomere length measurements in nucleated blood cells requires tight adherence to an optimized protocol. The method described here can be used to determine rapidly the telomere length in subsets of nucleated blood cells. Cytometry 47:89–99, 2002. © 2002 Wiley‐Liss, Inc.
Flow cytometric S‐phase fraction measurement in breast carcinoma: Influence of software and histogram resolution
Authors: Jourdan Marie‐Lise , Ferrero‐Poüs Magali , Spyratos Frédérique , Romain Sylvie , Martin Pierre‐Marie , Chassevent Agnès
Published: August 2002

Background

S‐phase fraction (SPF) measurement by flow cytometry is a clinically useful prognostic factor in patients with breast carcinoma. Standardized SPF determination is essential. As part of a multicenter study, we evaluated the influence of the choice of software and histogram resolution (256, 512, or 1,024 channels) on SPF quantification.

Methods

One hundred thirty‐three DNA histograms were analyzed in three laboratories with Modfit 5.2, Modfit LT, and Multicycle AV software. Strict rules for histogram interpretation and software management were applied. The following five options were compared: MF 5.2 1024, MF 5.2 256, MF LT 256, MC AV 256, and MC AV 512.

Results

In the DNA diploid and aneuploid groups, SPF distributions were not statistically different among the five options. Excellent quantitative correlations were obtained between pairs of options. When using tertiles as cutpoints for SPF classification, concordance rates ranged from 79.7% to 93.2% for DNA diploid samples and from 87.8% to 95.9% for DNA aneuploid samples, the best results being obtained with software working with a similar histogram resolution.

Conclusions

Standardized use of commercially available software, including the choice of histogram resolution, provides comparable SPF results. Cytometry 48:66–70, 2002. © 2002 Wiley‐Liss, Inc.
Comparative genomic hybridization study of nasal‐type NK/T‐cell lymphoma
Authors: Ko Young H. , Choi Kyung E. , Han Jeong H. , Kim Jin M. , Ree Howe J.
Published: August 2002

BACKGROUND

Nasal‐type NK/T‐cell lymphoma is a rare type of non‐Hodgkin's lymphoma. The genetic changes associated with pathogenesis have not been well defined. This study investigates the nonrandom genetic alteration of nasal‐type NK/T‐cell lymphoma. Methods: Nine cases were studied. Comparative genomic hybridization (CGH) was carried out using fresh tumor tissues of seven nasal‐type NK/T‐cell lymphomas. To complement the data by CGH, loss of heterozygosity (LOH) of chromosomes 6q, 1p, and 17p using polymorphic markers and p53 gene mutation by polymerase chain reaction–single‐strand conformation polymorphism (PCR‐SSCP) were analyzed. Results: The DNA copy number changes of seven nasal‐type NK/T‐cell lymphomas were gains on chromosomes 2q(5), 13q(4), 10q(3), 21q(2), 3q(2), 5q(2), and 17q(2), and losses involving chromosomes 1p(4), 17p(4), 12q(3), 13q(2), and 6q(1). One of six cases informative for at least two markers for chromosome 6q showed LOH at D6S300, D6S1639, D6S261, D6S407, and D6S292. Two cases showing loss of 1p and 17q by CGH revealed LOH at D1S214, D1S503, and D17S559. P53 mutation was detected in exon 8 in one of nine cases. Conclusion: Frequent DNA losses at 1p, 17p, and 12q and gains at 2q, 13q, and 10q suggested that these regions could be targets for further molecular genetic analysis to investigate tumor suppressor genes or oncogenes associated with tumorigenesis of NK/T‐cell lymphoma. Infrequent alteration of 6q contrary to previous studies raises doubt about an implication of 6q loss in the pathogenesis of early‐stage NK/T‐cell lymphoma. Further studies on more defined cases are required to verify their association. Cytometry (Comm. Clin. Cytometry) 46:85–91, 2001. © 2001 Wiley‐Liss, Inc.
On the design of Robust‐WDM local area networks
Authors: El‐Bawab Tarek S. , Jayasumana Anura P.
Published: August 2002

