bluuebunny/crossref_metadata_2025 huggingface dataset:
Field mapping and digital elevation modelling of submerged and unsubmerged hydraulic jump regions in a bedrock step–pool channel
Authors: Vallé Brett L. , Pasternack Gregory B.
Published: February 2006

High‐resolution tacheometric field surveying was integrated with computer‐assisted drafting to visualize and contrast three‐dimensional bed and water surface digital elevation models (DEMs) for submerged and unsubmerged hydraulic jump regions in a bedrock step–pool channel. Measurements were conducted for two discharge conditions. Since previous applica‐tions of three‐dimensional field mapping and digital elevation modelling of stream channels have been limited to smoothly contiguous gravel‐bedded systems, surveying was optimized by topographic setting and scaled to localized bed and water surface discontinuities. Traces and visualizations of the jump regions indicated that dichotomous decimetre shifts in water surface topography occurred for both jump regions from lower to higher discharges. Systematic removal of the survey points and DEM differencing indicated that point densities of ten points per square metre, in conjunction with a survey structure targeting grade breaks of 0·3–0·5 m, were required to capture decimetre form variations of the natural jump regions. The DEMs highlight the importance of recognizing the relationship between transcritical flow structures and localized topographic heterogeneities in bedrock channels. Copyright © 2006 John Wiley & Sons, Ltd.
A bed‐load transport model for rough turbulent open‐channel flows on plane beds
Authors: Abrahams Athol D. , Gao Peng
Published: February 2006

Data from flume studies are used to develop a model for predicting bed‐load transport rates in rough turbulent two‐dimensional open‐channel flows moving well sorted non‐cohesive sediments over plane mobile beds. The object is not to predict transport rates in natural channel flows but rather to provide a standard against which measured bed‐load transport rates influenced by factors such as bed forms, bed armouring, or limited sediment availability may be compared in order to assess the impact of these factors on bed‐load transport rates. The model is based on a revised version of Bagnold's basic energy equation ibsb = ebω, where ib is the immersed bed‐load transport rate, ω is flow power per unit area, eb is the efficiency coefficient, and sb is the stress coefficient defined as the ratio of the tangential bed shear stress caused by grain collisions and fluid drag to the immersed weight of the bed load. Expressions are developed for sb and eb in terms of G, a normalized measure of sediment transport stage, and these expressions are substituted into the revised energy equation to obtain the bed‐load transport equation ib = ω G 3·4. This equation applies regardless of the mode of bed‐load transport (i.e. saltation or sheet flow) and reduces to ib = ω where G approaches 1 in the sheet‐flow regime. That ib = ω does not mean that all the available power is dissipated in transporting the bed load. Rather, it reflects the fact that ib is a transport rate that must be multiplied by sb to become a work rate before it can be compared with ω. It follows that the proportion of ω that is dissipated in the transport of bed load is ibsb/ω, which is approximately 0·6 when ib = ω. It is suggested that this remarkably high transport efficiency is achieved in sheet flow (1) because the ratio of grain‐to‐grain to grain‐to‐bed collisions increases with bed shear stress, and (2) because on average much more momentum is lost in a grain‐to‐bed collision than in a grain‐to‐grain one. Copyright © 2006 John Wiley & Sons, Ltd.
Geostatistical analysis in weathering studies: case study for Stanton Moor building sandstone
Authors: McKinley Jennifer M. , Warke Patricia , Lloyd Christopher. D. , Ruffell Alastair H. , Smith Bernard J.
Published: February 2006

Geostatistical techniques for spatial prediction and spatial simulation have been used in an innovative application to the study of weathering of natural building stone. The study investigates the differences in the spatial variation of permeability characteristics between fine‐ and coarse‐grained Stanton Moor building sandstone. Non‐destructive permeability measurements, using an unsteady‐state Portable Probe Permeameter, were made on three adjacent faces of two cubic blocks representative of fine‐ to medium‐grained and medium‐ to coarse‐grained Stanton Moor Sandstone. The findings provide greater understanding in the investigation of the durability characteristics of the Stanton Moor Sandstone and show that the spatial distribution and variability of permeability is more important in predicting the overall strength and weathering properties than mean permeability and absolute minimum and maximum values. The results suggest that both primary textural characteristics (such as grain size) and extent of cementation appear to be important factors in determining the overall durability properties of Stanton Moor Sandstone as a building stone. Geostatistical analysis has been shown to be an important tool in the characterization of spatial variation for the investigation of weathering of building stones. Copyright © 2006 John Wiley & Sons, Ltd.
Towards a multi‐criteria approach for priority setting: an application to Ghana
Authors: Baltussen Rob , Stolk Elly , Chisholm Dan , Aikins Moses
Published: February 2006

Background: Many criteria have been proposed to guide priority setting in health, but their relative importance has not yet been determined in a way that allows a rank ordering of interventions.

