bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotypic analysis of mice deficient in the major myelin protein MOBP, and evidence for a novel Mobp isoform
Authors: Yool D. , Montague P. , McLaughlin M. , McCulloch M.C. , Edgar J.M. , Nave K.‐A. , Davies R.W. , Griffiths I.R. , McCallion A.S.
Published: September 2002

Myelin‐associated oligodendrocytic basic protein (MOBP) is a recently identified major component of central nervous system (CNS) myelin. We previously reported a detailed characterization of the genomic region encompassing the Mobp gene, elucidating the complex series of transcript splicing responsible for the generation of its diverse family of protein isoforms. These basic, positively charged polypeptides display spatial and temporal expression patterns consistent with a potential role in the compaction and maintenance of the myelin sheath. MOBP isoforms have also been localized to the nucleus and the microtubular network of oligodendrocytes; transcript corresponding to one isoform is present during embryonic development. Recent reports have identified a role for this protein family in the pathogenesis of multiple sclerosis, but a clear function for the wild‐type protein has remained unclear. We report a detailed analysis of a targeted mutation of Mobp, which results in the deletion of the translational start site and most of the coding sequence of MOBP, and the deletion of the entire coding sequence corresponding to a novel, putative MOBP isoform. Our analyses clearly demonstrate that MOBP‐deficient mice develop normally, generate intact compact CNS myelin, and demonstrate no obvious clinical phenotype. Furthermore, in contrast with another recent study, we find that Mobp null mice demonstrate no significant influence on the axonal diameter of myelinated axons. Although MOBP is not essential for myelination, it appears that its absence is not simply compensated for by increased expression of the “classic” myelin basic protein (MBP). GLIA 39:256–267, 2002. © 2002 Wiley‐Liss, Inc.
Inflammatory mediators increase the expression of nociceptin/orphanin FQ in rat astrocytes in culture
Authors: Buzas Beata , Rosenberger J. , Kim Kee‐Won , Cox Brian M.
Published: September 2002

In the central nervous system, glial cells play an important role in inflammatory and immune responses, and opioid peptides have been identified as essential mediators between the nervous and the immune systems. We report the profound upregulation of the opioid‐related nociceptin/orphanin FQ (N/OFQ) by inflammatory mediators in astrocytes. The bacterial endotoxin, lipopolysaccharide (LPS), and the proinflammatory cytokines, interleukin‐β (IL‐1β) and tumor necrosis factor‐α (TNF‐α), induced levels of N/OFQ mRNA and immunoreactivity. HPLC analysis of the immunoreactivity in astrocyte extracts revealed that a large molecular weight precursor for N/OFQ is being synthesized and released in response to LPS and astrocytes appear to lack the enzymes required to process the precursor protein. Western blot analysis showed that LPS treatment elicited the activation of ERK 1/2 and p38 MAP kinases. Blockade of the p38 or the ERK MAP kinase pathways prevented the LPS‐induced increase in N/OFQ mRNA levels indicating a role for these cascades in the regulation of N/OFQ genes in response to LPS. Regulation of N/OFQ gene expression by ERK and p38 activation may be mediated through the transcription factor CREB. We observed CREB phosphorylation in response to LPS, which was also prevented by SB202190 and PD98059. The NFκB pathway also appears to be involved in the induction of N/OFQ transcription by LPS, since NFκB inhibitors antagonized the effect of LPS on N/OFQ expression. Regulation of N/OFQ by inflammatory mediators in astrocytes may suggest a role for N/OFQ in neural–glial communication and in inflammatory responses in certain neuropathophysiological conditions. GLIA 39:237–246, 2002. Published 2002 Wiley‐Liss, Inc.
Matrix metalloproteinases in neuroinflammation
Authors: Rosenberg Gary A.
Published: September 2002

Matrix metalloproteinases (MMPs) are a gene family of neutral proteases that are important in normal development, wound healing, and a wide variety of pathological processes, including the spread of metastatic cancer cells, arthritic destruction of joints, atherosclerosis, and neuroinflammation. In the central nervous system (CNS), MMPs have been shown to degrade components of the basal lamina, leading to disruption of the blood‐brain barrier (BBB), and to contribute to the neuroinflammatory response in many neurological diseases. Brain cells express both constitutive and inducible MMPs in response to cellular stress. MMPs are tightly regulated to avoid unwanted proteolysis. Secreted as inactive enzymes, the MMPs require activation by other proteases and free radicals. The MMPs are part of a larger class of metalloproteinases (MPs), which includes the recently discovered ADAMs (a disintegrin and metalloproteinase domain) and ADAMTS (a disintegrin and metalloproteinase thrombospondin) families. MPs have complex roles at the cell surface and within the extracellular matrix. At the cell surface, they act as sheddases, releasing growth factors, death receptors, and death‐inducing ligands, making them important in cell survival and death. Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors that regulate the activity of the MMPs. Synthetic inhibitors have been developed for the treatment of arthritis and cancer. These hydroxymate‐based compounds have been shown to reduce injury in experimental allergic encephalomyelitis (EAE), experimental allergic neuritis (EAN), cerebral ischemia, intracerebral hemorrhage, and viral and bacterial infections. MPs have both beneficial and detrimental roles; understanding their expression in various CNS insults will allow for the use of MMP inhibitors in the treatment of neurological disorders. GLIA 39:279–291, 2002. © 2002 Wiley‐Liss, Inc.
Multiple angiotensin receptor subtypes in normal and tumor astrocytes in vitro
Authors: Fogarty David J. , Sánchez‐Gómez M. Victoria , Matute Carlos
Published: September 2002