Robust wavelength division multiplexing (Robust‐WDM) is a proposal to realize cost‐effective WDM local area networks (LANs) which can get around the expensive need for laser wavelength stabilization. The type of these networks that relies on an access protocol with aperiodic reservations and lenient‐token‐passing based control channel (the AR/LTP protocol) is promising. We look at the deployment of the AR/LTP analytical model in designing this type of network. The model is used to predict the effect of component and network parameters on the waiting time characteristics of the network. An increase in node operation times (i.e. receiver response time, transmitter select time and reservation period) would result in increasing the average waiting time of a connection request, but the waiting time is more sensitive to the physical span of the network and its size. It is also observed that increasing the inter‐reservation threshold may result in little increase in waiting time up to some limit beyond which delay increases rapidly. Copyright © 2001 John Wiley & Sons, Ltd.
Dynamic bandwidth allocation and buffer dimensioning under equal segment scheme to support video‐on‐demand services
Authors: Zhang Liren , Fu Huirong , Ng Chee Hock
Published: August 2002

This paper focuses on the optimization of network bandwidth allocation and buffer dimensioning to transport pre‐stored MPEG video data from source to playback destination across ATM networks. This is one of the most important issues in the support of video‐on‐demand (VoD) service. This paper provides a novel scheme in the dynamic allocation of bandwidth to segments of video using ABR mode. The dynamic bandwidth allocation is based on a new concept, called playback tunnel which is obtained from the traffic characteristics of the pre‐stored MPEG video trace to determine the optimum of transmission bandwidth as well as the buffer capacity to ensure that the playback buffer neither underflows nor overflows. The proposed scheme is tested with real‐life MPEG video traces. The obtained results have shown its significant performance improvement in terms of the capacity of playback buffer, the start‐up playback delay, the size of video segment and the network multiplexing gain. Copyright © 2001 John Wiley & Sons, Ltd.
DRED: a random early detection algorithm for TCP/IP networks
Authors: Aweya James , Ouellette Michel , Montuno Delfin Y.
Published: August 2002

It is now widely accepted that a RED [2] controlled queue certainly performs better than a drop‐tail queue. But an inherent weakness of RED is that its equilibrium queue length cannot be maintained at a preset value independent of the number of TCP active connections. In addition, RED's optimal parameter setting is largely correlated with the number of connections, the round‐trip time, the buffer space, etc. In light of these observations, we propose DRED, a novel algorithm which uses the basic ideas of feedback control to randomly discard packets with a load‐dependent probability when a buffer in a router gets congested. Over a wide range of load levels, DRED is able to stabilize a router queue occupancy at a level independent of the number of active TCP connections. The benefits of stabilized queues in a network are high resources utilization, predictable maximum delays, more certain buffer provisioning, and traffic‐load‐independent network performance in terms of traffic intensity and number of connections. Copyright © 2002 John Wiley & Sons, Ltd.
Well‐differentiated villoglandular adenocarcinoma of the uterine cervix: Cytomorphologic observation of five cases
Authors: Khunamornpong Surapan , Siriaunkgul Sumalee , Suprasert Prapaporn
Published: August 2002

We retrospectively examined the cytologic findings of well‐differentiated villoglandular adenocarcinoma (VGA) treated in our hospital. Cervical smears of four cases and a touch preparation of another case of VGA formed the materials for the study. The cytologic features were correlated with the histomorphology of VGA. Architecturally, long slender papillae and cohesive branching epithelial sheets with smooth borders and a lack of feathery edge were observed. Crowding and overlapping of nuclei were noted. The nuclei were uniform, small, and round to oval‐shaped, with evenly distributed granular chromatin. Nucleoli were absent or inconspicuous. Mitoses were occasionally seen in all but one case. As the features of VGA are distinctive, the diagnosis could be possible on cytological grounds. Examination of cervical smears would be helpful for an early diagnosis of VGA or to suggest the coexistence of other neoplastic components. Diagn. Cytopathol. 2002;26:10–14. © 2002 Wiley‐Liss, Inc.
Limiting factors for cytopathological diagnosis of high‐grade squamous intraepithelial lesions: A cytohistological correlation between findings in cervical smears and loop electrical excision procedure
Authors: Pinto Álvaro P. , Tuon Felipe F.B. , Torres Luiz Fernando Bleggi , Collaço Luiz Martins
Published: August 2002

