bluuebunny/crossref_metadata_2025 huggingface dataset:
Pattern of expression of engrailed in relation to gamma‐aminobutyric acid immunoreactivity in the central nervous system of the adult grasshopper
Authors: Siegler Melody V.S. , Pankhaniya Ravi R. , Jia Xi Xi
Published: August 2002

Engrailed (En) protein expression in neurons of the mesothoracic and metathoracic ganglia of the adult grasshopper, Schistocerca americana, was examined by immunohistochemistry. Each neuromere had a dorsally located cluster of En‐positive neurons within the dorsal unpaired median (DUM) group, comprising one cluster in the mesothoracic ganglion (T2) and four clusters in the metathoracic ganglion, one for each component neuromere (T3, A1, A2, A3). Ventrally, En‐positive neurons occurred in the posterior one‐third of each neuromere. In T2 and T3, three ventral groups of neurons were labeled bilaterally. In the abdominal neuromeres, many fewer ventral neurons were En‐positive. These also were bilaterally symmetrical, but did not occur in patterns that allowed assignment of homology with the T2 and T3 groups. Altogether, En‐positive neurons comprised roughly 10% of the ganglionic populations. In the bilateral groups, as in the DUM groups, En expression was restricted to interneurons, consistent with the suggestion that En expression contributes to some aspect of interneuronal phenotype. En‐positive neurons in the DUM groups also expressed gamma‐aminobutyric acid (GABA) immunoreactivity. Further study showed that all neurons in one En‐positive bilateral group and some neurons in another bilateral group were GABA immunoreactive, but that neurons in a third bilateral group were En‐positive only. Additionally, several discrete clusters of neurons were GABA‐immunoreactive but En‐negative. A provisional morphological scheme is presented, which relates the several neuronal clusters to their likely neuroblasts of origin, as a basis for further research into the composition of neuronal lineages. J. Comp. Neurol. 440:85–96, 2001. © 2001 Wiley‐Liss, Inc.
Axon collaterals of meynert cells diverge over large portions of area V1 in the macaque monkey
Authors: Rockland Kathleen S. , Knutson Tina
Published: August 2002

Patchy intrinsic connections, originating mainly from horizontal collaterals of pyramidal neurons, have been demonstrated in area V1 and many other cortical areas. In this article, we identify a network of intrinsic connections concentrated in layer 6 of area V1. These are visualized by extracellular injections of anterograde tracers in V1, which label small clusters of large terminal boutons in layer 6, in conjunction with thick axon segments. These segments can be traced back to infragranular Meynert cells (n = 10), which are retrogradely labeled from the injections. By using serial section analysis, we identified the following features of this distinctive system of Meynert cell collaterals: (1) terminal clusters are relatively small (<100 μm); (2) each cluster has a small number of rather large boutons (up to 3.0 μm); (3) there is typically a termination‐free zone in the immediate vicinity (0.5–2.0 mm) of the cell body; (4) a single neuron has multiple branches that can extend up to 8.0 mm from the soma; and (5) the collaterals are concentrated in layer 6. These features are different from those of horizontal intrinsic connections in the supragranular layers of area V1. They are consistent with fast dynamics and a possible role in wide‐field motion processing, such as has been associated with Meynert cells from other studies. J. Comp. Neurol. 441:134–147, 2001. © 2001 Wiley‐Liss, Inc.
Dye exclusion artifact in flow cytometers
Authors: Steen Harald B. , Stokke Trond
Published: August 2002

Background

Cells exclude their own volume of dye solution in the sample flow which carries them through the flow chamber of the flow cytometer, thereby affecting the otherwise constant signal arising from the fluorescence of this solution. Under certain conditions, this phenomenon may significantly influence the fluorescence signal of the cells.

Materials and Methods

Using the slit scan technique, we studied this phenomenon as observed for monodisperse polystyrene particles in fluorescein solution.

Results

The measurements show that dye solution accumulates just in front of the particle and just behind it, with a relative void in between. This phenomenon is most likely caused by the rapid constriction of the flow as it enters the orifice of the nozzle or flow chamber, giving rise to a pulse of fluorescence which adds to that of the particle or cell itself. The magnitude of this artifact depends on the design and dimensions of the nozzle/flow chamber as well as on the rate of sample flow.

Conclusions

The dye exclusion artifact may affect measurements of cells when they are in a dye solution having a fluorescence per unit volume which is significant compared to that of the cells, especially at low sample flow rates. Cytometry 47:200–205, 2002. © 2002 Wiley‐Liss, Inc.
Mitochondrial and nonmitochondrial reduction of MTT: Interaction of MTT with TMRE, JC‐1, and NAO mitochondrial fluorescent probes
Authors: Bernas Tytus , Dobrucki Jurek
Published: August 2002

Background

Bioreduction of water‐soluble tetrazolium salts (e.g., MTS, XTT, and MTT) to their respective formazans is generally regarded as an indicator of cell “redox activity.” The reaction is attributed mainly to mitochondrial enzymes and electron carriers. However, MTT reduction may also be catalyzed by a number of other nonmitochondrial enzymes. The goal of this work was to establish the sites of MTT reduction in intact HepG2 human hepatoma cells in culture.

Methods

In order to establish the subcellular localization of the sites of reduction of MTT, we imaged the formation of MTT‐formazan deposits using backscattered light confocal microscopy. Mitochondria were visualized in viable cells using fluorescent dyes that bind in a manner dependent (JC‐1 and TMRE) or independent (NAO) of mitochondrial electric potential.