A role for neuropeptide receptors in glial tumorigenesis has recently been proposed. Although angiotensin receptors are known to mediate proliferative effects in many cell types, including brain astrocytes, the possible participation of these receptors in glial tumorigenesis remains unknown. In the present study, we have examined the expression of the molecularly defined angiotensin receptor subtypes AT1a, AT1b, and AT2 in normal perinatal rat astrocytes and in a panel of tumor adult astrocytoma cells, using the reverse transcriptase‐polymerase chain reaction (RT‐PCR). Subsequently, we compared the mitogenic effect of the angiotensins A(1–8), A(2–8), A(3–8) and the heptapeptide “metabolite” A(1–7), on both normal and tumor astrocytes, measured in terms of the incorporation of tritiated thymidine. Our results indicate that AT1a, AT1b, and AT2 angiotensin receptor mRNA is commonly expressed by many of these cells. Of notable exception is the astrocytoma U373 which was not found to express AT1 or AT2 mRNA. Chronic (24‐h) incubation of cells with A(1–8) and A(1–7) lead to the induction of mitogenesis, even in the AT1 and AT2 mRNA negative astrocytoma cell line U373. Moreover, pharmacological analysis indicated that the observed mitogenic effects are not mediated by the AT1 or AT2 type receptors, but rather by a novel, specific A(1–7) angiotensin receptor, since mitogenesis was shown to be partially blocked by the A(1–7) analogue D‐Ala7A(1–7) and by the protease inhibitor orthophenanthroline (100 μM). Using Fura‐2 spectrophotometry, we found that activation of this receptor does not alter intracellular calcium levels; however, preincubation with the protein kinase kinase inhibitor U0126 (10 μM) was found to inhibit these mitogenic effects partially. Overall, these results which demonstrate that normal and tumor astrocytes express a greater variety of angiotensin receptor subtypes than previously thought, support the idea that A(1–7) and its receptor signaling system may play an important role in shaping the astrocyte population during development. Moreover, the untimely expression of this A(1–7) receptor may represent an important etiological component in the development of brain astrocytomas. GLIA 39:304–313, 2002. © 2002 Wiley‐Liss, Inc.
Modulation of activity in temporal cortex during generation of inner speech
Authors: Shergill Sukhwinder S. , Brammer Michael J. , Fukuda Rimmei , Bullmore Ed , Amaro Edson , Murray Robin M. , McGuire Philip K.
Published: September 2002

Monitoring one's thoughts (in the verbal modality) is thought to be critically dependent on the interaction between areas that generate and perceive inner speech in the frontal and temporal cortex, respectively. We used functional magnetic resonance imaging (fMRI) to examine the relationship between activity in these areas while the rate of inner speech generation was varied experimentally. The faster rate was associated with activation in the left inferior frontal gyrus, the right pre‐ and postcentral gyri and both superior temporal gyri. Thus, temporal cortical activation was associated with increasing the rate of covert articulation, in the absence of external auditory input, suggesting that there is effective fronto‐temporal connectivity. Furthermore, this may provide support for the existence of feed forward models, which suggest that activity in regions responsible for verbal perception is modulated by activity in areas that generate inner speech. Hum. Brain Mapping 16:219–227, 2002. © 2002 Wiley‐Liss, Inc.
Comparison of spatial normalization procedures and their impact on functional maps
Authors: Crivello Fabrice , Schormann Thorsten , Tzourio‐Mazoyer Nathalie , Roland Per E. , Zilles Karl , Mazoyer Bernard M.
Published: September 2002

The alignment accuracy and impact on functional maps of four spatial normalization procedures have been compared using a set of high resolution brain MRIs and functional PET volumes acquired in 20 subjects. Simple affine (AFF), fifth order polynomial warp (WRP), discrete cosine basis functions (SPM), and a movement model based on full multi grid (FMG) approaches were applied on the same dataset for warping individual volumes onto the Human Brain Atlas (HBA) template. Intersubject averaged structural volumes and tissue probability maps were compared across normalization methods and to the standard brain. Thanks to the large number of degrees of freedom of the technique, FMG was found to provide enhanced alignment accuracy as compared to the other three methods, both for the grey and white matter tissues; WRP and SPM exhibited very similar performances whereas AFF had the lowest registration accuracy. SPM, however, was found to perform better than the other methods for the intra‐cerebral cerebrospinal fluid (mainly in the ventricular compartments). Limited differences in terms of activation morphology and detection sensitivity were found between low resolution functional maps (FWHM ∼10 mm) spatially normalized with the four methods, which overlapped in 42.8% of the total activation volume. These findings suggest that the functional variability is much larger than the anatomical one and that precise alignment of anatomical features has low influence on the resulting intersubject functional maps. When increasing the spatial resolution to approximately 6 mm, however, differences in localization of activated areas appear as a consequence of the different spatial normalization procedure used, restricting the overlap of the normalized activated volumes to only 6.2%. Hum. Brain Mapping 16:228–250, 2002. © 2002 Wiley‐Liss, Inc.
Structural reliability of building blocks in coordination framework design
Authors: Barnett Sarah. A. , Champness Neil R.
Published: September 2002