The present study sought possible factors leading to the cytological diagnosis of atypical squamous cells of uncertain significance (ASCUS) in cases of high‐grade squamous intraepithelial lesions (HSIL). Based on retrospective histopathological analysis of loop electrical excision procedure (LEEP) products that diagnosed HSIL, two study groups were randomly selected. The first was consisted of cases with two consecutive Papanicolaou (Pap) smears with the diagnosis of ASCUS. The second (control) group was represented by cases diagnosed as HSIL by cytology. From the Pap smears diagnosed as ASCUS, the sampling limitations was different from control group (P < 0.05). The median size of the largest lesion in each case with ASCUS was 2.66 mm (± 1.71 mm). In the control group, the median size of the largest lesion was 5.15 mm (±2.58 mm) (P < 0.05). The size of the lesion and sample limitations led patients with cervical intraepithelial neoplasms to be diagnosed as ASCUS for two consecutive times, after a 6‐mo period. Diagn. Cytopathol. 2002;26:15–18. © 2002 Wiley‐Liss, Inc.
TIA‐1+ cytotoxic large T‐cell lymphoma of the mediastinum: Case report
Authors: Yang Grace C.H. , Yee Herman T. , Wu C. Daniel , Aye Lwin M. , Chachoua Abraham
Published: August 2002

A 52‐year‐old previously healthy Caucasian woman presented with superior vena cava syndrome, secondary to compression of a bulky anterior mediastinal mass involving the right lung. Fine‐needle aspiration biopsy of the mediastinum yielded large epithelioid cells intermingled with small mature lymphocytes. The epithelioid cells are LCA positive, expressing cytoplasmic CD3 diffusely and TIA‐1 focally, but negative for EMA, CD4, CD8, CD15, CD20, CD30, and CD56. The TIA‐1+ cytoplasmic granules correlated to the azurophilic granules in Diff‐Quik‐stained cells, pink granules in Ultrafast Papanicolaou‐stained cells, and dense core granules in electron microscopy. In situ hybridization for Epstein‐Barr viral RNA was negative. The background small lymphocytes were composed of a majority of CD4+ T‐lymphocytes and minority of CD8+ T‐lymphocytes. The patient responded well to six cycles of CHOP chemotherapy, followed by radiation with a total dose of 4140 cGy delivered to the mediastinum in 23 fractions. On the chest X‐ray taken 6 mo later, there was minimal apical fibrosis with no evidence of an acute intrathoracic pathology. To the best of our knowledge, this case may be the first report of cytotoxic large T‐cell lymphoma of the mediastinum. Diagn. Cytopathol. 2002;26:154–157; DOI 10.1002/dc.10050 © 2002 Wiley‐Liss, Inc.
Dysphagia in a patient with a history of large B‐cell lymphoma: Esophageal disease with negative biopsy findings
Authors: Crook Terri W. , Robinson Robert A.
Published: August 2002

A patient with a previous diagnosis of lymphoma showed signs of dysphagia. Endoscopy found a lesion of the esophagus. Brush cytology and biopsy sampling were accomplished. The biopsy showed inflammation and granulation tissue but no tumor. The cytology specimen, however, was diagnostic of lymphoma. This case emphasizes the need for obtaining cytologic specimens concurrently with biopsies of esophageal lesions. Diagn. Cytopathol. 2002;26:167–169; DOI 10.1002/dc.10078 © 2002 Wiley‐Liss, Inc.
Estrogen and progesterone hormone receptor status in breast carcinoma: Comparison of immunocytochemistry and immunohistochemistry
Authors: Tafjord Svetlana , Bøhler Per J. , Risberg Bjørn , Torlakovic Emina
Published: August 2002

We evaluated the correlation between histologic and cytologic specimens in the determination of estrogen receptor (ER) and progesterone receptor (PR) status in breast carcinoma and investigated the causes of clinically significant discrepancies. We analyzed 70 immunoassays for ER and 60 for PR from 71 patients with breast carcinoma. Concordance between cytology and histology was 89% for ER and 63% for PR using scores from pathology reports. Concordance between cytology and histology was 98% for ER and 91% for PR using consensus scores (obtained after reevaluation by the team of pathologists). Thirty of 130 (23%) tests had clinically relevant discrepancies, 53% of which were caused by wrong interpretation of cytologic findings, 10% by wrong interpretation of histologic findings, 17% by sampling error and 20% were not available for reevaluation. Wrong interpretation of the results for ER and PR status in cytology was a far more frequent cause of clinically relevant discrepancies than sampling errors. The use of strict criteria is recommended. Diagn. Cytopathol. 2002;26:137–141; DOI 10.1002/dc.10079 © 2002 Wiley‐Liss, Inc.
Cytologic clue of so‐called nodular histiocytic hyperplasia of the pleura
Authors: Choi Yoon‐La , Song Sang‐Yong
Published: August 2002

