bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of HER‐2/neu expression in prostatic adenocarcinoma
Authors: Sanchez Katya M. , Sweeney Christopher J. , Mass Robert , Koch Michael O. , Eckert George J. , Geary William A. , Baldridge Lee Ann , Zhang Shaobo , Eble John N. , Cheng Liang
Published: October 2002

BACKGROUND

Some evidence suggests a role for HER‐2/neu overexpression in prostate carcinoma progression. Reported rates of HER‐2/neu overexpression in patients with prostate carcinoma vary greatly.

METHODS

The authors studied radical prostatectomy specimens from 38 patients who had biochemical failure after undergoing radical prostatectomy for prostate carcinoma. Immunohistochemistry for HER‐2/neu overexpression using the HercepTest kit (Dako Corporation, Carpenteria, CA) was employed. Two different antigen‐retrieval techniques were used: 1) the standard U.S. Food and Drug Administration (FDA)‐approved HercepTest assay and 2) a modified HercepTest, which employed an alkaline citrate buffer, pH 9.0, for antigen retrieval and a 1‐hour primary antibody incubation time. The level of HER‐2/neu expression was evaluated on a scale from 0 (no staining) to 3+ according to the published guidelines. Fluorescent in situ hybridization for gene amplification was performed on all specimens.

RESULTS

With the standard technique, only one specimen had 2+ staining, and no specimens had 3+ staining. With the modified technique, 10 specimens (26%) had 2+ staining, and 9 specimens (24%) had 3+ staining. There was a significant association between the level of HER‐2/neu expression shown with the modified technique and tumor stage (P = 0.03) as well as Gleason grade (P = 0.01). None of the specimens had HER‐2/neu gene amplification.

CONCLUSIONS

The authors report a simple modification of the HercepTest that resulted in an increased rate of HER‐2/neu expression, which was correlated with poor‐risk pathologic findings. The findings suggest that adenocarcinoma of the prostate should be evaluated for HER‐2/neu expression with a prostate specific immunohistochemical procedure that differs from the FDA‐approved standard procedure. Cancer 2002;95:1650–5. © 2002 American Cancer Society.

DOI 10.1002/cncr.10839
Peripheral glucose administration stimulates the translocation of GLUT8 glucose transporter to the endoplasmic reticulum in the rat hippocampus
Authors: Piroli Gerardo G. , Grillo Claudia A. , Hoskin Elena K. , Znamensky Vladimir , Katz Ellen B. , Milner Teresa A. , McEwen Bruce S. , Charron Maureen J. , Reagan Lawrence P.
Published: October 2002

The expression and localization of glucose transporter isoforms play essential roles in the glucoregulatory activities of the hippocampus and ultimately contribute to cognitive status in physiological and pathophysiological settings. The recently identified glucose transporter GLUT8 is uniquely expressed in neuronal cell bodies in the rat hippocampus and therefore may contribute to hippocampal glucoregulatory activities. We show here that GLUT8 has a novel intracellular distribution in hippocampal neurons and is translocated to intracellular membranes following glucose challenge. Immunoblot analysis revealed that GLUT8 is expressed in high‐density microsomes (HDM), suggesting that GLUT8 is associated with intracellular organelles under basal conditions. Immunogold electron microscopic analysis confirmed this observation, in that GLUT8 immunogold particles were associated with the rough endoplasmic reticulum (ER) and cytoplasm. Peripheral glucose administration produced a rapid twofold increase in GLUT8 levels in the HDM fraction while decreasing GLUT8 levels in low‐density microsomes. Similarly, peripheral glucose administration significantly increased GLUT8 association with the rough ER in the hippocampus. Conversely, under hyperglycemic/insulinopenic conditions, namely, in streptozotocin (STZ) diabetes, hippocampal GLUT8 protein levels were decreased in the HDM fraction. These results demonstrate that GLUT8 undergoes rapid translocation to the rough ER in the rat hippocampus following peripheral glucose administration, trafficking that is impaired in STZ diabetes, suggesting that insulin serves as a stimulus for GLUT8 translocation in hippocampal neurons. Because glucose is liberated from oligosaccharides during N‐linked glycosylation events in the rough ER, we propose that GLUT8 may serve to transport glucose out of the rough ER into the cytosol and in this manner contribute to glucose homeostasis in hippocampal neurons. J. Comp. Neurol. 452:103–114, 2002. © 2002 Wiley‐Liss, Inc.
Immunoreactivity against choline acetyltransferase, γ‐aminobutyric acid, histamine, octopamine, and serotonin in the larval chemosensory system of Dosophila melanogaster
Authors: Python François , Stocker Reinhard F.
Published: October 2002

We have studied the distribution of choline acetyltransferase (ChAT), γ‐aminobutyric acid (GABA), histamine, octopamine and serotonin in the larval chemosensory system of Drosophila melanogaster. Colocalization at the confocal level with green fluorescent protein (GFP) or Tau‐GFP reporters, expressed in selected P[GAL4] enhancer trap lines, was used to identify the cells making up these neurotransmitters. As in the adult fly, larval olfactory afferents project into the (larval) antennal lobe (LAL), where they synapse onto local interneurons and projection neurons, whereas gustatory afferents terminate essentially in the tritocerebral‐subesophageal (TR‐SOG) region. We demonstrate that the neuropils of the LAL and the TR‐SOG are immunoreactive to ChAT and GABA. In addition, serotonin‐ and octopamine‐immunoreactive fibers are present in the LAL. ChAT immunostaining is localized in subsets of olfactory and gustatory afferents and in many of the projection neurons. In contrast, GABA is expressed in most, and perhaps all, of the local interneurons. Serotonin immunoreactivity in the LAL derives from a single neuron that is situated close to the LAL and projects to additional neuropil regions. Taken together, these findings resemble the situation in the adult fly. Hence, given the highly reduced numbers of odorant receptor neurons in the larva, as shown in a previous study (Python and Stocker [2002] J. Comp. Neurol. 445:374–387), the larval system may become an attractive model system for studying the roles of neurotransmitters in olfactory processing. J. Comp. Neurol. 453:157–167, 2002. © 2002 Wiley‐Liss, Inc.
Neurogenesis and gliogenesis in the spinal cord of turtles
Authors: Fernández Anabel , Radmilovich Milka , Trujillo‐Cenóz Omar
Published: October 2002