Methods: In an explorative study, a discrete choice experiment was carried out to determine the relative importance of different criteria in identifying priority interventions in Ghana. Thirty respondents chose between 12 pairs of scenarios that described interventions in terms of medical and non‐medical criteria. Subsequently, a composite league table was constructed to rank order a set of interventions by mapping interventions on those criteria and considering the relative weights of different criteria.

Results: Interventions that are cost‐effective, reduce poverty, target severe diseases, or target the young had a higher probability of being chosen than others. The composite league table showed that high priority interventions in Ghana are prevention of mother to child transmission in HIV/AIDS control, and treatment of pneumonia and diarrhoea in childhood. Low priority interventions are certain interventions to control blood pressure, tobacco and alcohol abuse. The composite league table lead to a different and more differentiated rank ordering of interventions compared to pure efficiency ratings.

Conclusion: This explorative study has introduced a multi‐criteria approach to priority setting. It has shown the feasibility of accounting for efficiency, equity and other societal concerns in prioritization decisions, and its potentially large impact on priority setting. Copyright © 2006 John Wiley & Sons, Ltd.
Whither trial‐based economic evaluation for health care decision making?
Authors: Sculpher Mark J. , Claxton Karl , Drummond Mike , McCabe Chris
Published: February 2006

The randomised controlled trial (RCT) has developed a central role in applied cost‐effectiveness studies in health care as the vehicle for analysis. This paper considers the role of trial‐based economic evaluation in this era of explicit decision making. It is argued that any framework for economic analysis can only be judged insofar as it can inform two key decisions and be consistent with the objectives of a health care system subject to its resource constraints. The two decisions are, firstly, whether to adopt a health technology given existing evidence and, secondly, an assessment of whether more evidence is required to support this decision in the future. It is argued that a framework of economic analysis is needed which can estimate costs and effects, based on all the available evidence, relating to the full range of possible alternative interventions and clinical strategies, over an appropriate time horizon and for specific patient groups. It must also enable the accumulated evidence to be synthesised in an explicit and transparent way in order to fully represent the decision uncertainty. These requirements suggest that, in most circumstances, the use of a single RCT as a vehicle for economic analysis will be an inadequate and partial basis for decision making. It is argued that RCT evidence, with or without economic content, should be viewed as simply one of the sources of evidence, which must be placed in a broader framework of evidence synthesis and decision analysis. Copyright © 2006 John Wiley & Sons, Ltd.
A rapid microwave assisted synthesis of [U‐14C]isosorbide and dimethyl[U‐14C]isosorbide from D‐[U‐14C]glucose
Authors: Mathew K. M. , Ravi S. , Padmanabhan D. , Unny V. K. P. , Sivaprasad N.
Published: February 2006

[U‐14C]Isosorbide and [U‐14C]dimethyl isosorbide with a specific activity of 462 MBq/mmol was prepared from D‐[U‐14C]glucose, in an overall yield of 79%, under microwave heating conditions. Copyright © 2006 John Wiley & Sons, Ltd.
One‐pot synthesis of [11C]ureas via triphenylphosphinimines
Authors: van Tilburg Erica W. , Windhorst Albert D. , van der Mey Margreet , Herscheid Jacobus D. M.
Published: February 2006

A series of 11C‐labeled ureas was prepared using a rapid and efficient one‐pot procedure. First, the intermediate [11C]phenylisocyanate was formed with phenyltriphenylphosphinimine and [11C]CO2. A range of amines was then reacted with the [11C]phenylisocyanate yielding the [11C]urea derivatives in short synthesis times. This easy‐to‐handle method circumvents disadvantages of known procedures and generates the possibility to prepare other kinds of 11C‐labeled compounds using a variety of phenylphosphinimines in combination with different nucleophiles. The presented approach is an alternative to the use of established methods in 11C‐labeling chemistry. Copyright © 2006 John Wiley & Sons, Ltd.
Limiting Amplitude principle in the scattering by wedges
Authors: Komech A. I. , Merzon A. E.
Published: February 2006

We consider a nonstationary scattering of plane waves by a wedge. We prove that the Sommerfeld‐type integral, constructed in (Math. Meth. Appl. Sci. 2005; 28:147–183; Proc. Int. Seminar ‘Day on Diffraction‐2003’, University of St. Petersburg, 2003; 151–162), is a classical smooth solution from a functional space, and prove the Limiting Amplitude principle. Copyright © 2006 John Wiley & Sons, Ltd.
An implicit method for linear ill‐posed problems with perturbed operators
Authors: Tang Jian‐guo
Published: February 2006

