bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond anarchy: Self‐organized topology for peer‐to‐peer networks
Authors: Saffre Fabrice , Ghanea‐Hercock Robert
Published: February 2004

In this article, we discuss the new constraints that will apply to future, highly dynamic networks and investigate one of the major problems that is likely to affect their deployment: traffic/workload distribution. Starting with a very simple model, we demonstrate that a structure made of undifferentiated subunits will almost inevitably hit a scalability barrier, unless new design rules are applied. We then give quantitative evidence that a hybrid network topology termed the “hypergrid” could have the potential of solving some of the most critical problems (relay overload and network vulnerability), yet could still be produced by applying local rules only. © 2004 Wiley Periodicals, Inc. Complexity 9: 49–53, 2004
Kolmogorov complexity estimates for detection of viruses in biologically inspired security systems: A comparison with traditional approaches
Authors: Goel Sanjay , Bush Stephen F.
Published: February 2004

This article presents results in two mutually complementary areas: distributed immunological information assurance and a new signature‐matching technique based on Kolmogorov Complexity. This article introduces a distributed model for security based on biological paradigms of epidemiology and immunology. In this model each node in the network has an immune system that identifies and destroys pathogens in the incoming network traffic as well as files resident on the node. The network nodes present a collective defense to the pathogens by working symbiotically and sharing pathogen information with each other. Each node compiles a list of pathogens that are perceived as threats by using information provided from all the nodes in the network. The signatures for these pathogens are incorporated into the detector population of the immune systems to increase the probability of detection. Critical to the success of this system is the detection scheme, which should not only be accurate but also efficient. Three separate schemes for detecting pathogens are examined, namely, contiguous string matching, Hamming distance, and Kolmogorov Complexity. This work provides a model of the system and examines the efficiency of different detection schemes. A simulation model is built to study the sensitivity of model parameters, such as signature length, sampling rate, and network topology, to detection of pathogens. © 2004 Wiley Periodicals, Inc. Complexity 9: 54–73, 2004
Aspects of adaptive reconfiguration in a scalable intrusion tolerant system
Authors: Bryant Stephanie , Wang Feiyi
Published: February 2004

An Erratum has been published for this article in Complexity (2004) 9(4) 46

SITAR architecture integrates basic fault tolerant concepts along with adaptive reconfiguration in a security setting. It enables commercial‐off‐the‐shelf servers to continue operating despite intrusion or partial compromise. The adaptive reconfiguration dynamically changes the system configuration in response to environment threats to maintain service availability. The discussion covers important aspects of SITAR's adaptive reconfiguration mechanism, including its central algorithm, and mitigation of the oscillation problem. The mechanism uses a feedback loop model and techniques of mutual exclusion, steady state monitoring, and system observation to implement cooperative control. The adaptive mechanism is implemented and demonstrated as part of the SITAR prototype system. © 2004 Wiley Periodicals, Inc. Complexity 9: 74–83, 2004
Autonomic defense: Thwarting automated attacks via real‐time feedback control
Authors: Armstrong Derek , Carter Sam , Frazier Gregory , Frazier Tiffany
Published: February 2004

A critical threat to organizations, and the Internet itself, is a class of automated network attacks referred to as Internet worms. This article examines the use of mathematical models and optimization algorithms—specifically a partially‐observable Markov decision process (PO‐MDP) based feedback control system—as the basis for implementing an autonomic defense system (ADS) that can protect organizations against Internet worms. The PO‐MDP ADS introduced in this article is capable of detecting and responding to worms in real time. Furthermore, the PO‐MDP ADS can ameliorate the rate of incorrect control decisions that would normally occur in the presence of sensor false alarms. © 2004 Wiley Periodicals, Inc. Complexity 9: 41–48, 2004
Influence of complex formation upon inclusion of Mn(II), Co(II), Ni(II), and Cu(II) in ZnC2O4·2H2O
Authors: Donkova B. , Pencheva J. , Djarova M.
Published: February 2004

The inclusion of 3d‐impurities Mn(II), Co(II), Ni(II) and Cu(II) in a crystalline precipitate of ZnC2O4·2H2O is investigated. This study is a part of the systematic one deal with the mechanism of inclusion of 3d‐ions in sparingly soluble oxalate systems. The experiments are carried out in bi‐ end multi‐component systems at two different mediums – one with deficiency of oxalate ions, another with excess. The insertion of 3d‐ions upon mass crystallization of ZnC2O4·2H2O does not proceed by a simple ionic substitution. The results show that the inserted amount of impurity depends on some physicochemical characteristics of the neutral monooxalato complexes [MnC2O4]o, [CoC2O4]o, [NiC2O4]o and [CuC2O4]o. Good agreement between included impurity and the concentration of its complex in the solution is established. The stability constant of monooxalato complex affects the impurity inclusion. This effect depends on the medium nature. In the deficiency of oxalate ions the factor determining the inclusion is thermodynamic one – stability of monooxalato complexes. In the excess of oxalate ions inserted amount depends on kinetic factor – the formation rate of these complexes. In the term of that the insertion of Mn(II) is definitely different in the two mediums while that of the Ni (II) does not depend on the medium. The copper shows deviation from overall dependence in the two mediums due to the Jahn‐Teller distortion. Its double decreasing insertion in the excess of oxalate ions is related with stabilization of [Cu(C2O4)2]2‐. The conclusions presume that by varying the background medium and taking in view the ions present in the solution, the amount of inserted impurities can be predicted and controlled. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A study of primary nucleation of calcium oxalate monohydrate: I‐Effect of supersaturation
Authors: El‐Shall H. , Jeon Jin‐hwan , Abdel‐Aal E. A. , Khan S. , Gower L. , Rabinovich Y.
Published: February 2004