The use of the building‐block methodology in designing coordination framework materials are discussed, with particular reference to the structural reliability of a given building block. The term structural reliability is defined for a given metal containing moiety as the degree to which that building block reproducibly adopts a given, predicted, coordination arrangement when reacted with a series of chemically related bridging ligands. This terminology is discussed with respect to a range of coordination frameworks constructed using Cd(NO3)2 as a building‐block, which is demonstrated to be structurally unreliable. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:574–577, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10092
Relativistic effects in properties of gold
Authors: Schwerdtfeger Peter
Published: September 2002

Gold often shows unusual and sometimes surprising chemical and physical properties compared to its lighter group 11 elements (gold anomaly). Pyykkö and coworkers demonstrated in the mid seventies that this is due to effects from special relativity. Recent work in this field indeed indicates that the chemistry and physics of gold is dominated by relativistic effects. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:578–584, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10093
Designer haem proteins: What can we learn from protein engineering?
Authors: Raven Emma Lloyd
Published: September 2002

Iron protoporphyrin(IX) is one of the most versatile and widespread pieces of catalytic machinery known in biology and is a key component of a multitude of proteins and enzymes. One of most challenging questions in this area has been to identify and understand the relationships that exist between different classes of haem proteins and to use protein engineering methods to rationalize the mechanisms by which the protein structure controls the specific chemical reactivity of the haem group. The application of this approach to the haem enzyme ascorbate peroxidase and the haem protein leghaemoglobin is discussed. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:501–505, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10094
Intermetallic lithium compounds with two‐ and three‐dimensional polyanions—synthesis, structure, and lithium mobility
Authors: Pöttgen Rainer , Wu Zhiyun , Hoffmann Rolf‐Dieter , Kotzyba Gunter , Trill Henning , Senker Jürgen , Johrendt Dirk , Mosel Bernd D. , Eckert H.
Published: September 2002

Intermetallic lithium compounds are potential candidates as anode materials for battery applications. We report on the synthesis, crystal structures, and chemical bonding of lithium–transition metal–stannides and indides. These structures are composed of two‐ or three‐dimensionally infinite polyanions formed by the transition metal and tin (indium) atoms. Besides the crystal chemistry we report on magnetic properties, 7Li solid state NMR, and 119Sn Mössbauer spectroscopy data in order to elucidate structure‐property relations for this family of intermetallics. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:506–513, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10095
From heterobimetallic transition metal complexes to linear coordination polymers based on cis‐ and trans‐L2Pt(CCPh)2
Authors: Lang Heinrich , Leschke Marion
Published: September 2002

The reaction of cis‐(2,2′‐bipyridine) Pt(CCPh)2 cis‐(4,4′‐dimethyl‐2,2′‐bipyridine) Pt‐(CCPh)2 and trans‐(Ph3P)2Pt(CCPh)2 towards different group 11 transition‐metal salts [M′X] (M′ = Cu, Ag; X = inorganic ligand) to give heterobimetallic or linear oligomeric and polymeric transition metal complexes is described. Different coordination modes for M′, PhCC, PPh3, and X were found in these species. The structural aspects as well as the preference for one coordination mode over another is discussed. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:521–533, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10097
Organometallic chemistry of silver and copper N‐heterocyclic carbene complexes
Authors: Arnold Polly L.
Published: September 2002

The only stable organometallic carbene complexes of silver and copper are those of N‐heterocyclic carbenes, since formally these robust divalent carbon ligands bind only by a σ donor interaction to the metal. A survey of the range of complexes that have now been reported is presented. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:534–539, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10098
Cyclic polycarbene ligands with crown ether structure
Authors: Hahn F. Ekkehardt , Langenhahn Volker , Le Van Duc , Tamm Matthias , Wittenbecher Lars , Lügger Thomas
Published: September 2002

The cyclization reaction of coordinated β‐functional phenyl isocyanides was used to generate coordinated anellated N‐heterocyclic carbenes. Coordinated 2‐trimethylsiloxyphenyl isocyanide reacts, after SiO bond cleavage, to yield a complex with a coordinated benzoxazol‐2‐ylidene ligand. The cyclization reaction of coordinated 2‐aminophenyl isocyanide, obtained in situ from 2‐azidophenyl isocyanide, yields the coordinated benzimidazol‐2‐ylidene. Both ylidenes can be alkylated at the nitrogen atoms. Attempts to generate four benzimidazol‐2‐ylidenes at PtII and to bridge them by N‐alkylation leading to a crown ether‐like ligand with carbene donors are presented here. Free N‐heterocyclic carbenes derived from benzimidazole with large N‐substituents exist as monomers while they dimerize to dibenzotetraazafulvalenes when substituted with sterically
less‐demanding substituents at the ring nitrogen atoms. A chemical equilibrium between the monomeric carbene and its dimerized enetetraamine exists for the N,N′‐isopropyl substituted derivative. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:540–549, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10099
Recent developments in thio‐, seleno‐, and telluro‐ether ligand chemistry
Authors: Barton Andrew J. , Genge Anthony R. J. , Hill Nicholas J. , Levason William , Orchard Simon D. , Patel Bhavesh , Reid Gillian , Ward Antony J.
Published: September 2002

New routes developed recently to overcome the difficulties usually associated with the sequential introduction of Te centers into polytelluro‐ethers and the introduction of tellurium into macrocyclic compounds are described, including the synthesis of the first facultative telluro‐ethers, RTe(CH2)3Te(CH2)3TeR, R = Me or Ph, and the first tridentate S2Te‐donor macrocycles and a tetradentate S3Te‐donor macrocycle.