So‐called “nodular histiocytic hyperplasia” (NHH) is a benign histiocytic lesion caused by mechanical irritation, inflammation, and tumor. Frequently, it has been confused with mesothelial lesions and other malignant neoplasms. The diagnostic clue is proliferating cells in the lesion showing diffuse, strong immunoreactivity against the histiocytic marker, CD68. Recently, we encountered a case of so‐called NHH of the pleura and confused it with various malignant neoplasms on histologic examination. An 80‐yr‐old Korean female presented with ascites, pleural effusions, and nodules on the pleural base. Both ascites and pleural effusion tapping smears displayed moderate cellularity, vaguely nodular cellular aggregates mainly composed of mononuclear cells with bland morphology, entrapped mesothelial cells, and background lymphocytes. Pleural biopsy demonstrated vaguely nodular, compact cellular aggregates of reactive histiocytes which were immunoreactive against CD68. Based on our case, cytologic examination as well as immunohistochemical study should be stressed in the case of so‐called NHH. They can provide us more credible morphologic clues to reach a more accurate diagnosis than histologic examination alone, and we can avoid invasive procedures or unnecessary therapies to patients. To our best knowledge, this is the first report describing the cytologic features of so‐called NHH in the English‐language literature. Diagn. Cytopathol. 24:256–259, 2001. © 2001 Wiley‐Liss, Inc.
Cytologic spectrum of 227 fine‐needle aspiration cases of chest‐wall lesions
Authors: Goel Amit , Gupta S.K. , Dey P. , Radhika S. , Nijhawan R.
Published: August 2002

This study was carried out with the objective of studying the cytomorphology of the wide variety of chest‐wall lesions. Two hundred twenty‐seven chest‐wall lesions were studied over a period of 4 yr. Routine May‐Grünwald‐Giemsa (MGG) and hematoxylin‐eosin (H&E) slides were studied along with special stains, whenever required. The malignant lesions comprised 36.13% of all cases (81/227). Of the 126 benign lesions, the majority were inflammatory in nature (68/126), the next commonest lesion being lipoma (38/126). Rare cases of tuberculosis involving the sternum, epithelioid leiomyosarcoma, and neuroendocrine tumors involving ribs, malignant nerve sheath tumors involving the chest wall, metastatic carcinoma of the stomach and prostate, and papillary carcinoma thyroid are reported in this series. Histopathology was available in 24 cases, and hematological correlation in one case. A 100% cytohistological and cytohematological correlation was found, with no false positives or false negatives. In conclusion, fine‐needle aspiration cytology is a rapid, diagnostic tool, eliciting many interesting lesions in the chest wall. It is useful not only in detecting primary and metastatic lesions, but also in follow‐up of tumor recurrence. Diagn. Cytopathol. 24:384–388, 2001. © 2001 Wiley‐Liss, Inc.
Fine‐needle aspiration of hepatocellular carcinoma: False‐negative result due to epithelioid cells
Authors: Najat Mourra  , Flejou Jean‐François
Published: August 2002

The presence of epithelioid cells in fine‐needle aspirations of a liver nodule is rare, but may complicate the diagnosis of the nodule. We report on a case of a liver nodule in hepatitis C cirrhosis. Results of fine‐needle aspiration mainly revealed the presence of epithelioid cells, without any recognizable tumor cells. Histological examination of the nodule after surgical resection showed a hepatocellular carcinoma with numerous epithelioid and gigantocellular granulomas, without necrosis. Diagn. Cytopathol. 24:396–398, 2001. © 2001 Wiley‐Liss, Inc.
Myoepithelioma presenting as a midline cystic tongue lesion: Cytology, histology, ancillary studies, and differential diagnosis
Authors: De Las Casas Luis E. , Hoerl H.D. , Oberley T.D. , Hafez G.R. , Sempf J.M. , Shalkham J.E. , Kurtycz D.F.I.
Published: August 2002