An implicit iterative method is applied to solving linear ill‐posed problems with perturbed operators. It is proved that the optimal convergence rate can be obtained after choosing suitable number of iterations. A generalized Morozov's discrepancy principle is proposed for the problems, and then the optimal convergence rate can also be obtained by an a posteriori strategy. The convergence results show that the algorithm is a robust regularization method. Copyright © 2006 John Wiley & Sons, Ltd.
Architecture for dynamic and fair distribution of bandwidth
Authors: Hnatyshin Vasil , Sethi Adarshpal S.
Published: February 2006

The problem of fair distribution of available bandwidth among traffic flows or aggregates remains an essential issue in computer networks. This paper introduces a novel approach, called the ExactBandwidthDistributionScheme (X‐BDS), for dynamic and fair distribution of available bandwidth among individual flows. In this approach, the edge routers keep per‐flow information, while the core routers maintain the aggregate flow requirements. The X‐BDS approach employs a distributed message exchange protocol for providing network feedback and for distributing aggregate flow requirements among the nodes in the network. Based on the obtained feedback, the edge routers employ the X‐BDS resource management unit to dynamically distribute available bandwidth among individual flows. The X‐BDS admission control and resource management units are responsible for fair resource allocation that supports minimum bandwidth guarantees of individual flows. This paper evaluates the Bandwidth Distribution Scheme through simulation and shows that the X‐BDS is capable of supporting per‐flow bandwidth guarantees in a dynamically changing network environment. Copyright © 2006 John Wiley & Sons, Ltd.
XBGP‐MAN: an XML management architecture for BGP
Authors: Cridlig V , Abdelnur H , State R , Festor O
Published: February 2006

Network and system management paradigms have recently evolved towards flexible and lightweight integration approaches. These approaches are based on the transparent information‐processing capabilities offered by both generous support for self‐describing data enabled by XML as well as from the large base of existing underlying tools. BGP is, from a configuration point of view, one of the most complex protocols of the Internet and as such a very good validation environment for new management frameworks. This paper describes the practical experience gathered from the design, implementation and deployment of a comprehensive XML‐based management architecture for the Border Router Gateway Protocol. Copyright © 2006 John Wiley & Sons, Ltd.
A novel fault management approach for DWDM optical networks
Authors: Fawaz W. , Martignon F. , Chen K. , Pujolle G.
Published: February 2006

Connection availability is considered as a critical metric when providing differentiated services in Wavelength‐Division Multiplexing mesh networks. Indeed, one of the major concerns of optical network operators is related to improving the availability of services provided to their highest‐class clients. Achieving this objective is possible through managing faults using the different classical protection schemes, namely the so‐called dedicated and shared protection schemes. However, the majority of the work concerning protection schemes has considered the primary connections as equally important when contending for the use of the backup resources. As a main contribution in this paper, we therefore propose an improvement of the existing protection schemes through the introduction of relative priorities among the different primary connections contending for the access to the protection path. To evaluate numerically the benefits of the service differentiation feature introduced in our proposal, we first develop a mathematical model, based on which we derive explicit expressions for the average connection availabilities that result from both the classical protection schemes and the proposed priority‐aware one. Through this model, we show how the availability of the highest‐class clients is improved when deploying the proposed priority‐aware protection scheme. Finally, with the same objective in mind, we develop a simulation study, where a given set of connection demands with predefined availability requirements is provisioned using different protection strategies. Through this study, we show that the priority‐aware protection strategy satisfies service‐availability requirements in a cost‐effective manner compared with the classical protection schemes.Copyright © 2006 John Wiley & Sons, Ltd.
Adaptive robust attitude control of a flexible spacecraft
Authors: Shahravi Morteza , Kabganian Mansour , Alasty Aria
Published: February 2006

A new attitude control strategy for rotational manoeuvre of an elastic spacecraft is presented. Adaptive sliding mode control with hybrid sliding surface (HSS) is used to minimize the effects of uncertainties, disturbances and the difficulties arising from measurement of flexible dynamic co‐ordinates. The model of the spacecraft considered as rigid central hub and two elastic appendages. Collocated actuators and sensors are placed on the rigid central hub. Stability proof of the overall closed‐loop system is given via Lyapunov analysis. Numerical simulations show that the attitude manoeuvres can be performed precisely and the elastic deformations of the flexible substructures are suppressed as well. Copyright © 2006 John Wiley & Sons, Ltd.
Molecular species of phosphatidylethanolamine from continuous cultures of Saccharomyces pastorianus syn. carlsbergensis strains
Authors: Tosch W. , Lanthaler K. , Boote V. , Stretz D. , Robson G. D. , Geiger E. , Drucker D. B.
Published: February 2006