Results

Only 25–45% of MTT‐formazan was associated with mitochondria after 25 min of incubation. No more than 25% of the mitochondrial area on images was occupied by MTT‐formazan. Mitochondrial fluorescence of TMRE, NAO, and the monomeric form of JC‐1 decreased rapidly in cells incubated with MTT. However, the intensity of fluorescence of JC‐1 aggregates dropped by less than 30% at the onset of incubation and remained constant as reduction of MTT proceeded further.

Conclusions

(1) Most of MTT‐formazan deposits are not coincident with mitochondria. (2) Monomeric JC‐1, as well as TMRE and NAO, accumulating in mitochondria may be displaced by MTT. Thus, the presence of positively charged organic compounds (like MTT) may distort measurements of mitochondrial transmembrane electric potential, which are based on accumulation of fluorescent dyes. Cytometry 47:236–242, 2002. © 2002 Wiley‐Liss, Inc.
Comparison between different laboratory tests for the detection and prevention of heparin‐induced thrombocytopenia
Authors: Vitale Marco , Tazzari Pierluigi , Ricci Francesca , Mazza Maria Anna , Zauli Giorgio , Martini Giuliana , Caimi Luigi , Manzoli Francesco A. , Conte Roberto
Published: August 2002

Background: Heparin‐induced thrombocytopenia (HIT) is a possible complication of heparin therapy that can evolve with life‐threatening thromboembolism, for which early diagnosis is essential. However, the specific laboratory approach to the diagnosis of HIT is still controversial. Methods: Sera from 13 patients with HIT, from 15 patients with non‐HIT thrombocytopenia, and from 10 normal subjects were used to compare nonfunctional and functional methods to detect anti‐heparin:PF‐4 antibodies and platelet activation. We used three enzyme‐linked immunosorbent assays (ELISAs) and the particle gel immunoassay as nonfunctional tests, and platelet aggregometry, CD62p (p‐selectin) phenotypical expression, and Annexin V binding as functional assays. Results: CD62p expression was positive in 85% of the cases and Annexin V was positive in 40% of the HIT cases examined. Aggregometry gave variable results that depend strongly on the donor. Conclusion: Functional tests for platelet activation are more reliable for HIT diagnosis than the nonfunctional tests. We conclude that the phenotypical expression of p‐selectin detected by flow cytometry on activated platelets appears to be a good functional marker for the diagnosis of HIT and its possible thromboembolic complications. Cytometry (Comm. Clin. Cytometry) 46:290–295, 2001. © 2001 Wiley‐Liss, Inc.
Advances in optical networking
Authors: Papadimitriou G. I. , Obaidat M. S. , Pomportsis A. S.
Published: August 2002

An overview of optical networks is provided. An introduction into the area of optical networks, their abilities and characteristics and their place in today's communication technology are made. The various components that an optical network consists of are examined. These include examination of the structure and operation of optical fibres, optical transmitters and receivers, optical amplifiers and other related optical components. The various classes of optical networks—optical link networks, broadcast and select networks, wavelength‐routed networks, photonic packet‐switching networks and optical burst switching ones—are then explained. Finally, an examination of various trends in the optical networking area is made. Copyright © 2001 John Wiley & Sons, Ltd.
Desmoplastic small round cell tumor presenting as a neck mass: A case report
Authors: Mihok Nicole A. , Cha Imok
Published: August 2002

An unusual case study of a desmoplastic small round cell tumor presenting as a 3.5‐cm, firm, supraclavicular neck mass and diagnosed by fine‐needle aspirate biopsy in a 16‐yr‐old male is reported. Clinical, cytologic, and immunocytochemical findings are described. Histologic, immunohistochemical, and genetic features are discussed. Desmoplastic small round cell tumor should be considered in the differential diagnosis of small round cell tumors of any site; the importance of ancillary studies in arriving at the correct diagnosis is emphasized. Diagn. Cytopathol. 25:68–72, 2001. © 2001 Wiley‐Liss, Inc.
Therapeutic potential of nucleotides in the eye
Authors: Pintor Jesús , Peral Assumpta
Published: August 2002

Adenine mononucleotides present the ability to produce changes in the intraocular pressure in New Zealand rabbits. Two main groups of compounds were found in terms of their behaviour—on the one hand, those that increased intraocular pressure, and on the other hand, those that reduced it. The hypotensive compounds showed a concentration–response behaviour, and were blocked by the P2 receptor antagonist pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulfonic acid. Moreover, the hypotensive compounds were unaffected by the pretreatment with sympathetic antagonists but were completely abolished by the parasympathetic antagonists. This fact suggests the possibility of these P2 receptors to be present at the cholinergic terminal that control intraocular pressure. Adenine mononucleotides also were assayed in their ability to increase tear secretion rate. This study showed that tear secretion is stimulated via P2Y2 receptors. Drug Dev. Res. 52:190–195, 2001. © 2001 Wiley‐Liss, Inc.
Neuroprotection by A2A receptor antagonists
Authors: Stone Trevor W. , Jones Paul A. , Smith Robert A.
Published: August 2002