A 5‐bromo‐3′‐deoxyuridine (BrdU) pulse administered to juvenile turtles resulted in cell labeling throughout the gray matter (GM) and white matter (WM) of the spinal cord. One and twenty‐four hours postinjection, larger densities of BrdU‐labeled nuclei (LN) occurred within the GM, with a density peak localized in the central region (CR). Seven days later, density differences between GM and WM disappeared, accompanying a more uniform distribution of LN in the GM (absence of the central peak). Multiple injection experiments also showed similar evolution in the distribution of LN. Morphometric studies revealed that the size of LN had undergone time‐related increments: Larger nuclei appeared at protracted fixation time points. Double‐labeling experiments indicated that BrdU‐labeled cells expressed neuroactive substances, such as γ‐aminobutyric acid (GABA), neuron‐specific nuclear protein (NeuN), and the cytoplasmic early postmitotic neuronal marker (TUC‐4). Other BrdU‐labeled cells expressed the glial‐specific protein (GFAP). GABA‐BrdU, TUC‐4‐BrdU, and GFAP‐BrdU double‐labeled cells were recognized 6 days after the first BrdU injection. NeuN‐BrdU double‐labeled cells were found at 50 days postinjection. Three‐dimensional transmission electron microscopy revealed the presence of synapses and typical kinocilia in putative immature nerve cells. Kinocilia were also found in putative immature glial cells. In consideration of the scattered distribution pattern of BrdU‐labeled cells, in animals fixed 1 hour postinjection, the existence of a single proliferating center was discarded. The CR, including the ependymal epithelium, showed the highest density of LN. J. Comp. Neurol. 453:131–144, 2002. © 2002 Wiley‐Liss, Inc.
Early development of the hypothalamus of a wallaby (Macropus eugenii)
Authors: Cheng Gang , Marotte Lauren R. , Mai Jürgen K. , Ashwell Ken W.S.
Published: October 2002

We have studied the development of the hypothalamus of an Australian marsupial, the tammar wallaby (Macropus eugenii), to provide an initial anatomic framework for future research on the developing hypothalamus of diprotodontid metatheria. Cytoarchitectural (hematoxylin and eosin), immunohistochemical (CD15 and growth associated protein, GAP‐43), tritiated thymidine autoradiography, and carbocyanine dye tracing techniques were applied. Until 12 days after birth (P12), the developing hypothalamus consisted of mainly a ventricular germinal zone with a thin marginal layer, but by P25, most hypothalamic nuclei were well differentiated, indicating that the bulk of hypothalamic cytoarchitectural development occurs between P12 and P25. Strong CD15 immunoreactivity was found in radial glial fibers in the rostral hypothalamus during early developmental ages, separating individual hypothalamic compartments. Immunoreactivity for GAP‐43 was used to reveal developing fiber bundles. The medial forebrain bundle was apparent by P0, and the fornix appeared at P12. Tritiated thymidine autoradiography revealed lateral‐to‐medial and dorsal‐to‐ventral neurogenetic gradients similar to those seen in rodents. Dye tracing showed that projections to the posterior pituitary arose from the supraoptic nucleus at P5 and from the paraventricular nucleus at P10. Projections to the medulla were first found from the lateral hypothalamic area at P0 and paraventricular nucleus at P10. In conclusion, the pattern of development of the wallaby hypothalamus is broadly similar to that found in eutheria, with comparable neurogenetic compartments to those identified in rodents. Because most hypothalamic maturation takes place after birth, wallabies provide a useful model for experimentally manipulating the developing mammalian hypothalamus. J. Comp. Neurol. 453:199–215, 2002. © 2002 Wiley‐Liss, Inc.
Cellular localization of cyclooxygenase‐1 and cyclooxygenase‐2 in the normal mouse, rat, and human retina
Authors: Ju Won‐Kyu , Neufeld Arthur H.
Published: October 2002