Saccharomyces pastorianus syn. carlsbergensis strain 34/70 is well known to be the most used strain for lager beer production. The difference between this strain and very closely related strain 34/78 is the latter's greater flocculating character. This single physiological trait can cause technical difficulties in beer production. The aim of this study was to determine whether lipid analysis by a combination of thin layer chromatography (TLC) with electrospray ionization mass spectrometry (ESI–MS) could be used as a strain‐typing technique in order to distinguish S. pastorianus syn. carlsbergensis strain 34/70 from strain 34/78. Both strains (34/70 and 34/78) were harvested after continuous culture under standard conditions. Polar lipids were then extracted from lyophilized cultures and analysed by TLC in order to separate phospholipid families. Phosphatidylethanolamine (PE) was extracted and investigated using ESI–MS, to gain further information on individual molecular species. Using TLC analysis, lipids were separated corresponding to standards for PE, phosphatidylcholine (PC), phosphatidylglycerol (PG), cardiolipin (CL), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidic acid (PA) and sphingomyelin (SM). ESI–MS of the PE band, separated by TLC, showed that electrospray mass spectra were highly reproducible for repeat cultures. Novel findings were that both brewing strains displayed major phospholipid peaks with m/z 714, PE (34 : 2) m/z 742, PE (36 : 2) and m/z 758, PE (37 : 1). However, strain 34/78 had additional peaks of m/z 700, PE (33 : 2) and m/z 728, PE (35 : 2). Strain 34/70 had an extra peak with m/z 686 PE (32 : 2). We conclude that combined TLC/ESI–MS can distinguish between S. pastorianus syn. carlsbergensis 34/70 and 34/78 and may be a useful typing technique for differentiation of closely related yeast strains. This novel approach may aid quality assurance and could be suitable for yeast collections and larger industrial companies. Copyright © 2006 John Wiley & Sons, Ltd.
Phenotypes of yeast mutants lacking the mitochondrial protein Pet20p
Authors: Polevoda Bogdan , Panciera Yana , Brown Steven P. , Wei Jun , Sherman Fred
Published: February 2006

The pet20‐Δ deletion in Saccharomyces cerevisiae causes diminished growth on media containing non‐fermentable carbon sources when incubated at both above and below the 30 °C optimal growth temperature. Furthermore, the pet20‐Δ strain has a greatly reduced level of cytochrome c, especially at 37 °C. The pet20‐Δ strain was sensitive to high NaCl and CaCl2 concentrations, hydrogen peroxide, oligomycin, polymixin B, amphotericin B and fluconazole. Biochemical fractionation and immunofluorescence staining demonstrated that Pet20p is located primarily in the mitochondria. Rhodamine B staining of pet20‐Δ cells showed an altered mitochondrial staining, indicating the possible lack of the mitochondrial membrane potential. We suggest that PET20 encodes a protein required for proper assembly or maintenance of mitochondrial components, but does not serve an enzymatic role. It is also possible that Pet20p may constitute a non‐catalytic subunit of an uncharacterized mitochondrial complex or serve as a transporter or a coupling factor. Copyright © 2006 John Wiley & Sons, Ltd.
Construction of a protease‐deficient strain set for the fission yeast Schizosaccharomyces pombe, useful for effective production of protease‐sensitive heterologous proteins
Authors: Idiris Alimjan , Bi Kewei , Tohda Hideki , Kumagai Hiromichi , Giga‐Hama Yuko
Published: February 2006

One of the major problems hindering effective production and purification of heterologous proteins from the fission yeast Schizosaccharomyces pombe is proteolytic degradation of the recombinant gene products by host‐specific proteases. As an initial solution to this problem, we constructed a protease‐deficient disruptant set by respective disruption of 52 Sz. pombe protease genes. Functional screening of the resultant set was performed by observing secretory production of a proteolytically sensitive model protein, human growth hormone (hGH). The results indicated that some of the resultant disruptants were effective in reducing hGH degradation, as observed during the hGH expression procedure and mainly as a result of unknown serine‐ and/or cysteine‐type proteases in the culture medium. These findings also demonstrated that construction of a protease‐deficient strain set is not only useful for practical application in protein production, but also for functional screening, specification and modification of proteases in Sz. pombe, where further investigations of proteolytic processes and improvement through multiple gene manipulations are required. Copyright © 2006 John Wiley & Sons, Ltd.
Purification and biochemical characterization of an α‐glucosidase from Xanthophyllomyces dendrorhous
Authors: Marín Dolores , Linde Dolores , Lobato María Fernández
Published: February 2006