Activation of A2A receptors has been shown to protect neurons in the hippocampus from damage caused by excitotoxins or from cerebral insults such as ischaemia. For example, the A2A agonist 2‐p‐(2‐carboxyethyl)phenethylamino‐5′‐N‐ethylcarboxamidoadenosine hydrochloride (CGS 21680) protects the hippocampus at concentrations which are only partially blocked by the centrally acting adenosine A1 receptor antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine (CPX), suggesting that protection is mediated largely by the A2A receptor. However, selective antagonists at the A2A receptor, such as 4‐(2‐[7‐amino‐2‐{2‐furyl}{1,2,4}triazolo{2,3‐a}{1,3,5}triazin‐5‐yl‐amino]ethyl)phenol (ZM 241385), also show protection against neuronal death produced by ischaemia or excitotoxicity. In addition, A2A receptor antagonists can reduce damage produced by combinations of subthreshold doses of the endogenous excitotoxin quinolinic acid and free radicals. The TdT‐mediated dUTP‐biotin nick end labeling (TUNEL) method has revealed that, after systemic kainic acid administration, staining was apparent in the CA1 region of the hippocampus only, even though damage was present in both the CA1 and CA3a areas. In animals injected intrahippocampally, both apoptosis and damage were limited to the CA3 region. Intrahippocampal co‐injection of kainate together with ZM 241385 did not induce apoptosis even though damage was apparent. This suggests that the adenosine A2A receptor may play a role in the route by which cells die during excitotoxicity. Overall, A2A receptor antagonists appear to be promising candidates as new drugs for the prevention of neuronal damage and death in the central nervous system. Drug Dev. Res. 52:323–330, 2001. © 2001 Wiley‐Liss, Inc.
The lesion methodology: Contrasting views from adult and child studies
Authors: Moses Pamela , Stiles Joan
Published: August 2002

A traditional approach for examining brain–behavior relations has been the lesion method. This method assumes a direct correspondence between the cognitive process compromised and the site of lesion. Historically, studies with adults have used this framework to map brain functions. In contrast, studies of children with early injury have addressed quite different issues. Developmental animal lesion studies and pediatric neuropsychology studies have focused on the level of plasticity exhibited following early injury. Resilency in behavioral development has suggested change in the underlying neural substrate. A new set of studies has applied converging, MRI‐based methods to examine anatomical and functional development in intact brain regions following early injury and compared these data with behavioral outcomes on the same children. The findings reveal an interaction between early injury and normal mechanisms of development, which manifest as atypical behavioral, structural, and functional development. © 2002 Wiley Periodicals, Inc. Dev Psychobiol 40: 266–277, 2002. DOI 10.1002/dev.10031
Attachment and sleep: A study of night waking in 12‐month‐old infants
Authors: Scher Anat
Published: August 2002

Sleep regulation was examined from a mother–child relational perspective. Although the link between sleep and attachment has been previously discussed, empirical support is rather limited. This report, which is a part of a longitudinal investigation of sleep in infancy, examines the association between the child's sleep pattern and mother–infant attachment in 94 mother–infant dyads. At 12 months each dyad participated in the Strange Situation procedure; 77% were securely attached. Mothers' description of the infant's fussiness was not found to predict the attachment pattern, but was associated with the sleep habits. It was found that 55% of the secure and 60% of the ambivalent children were described as night wakers. To a sub‐group of 37 infants, a sleep monitor (actigraph) was provided for two nights' recordings. The frequency of the objective awakenings was higher than what mothers reported but similar for the secure and insecure infants. The findings confirm that night waking at the end of the first year is a common developmental phenomenon. Among this group of non‐risk infants, sleep characteristics were only marginally associated with the quality of the child's attachment relationship. © 2001 John Wiley & Sons, Inc. Dev Psychobiol 38: 274–285, 2001
Convergence marketing
Authors: Wind Yoram , Mahajan Vijay
Published: August 2002

The authors discuss two enduring lessons of the Internet revolution: The first is that new technologies do not replace the old. They live side by side. They converge. The second is that people are complex, combining new technology and behaviors with enduring human needs. Like the mythical centaur, they run on the fleet hooves of the new technology but still carry the same human heart. These lessons of convergence shaped the unfolding of Internet technology—contributing to the decline of dot-coms and the missed opportunities of incumbent firms—and these lessons will shape the technological revolutions to come. In this article, Jerry Wind and Vijay Mahajan examine the implications of these lessons for marketing and business strategy in five specific areas of convergence—customerization (customization of marketing and product or service offering), community, channels, competitive value and choice tools. In each of these areas the greatest opportunities may be in strategies that emphasize convergence of old and new, online and offline, traditional and revolutionary.
Antecedents and consequences of consumer privacy concerns: An empirical investigation
Authors: Phelps Joseph E. , D'Souza Giles , Nowak Glen J.
Published: August 2002

The present study examines the interrelationships among antecedents and consequences of privacy concerns. The results indicate, among other things, that a consumer's attitude toward direct marketing and his/her desire for information control act as antecedents to privacy concerns. Privacy concerns, in turn, are negatively related to purchase behavior and the purchase decision process. Understanding the antecedents of privacy concerns provides a foundation for developing effective policies and practices to reduce such concerns while understanding the consequences of privacy concerns is essential to gauging just how important dealing with these concerns really are for marketers.
Understanding IT-enabled interactivity in contemporary marketing
Authors: Coviello Nicole , Milley Roger , Marcolin Barbara
Published: August 2002

The past decade has witnessed the emergence of a new phenomenon in marketing practice and research in terms of the rapid and widespread diffusion of information technology. Of particular interest in the marketing literature is the notion of interactivity within and among firms and customers. To better understand how IT-enabled interactivity impacts contemporary marketing practice, this paper synthesizes the extant and emerging literature to develop two related conceptual frameworks useful for discussion and empirical investigation. Building on an established conceptualization of marketing practices that comprises four different approaches (Transaction, Database, Interaction, and Network marketing), the first framework introduces a fifth approach: e-Marketing. The second framework relates these five marketing approaches to three distinct roles for information technology in the organization. Implications are offered for both managers and researchers.
Article not available electronically
Authors: Lal Rajiv , Kochikar Purnima
Published: August 2002

This article is not available electronically because the copyright is held by the President and Fellows of Harvard College and permission was only granted for print publication.