Prostaglandins, synthesized by cyclooxygenase (COX), regulate diverse neurophysiological actions such as regulation of autonomic responses, transmission of pain, generation of fever, control of sleep‐wake cycle, synaptic signaling, and cross‐talk between neurons and glia in the central nervous system. Although prostaglandins have been widely studied in the anterior segment tissues of the eye, relatively little is known about prostaglandins in the neural retina. By using immunohistochemistry, we have compared the cellular expression and localization of COX‐1 and COX‐2 in the normal mouse, rat, and human retina. In the normal mouse retina, COX‐1 immunoreactivity is present in the outer segments of photoreceptor cells, horizontal cells, microglia, retinal ganglion cells, and displaced amacrine cells. In the normal rat retina, COX‐1 immunoreactivity is present in microglia, retinal ganglion cells, and displaced amacrine cells. In the normal human retina, COX‐1 immunoreactivity is present in microglia, astrocytes, retinal ganglion cells, and displaced amacrine cells. In the normal mouse and rat retina, COX‐2 immunoreactivity is present in processes of the outer plexiform layer and in certain amacrine cells and retinal ganglion cells. In the normal human retina, COX‐2 immunoreactivity is only present in processes of the outer plexiform layer. These results suggest that prostaglandins, synthesized by COX‐1 or COX‐2, may contribute to normal physiological and homeostatic functions in the retina. J. Comp. Neurol. 452:392–399, 2002. © 2002 Wiley‐Liss, Inc.
Intrahippocampal connections in the pigeon (Columba livia) as revealed by stimulation evoked field potentials
Authors: Hough Gerald E. , Pang Kevin C.H. , Bingman Verner P.
Published: October 2002

The hippocampal formation (HF) of mammals and birds is crucial for spatial learning and memory. However, although the underlying synaptic organization and connectivity of the mammalian HF are well characterized, comparatively little is known about the avian HF. Localized regions of the homing pigeon HF were stimulated at 400–600 μA while evoked field potentials (EFPs) were recorded from adjacent and more distant HF areas relative to the stimulation site. The shortest discernible EFP latency was 12.2 msec. The emerging connectivity profile (using the location of peak EFP amplitude after stimulation and making no determination of the number of intervening synapses) was characterized by projections from the dorsolateral (DL) HF to the dorsomedial (DM) HF (15‐msec latency) at the same anterior/posterior (A/P) level, DM to ventrolateral (VL) and ventromedial (VM; 15 msec) HF across A/P levels, VM to VL (12 msec) and contralateral VM (15 msec) at the same A/P level, and VL to ventral DL (DLv; 15 msec) across A/P levels posterior to the stimulation site. Using these data as a first approximation, connectivity through the avian HF appears to be characterized by a discernible feed‐forward network starting with a projection from DL to DM, DM to VL, VM, and contralateral VM, VM to VL, and VL to posterior ventral DLv. Although still speculative, the results suggest that the internal connectivity of the avian HF is similar to that of the mammalian HF, despite the large evolutionary divergence between the two taxa. J. Comp. Neurol. 452:297–309, 2002. © 2002 Wiley‐Liss, Inc.
Organizational sticking points on NK Landscapes
Authors: Rivkin Jan W. , Siggelkow Nicolaj
Published: October 2002

Scholars studying human organizations have recently adopted the notion of fitness landscapes, a concept pioneered in the biological and physical sciences. Such scholars have generally assumed that organizations will migrate toward the local peaks of these landscapes, as biological and physical entities do. We use an agent‐based simulation to show, to the contrary, that a hierarchical human organization may very well come to rest at a “sticking point” that is not a local peak on the fitness landscape of the overall organization. Three pervasive features of human organizations create the distinction between sticking points and local peaks: the delegation of choices to separate decision makers, interdependencies between the domains of those decision makers, and differences between local incentives and global incentives. Our results illustrate both that it is valuable to use tools developed to study one type of complex adaptive system in order to examine another type and that researchers must adapt the tools with care as they attempt to do so. © 2002 Wiley Periodicals, Inc.
Acinic‐cell carcinoma, papillary‐cystic variant: A diagnostic dilemma in salivary gland aspiration
Authors: Ali Syed Z.
Published: October 2002

Fine‐needle aspiration (FNA) plays a pivotal role as the initial diagnostic modality of choice when dealing with salivary gland (SG) lesions. Due to the heterogeneous nature of most SG neoplasms, cytologic interpretation on FNA can be quite challenging. This is particularly valid when dealing with rare tumor types, such as the papillary‐cystic variant of acinic‐cell carcinoma (ACC‐PCV), resulting in a high rate of false‐negative cytologic diagnoses. Seven cases of ACC‐PCV diagnosed on tissue resection with a prior FNA performed in cytology were studied. Material consisted of Diff‐Quik and Papanicolaou stained cytologic smears, as well as hematoxylin‐eosin stained cell block and histopathologic sections. In no case did the FNA performed prior to the surgical resection eventuate in a cytopathologic diagnosis of cancer. A retrospective morphologic review of the smears disclosed several characteristics common to all 7 cases, i.e., mostly tightly cohesive fragments of neoplastic epithelium seen as monolayered sheets or with a prominent papillary architecture, high nuclear:cytoplasmic ratio ductal‐type epithelium, cystic material and degenerated cellular debris, histiocytes, cells with squamoid and metaplastic oncocytic changes, vacuolated and pigmented histiocyte‐like tumor cells, and lack of a predominant single‐cell component or naked neoplastic cell nuclei. ACC‐PCV represents a rare yet significant cause of false‐negative results for cancer on SG aspirations. An erroneous interpretation may occur due to lack of experience in dealing with this tumor type, the rarity of published literature on ACC‐PCV, and a predominantly cystic, somewhat variegated appearance of the tumor mimicking other benign and malignant SG lesions. Diagn. Cytopathol. 2002;27:244–250. © 2002 Wiley‐Liss, Inc.
Fine‐needle aspiration biopsy of invasive micropapillary carcinoma of the breast: A report of five cases
Authors: Bayramoglu Hatice , Zekioglu Osman , Erhan Yildiz , Çiriş Metin , Özdemir Necmettin
Published: October 2002

Invasive micropapillary carcinoma of the breast is an uncommon variant of infiltrating ductal carcinoma. Observing its distinctive cytologic appearance and aggressive behavior is important for early diagnosis by fine‐needle aspiration cytology (FNAC). There are only a few reported cases in the literature.