Xanthophyllomyces dendrorhous grown in different media shows amylolytic activity, consisting in an extracellular exo‐acting enzyme able to hydrolysed α,1–4 glycosidic bonds from soluble starch, which also cleaves maltose and malto‐oligosaccharides. The enzyme was purified, using basically a couple of chromatography process on DEAE–Sephacel. It is a glycoprotein with a molecular weight estimated to be 60.2 kDa based on its mobility in SDS–PAGE and 115 kDa based on gel filtration. N‐linked carbohydrate accounts for 12% of the total mass. It exhibited optimum activity at pH 5.5 and 45 °C. Thermostability analysis indicated that it was stable to thermal treatment up to 50 °C; 50% of the activity was maintained after 3 h. The rate parameters measured for the hydrolysis of starch and various chain length malto‐oligosaccharides shows high catalytic efficiency, calculated by the relationship Vcat/Km, for malto‐oligosaccharides, such as maltotriose (873 mM−1 min−1), or maltoheptose (698 mM−1 min−1). The new enzyme hydrolysed soluble starch with nearly 3.5‐ and 1.4‐fold lower efficiency than that for maltotriose and maltose, respectively. No activity was found on heterogeneous substrates, such as sucrose and aryl α‐glucoside, or on isomalto‐oligosaccharides. In accordance to substrate specificity profile, the new enzyme was classified as an α‐glucosidase. Copyright © 2006 John Wiley & Sons, Ltd.
Pain in older adults: A prevalence study in the Mediterranean region of Catalonia
Authors: Miró Jordi , Paredes Saida , Rull Maria , Queral Rosa , Miralles Rodrigo , Nieto Rubén , Huguet Anna , Baos Judith
Published: February 2006

Although information is available about the prevalence of pain in older adults in Anglo‐Saxon and Scandinavian countries, very little is known about older adults in other parts of the world. This study reports the prevalence of pain in a randomly selected sample of older adults living in the Mediterranean region of Catalonia. Besides studying the existence of pain at the time of interview, the authors investigated several characteristics of the participants' pain experience: pain onset, number and location of pain sites, intensity of pain, number of days in pain, severity of pain, the extent to which pain interfered with daily life, and expressed needs in relation to pain. A cross‐sectional survey was conducted of adults aged 65 years and over living in Catalonia. A total of 592 individuals participated in the study, and data was collected through personal interviews with participants. The prevalence of any pain was 73.5%, and similar across age groups but higher in females than in males. Among individuals suffering from pain, 94.2 were experiencing chronic pain (i.e., pain of three months' duration or more). The mean number of painful areas (out of 10) was 4.48. No clear pattern of the prevalence of regional pain was observed, although joints were the most frequently reported painful place. Pain interfered in the life of a considerable number of participants (35.5%), but no differences in the level of expressed needs was detected between those that were affected and those that were not. This study provides new evidence that pain is an important problem for the older adult, one that severely impacts on their health status, causing disability and reduced ability to function, particularly in older women.
Phantom breast sensations and phantom breast pain: A 2‐year prospective study and a methodological analysis of literature
Authors: Dijkstra Pieter U. , Rietman Johan S. , Geertzen Jan H.B.
Published: February 2006

The first aim of this study was to assess prospectively the incidence of phantom breast sensations (PB sensations) and phantom breast pain (PB pain) in a sample of patients treated for breast cancer (n = 204) by means of a modified radical mastectomy (n = 82). Patients were assessed 6 weeks, 6, 12 and 24 months after mastectomy, by means of a questionnaire. After 24 months, assessments of 74 (90%) patients were available.

Two years after mastectomy, PB sensations were present in 19% (n = 14) of the patients and PB pain was present in 1% (n = 1) of the patients. Over time the percentage of patients with PB sensations remained relatively stable (around 20%) but for PB pain the percentage reduced from 7% to 1%. The amount of suffering as a result of PB sensations or PB pain was very limited. PB sensations and PB pain are of little clinical relevance in the 24 months following mastectomy.

The second aim of this paper was to analyse the influence of research methodology on the prevalences of PB sensations and PB pain previously reported.

Research design, assessment method and publication date were recorded. Data were weighted according to the number of women investigated. Linear regression analysis was performed to analyse the influences of methodology on the prevalences of PB sensations and PB pain.

Of the 29 studies identified, 23 were cross‐sectional and 6 were prospective. In 17 studies patients were interviewed and in 12 studies a questionnaire was used.

A prospective design resulted in prevalences of PB sensations and PB pain averagely 8% lower respectively 9% higher than in cross‐sectional studies. The use of an interview resulted in prevalences of PB sensations and PB pain averagely 13% lower respectively 5% lower than questionnaire use. Prevalences of PB sensations and PB pain reduce averagely with 0.08% respectively 0.13% per year since 1950.