The first systematic investigations into the preparation and characterization of coordination complexes of MX3 (M = As, Sb, Bi; X = Cl, Br, I) involving polydentate and macrocyclic thio‐ and seleno‐ether ligands are then discussed. The structures of examples of each class of compound are described, including the first examples of seleno‐ether adducts of the group 15 acceptors. A more limited range of telluro‐ether derivatives has been identified and the structure of the first example of this type is included. These species serve to demonstrate the wide structural diversity exhibited by these systems and the factors directing the assembly of these structures are highlighted. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:550–560, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10100
Bayesian estimation, simulation and uncertainty analysis: the cost‐effectiveness of ganciclovir prophylaxis in liver transplantation
Authors: Vanness David J. , Ray Kim W.
Published: September 2002

This paper demonstrates the usefulness of combining simulation with Bayesian estimation methods in analysis of cost‐effectiveness data collected alongside a clinical trial. Specifically, we use Markov Chain Monte Carlo (MCMC) to estimate a system of generalized linear models relating costs and outcomes to a disease process affected by treatment under alternative therapies. The MCMC draws are used as parameters in simulations which yield inference about the relative cost‐effectiveness of the novel therapy under a variety of scenarios. Total parametric uncertainty is assessed directly by examining the joint distribution of simulated average incremental cost and effectiveness. The approach allows flexibility in assessing treatment in various counterfactual premises and quantifies the global effect of parametric uncertainty on a decision‐maker's confidence in adopting one therapy over the other. Copyright © 2002 John Wiley & Sons, Ltd.
How important are tobacco prices in the propensity to start and quit smoking? An analysis of smoking histories from the Spanish National Health Survey
Authors: Nicolás Angel López
Published: September 2002

This paper presents an econometric analysis of the effect of policy instruments such as prices, restrictions to use and health warnings on the decisions to start and quit smoking. The duration up to starting and up to quitting is represented with several parametric models for the hazard function, and statistical tests are used to choose the best specification. The estimates reveal that prices have a very weak effect on the duration up to starting. On the contrary, the duration up to quitting is shortened by increases in the prices of the cheapest varieties of cigarrettes in the Spanish market. This evidence suggests specific directions for change in the structure of tobacco taxes. Copyright © 2002 John Wiley & Sons, Ltd.
An econometric analysis of the mental‐health effects of major events in the life of older individuals
Authors: Lindeboom Maarten , Portrait France , van den Berg Gerard J.
Published: September 2002

Major events in the life of an older individual, such as retirement, a significant decrease in income, death of the spouse, disability, and a move to a nursing home, may affect the mental‐health status of the individual. For example, the individual may enter a prolonged depression. We investigate this using unique longitudinal panel data that track labor market behavior, health status, and major life events, over time. To deal with endogenous aspects of these events we apply fixed effects estimation methods. We find some strikingly large effects of certain events on the occurrence of depression. We relate the results to the health care and labor market policy towards older individuals. Copyright © 2002 John Wiley & Sons, Ltd.
Vertical and horizontal aspects of socio‐economic inequity in general practitioner contacts in Scotland
Authors: Sutton Matthew
Published: September 2002

Health status varies across socio‐economic groups and health status is generally assumed to predict health care needs. Therefore the need for health care varies across socio‐economic groups, and studies of equity in the distribution of health care between socio‐economic groups must compare levels of utilisation with levels of need. Economic studies of equity in health care generally assume that health care needs can be derived from the current health–health care relationship. They therefore do not consider whether the current health–health care relationship is (vertically) equitable and the focus is restricted to horizontal inequity. This paper proposes a framework for incorporating the implications of vertical inequity for the socio‐economic distribution of health care. An alternative to the current health–health care relationship is proposed using a restriction on the health‐elasticity of health care. The health‐elasticity of general practitioner contacts in Scotland is found to be generally negative, but positive at low levels of health status. Pro‐rich estimates of horizontal inequity and vertical inequity are obtained but neither is statistically significant. Further analysis demonstrates that the magnitude of vertical inequity in health care may be larger than horizontal inequity. Copyright © 2002 John Wiley & Sons, Ltd.
Disentangling the effects of morbidity and life expectancy on labor market outcomes
Authors: Auld M. Christopher
Published: September 2002

Using a unique longitudinal dataset tracking the experiences of patients diagnosed with HIV+ disease, this paper develops and estimates a model capable of recovering the effect of revisions in life expectancy on labor market outcomes. The data allow us to estimate the effect of changes in health status (as objectively measured by CD4 counts) and the impact of learning that one is HIV+, which we interpret as a negative shock to life expectancy. Both parametric and distribution‐free models robustly indicate that decreases in health have little effect on labor demand but decrease probability of employment. We conclude that, in this sample, negative association between income and health is attributable mostly to the effect of altered incentives induced by changes in life expectancy. Copyright © 2002 John Wiley & Sons, Ltd.
B‐chronic lymphocytic leukemia: practical aspects
Authors: Pangalis Gerassimos A. , Vassilakopoulos Theodoros P. , Dimopoulou Maria N. , Siakantaris Marina P. , Kontopidou Flora N. , Angelopoulou Maria K.
Published: September 2002