There are various organic and inorganic constituents in kidney stones. Among them, calcium oxalate monohydrate (COM) is the primary inorganic constituent of kidney stones. However, the mechanisms of formation of kidney stones are not well understood. In this regard, a basic study is carried out for better understanding of nucleation, crystal growth and/or aggregation of formed COM crystals. The primary nucleation of calcium oxalate monohydrate is studied at the laboratory scale using turbidity measurements. Calcium chloride and potassium oxalate solutions are mixed and then added to a Turbidimeter tube for continuous recording of turbidity. Induction time (time to induce formation of detectable crystals) is estimated from time‐turbidity graphs. The effect of some urinary species, such as oxalate and calcium, on nucleation and crystallization characteristics of COM is determined by particle size distribution analysis, measuring weight of crystals and calculation of relative supersaturation. The classical nucleation theory is applied at high supersaturation ratios (SR) ranging from 1.6 to 2.2. The results indicate that nucleation rate increases with increasing supersaturation ratio from 0.81 × 1028 nuclei/cm3.sec at 1.6 SR, to 18.02 × 1028 nuclei/cm3.sec at 2.2 SR. On the other hand, free energy change and radius of critical nucleus are decreased as supersaturation ratio is increased. The nucleation rates are higher than those reported in literature. Such discrepancy is discussed on the bases of differences in experimental techniques. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Effects of cadmium on crystallization of calcium phosphates
Authors: Lundager Madsen H. E. , Abbona F. , Barrese E.
Published: February 2004

The precipitation of calcium phosphates in the presence of increasing cadmium amount was studied at 25 °C in dilute ammoniacal solutions ([Ca] = [P] = 0.005 M). An amorphous precipitate, an apatite‐like calcium phosphate and the compound Cd5H2(PO4)4·4H2O are found according to pH and Cd concentration. The nucleation of hydroxyapatite is greatly delayed by cadmium, which influences also its crystallinity, but the effect tends to vanish with time. The role of cadmium is discussed. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
High‐temperature heat capacity and lattice anharmonicity of LiGaO2
Authors: Neumann H.
Published: February 2004

The first three even moments of the phonon density of states of LiGaO2and the anharmonic contribution to the heat capacity at constant volume of the compound are estimated from experimental heat capacity data. The effect of lattice anharmonicity is discussed in terms of perturbation theory. The temperature dependent principal Grüneisen functions of LiGaO2are calculated. The results obtained for LiGaO2are compared with existing literature for other ternary lithium compounds. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Voltage‐current characteristics of Bi‐2223 superconducting tape near Tc under γ irradiation
Authors: Kayed T. S. , Ercan I.
Published: February 2004

Voltage‐current characteristics at four different applied magnetic fields (7, 20, 30, and 40 mT) of Bi2Sr2Ca2Cu3Ox superconducting tape were measured in the temperature range from 100 to 115 K. They were also measured at zero magnetic field before and after γ irradiations up to 10 MRad at different temperatures just below the critical temperature. The data were fitted to a power law expression V = I β(T) in which the exponential parameter β under 20 mT field and after irradiation is found to fluctuate around three and then drops to unity near the critical temperature which may be interpreted as a sign of Kosterlitz‐Thouless transition. The electrical properties of the tape were found to be very sensitive to γ irradiation where most of the changes take place in low γ doses. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Structural, thermal and optical characterizations of a NLO material: L‐alaninium oxalate
Authors: Dhanuskodi S. , Vasantha K.
Published: February 2004

An organic electro‐optic and nonlinear optical (NLO) material, L‐alaninium oxalate, was synthesized by the standard method. The synthesized material was purified by repeated recrystallization. Single crystals were grown by the slow evaporation technique. The grown crystals were transparent and had optimum dimensions (20 × 3 × 2 mm3) and were characterized by single crystal XRD, FT‐NMR, FT‐IR, TGA‐DTA and UV‐Vis‐NIR techniques. The second harmonic generation (SHG) from the material was confirmed using Nd:YAG laser. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Crystal structure of DL‐Tryptophan at 173K
Authors: Hübschle Ch. B. , Messerschmidt M. , Luger P.
Published: February 2004

The crystal structure of pure DL‐tryptophan has been determined at 173 K, using large but thin plate formed crystals of C11H12N2O2, which were grown by cooling down a saturated solution of DL‐tryptophan in isopropanole / formic acid. The crystals are monoclinic, space group P 21/c, with the unit cell constants: a = 18.899(2), b = 5.7445(6), c = 9.309(1) Å, β = 101.776(2), V = 989.4(4) , Dcalc = 1.371, Z = 4, F(000) = 432, λ(MoKα) = 0.71073 Å, μ = 0.096 mm‐1. The crystal structure was solved by direct methods and refined by full‐matrix least squares to a final R‐factor = 4.03 % with 3343 unique reflections of which 2104 were observed. The molecule is zwitterionic in the crystal with the protonated amino group and the carboxylate group in unusual conformations with respect to the indole ring system compared to other tryptophan derivatives. A D‐ and L‐ molecular pair forms a dimer by N – H … O hydrogen bonds via a crystallographic inversion center. The dimers are linked by further N – H … O hydrogen bonds to form a head to head bilayer arrangement of the molecules in the crystal lattice. Except for weak van der Waals contacts there is no relation between indole tails of neighboured bilayers. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Crystallization and structural studies of n‐benzyloxycarbonyl‐L‐tyrosine‐L‐glycine‐ethyl ester (Z‐Tyr‐Gly‐OEt)
Authors: Nallini A. , Saraboji K. , Ponnuswamy M. N. , Katti S. B.
Published: February 2004