Salivary gland myoepithelioma (ME) is a neoplasm derived from myoepithelial cells that lacks the ductal and broad mesenchymal differentiation seen in the vast majority of mixed tumors. This report describes the cytologic findings of a cystic ME presenting in the midline of the dorsal tongue, a site where no salivary glands are generally present. The tumor was well circumscribed and composed of sheets of monotonous epithelioid cells without ductal cells. The cells were positive for S‐100 protein and ultrastructurally had features of myoepithelial cells. The fine needle aspiration (FNA) biopsy findings, differential diagnosis, histology, immunohistochemistry, and electron microscopic features of this interesting and uncommon neoplasm are presented. To the best of our knowledge, there have been no cytologic reports of ME of the tongue. Diagn. Cytopathol. 24:403–407, 2001. © 2001 Wiley‐Liss, Inc.
Neural network‐based screening (NNS) in cervical cytology: No need for the light microscope?
Authors: Kok Myrthe R. , van der Schouw Yvonne T. , Boon Mathilde E. , Grobbee Diederick E. , Kok Lambrecht P. , Schreiner‐Kok Petra G. , van der Graaf Yolanda , Doornewaard Heleen , van den Tweel Jan G.
Published: August 2002

Neural network‐based screening (NNS) of cervical smears can be performed as a so‐called “hybrid screening method,” in which parts of the cases are additionally studied by light microscope, and it can also be used as “pure” NNS, in which the cytological diagnosis is based only on the digital images, generated by the NNS system. A random enriched sample of 985 cases, in a previous study diagnosed by hybrid NNS, was drawn to be screened by pure NNS. This study population comprised 192 women with (pre)neoplasia of the cervix, and 793 negative cases. With pure NNS, more cases were recognized as severely abnormal; with hybrid NNS, more cases were cytologically diagnosed as low‐grade. For a threshold value ≥HSIL (high‐grade squamous intraepithelial lesions), the areas under the receiver operating characteristic (ROC) curves (AUC) were 81% (95% CI, 75–88%) for pure NNS vs. 78% (95% CI, 75–81%) for hybrid NNS. For low‐grade squamous intraepithelial lesions (LSIL), the AUC was significantly higher for hybrid NNS (81%; 95% CI, 77–85%) than for pure NNS (75%; 95% CI, 70–80%). Pure NNS provides optimized prediction of HSIL cases or negative outcome. For the detection of LSIL, light microscopy has additional value. Diagn. Cytopathol. 24:426–434, 2001. © 2001 Wiley‐Liss, Inc.
Tophaceous pseudogout: A pitfall in the diagnosis of chondrosarcoma
Authors: Lambrecht Nils , Nelson Scott D. , Seeger Leanne , Bose Shikha
Published: August 2002

Tumoral calcium pyrophosphate dihydrate deposition disease (TCPPD, tumoral or tophaceous pseudogout) is a rare nonneoplastic entity which mimics soft‐tissue or skeletal malignancy. We present here the fine‐needle aspiration cytology findings of a unique case of TCPPD in a 76‐yr‐old woman, with a large paraischial soft‐tissue mass diagnosed as a malignant neoplasm. The difficulty in diagnosing such lesions by fine‐needle aspirates is discussed and reviewed in the context of known cases from the literature. Diagn. Cytopathol. 25:258–261, 2001. © 2001 Wiley‐Liss, Inc.
Differential action of KR‐31378, a novel potassium channel activator, on cardioprotective and hemodynamic effects
Authors: Lee Byung Ho , Seo Ho Won , Yoo Sung‐Eun , Kim Sun‐Ok , Lim Hong , Shin Hwa Sup
Published: August 2002

The cardioprotective and hemodynamic effects of KR‐31378, a highly cardioselective ATP‐sensitive potassium channel activator with minimal hypotensive effect, were evaluated in rats and dogs, and compared with those of BMS‐191095 and lemakalim. KR‐31378 did not show any significant effect on methoxamine‐induced aortic constriction up to doses of 300 μM, whereas BMS 191095 produced a moderately potent relaxant effect (IC50: 9.0 μM). In conscious rats, KR‐31378 slightly increased blood pressure only at high dose (100 mg/kg, iv), unlike BMS‐191095 that dose‐dependently decreased blood pressure (ED20: 2.03 mg/kg). In anesthetized beagle dogs, KR‐31378 was approximately 100‐fold less potent than BMS‐191095 for most hemodynamic parameters (iv ED20 for blood pressure lowering: 33.7 and 0.37 mg/kg, respectively). In anesthetized rats subjected to 45‐min coronary occlusion and 90‐min reperfusion, KR‐31378 (iv) dose‐dependently reduced the infarct zone from 58.6% to 42.1%, 36.6%, and 34.3% for 0.1, 0.3, and 1.0 mg/kg, respectively (P < 0.05), the effects being comparable to those of BMS 191095. In anesthetized beagle dogs that underwent 2‐h occlusion followed by 4.5‐h reperfusion, KR‐31378 (2 mg/kg, iv infusion) markedly reduced the infarct zone from 48.7% in controls to 19.1% at a dose of 2 mg/kg (P < 0.05). The reduction in infarct zone afforded by KR‐31378 in rats was inhibited by pretreatment with selective ATP‐sensitive potassium channel blockers, sodium 5‐hydroxydecanoate and glibenclamide. These results indicate that KR‐31378 is a potent cardioprotective agent with potentially minimal hypotensive effects. Thus, it could be potentially useful in the prevention and treatment of acute myocardial infarction. Drug Dev. Res. 54:182–190, 2001. © 2002 Wiley‐Liss, Inc.
Effect of long‐term stabilization of cationic liposomes as defibrotide delivery system for antithrombotic activity
Authors: Esposito Elisabetta , Cortesi Rita , Porta Roberto , Trento Fabio , Nastruzzi Claudio
Published: August 2002