To order copies or request permission to reproduce materials go to http://harvardbusiness.org .

The Publisher regrets any inconvenience this may cause.
Adipose tissue: A vital in vivo role in mammary gland development but not differentiation
Authors: Couldrey Christine , Moitra Jaideep , Vinson Charles , Anver Miriam , Nagashima Kunio , Green Jeffrey
Published: August 2002

Development and differentiation of the mammary gland occurs by means of critical stromal‐epithelial interactions. Although many studies have attempted to understand these complex interactions, it has been difficult to demonstrate the essential role of adipose tissue in the development and function of the mammary gland. By using the A‐ZIP/F‐1 transgenic mice lacking in white adipose tissue (WAT), we have studied the role of adipocytes in mammary gland development and differentiation. In the absence of WAT, rudimentary mammary anlagen form but are unable to grow and branch normally, resulting in a few, short, severely distended ducts. However, during pregnancy, a tremendous amount of epithelial cell division and alveolar cell formation occurs even in the absence of adipocytes, illustrating that adipose tissue is not required for mammary gland differentiation. Mammary gland transplantation revealed that epithelial cells from these transgenic mice possess the potential for normal growth and differentiation when placed into a normal stromal environment. These experiments clearly demonstrate that the absence of adipocytes in the mammary gland results in disruption of stromal‐epithelial interactions that prevent normal mammary gland development. The rudimentary epithelial anlage, however, contain mammary stem cells, which are fully capable of alveolar differentiation. Published 2002 Wiley‐Liss, Inc.
Induced effects on body sway by the synchronous presentation of a visual wide‐field stimulus with an auditory stimulus
Authors: Shimizu Toshihiro , Yano Sumio
Published: August 2002

This paper discusses the induced effect on the body sway when an iteratively rotating visual wide‐field stimulus and an auditory stimulus with a moving sound image are presented simultaneously with synchronization. When the sound image is iteratively rotated in phase relative to the iteratively rotating visual stimulus, the induced effect on the body sway increases when the visual angle of the visual stimulus is increased, compared to the case in which the auditory stimulus is presented in the opposite phase. When the visual angle of the visual stimulus is reduced, on the other hand, there is no difference in the induced effects between the in‐phase and opposite‐phase conditions. These results suggest that when the visual and auditory stimuli are simultaneously presented, the induced effects of the visual and auditory stimuli on body sway are not simply added, but that there is an interaction between the two effects. It is suggested that the induced effect due to the interaction between the visual and auditory stimuli depends on the visual angle of the visual stimulus, and is enhanced by the wider field visual stimulus. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 85(10): 31–39, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.1123
Point mutations induced by 1,2‐epoxy‐3‐butene N1 deoxyinosine adducts
Authors: Rodriguez David A. , Kowalczyk Agnieszka , Ward Jonathan B. , Harris Constance M. , Harris Thomas M. , Lloyd R. Stephen
Published: August 2002

The National Toxicology Program has recently classified 1,3‐butadiene (BD) as a human carcinogen. BD is metabolized to the intermediates 1,2‐epoxy‐3‐butene (EB), 1,2:3,4‐diepoxybutane (DEB), and 1,2‐dihydroxy‐3,4‐epoxybutane. All three metabolites have been implicated in producing specific types of DNA damage and as genotoxic agents in mice, rat, and human cells. This study has focused on EB‐induced N1 deoxyinosine lesions that are formed by deamination of deoxyadenosine following reaction of the epoxide at the N1 position. The R and S stereoisomers of this lesion were incorporated site‐specifically within the context of an 11‐mer oligodeoxynucleotide, incorporated into M13mp7L2 single‐stranded DNA, and transfected into E. coli. Both stereoisomers modestly reduced plaque‐forming ability, indicating that neither lesion presents a base modification that cannot be bypassed. The resulting plaques were assessed for point mutations using differential hybridization and DNA sequence analyses. The overall mutagenic spectrum revealed that the N1 adducts were highly mutagenic (∼90% per replication cycle), causing a predominance of A → G transitions. Environ. Mol. Mutagen. 38:292–296, 2001. © 2001 Wiley‐Liss, Inc.
Neoplastic transformation of human breast epithelial cells by estrogens and chemical carcinogens
Authors: Russo Jose , Tahin Quivo , Lareef M. Hasan , Hu Yun‐Fu , Russo Irma H.
Published: August 2002