It is axiomatic that efficient crystal production reflects upon the quality of structure. An empirical relation for mass proportions of two solvents in crystallization of Z‐Tyr‐Gly‐OEt shows a linear relationship. The dipeptide crystallizes in orthorhombic space group P212121, with cell parameters a = 5.0680(1) Å, b = 13.8650(1) Å and c = 28.2630(1) Å, Z = 4, Dcalc= 1.339Mg/m3, μ=0.820mm‐1, F000=848, CuKα = 1.5418 Å. The structure was solved by direct methods and final R1 and wR2 are 0.444 and 0.1276, respectively. The structure analysis reveals the trans conformation of the peptide unit with ω = ‐178.2(5)°, implying only a slight deviation from planarity. The torsion angles at glycine [ϕ, ψ = ‐84.4(7)°, 179.9(5)°] are characteristic of left‐handed poly glycine II helices. A number of N‐H…O, O‐H…O and C‐H…O hydrogen bondings play a role in stabilizing the molecules within unit cell. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
An environment for prosperity and quality living accommodating growth in the Thames Valley
Authors: Howes Hugh
Published: February 2004

The Thames Valley is seen as the powerhouse of the British economy, and one of the best performing regions in Europe. This economic base offers opportunities for expansion with the potential for it to become the knowledge capital of Europe. Business interests view the area as a highly desirable location, not only because of its markets, skills and proximity to the City and Heathrow but also because of its high quality environment.

Companies, however, complain of skills shortages, traffic congestion, lack of suitable premises and housing that is affordable to the workforce. Much of the Thames Valley is either Green Belt or Areas of Outstanding Natural Beauty. Furthermore, the availability of future water supplies, the maintenance of the quality of water in the rivers and managing flood risk are also likely to act as constraints on development in the future.

How economic growth is to be achieved with minimal additional development and without detriment to the environment is the central question that is likely to dominate planning in the this region over the next few years. Is it possible to achieve more with existing resources? Copyright © 2004 John Wiley & Sons, Ltd and ERP Environment.
Different approaches to standardized environmental management systems in local authorities – two case studies in Gothenburg and Newcastle
Authors: Emilsson Sara , Hjelm Olof
Published: February 2004

Local authorities have shown an increased interest in committing to voluntary environmental commitment. This paper analyses the use of one of them, standardized environmental management systems (EMSs). It examines how local authorities approach EMS implementation, using two case studies in two European cities, Newcastle City Council (UK) and Gothenburg City Council (Sweden). The research departs from four research topics: drivers; strategy for EMS implementation; integration, dissemination and acceptance; future development of the EMS work. The case study cities' EMS approaches are analysed starting from the three pillars of institutions: the regulative, normative and cultural–cognitive. The analyses reveal that both Newcastle and Gothenburg mainly use a normative approach to EMS implementation; however, there is a regulative inclination in Newcastle's approach. It has also been noted that there is a difference between the standards (e.g. ISO 14001 and EMAS) and the actual use of the standards. The standards are fairly regulative while the application of the standards varies from organization to organization. Copyright © 2004 John Wiley & Sons, Ltd and ERP Environment.
Androgen and vitamin D receptor expression in archival human breast tumors
Authors: Krishan Awtar , Arya Poonam , Ganjei‐Azar Parvin , Shirley Suzanne E. , Escoffery Carlos T. , Nadji Mehrdad
Published: February 2004

Background

The present study was undertaken for quantitation of androgen (AR) and vitamin D (VDR) receptor expression in human male and female breast tumors by flow cytometry.

Methods

Nuclei isolated from sections of paraffin‐embedded tumors by pepsin digestion were treated for antigen unmasking and incubated with antibodies to AR and VDR. Flow cytometric analysis was used to determine the percentage of receptor‐positive nuclei with fluorescence greater than 95% of the isotype nuclei. Mean log fluorescence channel values were used for comparing antigen density of the isotype and the antibody‐treated nuclei.

Results

Six of 23 female breast tumors had aneuploid DNA content. Nineteen of 20 estrogen receptor–positive female tumors by immunohistochemical analysis (IHC) were also AR positive by flow analysis. Aneuploid subpopulations had higher percentages of AR‐positive nuclei than did diploid populations. Eight of 33 male breast tumors had aneuploid DNA content. Twenty‐three of 33 male breast tumors were AR positive by flow analysis compared with six that were AR positive by IHC. Six AR‐positive (IHC) male tumors were also AR positive by flow analysis. VDR expression was higher in diploid female tumors than in aneuploid tumors.

