bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Cystine Knots in Collagen Folding and Stability, Part I. Conformational Properties of (Pro‐Hyp‐Gly)5 and (Pro‐(4S)‐FPro‐Gly)5 Model Trimers with an Artificial Cystine Knot
Authors: Barth Dirk , Musiol Hans‐Jürgen , Schütt Markus , Fiori Stella , Milbradt Alexander G. , Renner Christian , Moroder Luis
Published: July 2003

In analogy to the cystine knots present in natural collagens, a simplified disulfide cross‐link was used to analyse the conformational effects of a C‐terminal artificial cystine knot on the folding of collagenous peptides consisting of solely (Pro‐Hyp‐Gly) repeating units. Assembly of the α chains into a heterotrimer by previously applied regioselective disulfide‐bridging strategies failed because of the high tendency of (Pro‐Hyp‐Gly)5 peptides to self‐associate and form homotrimers. Only when side‐chain‐protected peptides were used, for example in the Hyp(tBu) form, and a new protection scheme was adopted, selective interchain‐disulfide cross‐linking into the heterotrimer in organic solvents was successful. This unexpected strong effect of the conformational properties on the efficiency of well‐established reactions was further supported by replacing the Hyp residues with (4S)‐fluoroproline, which is known to destabilise triple‐helical structures. With the related [Pro‐(4S)‐FPro‐Gly]5 peptides, assembly of the heterotrimer in aqueous solution proceeded in a satisfactory manner. Both the intermediates and the final fluorinated heterotrimer are fully unfolded in aqueous solution even at 4 °C. Conversely, the disulfide‐crossbridged (Pro‐Hyp‐Gly)5 heterotrimer forms a very stable triple helix. The observation that thermal unfolding leads to scrambling of the disulfide bridges was unexpected. Although NMR experiments support an extension of the triple helix into the cystine knot, thermolysis is not associated with the unfolding process. In fact, the unstructured fluorinated trimer undergoes an equally facile thermodegradation associated with the intrinsic tendency of unsymmetrical disulfides to disproportionate into symmetrical disulfides under favourable conditions. The experimental results obtained with the model peptides fully support the role of triple‐helix nucleation and stabilisation by the artificial cystine knot as previously suggested for the natural cystine knots in collagens.
The Role of Cystine Knots in Collagen Folding and Stability, Part II. Conformational Properties of (Pro‐Hyp‐Gly)n Model Trimers with N‐ and C‐Terminal Collagen Type III Cystine Knots
Authors: Barth Dirk , Kyrieleis Otto , Frank Sabine , Renner Christian , Moroder Luis
Published: July 2003

In mature collagen type III the homotrimer is C‐terminally cross‐linked by an interchain cystine knot consisting of three disulfide bridges of unknown connectivity. This cystine knot with two adjacent cysteine residues on each of the three α chains has recently been used for the synthesis and expression of model homotrimers. To investigate the origin of correct interchain cysteine pairings, (Pro‐Hyp‐Gly)n peptides of increasing triplet number and containing the biscysteinyl sequence C‐ and N‐terminally were synthesised. The possibilities were that this origin may be thermodynamically coupled to the formation of the collagen triple helix as happens in the oxidative folding of proteins, or it could represent a post‐folding event. Only with five triplets, which is known to represent the minimum number for self‐association of collagenous peptides into a triple helix, air‐oxidation produces the homotrimer in good yields (70 %), the rest being intrachain oxidised monomers. Increasing the number of triplets has no effect on yield suggesting the formation of kinetically trapped intermediates, which are not reshuffled by the glutathione redox buffer. N‐terminal incorporation of the cystine knot is significantly less efficient in the homotrimerisation step and also in terms of triple‐helix stabilisation. Compared to an artificial C‐terminal cystine knot consisting of two interchain disulfide bridges, the collagen type III cystine knot produces collagenous homotrimers of remarkably high thermostability, although the concentration‐independent refolding rates are not affected by the type of disulfide bridging. Since the natural cystine knot allows ready access to homotrimeric collagenous peptides of significantly enhanced triple‐helix thermostability it may well represent a promising approach for the preparation of collagen‐like innovative biomaterials. Conversely, the more laborious regioselectively formed artificial cystine knot still represents the only synthetic strategy for heterotrimeric collagenous peptides.
Construction of Artificial Signal Transducers on a Lectin Surface by Post‐Photoaffinity‐Labeling Modification for Fluorescent Saccharide Biosensors
Authors: Nagase Tsuyoshi , Nakata Eiji , Shinkai Seiji , Hamachi Itaru
Published: July 2003

