bluuebunny/crossref_metadata_2025 huggingface dataset:
Augmentation by zinc of NMDA receptor‐mediated synaptic responses in CA1 of rat hippocampal slices: Mediation by Src family tyrosine kinases
Authors: Kim Tae‐Youn , Hwang Jung‐Jin , Hwan Yun Sung , Whan Jung Min , Koh Jae‐Young
Published: October 2002

Normal neuronal activity results in the release of zinc from the synaptic vesicles of glutamatergic terminals and subsequent entry into postsynaptic neurons. Although the exact physiological role of zinc translocation is currently unknown, it is very likely that intracellular zinc exerts long‐term modulatory effects upon synaptic transmission since zinc affects various molecules involved in signaling pathways. In this study we used rat hippocampal slices to examine the effect of zinc on glutamatergic synaptic transmission in the Schaffer collateral‐CA1 synapses. Following a 10‐min exposure to 0.3–1 mM zinc, the magnitude of NMDA receptor‐mediated field excitatory postsynaptic potentials (fEPSP) gradually increased over the subsequent 30–40 min. In contrast, the magnitude of AMPA/kainate receptor‐mediated fEPSPs remained unchanged. The selective potentiation of NMDA receptor‐mediated fEPSPs by zinc was unlikely to be a presynaptic event, since the degree of paired‐pulse facilitation was unaltered. Interestingly, the specific Src family tyrosine kinase inhibitor PP2 completely blocked zinc‐induced potentiation of NMDA receptor‐mediated fEPSP while the inactive analog PP3 had no effect, thereby suggesting the involvement of Src family tyrosine kinases. Furthermore, zinc exposure increased levels of total and tyrosine‐phosphorylated forms of NR2A and NR2B in a PP2‐dependent manner in both hippocampal slices and cell cultures. In addition, zinc treatment of hippocampal cultures increased the levels of tyrosine phosphorylation at the two positive regulatory sites of Src family tyrosine kinases. Our results demonstrate that zinc increases NMDA receptor function via Src family tyrosine kinase‐mediated increases of NR2A and 2B tyrosine phosphorylation. We speculate that intense release of endogenous synaptic zinc may potentiate NMDA receptor‐mediated transmission in zinc‐containing glutamatergic pathways by a similar mechanism. Synapse 46:49–56, 2002. © 2002 Wiley‐Liss, Inc.
Amazonian Paleodunes Provide Evidence for Drier Climate Phases during the Late Pleistocene–Holocene
Authors: Filho Arnaldo Carneiro , Schwartz Dominique , Tatumi Sonia H. , Rosique Thierry
Published: October 2002

Recent studies on relict eolian dunes in the Rio Negro basin, northern Amazon, Brazil (00°35′N, 63°14′W), indicate a drier climate regime during the Late Pleistocene–Holocene transition that is different from the present humid climate. The eolian sands form long chains of linear dunes bordering the Rio Negro River and some tributaries. Here, we present thermoluminescence (TL) ages spanning the period 32,000–8000 yr B.P. The final dune stabilization took place after 8,000 yr B.P. and now the bases of the dunes are fixed by vegetation. Clustering of the TL dates suggests that the dry climate in the Amazon Basin occurred in distinct episodes and argues against current opinions that drastic ecological changes did not affect in the Amazon during the last global glaciation.
CD44 signaling through focal adhesion kinase and its anti‐apoptotic effect
Authors: Fujita Yoshihisa , Kitagawa Motoo , Nakamura Sukeyuki , Azuma Kazuhiko , Ishii Genichiro , Higashi Morihiro , Kishi Hirohisa , Hiwasa Takaki , Koda Keiji , Nakajima Nobuyuki , Harigaya Kenichi
Published: October 2002

Adhesion molecules can initiate intracellular signaling. Engagement of CD44 either by its natural ligand hyaluronan or a specific antibody on a cell line induced tyrosine phosphorylation and activation of focal adhesion kinase (FAK), which then associated with phosphatidylinositol 3‐kinase (PI3K) and activated mitogen‐activated protein kinase at its downstream. However, the introduction of dominant negative Rho into the cells inhibited the CD44‐stimulated FAK phosphorylation. Cells expressing CD44 were significantly resistant to etoposide‐induced apoptosis. This anti‐apoptotic effect was cancelled by the inhibition of either Rho, FAK or PI3K. These results may indicate a signaling pathway from CD44 to mediate the resistance against drug‐induced apoptosis in cancer cells.
Formal education does not improve the acceptance of cesarean section among pregnant Nigerian women
Authors: Onah H.E
Published: October 2002

Objectives: To investigate the relationship between formal education, personal beliefs and the acceptance of cesarean section among pregnant Nigerians. Methods: A questionnaire survey was made of antenatal mothers seen over a 5‐month period at a tertiary hospital in Enugu, Nigeria. Results: A total of 1148 subjects were interviewed. Although as a single variable, formal education was significantly related to a more favorable attitude to cesarean section among the respondents, it ceased to be related when their beliefs about the operation were corrected for. Conclusions: Pregnant Nigerians’ beliefs about cesarean section are more important than formal education in determining whether or not they accept it, hence the need to correct such false beliefs during antenatal classes.
On some periodic Hartree-type models for crystals
Authors: Le Bris C. , Lions P.-L. , Catto I.
Published: October 2002

We continue here our study of the thermodynamic limit for various models of Quantum Chemistry. More specifically, we study the Hartree and the restricted Hartree model. For the restricted Hartree model, we prove the existence of the thermodynamic limit for the energy per unit volume. We also define a periodic problem associated to the Hartree model, and we prove that it is well-posed.

