bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of thiazolidines in guava: stereochemical studies
Authors: Fernandez Xavier , Duñach Elisabet , Fellous Roland , Lizzani‐Cuvelier Louisette , Loiseau Michel , Dompe Vincent , Cozzolino Francis , George Gérard , Rochard Sophie , Schippa Christine
Published: September 2002

Volatile compounds from guava (Psidium guajava L.) were extracted using dichloromethane. Among these volatile compounds, methyl 2‐methyl‐thiazolidine‐4‐(R)‐carboxylate (cis and trans) and the ethyl 2‐methyl‐thiazolidine‐4‐(R)‐carboxylate (cis and trans) could be identified for the first time in fruits. The chemical synthesis of the reference compounds and other analogues allowed the further comparison with the guava extracted thiazolidines. The absolute configuration of the cis/trans isomers was determined by nuclear magnetic resonance (1H‐NMR) and by nuclear overhauser enhancement (2D NMR NOESY). Copyright © 2001 John Wiley & Sons, Ltd.
A parallel pressure implicit splitting of operators algorithm applied to flows at all speeds
Authors: Bressloff N. W.
Published: September 2002

A parallel implementation of the pressure‐based implicit splitting of operators (PISO) method is described and applied to both compressible and incompressible flows. The treatment of variables at the interfaces between adjacent blocks is highlighted, and, for compressible flow, a straightforward method for the implicit handling of density is described. Steady state and oscillatory flow through a sudden expansion are considered at low speeds for both two‐ and three‐dimensional geometries. Extension of the incompressible method to compressible flow is assessed for subsonic, transonic and supersonic flow through a two‐dimensional bump. Although good accuracy is achieved in these high‐speed flows, including the automatic capturing of shock waves, the method is deemed unsuitable for simulating steady state high‐speed flows on fine grids due to the requirement of very small time steps. Copyright © 2001 John Wiley & Sons, Ltd.
Iterative explicit simulation of 1D surges and dam‐break flows
Authors: Hsu Chih‐Tsung , Yeh Keh‐Chia
Published: September 2002

The one‐dimensional Saint Venant equations for shallow‐water flows are used to simulate the flood wave resulting from the sudden opening (or closure) of a gate or collapse of a dam. An iterative explicit characteristics‐based finite‐difference method, based on the explicit finite analytic method, is proposed to discretize the dynamic equation, and the conservative control volume method is used for the discretization of the continuity equation. Surge and dam‐break flows in a horizontal, rectangular and frictionless channel were first considered, under such conditions the analytic solutions exist. For the surge simulation, numerical results of the proposed scheme are nearly identical to those obtained from the Preissmann scheme. For the dam‐break simulations addressing three ratios of tailwater depth to water depth in the reservoir, the proposed scheme, as compared with the analytic solutions, yields better results than those obtained by the MacCormack scheme, the Gabutti scheme, and Jha et al.'s flux splitting scheme (J. Hydraul. Res. 1996; 34(5):605–621). As the depth ratio approaches zero, the accuracy of the proposed scheme is still satisfactory, even with the dry‐bed condition. Investigations then were made for more realistic dam‐break flow waves propogating in a sloped and frictional channel. Lacking analytic solutions, the simulating results from the proposed scheme as well as those from Chen's scheme (J. Hydraul. Div. 1980; 106(HY4):535–556) were compared with the laboratory data collected in 1960–1961 at the United States Army Engineer Waterways Experiments Station (WES). An assumed initial flow was required for the computer‐simulated condition in Chen's model. However, this is not the case in the proposed model, i.e., a real dry‐bed condition was set as the initial condition in the downstream channel of the dam. The consistency between the two simulated results is obvious compared with the experimental data. Copyright © 2002 John Wiley & Sons, Ltd.
Eddy resolving simulations of turbulent solar convection
Authors: Elliott Julian R. , Smolarkiewicz Piotr K.
Published: September 2002

Deep convection occurs in the outer one‐third of the solar interior and transports energy generated by nuclear reactions to the surface.It leads to a characteristic pattern of time‐averaged differential rotation, with the poles rotating significantly slower (approximately 25 per cent) than the equator. This differential rotation results from Reynolds stresses that are associated with correlations of the longitudinal velocity with the radial and latitudinal velocities. One particularly interesting feature of the solar differential rotation is that it shows significant tilting of angular velocity contours away from the rotation axis (i.e. breaking of the Taylor–Proudman state of rotation rate constant on cylinders aligned with the rotation axis), in contrast to the results from early numerical simulations. In spite of such discrepancies, numerical simulations provide the best chance of making progress in understanding the observations. Many studies have adopted the DNS approach and have justified the artificially large viscosities and thermal diffusivities used as modelling transport by unresolved eddies. LES techniques (which use a turbulence closure to relate transport coefficients to local properties of the flow) offer a superior alternative, but face the problem of defining the turbulence closure, which is potentially difficult in the presence of stratification, rotation and other complicating factors. This problem can be avoided by shifting the responsibility for truncating the turbulent cascade from an explicit turbulence closure to the numerical scheme itself. Since this approach abandons the rigorous notions of the LES approach, we refer to it as a VLES (Very Large Eddy Simulation). This paper compares results of DNS simulations carried out with a spherical‐harmonic code, and preliminary results obtained using a VLES‐type code. Both make the anelastic approximation. Copyright © 2002 John Wiley & Sons, Ltd.
A forecasting comparison of classical and Bayesian methods for modelling logistic diffusion
Authors: Bewley Ronald , Griffiths William E.
Published: September 2002