Five women presented with breast masses. FNAC showed malignant epithelial tumors, and mastectomy materials showed invasive micropapillary carcinoma for all of them. Three patients had axillary lymph node metastases.

Invasive micropapillary carcinoma, with its angulated papillary clusters lacking a fibrovascular core, and irregular crowded nuclei, has a distinctive cytologic appearance which correlates with its histological features. A differential diagnosis from other primary or metastatic papillary lesions of the breast may be possible using immunohistochemistry and some cytologic features. The limited experience with invasive micropapillary carcinoma should not discourage others from undetaking further studies. Diagn. Cytopathol. 2002;27:214–217. © 2002 Wiley‐Liss, Inc.
Current drug targets for Alzheimer's disease treatment
Authors: Lahiri Debomoy K. , Farlow Martin R. , Greig Nigel H. , Sambamurti Kumar
Published: October 2002

Alzheimer's disease (AD), the most common form of dementia among the elderly, is a progressive, degenerative disorder of the brain with a loss of memory and cognition. A defining characteristic of AD is the deposition of amyloid fibrils and neurofibrillary tangles in the brain of afflicted individuals. Biochemically, they are mainly composed of β‐amyloid protein (Aβ) and phosphorylated tau proteins, respectively. There is also a loss of the presynaptic markers of the cholinergic system, such as acetylcholine, in the brain areas related to memory and learning. The biochemical pathways leading to AD are presently unknown and are a subject of intensive study with current theories favoring a hypothesis where Aβ aggregates to toxic forms that induce tau phosphorylation and aggregation. It is believed that this ultimately leads to dysfunction and death of cholinergic neurons, and compensation for this loss had been the primary focus of first generation therapeutic agents. The amyloid and tau hypotheses have lead to a focus on amyloid and tau as therapeutic targets. The current therapeutic goals are to reduce amyloid levels, prevention of amyloid aggregation/toxicity and tau phosphorylation/aggregation. AD has a heterogeneous etiology with a large percentage termed sporadic AD arising from unknown causes and a smaller fraction of early onset familial AD (FAD) caused by mutations in several genes, such as the β‐amyloid precursor protein (APP) and presenilins (PS1, PS2). Other genes, such as apolipoprotein E (APOE), are considered to be risk factors for AD. Several proteins, such as APP, APOE, BACE (β‐amyloid cleaving enzyme), PS1/2, secretases, and tau play important roles in the pathology of AD. Therefore, attempts are being made to develop new inhibitors for BACE, PS‐1 and γ‐secretase for treatment of AD. There is also a significant advancement in understanding the function of cholinesterase (ChE) in the brain and the use of ChE inhibitors in AD. The mechanism of a new generation of acetyl‐ and butyrylChE inhibitors is being studied and tested in human clinical trials for AD. Other strategies, such as vaccination, anti‐inflammatory agents, cholesterol‐lowering agents, anti‐oxidants and hormone therapy, are also being studied for treating or slowing the progression of AD. Developments of early diagnostic tools based on quantitative biochemical markers will be useful to better follow the course of the disease and to evaluate different therapeutic strategies. In the present review, we attempt to critically examine recent trends in AD research from neurochemical to clinical areas. We analyze various neurobiological mechanisms that provide the basis of new targets for AD drug development. These current research efforts should lead to a deeper understanding of the pathobiochemical processes that occur in the AD brain to effectively diagnose and prevent their occurrence. Drug Dev. Res. 56:267–281, 2002. © 2002 Wiley‐Liss, Inc.
Preclinical progress with CHF2819, a novel orally active acetylcholinesterase inhibitor
Authors: Cassano Tommaso , Carratù M. Rosaria , Coluccia Addolorata , Di Giovanni Vincenzo , Steardo Luca , Cuomo Vincenzo , Trabace Luigia
Published: October 2002

(‐)‐(3aS,8aS,1S)‐1,2,3,3a,8,8a‐hexahydro‐1,3a,8‐trimethylpyrrolo[2,3‐b]indol‐5‐ol‐2′‐ethylphenylcarbamate N‐oxide hydrochloride (CHF2819) is a novel, orally active acetylcholinesterase inhibitor (AChEI) for Alzheimer's disease (AD). CHF2819 appears as a selective inhibitor of AChE, being 115 times more potent against this enzyme than butyrylcholinesterase (BuChE). Moreover, CHF2819 appears more selective for inhibiting central (brain) than peripheral (heart) AChE. In vivo studies show that CHF2819 significantly increases acetylcholine (ACh) levels in young adult rat hippocampus in a dose‐dependent manner. Moreover, aged animals exhibit a marked increase in hippocampal concentrations of this neurotransmitter after the administration of CHF2819. This compound attenuates scopolamine‐induced amnesia in a passive avoidance task. Furthermore, CHF2819 induces a significant decrease in dopamine (DA) levels and a significant elevation of hippocampal extracellular concentrations of 5‐hydroxytryptamine (5‐HT), while it does not modify noradrenaline (NA) levels. Oral administration of CHF2819 does not affect hippocampal extracellular glutamate (Glu), aspartate (Asp), γ‐aminobutyric acid (GABA), taurine (Tau), arginine (Arg), and citrulline (Cit) concentrations of young adult rats. Functional observational battery (FOB) screening demonstrates that CHF2819 (1.5 and 4.5 mg/kg p.o.) does not affect activity, excitability, autonomic, neuromuscular, and sensorimotor domains, as well as physiological endpoints. However, this compound induces involuntary motor movements in a dose‐dependent manner. In conclusion, the neurochemical and behavioral profile of CHF2819 suggests that this orally active novel AChEI could be of clinical interest for the treatment of Alzheimer‐type dementia associated with multiple neurotransmitter abnormalities in the brain. In particular, CHF2819 might be a useful therapeutic drug for AD patients in which the cognitive impairment is accompanied by a depressive syndrome. Drug Dev. Res. 56:354–368, 2002. © 2002 Wiley‐Liss, Inc.
Oxidative imbalance and lipid peroxidation in Alzheimer's disease
Authors: Praticò Domenico
Published: October 2002