A new general method, post‐photoaffinity‐labeling modification (PPALM), for constructing fluorescent saccharide biosensors based on naturally occurring saccharide‐binding proteins, lectins, is described in detail. An active‐site‐directed incorporation of a masked reactive site into a lectin was conducted by using a photoaffinity labeling technique followed by demasking and then chemical modification to yield a fluorescent lectin. Two photoaffinity labeling reagents were designed and synthesized in this study. The labeling reagent with a photoreactive site appended through a disulfide link to a mannoside unit was bound to the saccharide‐binding pocket of the lectin concanavalin A (Con A). After light irradiation, the mannoside unit was cleaved by reduction. The unique thiol group thus produced was site‐specifically modified with various fluorescent groups (dansyl, coumarin, or dimethylaminobenzoate derivatives) to afford fluorescent Con As. The labeling site was characterized by protease‐catalyzed digestion followed by HPLC, MALDI‐TOF MS, and tandem mass–mass spectrometry; these methods indicated that the photolabeling step is remarkably site specific. Strong fluorescence was observed in the engineered Con A with a fluorophore, and the emission changed sensitively upon saccharide complexation. The binding constants for various saccharides were determined by fluorescence titration and demonstrated that the binding selectivity and affinity of the engineered Con As are comparable to those of native Con A. The red shift of the emission maximum, the decrease in the fluorescence anisotropy of the dansyl unit, and the increase in the twisted intramolecular charge transfer emission caused by sugar binding to the engineered Con A explicitly indicate that the microenvironment of the appended fluorophores changes from a restricted and relatively hydrophobic environment into a rather freely mobile and hydrophilic environment.
Intramolecular Dimers: A New Design Strategy for Fluorescence‐Quenched Probes
Authors: Johansson Mary Katherine , Cook Ronald M.
Published: July 2003

Fluorogenic probes dual‐labeled with reporter and quencher dyes use a change in fluorescence to monitor biochemical events (e.g., substrate binding or enzyme digestion). Such events change the reporter–quencher distance, which affects fluorescence. Recently, it is has been shown that static quenching through intramolecular dimers is an important mechanism that can sometimes be more efficient than Förster resonance energy transfer (FRET).
Cover Picture: Intramolecular Dimers: A New Design Strategy for Fluorescence‐Quenched Probes (Chem. Eur. J. 15/2003)
Authors: Johansson Mary Katherine , Cook Ronald M.
Published: July 2003

The cover picture shows a 96‐well plate illuminated by a UV lamp and viewed through a cutoff filter. All wells contain a Cy3.5‐BHQ1 (reporter quencher) dual‐labeled oligonucleotide probe in buffer. Complementary sequence was added to three columns. The probe is virtually nonfluorescent due to static quenching through formation of an intramolecular dimer. Addition of complement separates the dye and quencher, causing fluorescence. Intramolecular dimers as a new design strategy for fluorescence‐quenched probes is discussed by M. K. Johansson and R. M. Cook in the Concepts article on p. 3466 ff.
Organization of glomeruli in the main olfactory bulb of Xenopus laevis tadpoles
Authors: Nezlin Leonid P. , Heermann Stephan , Schild Detlev , Rössler Wolfgang
Published: July 2003

Structural and functional investigations were carried out to study olfactory glomeruli in the main olfactory bulb (OB) in tadpoles of the clawed frog, Xenopus laevis. Calcium imaging of odor response patterns of OB neurons revealed that the synapses within the glomeruli are functional. Tracing axons of individual olfactory receptor neurons (ORNs), dendrites of mitral/tufted (M/T) cells and processes of periglomerular interneurons indicate that the glomerular architecture is solely determined by terminal branches of ORN axons and tufts of M/T primary dendrites. The small population of periglomerular neurons forms wide‐field arborizations that always extend over many glomeruli, enter the glomeruli, but lack any glomerular tufts. Antibodies to synaptophysin indicate a high density of synapses within glomeruli, which was further confirmed at the ultrastructural level and quantified to approximately 0.5 synaptic sites per μm2. Combining immunocytochemistry and ultrastructural investigations, we show that glomeruli in Xenopus laevis tadpoles lack any cellular borders. Glomeruli are surrounded neither by periglomerular somata nor by glial processes. Taken together, our results demonstrate that olfactory glomeruli in Xenopus laevis tadpoles (1) are fully functional, (2) are spheroidal neuropil aggregations of terminal tufts of ORNs and tufts of primary dendrites of M/T cells, and (3) are not enwrapped by a border formed by juxtaglomerular cells. J. Comp. Neurol. 464:257–268, 2003. © 2003 Wiley‐Liss, Inc.
Load redundancy elimination on executable code
Authors: Fernández Manel , Espasa Roger , Debray Saumya
Published: August 2003

Optimizations performed at link time or directly applied to final program executables have received increased attention in recent years. This paper discusses the discovery and elimination of redundant load operations in the context of a link‐time optimizer, an optimization that we callLoad Redundancy Elimination (LRE). Our experiments show that between 50% and 75% of a program's memory references can be considered redundant because they are accessing memory locations that have been referenced less than 200–400 instructions away. We then present three profile‐based LRE algorithms targeted at optimizing away these redundancies. Our results show that between 5% and 30% of the redundancy detected can indeed be eliminated, which translates into program speedups of around 8%. We also test our algorithm assuming different cache latencies, and show that, if latencies continue to grow, the load redundancy elimination will become more important. Copyright © 2003 John Wiley & Sons, Ltd.
Tractable inference for probabilistic data models
Authors: Csato Lehel , Opper Manfred , Winther Ole
Published: August 2003