A Bayesian procedure for forecasting S‐shaped growth is introduced and compared to classical methods of estimation and prediction using three variants of the logistic functional form and annual times series of the diffusion of music compact discs in twelve countries. The Bayesian procedure was found not only to improve forecast accuracy, using the medians of the predictive densities as point forecasts, but also to produce intervals with a width and asymmetry more in accord with the outcomes than intervals from the classical alternative. While the analysis in this paper focuses on logistic growth, the problem is set up so that the methods are transportable to other characterizations of the growth process. Copyright © 2001 John Wiley & Sons, Ltd.
Identification of asymmetric prediction intervals through causal forces
Authors: Armstrong J. Scott , Collopy Fred
Published: September 2002

When causal forces are specified, the expected direction of the trend can be compared with the trend based on extrapolation. Series in which the expected trend conflicts with the extrapolated trend are called contrary series. We hypothesized that contrary series would have asymmetric forecast errors, with larger errors in the direction of the expected trend. Using annual series that contained minimal information about causality, we examined 671 contrary forecasts. As expected, most (81%) of the errors were in the direction of the causal forces. Also as expected, the asymmetries were more likely for longer forecast horizons; for six‐year‐ahead forecasts, 89% of the forecasts were in the expected direction. The asymmetries were often substantial. Contrary series should be flagged and treated separately when prediction intervals are estimated, perhaps by shifting the interval in the direction of the causal forces. Copyright © 2001 John Wiley & Sons, Ltd.
Modelling the development of supply‐restricted telecommunications markets
Authors: Islam Towhidul , Fiebig Denzil G.
Published: September 2002

A large proportion of the world telecommunications market can be characterized as supply restricted. In ITU (1999) official waiting lists numbered about 50 million worldwide with an average waiting time of two years. More than 100 countries had not eliminated the waiting list for telephone connections and hence a supply restricted market prevailed in all of these countries. Only about 25 countries have succeeded in eradicating their waiting list for basic telephone service. In terms of the pattern of diffusion, the subscriber's flow from waiting applicants to adopters is controlled by supply restrictions adding an important dimension that needs to be addressed when modeling and forecasting demand. An empirical analysis of the diffusion of main telephones in 46 supply‐restricted countries is presented to demonstrate the usefulness of a three‐stage Bass model that has been proposed to capture the dynamics of supply restrictions. We also compare the forecasting ability of different approaches to estimation when panel data are available. Copyright © 2001 John Wiley & Sons, Ltd.
Molecular‐cytogenetic comparison of mucosa‐associated marginal zone B‐cell lymphoma and large B‐cell lymphoma arising in the gastro‐intestinal tract
Authors: Barth Thomas F.E. , Bentz Martin , Leithäuser Frank , Stilgenbauer Stephan , Siebert Reiner , Schlotter Magdalena , Schlenk Richard F. , Döhner Hartmut , Möller Peter
Published: September 2002

Extranodal B‐cell lymphoma of mucosa‐associated lymphoid tissue (MALT) type may represent a model of lymphoma progression, because a small cell component frequently occurs in the large cell variants. We studied 52 extranodal B‐cell lymphomas: 18 extranodal marginal zone B‐cell lymphomas of MALT type (MZBL,MT), 7 MZBL,MT of the gastro‐intestinal tract with a diffuse large B‐cell component (giMZBLplusLBCL), and 27 diffuse large B‐cell lymphomas of the gastro‐intestinal tract without small cell component (giLBCL). Analytical techniques were comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). The translocation t(11;18) was found as the sole aberration in two MZBL,MT only. In contrast to this, t(11;18)‐negative MZBL,MT were characterized by frequent gains on chromosome 3 and DNA amplifications on 2p13–p15. Furthermore, we found a clonal lymphoma progression from the small to the large cell component with accumulation of gains and losses of chromosomal material in the large cell component in giMZBLplusLBCL. Aberrations overlapping with MZBL,MT and giMZBLplusLBCL included losses on chromosome 13, amplifications of the REL proto‐oncogene, or gains on chromosome 12. In addition, the large cell component revealed gains on 8q24, including amplifications of the MYC proto‐oncogene, and losses on 2q. The giLBCL had frequent gains on chromosomes 12 and 9, as well as on 11q, and losses on 6q. We conclude that, based on the distinctive and partly overlapping patterns of genetic aberrations, MALT lymphomas can be divided into different genetic subgroups. © 2001 Wiley‐Liss, Inc.
Analysis of loss of heterozygosity in lymphoma and leukaemia arising in F1 hybrid mice locates a common region of chromosome 4 loss
Authors: Meijne Emmy , Huiskamp Rene , Haines Jackie , Moody John , Finnon Rosemary , Wilding Jennifer , Spanjer Sylvia , Bouffler Simon , Edwards Alan , Cox Roger , Silver Andrew
Published: September 2002