Nous poursuivons dans cet article notre étude systématique de la limite thermodynamique de divers modèles issus de la Chimie Quantique Moléculaire. Nous étudions plus spécifiquement les modèles de Hartree et de Hartree restreint. Pour le modèle de Hartree restreint, nous prouvons l'existence de la limite thermodynamique de l'énergie par unité de volume. Nous définissons également un modèle périodique associé au modèle de Hartree, et nous démontrons qu'il est bien posé.
Effect of pulsed electromagnetic fields (PEMF) on late‐phase osteotomy gap healing in a canine tibial model
Authors: Inoue Nozomu , Ohnishi Isao , Chen Dongan , Deitz Luke W. , Schwardt Jeffrey D. , Chao Edmund Y. S.
Published: October 2002

The effects of a pulsed electromagnetic field (PEMF) on late bone healing phases using an osteotomy gap model in the canine mid‐tibia were investigated. A transverse mid‐diaphyseal tibial osteotomy with a 2‐mm gap was performed unilaterally in 12 adult mixed‐breed dogs and stabilized with external fixation. Animals in the variable group (n = 6) were treated with PEMF for 1 h daily starting 4 weeks after surgery for a total of 8 weeks, whereas no stimulation signal was generated in the control group (n = 6). Functional load‐bearing and radiographic assessments were conducted time‐sequentially until euthanasia 12 weeks after surgery. Torsional tests and an analysis of undecalcified histology were performed on the retrieved mid‐tibial diaphysis containing the osteotomy site. In the PEMF group, load‐bearing of the operated limb recovered earlier when compared to the control group (p < 0.05). Load‐bearing in the PEMF group at 8 weeks was greater than in the control group (p < 0.02). The periosteal callus area increased following surgery at 6 weeks (p < 0.05) and thereafter (p < 0.01) in the PEMF group, while a significant increase was observed at 8 and 10 weeks after surgery (p < 0.05) in the control group. Both the normalized maximum torque and torsional stiffness of the PEMF group were significantly greater than those of the control group (p < 0.04 and p < 0.007, respectively). Histomorphometric analyses revealed greater new‐bone formation (p < 0.05) in the osteotomy gap tissue and increased mineral apposition rate (p < 0.04) and decreased porosity in the cortex adjacent to the osteotomy line (p < 0.02) in the PEMF group. PEMF stimulation of 1 h per day for 8 weeks provided faster recovery of load‐bearing, a significant increase in new bone formation, and a higher mechanical strength of the healing mid‐tibial osteotomy. This study revealed enhancing effects of PEMF on callus formation and maturation in the late‐phase of bone healing.

© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Longitudinal changes in net worth by household income and demographic characteristics for the first three waves of the HRS
Authors: Lahey Karen Eilers , Kim Doseong
Published: October 2002

The purpose of this study is to provide an initial examination of the first three waves of the HRS in terms of non-housing net worth by gender, education, race, religion, income, and age. The longitudinal data that is available for a sample of those who are nearing retirement or in retirement allows a picture of their ®nancial condition to be drawn. Statistical analysis indicates that there is a difference in non-housing net worth by demographic characteristics and marital status for each wave of the HRS and between the waves. Copyright 2001 Published by Elsevier Science Inc.
A Tax-Free Exploitation of the Turn-of-the-Month Effect: C.R.E.F.
Authors: Compton William S. , Kunkel Robert A.
Published: October 2002

By applying knowledge of the "turn-of-the-month" effect investors will improve the risk-adjusted performance of their retirement accounts by using a simple and easily implemented "switching" strategy. Our exploitation of the turn-of-the-month anomaly achieves a 17.7 percent average annual rate of return by switching between a money market account and a broad market indexed stock account. This is compared to a 15.6 percent average annual rate achieved by simply buying and holding the stock account, or a 5.8 percent rate on the money market account. Additionally, volatility is cut in half and there are no tax consequences or transactions fees when the switching strategy is used within a retirement account. Our results suggests that this strategy might be suc- cessfully implemented, under current tax laws, in qualified retirement plans and in variable annuities.
Complex acts of knowing: paradox and descriptive self‐awareness
Authors: Snowden David
Published: October 2002

We are reaching the end of the second generation of knowledge management, with its focus on tacit‐explicit knowledge conversion. Triggered by the SECI model of Nonaka, it replaced a first generation focus on timely information provision for decision support and in support of BPR initiatives. Like BPR it has substantially failed to deliver on its promised benefits. The third generation requires the clear separation of context, narrative and content management and challenges the orthodoxy of scientific management. Complex adaptive systems theory is used to create a sense‐making model that utilises self‐organising capabilities of the informal communities and identifies a natural flow model of knowledge creation, disruption and utilisation. However, the argument from nature of many complexity thinkers is rejected given the human capability to create order and predictability through collective and individual acts of freewill. Knowledge is seen paradoxically, as both a thing and a flow requiring diverse management approaches.
Molecular-assembled Complexes of Mixed-valent Ruthenium Dimer with Hexacyanoferrate(III) and Hexacyanocobaltate(III) Ions
Authors: Yoshioka Daisuke , Mikuriya Masahiro , Handa Makoto
Published: October 2002

The three-dimensional coordination polymers, [{Ru2(piv)4}3(H2O)M(CN)6] [M=Fe (1) and Co (2), Hpiv = pivalic acid], have been synthesized and characterized by X-ray crystallography, electronic spectroscopy and magnetic susceptibility measurement.
Novel π-Electron Donors for Magnetic Conductors Containing a PROXYL Radical
Authors: Fujiwara Hideki , Fujiwara Emiko , Kobayashi Hayao
Published: October 2002