We present an approximation technique for probabilistic data models with a large number of hidden variables, based on ideas from statistical physics. We give examples for two nontrivial applications. © 2003 Wiley Periodicals, Inc.
Perspectives of the high‐dimensional dynamics of neural microcircuits from the point of view of low‐dimensional readouts
Authors: Häusler Stefan , Markram Henry , Maass Wolfgang
Published: August 2003

We investigate generic models for cortical microcircuits, i.e., recurrent circuits of integrate‐and‐fire neurons with dynamic synapses. These complex dynamic systems subserve the amazing information processing capabilities of the cortex, but are at the present time very little understood. We analyze the transient dynamics of models for neural microcircuits from the point of view of one or two readout neurons that collapse the high‐dimensional transient dynamics of a neural circuit into a one‐ or two‐dimensional output stream. This stream may for example represent the information that is projected from such circuit to some particular other brain area or actuators. It is shown that simple local learning rules enable a readout neuron to extract from the high‐dimensional transient dynamics of a recurrent neural circuit quite different low‐dimensional projections, which even may contain “virtual attractors” that are not apparent in the high‐dimensional dynamics of the circuit itself. Furthermore it is demonstrated that the information extraction capabilities of linear readout neurons are boosted by the computational operations of a sufficiently large preceding neural microcircuit. Hence a generic neural microcircuit may play a similar role for information processing as a kernel for support vector machines in machine learning. We demonstrate that the projection of time‐varying inputs into a large recurrent neural circuit enables a linear readout neuron to classify the time‐varying circuit inputs with the same power as complex nonlinear classifiers, such as a pool of perceptrons trained by the p‐delta rule or a feedforward sigmoidal neural net trained by backprop, provided that the size of the recurrent circuit is sufficiently large. At the same time such readout neurons can exploit the stability and speed of learning rules for linear classifiers, thereby overcoming the problems caused by local minima in the error function of nonlinear classifiers. In addition it is demonstrated that pairs of readout neurons can transform the complex trajectory of transient states of a large neural circuit into a simple and clearly structured two‐dimensional trajectory. This two‐dimensional projection of the high‐dimensional trajectory can even exhibit convergence to virtual attractors that are not apparent in the high‐dimensional trajectory. © 2003 Wiley Periodicals, Inc.
Nonequilibrium statistical mechanics of swarms of driven particles
Authors: Ebeling Werner , Erdmann Udo
Published: August 2003

As a rough model for the collective motions of cells and organisms we develop here the statistical mechanics of swarms of self‐propelled particles. Our approach is closely related to the recently developed theory of active Brownian motion and the theory of canonical‐dissipative systems. Free motion and motion of a swarms confined in an external field is studied. Briefly, the case of particles confined on a ring and interacting by repulsive forces is studied. In more detail we investigate self‐confinement by Morse‐type attracting forces. We begin with pairs N = 2; the attractors and distribution functions are discussed, then the case N > 2 is discussed. Simulations for several dynamical modes of swarms of active Brownian particles interacting by Morse forces are presented. In particular we study rotations, drift, fluctuations of shape, and cluster formation. © 2003 Wiley Periodicals, Inc.
Statistical learning theory, capacity, and complexity
Authors: Schölkopf Bernhard
Published: August 2003

We give an exposition of the ideas of statistical learning theory, followed by a discussion of how a reinterpretation of the insights of learning theory could potentially also benefit our understanding of a certain notion of complexity. © 2003 Wiley Periodicals, Inc.
Expandable graphite: A fire retardant additive for polyurethane coatings
Authors: Duquesne Sophie , Bras Michel Le , Bourbigot Serge , Delobel René , Vezin Hervé , Camino Giovanni , Eling Berend , Lindsay Chris , Roels Toon
Published: July 2003

The study investigates the mechanism of fire retardancy induced by expandable graphite in a polyurethane coating. A complementary investigation to the spectroscopic study performed previously confirms that little interaction occurs between the matrix and the additive. X‐ray diffraction study demonstrates that the crystalline structure of the graphite is maintained during the intumescent process. The presence of free radicals in the protective shield is then demonstrated but at low concentration compared with classical intumescent systems, such as for example polyurethane/ammonium polyphosphate. Finally, the physical properties of the char are then investigated. Blowing measurement demonstrates the high degree of expansion of the layer which may partially explain the fire retardant performance of expandable graphite in polyurethane. Surface analyses by optical microscopy and optical profilometry also enable a better understanding of the efficiency of expandable graphite. In the absence of a fire retardant additive the coating displays cracks and holes, providing a pathway for oxygen diffusion as well as heat and mass transfer between the flame and the virgin polymer. Both phenomena are limited when expandable graphite is added to polyurethane. Consequently, fire retardancy of expandable graphite results more from a physical than from a chemical action. Copyright © 2003 John Wiley & Sons, Ltd.
Ignition and combustion of low‐density polyimide foam
Authors: Hshieh Fu‐Yu , Hirsch David B. , Beeson Harold D.
Published: July 2003