Conclusions

Lack of a strong correlation between IHC and flow analysis may be due to differences in criteria used for identification of receptor‐positive and ‐negative tumors by the two methods. © 2003 Wiley‐Liss, Inc.
New laboratory test in flow cytometry for the combined analysis of serologic and cellular parameters in the diagnosis of heparin‐induced thrombocytopenia
Authors: Gobbi Giuliana , Mirandola Prisco , Tazzari Pier Luigi , Talarico Enrica , Caimi Luigi , Martini Giuliana , Papa Stefano , Conte Roberto , Manzoli Francesco A. , Vitale Marco
Published: February 2004

Background

Heparin‐induced thrombocytopenia (HIT) is a major complication of heparin therapy. A quick and reliable laboratory assay for the combined determination of pathogenic anti‐heparin and platelet factor 4 (H:PF4) antibodies in the serum and platelet activation is not currently available.

Methods

We developed a new single‐tube assay in flow cytometry that combines the detection of antibodies in the serum and their activatory properties on platelets. The assay was tested on 13 serum samples from patients with suspected HIT and six samples from normal donors. The presence of anti‐H:PF4 antibody complexes was detected by H:PF4‐coated beads, and donor platelet activation induced by HIT sera was determined by Annexin V binding. All data were compared with the patients' clinical setting, laboratory tests, and standard enzyme‐linked immunosorbent assay detection of anti‐H:PF4 antibodies.

Results

This flow cytometry assay allowed unequivocal, simultaneous detection of anti‐H:PF4 antibodies in sera and their activatory properties on platelets. All cases for which the diagnosis of HIT was confirmed were detected by the flow assay.

Conclusions

This assay, combining for the first time functional and nonfunctional testing on anti‐H:PF4 antibodies, is likely to influence the clinical decision for the management of HIT patients. © 2003 Wiley‐Liss, Inc.
Automation of bone marrow aspirate examination using the XE‐2100 automated hematology analyzer
Authors: Mori Yusuke , Mizukami Toshihiro , Hamaguchi Yukio , Tsuruda Kazuto , Yamada Yasuaki , Kamihira Shimeru
Published: February 2004

Background

Attempts to analyze bone marrow aspirates have been reported with the use of several automated blood cell counters, but sufficient accuracy in examination is not acquired yet. Major problems have included difficulties in correctly differentiating various immature cells and interference by lipid in bone marrow aspirates. The goal of this study was to solve these problems to attain more accurate assessment of bone marrow aspirates with automated blood cell counters.

Methods

We modified the XE‐2100 Automated Hematology Analyzer (Sysmex Corporation, Kobe, Japan) to fit it for bone marrow aspirate measurement and evaluated its performance. Measurements were performed with the modified XE‐2100 on 81 patient samples of bone marrow aspirates; as a reference, the manual visual method was used and flow cytometric analysis were carried out.

Results

Good correlations between results with the modified XE‐2100 and the manual visual method were obtained for total nucleated cell count (TNCC; r = 0.99), erythroblast/TNCC ratio (r = 0.93), and myeloid cell/TNCC ratio (r = 0.75).

Conclusions

When this device is used, bone marrow aspirate differentials can be determined quickly and easily. This device will be useful for preliminary examination to obtain a summary of various blood cell ratios in bone marrow aspirates before performance of microscopic examination. © 2004 Wiley‐Liss, Inc.
DRAQ5‐based DNA content analysis of hematolymphoid cell subpopulations discriminated by surface antigens and light scatter properties
Authors: Yuan Constance M. , Douglas‐Nikitin Vonda K. , Ahrens Kim P. , Luchetta Gabriel R. , Braylan Raul C. , Yang Lijun
Published: February 2004

Background

Analysis of cell cycle kinetics offers important information regarding the behavior of normal and neoplastic cells. Most often, cell cycle determinations by flow cytometry (FCM) have been performed using whole‐sample analysis with intercalating dyes like propidium iodide (PI). The cell cycle phase assessment in individual cell subsets in heterogeneous samples is best performed using combined antigen/scatter and DNA analysis. DRAQ5, a novel DNA binding dye that excites at 488 nm and emits in the far red spectra, rapidly penetrates intact live cells while preserving their light scatter properties and expression of surface antigens. We evaluated the ability of this dye to measure cell cycle phases in a variety of clinical hematolymphoid samples.

Methods

We first compared whole sample DRAQ5 and PI cell cycle analyses in 26 clinical hematolymphoid samples. Next, we analyzed cell subpopulations in 39 samples of nonpathologic bone marrow by performing simultaneous CD45/CD34 and DRAQ5 staining. We assessed cell cycle characteristics specific to each population identified by CD45/CD34/side light scatter: lymphocytes, monocytes, immature and mature granulocytes, nucleated erythroid cells, and early precursors.

Results

Whole sample DNA cell cycle analyses by DRAQ5 and PI showed no significant differences in S‐phase. DRAQ5, however, produced slightly larger coefficients of variation. DRAQ5‐based DNA content analysis was easily performed on the distinct marrow cell subpopulations, since light scatter and antigen expression were completely preserved. Significant differences in S‐phase were noted between subpopulations of cells exhibiting different degrees of maturation.