Previous studies have identified five lymphoma‐related tumour suppressor gene regions on murine chromosome 4. Using detailed allelotype analysis on a range of lympho‐haematopoietic tumour types arising in F1 hybrid mice, we now show a consistent pattern of loss of heterozygosity (LOH) which identifies a common region of loss delineated by microsatellites D4Mit21 and D4Mit53 on proximal chromosome 4. This critical segment corresponds to the thymic lymphoma tumour suppressor region 5 (TLSR5) identified in an earlier study. Tumours of this type have also been reported as showing allelic loss from the Trp53 and Ikaros regions on chromosome 11. In the present study, only a small fraction of tumours showed LOH in the Ikaros region, while a minority of lymphomas, but not acute myeloid leukaemias, showed allelic loss of the chromosome 11 segment encoding Trp53. These and other data indicate strongly that the genomic regions identified as showing recurrent LOH depend on the genetic background of the mice. Overall, the results indicate a key role for a tumour suppressor gene(s) encoded in an ∼3 cM segment on proximal chromosome 4 and provide an experimental basis for the further investigation of the functional role of candidate genes which include Pax5 and Tgfbr1. © 2001 Wiley‐Liss, Inc.
The fluvial and geomorphic context of Indian Knoll, an Archaic shell midden in West‐Central Kentucky
Authors: Morey Darcy F. , Crothers George M. , Stein Julie K. , Fenton James P. , Herrmann Nicholas P.
Published: September 2002

Indian Knoll is the largest Archaic shell midden excavated by WPA archaeologists in Kentucky. Situated in a large alluvial valley, the site is not associated with a known river shoal as might be expected, making its fluvial and geomorphic setting of interest. Based on sediment cores and auger samples, undisturbed portions of the site remain despite extensive excavations. In undisturbed portions, a shell‐bearing layer is overlain by a shell‐free midden layer. Profiles of organic matter and calcium carbonate content for both layers are similar to those of other Green River shell middens. New radiocarbon determinations date the shell deposit at 5590–4530 cal yr B.P. Analysis of mussel species collected from the Indian Knoll indicates that shell fishing took place in a swiftly flowing, shallow to moderately deep setting of the main river channel. Overall, the prehistoric river setting adjacent to Indian Knoll was characterized by deeper water on average with variable but finer‐grained substrate compared to other Green River shell midden sites. © 2002 Wiley Periodicals, Inc.
A comparative electron microprobe study of “Aeginetan” wares with potential raw material sources from Aegina, Methana, and Poros, Greece
Authors: Dorais Michael J. , Shriner Christine M.
Published: September 2002

Qualitative stylistic evidence from ceramic vessels and limited petrographic analysis suggested that a distinctive group of ceramics with visible inclusions of biotite (Gold Mica Fabric) was produced on the island of Aegina, Greece, during the Middle Helladic and Late Helladic I periods. To quantitatively evaluate this provenance, we sampled all potential source rocks on Aegina, Methana, and Poros. Electron microprobe analysis of amphibole in these samples revealed that each of these volcanic centers has its own unique mineralogical signature. Comparative analyses of amphibole in Zerner's original stylistic “Gold Mica Fabric” type sample with the reference samples reveal that two sherds are Aeginetan. Three additional sherds from this sample may have a non‐Aeginetan provenance, probably from a back‐arc setting outside the Saronic Gulf. These results suggest that the hypothesis of a single source production site for Aeginetan Ware should be reexamined. © 2002 Wiley Periodicals, Inc.
Effect of polygenes on Xiong’s transmission disequilibrium test of a QTL in nuclear families with multiple children
Authors: Deng Hong‐Wen , Li Jing , Recker Robert R.
Published: September 2002

The transmission disequilibrium test (TDT), originally developed for mapping disease genes, has recently been extended to identify quantitative trait loci (QTL). For quantitative traits important for human health, generally multiple QTLs are involved. In the investigation of the statistical properties of the TDT, background polygenes (QTLs other than the QTL under test) generally have not been explicitly considered. The effects of background polygenes on the statistical properties of the TDT are thus largely unknown. Investigation of these effects will provide more realistic analyses of the statistical properties of the TDT under biologically plausible situations, and thus provide more accurate guidelines on the application of the TDT in practice. A general TDT (TDTG) has been developed to test linkage of a QTL in nuclear families that may be composed of more than one heterozygous parent and multiple children. Using the TDTG as an example, we develop an analytical method to investigate the effects of background polygenes on the power of the TDT. The accuracy of our analytical method is validated by computation simulations. We found that the power of the TDTG is increased with background polygenes when more than one child is employed in nuclear families, and the effect is stronger with more children per family recruited for study. The power of the TDTG increases dramatically when the number of children recruited from each nuclear family increases from one to two or from two to three. The type one error rate is not affected by the presence of background polygenes. The results of this study should be of theoretical significance in generalizing the investigation of the TDT to biologically plausible situations with background polygenes. They should also be of practical values in providing guidance on the recruitment of nuclear families with multiple children with the TDTG. Genet. Epidemiol. 21:243–265, 2001. © 2001 Wiley‐Liss, Inc.
Book Review: Newtonian physic
Authors: Weiss Kenneth M.
Published: September 2002

Genetic Dissection of Complex Traits. D.C. Rao, M.A. Province. San Diego, Academic Press, 2001, xxi + 583 pp, $120 (formally, this is Advances in Genetics, vol 42)
Hydrolysis of an isolable selenoseleninate under acidic and alkaline conditions
Authors: Ishii Akihiko , Takahashi Takeshi , Nakayama Juzo
Published: September 2002

Acid‐catalyzed hydrolysis of a selenoseleninate [TripSe(O)SeTrip](Trip = 9‐triptycyl) in 2 M HClO4‐1,4‐dioxane at room temperature yielded the selenenic acid (TripSeOH). Alkaline hydrolysis of TripSe(O)SeTrip gave the diselenide (TripSeSeTrip) and the seleninic acid (TripSeO2H), where air oxidations of the resulting selenol (TripSeH) and TripSeOH occur at a considerable rate. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:198–203, 2001
Oxidation of 1,4‐dihydro‐1,4‐diphenyl‐2,3‐benzodithiin
Authors: Sato Ryu , Takeda Eiji , Nakajo Shiduko , Kimura Takeshi , Ogawa Satoshi , Kawai Yasushi
Published: September 2002