Sporadic breast cancer, the most common cancer diagnosed in American and Northern European women, is gradually increasing in incidence in most Western countries. Prevention would be the most efficient way of eradicating this disease. This goal, however, cannot be accomplished until the specific agent(s) or mechanisms that initiate the neoplastic process are identified. Experimental studies have demonstrated that mammary cancer is a hormone‐dependent multistep process that can be induced by a variety of compounds and mechanisms, that is, hormones, chemicals, radiation, and viruses, in addition to or in combination with genetic factors. Although estrogens have been shown to play a central role in breast cancer development, their carcinogenicity on human breast epithelial cells (HBECs) has not yet been clearly demonstrated. Breast cancer initiates in the undifferentiated lobules type 1, which are composed of three cell types: highly proliferating cells that are estrogen‐receptor negative (ER−), nonproliferating cells that are ER positive (ER+), and very few (<1%) ER+ cells that proliferate. Interestingly, endogenous 17β‐estradiol (E2) is metabolized by the cytochrome P450 enzyme isoforms CYP1A1 and CYP1B1, which also activate benzo[a]pyrene (B[a]P), a carcinogen contained in cigarette smoke. We postulate that if estrogens are carcinogenic in HBECs, they should induce the same transformation phenotypes induced by chemical carcinogens and ultimately genomic changes observed in spontaneously developing primary breast cancers. To test this hypothesis we compared the transforming potential of E2 on the HBEC MCF‐10F with that of B[a]P. Both E2 and B[a]P induced anchorage‐independent growth, colony formation in agar methocel, and loss of ductulogenic capacity in collagen gel, all parameters indicative of cell transformation. In addition, the DNA of E2‐transformed cells expressed LOH in chromosome 11 at 11q23.3, 11q24.2–q25, and LOH at 13q12–q13. B[a]P‐induced cell transformation was also associated with LOH at 13q12–q13 and at 17p13.2. The relevance of these findings is highlighted by the observation that E2‐ and B[a]P‐induced genomic alterations in the same loci found in ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma of the breast. Environ. Mol. Mutagen. 39:254–263, 2002. © 2002 Wiley‐Liss, Inc.
Mammary gland carcinogenesis by food‐derived heterocyclic amines: Metabolism and additional factors influencing carcinogenesis by 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP)
Authors: Snyderwine Elizabeth G.
Published: August 2002

The heterocyclic amines (HCAs) are a family of mutagenic/carcinogenic compounds found in cooked meats. Several HCAs are mammary gland carcinogens in rats. Of these compounds, 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) is the major one present in the human diet. This report reviews the studies on rat mammary gland carcinogenesis by HCAs; discusses what is currently known regarding mechanisms of mammary gland carcinogenesis of PhIP, especially the significance of metabolic processing; and further highlights the evidence for the possible role of PhIP in human breast cancer. Environ. Mol. Mutagen. 39:165–170, 2002. Published 2002 Wiley‐Liss, Inc.
Genotoxic effects of carbon black particles, diesel exhaust particles, and urban air particulates and their extracts on a human alveolar epithelial cell line (A549) and a human monocytic cell line (THP‐1)
Authors: Don Porto Carero A. , Hoet P.H.M. , Verschaeve L. , Schoeters G. , Nemery B.
Published: August 2002

The possible genotoxicity of small particulate matter has been under investigation for the last 10 years. Diesel exhaust particles (DEP) are considered as “probably carcinogenic” (IARC group 2A) and a number of studies show genotoxic effects of urban particulate matter (UPM). Carbon black (CB) is carcinogenic in rats. In this study the cytotoxic and genotoxic potency of these three particle types was investigated by exposing human cells (A549 and THP‐1 cell lines) in vitro to CB, DEP (SRM 1650, NIST), and UPM (SRM 1648, NIST) for 48 hr. Cytotoxicity was assessed using the AlamarBlue assay, whereas genotoxicity was assessed using the single‐cell gel electrophoresis (comet assay). The particles were characterized with regard to their mean diameter in tissue culture medium (CB 100 nm, DEP 400 nm, UPM 2 μm), their total carbon content (CB 99%, DEP 85%, UPM 15%), and their acid‐soluble metal composition (UPM ≫ CB ∼ DEP). The concentrations ranged from 16 ng/ml to 16 μg/ml for cytotoxicity tests and from 16 ng/ml to 1.6 μg/ml for genotoxicity tests. In both assays, paraquat was used as a reference chemical. The CB, DEP, and UPM particles showed no significant cytotoxicity. However, all three particles were able to cause significant DNA damage, although to a different extent in the two cell lines. The genotoxicity of washed particles and dichloromethane extracts was also investigated. In THP‐1 cells CB washed particles and DEP extracts caused significant DNA damage. This difference in effect may be related to differences in size, structure, and composition of the particles. These results suggest that CB, DEP, and UPM are able to cause DNA damage and, therefore, may contribute to the causation of lung cancer. More detailed studies on influence of size, structure, and composition of the particles are needed. Environ. Mol. Mutagen. 37:155–163, 2001 © 2001 Wiley‐Liss, Inc.
Effect of earthquake ground motions on fragility curves of highway bridge piers based on numerical simulation
Authors: Karim Kazi R. , Yamazaki Fumio
Published: August 2002

Fragility curves express the probability of structural damage due to earthquakes as a function of ground motion indices, e.g., PGA, PGV. Based on the actual damage data of highway bridges from the 1995 Hyogoken‐Nanbu (Kobe) earthquake, a set of empirical fragility curves was constructed. However, the type of structure, structural performance (static and dynamic) and variation of input ground motion were not considered to construct the empirical fragility curves. In this study, an analytical approach was adopted to construct fragility curves for highway bridge piers of specific bridges. A typical bridge structure was considered and its piers were designed according to the seismic design codes in Japan. Using the strong motion records from Japan and the United States, non‐linear dynamic response analyses were performed, and the damage indices for the bridge piers were obtained. Using the damage indices and ground motion indices, fragility curves for the bridge piers were constructed assuming a lognormal distribution. The analytical fragility curves were compared with the empirical ones. The proposed approach may be used in constructing the fragility curves for highway bridge structures. Copyright © 2001 John Wiley & Sons, Ltd.
New observations on the geomorphology and origins of Mountain Lake, Virginia
Authors: Cawley Jon C. , Parker Bruce C. , Perren Lee J.
Published: August 2002