It is concluded that research design and assessment method have a significant influence on reported prevalence of PB sensations and PB pain.
Exploring beliefs and practice of opioid prescribing for persistent non‐cancer pain by general practitioners
Authors: Hutchinson Kirsty , Moreland Annie M.E. , de Williams Amanda C.C. , Weinman John , Horne Rob
Published: February 2006

Persistent non‐cancer pain is a common reason for consultation in primary care but treatment options, including non‐opioid analgesics, are limited, and neither strong evidence nor established guidelines address when and how primary care doctors should prescribe opioid analgesics for persistent non‐cancer pain. The aim of this study was to investigate associations between doctors' prescribing patterns for persistent non‐cancer pain in primary care and their personal and practice characteristics and beliefs about appropriateness and risks of opioids. A pilot survey sampled beliefs concerning the need for and risks of opioid prescribing for persistent non‐cancer pain among volunteers from primary care practices and postgraduate educational events, using a self‐report questionnaire, and related these beliefs to their reported opioid prescribing. One quarter of the sample prescribed no opioids for persistent non‐cancer pain. Prescribing opioids was predicted by moderate belief in the appropriateness of opioids within certain constraints, and to a lesser extent by younger age. While some beliefs distinguished prescribers from non‐prescribers, predicting non‐prescribing was poor. Both prescribers and non‐prescribers expressed concern about the risks of opioids. In addition, most primary care doctors were dissatisfied with their training on pain; few had prescribing guidelines; and neither training nor guidelines influenced prescribing. In conclusion, whether or not GPs prescribe opioids for persistent non‐cancer pain is mainly determined by their personal beliefs about appropriateness of opioids for this problem.
Chemical glycosylation: New insights on the interrelation between protein structural mobility, thermodynamic stability, and catalysis
Authors: Solá Ricardo J. , Griebenow Kai
Published: February 2006

Chemical protein glycosylation was employed to sequentially modulate the structural dynamics of the serine protease α‐chymotrypsin as evidenced from amide H/D exchange kinetics. The reduction in α‐CT's structural dynamics at increasing glycan molar contents statistically correlated with the increased thermodynamic stability (T
m) and reduced rate of enzyme catalysis (k
cat) exhibited by the enzyme upon chemical glycosylation. Temperature‐dependant experiments revealed that native‐like structural dynamics and function could be restored for the glycosylated conjugates at temperature values close to their thermodynamic stability suggesting that the concept of “corresponding states” can be extended to glycoproteins. These results demonstrate the value of chemical glycosylation as a tool for studying the role of protein structural dynamics on protein biophysical properties; e.g. enzyme stability and function.
A GABAAreceptor of defined subunit composition and positioning: Concatenation of five subunits
Authors: Baur Roland , Minier Frédéric , Sigel Erwin
Published: February 2006

We show that the five subunits of a γ‐aminobutyric acid type A receptor (GABAAreceptor) can be concatenated to yield a functional receptor. This concatenated receptor α1–β2–α1–γ2–β2has the advantage of a known subunit arrangement. Most of its functional properties are not significantly different from a receptor formed by individual subunits. Extent of expression amounted to about 40% of that of non‐concatenated receptors in Xenopus oocytes, after injection of oocytes with comparable amounts of cRNA coding for concatenated and non‐concatenated receptors. The ability to express receptors consisting of five subunits enables detailed studies of GABAAreceptor subtype selective compounds.
A complete small molecule dataset from the protein data bank
Authors: Feldman Howard J. , Snyder Kevin A. , Ticoll Amy , Pintilie Greg , Hogue Christopher W.V.
Published: February 2006

A complete set of 6300 small molecule ligands was extracted from the protein data bank, and deposited online in PubChem as data source ‘SMID’. This set's major improvement over prior methods is the inclusion of cyclic polypeptides and branched polysaccharides, including an unambiguous nomenclature, in addition to normal monomeric ligands. Only the best available example of each ligand structure is retained, and an additional dataset is maintained containing co‐ordinates for all examples of each structure. Attempts are made to correct ambiguous atomic elements and other common errors, and a perception algorithm was used to determine bond order and aromaticity when no other information was available.
Anthocyanidin synthase from Gerbera hybrida catalyzes the conversion of (+)‐catechin to cyanidin and a novel procyanidin
Authors: Wellmann Frank , Griesser Markus , Schwab Wilfried , Martens Stefan , Eisenreich Wolfgang , Matern Ulrich , Lukačin Richard
Published: February 2006