1,4‐Dihydro‐1,4‐diphenyl‐2,3‐benzodithiin (3), synthesized from 1,2‐bis(phenylmethyl)benzene (1), was subjected to oxidation to give 1,4‐dihydro‐1,4‐diphenyl‐2,3‐benzodithiin 2‐oxide (4) as a mixture of diastereomers separable by column chromatography. (1R*,2R*,4S*)‐1,4‐Dihydro‐1,4‐diphenyl‐2,3‐benzodithiin 2‐oxide (4‐meso‐1) was obtained preferentially from (1R*,4S*)‐1,4‐dihydro‐1,4‐diphenyl‐2,3‐benzodithiin (3‐meso) with m‐chloroperbenzoic acid (m‐CPBA). The 4‐meso‐1 stereoisomer afforded an unexpected product 1,3‐diphenylbenzo[c]thiophene (5) upon further oxidation with mCPBA. On the other hand, oxidation of 1,4‐dihydro‐1,4‐diphenyl‐2,3‐benzodithiin 2‐oxides (4‐dl and 4‐meso), with Oxone gave 1,4‐dihydro‐1,4‐diphenyl‐2,3‐benzodithiin 2,2‐dioxide (7). © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:209–216, 2001
Crystal structure of 2,4,6‐tri‐tert‐butylphenyltrichlorogermane and 2,4,6‐tri‐tert‐butylphenylgermane
Authors: Unno Masafumi , Kawai Yuuki , Matsumoto Hideyuki
Published: September 2002

Two organogermanium compounds, 2,4,6‐(t‐Bu)3C6H2GeCl3 (1) and 2,4,6‐(t‐Bu)3C6H2GeH3 (2), were prepared, and the structures were determined by X‐ray crystallography. Compound 1 exhibits unusual structural parameters due to the strong repulsion of the bulky t‐butyl substituents and GeCl3 moiety; the benzene ring assumes a boat conformation, and the GeCl3 group as well as the o‐t‐butyl groups stay significantly away from the benzene ring. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:238–243, 2001
Budget
Authors: Antolovic’ Laurie G.
Published: September 2002

The implementation of new information technologies or deployment of new information services poses challenges for budget planners that must be met with a thorough understanding of the nature of communication and information systems infrastructures.
Higher Education Communication and Information Systems Policy
Authors: Eisler David L.
Published: September 2002

Effective use of new technologies calls for the development of institutional policies in equally new areas of concern.
Limitations to enhancing the speed of onset of antidepressants — are rapid action antidepressants possible?
Authors: Artigas Francesc
Published: September 2002

Existing antidepressant treatments suffer from a limited efficacy and a slow onset of action. Some first‐generation antidepressant drugs are still among the most effective treatments. Several neurobiological adaptive mechanisms are involved in the delayed action of antidepressants. Among these, a negative feed‐back involving somatodendritic autoreceptors plays an important role in such delay. In the case of the SSRIs, the prevention of this effect with 5‐HT1A autoreceptor antagonists enhances their effects at experimental level. Open‐label and placebo‐controlled trials with the mixed β‐adrenoceptor/5‐HT1A antagonist pindolol support that this agent reduces the latency to achieve a clinical improvement when used in combination with SSRIs. Displacement studies support that this action is mediated by its interaction with 5‐HT1A receptors. The design of clinical trials for the evaluation of fast‐acting antidepressants is critical. The use of loose criteria of response may result in a poor discriminating power. Conversely, stringent clinical criteria may be more helpful in revealing the differences between treatments. The data of a double‐blind, placebo‐controlled trial comparing fluoxetine plus placebo and fluoxetine plus pindolol suggests that the use of sustained response (i.e., one maintained until the end of the trial) is critical for the establishment of differences between treatments. Other factors, such as a placebo lead‐in phase or the frequency of visits, appear to play a minor role. Overall, these data indicate that faster antidepressant drugs can be obtained through a better knowledge of their actions in CNS. Copyright © 2001 John Wiley & Sons, Ltd.
Combination of antidepressant drugs: the case of inositol
Authors: Nemets Boris , Fux Mendel , Levine Joseph , Belmaker R. H
Published: September 2002

Inositol is a second messenger precursor that is effective in depression and obsessive‐compulsive disorder via a mechanism different from serotonin reuptake inhibitors. However, controlled trials of inositol combined with serotonin reuptake inhibitors in depression or in reuptake inhibitor resistant depressed patients, or in partially responsive obsessive‐compulsive patients, did not reveal added benefit. This is comparable to results with combinations of other antidepressant treatments, such as tricyclics plus monoamine oxidase inhibitors. Copyright © 2001 John Wiley & Sons, Ltd.
Neurotrophins: possible role in affective disorders
Authors: Sandler M
Published: September 2002

Various monoamine hypotheses of affective disorders have been unable to provide a complete explanation for the observed clinical findings. Recently Duman et al. (1997) have produced a molecular and cellular theory of depression which seems to be a worthy successor to these hypotheses. Whereas the earlier theories were unable to explain the time lag between antidepressant drug administration and lightening of affect, Duman's group pinpoints intracellular mechanisms, in the right time frame, which decrease or increase the generation of neurotrophic factors necessary for the survival of certain neurons, particularly in the hippocampus. This new concept may lead to novel therapeutic approaches. Copyright © 2001 John Wiley & Sons, Ltd.
The immunoregulatory effects of antidepressants
Authors: Maes Michael
Published: September 2002