The general goal of this study was to produce cationic liposome formulations suitable for the in vivo administration of defibrotide (DFT) (a DNA‐based drug) and to investigate in vitro and in vivo the stability of such a formulation. This article describes the freeze‐drying of cationic liposomes using as cryoprotectants different carbohydrates, such as sorbitol, mannitol, and sucrose. Liposome characteristics before and after freeze‐drying, such as size, morphology, and ability in complexing a DNA‐based drug, have been investigated. The in vitro studies indicate that cationic liposomes sufficiently maintain the initial characteristics after lyophilization and rehydration including the ability to complex DFT. The in vivo data show that lyophilized cationic liposome formulations can be safely stored for at least 3 months. Before in vivo use, liposomes can be rehydrated with DFT solutions, resulting in the formation of stable complexes retaining an in vivo activity comparable to that of the freshly prepared formulation. Drug Dev. Res. 55:127–138, 2002. © 2002 Wiley‐Liss, Inc.
KMUP 880708: A vanyllilamide‐based β1‐adrenoceptor antagonist with α‐adrenoceptor blocking and potassium channel opening activities
Authors: Chiu Chaw‐Chi , Chen Yea‐Wen , Wu Jiunn‐Ren , Lin Young‐Tso , Chen Ing‐Jun , Yeh Jwu‐Lai
Published: August 2002

A vanillylamide‐based propanolamine derivative, KMUP 880708, was first investigated both in vivo and in vitro. KMUP 880708 (0.1, 0.5, 1.0, and 2.0 mg kg–1, iv) produced dose‐dependent hypotensive and bradycardia responses in pentobarbital‐anesthetized Wistar rats. KMUP 880708 (0.1, 0.5, and 1.0 mg kg–1, iv) also markedly inhibited both the tachycardia effects induced by (–)isoproterenol and arterial pressor responses induced by phenylephrine. KMUP 880708 competitively antagonized (–)isoproterenol‐induced positive inotropic and chronotropic effects of the atria and tracheal relaxation responses on isolated guinea pig tissues. The apparent pA2 values for KMUP 880708 was 7.82 ± 0.06 in the right atria, 7.51 ± 0.13 in the left atria, and 6.31 ± 0.07 in the trachea, respectively, indicating that KMUP 880708 was selective β1‐adrenoceptor blocker. In thoracic aorta experiments, KMUP 880708 also produced a competitive antagonism of norepinephrine‐induced contraction with pA2 value of 7.92 ± 0.52, indicating that KMUP 880708 was α‐adrenoceptor antagonist. In isolated rat thoracic aorta, KMUP 880708 more potently relaxed the contractions induced by phenylephrine (10–5 M) than those by high K+ (75 mM). KMUP 880708‐induced relaxation was significantly reduced by endothelium removal and by exposure to L‐NG‐nitro arginine methyl ester (L‐NAME, 1 and 3 × 10–4 M), indomethacin (3 × 10–5 M), methylene blue (10–5 M) and 1H‐[1,2,4]oxadiazolol[4,3,‐a]quinoxalin‐1‐one (ODQ, 10–6 M). The vasorelaxant effect of KMUP 880708 on phenylephrine‐induced contraction was attenuated by the pretreatment with tetraethylammonium (TEA), glibenclamide, charybdotoxin, and apamin, but not by 4‐aminopyridine (4‐AP). In addition, KMUP 880708 inhibited phenylephrine‐induced biphasic contraction and affected the fast‐twitch phase more significantly than the slow tonic phase. In the radioligand‐binding assay, the Ki values of [3H]CGP‐12177 binding to rat ventricle and lung membranes were 15.14 and 524.81 nM, respectively, and the value of [3H]prazosin binding to rat brain membrane was 3.89 nM. The ranking order of inhibition for [3H]CGP‐12177 binding on β‐adrenoceptor was propranolol > labetalol > KMUP 880708 > atenolol, and that for [3H]prazosin binding to α‐adrenoceptor was KMUP 880708 > labetalol. In conclusion, KMUP 880708 was found to be a new generation α/β‐adrenoceptor blocker with selective β1‐adrenoceptor blocking and vascular smooth muscle relaxation activities. Furthermore, the vasodilator effect of KMUP 880708 is attributed to the release of NO or NO‐related substance from vascular endothelium. While the endothelium‐independent mechanism involved in the relaxation of KMUP 880708 is probably linked to K+ channel activation in these vessels. Drug Dev. Res. 55:104–117, 2002. © 2002 Wiley‐Liss, Inc.
Probing adenosine and P2 receptors: Design of novel purines and nonpurines as selective ligands
Authors: Jacobson Kenneth A.
Published: August 2002