The ignition, flaming and smoldering combustion of low‐density polyimide foam have been studied using a cone calorimeter. Low‐density polyimide foam exhibits a high ignition resistance. The minimum heat flux for the ignition of flaming combustion ranges from 48 to 54 kW/m2. This minimum heat flux also indicates the heat flux for transition from smoldering to flaming combustion. The flaming combustion results show that the heat release rate of low‐density polyimide foam is very low even at a high incident heat flux of 75 kW/m2. The smoldering combustion results show that the smoldering of low‐density polyimide foam becomes significant when the incident heat flux is greater than 30 kW/m2. The smoldering combustion of low‐density polyimide foam cannot be self‐sustaining when the external heat source is removed. Copyright © 2003 John Wiley & Sons, Ltd.
Characterization of the fire environments in central offices of the telecommunications industry
Authors: Tewarson Archibald
Published: July 2003

Eight free burning and two sprinklered fire tests were performed with electrical cable trays and live digital switch racks in a large enclosure to simulate telecommunications central office (TCO) fires started by electrical overheating. Very‐slow‐growing (non‐flaming), slower‐growing (partially flaming) and low‐intensity‐faster‐growing (flaming) fires releasing gray‐white, gray, and black smoke, respectively, were observed in the tests. Under quiescent conditions present in the unvented enclosure fire tests for cables, very‐slow‐growing fires were detected in about 1452 s, whereas the slower‐growing fires were detected in about 222 s by commercial fire detectors. Under ventilation conditions typical of TCOs, detection times were very similar for the five types of commercial TCOs fire detectors used in the tests. The average detection times for slower‐growing fires (cable fires) and low‐intensity‐faster‐growing fires (digital switch rack fires) were 242±17% and 249±11%s respectively.

The TCO procedures to reduce smoke damage from fires (on fire detection, inlet ventilation flow is turned off and exhaust flow is turned on) were found to be beneficial. The extent of smoke damage decreased significantly with an increase in the exhaust flow rate. The chloride ion mass deposition suggested that equipment recovery would be possible in the smoke environment if the cable vapor concentration could be reduced below about 3 g/m3.

The metal corrosion rate was found proportional to the 0.6th power of the smoke concentration, similar to that found for the corrosion of metal surfaces exposed to aqueous solutions of HCl and HNO3 and for acid rain with no protective layer at the surface. Sprinkler water was found to wash down the smoke deposits on the surfaces with little indication of corrosion enhancement. Copyright © 2003 John Wiley & Sons, Ltd.
The value of the change in health in Sweden 1980/81 to 1996/97
Authors: Burström Kristina , Johannesson Magnus , Diderichsen Finn
Published: July 2003

The study aimed to estimate the value of the change in health in Sweden 1980/81 to 1996/97. Quality‐adjusted life years (QALYs) for men and women at specific ages were estimated for 1980/81, 1988/89 and 1996/97, by combining survival rates and health state scores. Data from the Swedish Survey of Living Conditions (n=39 966) were used to estimate age‐specific health state scores. Responses to selected survey questions were mapped into the EQ‐5D measure, using the UK EQ‐5D index tariff to derive health state scores. The monetary value of a QALY was assumed to be $100 000. Life expectancy for infants increased by 3.68 years for males and 2.70 years for females between 1980/81 and 1996/97. Average health status decreased in younger age groups whereas it increased in older age groups. Expected QALYs for infants increased by 2.64 for males and 0.54 for females. With 3% discounting the gain was 0.11 QALYs ($11 000) among males and a loss by 0.58 QALYs ($58 000) among females. The corresponding gain in discounted QALYs for a 75‐year‐old was 1.15 ($115 000) and 0.80 ($80 000), respectively. It is concluded that older persons have experienced considerable health gains whereas the health gains have been small or non‐existent for younger women. Copyright © 2002 John Wiley & Sons, Ltd.
Construction of the contingent valuation market in health care:a critical assessment
Authors: Smith Richard D.
Published: July 2003

Contingent valuation (CV) has been criticised for being too hypothetical, with expressed values bearing little relation to actual values. The magnitude of this divergence, however, depends upon how realistic and believable the contingent market is. This paper presents an overview of five key aspects in the construction of the contingent market: (i) scenario development and presentation; (ii) payment vehicle; (iii) expression of risk; (iv) time period of valuation; and (v) survey administration. CV studies in health care since 1985, totalling 111, are critically reviewed with respect to these five aspects. It is concluded that CV studies in health care have performed poorly in the construction, specification and presentation of the contingent market, and that there has been little, if any, improvement in this respect over the last 15 years. Suggestions are made concerning why this may be the case, and how the construction of the contingent market may be improved in future. Copyright © 2002 John Wiley & Sons, Ltd.
Hospital efficiency targets
Authors: Jacobs Rowena , Dawson Diane
Published: July 2003