Synthesis, structure and physical properties of novel π-electron donors containing a TTF moiety and a PROXYL radical within a single molecule designed for the development of magnetic conductors are reported. We also clarified the physical properties of the iodine complex of the ethylenedithio derivative.
Acute myeloid leukemia with inv(16)(p13q22): Involvement of cervical lymph nodes and tonsils is common and may be a negative prognostic sign
Authors: Billström R. , Ahlgren T. , Békássy A.N. , Malm C. , Olofsson T. , Höglund M. , Mitelman F. , Johansson B.
Published: October 2002

Acute myeloid leukemia (AML) with inv(16)(p13q22) or the variant t(16;16)(p13;q22), is strongly associated with the FAB subtype M4Eo. A high incidence of CNS involvement was reported in the 1980s, but otherwise little is known about the pattern of extamedullary leukemia (EML) manifestations in this AML type. We have compiled clinical and cytogenetic data on 27 consecutive AML cases with inv(16)/t(16;16) from southern Sweden. In general, these AMLs displayed the clinical features that have previously been described as characteristic for this disease entity: low median age, hyperleukocytosis, M4Eo morphology, and a favorable prognosis. However, CNS leukemia was only seen in relapse in one patient diagnosed in 1980, whereas the most common EML manifestation in our series was lymphadenopathy (5/27, 19%), most often cervical with or without gross tonsillar enlargement. A review of previously published, clinically informative cases corroborates that lymphadenopathy, with preference for the cervical region, is the most common EML at diagnosis in inv(16)‐positive AML (58/175, 33%). CNS leukemia, on the other hand, has been reported in only 17% of the cases, mostly in the relapse setting, with a diminishing frequency over time, possibly due to protective effects of high‐dose cytarabine. Other reported EML sites include the scalp, ovaries, and the intestine. Cervicotonsillar EML was in our series associated with a shorter duration of first remission, (P < 0.05), and may hence prove to be an important clinical parameter when deciding treatment strategies in AML with inv(16)/t(16;16). Am. J. Hematol. 71:15–19, 2002. © 2002 Wiley‐Liss, Inc.
Spontaneous mutations in the prion protein gene causing transmissible spongiform encephalopathy
Authors: Dagvadorj Ayush , Petersen Robert B. , Lee Hee Suk , Cervenakova Larisa , Shatunov Alexey , Budka Herbert , Brown Paul , Gambetti Pierluigi , Goldfarb Lev G.
Published: October 2002

We analyzed the prion protein gene (PRNP) region in patients with transmissible spongiform encephalopathy associated with the PRNP D178N mutation. The results suggest that the D178N chromosomes had independent origins in each affected pedigree or apparently sporadic case. A de novo spontaneous PRNP mutation was observed. We provide evidence that hereditary and apparently sporadic transmissible spongiform encephalopathy cases associated with the D178N mutation result from multiple recurrent mutational events.
Fabrication and characterization of planar and channel polymer waveguides. III. Compositional distribution and solute loss in polymer thin films
Authors: Banach Michael J. , Clarson Stephen J. , Beaucage Gregory , Benkoski Jason , Mates Tom , Kramer Edward J. , Vaia Richard A.
Published: October 2002

For many microelectronic and optoelectronic applications, polymer thin films require the addition of small molecules. However, the thin‐film geometry and associated processing techniques will influence the final morphology and compositional distribution of the constituents. It is therefore important that these be examined directly rather than inferred from bulk measurements. As an example system, the concentration and distribution of Disperse Red 1 (DR1) molecules in poly(methyl methacrylate) thin films were examined. Ultraviolet visibility spectroscopy and dynamic secondary ion mass spectrometry indicate that the composition of the molecules decreased dramatically with thermal treatment of the film. The sublimation of the chromophore was observed to occur at temperatures well below the melting point of the small molecule and the glass transition of the pure polymer; this solute loss manifested itself in changes in the glass transition temperature of the film. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 2021–2024, 2002
Morphological influence of ascorbic acid deficiency on endochondral ossification in osteogenic disorder Shionogi rat
Authors: Sakamoto Yujiro , Takano Yoshiro
Published: October 2002

The influences of chronic deficiency of L‐ascorbic acid (AsA) on the differentiation of osteo‐chondrogenic cells and the process of endochondral ossification were examined in the mandibular condyle and the tibial epiphysis and metaphysis by using Osteogenic Disorder Shionogi (ODS) rats that bear an inborn deficiency of L‐gulonolactone oxidase. Weanling male rats were kept on an AsA‐free diet for up to 4 weeks, until the symptoms of scurvy became evident. The tibiae and condylar processes of scorbutic rats displayed undersized and distorted profiles with thin cortical and scanty cancellous bones. In these scorbutic bones, the osteoblasts showed characteristic expanded round profiles of rough endoplasmic reticulum, and lay on the bone surface where the osteoid layer was missing. Trabeculae formation was deadlocked, although calcification of the cartilage matrix proceeded in both types of bone. Scorbutic condylar cartilage showed severe disorganization of cell zones, such as unusual thickening of the calcification zone, whereas the tibial cartilage showed no particular alterations (except for a moderately decreased population of chondrocytes). In condylar cartilage, hypertrophic chondrocytes were encased in a thickened calcification zone, and groups of nonhypertrophic chondrocytes occasionally formed cell nests surrounded by a metachromatic matrix in the hypertrophic cell zone. These results indicate that during endochondral ossification, chronic AsA deficiency depresses osteoblast function and disturbs the differentiation pathway of chondrocytes. The influence of scurvy on mandibular condyle cartilage is different from that on articular and epiphyseal cartilage of the tibia, suggesting that AsA plays different roles in endochondral ossification in the mandibular condyle and long bones. Anat Rec 268:93–104, 2002. © 2002 Wiley‐Liss, Inc.
The power binomial distribution: a flexible (two‐parameter) finite probability distribution
Authors: Fisher N. I.
Published: October 2002

This note presents a two‐parameter generalization of the Binomial distribution that provides flexibility in simulating discrete finite distributions.