There is some evidence that major depression is accompanied by activation of the inflammatory‐response system (IRS). It has been hypothesized that increased production of proinflammatory cytokines may play a role in the etiology of major depression. If increased production of proinflammatory cytokines is at all involved in the etiology of depression, one would expect antidepressive treatments to have negative immunoregulatory effects. This paper reviews the effects of antidepressants, such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), heterocyclic antidepressants (HCAs), serotonin‐noradrenaline reuptake inhibitors (SNRIs), lithium,l‐5‐hydroxytroptophan (L‐5‐HTP), reversible inhibitors of MAO‐A (RIMA) on the production of proinflammatory cytokines, e.g. interferon‐γ (IFNγ), and negative immunoregulatory cytokines and agents, e.g. interleukin‐10 (IL‐10). In depressed patients, prolonged treatment with antidepressants and mood stabilizers normalizes signs of activation of the IRS, such as increased serum IL‐6 and acute phase protein concentrations. In vitro, it has been shown that various types of antidepressive drugs, including TCAs (imipramine; clomipramine); SSRIs (citalopram, fluoxetine, sertraline); lithium; SNRIs (venlafaxine); HCAs (trazodone); RIMAs (moclobemide) and L‐5‐HTP significantly suppress the ratio of IFNγ/IL‐10 production by peripheral blood immunocytes. These antidepressant drugs appear to have a common effect on the IRS, i.e. in vitro they increase the production of IL‐10 by peripheral blood leukocytes. Thus, the results suggest that antidepressants have negative immunoregulatory effects. It may be speculated that antidepressants exert some of their antidepressant effects through their negative immunoregulatory capacities. Copyright © 2001 John Wiley & Sons, Ltd.
Ontogenetic effects of MAO‐A inhibition on rat pineal n‐acetylserotonin and melatonin during the first month of neonatal life
Authors: Oxenkrug Gregory F , Requintina Pura J , Yuwiler A
Published: September 2002

Inhibitors of monoamine oxidase A (MAO‐A) but not MAO‐B stimulate the activity of pineal serotonin N‐acetyltransferase (AANAT) in the adult rat pineal leading to increased formation of N‐acetyl serotonin (NAS) and melatonin (MEL). The pineal gland of the neonatal rat has AANAT activity, but the second enzyme in melatonin biosynthesis, HIOMT (hydroxyindole‐O‐methyltransferase) converting NAS to MEL, is absent during the first week of neonatal life. In this study we examined the effects of acute clorgyline treatment in vitro and in vivo, on pineal indoles over the first month of neonatal life. The results show that clorgyline stimulates NAS production by pineal both in vitro and in vivo from day five on with a marked increase between day 14 and day 21. In contrast, MEL is not increased until day 21, with a sharp rise thereafter. Copyright © 2000 John Wiley & Sons, Ltd.
Functional magnetic resonance imaging reflects changes in brain functioning with sedation
Authors: Starbuck Victoria N , Kay Gary G , Platenberg R. Craig , Lin Chin‐shoou , Zielinski Brandon A
Published: September 2002

Functional magnetic resonance imaging (fMRI) studies have demonstrated localized brain activation during cognitive tasks. Brain activation increases with task complexity and decreases with familiarity. This study investigates how sleepiness alters the relationship between brain activation and task familiarity. We hypothesize that sleepiness prevents the reduction in activation associated with practice. Twenty‐nine individuals rated their sleepiness using the Stanford Sleepiness Scale before fMRI. During imaging, subjects performed the Paced Auditory Serial Addition Test, a continuous mental arithmetic task. A positive correlation was observed between self‐rated sleepiness and frontal brain activation. Fourteen subjects participated in phase 2. Sleepiness was induced by evening dosing with chlorpheniramine (CP) (8 mg or 12 mg) and terfenadine (60 mg) in the morning for 3 days before the second fMRI scan. The Multiple Sleep Latency Test (MSLT) was also performed. Results revealed a significant increase in fMRI activation in proportion to the dose of CP. In contrast, for all subjects receiving placebo there was a reduction in brain activation. MSLT revealed significant daytime sleepiness for subjects receiving CP. These findings suggest that sleepiness interferes with efficiency of brain functioning. The sleepy or sedated brain shows increased oxygen utilization during performance of a familiar cognitive task. Thus, the beneficial effect of prior task exposure is lost under conditions of sedation. Copyright © 2000 John Wiley & Sons, Ltd.
A simple rainfall–runoff model based on hydrological units applied to the Teba catchment (south‐east Spain)
Authors: Donker N. H. W.
Published: September 2002

A hydrological model (YWB, yearly water balance) has been developed to model the daily rainfall–runoff relationship of the 202 km2 Teba river catchment, located in semi‐arid south‐eastern Spain. The period of available data (1976–1993) includes some very rainy years with intensive storms (responsible for flooding parts of the town of Malaga) and also some very dry years.

The YWB model is in essence a simple tank model in which the catchment is subdivided into a limited number of meaningful hydrological units. Instead of generating per unit surface runoff resulting from infiltration excess, runoff has been made the result of storage excess. Actual evapotranspiration is obtained by means of curves, included in the software, representing the relationship between the ratio of actual to potential evapotranspiration as a function of soil moisture content for three soil texture classes.

The total runoff generated is split between base flow and surface runoff according to a given baseflow index. The two components are routed separately and subsequently joined. A large number of sequential years can be processed, and the results of each year are summarized by a water balance table and a daily based rainfall runoff time series. An attempt has been made to restrict the amount of input data to the minimum.