Cost‐efficiency targets, used to encourage downward pressure on hospital unit costs, have been employed within the UK NHS for many years. There has been considerable speculation that these targets create incentives to reduce beds and increase occupancy rates at the expense of holding spare capacity to accommodate fluctuations in emergency admissions. This research used panel data for the period 1994/1995–1999/2000, supplemented by a series of semi‐structured interviews, to explore the strategies Trusts employ to reduce unit costs. No relationship could be found between published targets and changes in unit costs, nor that targets were successful in reducing the dispersion of unit costs over time. Interviews revealed that efficiency gains required of Trusts, usually dictated by the local health economy, often bore no correspondence to the national or regional published targets. Results further indicated that contrary to prior speculation, Trusts divide into two distinct groups, those with high occupancy rates and those with a high proportion of free beds to accommodate emergencies, with Trust characteristics displaying stability over time. A pressing need for future work is the development of measures to encourage efficiency that take account of quality improvement. Copyright © 2002 John Wiley & Sons, Ltd.
Public spending on health care and the poor
Authors: Gupta Sanjeev , Verhoeven Marijn , Tiongson Erwin R.
Published: July 2003

This paper uses new cross‐country data to assess the relationship between public spending on health care and the health status of the poor. Data are drawn from two sources: (i) existing data on health status by income quintile tabulated from demographic health surveys in 44 countries; and (ii) our estimates of the health status of the poor in over 70 countries drawn from a new technique in decomposing social indicators. Our estimates confirm that the poor have significantly worse health status than the nonpoor and the regression results provide new evidence that public spending on health care matters more to them. However, the results suggest that increased public spending alone will not be sufficient to significantly improve health status. Copyright © 2002 John Wiley & Sons, Ltd.
The missing link: on the line between C and E
Authors: Brouwer Werner B.F. , Rutten Frans F.H.
Published: July 2003

In this paper it is argued that the separation of elements associated with the time spent by the patient is not conducted in a consistent way. This is the case for income (for which there at least has been some attention) and for other time elements like lost unpaid work, leisure and role‐functioning. The use of general rather than specific preferences in health state assessments makes the separation of time‐elements into costs and effects difficult. While costs are calculated specifically for the patient group under study, effects are normally derived from preferences in the general public. The characteristics of these two groups in terms of (the opportunity of) spending time on activities need not coincide. The use of specific time‐group valuations of health states may be a good alternative to using general health state valuations. Copyright © 2002 John Wiley & Sons, Ltd.
The TTO method and procedural invariance
Authors: Spencer Anne
Published: July 2003

In a pilot study we investigate whether the inferences we draw about people's preferences towards health care treatments are altered if we vary the procedure that is used to elicit these preferences. In a conventional time trade‐off (TTO) question, respondents express their preferences towards treatment by comparing a period of ill‐health with a shorter period in a higher quality of life. In our less conventional TTO question, we vary the procedure by asking respondents their preferences towards treatment by comparing a period of ill‐health with a longer period in a lower quality of life. The quantitative data are equivocal about whether preferences for treatment differ between the conventional and unconventional questions. The qualitative data support the notion of contrasting issues in the questions that involve prolonging time in a lower quality of life and appear to account for a failure to find quantitative differences in all of the questions. Copyright © 2002 John Wiley & Sons, Ltd.
Methodological issues raised by preference‐based approaches to measuring the health status of children
Authors: Petrou Stavros
Published: July 2003

This paper identifies and discusses a number of methodological issues that require consideration when applying preference‐based approaches to the measurement of the health status of children. It is argued that the decision about which dimensions of health status to incorporate into health state descriptions or classifications should depend, in part, upon whether the measure will be used to inform resource allocation within or across age groups. In addition, the paper identifies and discusses a number of methodological issues surrounding the appropriate respondents for descriptions and valuations of health status in different contexts; potential sources of bias in the description and valuation processes; and the psychometric integrity of alternative measurement approaches. Copyright © 2003 John Wiley & Sons, Ltd.
Sediment transport problems in Nepal evaluated by the SETRIC model
Authors: Depeweg Herman , Paudel K. P.
Published: July 2003

The SETRIC mathematical model has been developed to study the interrelationship between water flow and sediment transport in irrigation canals under changing flow conditions. The effects of flow control structures, water delivery schedules and maintenance plans on the overall response of the canal with respect to sediment transport can be studied with this model. The earlier model in QuickBasic has been transferred to a Visual Basic environment, which has resulted in an interactive and user‐friendly interface.

The model has been used to evaluate the design of the Sunsari Morang irrigation system in Nepal for different operation and maintenance plans. With the model, a simultaneous simulation of a wide range of variables has been studied that affect the sediment transport performance of the canal. Even though it might be premature to present quantitative results without detailed calibration of the model, the qualitative results of the model are encouraging. The simulation results revealed some fundamental issues, which, if addressed properly during the design, will lead to a improved canal system in terms of operation and maintenance. Copyright © 2003 John Wiley & Sons, Ltd.
Frequency analysis of extreme rainfall using L‐moment
Authors: Lee Soon H. , Maeng Sung J.
Published: July 2003