Alzheimer's disease (AD) is a growing serious public health problem worldwide. Clinically, AD is a progressive neurodegenerative disorder characterized by a global cognitive decline. There is significant evidence that reactive oxygen species‐mediated reactions, particularly of neuronal lipids, are extensive in those AD brain areas directly involved in the disease processes. Traditional views claim that oxidative‐mediated tissue injury in the AD brain is the result of neurodegeneration. In recent years, numerous investigations have pointed to the functional importance of oxidative imbalance as a crucial event in mediating AD pathogenesis. The availability of specific and sensitive markers to monitor in vivo oxidative imbalance, in combination with studies performed in living patients with clinical diagnosis of AD, are helping to elucidate these issues. Here, I summarize some of the most recent research on the relevance that oxidative imbalance and lipid peroxidation have in AD. The evidence accumulated so far clearly indicates that oxidative imbalance is an early event during the evolution of this devastating disease. This new concept implies that this phenomenon may play a more important role in AD pathogenesis than previously anticipated. Drug Dev. Res. 56:446–451, 2002. © 2002 Wiley‐Liss, Inc.
The case for iron chelation and/or antioxidant therapy in Alzheimer's disease
Authors: Malecki Elise A. , Connor James R.
Published: October 2002

Iron is involved in the pathogenesis of Alzheimer's disease by multiple mechanisms. We discuss the role of iron in catalysis of reactive oxygen and nitrogen species, protein physical chemistry, and inflammation. Strategies to deal with iron and its effects have a place in the prevention and treatment of Alzheimer's disease. Therapies utilizing these strategies include iron chelators and antioxidants. Drug Dev. Res. 56:526–530, 2002. © 2002 Wiley‐Liss, Inc.
Patterns of cortisol reactivity in African‐American neonates from low‐income environments
Authors: Keenan Kate , Gunthorpe Dana , Young Desia
Published: October 2002

Individual differences and stability in patterns of salivary cortisol reactivity were examined in 100 African‐American neonates from low‐income environments. A pattern of reactivity was defined by the change from prestressor to poststressor cortisol concentrations and the change following the poststressor during a recovery phase. Cortisol reactivity was measured in response to two stressors: the Neonatal Behavioral Assessment Scale (NBAS; T. B. Brazelton & J. K. Nugent) and the routine hospital heels‐tick procedure. The use of two stressors allowed an examination of whether patterns of reactivity to different stimuli vary and whether there is individual stability in patterns of cortisol reactivity. Cortisol concentrations changed significantly across the three time points. The magnitude of change during the recovery period differed across stressors. Prestressor cortisol values were associated with cortisol reactivity. Both prestressor cortisol concentrations and pattern of cortisol response were significantly associated within individuals. © 2002 Wiley Periodicals, Inc. Dev Psychobiol 41: 265–276, 2002. Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/dev.10048
Sucking, not milk, is important for the rapid learning of nipple‐search odors in newborn rabbits
Authors: Hudson Robyn , Labra‐Cardero Daniela , Mendoza‐Soylovna Adela
Published: October 2002

Newborn rabbits are only nursed once a day for 3 to 4 min and are completely dependent on a pheromone on the mother's ventrum for the release of nipple‐search behavior and sucking. However, if the mother's ventrum is perfumed, pups can be conditioned in just one 3‐min nursing session to respond with nipple searching to the novel odorant. To define more precisely the reinforcing properties of the nursing situation supporting such rapid learning, odor conditioning was conducted in independent groups of 2‐day‐old pups after successively eliminating potential reinforcing stimuli such as the doe's behavior, milk ingestion, nipple‐search behavior, or sucking nipples. All experimental groups showed significant conditioning compared to control groups subjected to similar treatments on unscented does, with the strength of conditioning indicating that behavior of the doe, milk consumption, or arousal during performance of the search behavior were not major reinforcers, but rather the opportunity to suck nipples. Thus, this study suggests intraoral stimulation associated with sucking to be an important reinforcer in this paradigm, as for early olfactory learning in other young mammals. © 2002 Wiley Periodicals, Inc. Dev Psychobiol 41: 226–235, 2002. Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/dev.10073
Application of multiple adaptive regression splines (MARS) in direct response modeling
Authors: Deichmann Joel , Eshghi Abdolreza , Haughton Dominique , Sayek Selin , Teebagy Nicholas
Published: October 2002

Increasing costs of direct marketing campaigns coupled with declining response rates have prompted many direct marketers to turn to more sophisticated techniques to model response behavior. The underlying premise is that even a small improvement in response rate can have significant implications for the bottom line. This article investigates the use of a recently developed technique, Multiple Adaptive Regression Splines (MARS), together with logistic regression in the context of modeling direct response. Specifically, our goal is to assess the relative effectiveness of MARS models vis-à-vis logistic regression with original predictor variables in modeling direct response behavior. Our analysis shows that the MARS models outperforms the logistic model in general, leading us to conclude that MARS offers a number of advantages over a logistic model. Direct marketing strategy implications are also discussed.
Analysis of N‐cadherin function in limb mesenchymal chondrogenesis in vitro
Authors: Delise Anthony M. , Tuan Rocky S.
Published: October 2002