Anthocyanidins were proposed to derive from (+)‐naringenin via (2R,3R)‐dihydroflavonol(s) and (2R,3S,4S)‐leucocyanidin(s) which are eventually oxidized by anthocyanidin synthase (ANS). Recently, the role of ANS has been put into question, because the recombinant enzyme from Arabidopsis exhibited primarily flavonol synthase (FLS) activity with negligible ANS activity. This and other studies led to the proposal that ANS as well as FLS may select for dihydroflavonoid substrates carrying a “β‐face” C‐3 hydroxyl group and initially form the 3‐geminal diol by “α‐face” hydroxylation. Assays with recombinant ANS from Gerbera hybrida fully supported the proposal and were extended to catechin and epicatechin isomers as potential substrates to delineate the enzyme specificity. Gerbera ANS converted (+)‐catechin to two major and one minor product, whereas ent(−)‐catechin (2S,3R‐trans‐catechin), (−)‐epicatechin, ent(+)‐epicatechin (2S,3S‐cis‐epicatechin) and (−)‐gallocatechin were not accepted. The K
m value for (+)‐catechin was determined at 175 μM, and the products were identified by LC–MSn and NMR as the 4,4‐dimer of oxidized (+)‐catechin (93%), cyanidin (7%) and quercetin (trace). When these incubations were repeated in the presence of UDP‐glucose:flavonoid 3‐O‐glucosyltransferase from Fragaria
×
ananassa (FaGT1), the product ratio shifted to cyanidin 3‐O‐glucoside (60%), cyanidin (14%) and dimeric oxidized (+)‐catechin (26%) at an overall equivalent rate of conversion. The data appear to identify (+)‐catechin as another substrate of ANS in vivo and shed new light on the mechanism of its catalysis. Moreover, the enzymatic dimerization of catechin monomers is reported for the first time suggesting a role for ANS beyond the oxidation of leucocyanidins.
Analysis of the effect of tetrahydrobiopterin on PAH gene expression in hepatoma cells
Authors: Aguado Cristina , Pérez Belén , Ugarte Magdalena , Desviat Lourdes R.
Published: February 2006

Tetrahydrobiopterin (BH4)‐responsive phenylalanine hydroxylase (PAH) deficiency is a recently recognized variant of phenylketonuria, with a probable multifactorial molecular basis. In this study we have investigated the effect of BH4 on PAH gene expression in human hepatoma. Our results show that increased BH4 levels result in an enhancement of PAH activity and PAH protein, due to longer turnover rates, while PAH mRNA levels remain unchanged. This was confirmed for mutant PAH proteins (A309V, V388M and Y414C) associated to in vivo BH4 responsiveness, validating previous studies. We can conclude that there is no effect of the cofactor on PAH gene transcription, probably being the chemical chaperone effect of BH4 stabilizing mutant PAH proteins the major underlying mechanism of the response.
Covalent labeling of cell‐surface proteins for in‐vivo FRET studies
Authors: Meyer Bruno H. , Martinez Karen L. , Segura Jean-Manuel , Pascoal Pedro , Hovius Ruud , George Nathalie , Johnsson Kai , Vogel Horst
Published: February 2006

Fluorescence resonance energy transfer (FRET) is a powerful technique to reveal interactions between membrane proteins in live cells. Fluorescence labeling for FRET is typically performed by fusion with fluorescent proteins (FP) with the drawbacks of a limited choice of fluorophores, an arduous control of donor–acceptor ratio and high background fluorescence arising from intracellular FPs. Here we show that these shortcomings can be overcome by using the acyl carrier protein labeling technique. FRET revealed interactions between cell‐surface neurokinin‐1 receptors simultaneously labeled with a controlled ratio of donors and acceptors. Moreover, using FRET the specific binding of fluorescent agonists could be monitored.
Four gene products are required for the fungal synthesis of the indole‐diterpene, paspaline
Authors: Saikia Sanjay , Parker Emily J. , Koulman Albert , Scott Barry
Published: February 2006

Paspaline belongs to a large, structurally and functionally diverse group of indole‐diterpenes synthesized by filamentous fungi. However, the identity of the gene products required for the biosynthesis of paspaline, a key intermediate for the synthesis of paxilline and other indole‐diterpenes, is not known. Transfer of constructs containing different pax gene combinations into a paxilline negative deletion derivative of Penicillium paxilli demonstrated that just four proteins, PaxG, a geranylgeranyl diphosphate synthase, PaxM, a FAD‐dependent monooxygenase, PaxB, a putative membrane protein, and PaxC, a prenyl transferase, are required for the biosynthesis of paspaline.
Biochemical and mutational analysis of EcoRII functional domains reveals evolutionary links between restriction enzymes
Authors: Tamulaitis Gintautas , Mucke Merlind , Siksnys Virginijus
Published: February 2006