Mountain Lake is the only natural lake of significance in the unglaciated southern Appalachian Highlands. It is located near the summit of Salt Pond Mountain, Giles County Virginia, at an elevation of 1177 m. It is underlain by Ordovician and Silurian non‐calcareous shale and sandstone of the Martinsburg, Juniata and Clinch formations. Historical (250 years) and sediment (6000 years) records suggest that the size of the lake has varied periodically. In the 1930s lake origin was proposed as due to valley damming by a lateral landslide (Hutchinson and Pickford, 1932) or damming by scree (Sharp, 1933). A later theory modified the landslide hypothesis to the primarily vertical collapse of a canyon feature in the Clinch (Parker et al., 1975). Fracture trace analysis now reveals a regional lineation feature associated with the lake. This feature is present surficially both downgradient from the lake to the northwest, and upgradient to the southeast. Sonar bathymetry and diver reconnaissance show it expressed as a (relatively sediment‐free) narrow open crevice in the deepest (33 m) portion of the lake, probably a fault. Hydrologic observation and resistivity suggest preferential water movement along this fracture, as well as leakage directly from the lake. The present study suggests conduit erosion within this feature and periodic vertical downsettling of overlying Clinch material as the primary mechanism of lake origin and water‐level fluctuations through time. Copyright © 2001 John Wiley & Sons, Ltd.
Trapping of aeolian sediments and build‐up of the ice cover of a dry‐based Antarctic lake
Authors: Sleewaegen S. , Lorrain R. , Offer Z. , Azmon E. , Fitzsimons S. , Souchez R.
Published: August 2002

Among the perennially frozen lakes of the Dry Valleys of South Victoria Land (Antarctica), some are dry‐based, i.e. frozen to the bottom. One of these is studied here by a multiparametric investigation (isotopic composition in δD and δ18O, ions, gas and ice texture analyses). A sediment layer about 10 cm thick appearing at a depth of 3·5 m is also studied by grain size, X‐ray diffraction and scanning electron microscope analyses. The information retrieved indicates that this ice‐block lake results from a build‐up in two steps and explains how aeolian sediments were included as a layer into the ice. Copyright © 2002 John Wiley & Sons, Ltd.
Chemical composition of leaf and flower essential oil of Lantana camara from India
Authors: Khan M. , Srivastava S. K. , Syamasundar K. V. , Singh M. , Naqvi A. A.
Published: August 2002

The chemical composition of leaves and flowers essential oils of Lantana camara from India were analysed by GC and GC–MS, which resulted in the identification of 71 and 64 constituents, representing 99.0% and 97.0% of the oils, respectively. The major constituents in the leaf oil were germacrene‐D (20.5%), γ‐elemene (10.3%), β‐caryophyllene (9.4%), β‐elemene (7.3%), α‐copaene (5.0%) and α‐cadinene (3.3%), while the major constituents in the flower oil were β‐elemene (14.5%), germacrene‐D (10.6%), α‐copaene (10.7%), α‐cadinene (7.2%), β‐caryophyllene (7.0%) and γ‐elemene (6.8%). A comparison with the chemical composition of L. camara oils of different origin showed that our oils were significantly different from others with respect to their major constituents. Copyright © 2001 John Wiley & Sons, Ltd.
Computing singular solutions of the Navier–Stokes equations with the Chebyshev‐collocation method
Authors: Botella O. , Peyret R.
Published: August 2002

The solution of fluid flow problems exhibits a singular behaviour when the conditions imposed on the boundary display some discontinuities or change in type. A treatment of these singularities has to be considered in order to preserve the accuracy of high‐order methods, such as spectral methods. The present work concerns the computation of a singular solution of the Navier–Stokes equations using the Chebyshev‐collocation method. A singularity subtraction technique is employed, which amounts to computing a smooth solution thanks to the subtraction of the leading part of the singular solution. The latter is determined from an asymptotic expansion of the solution near the singular points. In the case of non‐homogeneous boundary conditions, where the leading terms of the expansion are completely determined by the local analysis, the high accuracy of the method is assessed on both steady and unsteady lid‐driven cavity flows. An extension of this technique suitable for homogenous boundary conditions is developed for the injection of fluid into a channel. The ability of the method to compute high‐Reynolds number flows is demonstrated on a piston‐driven two‐dimensional flow. Copyright © 2001 John Wiley & Sons, Ltd.
Measuring and forecasting S&P 500 index‐futures volatility using high‐frequency data
Authors: Martens Martin
Published: August 2002

In the 24‐hr foreign exchange market, Andersen and Bollerslev measure and forecast volatility using
intraday returns rather than daily returns. Trading in equity markets only occurs during part of the day, and
volatility during nontrading hours may differ from the volatility during trading hours. This paper compares
various measures and forecasts of volatility in equity markets. In the absence of overnight trading it is shown
that the daily volatility is best measured by the sum of intraday squared 5‐min returns,
excluding the overnight return. In the absence of overnight trading, the best daily forecast of
volatility is produced by modeling overnight volatility differently from intraday volatility. © 2002 Wiley
Periodicals, Inc. Jrl Fut Mark 22:497–518, 2002
The effect of the introduction of Cubes on the Nasdaq‐100 index spot‐futures pricing relationship
Authors: Kurov Alexander A. , Lasser Dennis J.
Published: August 2002