B‐CLL is the most common adult leukemia in the Western world. It is a neoplasia of mature looking B‐monoclonal lymphocytes co‐expressing the CD5 antigen (involving the blood, the bone marrow, the lymph nodes and related organs). Much new information about the nature of the neoplastic cells, including chromosomal and molecular changes as well as mechanisms participating in the survival of the leukemic clone have been published recently, in an attempt to elucidate the biology of the disease and identify prognostic subgroups. For the time being, clinical stage based on Rai and Binet staging systems remains the strongest predictor of prognosis and patients' survival, and therefore it affects treatment decisions. In the early stages treatment may be delayed until progression. When treatment is necessary according to well‐established criteria, there are nowadays many different options. Chlorambucil has been the standard regimen for many years. During the last decade novel modalities have been tried with the emphasis on fludarabine and 2‐chlorodeoxyadenosine and their combinations with other drugs. Such an approach offers greater probability of a durable complete remission but no effect on overall survival has been clearly proven so far. Other modalities, included in the therapeutic armamentarium, are monoclonal antibodies, stem cell transplantation (autologous or allogeneic) and new experimental drugs. Supportive care is an important part of patient management and it involves restoring hypogammaglobulinemia and disease‐related anemia by polyvalent immunoglobulin administration and erythropoietin respectively. Copyright © 2002 John Wiley & Sons, Ltd.
Infiltration, runoff and sediment production in blanket peat catchments: implications of field rainfall simulation experiments
Authors: Holden J. , Burt T. P.
Published: September 2002

Blanket peat covers the headwaters of many major European rivers. Runoff production in upland blanket peat catchments is flashy with large flood peaks and short lag times; there is minimal baseflow. Little is known about the exact processes of infiltration and runoff generation within these upland headwaters. This paper presents results from a set of rainfall simulation experiments performed on the blanket peat moorland of the North Pennines, UK. Rainfall was simulated at low intensities (3–12 mm h−1), typical of natural rainfall, on bare and vegetated peat surfaces. Runoff response shows that infiltration rate increases with rainfall intensity; the use of low‐intensity rainfall therefore allows a more realistic evaluation of infiltration rates and flow processes than previous studies. Overland flow is shown to be common on both vegetated and bare peat surfaces although surface cover does exert some control. Most runoff is produced within the top few centimetres of the peat and runoff response decreases rapidly with depth. Little vertical percolation takes place to depths greater than 10 cm owing to the saturation of the peat mass. This study provides evidence that the quickflow response of upland blanket peat catchments is a result of saturation‐excess overland flow generation. Rainfall–runoff response from small plots varies with season. Following warm, dry weather, rainfall tends to infiltrate more readily into blanket peat, not just initially but to the extent that steady‐state surface runoff rates are reduced and more flow takes place within the peat, albeit at shallow depth. Sediment erosion from bare peat plots tends to be supply limited. Seasonal weather conditions may affect this in that after a warm, dry spell, surface desiccation allows sediment erosion to become transport limited. Copyright © 2002 John Wiley & Sons, Ltd.
Some early Russian studies of subsurface storm‐flow processes
Authors: Smakhtin V. U.
Published: September 2002

Subsurface flow is an important component of the catchment hydrological cycle. Various mechanisms of this process and their role in storm‐flow generation attracted the attention of many researchers throughout the twentieth century. The results of most of these studies are well documented. However, similar studies conducted in the past by many Russian hydrologists have never been made available to the English speaking hydrological community. This paper attempts to fill this gap and briefly review some of these investigations, focusing on their main results. It starts with the review of the early experimental studies (after 1930s–1950s), which allow the main characteristics of subsurface storm flow to be established. This is followed by a review of the research conducted in 1960s, which resulted in some conceptualization of the subsurface flow mechanisms. The paper also draws some parallels between this, mostly unknown, subsurface flow research in Russia and the better‐known contemporary studies of this process. Copyright © 2002 John Wiley & Sons, Ltd.
The solute budget of a forest catchment and solute fluxes within a Pinus radiata and a secondary native forest site, southern Chile
Authors: Uyttendaele Geertrui Y. P. , Iroumé Andrés
Published: September 2002

Solute concentrations and fluxes in rainfall, throughfall and stemflow in two forest types, and stream flow in a 90 ha catchment in southern Chile (39°44′S, 73°10′W) were measured. Bulk precipitation pH was 6·1 and conductivity was low. Cation concentrations in rainfall were low (0·58 mg Ca2+ l−1, 0·13 mg K+ l−1, 0·11 mg Mg2+ l−1 and <0·08 mg NH4–N l−1), except for sodium (1·10 mg l−1). Unexpected high levels of nitrate deposition in rainfall (mean concentration 0·38 mg NO3–N l−1, total flux 6·3 kg NO3–N ha−1) were measured. Concentrations of soluble phosphorous in bulk precipitation and stream flow were below detection limits (<0·09 mg l−1) for all events. Stream‐flow pH was 6·3 and conductivity was 28·3 μs. Stream‐water chemistry was also dominated by sodium (2·70 mg l−1) followed by Ca, Mg and K (1·31, 0·70 and 0·36 mg l−1). The solute budget indicated a net loss of 3·8 kg Na+ ha−1 year−1, 5·4 kg Mg2+ ha−1 year−1, 1·5 kg Ca2+ ha−1 year−1 and 0·9 kg K+ ha−1 year−1, while 4·9 kg NO3–N ha−1 year−1 was retained by the ecosystem. Stream water is not suitable for domestic use owing to high manganese and, especially, iron concentrations.