Conclusions

Because of its simplicity of use, excitability with 488 nm lasers, and the ability to stain viable cells, DRAQ5 should prove most useful in the kinetic evaluation of normal and neoplastic hematolymphoid cell subsets identified by light scatter and antigenic expression. © 2004 Wiley‐Liss, Inc.
Fine‐needle aspiration of abdominal fat pad for amyloid detection: A clinically useful test?
Authors: Ansari‐Lari M. Ali , Ali Syed Z.
Published: February 2004

Fine‐needle aspiration of abdominal fat pad (FNAFP) is commonly employed for the diagnosis of systemic amyloidosis, a disease with highly variable clinical manifestations, often presenting difficult patient management problems. We evaluated the role of FNAFP particularly in reference to its clinical usefulness. Pathology reports and clinical histories of 91 consecutive cases of FNAFP with Congo red (CR) staining at The Johns Hopkins Hospital (1999–2000) were reviewed. Major emphases were assessment of the clinical utility of the test, correlation with concurrent or subsequent biopsies, and treatment strategies. The primary indications for FNAFP were monoclonal gammopathy (34%), cardiomyopathy (22%), renal insufficiency (20%), neuropathy (8%), plasma cell dyscrasia (6%), and other conditions (10%). Of the 91 patients who underwent FNAFP, the results were as follows; 20 cases (22%) positive; 62 cases (68%) negative; eight cases (9%) insufficient for diagnosis; and one case (1%) equivocal. Of the 20 positive cases, follow‐up biopsies were performed on 11 cases, of which six were positive and five were negative for amyloid by CR. Of the 62 negative cases, follow‐up biopsies were performed on 19 cases, 14 of which were negative and five positive for amyloid by CR. A follow‐up biopsy on the single equivocal case was positive for amyloid by CR. Twenty‐one patients positive for amyloid, based on initial or follow‐up biopsies, were managed symptomatically without any specific treatment for amyloidosis. One patient, who was specifically treated for amyloidosis by melphalan and dexamethasone, died 1 wk after therapy. Three patients with multiple myeloma and amyloidosis underwent chemotherapy. We conclude that primary clinical indications for FNAFP for amyloidosis are highly variable. An FNAFP result is often not considered clinically conclusive and is followed by further invasive procedures to detect amyloid (55% of our positive and 31% of our negative FNAFP cases were rebiopsied). The estimated sensitivity and specificity of FNAFP were 75% and 92%, respectively. Overall, the reliance on the results of FNAFP depended on the degree of clinical suspicion of the treating physician. Although in the majority of cases diagnosis of amyloidosis did not alter the treatment strategies, a conclusive positive result helped in ruling out other underlying conditions as the cause of patients' symptoms. Diagn. Cytopathol. 2004;30:178–181. © 2004 Wiley‐Liss, Inc.
Fine‐needle aspiration of Riedel's disease: Report of a case and review of the literature
Authors: Harigopal Malini , Sahoo Sunati , Recant Wendy M. , DeMay Richard M.
Published: February 2004

The cytomorphological features of a case of Riedel's thyroiditis (Riedel's disease) in a 37‐yr‐old woman are reviewed. The patient presented with a diffusely enlarged thyroid gland with extension to carotid and jugular vessels bilaterally. A fine‐needle aspiration of the right lobe of the thyroid demonstrated moderate cellularity with fragments of fibrous tissue with bland spindle‐shaped cells and myofibroblasts. The patient subsequently underwent a bilateral subtotal thyroidectomy with removal of two‐thirds of both lobes of the thyroid. A frozen section diagnosis of Riedel's disease was later confirmed on paraffin sections. Here we describe the cytological findings of a case of Riedel's disease and provide some helpful clues in distinguishing it from other forms of thyroiditis such as fibrosing variant of Hashimoto's thyroiditis, subacute thyroiditis, or granulomatous thyroiditis and from malignancy with which it can be confused both clinically and cytologically. Diagn. Cytopathol. 2004;30:193–197. © 2004 Wiley‐Liss, Inc.
Stromal infiltration as a predictor of tumor invasion in breast fine‐needle aspiration biopsy
Authors: Klijanienko Jerzy , Katsahian Sandrine , Vielh Philippe , Masood Shahla
Published: February 2004

Clinical management of in situ carcinoma of the breast is different from invasive carcinomas. Thus, it is important to find cytomorphologic criteria to distinguish between these two entities. The current study is designed to assess whether, by applying strict cytologic criteria, the status of stromal invasion can be predicted. In this retrospective study, 223 consecutive nonpalpable tumors sampled by ultrasound‐guided breast fine‐needle aspirates with diagnosis of in situ and invasive carcinoma with histologic follow‐up evaluation were retrieved. Ten cytologic parameters were evaluated, which included cellular clustering, eosinophilic differentiation, necrosis, tubular structures, dirty background, nuclear anisonucleosis, cellular pleomorphism, cribriform pattern, tubular structures, and stromal infiltration. Among all the parameters examined, stromal infiltration was the most powerful predictor of status of invasion. Stromal infiltration was significantly higher in invasive (88%) than in situ (11%), P < 0.0001. In contrast, cribriform pattern (16% vs 36%) and necrosis (19% vs 59%) were more frequently seen in situ than in invasive carcinomas with P‐values of 0.0008 and <0.0001, respectively. This study demonstrates that stromal infiltration defined by strict criteria may predict the status of tumor invasion in breast fine‐needle aspirates. The combination of stromal infiltration and cribriform pattern and necrosis in aspirates may provide an opportunity in introducing a “predictive index” to differentiate between an in situ versus an invasive process. Diagn. Cytopathol. 2004;30:182–186. © 2004 Wiley‐Liss, Inc.
Ductal lavage and its histopathologic basis: A cautionary tale
Authors: Badve Sunil
Published: February 2004