This paper examines the impact of the introduction of the Nasdaq‐100 Index Tracking Stock
(referred to as Cubes) on the pricing relationship between Nasdaq‐100 futures and the
underlying index. Observations obtained from tick‐by‐tick Nasdaq‐100 futures transactions
and index value data support the hypothesis that the introduction of Cubes in March 1999 has led to improvements
in the Nasdaq‐100 index futures pricing efficiency. Both the size and frequency of violations in futures
price boundaries appear to be reduced. Furthermore, there appears to be an increase in the speed of the market
response to observed violations. These results are attributed to the increased ease in establishing a spot
Nasdaq‐100 index position after the introduction of the tracking stock. © 2002 John Wiley &
Sons, Inc. Jrl Fut Mark 22: 197–218, 2002
Somatic mutation of vascular endothelial growth factor receptors in juvenile hemangioma
Authors: Walter Jeffrey W. , North Paula E. , Waner Milton , Mizeracki Adam , Blei Francine , Walker John W. T. , Reinisch John F. , Marchuk Douglas A.
Published: August 2002

Juvenile hemangiomas are the most common tumors of infancy, occurring in as many as 10% of all births. These benign vascular lesions enlarge rapidly during the first year of life by hyperplasia of endothelial cells and attendant pericytes and then spontaneously involute over a period of years, leaving loose fibrofatty tissue. Several hypotheses have been put forth concerning hemangiogenesis, including the possibility that the tumor is the result of somatic mutation in one or more components of critical vascular growth‐regulatory pathways. To test this hypothesis, we obtained 15 proliferative‐phase hemangiomas after surgical resection and dissected them to enrich for the lesional (endothelial and pericytic) components of each specimen. To determine whether hemangiomas represent a clonal expansion from a single progenitor cell, we assayed X‐inactivation patterns for each lesion by using the polymorphic X‐linked human androgen receptor gene. Twelve of 14 informative hemangiomas showed a significant degree of allelic loss after methylation‐based and transcription‐based polymerase chain reaction clonality assays, suggesting a nonrandom X‐inactivation pattern and, thus, a monoclonal origin. We then sequenced genes encoding the receptors of the vascular endothelial growth factors (VEGFs) as candidates for potential somatic mutation. Mutations were found in two of the 15 hemangioma specimens: a missense mutation (P1147S) in the kinase domain of the VEGFR2 (FLK1/KDR) gene in one specimen and a missense mutation (P954S) in the kinase insert of the VEGFR3 (FLT4) gene in another specimen. In each case, the mutation was detected in tumor tissue but not in adjacent normal tissue. These results suggest that one potential mechanism involved in hemangioma formation is the alteration of the VEGF signaling pathway in endothelial and/or pericytic cells. © 2002 Wiley‐Liss, Inc.
Detection of unidentified chromosome abnormalities in human neuroblastoma by spectral karyotyping (SKY)
Authors: Cohen Ninette , Betts David R. , Trakhtenbrot Luba , Niggli Felix K. , Amariglio Ninette , Brok‐Simoni Frida , Rechavi Gideon , Meitar Dafna
Published: August 2002

Spectral karyotyping (SKY) is a novel technique based on the simultaneous hybridization of 24 fluorescently labeled chromosome painting probes. It provides a valuable addition to the investigation of many tumors that can be difficult to define by conventional banding techniques. One such tumor is neuroblastoma, which is often characterized by poor chromosome morphology and complex karyotypes. Ten primary neuroblastoma tumor samples initially analyzed by G‐banding were analyzed by SKY. In 8/10 tumors, we were able to obtain additional cytogenetic information. This included the identification of complex rearrangements and material of previously unknown origin. Structurally rearranged chromosomes can be identified even in highly condensed metaphase chromosomes. Following the SKY results, the G‐banding findings were reevaluated, and the combination of the two techniques resulted in a more accurate karyotype. This combination allows identification not only of material gained and lost, but also of breakpoints and chromosomal associations. The use of SKY is therefore a powerful tool in the genetic characterization of neuroblastoma and can contribute to a better understanding of the molecular events associated with this tumor. © 2001 Wiley‐Liss, Inc.
Chronic myelogenous leukemia: Laboratory diagnosis and monitoring
Authors: Wang Y. Lynn , Bagg Adam , Pear Warren , Nowell Peter C. , Hess Jay L.
Published: August 2002

Rapid developments have occurred both in laboratory medicine and in therapeutic interventions for the management of patients with chronic myelogenous leukemia (CML). With a wide array of laboratory tests available, selecting the appropriate test for a specific diagnostic or therapeutic setting has become increasingly difficult. In this review, we first discuss, from the point of view of laboratory medicine, the advantages and disadvantages of several commonly used laboratory assays, including cytogenetics, fluorescence in situ hybridization (FISH), and qualitative and quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR). We then discuss, from the point of view of clinical care, the test(s) of choice for the most common clinical scenarios, including diagnosis and monitoring of the therapeutic response and minimal residual disease in patients treated with different therapies. The purpose of this review is to help clinicians and laboratory physicians select appropriate tests for the diagnosis and monitoring of CML, with the ultimate goal of improving the cost‐effective usage of clinical laboratories and improving patient care. © 2001 Wiley‐Liss, Inc.
Genetic evidence that Sil is required for the sonic hedgehog response pathway
Authors: Izraeli Shai , Lowe Linda A. , Bertness Virginia L. , Campaner Stefano , Hahn Heidi , Kirsch Ilan R. , Kuehn Michael R.
Published: August 2002