Throughfall and stemflow chemistry at a pine stand (Pinus radiata D. Don) and a native forest site (Siempreverde type), both located within the catchment, were compared. Nitrate fluxes within both forest sites were similar (1·3 kg NO3–N ha−1 year−1 as throughfall). Cation fluxes in net rainfall (throughfall plus stemflow) at the pine stand generally were higher (34·8 kg Na+ ha−1 year−1, 21·5 kg K+ ha−1 year−1, 5·1 kg Mg2+ ha−1 year−1) compared with the secondary native forest site (24·7 kg Na+ ha−1 year−1, 18·9 kg K+ ha−1 year−1 and 4·4 kg Mg2+ ha−1 year−1). However, calcium deposition beneath the native forest stand was higher (15·9 kg Ca2+ ha−1 year−1) compared with the pine stand (12·6 kg Ca2+ ha−1 year−1). Copyright © 2002 John Wiley & Sons, Ltd.
Measuring the flow resistance of submerged grass
Authors: Wilson C. A. M. E. , Horritt M. S.
Published: September 2002

Through laboratory experiments conducted in a grass‐lined flume, the hydraulic resistance of grass is measured and quantified. For the grass examined, it is found that Manning's n value is greater than those recommended in well‐established texts such as Chow (1959. Open Channel Flow. McGraw‐Hill: Singapore), relatively lower than those predicted by n‐UR methods, but corresponds well with the value found from calibration studies of two‐ and three‐dimensional numerical models. The assumption of a uniform Manning's n value with flow depth, which is often made in numerical modelling, may be invalid depending on the relative submergence of the vegetation. Drag coefficients are evaluated for a method applicable to three‐dimensional numerical models. Further detailed experimental investigation and application of these approaches within a numerical modelling framework is now recommended. Copyright © 2002 John Wiley & Sons, Ltd.
Impact of an unsealed forest road stream crossing: water quality and sediment sources
Authors: Lane Patrick N. J. , Sheridan Gary J.
Published: September 2002

Turbidity monitoring and rainfall and runoff simulation experiments were conducted at a newly constructed unsealed road stream crossing to determine the quantity and sources of sediment entering the stream. Continuous measurements of turbidity and estimation of total suspended solids (TSS) concentration upstream and downstream of the stream culvert were taken over a 5 month period. There was a statistically significant difference in turbidity and TSS downstream of the crossing during baseflow conditions, but the quality of the water column remained good during non‐rain periods. Rainfall events comprised around 20% of the observation period and led to decreases in water quality downstream of the crossing. Water quality could be considered as degraded for 10% of the observations. This was during a period when the rainfall was 65% of the long‐term average. Calculated suspended sediment loads were 0·78 t upstream and 2·77 t downstream, an increase of 3·5. It was estimated that at least 2–3 t of bedload material was also added to the stream during the crossing construction and from subsequent erosion. This material is a deposit on the cobble stream bed, and is most likely to degrade aquatic ecosystem values. Rainfall and runoff simulation revealed the principal sediment sources to be a fillslope that contributed coarse bedload material through rill erosion and unprotected toe scour, and the unmetalled road verge that provided fines. Although the quality of water column was good for the majority of the observations, the new Australian and New Zealand Water Quality Guidelines for Fresh and Marine Waters suggest this site exceeded ‘trigger levels’ that would warrant further investigation for both the water column and the bed deposits. Copyright © 2002 John Wiley & Sons, Ltd.
Influence of soil‐surface types on the overall runoff of the Tabernas badlands (south‐east Spain): field data and model approaches
Authors: Cantón Y. , Domingo F. , Solé‐Benet A. , Puigdefábregas J.
Published: September 2002

The Tabernas desert, an extensive badlands area in Almeria province (south‐east Spain), is characterized by a high variability in soil surface cover and soil properties along with important topographical contrasts giving rise to a wide range of hydrological behaviour. A double approach through field monitoring and modelling has been used to ascertain the influence of soil‐surface variability on the overall hydrological response.

Small plots were monitored for 3 years to assess runoff from the different surface types. Data provided by the long‐term monitoring of three small catchments formed by different soil surfaces were used to find out the specific contribution of each soil surface to the catchment runoff.