Ductal lavage has been touted as a possible screening tool for patients with a high risk for the development of breast cancer. This article examines the fundamental concepts underlying the procedure and critically evaluates its possible utility in light of the known molecular and surgical pathologic data. It highlights the fact that risk assessment in breast cancer is far from an exact science, since most women who develop breast cancers are not identified as high‐risk by the Gail model. The utility of ductal lavage has as yet not been proven, and even if it were useful, it is likely to benefit only a subset of all breast cancer patients. Further studies, preferably controlled clinical trials, are necessary before routine use of the procedure can be recommended. Diagn. Cytopathol. 2004;30:166–171. © 2004 Wiley‐Liss, Inc.
Cytology of ductal lavage fluid of the breast
Authors: Ljung Britt‐Marie , Chew Karen L. , Moore Dan H. , King Eileen B.
Published: February 2004

The cytologic evaluation of nipple aspirate fluids has been shown to identify women at increased risk for developing breast cancer. One limitation of this assay is the often scant cellularity of the specimen. An improved technique, ductal lavage, utilizes a microcatheter inserted into individual breast ducts to collect large numbers of cells for cytologic evaluation. Epithelial cells in ductal lavage fluids can be categorized as benign, malignant, or showing mildly or markedly atypical changes. The cell characteristics which were most helpful in identifying abnormal cells were related to cell arrangement, cell size, nuclear size, and size variation, nuclear membrane irregularity, chromatin granularity, and the presence of large nucleoli. Cell size, nuclear size variation, and large nucleoli were the most robust features, as determined by agreement between two pathologists. Moderate cell enlargement and the presence of large nucleoli were the features selected by structured tree analysis for classifying the specimens into the diagnostic groups. The similarity of the cytology of ductal lavage fluid to nipple aspirate fluid strongly suggests that these specimens will also be useful for predicting breast cancer risk. Diagn. Cytopathol. 2004;30:143–150. © 2004 Wiley‐Liss, Inc.
Atypia in the assessment of breast cancer risk: Implications for management
Authors: Vogel Victor G.
Published: February 2004

Proliferative disease accounts for as much as one‐third of all biopsies for benign disease and 5–10% of proliferative lesions show atypia ductal or lobular hyperplasia. Nearly 40% of women with a family history of breast cancer and atypical hyperplasia subsequently develop breast cancer. A quantitative model developed by Gail and colleagues estimates the probability of developing breast cancer over time. Risk factors in the model include current age, ages at menarche and first live birth, number of previous biopsies, the presence of cellular atypia, and the number of first‐degree relatives with breast cancer. Atypical hyperplasia approximately doubles the risk of developing invasive breast cancer within any quantitative risk profile. Ductal lavage provides a minimally invasive method of collecting breast epithelial cells. The procedure opens the possibility of repeatable tracking of breast cytology over time, but its role as a risk assessment tool remains to be fully defined. Diagn. Cytopathol. 2004;30:151‐157. © 2004 Wiley‐Liss, Inc.
Utility of cytologic specimens in the evaluation of prognostic and predictive factors of breast cancer: Current issues and future directions
Authors: Sneige Nour
Published: February 2004

Although numerous biological and molecular markers of breast cancer have been identified over the past two decades, traditional factors such as estrogen receptor (ER), progesterone receptor (PR), and HER‐2 remain among the most useful indicators of prognosis and therapeutic response to treatment. These markers can be reliably evaluated in cytologic specimens, particularly in fine‐needle aspirates (FNA) of primary or metastatic breast cancer. Accurate assessment of ER, PR, and HER‐2 is critical in the treatment of breast cancer patients. A review of the literature, however, shows considerable interlaboratory variability in the detection of these markers and reporting of the test results. Because therapies are now being directed toward individual molecular targets, there is a need for increased standardization of such analyses. Current practices should follow consensus recommendations set by the College of American Pathologists and the American Society for Clinical Oncology, and the results should be monitored through quality‐assurance programs. The utility of cytologic specimens of breast lesions is also not limited to evaluation of individual prognostic and predictive factors. Cytologic specimens have been used successfully for genomic and proteomic studies. Such investigational studies are under way and offer great potential for revolutionizing the prediction of patient outcomes and disease response to therapy, as well as assessment of risk of developing breast cancer. Diagn. Cytopathol. 2004;30:158–165. © 2004 Wiley‐Liss, Inc.
Dark and pale cerebriform nuclei in FNA smears of usual papillary thyroid carcinoma and its variants
Authors: Mallik Mrinmay K. , Das Dilip K. , Mallik Anupama A. , Madda John P. , Mirza Kahvic , Al‐Bishi Khalida Khalid , George Sarah S. , Junaid T.A.
Published: February 2004