The two parameters may be interpreted directly as location and dispersion, making the power binomial family suitable for simulating the sorts of samples that arise in certain forms of customer satisfaction surveys. Copyright © 2002 John Wiley & Sons, Ltd.
Statistical design of double EWMA controller
Authors: Tseng Sheng‐Tsaing , Chou Rouh‐Jane , Lee Shui‐Pin
Published: October 2002

The double exponentially weighted moving average (dEWMA) feedback controller is a popular run‐by‐run (RbR) control scheme for adjusting certain semi‐conductor manufacturing process with a linear drift. Del Castillo (IIE Trans. 1999; 31:1157) introduced an interesting state–space representation of the process output of this control scheme, and then the long‐term stability conditions of this closed‐loop system can be derived. The results; however, are very restricted to the case when the process disturbance follows a white noise series or an IMA(1, q) series. For a general process disturbance such as an ARIMA(p, d, q) model, it is not easy to obtain a state–space representation of the process output of this controller. Hence, some statistical properties (such as stability conditions and process yield) of this controller cannot be addressed by using the state–space theory. To overcome this difficulty, this paper first proposed an analytical expression for the process output of this dEWMA controller. Then the stability conditions and the optimal discount factors of this control scheme (based on the criterion of minimizing the average process fallout rate) can be obtained successfully. Finally, we also address some concluding remarks at the end of this paper. Copyright © 2002 John Wiley & Sons, Ltd.
Surface plasmon resonance spectroscopy: An emerging tool for the study of peptide–membrane interactions
Authors: Mozsolits Henriette , Aguilar Marie‐Isabel
Published: October 2002

The interactions between peptides and membranes mediate a wide variety of biological processes, and characterization of the molecular details of these interactions is central to our understanding of cellular events such as protein trafficking, cellular signaling and ion‐channel formation. A wide variety of biophysical techniques have been combined with the use of model membrane systems to study peptide–membrane interactions, and have provided important information on the relationship between membrane‐active peptide structure and their biological function. However, what has generally not been reported is a detailed analysis of the affinity of peptide for different membrane systems, which has largely been due to the difficulty in obtaining this information. To address this issue, surface plasmon resonance (SPR) spectroscopy has recently been applied to the study of biomembrane‐based systems using both planar mono‐ or bilayers or liposomes. This article provides an overview of these recent applications that demonstrate the potential of SPR to enhance our molecular understanding of membrane‐mediated peptide function. © 2002 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 66: 3–18, 2002
Metabolic characterization of childhood brain tumors
Authors: Utriainen Meri , Metsähonkala Liisa , Salmi Toivo T. , Utriainen Tapio , Kalimo Hannu , Pihko Helena , Mäkipernaa Anne , Harila‐Saari Arja , Jyrkkiö Sirkku , Laine Jukka , Någren Kjell , Minn Heikki
Published: October 2002

BACKGROUND

Positron emission tomography (PET) scans of primary brain tumors were performed in pediatric patients to examine whether metabolic characteristics could be used as an index of clinical aggressiveness.

METHODS

Twenty‐seven pediatric patients with untreated primary central nervous system neoplasms were studied with PET scans using 2‐[18F] fluoro‐2‐deoxy‐D‐glucose (FDG) and/or L‐[methyl‐11C] methionine (MET). Metabolic characteristics as assessed with FDG and MET standardized uptake values (SUV) and SUV‐to‐normal brain ratios were compared with histopathology and selected histochemical features such as proliferation activity (Ki‐67MIB‐1) and apoptotic, vascular, and cell density indices. The median followup time was 43 months.

RESULTS

The accumulation of both FDG and MET was significantly higher in high‐grade than in low‐grade tumors, but a considerable overlap was found. The accumulation of both tracers was associated positively with age. High‐grade tumors showed higher proliferative activity and vascularity than the low‐grade tumors. In univariate analysis, FDG‐PET, MET‐PET, and apoptotic index were independent predictors of event‐free survival.

CONCLUSION

We found that both FDG and MET uptake in pediatric brain tumors are associated with malignancy grade. However, no clear limits of SUVs and SUV‐to‐normal brain ratios can be set between low‐grade and high‐grade tumors, which makes the assessment of malignancy grade using metabolic imaging with PET scan difficult in individual cases. Although FDG‐PET and MET‐PET do not compensate for histopathologic evaluation, they may give valuable additional information especially if invasive procedures to obtain histopathologic samples are not feasible. Cancer 2002;95:1376–86. © 2002 American Cancer Society.