A simple spatially distributed model was built to predict runoff generation based on the infiltration rate of each soil‐surface type (defined as terrain units with the same cover, the same soil type and on the same landform). Plot results prove that the soil surface units within the study area behave differently in terms of hydrological response to natural rainfall. These responses are explained by the types of cover, topographical characteristics and soil properties. When runoff events are simple (with one or two runoff peaks), the modelled hydrographs reproduce the hydrographs observed reasonably well, but in complex events (with several runoff peaks) the adjustment is not as good. The model also shows the influence of the spatial distribution of soil surfaces on the overall runoff, aiding exploration of the spatial hydrological relationships among different landscape units. Copyright © 2002 John Wiley & Sons, Ltd.
System dynamics model for predicting floods from snowmelt in North American prairie watersheds
Authors: Li L. , Simonovic S. P.
Published: September 2002

This study uses a system dynamics approach to explore hydrological processes in the geographic locations where the main contribution to flooding is coming from the snowmelt. Temperature is identified as a critical factor that affects watershed hydrological processes. Based on the dynamic processes of the hydrologic cycle occurring in a watershed, the feedback relationships linking the watershed structure, as well as the climate factors, to the streamflow generation were identified prior to the development of a system dynamics model. The model is used to simulate flood patterns generated by snowmelt under temperature change in the spring. Model structure captures a vertical water balance using five tanks representing snow, interception, surface, subsurface and groundwater storage. Calibration and verification results show that temperature change and snowmelt play a key role in flood generation. Results indicate that simulated values match observed data very well. The goodness‐of‐fit between simulated and observed peak flow data is measured using coefficient of efficiency, coefficient of determination and square of the residual mass curve coefficient. For the Assiniboine River all three measures were in the interval between 0·92 and 0·96 and for the Red River between 0·89 and 0·97. The model is capable of capturing the essential dynamics of streamflow formation. Model input requires a set of initial values for all state variables and the time series of daily temperature and precipitation information. Data from the Red River Basin, shared by Canada and the USA, are used in the model development and testing. Copyright © 2002 John Wiley & Sons, Ltd.
Hydrological response types for gypsiferous soils in a semi‐arid region during nine years of continuous record
Authors: Desir G.
Published: September 2002

A 9‐year rainfall, sediment yield and runoff generation record from four experimental plots has been studied. Plots are located in the central Ebro Basin over smooth hillslope developed over gypsum and marl Miocene deposits. The hydrological response of these areas is a function of soil properties, final infiltration capacity and permeability of soils and rainfall characteristics, such as intensity and amount. Results show that there are two types of hydrological response in these areas. First is Hortonian like, which takes place during wet periods and it is responsible for the main part of total sediment yield. Second is like saturation excess overland flow, and it appears after long period. The presence of either type is controlled by a double threshold, starting from when runoff is significant. Copyright © 2002 John Wiley & Sons, Ltd.
Individual differences in children's understanding of social evaluation concerns
Authors: Banerjee Robin
Published: September 2002

Recent research suggests that children's understanding of self‐presentational behaviour—behaviour designed to shape social evaluation—is a function of both cognitive and motivational variables. Furthermore, the motivational factors involved are likely to reflect individual differences in the salience of concerns about social evaluation. The present research represents a first effort to determine whether measures of such differences are indeed associated with the understanding of self‐presentational behaviour. In a first experiment, a teacher rating measure of self‐monitoring was found to be positively associated with the understanding of self‐presentational motives. In a second experiment, a more narrowly specified self‐report measure of public self‐consciousness was found to have a similar association with the understanding of self‐presentation, with no such association found for private self‐consciousness. These preliminary results make it clear that our formulations of development in social cognition must indeed include a consideration of individual differences in motivational orientations. Copyright © 2002 John Wiley & Sons, Ltd.
Processing of facial and non‐facial visual stimuli in 2–5‐year‐old children
Authors: Schwarzer Gudrun
Published: September 2002

The present experiments examined the degree to which analytic and holistic modes of processing play a role in the way 2–5‐year‐old children process facial and non‐facial visual stimuli. Children between 2 and 5 years of age were instructed to categorize faces (in Experiment 1) and non‐facial visual stimuli, such as birds and planes (in Experiment 2), into two categories. The categories were so constructed as to allow the children to categorize the facial and non‐facial stimuli either analytically (by focusing on a single attribute) or holistically (in terms of overall similarity). The results demonstrated that the previous conclusions concerning older children's (from 6 years onwards) holistic mode of facial processing could not be generalized to younger children because most of the 2–5‐year olds processed the faces by taking single facial attributes into account. A similar pattern of results emerged for the processing of objects, showing that the majority of the children focused on single attributes. Thus, for both visual domains, holistic processing was the exception rather than the rule. Copyright © 2002 John Wiley & Sons, Ltd.
Proneural and proneuroendocrine transcription factor expression in cutaneous mechanoreceptor (Merkel) cells and Merkel cell carcinoma
Authors: Leonard J. Helen , Cook Anthony L. , Van Gele Mireille , Boyle Glen M. , Inglis Kelly J. , Speleman Frank , Sturm Richard A.
Published: September 2002