During embryonic limb development, cartilage formation is presaged by a crucial mesenchymal cell condensation phase. N‐Cadherin, a Ca2+‐dependent cell–cell adhesion molecule, is expressed in embryonic chick limb buds in a spatiotemporal pattern suggestive of its involvement during cellular condensation; functional blocking of N‐cadherin homotypic binding, by using a neutralizing monoclonal antibody, results in perturbed chondrogenesis in vitro and in vivo. In high‐density micromass cultures of embryonic limb mesenchymal cells, N‐cadherin expression level is high during days 1 and 2, coincident with active cellular condensation, and decreases upon overt chondrogenic differentiation from day 3 on. In this study, we have used a transfection approach to evaluate the effects of gain‐ and loss‐of‐function expression of N‐cadherin constructs on mesenchymal condensation and chondrogenesis in vitro. Chick limb mesenchymal cells were transfected by electroporation with recombinant expression plasmids encoding wild‐type or two mutant extracellular/cytoplasmic deletion forms of N‐cadherin. Expression of the transfected N‐cadherin forms showed a transient profile, being high on days 1–2 of culture, and decreasing by day 3, fortuitously coincident with the temporal profile of endogenous N‐cadherin gene expression. Examined by means of peanut agglutinin (PNA) staining for condensing precartilage mesenchymal cells, cultures overexpressing wild‐type N‐cadherin showed enhanced cellular condensation on culture days 2 and 3, whereas expression of the deletion mutant forms (extracellular/cytoplasmic) of N‐cadherin resulted in a decrease in PNA staining, suggesting that a complete N‐cadherin protein is required for normal cellular condensation to occur. Subsequent chondrogenesis was also affected. Cultures overexpressing the wild‐type N‐cadherin protein showed enhanced chondrogenesis, indicated by increased production of cartilage matrix (sulfated proteoglycans, collagen type II, and cartilage proteoglycan link protein), as well as increased cartilage nodule number and size of individual nodules, compared with control cultures and cultures transfected with either of the two mutant N‐cadherin constructs. These results demonstrate that complete N‐cadherin function, at the levels of both extracellular homotypic binding and cytoplasmic linkage to the cytoskeleton by means of the catenin complex, is required for chondrogenesis by mediating functional mesenchymal cell condensation. © 2002 Wiley‐Liss, Inc.
2D adaptive state‐space filters suitable for parallel processing using state‐space model with general form
Authors: Ishizaki Naoya , Muneyasu Mitsuji , Hinamoto Takao
Published: October 2002

This paper proposes a realization of a two‐dimensional adaptive state‐space filter for parallel processing using state‐space model with a general form. For the modeling of the filter, a generalized model realized for parallel processing is used and the conventional denominator‐separation type model is extended. Further, the LMS (Least Mean Square) algorithm is used to construct an adaptive algorithm and its processing speed and computational effort are evaluated. By means of this method, the hardware content can be reduced while the processing speed is maintained almost the same as in the complete generalized model. Finally, in order to verify the effectiveness of the present method, an example is presented in which a two‐dimensional adaptive filter is applied to the spatial domain design as a system identification problem. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 86(1): 46–57, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.10019
Association of prostate cancer with rapid N‐acetyltransferase 1 (NAT1*10) in combination with slow N‐acetyltransferase 2 acetylator genotypes in a pilot case‐control study
Authors: Hein David W. , Leff Matthew A. , Ishibe Naoko , Sinha Rashmi , Frazier Harold A. , Doll Mark A. , Xiao Gong H. , Weinrich Martin C. , Caporaso Neil E.
Published: October 2002

N‐acetyltransferase‐1 (NAT1) and N‐acetyltransferase‐2 (NAT2) are important in the metabolism of aromatic and heterocyclic amine carcinogens that induce prostate tumors in the rat. We investigated the association of genetic polymorphisms in NAT1 and NAT2, alone and in combination, with human prostate cancer. Incident prostate cancer cases and controls in a hospital‐based case‐control study were frequency‐matched for age, race, and referral pattern. The frequency of slow acetylator NAT1 genotypes (NAT1*14, *15, *17) was 5.8% in controls but absent in cases. In contrast, in comparison with all other NAT1 genotypes the putative rapid acetylator NAT1 genotype (NAT1*10) was significantly higher in prostate cancer cases than controls (OR, 2.17; 95% CI, 1.08–4.33; P = 0.03). Combinations of NAT1*10 with NAT2 slow acetylator genotypes (OR, 5.08; 95% CI, 1.56–16.5; P = 0.008) or with NAT2 very slow (homozygous NAT2*5) acetylator genotypes (OR, 7.50; 95% CI, 1.55–15.4; P = 0.016) further increased prostate cancer risk. The results of this small pilot study suggest increased susceptibility to prostate cancer for subjects with combinations of NAT1*10 and slow (particularly very slow) NAT2 acetylator genotypes. This finding should be investigated further in larger cohorts and in other ethnic populations. Environ. Mol. Mutagen. 40:161–167, 2002. © 2002 Wiley‐Liss, Inc.
On sampling and experiments
Authors: Thompson Steven K.
Published: October 2002