Summary: The Sil gene encodes a cytosolic protein required for mouse embryonic midline and left/right axial development. Based on the phenotype of Sil mutant embryos, we hypothesized that Sil may be required for the activity of Sonic Hedgehog (Shh), a secreted signaling molecule also critically important for the development of the embryonic axes and found mutated in multiple types of cancer. Here we tested the genetic interaction between Sil and the Shh pathway by generating and analyzing embryos carrying mutations in both Sil and Patched (Ptch), a Shh receptor that normally inhibits the signaling pathway in the absence of ligand and when mutated leads to constitutive activation of the pathway. We find that Sil−/− Ptch−/− embryos do not activate the Shh pathway and instead have a phenotype indistinguishable from Sil−/− embryos, in which there is a loss of activity of Shh. These results provide genetic evidence that Sil is an essential component of the Shh response, acting downstream to Ptch. genesis 31:72–77, 2001. © 2001 Wiley‐Liss, Inc.
hGFAP‐cre transgenic mice for manipulation of glial and neuronal function in vivo
Authors: Zhuo Lang , Theis Martin , Alvarez‐Maya Ikuri , Brenner Michael , Willecke Klaus , Messing Albee
Published: August 2002

With the goal of performing astrocyte‐specific modification of genes in the mouse, we have generated a transgenic line expressing Cre recombinase under the control of the human glial fibrillary acidic protein (hGFAP) promoter. Activity was monitored by crossing the hGFAP‐cre transgenics with either of two reporter lines carrying a lacZ gene whose expression requires excision of loxP‐flanked stop sequences. We found that lacZ expression was primarily limited to the central nervous system, but therein was widespread in neurons and ependyma. Cell types within the brain that notably failed to activate lacZ expression included Purkinje neurons of the cerebellum and choroid plexus epithelium. Onset of Cre expression began in the forebrain by e13.5, suggesting that the hGFAP promoter is active in a multi‐potential neural stem cell. genesis 31:85–94, 2001. © 2001 Wiley‐Liss, Inc.
Oosp1 encodes a novel mouse oocyte‐secreted protein
Authors: Yan Changning , Pendola Frank L. , Jacob Renu , Lau Anthony L. , Eppig John J. , Matzuk Martin M.
Published: August 2002

Summary: Oocyte‐somatic cell communication is necessary for normal ovarian function. However, the identities of the majority of oocyte‐secreted proteins remain unknown. A novel cDNA encoding mouse oocyte‐secreted protein 1 (OOSP1) was identified using a modified subtractive hybridization screen. The Oosp1 cDNA encodes a 202‐amino acid protein that contains a 21‐amino acid signal peptide sequence, 5 putative N‐linked glycosylation consensus sequences, and 6 cysteines that are predicted to form 3 disulfide bonds. OOSP1 shares amino acid identity with placental‐specific protein 1 (PLAC1), a secreted protein expressed in the placenta and the ectoplacental cone. The Oosp1 mRNA is approximately 1.0 kb and is present at high levels in the oocytes of adult ovaries and at lower levels in the spleen. The mouse Oosp1 gene is 5 exons, spans greater than 16.4 kb, and localizes to chromosome 19 at a position that shares synteny with human chromosome 11q12–11q13. The identification of OOSP1 as a new oocyte‐secreted protein permits future in vitro and in vivo functional analyses to define its role in ovarian folliculogenesis. genesis 31:105–110, 2001. © 2001 Wiley‐Liss, Inc.
Glucose deprivation decreases nitric oxide production via NADPH depletion in immunostimulated rat primary astrocytes
Authors: Shin Chan Young , Choi Ji Woong , Ryu Jae Ryun , Ko Kwang Ho , Choi Jung‐Jin , Kim Hyun‐Soo , Kim Hee‐Sun , Lee Jae‐Chul , Lee Sun Jung , Kim Hyoung Chun , Kim Won‐Ki
Published: August 2002

We have previously reported that the production of nitric oxide (NO) in immunostimulated astrocytes was markedly decreased under glucose‐deprived conditions. The present study was undertaken to find the contributing factor(s) for the decreased NO production in glucose‐deprived immunostimulated astrocytes. NO production in rat primary astrocytes was stimulated for 24–48 h by cotreatment with lipopolysaccharides (1 μg/ml) and interferon‐γ (100 U/ml). Decreased NO production in immunostimulated astrocytes by glucose deprivation was mimicked by the glycolytic inhibitor 2‐deoxyglucose and reversed by addition of pyruvate and lactate. Glucose deprivation did not alter the expression of inducible nitric oxide synthase (iNOS) in immunostimulated astrocytes. Addition of β‐NADPH, but not tetrahydrobiopterine, both of which are essential cofactors for NOS function, completely restored the NO production that was decreased in glucose‐deprived immunostimulated astrocytes. Glucose deprivation and immunostimulation synergistically reduced intracellular NADPH level in astrocytes. The results indicate that glucose deprivation decreases NO production in immunostimulated astrocytes by depleting intracellular NADPH, a cofactor of iNOS. GLIA 37:268–274, 2002. © 2002 Wiley‐Liss, Inc.