DOI 10.1002/cncr.10798
Vitamin B12, folate, and Alzheimer's disease
Authors: Wang H.‐X.
Published: October 2002

Vitamin B12 and folate have been suspected to be involved in the etiopathogenesis of dementia and Alzheimer's disease (AD) for years, as a deficiency of either vitamin may produce severe neurological consequences, including confusion and memory loss. This review briefly summarizes the major studies published in the literature concerning vitamin B12, folate, and AD. Using a number of study designs and exposure assessments, findings from studies conducted from different countries suggest that vitamin B12 deficiency/low level is more often found in AD patients than nondemented persons. The results of folate in relation to AD have been inconsistent. Generally, population‐based studies indicate that folate deficiency/low level is not only related to AD but also all types of dementia. Results from studies on the combination of the two vitamins suggest that vitamin B12 and folate may be equally important in the etiology of AD. The null findings from some of the studies may have resulted from the differences in study design, population, control selections, as well as methods of exposure assessment and cut‐offs chosen. It may be premature to reach any conclusions at the moment based on the limited studies available, especially the lack of prospective studies and randomized clinical trials. Studies conducted up to the present suggest that deficiency / low level of vitamin B12 and folate may be of etiological importance for AD. Drug Dev. Res. 56:111–122, 2002. © 2002 Wiley‐Liss, Inc.
β‐Amyloid immunization approaches for Alzheimer's disease
Authors: Imbimbo Bruno P.
Published: October 2002

Alzheimer's disease (AD) represents the third leading cause of death in the U.S. and the leading cause of dementia in the elderly population. Until recently, there was little hope of efficiently combating this devastating disease. The deposition of β‐amyloid (Aβ) is the major pathological hallmark of AD brains. Genetic, biochemical, and pharmacological evidence support the hypothesis that Aβ plays a key role in the development of the disease. Thus, in the last 5 years a number of pharmacological strategies have been developed to interfere with the Aβ cascade. The most revolutionary of these approaches was proposed in 1999 by scientists at Elan Pharmaceuticals, which immunized against Aβ transgenic mice with spontaneously developing Aβ pathology. The immunization was achieved by subcutaneous injections of a preaggregated form of the synthetic human 42‐amino acid Aβ emulsified with Freund's adjuvant, an immune stimulant. The vaccination caused a near complete inhibition of Aβ plaque formation in younger animals and a marked reduction of the Aβ burden in older animals. The effects on Aβ plaques were accompanied by a reduction of Aβ‐associated astrogliosis and neuritic dystrophy. These results were later confirmed by other groups with similar vaccination protocols, which also demonstrated that the Aβ immunization of transgenic animals normalize or reduce the cognitive impairment associated with Aβ pathology. Interestingly, effective removal of brain Aβ plaques was also obtained by peripherally administering Aβ antibodies. The mechanism with which the vaccine increases Aβ clearance is not fully understood. Centrally, the vaccine appears to activate Aβ phagocytosis by microglial monocytes. Peripherally, serum Aβ antibodies bind and sequester Aβ, thus altering its equilibrium between CNS and plasma. The dramatic results obtained in animal models of AD raised unprecedented hopes for both a preventive and a curative intervention for this devastating disorder. A vaccine preparation for human use (AN‐1792) composed of preaggregated human Aβ42 peptide and a highly purified saponin derivative (QS‐21) was developed by Elan Pharmaceuticals and Wyeth Ayerst and tested in AD patients. Unfortunately, a Phase IIa study aimed at evaluating the safety and immunological activity of AN‐1792 in 360 AD patients was discontinued because 15 subjects receiving the vaccine developed serious signs of CNS inflammation. Both central activation of cytotoxic T cells and autoimmune reactions were proposed as potential mechanisms of toxicity. Other therapeutic Aβ vaccination strategies are being pursued, including immuno‐conjugates and monoclonal antibodies. The future of these and other Aβ immunization approaches depend on a clear understanding of the mechanism of Aβ clearance and additional insight into the role of inflammation in the AD brain. Drug Dev. Res. 56:150–162, 2002. © 2002 Wiley‐Liss, Inc.
Secretases as targets for beta‐amyloid lowering drugs
Authors: Walter Jochen , Haass Christian
Published: October 2002

Alzheimer's disease is characterized by the accumulation of neuritic plaques in the brain parenchyma. These plaques contain fibrillar forms of the amyloid β‐peptide (Aβ), which derives from the β‐amyloid precursor protein (βAPP) by proteolytic processing. It is now commonly believed that Aβ plays a crucial role in the pathogenesis of AD, and inhibition of its production is therefore a rational strategy to treat or prevent the disease. Substantial progress has been made in deciphering the molecular mechanisms underlying Alzheimer's disease (AD). In particular, with β‐secretase and the presenilins, two essential factors in the proteolytic generation of Aβ have been identified. Inhibitors of these proteins have already been developed and might serve as lead compounds for Aβ‐lowering drugs of clinical use. Drug Dev. Res. 56, 201–210 2002. © 2002 Wiley‐Liss, Inc.
The impact of recent climate change on flooding and sediment supply within a Mediterranean mountain catchment, southwestern Crete, Greece
Authors: Maas Glenn. S. , Macklin Mark. G.
Published: October 2002

This paper presents work from a geomorphological investigation carried out in the Aradena Gorge, southwestern Crete, Greece. The gorge is typical of many steepland fluvial systems in the Mediterranean, with steep relief, coarse‐gravel sediments and high rates of sedimentation generated during intense winter storm events. Hillslope deposits and coarse‐gravel flood units within a 5 km section of the gorge have been mapped, dated (using lichenometry and dendrochronology), and their sedimentological characteristics recorded to establish a c. 200‐year record of flood frequency/magnitude and hillslope/channel sediment supply variability. This record has been compared with instrumented and previously published records of climate change from Crete and the Mediterranean region and used to establish the major controls on flooding and sediment dynamics within the Aradena Gorge.