Sampling generally concerns how a sample of units is selected from a population, while experiments deal with the effects of a treatment or exposure on units and are concerned with the assignment of treatments to units. Real studies typically involve elements of both, with varying control by investigators over sample selection and treatment assignment aspects. Design and model based approaches in sampling and experiments, and in particular studies which combine both elements, are examined in this article. Within a model based approach design based methods can be used based on a conditioning argument which is necessarily somewhat more complex in the case of experimental studies than in studies involving only sampling. Copyright © 2002 John Wiley & Sons, Ltd.
Accounting for measurement error in uncertainty modeling and decision‐making using indicator kriging andp‐field simulation: application to a dioxin contaminated site
Authors: Saito Hirotaka , Goovaerts Pierre
Published: October 2002

In many environmental studies spatial variability is viewed as the only source of uncertainty while measurement errors tend to be ignored. This article presents an indicator kriging‐based approach to account for measurement errors in the modeling of uncertainty prevailing at unsampled locations. Probability field simulation is then used to assess the probability that the average pollutant concentration within remediation units exceeds a regulatory threshold, and probability maps are used to identify hazardous units that need to be remediated. This approach is applied to two types of dioxin data (composite and single spoon samples) with different measurement errors which were collected at the Piazza Road dioxin site, an EPA Superfund site located in Missouri. A validation study shows that the proportion of contaminated soil cores provides a reasonable probability threshold to identify hazardous remediation units. When a lower probability threshold is chosen, the total remediation costs are unreasonably high while false negatives are unacceptably frequent for a higher probability threshold. The choice of this threshold becomes critical as the sampling density decreases. Copyright © 2002 John Wiley & Sons, Ltd.
Computing the Bayesian highest posterior density credible sets for the lognormal mean
Authors: Dalpatadu Rohan , Gewali L. , Singh A. K.
Published: October 2002

Contaminant concentration data collected at Superfund sites are typically positively skewed, and the log‐normal distribution is commonly used to model such data distribution. U.S. EPA guidance documents recommend the use of H‐statistics to compute the upper confidence limit (UCL) of the mean of a log‐normal distribution. Recent work reported in the statistical literature has shown that the UCL calculated from the H‐statistics can yield extremely high false positives. In the present article we compute the Bayesian highest posterior density (HPD) credible set of the log‐normal mean. Simulated results using techniques of computational geometry are presented. Several experimental results on environmental data sets reveal that the UCL obtained by using the proposed Bayesian approach is more reasonable than those obtained by using other techniques. Copyright © 2002 John Wiley & Sons, Ltd.
Bootstrap upper bounds for the arithmetic mean of right‐skewed data, and the use of censored data
Authors: Ginevan Michael E. , Splitstone Douglas E.
Published: October 2002

Environmental contamination data frequently follow an extremely right skewed distribution, which is often approximated by a log‐normal distribution. For the purpose of risk assessment it is of interest to use the sample data to calculate an upper bound on the population arithmetic mean. This article reviews the usual upper bound estimator calculated assuming a log‐normal distribution and shows that, when the log‐normal assumption is not satisfied, this method can result in severe over‐estimation of the upper bound for the arithmetic mean. We then show, using Monte Carlo simulation, that a bootstrap upper bound is a much better approximation to the true upper bound on the population arithmetic mean. Finally, we present a bootstrap procedure for use when the data are left censored by detection/quantification limits and discuss Monte Carlo results that support the use of this procedure when as much as one‐half of the sample consists of censored observations. Copyright © 2002 John Wiley & Sons, Ltd.
An evaluation of the Confidence Removal Goal approach for making remediation decisions at Superfund sites
Authors: Schultz Brad , Singh Ashok K. , Singh Anita
Published: October 2002

The Confidence Removal Goal approach was developed by the Gradient Corporation for the cleanup decisions at the METCOA Superfund Site. The CRG approach is a statistical approach to meet site cleanup goals based on the arithmetic mean of the contaminant concentration distribution. The CRG approach involves computing a threshold value c* (called the CRG value) from observed sample values in cases where the data distribution is log‐normal and the UCL of the population mean calculated for the sample exceeds the Cleanup Goal (CUG). The cleanup would then consist of removing all soils from the site with observed concentrations higher than the CRG value c*. At the METCOA site, the cadmium (Cd) and nickel (Ni) concentrations passed the test of log‐normality, and the UCL of the means exceeded their respective CUG values. The CRG values were then computed for observed Cd and Ni concentrations. In both cases, the CRG values turned out to be much higher than the respective observed maximum concentration. Based on these CRG values, it would appear that no cleanup would be needed at the METCOA site. A Monte Carlo simulation experiment was conducted by two of the authors of this article to investigate the performance of the CRG approach. The simulation experiments showed that the CRG approach had a rather high percentage of false negatives, i.e. it recommended no cleanup a large number of times when the simulation was performed for contaminated site conditions. The present article investigates the performance of the CRG approach for normal, uniform and exponential distributions, in addition to the log‐normal distribution. The CRG approach gives reasonable results for all models considered in this article, except for the log‐normal model, suggesting the inadequacy of the log‐normal distribution for modeling skewed environmental data. Copyright © 2002 John Wiley & Sons, Ltd.
Finite volume evolution Galerkin methods for Euler equations of gas dynamics
Authors: Lukáčová‐Medvid'ová M. , Morton K. W. , Warnecke G.
Published: October 2002