Recent approaches to the design of selective agonists and antagonists at adenosine (AR) and P2 receptors include both modifying known receptor ligands and searching for structurally diverse antagonists. The ribose‐like moiety of nucleoside/nucleotide derivatives was rigidified with a methanocarba (mc) modification, to constrain the ring in a conformation that was favored in binding to ARs or P2Y receptors. (N)‐mc analogs of various N6‐substituted adenosine derivatives, including cyclopentyl and 3‐iodobenzyl, in which the parent compounds are potent agonists at either A1 or A3ARs, respectively, retained high receptor affinity and selectivity. For nucleotides acting as P2Y1 receptor antagonists, the (N)‐mc analog MRS 2279 ((1R,2S,4S,5S)‐1‐[(phosphato)methyl]‐4‐(2‐chloro‐6‐methylaminopurin‐9‐yl) bicyclo [3.1.0]‐hexane‐2‐phosphate) proved to be a selective antagonist, with an IC50 of 52 nM. Other ribose substitutions possible in P2Y1 receptor antagonists were 4‐ and 6‐membered rings and acyclic derivatives. High affinity for the A2BAR was achieved through the formation of anilides and benzylamides of XCC (8‐[4‐[[[carboxy]methyl]oxy]phenyl]‐1,3‐dipropylxanthine). A p‐cyanoaniline derivative (MRS 1754, Ki value 1.97 nM) was 205‐, 255‐, and 289‐fold selective for the human A2BARs vs. human A1/A2A/A3 ARs, respectively. A template approach based on the pyridine family, i.e., 1,4‐dihydropyridine nucleus and the corresponding 3,5‐diacylpyridines, was used for the design of novel adenosine antagonists. The pyridine derivative MRS 1523 (5‐propyl‐2‐ethyl‐4‐propyl‐3‐(ethylsulfanylcarbonyl)‐6‐phenylpyridine‐5‐carboxylate) was shown to be a selective antagonist at the rat A3AR as well as the human A3AR. Chemical libraries were screened computationally and using binding assays to identify novel AR antagonists. Molecular modeling of ARs and P2Y receptors provided hypotheses for ligand docking. Drug Dev. Res. 52:178–186, 2001. Published 2001 Wiley‐Liss, Inc.
Adenosine A2A receptor ligands: Effects on neuronal excitability
Authors: Phillis John W.
Published: August 2002