Rates of colluviation and sediment delivery to the channel appear to have been greater than the present sometime before c. AD 1800 and may be related to cooler climates with a more seasonal precipitation regime during the Little Ice Age (c. AD 1450 to 1850). In gorge sections where the present rate of sediment supply from hillslope colluvium is very low, the channel has incised into older alluvial and colluvial deposits. Conversely, in the few sections where sediment supply is currently very high, the channel is aggrading with a braided pattern. Major rock‐fall deposits at certain locations in the gorge have restricted any major downstream sediment transfer.

Twelve periods of increased flooding during the last 150 years have been identified and these correlate quite well with negative or declining phases of the North Atlantic Oscillation (NAO). Analysis of daily precipitation data from Crete suggests negative phases of the winter NAO are characterized by an increase in the number of long‐duration, high‐intensity storms. These storms, particularly those with five‐day and greater duration, appear to be significant in triggering major floods in the Aradena Gorge. During the last 40 years the NAO index has been increasing and become locked into a positive phase. As a consequence of this, major flooding appears to have declined during the same period. Copyright © 2002 John Wiley & Sons, Ltd.
Genetic alterations in cervical carcinomas: Frequent low‐level amplifications of oncogenes are associated with human papillomavirus infection
Authors: Zhang Anju , Månér Susanne , Betz Regina , Ångström Tord , Stendahl Ulf , Bergman Frank , Zetterberg Anders , Wallin Keng‐Ling
Published: October 2002

The development of cervical carcinoma is closely associated with HPV infection. However, other genetic alterations also play an important role. In this study, we analyzed copy number alterations of several oncogene loci in a panel of 84 cervical tumors. Sixty‐five (77%) tumors were HPV DNA‐positive, and most were infected with type 16 or type 18 or both. The oncogenes studied include PIK3CA at 3q26.3, TERT at 5p15.33, C‐MYC at 8q24, CCND1 at 11q13.3, ERBB2 at 17q21.2 and locus region 20q13.2. Amplification of 1 or more genes was detected in 55 (65%) cases using interphase FISH. PIK3CA was amplified in 43% of tumors, followed by TERT (33%), 20q13.2 (30%), ERBB2 (29%), C‐MYC (25%) and CCND1 (12%). Most tumors showed low‐level amplification with 3–7 copies of these genes, and complex changes involving 3 or more genes occur more frequently in tumors at advanced stages. Increased protein expression of c‐erbB2 and c‐myc was observed in tumors with the corresponding gene amplification. Oncogene alterations were found more often in HPV‐infected cases, particularly for C‐MYC and TERT. These findings indicate that HPV‐associated cervical carcinomas bear frequent alterations of these genes, which may have critical biologic impact on the development and progression of carcinoma of the uterine cervix. © 2002 Wiley‐Liss, Inc.
CHIMERA: A software tool for reaction rate calculations and kinetics and thermodynamics analysis
Authors: Novoselov Konstantin P. , Shirabaikin Denis B. , Umanskii Stanislav Ya. , Vladimirov Alexander S. , Minushev Airat Kh. , Korkin Anatoli A.
Published: October 2002

This article presents and overviews the CHIMERA program package, which provides a user‐friendly graphical interface between quantum chemistry and chemical kinetics programs. CHIMERA facilitates calculations of rate constants for gas‐phase reactions using transition state and Rice–Ramsperger–Kassel–Marcus theories. The program includes computational modules for simulation of gas‐phase kinetics using simplified reactor models and for computation of chemical equilibria. The review includes a description of the theory implemented in the code, the program description, the general strategy of calculations using CHIMERA, and illustrative examples of the program application. © 2002 Wiley Periodicals, Inc. J Comput Chem 14: 1375–1389, 2002
Molecular epidemiology of human calicivirus gastroenteritis outbreaks in Hungary, 1998 to 2000
Authors: Reuter Gábor , Farkas Tibor , Berke Tamás , Jiang Xi , Matson David O. , Szücs György
Published: October 2002

Between November 1998 and November 2000, 196 stool specimens from 21 outbreaks of acute nonbacterial gastroenteritis occurring in 11 of the 19 counties of Hungary were collected and tested for human caliciviruses. Human caliciviruses were detected and characterized by a type‐common enzyme‐linked immunosorbent assay (EIA) and reverse transcription‐polymerase chain reaction (RT‐PCR) followed by cloning and sequencing. Twenty (95%) and 14 (67%) outbreaks were positive by EIA and RT‐PCR, respectively, and 12 RT‐PCR‐positive outbreaks were also confirmed by sequencing. Comparative sequence analysis revealed 13 Norwalk‐like virus sequences in the 12 outbreaks, including 11 Norwalk‐like virus genogroup II (seven in Hawaii‐like, two Lordsdale‐like, one Melksham‐like, and one Hillingdon‐like) and two Norwalk‐like virus genogroup I (related to Southampton‐like and Desert Shield‐like clusters) viruses. Multiple Norwalk‐like virus clusters, with a predominance of Hawaii‐like viruses, played an important role in nonbacterial gastroenteritis outbreaks during the study period. This is the first country‐wide molecular epidemiological investigation of human calicivirus‐associated, gastroenteritis outbreaks in Hungary and Central‐Eastern Europe. J. Med. Virol. 68:390–398, 2002. © 2002 Wiley‐Liss, Inc.
Relative importance of stakeholders: analysing speech acts in a layoff
Authors: Guild Wendy L.
Published: October 2002