The aim of this paper is a derivation of a new multidimensional high‐resolution finite volume evolution Galerkin method for system of the Euler equations of gas dynamics. Instead of solving one‐dimensional Riemann problems in directions normal to cell interfaces the finite volume evolution Galerkin schemes are based on a genuinely multidimensional approach. The approximate solution at cell interfaces is computed by means of an approximate evolution operator taking all of the infinitely many bicharacteristics explicitly into account. Integrals along the Mach cones are evaluated exactly or by means of numerical quadratures. Second‐order resolution is obtained with a conservative piecewise bilinear recovery and the second‐order midpoint rule for the time integration. A numerical experiment which illustrates the good multidimensional approximation as well as higher‐order resolution is presented. Copyright © 2002 John Wiley & Sons, Ltd.
Estimation of systematic error in an equatorial ocean model using data assimilation
Authors: Martin M. J. , Bell M. J. , Nichols N. K.
Published: October 2002

Assimilation of temperature observations into an ocean model near the equator often results in a dynamically unbalanced state with unrealistic overturning circulations. The way in which these circulations arise from systematic errors in the model or its forcing is discussed. A scheme is proposed, based on the theory of state augmentation, which uses the departures of the model state from the observations to update slowly evolving bias fields. Results are summarized from an experiment applying this bias correction scheme to an ocean general circulation model. They show that the method produces more balanced analyses and a better fit to the temperature observations. © Crown copyright 2002. Reproduced with the permission of Her Majesty's Stationery Office. Published by John Wiley & Sons, Ltd.
Integral boundary conditions for unsteady biomedical CFD applications
Authors: Nicoud F. , Schönfeld T.
Published: October 2002

A methodology to prescribe integral boundary conditions is proposed. The approach makes use of the decomposition of the solution into waves. It applies to any numerical method solving hyperbolic equations, including the compressible Navier–Stokes equations or their incompressible counterpart when solved through an artificial compressibility method. For any physical quantity to be imposed (e.g. the mass flow rate entering the computational domain), the boundary treatment consists in imposing a 1D incoming ‘acoustic’ wave proportional to the difference between the mean quantity of interest (e.g. the mean mass flow rate) over the boundary and its prescribed target value. The approach is validated by computing both steady and pulsated channel flows for Womersley number upto 15. Results from a 3D simulation of the blood flow within a human aortic arch are briefly discussed. Copyright © 2002 John Wiley & Sons, Ltd.
A parallel adaptive projection method for low Mach number flows
Authors: Bell J. B. , Day M. S. , Almgren A. S. , Lijewski M. J. , Rendleman C. A.
Published: October 2002

We describe an adaptive projection method for numerically simulating low Mach number flows. The projection method formulation enforces the velocity divergence constraint resulting from the low Mach number approximation. It is implemented on an adaptive hierarchy of logically rectangular grids, where each finer level is refined in space and in time. The adaptive algorithm has been shown in previous papers to be robust and second‐order accurate, and to satisfy the principles of conservation and free‐stream preservation as applicable. Here, the parallelization is described in some detail, and the methodology is demonstrated on two examples from premixed, low Mach number combustion. Published in 2002 by John Wiley & Sons, Ltd.
Anisotropic adaptation and multigrid for hybrid grids
Authors: Müller Jens‐Dominik
Published: October 2002

An anisotropic refinement method for 2D and 3D hybrid grids is presented and applied to viscous flow problems. The algorithm is unique in that it is not limited to a particular grid structure, e.g. hexahedral elements, but allows the anisotropic division of hexahedra and prisms in 3D, quadrilaterals in 2D and the isotropic division of the other element types. At the core of the method is a novel surface tessellation of an element with hanging nodes which guarantees mesh consistency also in the case of arbitrary directional refinement over an arbitrary number of levels. The efficiency of the anisotropic refinement algorithm is evaluated on viscous flow testcases. The resulting grid sequence is compared to an element‐collapse sequence for its suitability for directionally coarsened multigrid. Copyright © 2002 John Wiley & Sons, Ltd.
Agglomerated multigrid on hybrid unstructured meshes for compressible flow
Authors: Sørensen K. A. , Hassan O. , Morgan K. , Weatherill N. P.
Published: October 2002

A review of the applicability of the agglomerated multigrid solution acceleration approach for the simulation of compressible flows is presented. The flow descriptions are wide ranging, spanning from inviscid to turbulent and from steady state to transient. The spatial discretization is performed by a node‐centred finite volume scheme, with explicit addition of fourth‐order artificial dissipation. The improved performance resulting from the introduction of unstructured hybrid meshes is illustrated. For time‐dependent flows involving moving geometries, a second order geometrically conservative scheme is applied, with multigrid accelerated implicit timestepping. Copyright © 2002 John Wiley & Sons, Ltd.
A shape function approach for high‐ and low‐ Reynoldsnear‐wall turbulence models
Authors: Boyer V. , Laurence D.
Published: October 2002

A new numerical approach for wall functions is proposed, in order to bridge the gap between low‐ and high‐Reynolds near‐wall turbulence modelling. It allows arbitrary sizes of near‐wall cells with the objective of using local grid refinement or adaptive meshes in industrial calculations. This finite volume‐finite element approach is based on the introduction of assumed shape functions into the energy conservation equations, for the determination of four wall scalings factors. Equilibrium assumptions are avoided, and replaced by formal integration of budget equations in the first cell. The approach is proved accurate and stable in a simple channel flow, but the formalism was developed for non‐equilibrium situations where it still needs to be tested. Copyright © 2002 John Wiley & Sons, Ltd.