Interactive manual calibration is advocated in order to allow better incorporation of field evidence and the experience of the model user. Field observations allowed for an approximate calibration at the hydrological unit level. Copyright © 2001 John Wiley & Sons, Ltd.
Measurement of atmospheric water vapour on the ground's surface by radio waves
Authors: Kishii Tokuo , Kuzuha Yasuhisa , Sugita Fumi , Hayano Michiko
Published: September 2002

Water vapour in the atmosphere and various meteorological phenomena are essential to the understanding of the mechanism of the water cycle. However, it is very difficult to observe water vapour in the atmosphere because the quantities are usually observed at a single point not over long intervals or in a specific plane or volume. Accordingly, the use of radio waves is considered to be necessary to observe water vapour. Radio waves can be transmitted over long intervals and across large areas, and generally speaking, the characteristics of radio waves change due to material in the atmosphere, especially water vapour. Usually absorption is used to observe the quantity of water vapour. But the relationship between absorption and the quantity of water vapour is not linear, so we try to utilize the phase difference between two radio waves as an alternative method. First, the relationship between the phase delay and the water vapour was induced by a physical equation and the resulting phase delay was found to be proportional to the quantity of water vapour. Furthermore, the phase difference between two separate points was observed by use of two radio waves in the field, specifically 84 GHz and 245 GHz. For reference and comparison, water vapour density in the atmosphere was simultaneously observed by meteorological observation. As a result, the density of the water vapour was found to be proportional to the phase difference between the two radio waves. The result also shows that this method is able to measure the diurnal changes in water vapour density in each season. Copyright © 2001 John Wiley & Sons, Ltd.
Evaluating the spatial and temporal distribution of snow accumulation, snowmelts and discharge in a multi basin scale: an application to the Tohoku Region, Japan
Authors: Motoya Ken , Yamazaki Takeshi , Yasuda Nobuhisa
Published: September 2002

The main aim of this study is to discuss the temporal and spatial distributions of the snow water equivalent, snowmelt and discharge in a multibasin scale (Tohoku Region, Japan; covering about 77 000 km2), using the heat budget model with the help of remote sensing (satellite images and meteorological radar). The calculated distributions of snow water equivalent were similar to that of the snow map obtained from the satellite images. At the same time, the seasonal variation of discharge in the three basins investigated (Yuda, covering 583 km2, Shichikasyuku, 237 km2 and Okutadami, 426 km2) was in good agreement with the observed one at the dam. Moreover, we conducted sensitivity tests for increasing solar radiation and air temperature by adding 10 W/m2 to the solar radiation and 1 degree to air temperature, respectively. The peaks of the snow cover area did not change so much, although the area in the snowmelt season decreased in these cases. The snow water equivalent in both cases became smaller than the control, particularly in the case of a 1 degree increase in air temperature. The snowmelt and discharge increased in the first half of the snowmelt period but were less than the control in the latter half. The model suggested in this study will be able to estimate changes in the hydrological elements related to snow, if a scenario of the climate change is provided. Copyright © 2001 John Wiley & Sons, Ltd.
Inhibition of glutathione S‐transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance
Authors: Mukanganyama Stanley , Widersten Mikael , Naik Yogeshkumar S. , Mannervik Bengt , Hasler Julia A.
Published: September 2002

A strategy to overcome multidrug resistance in cancer cells involves treatment with a combination of the antineoplastic agent and a chemomodulator that inhibits the activity of the resistance‐causing protein. The aim of our study was to investigate the effects of antimalarial drugs on human recombinant glutathione S‐transferase (GSTs) activity in the context of searching for effective and clinically acceptable inhibitors of these enzymes. Human recombinant GSTs heterologously expressed in Escherichia coli were used for inhibition studies. GST A1‐1 activity was inhibited by artemisinin with an IC50 of 6 μM, whilst GST M1‐1 was inhibited by quinidine and its diastereoisomer quinine with IC50s of 12 μM and 17 μM, respectively. GST M3‐3 was inhibited by tetracycline only with an IC50 of 47 μM. GST P1‐1 was the most susceptible enzyme to inhibition by antimalarials with IC50 values of 1, 2, 1, 4, and 13 μM for pyrimethamine, artemisinin, quinidine, quinine and tetracycline, respectively. The IC50 values obtained for artemisinin, quinine, quinidine and tetracycline are below peak plasma concentrations obtained during therapy of malaria with these drugs. It seems likely, therefore, that GSTs may be inhibited in vivo at doses normally used in clinical practice. Using the substrate ethacrynic acid, a diuretic drug also used as a modulator to overcome drug resistance in tumour cells, GST P1‐1 activity was inhibited by tetracycline, quinine, pyrimethamine and quinidine with IC50 values of 18, 27, 45 and 70 μM, respectively. The ubiquitous expression of GSTs in different malignancies suggests that the addition of nontoxic reversing agents such as antimalarials could enhance the efficacy of a variety of alkylating agents. © 2001 Wiley‐Liss, Inc.
Breast cancer incidence and estrogen receptor α in normal mammary tissue—An epidemiologic study among Japanese women in Japan and Hawaii
Authors: Lawson James S. , Field Andrew S. , Tran Dinh D. , Killeen Jeffrey , Maskarenic Gertraud , Ishikura Hiroshi , Trichopoulos Dimitrios
Published: September 2002