Merkel cells form part of the peripheral neuroendocrine system of the skin and act as mechanoreceptors in touch response. Merkel cell carcinoma (MCC) is a rare, aggressive disease with similarities to small cell lung cancer (SCLC), which is also of neuroendocrine origin. We previously identified a novel DNA binding protein complex specific for MCC suspension cell lines, termed Merkel nuclear factor (MNF) by its binding to the POU‐IV family DNA binding consensus sequence. Here we report that MNF contains the POU‐IV family member Brn‐3c and that Brn‐3c is expressed in normal Merkel cells. Additionally, Brn‐3c protein reactivity is restricted to a subset of MCC biopsies and is not seen in biopsies revealing adherent, variant cell lines lacking neuroendocrine markers. Recently, proper development of murine Merkel cells was shown to require the proneural basic helix‐loop‐helix transcription factor, atonal family member, MATH1. We demonstrate a correlation between Brn‐3c and HATH1 reactivity in MCC biopsies and cell lines with retention of neuroendocrine phenotype. In SCLC, the related basic helix‐loop‐helix transcription factor HASH1 is responsible for neuroendocrine phenotype, but HASH1 transcripts were not detected in MCC cell lines. We propose that HATH1 and Brn‐3c may form a transcriptional hierarchy responsible for determining neuroendocrine phenotype in Merkel cells and that lack of Brn‐3c and/or HATH1 in MCC may indicate a more aggressive disease requiring closer patient follow‐up. © 2002 Wiley‐Liss, Inc.
Role of Wnt pathway in medulloblastoma oncogenesis
Authors: Yokota Naoki , Nishizawa Shigeru , Ohta Seiji , Date Hiroaki , Sugimura Haruhiko , Namba Hiroki , Maekawa Masato
Published: September 2002

To clarify the roles of Wnt pathway in medulloblastoma oncogenesis, immunohistochemical staining of β‐catenin and Wnt‐1 and genomic analyses of CTNNB1 (β‐catenin) and AXIN1 (axin 1) were examined in 23 sporadic cases. Accumulation of β‐catenin in tumor cells was immunohistochemically proven in 5 cases; 2 cases showed positive immunoreactivity for Wnt‐1 and another 2 showed mutation of either CTNNB1 or AXIN1. AXIN1 mutation was in exon 3, corresponding to GSK‐3β binding site and CTNNB1 mutation was in exon 3, corresponding to its phosphorylation site. Disruption of these proteins could result in upregulation of the Wnt signaling and accumulation of β‐catenin, followed by cell proliferation and medulloblastoma oncogenesis. © 2002 Wiley‐Liss, Inc.
Antagonistic and agonistic effects of quinazoline tyrosine kinase inhibitors on mutant EGF receptor function
Authors: Montgomery R. Bruce
Published: September 2002

A mutated form of the EGF receptor (EGFRvIII), resulting from deletion of exons 2–7, is an oncogenic protein that is expressed in multiple human tumors. This mutation induces ligand‐independent activation of the EGFR tyrosine kinase and thereby can initiate unregulated cell growth and tumorigenesis. Thus, inhibition of the kinase activity of EGFRvIII is a potential means of suppressing its oncogenic properties. Certain tyrosine kinase inhibitors (tyrphostins) specifically inhibit the wild‐type EGFR and thereby inhibit tumor growth both in vitro and in vivo. We demonstrate that the quinazoline tyrphostins AG 1478 and AG 1517 can suppress morphologic transformation of cell lines by EGFRvIII. Quinazolines were found to inhibit receptor autophosphorylation and signaling through MAP kinase, but had minimal effects on association of EGFRvIII with Grb2/SOS. Low concentrations of quinazoline also increased receptor dimerization and phosphotyrosine content. This was associated with increases in colony formation in soft agar and increased invasion through matrigel for AG 1478. Thus, both AG 1478 and AG 1517 can inhibit multiple EGFRvIII signaling pathways, but at low concentrations AG 1478 can enhance colony formation, presumably related to augmented homodimerization of the receptor and activation of downstream signaling. © 2002 Wiley‐Liss, Inc.
Intraperitoneal bispecific antibody (HEA125xOKT3) therapy inhibits malignant ascites production in advanced ovarian carcinoma
Authors: Marmé Alexander , Strauß Gudrun , Bastert Gunther , Grischke Eva‐Maria , Moldenhauer Gerhard
Published: September 2002

Bispecific antibody HEA125xOKT3 was shown to redirect T lymphocytes toward carcinoma cells and to induce tumor cell lysis in vitro. Preclinical studies have demonstrated that tumor‐associated lymphocytes (TAL) derived from malignant ascites can be used as effector cells with a high efficacy and without prior stimulation. These data provided the rationale for a clinical trial to investigate whether bsAb HEA125xOKT3 is also able to induce tumor cell lysis in vivo and can be used for local treatment of malignant ascites arising from ovarian carcinoma. Ten ovarian carcinoma patients presenting with malignant ascites resistant to chemotherapy were enrolled in the study. They received weekly intraperitoneal injections of 1 mg bsAb diluted in 500 ml NaCl solution to allow homogeneous antibody distribution within the peritoneal cavity. All patients responded clinically well to the therapy. Eight patients experienced a complete and 2 patients a partial reduction of ascites production. A decrease or stabilization of tumor marker CA125 was detected in the sera of 8 patients. Only WHO Grade I and II toxicity was observed including mild fever, chills and allergic eczema. Thus, intraperitoneal application of bsAb HEA125xOKT3 appears to be an easy and cost effective palliative treatment for ovarian carcinoma with recurrent ascites that leads to a substantially increased quality of life for the patients. During therapy TNF‐α concentrations raised markedly in the ascites fluid whereas VEGF and sFLT‐1 ascites levels declined. This indicates that not only T cell‐mediated tumor cell lysis but also changes in vascular permeability due to downregulation of VEGF and its receptors might be responsible for the beneficial therapeutic effect. © 2002 Wiley‐Liss, Inc.