This research seeks to derive the design rainfalls through the L‐moment with the test of homogeneity, independence and outlier of data on annual maximum daily rainfall in 38 Korean rainfall stations. To select the appropriate distribution of annual maximum daily rainfall data according to rainfall station, generalized extreme value (GEV), generalized logistic (GLO) and generalized pareto (GPA) probability distributions were applied and their aptness was judged using an L‐moment ratio diagram and the Kolmogorov–Smirnov (K–S) test. The GEV and GLO distributions were selected as the appropriate distributions. Their parameters were estimated from the observed and simulated annual maximum daily rainfall using Monte Carlo techniques. Design rainfalls were then derived using the L‐moment. Appropriate design rainfalls were suggested by doing a comparative analysis of design rainfall from the GEV and GLO distributions according to rainfall stations. Copyright © 2003 John Wiley & Sons, Ltd.
Comparison and analysis of design floods by the change in the order of LH‐moment methods
Authors: Lee Soon H. , Maeng Sung J.
Published: July 2003

This research seeks to derive the design floods through the appropriate order of LH‐moments with the test of homogeneity, independence and outlier of data on annual maximum floods in six Korean watersheds. To select the appropriate probability distribution for annual maximum flood data according to watershed, we applied the generalized extreme value (GEV), generalized logistic (GLO) and generalized Pareto (GPA) distributions. We arranged L, L1, L2, L3 and L4‐moment method theories by the change in the order of LH‐moment (parameter estimation method) according to three probability distributions, and presented LH‐moment ratio diagrams, i.e. L, L1, L2, L3 and L4‐moment ratio diagrams. We judged the suitability of the applied GEV, GLO and GPA distributions through the LH‐moment ratio diagrams and the Kolmogorov–Smirnov (K–S) test. We derived the parameter and design flood of the appropriate distribution using L, L1, L2, L3 and L4‐moment methods, targeting the observed and the simulated annual maximum flood through Monte Carlo techniques. By comparing and analyzing design floods derived through LH‐moment methods and the appropriate distribution according to watershed, we presented the appropriate order of LH‐moments that can derive appropriate design floods. Copyright © 2003 John Wiley & Sons, Ltd.
Coercive and cooperative policy designs: moving beyond the irrigation system
Authors: Johnson Clare L. , Handmer John W.
Published: July 2003

The governance and management of large‐scale irrigation schemes involves the integration of the formal and informal rules and responsibilities of actors at different system spatial scales. To achieve sustainable water management in the irrigated sector an understanding of the interlinkage between these actors is essential. It is to this interlinkage that this paper is focused.

Drawing on research in environmental and hazard management, this paper explores the usefulness of applying a coercive/cooperative policy design framework to the study of irrigation management in a developing country context. It is argued that such a framework is a useful theoretical construct for exploring the multi‐level relationships between governments, irrigation agencies and farmers in the governance and management of large‐scale irrigated agriculture. Using the Muda irrigation scheme as a case study, this framework illustrates how an apparent mismatch between coercive governance and cooperative management influences the attainment of key policy objectives. Copyright © 2003 John Wiley & Sons, Ltd.
Irrigation management turnover: an option for improved utilization of limited water resources in Pakistan
Authors: Latif Muhammad , Pomee Muhammad Saleem
Published: July 2003

Underperformance of the irrigation systems and poor cost recovery from irrigated area in Pakistan have been a source of concern for the last few decades and since then it has been the subject of considerable external assistance and internal policy reforms. To address these problems in the management of irrigation systems, the World Bank proposed a number of institutional changes for irrigation management turnover (IMT). After thorough consideration it was decided to decentralize instead of privatizing the irrigation system management and to promote farmers' participation in the system management. Under these reforms, management at secondary canal level has recently been handed over to the farmers' organizations (FOs) of selected distributaries at a pilot scale.

This study was designed to evaluate the farmer‐managed distributary in southern Punjab. Initial field measurements revealed that hydraulic aspects of the irrigation service delivered by the FO management have been significantly improved and as a result a highly proportionate and equitable water distribution pattern was observed, particularly at the tail reaches of the distributary during the post‐transfer scenario. Due to effective FO management farmers' interventions to increase the outlet discharge by illegal means have almost ceased. As a result of these improvements made by the FO in system management the extent of irrigated area has on average increased by 6–7% even under severe drought and continued famine‐like conditions prevailing in the country during recent years. Most importantly, cost recoveries have increased by an amount of 14% for summer and 23% for winter growing seasons respectively from the irrigated area of the distributary. Thus experience from the Hakra 4‐R distributary has shown that even under undesirable natural circumstances IMT was quite effective in achieving the key targets of the institutional reforms launched at pilot scale in the country. Copyright © 2003 John Wiley & Sons, Ltd.
Comparison of three calibration procedures for TDR soil moisture sensors
Authors: Quinones H. , Ruelle P. , Nemeth I.
Published: July 2003