The dark (hyperchromatic) cerebriform nucleus was recently described as a frequent finding in histopathology sections of papillary carcinoma of the thyroid. In the present study, we tried to determine the frequency of dark cerebriform nuclei in the fine‐needle aspiration (FNA) smears of papillary thyroid carcinomas and compared it with those of other thyroid lesions, such as follicular neoplasms and benign hyperplastic lesions. In addition to the above‐mentioned nuclear feature, pale (hypochromatic) cerebriform nucleus and other well‐established cytomorphological criteria used in the diagnosis of papillary thyroid carcinomas were analyzed. FNA smears of a total of 102 cases comprising of 61 papillary carcinomas, 10 cases of suspicious papillary carcinomas, 12 follicular neoplasms, and 19 benign hyperplastic lesions were studied. Both the dark and pale cerebriform nuclei were found in a significantly higher number of cases of papillary thyroid carcinomas compared with follicular neoplasms (P = 0.0003 and P < 0.0001, respectively) or benign hyperplastic lesions (P = 0.0004 and P < 0.0001, respectively). Review sections available in 24 cases showed agreement between the cytopathological and the histopathological diagnoses in 18 (94.7%) of 19 papillary carcinomas. Thus, the dark and pale cerebriform nuclei can be regarded as useful cytomorphological parameters in the diagnosis of papillary thyroid carcinoma. Diagn. Cytopathol. 2004;30:187–192. © 2004 Wiley‐Liss, Inc.
The effect of familiarization time, retention interval, and context change on adults' performance in the visual paired‐comparison task
Authors: Richmond Jenny , Sowerby Paula , Colombo Michael , Hayne Harlene
Published: February 2004

In a series of three experiments, we examined the effects of familiarization time, retention interval, and changes in environmental context on adults' performance in the visual paired‐comparison (VPC) task. The magnitude of adults' novelty preference increased as familiarization time increased, decreased as retention interval increased, and was impaired by a change in context after a delay. These data are highly consistent with data obtained in prior studies using the VPC task with infants and suggest that the VPC task could be used to measure memory across the life span. © 2004 Wiley Periodicals, Inc. Dev Psychobiol 44: 146–155, 2004.
Spontaneous eye blinking in human infants: A review
Authors: Bacher Leigh F. , Smotherman William P.
Published: February 2004

Spontaneous eye blinking has been studied in clinical and neuropharmacological research in adult humans and nonhuman primates as a putative index of central dopamine system activity. One purpose of this review is to provide a general overview of the research on spontaneous eye blinking with an emphasis on the relationship between spontaneous eye blinking and central dopamine systems. We suggest that the body of research from human (adults, children, and infants) and nonhuman primates supports the continued empirical investigation of spontaneous eye blinking in human infants. A second purpose is to present approaches for empirical work to further investigate the development, correlates, and mechanisms of spontaneous eye blinking in human infants. The results of further investigation may reveal new insights into relationships between the central nervous system activity and behavior in early human development. © 2004 Wiley Periodicals, Inc. Dev Psychobiol 44: 95–102, 2004.
Social learning about ethanol in preweanling rats: Role of endogenous opioids
Authors: Hallmark Rachel A. , Hunt Pamela S.
Published: February 2004

The role of the endogenous opioid system in social learning about ethanol was examined in three experiments using preweanling rats. Experiment 1 showed that interactions with intoxicated siblings in the home cage on postnatal Days (PD) 12, 14, and 16 results in increased voluntary intake of ethanol when subjects are tested 24 hr after the final exposure. The results also suggested that the endogenous opioid system is not involved in acquisition. Administration of naloxone during social exposure to ethanol had no effect on later ethanol intake. Experiment 2 examined the effects of receptor‐selective antagonists administered prior to test. For subjects that had social exposure to ethanol, intake of ethanol was completely suppressed by either naloxone or the δ antagonist naltrindole. For ethanol‐naïve subjects, intake also was completely suppressed by naloxone. However, intake was partially blocked by naltrindole or the μ antagonist β‐FNA. Experiment 3 confirmed the differential involvement of μ and δ receptors in ethanol intake through a more comprehensive dose–response analysis of β‐FNA and naltrindole. Collectively, these data reveal that learning about ethanol from intoxicated conspecifics not only affects voluntary intake of ethanol but also alters the opioidergic response to ethanol consumption. © 2004 Wiley Periodicals, Inc. Dev Psychobiol 44: 132–139, 2004.
Sex differences and developmental effects of manipulations of oxytocin on alloparenting and anxiety in prairie voles
Authors: Bales Karen L. , Pfeifer Lisa A. , Carter C. Sue
Published: February 2004

In adult animals, peptide hormones, including oxytocin and arginine vasopressin, have been implicated in both parental behavior and the modulation of anxiety. The purpose of this study was to examine the consequences of developmental manipulations of oxytocin for the later expression of alloparental behavior as well as behavioral responses to a novel environment, the elevated plus maze (EPM). Prairie voles (Microtus ochrogaster), a cooperatively breeding species, were selected for this study. On neonatal Day 1, pups received an ip injection of oxytocin or oxytocin antagonist, or were controls, receiving either saline or handling only. At 21 and approximately 60 days of age, each animal was tested for parental care toward novel stimulus pups. At approximately 67 days, an EPM test was administered. Control females at 60 days of age were more likely to attack pups and spent less time in the open arm of the EPM, both of which might reflect higher levels of anxiety in females than males. In males, neonatal treatment with oxytocin antagonist was associated with reductions in parental care, especially during the initial exposure to pups on Day 21. Female behavior was not significantly changed as a function of neonatal treatments. Findings to date implicate vasopressin in the behavioral changes in males, that in later life followed a single exposure to an oxytocin antagonist, and suggest caution in the clinical use of agents such as Atosiban, which may have the potential to influence infant development. © 2004 Wiley Periodicals, Inc. Dev Psychobiol 44: 123–131, 2004.
Contribution of mesothelium‐derived cells to liver sinusoids in avian embryos
Authors: Pérez‐Pomares J.M. , Carmona R. , González‐Iriarte M. , Macías D. , Guadix J.A. , Muñoz‐Chápuli R.
Published: February 2004