We have undertaken a study to examine whether the difference in breast cancer incidence between 2 populations of similar genetic background is reflected in a similar pattern of estrogen receptor α expression in normal mammary gland. Study participants were 92 Japanese women from Sapporo, Japan (mean age 48.2 years) and 49 Japanese women from Honolulu, Hawaii (mean age 45.4 years), who underwent biopsy indicating normal breast tissue or benign, nonproliferative breast disease in hospitals in Sapporo, Japan and Honolulu, Hawaii. The breast tissue samples were formalin‐fixed and paraffin‐embedded. The estrogen receptor immunohistochemistry assays were conducted using Dako kits. Japanese women in Hawaii, who have a higher incidence of breast cancer compared with Japanese women in Sapporo, also had, as predicted, higher mean percentage of estrogen receptor α‐positive normal mammary cells (2‐tailed test, p ∼ 0.09). The results of our study are compatible with the hypothesis that estrogen receptor α expression in normal mammary tissue increases breast cancer risk and they also indicate that the expression of these receptors is dependent, at least in part, on nongenetic factors. © 2001 Wiley‐Liss, Inc.
Lung cancer incidence in Australia: Impact of filter‐tip cigarettes with unchanged tar yields
Authors: Blizzard Leigh , Dwyer Terence
Published: September 2002

Filter‐tip cigarettes became popular in Australia in the late 1950s, but “tar” yields remained high for another decade. Because of this, the effect of filters independently of tar reductions can be estimated by comparing the age‐adjusted incidence of lung cancer for relevant birth cohorts of Australians. Separate analyses by histologic type may throw some light on the specific effects of filters. Age‐adjusted incidence of squamous cell carcinoma (SCC), small cell lung carcinoma (SCLC) and adenocarcinoma (AC) was estimated by Poisson regression for 5‐year birth cohorts of Australians using lung cancer registration data for 1982–95. To take account of changes in smoking prevalence, ever‐smoker less never‐smoker differences in age‐adjusted incidence were estimated. Comparisons were made for smokers born during 1930–34 and 1940–44. Smokers born in 1940–44 commenced smoking at the time of introduction of filter‐tips. Age‐adjusted incidence of SCC (−23%) and SCLC (−21%) but not AC (+7%) was lower for female smokers born during 1940–44. For male smokers, rates of SCC (−42%), SCLC (−43%) and AC (−24%) were each lower. The high rates overall of 1940s‐born women were due to disproportionately higher incidence of AC, the type that comprised 42% of diagnoses with histologic confirmation. In Australia, the switch to filter‐tip cigarettes prior to any reduction in tar yields was associated with reduced incidence of SCC and SCLC, and of AC for men only. Rates of AC were not reduced for women, indicating that other factors were important for this type of lung cancer. © 2001 Wiley‐Liss, Inc.
Family history and the risk of stomach cancer death in Japan: Differences by age and gender
Authors: Yatsuya Hiroshi , Toyoshima Hideaki , Mizoue Tetsuya , Kondo Takaaki , Tamakoshi Koji , Hori Yoko , Tokui Noritaka , Hoshiyama Yoshiharu , Kikuchi Shogo , Sakata Kiyomi , Hayakawa Norihiko , Tamakoshi Akiko , Ohno Yoshiyuki , Yoshimura Takesumi
Published: September 2002

Familial aggregation of stomach cancer has long been observed. The effect on disease risk of family history and its magnitude according to the type of affected relatives, however, is not well known. We conducted a prospective analysis using the JACC study (Japan Collaborative Cohort Study For Evaluation of Cancer Risk, sponsored by Monbusho) data. During the follow‐up period, 662 stomach cancer deaths were documented. A positive history of stomach cancer in one or more first‐degree relatives was associated with a significantly increased risk of death from the disease in both men (RR 1.60; 95% CI 1.11–2.31) and women (RR 2.47; 95% CI 1.50–4.06). In the subanalysis stratified by age, the association between positive family history and stomach cancer was stronger in the age group from 40–59 (RR 2.62; 95% CI 1.34–5.11 for men and RR 5.88; 95% CI 2.70–12.82 for women) than in the age group from 60–79 (RR 1.31; 95% CI 0.84–2.05 for men and RR 1.44; 95% CI 0.72–2.88 for women). In the age group from 40–59, men with father's history and women with mother's and sister's history of the disease had a significantly increased risk (RR 3.14; 95% CI 1.51–6.55, RR 10.46; 95% CI 4.54–24.12, RR 13.39; 95% CI 3.89–46.12, respectively). When 2 or more family members were affected, the increment in the risk was prominent especially in women (RR 9.45; 95% CI 4.46–20.05). These results suggest the existence of a certain subtype of stomach cancer that is inherited more often by women from one generation to the next in gender‐influenced fashion. Any preventive strategy should take into account the degree of individual susceptibility. © 2001 Wiley‐Liss, Inc.
Inhibition of tumor growth and metastatic spreading by overexpression of inter‐alpha‐trypsin inhibitor family chains
Authors: Paris Sébastien , Sesboüé Richard , Delpech Bertrand , Chauzy Claude , Thiberville Luc , Martin Jean‐Pierre , Frébourg Thierry , Diarra‐Mehrpour Maryam
Published: September 2002