The application of time domain reflectometry (TDR) principles to determine soil water content has been widely accepted as an alternative method since Topp et al. (1980) proposed an empirical relationship between the dielectric constant of soil and soil moisture content. However, a wide range of studies have made it clear that the proposed function has only restricted validity. Although the response of the TDR signal shows a steady correlation with soil moisture, it is also affected by others factors related to the physical and chemical nature of soil and the solute characteristics of soil solution. It is therefore necessary to determine a particular calibration for each situation. Three methods are used to calibrate a TDR sensor. First, two well‐known methods are compared: non‐continuous wetting on one hand, and continuous wetting by dripping of a soil sample on the other. The third consists of the progressive introduction of a sensor in a soil sample with a known moisture content. The three methods all lead to similar consistent relationships. The methods are validated using field data taking into account spatial variation of measurement at a given date and water inputs and uptakes under an irrigated corn crop during a growing season. Copyright © 2003 John Wiley & Sons, Ltd.
A method to estimate soil‐water movement under a trickle surface line source, with water extraction by roots
Authors: Elmaloglou St. , Malamos N.
Published: July 2003

The analysis of local infiltration from a surface line source of trickle irrigation in two homogeneous, unsaturated soils, using three wetting rates in each soil is presented. A method to determine the depth of the wetted soil volume under a trickle line is described. The proposed method is based on numerical results from a plane flow model, which takes into account water uptake by roots, and separates the phenomenon in two phases; the length of each phase depends on the duration of the irrigation and the soil. The empirical relationships, an exponential for the stage of the infiltration and a polynomial for the stage after the end of the irrigation, are only time dependent in order to achieve simplicity. Five statistical criteria were used to evaluate the quality of the method's results: average error (AE), root mean square error (RMSE), root mean square (RMS), modeling efficiency (EF) and coefficient of residual mass (CRM), in combination with goodness of fit, R2. The agreement between the numerical results and the values calculated by the empirical relationships was very satisfactory, showing that the combined use of an exponential and a polynomial empirical relationship can reasonably be used to calculate the vertical movement of the wetting front through the soil profile. Copyright © 2003 John Wiley & Sons, Ltd.
In vitro human phase I metabolism of xenobiotics I: Pesticides and related compounds used in agriculture and public health, may 2003
Authors: Hodgson Ernest
Published: July 2003

This is the first revision of a database covering human phase I enzymes and their isoforms that metabolize pesticides and related compounds. The original version included enzymes that metabolize chloroacetamide and triazine herbicides, and organophosphorus insecticides. This revision also includes carbamate, nicotinoid, and pyrethroid insecticides and insect repellents. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:201–206, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10080
Diabetes and mitochondrial bioenergetics: Alterations with age
Authors: Ferreira Fernanda M. , Palmeira Carlos M. , Seiça Raquel , Moreno António J. , Santos Maria S.
Published: July 2003

Several studies have been carried out to evaluate the alterations in mitochondrial functions of diabetic rats. However, some of the results reported are controversial, since experimental conditions, such as aging, and/or strain of animals used were different. The purpose of this study was to evaluate the metabolic changes in liver mitochondria, both in the presence of severe hyperglycaemia (STZ‐treated rats) and mild hyperglycaemia (Goto‐Kakizaki (GK) rats). Moreover, metabolic alterations were evaluated both at initial and at advanced states of the disease.

We observed that both models of type 1 and type 2 diabetes presented alterations on respiratory chain activity. Because of continual severe hyperglycaemia, 9 weeks after the induction of diabetes, the respiratory function declined in STZ‐treated rats, as observed by membrane potential and respiratory ratios (RCR, P/O, and FCCP‐stimulated respiration) assessment. In contrast, GK rats of 6 months age presented increased respiratory ratios.

To localize which respiratory complexes are affected by diabetes, enzymatic respiratory chain activities were evaluated. We observed that succinate dehydrogenase and cytochrome c oxidase activities were significantly augmented both in STZ‐treated rats and GK rats of 6 months age. Moreover, H+‐ATPase activity was also significantly increased in STZ‐treated rats with 3 weeks of diabetes and in GK rats of 6 months age as compared to controls. Therefore, these results clearly suggest that both animal models of diabetes present some metabolic adjustments in order to circumvent the deleterious effects promoted by the high glucose levels typical of the disease. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:214–222, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10081
Argemone oil induced cellular damage in the reproductive tissues of transgenic Drosophila melanogaster: Protective role of 70 kDa heat shock protein
Authors: Mukhopadhyay Indranil , Saxena D. K. , Bajpai V. K. , Chowdhuri D. Kar
Published: July 2003