The developing liver is vascularized through a complex process of vasculogenesis that leads to the differentiation of the sinusoids. The main structural elements of the sinusoidal wall are endothelial and stellate (Ito) cells. We have studied the differentiation of the hepatic sinusoids in avian embryos through confocal colocalization of differentiation markers, in ovo direct labeling of the liver mesothelium, induced invasion of the developing chick liver by quail proepicardial cells, and in vitro culture of chimeric aggregates. Our results show that liver mesothelial cells give rise to mesenchymal cells which intermingle between the growing hepatoblast cords and become incorporated to the sinusoidal wall, contributing to both endothelial and stellate cell populations. We have also shown that the proepicardium, a mesothelial tissue anatomically continuous with liver mesothelium, is able to form sinusoid‐like vessels into the hepatic primordium as well as in cultured aggregates of hepatoblasts. Thus, both intrinsic or extrinsic mesothelium‐derived cells have the developmental potential to contribute to the establishment of liver sinusoids. Developmental Dynamics 229:465–474, 2004. © 2004 Wiley‐Liss, Inc.
Induction and patterning of the primitive streak, an organizing center of gastrulation in the amniote
Authors: Mikawa Takashi , Poh Alisa M. , Kelly Kristine A. , Ishii Yasuo , Reese David E.
Published: February 2004

The primitive streak is the organizing center for amniote gastrulation. It defines the future embryonic midline and serves as a conduit of cell migration for germ layer formation. The migration patterns of endodermal and mesodermal precursors through the streak have been studied in great detail. Additional new breakthroughs recently have revealed the cell biological and molecular mechanisms that govern streak induction and patterning. These findings include (1) identification of the ontogeny and inductive signals of streak precursors, (2) the potential cellular mechanism of streak extension, and (3) the molecular and functional diversification along the anterior–posterior and mediolateral axes within the primitive streak. These findings indicate that amniote embryos initiate gastrulation by using both evolutionarily conserved and divergent mechanisms. The data also provide a foundation for understanding how the midline axis is defined and maintained during gastrulation of the amniotes. Developmental Dynamics 229:422–432, 2004. © 2004 Wiley‐Liss, Inc.
Folding of the tectal cortex by local remodeling of neural differentiation
Authors: Mima Tatsuo , Mikawa Takashi
Published: February 2004

The folding pattern of the brain cortex is a precisely regulated process, but the mechanism involved during development remains unclear. A proposed theory predicts that the initiation of cortical folding depends, at least partly, on nonuniform distribution of neuronal differentiation and neurite growth. We tested this theory experimentally, by remodeling the normal pattern of neuronal cell differentiation within the embryonic optic tectum. Multiple foci of activated fibroblast growth factor signaling were created in the tectal cortex to locally change the neural differentiation and axonal growth patterns. At these foci, tectal cells remained undifferentiated and their radial and tangential migration was suppressed. These local changes in the neuronal cell differentiation resulted in a conversion of the tectal cortex from smoothly extended into precociously folded. The results provide in vivo experimental evidence that microscopic changes in the neuronal cell differentiation pattern can induce or remodel the folding pattern of the brain cortex. Developmental Dynamics 229:475–479, 2004. © 2004 Wiley‐Liss, Inc.
Status of transgenic chicken models for developmental biology
Authors: Mozdziak Paul E. , Petitte James N.
Published: February 2004

The chick embryo is a classic model that has been used to gain insight into developmental processes and cell fate within the embryo for over a century. For the most part, investigators have implanted quail cells into a chicken embryo. A more powerful tool for developmental biology research than the quail:chick chimera system would be to have lines of transgenic chickens expressing reporter genes that are readily available to the research community. However, avian transgenic technology has been fraught with technical difficulties, and transgenic chickens expressing reporter genes have only recently been developed. The goal of this review is to report the technologies that have been used to generate transgenic chickens and to discuss the challenges in generating avian transgenics for developmental biology research. Developmental Dynamics 229:414–421, 2004. © 2004 Wiley‐Liss, Inc.
Patterns of gene expression in the developing chick thymus
Authors: Cui Jing , Sofer Luc , Cloud Sandra S. , Burnside Joan
Published: February 2004

Gene expression in thymic T cells during late embryogenesis and early growth in chicks was examined using cDNA microarrays. Gene expression patterns were profiled into nine clusters by using self‐organizing maps (SOM) clustering analysis. The expression patterns for a set of genes confirmed current information on the development of immune response. Expression of cell surface markers (MHC class I α chain, MHC class II associated invariant chain, CD8 β chain, CD18, and β2‐microglobulin), and genes involved in the innate immune response (NK lysin‐like) increased with age, and these patterns were consistent with an increase in the immune responsiveness of the young chick. The expression of cytokine receptor common gamma chain (γc), death receptor‐3 (DR3), and TCR α chain increased up to 1 day of age and then decreased. DR3 could play a role in the apoptosis during T‐cell maturation, while the differential expression of TCR genes could reflect regulation of the rearrangement of TCR genes and TCR‐mediated signal transduction during T cell development. Three genes coding for previously uncharacterized proteins are included in the clusters. These gene expression profiling studies provide background information on the developing chick immune system and provide preliminary functional information on unknown proteins. Developmental Dynamics 229:480–488, 2004. © 2004 Wiley‐Liss, Inc.