Grounded in a participant observation study of a ski resort, this paper explores the (re)production of legitimate discourses through speech acts pertaining to an organizational event, a layoff. Manager's justifications and employees' reactions and critiques put sanctioned discourses into play. And while the stated organizational values include shareholder, customer, and employee concerns, the relative importance of these stakeholders is only made clear through the conversation of the speech acts and their reception. The shape of the conversation, in locution, illocution and perlocution, shifts the relations between managers and the employees and creates longer term consequences for the organization. This focus on language use serves as a micro‐foundation for the study of legitimation processes and its consequences within organizations. Copyright © 2002 John Wiley & Sons, Ltd.
Measurement of adhesive forces between S. epidermidis and fibronectin‐coated surfaces using optical tweezers
Authors: Simpson Kathryn Hicks , Bowden M. Gabriela , Höök Magnus , Anvari Bahman
Published: October 2002

Background and Objectives

Biomaterial‐mediated infection, a common cause of medical device failure, is initiated by bacterial adhesion to an adsorbed protein layer on the implant surface. This adhesion is thought to be mediated by specific molecules present on the bacterial cell surface. Optical tweezers can be used to measure the adhesive force between a single bacterium and a protein‐coated surface.

Study Design/Materials and Methods

Using optical tweezers, a bacterium was trapped and brought in contact with a 10‐μm diameter polystyrene microsphere coated with fibronectin. The minimum force required to detach the cell from the bead was determined over a range of fibronectin concentrations and contact times.

Results

The detachment forces were integer multiples of an 18‐pN base value that was independent of contact time and coating concentration; we propose that the variation in force is related to the number of bonds formed.

Conclusions

These experiments demonstrate that optical tweezers can be used to investigate the adhesion of individual bacteria to surfaces. The results suggest that S. epidermidis has surface proteins capable of binding fibronectin. Lasers Surg. Med. 31:45–52, 2002. © 2002 Wiley‐Liss, Inc.
Effect of Er:YAG laser on bond strength to dentin of a self‐etching primer and two single‐bottle adhesive systems
Authors: Ramos Renata P. , Chimello Daniela T. , Chinelatti Michelle A. , Nonaka Tomio , Pécora Jesus D. , Palma Dibb Regina G.
Published: October 2002

Background and Objectives

To assess the effect of erbium:yttrium aluminium garnet (Er:YAG) laser on bond strength to dentin of a self‐etching primer (Clearfil Liner Bond 2V, CL2V) and two single‐bottle agents (Excite, EX; Gluma One Bond, GB).

Study Design/Materials and Methods

Thirty human molars were selected, roots were removed and crowns were bisected, providing 60 halves. Specimens were included and ground to expose dentin. Bonding site was limited and samples were assigned to three groups: I, CL2V; II, EX; III, GB. Dentin was either conventionally treated or submitted to laser conditioning + conventional treatment. The adhesive protocol was performed, samples were stored for 24 hours and bond strength was tested to failure (0.5 mm/min).

Results

Statistical analysis showed a decrease in bond strength for lased subgroups and this drop was more evident for EX. CL2V provided the best overall results, regardless of the surface treatment.

Conclusions

Er:YAG laser may adversely affect bond strength in higher or lesser degree, depending on the adhesive system used. Lasers Surg. Med. 31:164–170, 2002. © 2002 Wiley‐Liss, Inc.
Protein serine and threonine phosphorylation, hyperactivation and acrosome reaction in in vitro capacitated hamster spermatozoa
Authors: Jha Kula Nand , Shivaji S.
Published: October 2002

Monoclonal antibodies against phosphoserine and phosphothreonine were used in the present study to investigate the changes in serine and threonine phosphorylation respectectively during capacitation of hamster spermatozoa. Immunoblot analysis of hamster spermatozoa capacitated in TALP, a medium that supports capacitation, showed that a set of four proteins of molecular weight 56, 63, 66, and 100 kDa was phosphorylated both at the serine and threonine residues. In addtion, five other proteins of molecular weight 32, 39, 45, 53, and 61 kDa were phosphorylated specifically at the threonine residues. Of these nine proteins, the 100 kDa protein showed a time dependent or capacitation‐dependent decrease in intensity which coincided with the percentage acrosome‐reacted spermatozoa. In contrast, the 49 and 63 kDa threonine phosphorylated proteins showed increased phosphorylation coinciding with capacitation. H8 (a serine and threonine kinase inhibitor) had a transient effect on the phosphorylation of these two phosphothreonine proteins but inhibited acrosome reaction substantially all through the treatment period. Okadaic acid (OA) (a serine and threonine protein phosphatase inhibitor) inhibited hyperactivation but had no effect on acrosome reaction. In fact, OA stimulated acrosome reaction. Finally the immunofluorescence studies indicated localization of the serine phosphorylated proteins in tail as well as in head of the capacitated hamster spermatozoa whereas the threonine phosphorylated proteins were localized mostly in the tail of the spermatozoa. The findings of the present study suggest that serine/threonine phosphorylation and the enzymes responsible for regulating the level of phosphorylation play an important role in capacitation and capacitation‐associated events namely hyperactivation and acrosome reaction. However, further studies are needed in order to establish the exact role of these proteins in capacitation of spermatozoa. Mol. Reprod. Dev. 63: 119–130, 2002. © 2002 Wiley‐Liss, Inc.
Inheritance of resistance of bovine preimplantation embryos to heat shock: Relative importance of the maternal versus paternal contribution
Authors: Block J. , Chase C.C. , Hansen P.J.
Published: October 2002