We explored the reproductive toxicity of argemone oil and its principal alkaloid fraction in transgenic Drosophila melanogaster (hsp70‐lacZ) Bg9. The toxicity of argemone oil has been attributed to two of its physiologically active benzophenanthridine alkaloids, sanguinarine and dihydrosanguinarine. Freshly eclosed first instar larvae of transgenic Drosophila melanogaster were transferred to different concentrations of argemone oil and its alkaloid fraction contaminated food. Virgin flies that eclosed from the contaminated food were pair‐mated to look into the effect on reproduction. The study was further extended by investigating hsp70 expression and tissue damage in larval gonads, genital discs, and reproductive organs of adult fly. Our results showed that argemone oil was more cytotoxic than its principal alkaloid fraction. Moreover, it was the male fly that was more affected compared to its opposite number. The accessory glands of male reproductive system of the fly, which did not express hsp70, exhibited severe damage as evidenced by Trypan blue staining. This prompted us to explore the ultrastructural morphology of the gland, which showed acute signs of necrosis in both the cell types as evident by necrotic nuclei, higher vacuolization, and disorganized endoplasmic reticulum, decrease in the number of Golgi vesicles and disorganized, loosely packed filamentous structures in the lumen of the accessory gland, at the higher concentrations of the adulterant. The study showed the reproductive toxicity of argemone oil and its alkaloid fraction in transgenic Drosophila melanogaster and further confirmed the cytoprotective role of hsp70. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:223–234, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10082.
Evidence for the existence of a common ancestor of scorpion toxins affecting ion channels
Authors: Zhijian Cao , Yingliang Wu , Jiqun Sheng , Wanhong Liu , Fan Xiao , Xin Mao , Hui Liu , Dahe Jiang , Wenxin Li
Published: July 2003

All scorpion toxins from different 30 species are simply reviewed. A new classification system of scorpion toxins is first proposed: scorpion toxins are classified into three families (long‐chain scorpion toxins with 4 disulfide bridges, short‐chain scorpion toxins with 3 disulfide bridges, and intermediate‐type scorpion toxins with 3 or 4 disulfide bridges). Intermediate‐type scorpion toxins provide a strong proof for the conclusion that channel toxins from scorpion venoms evolve from a common ancestor. Common organization of precursor nucleotides and genomic sequence, similar 3‐dimensional structure, and the existence of intermediate type scorpion toxins and functionally intercrossing scorpion toxins show that all scorpion toxins affecting ion channels evolve from the common ancestor, which produce millions of scorpion toxins with function‐diversity. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:235–238, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10083
Binding of 3‐hydroxybenzo[a]pyrene to bovine hemoglobin and albumin
Authors: Sugihara Narumi , James Margaret O.
Published: July 2003

Previous studies examined the bioavailability and first‐pass biotransformation of 3‐hydroxy[3H]benzo[a]pyrene ([3H]‐3‐OHBaP) in an isolated perfused catfish intestinal model. This work showed that 3‐OHBaP, or a metabolite formed in intestine, bound covalently to blood protein. In this study, the blood adducts were characterized in vitro by incubating bovine ferric hemoglobin or albumin with [3H]‐3OHBaP under various conditions. Incubation of 2 μM [3H]‐3‐OHBaP with hemoglobin for 1 h resulted in 7.49 pmol bound/mg protein, while albumin binding was 1.37 pmol/mg protein. Mild acid hydrolysis released only 5% of the radioactivity from 3‐OHBaP–hemoglobin adducts. After gel filtration, the 3‐OHBaP–hemoglobin adducts were examined by HPLC analysis. A single peak of radioactivity was detected at the same retention time as the heme component of hemoglobin. Unbound 3‐OHBaP was oxidized to BaP‐3,6‐dione during incubation with ferric hemoglobin. Treatment of hemoglobin with ascorbic acid decreased the formation of hemoglobin adducts by 33%, while hydrogen peroxide treatment increased adduct formation by 44%. Incubation of [3H]‐BaP‐3‐β‐D‐glucuronide (BaP‐3G) with hemoglobin and β‐glucuronidase resulted in greater binding to hemoglobin than incubation with [3H]‐3‐OHBaP alone. The hemoglobin adduct obtained from [3H]‐BaP‐3G also co‐migrated with heme. These results indicate that an oxidative process is involved in formation of the heme adduct and that 3‐OHBaP or BaP‐3G might be a precursor of the bound metabolite. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:239–247, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10084
Influence of culture time on the expression of drug‐metabolizing enzymes in primary human hepatocytes and hepatoma cell line HepG2
Authors: Wilkening Stefan , Bader Augustinus
Published: July 2003

Primary cultures of human hepatocytes and hepatoma cell line HepG2 are frequently used to evaluate the hepatic disposition of drugs and other xenobiotics. To check the variability of the expression of drug‐metabolizing enzymes in these in vitro models, expression of genes coding for several cytochrome P450 isoforms and phase II enzymes was quantified during culture time by real‐time RT‐PCR. Gene expression was determined daily for primary hepatocytes maintained in a sandwich culture over 1 week and for HepG2, during the first 10 passages. In primary hepatocytes characteristic expression trends were observed which could be abstracted into three major classes of time curves. Genes of the first and the second class had an expression maximum around day 6 and day 4 in culture, respectively. The third class of genes had two expression peaks: at day 1 and 5 in culture. Surprisingly, also the cell line HepG2 showed significant expression changes during passages. For example, gene expression of cytochrome 1A1 varied 8‐fold, that of cytochrome 2B6 30‐fold, and that of NADP‐quinone reductase 1 more than 200‐fold within the first 10 passages. In conclusion, neither primary hepatocytes nor HepG2 cell line display a model for constant expression of drug‐metabolizing enzymes. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:207–213, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10085