The inter‐α trypsin inhibitor (ITI) family is a group of proteins built up from different combinations of 1 light chain (ITI‐L) and 3 highly homologous heavy chains (ITI‐H1, ‐H2 and ‐H3). To investigate a potential role of the ITI family chains in cancer and metastasis spreading, we engineered human H460M cell lines expressing both the green fluorescent protein (GFP) and one of these chains. These clones were subcutaneously injected in athymic nude mice, and lung metastasis number and primary tumor weight were determined after 28 days. Expression of the ITI‐L chain considerably decreased tumor weight and fluorescent lung metastasis number. ITI‐H1 and ITI‐H3 chain expression induced a significant decrease of metastasis number, whereas no decrease of tumor weight could be detected. In vitro, ITI‐L expression significantly decreased chemotaxis and ITI‐H1 and ITI‐H3 expression increased cell attachment. These results argue for the antitumoral or antimetastatic properties of ITI‐L, ‐H1 and ‐H3 chains. © 2001 Wiley‐Liss, Inc.
Transcriptional profiling of a human papillomavirus 33–positive squamous epithelial cell line which acquired a selective growth advantage after viral integration
Authors: Ruutu Merja , Peitsaro Panu , Johansson Bo , Syrjänen Stina
Published: September 2002

Alterations in gene expression represent key events in carcinogenesis. We have studied HPV‐induced cervical carcinogenesis, using an HPV‐33‐positive cell line (UT‐DEC‐1) established from a low‐grade vaginal dysplasia (VAIN‐I). Early‐passage cells contained HPV‐33 in episomal form, but these were superseded at later passages by cells carrying only integrated virus. To gain insight into the biologic significance of HPV integration, we compared the level of gene expression in normal vaginal keratinocytes, early‐passage and late‐passage UT‐DEC‐1 cells, using cDNA microarrays. Total RNA was isolated from cells by CsCl‐gradient centrifugation, reverse‐transcribed with MMLV reverse transcriptase and labeled with α‐32P ATP. A cDNA microarray expression profile analysis was performed with Clontech's Human Cancer 1.2 cDNA expression array kit. The 16 upregulated genes (cut‐off 2‐fold), identified by comparing both cell types to control keratinocytes, appeared to support cell‐cycle progression or to be functional in mitosis. These included, e.g., MCM4 DNA replication licensing factor, cdc2p34 and chromatin assembly factor 1 p48 subunit. Downregulated genes (44 altogether) interfered with apoptosis and cell adhesion, including the apoptosis‐inducing genes FRAP, Bik and caspase‐9 precursor. The most significant differences between the late and early passages (29 and 46 constantly up‐ and downregulated genes without any fluctuation) were overexpression of the transcription factors E2F5 with its dimerization partner DP1, NF‐κB and serine/threonine kinases and underexpression of enzymes of the MAPK pathway. Acquisition of a selective growth advantage after viral integration might be explained by a major shift from a MAPK pathway to cell‐cycle dysregulation (G2/M). © 2002 Wiley‐Liss, Inc.
Pharmacokinetic and tumor‐seeking properties of recombinant and nonrecombinant anti‐carcinoembryonic antigen antibody fragments
Authors: Groulet Agnès , Dorvillius Mylène , Pèlegrin André , Barbet Jacques , Baty Daniel
Published: September 2002

Production of recombinant antibody fragments in bacterial expression systems results in intentional or fortuitous differences compared to the original products prepared by hybridoma technology. These differences may have significant effects not only on antigen‐binding properties but also on pharmacokinetic and tumor‐seeking properties. Our major goal was to investigate some of these possible differences. We produced in Escherichia coli an rFab′ fragment containing only 1 cysteine residue in the hinge region; the fragment was derived from a mouse MAb (F6) specific for CEA. The rFab′ had a slightly lower m.w. and a higher isoelectric point relative to the corresponding nonrecombinant fragment (pFab′). This was explained by the absence of N‐glycosylation on the Vκ domain of rFab′. Vκ glycosylation had no significant effect on antibody‐binding affinity and kinetics. However, rFab′ was eliminated from the circulation much faster than pFab′, and the maximal dose accumulated in the tumor was reduced relative to pFab′. Thus, glycosylation appears to modify the targeting efficiency of antibody fragments. rF(ab′)2 fragments were obtained either spontaneously from the culture supernatant of E. coli or by chemical cross‐linking [rcF(ab′)2]. We observed improved tumor targeting with rcF(ab′)2 compared to rF(ab′)2, which could be explained by the greater stability of the thioether compared to the disulfide linkage. These results demonstrate that a single cysteine residue in the hinge region of rFab′ is particularly well suited to prepare stable, chemically coupled, bivalent or bispecific antibodies, avoiding intrahinge disulfide bonding and thus achieving higher production yields. © 2002 Wiley‐Liss, Inc.
Specific immunotherapy against occult cancer metastases
Authors: Lu Weixin , Dong Zhongyun , Donawho Cherrie , Fidler Isaiah J.
Published: September 2002

We investigated the efficacy of a preparation containing High Five (H5) insect cells infected with recombinant baculovirus encoding the murine interferon‐β gene (H5BVIFN‐β) against established primary tumors and occult lung metastases. Injection of live or lyophilized H5BVIFN‐β into established subcutaneous tumors of the highly metastatic murine UV‐2237m fibrosarcoma or K‐1735M2 melanoma in syngeneic mice eradicated both primary tumors and preexisting lung metastases. The therapeutic effects of H5BVIFN‐β were not observed in nude mice and were diminished in syngeneic mice depleted of CD4+ and CD8+ T cells. Immunohistochemical staining showed that tumors injected with H5BVIFN‐β were densely infiltrated by CD4+ and CD8+ T cells in mice with normal CD4/CD8 complement. These data demonstrate that, unlike most immunologic approaches in which prophylaxis can be achieved but eradication of established tumor is rare, lyophilized preparations of H5BVIFN‐β can serve as a novel immunotherapy against both primary tumors and their occult metastases. © 2002 Wiley‐Liss, Inc.