Our evolving understanding of the mechanisms involved in the actions of adenosine on central neurons during the course of the past three decades has largely been a consequence of certain specific advances. Early recognition that adenosine could either inhibit or stimulate cyclic AMP formation led to the concept of A1 (inhibitory) or A2 (stimulatory) receptors coupled via G proteins to adenylate cyclase. The early development of selective agonists and antagonists for the A1 binding site then stimulated a considerable volume of pharmacological research on the actions of this receptor. Evidence for the existence of more than one type of A2 receptor also accumulated, culminating in the cloning of two receptors, the high‐affinity A2A and lower‐affinity A2B receptors. The synthesis and availability of CGS 21680, a selective agonist for the A2A receptor, made possible studies on the pharmacological effects of its activation and the subsequent development of a series of A2A receptor antagonists has further clarified the roles that this receptor plays in the central nervous system. Whereas A1 receptor activation inhibits synaptic transmission, primarily by decreasing excitatory neurotransmitter release from presynaptic nerve terminals, A2A receptor stimulation appears to enhance neurotransmitter release as a result of increased Ca2+ uptake. In brain slices, CGS 21680 facilitates excitatory transmission by increasing glutamate and acetylcholine release. However, when tested in vivo on central neurons by iontophoretic application, CGS 21680 has had a powerful depressant effect on neuronal activity which was blocked by coapplication of an A2A receptor antagonist but not by a selective A1 receptor antagonist. Further studies with the GABAA antagonists bicuculline and picrotoxin, which also block the inhibitory actions of CGS 21680, revealed that in this instance A2A receptor activation facilitates GABA release, causing inhibition of neuronal firing. Whether the GABA release is a consequence of enhanced excitatory drive to GABAergic neurons or is a direct effect of an action at A2A receptors on GABAergic nerve terminals remains uncertain. Drug Dev. Res. 52:331–336, 2001. © 2001 Wiley‐Liss, Inc.
Classical conditioning in the rat fetus: Involvement of mu and kappa opioid systems in the conditioned response
Authors: Smotherman William P.
Published: August 2002

When the Embryonic Day 20 (E20) rat fetus is given a conditioning trial involving a paired presentation of an artificial nipple (the conditioned stimulus; CS) with an intraoral infusion of milk (the unconditioned stimulus; US), it shows evidence of classical conditioning when again exposed to the CS during a test trial. Specifically, the fetus shows fewer oral grasp responses (the conditioned response; CR) when continuously presented with the artificial nipple. The present study further investigated this classically conditioned reduction in oral grasping. Separate experiments (a) examined the time course of the reduction in oral grasping (Experiment 1), (b) characterized the time course of mu opioid (Experiment 2) and kappa opioid (Experiment 3) involvement in the CR, and (c) described changes in fetal behavior (Experiment 4) associated with mu and kappa opioid effects on responding to the artificial nipple. The results are discussed in terms of opioid involvement in establishing and maintaining early suckling behavior. © 2002 Wiley Periodicals, Inc. Dev Psychobiol 40: 104–115, 2002. DOI 10.1002/dev.10016
Converging methods in developmental science: An introduction
Authors: Casey B. J. , Munakata Yuko
Published: August 2002

This special issue of Developmental Psychobiology reflects a number of recent advances in the field of developmental neuroscience. The most evident are methodological advances in noninvasive neuroimaging such as those described in a parallel special issue of Developmental Science, Volume 5, 2002. While advances in imaging methods offer a new era in developmental research, other methods (e.g., animal, computational, lesion, and genetic) remain essential in constraining and informing theories of brain and behavioral development. The papers in this issue highlight the importance of a converging methods approach to the study of developmental science and illustrate how a variety of available tools allow insights into both new and classic developmental questions. © 2002 Wiley Periodicals, Inc. Dev Psychobiol 40: 197–199, 2002. DOI 10.1002/dev.10026
Adrenomedullin and diabetes mellitus
Authors: Ruzicska Eva , Toth Miklos , Tulassay Zsolt , Somogyi Aniko
Published: August 2002

Adrenomedullin (AM) is a novel 52 amino acid peptide hormone, originally isolated from human pheochromocytoma. AM acts as a local autocrine and/or paracrine vasoactive hormone and has vasodilator and blood pressure lowering properties. AM as a vasodilative molecule protects the vascular wall but its exact role is still uncertain. AM is considered to play an important endocrine role in various tissues in maintaining electrolyte and fluid homeostasis. Its plasma concentration in healthy conditions is low. In hypertension, chronic renal failure and congestive heart failure its plasma concentration increases in a parallel manner with the severity of the disease. It is assumed that this peptide plays an important role in physiological and pathological conditions compensating the effects of vasoconstrictive molecules. Investigations have proven that in diabetic angiopathies the levels and production of vasoconstrictive factors and AM are increased, while other relaxing substances such as nitric oxide (NO) are decreased. It is still uncertain whether the increased release of AM is a compensatory mechanism or a coincidental event. Although the precise role of AM in the pathogenesis of diabetic complications is still to be elucidated, the altered concentration of AM in diabetes could indicate a certain interaction between AM induction and vascular function. Hence, the induction of vascular AM can be a new target of therapeutic approach to diabetic complications. Copyright © 2001 John Wiley & Sons, Ltd.