Brahman preimplantation embryos are less affected by exposure to heat shock than Holstein embryos. Two experiments were conducted to test whether the ability of Brahman embryos to resist the deleterious effects of heat shock was a result of the genetic and cellular contributions from the oocyte, spermatozoa, or a combination of both. In the first experiment, Brahman and Holstein oocytes were collected from slaughterhouse ovaries and fertilized with spermatozoa from an Angus bull. A different bull was used for each replicate to eliminate bull effects. On day 4 after fertilization, embryos ≥ 9 cells were collected and randomly assigned to control (38.5°C) or heat shock (41°C for 6 hr) treatments. The proportion of embryos developing to the blastocyst (BL) and advanced blastocyst (ABL; expanded and hatched) stages was recorded on day 8. Heat shock reduced the number of embryos produced from Holstein oocytes that developed to BL (P < 0.001, 55.6 ± 4.2% vs. 29.8 ± 4.2%) and ABL (P < 0.01, 37.7 ± 3.6% vs. 12.2 ± 3.6%) on day 8 as compared to controls. In contrast, heat shock did not reduce development of embryos produced from Brahman oocytes (BL = 42.1 ± 4.8% vs. 55.6 ± 4.8% for 38.5 and 41°C, respectively; ABL = 17.6 ± 4.2% vs. 32.4 ± 4.2%). In the second experiment, oocytes from Holstein cows were fertilized with semen from bulls of either Brahman or Angus breeds. Heat shock of embryos ≥ 9 cells reduced development to BL (P < 0.002) and ABL (P < 0.005) for embryos sired by both Brahman (BL = 54.3 ± 7.7% vs. 23.4 ± 7.7%; ABL = 43. ± 7.4% vs. 7.9 ± 7.4%, for 38.5 and 41°C, respectively) and Angus bulls (BL = 57.9 ±  7.7% vs. 31.0 ± 7.7%; ABL = 33.6 ± 7.4% vs. 18.4 ± 7.4%, for 38.5 and 41°C, respectively). There were no breed × temperature interactions. Results suggest that the oocyte plays a more significant role in the resistance of Brahman embryos to the deleterious effects of heat shock than the spermatozoa. Mol. Reprod. Dev. 63: 32–37, 2002. © 2002 Wiley‐Liss, Inc.
HPLC analysis of fusaric acid, 9,10‐dehydrofusaric acid and their methyl esters, toxic metabolites from weed pathogenic Fusarium species
Authors: Amalfitano Carmine , Pengue Raffaele , Andolfi Anna , Vurro Maurizio , Zonno Maria C. , Evidente Antonio
Published: October 2002

A simple and rapid HPLC method, using a high‐density C18 column, has been developed for the quantitative analysis of fusaric and dehydrofusaric acids and their methyl esters in the methanol extract of lyophilised culture filtrates of species of Fusarium. The method has been used to determine the content of these metabolites in two strains of Fusarium oxysporum and in strains of F. nygamai and F. udum. Fusaric acid has been isolated and identified from a strain of F. udum for the first time. Copyright © 2002 John Wiley & Sons, Ltd.
Initiation mechanisms of an anionic ring‐opening polymerization of lactam‐12
Authors: Luisier A. , Bourban P.‐E. , Månson J.‐A. E.
Published: October 2002

A novel liquid system has been developed to initiate the anionic polymerization of lactam‐12. This system, containing both an activator and a catalyst, has the primary advantage over previous systems of permitting infinite storage of the reactant, and it avoids premixing of batches. The anionic species of the system were identified with matrix‐assisted laser desorption/ionization time‐of‐flight measurements, and Fourier transform infrared was used to measure the change in their concentrations during the polymerization. A guanidine anion was formed, and the system initiated the polymerization by this guanidine and by the catalyst. The kinetics of the anionic polymerization of lactam‐12 into polyamide‐12 were followed with differential scanning calorimetry measurements. The determined reaction rates indicated that this liquid system was particularly well suited for initiating in situ polymerization during liquid molding. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 3406–3415, 2002
Non‐native interactions, effective contact order, and protein folding: A mutational investigation with the energetically frustrated hydrophobic model
Authors: Treptow Werner L. , Barbosa Marco Aurélio A. , Garcia Leandro G. , Pereira de Araújo Antônio F.
Published: October 2002

By Monte Carlo simulations, we explored the effect of single mutations on the thermodynamics and kinetics of the folding of a two‐dimensional, energetically frustrated, hydrophobic protein model. Φ‐Value analysis, corroborated by simulations beginning from given sets of judiciously chosen initial contacts, suggests that the transition state of the model consists of a limited region of the native structure, that is, a folding nucleus. It seems that the most important contacts in the transition state (large and positive Φ) are not the ones with the highest contact order, because in this case the entropic cost of their formation would be too high, but exactly the ones that decrease the entropic cost of difficult contacts, reducing their effective contact order. Mutations of internal monomers involved in high‐order contacts were actually the ones resulting in the fastest kinetics (and Φ < 0), indicating they tend to make low order, non‐native contacts of low entropic cost that stabilize the unfolded state with respect to the transition state. Folding acceleration by other non‐native interactions was also observed and a simple general mechanism is proposed according to which non‐native contacts can act indirectly over the folding nucleus, “chelating” out potentially harmful contacts. The polymer graph of our model, which facilitates the visualization of effective contact orders, successfully suggests the relative kinetic importance of different contacts and is reasonably consistent with analogous graphs for the well characterized family of SH3 domains. Proteins 2002;49:167–180. © 2002 Wiley‐Liss, Inc.