The archetypal Type IIE restriction endonuclease EcoRII is a dimer that has a modular structure. DNA binding studies indicate that the isolated C‐terminal domain dimer has an interface that binds a single cognate DNA molecule whereas the N‐terminal domain is a monomer that also binds a single copy of cognate DNA. Hence, the full‐length EcoRII contains three putative DNA binding interfaces: one at the C‐terminal domain dimer and two at each of the N‐terminal domains. Mutational analysis indicates that the C‐terminal domain shares conserved active site architecture and DNA binding elements with the tetrameric restriction enzyme NgoMIV. Data provided here suggest possible evolutionary relationships between different subfamilies of restriction enzymes.
Sumoylation of the SOX10 transcription factor regulates its transcriptional activity
Authors: Girard Mathilde , Goossens Michel
Published: February 2006

SRY‐related HMG box‐containing factor 10 (SOX10) is a transcription factor essential for neural crest development and differentiation, and involved in Waardenburg syndrome type IV and PCWH syndrome. Here we show that the SOX10 protein is modified by sumoylation, a highly dynamic post‐translational modification that affects stability, activity and localisation of some specific transcription factors. Three sumoylation consensus sites were found in the SOX10 protein, all of them are functional and modulate SOX10 activity. Sumoylation does not affect SOX10 sub‐cellular localisation, but represses its transcriptional activity on two of its target genes, GJB1 and MITF, and modulates its synergy with its cofactors EGR2 and PAX3 on these promoters.
Purified recombinant hARD1 does not catalyse acetylation of Lys532 of HIF‐1α fragments in vitro
Authors: Murray-Rust Thomas A. , Oldham Neil J. , Hewitson Kirsty S. , Schofield Christopher J.
Published: February 2006

In humans, many responses to hypoxia including angiogenesis and erythropoiesis are mediated by the α/β‐heterodimeric transcription factor hypoxia inducible factor (HIF). The stability and/or activity of human HIF‐1α are modulated by post‐translational modifications including prolyl and asparaginyl hydroxylation, phosphorylation, and reportedly by acetylation of the side‐chain of Lys532 by ARD1 (arrest defective protein 1 homologue), an acetyltransferase. Using purified recombinant human ARD1 (hARD1) we did not observe ARD1‐mediated N‐acetylation of Lys532 using fragments of HIF‐1α. However, recombinant hARD1 from Escherichia coli was produced with partial N‐terminal acetylation and was observed to undergo slow self‐mediated N‐terminal acetylation. The observations are consistent with the other data indicating that hARD1, at least alone, does not acetylate HIF‐1α, and with reports on the N‐terminal acetyltransferase activity of a recently reported heterodimeric complex comprising hARD1 and N‐acetyltransferase protein.
Optimal growth temperature of prokaryotes correlates with class II amino acid composition
Authors: Klipcan Liron , Safro Ilya , Temkin Boris , Safro Mark
Published: February 2006

Partitioning of aminoacyl‐tRNA synthetases and their associated amino acids into two classes allows us to distinguish between thermophilic and mesophilic species based only on amino acids composition. The CLASSDB program has been developed for amino acid content analysis in organisms treated individually or pooled together to form a pattern of characteristic properties. A strong correlation has been observed between optimal growth temperature (OGT) of organisms and class II amino acids content. Amino acid composition in organisms closely related phylogenetically but dissimilar in their OGT testifies that thermo‐adaptation happens rather rapidly on the time scale of evolution.
Androgen receptor auto‐regulates its expression by a negative feedback loop through upregulation of IFI16 protein
Authors: Alimirah Fatouma , Chen Jianming , Xin Hong , Choubey Divaker
Published: February 2006

Expression of androgen receptor (AR) in prostate epithelial cells is thought to regulate cell proliferation, differentiation, and survival. However, the molecular mechanisms remain unclear. We report that re‐expression of AR in PC‐3 human prostate cancer cell line resulted in upregulation of IFI16 protein, a negative regulator of cell growth. We found that the IFI16 protein bound to AR in a ligand‐dependent manner and the DNA‐binding domain (DBD) of the AR was sufficient to bind IFI16. Furthermore, re‐expression of IFI16 protein in LNCaP prostate cancer cells, which do not express IFI16 protein, resulted in downregulation of AR expression and an inhibition of the expression of AR target genes. Our observations identify a role for IFI16 protein in AR‐mediated functions.
Expression of mouse liver receptor homologue 1 in embryonic stem cells is directed by a novel promoter
Authors: Gao Da-ming , Wang Lin-fang , Liu Jing , Kong Yu-ying , Wang Yuan , Xie You-hua
Published: February 2006

Liver receptor homologue 1 (LRH‐1) plays important roles in many physiological processes and embryogenesis. However, little is known about the developmental regulation of lrh‐1 expression. We identified a novel transcript of mouse lrh‐1 (mlrh‐1v2) from embryonic stem (ES) cells. mlrh‐1v2 is expressed throughout embryogenesis and in several adult tissues, while the known transcript (mlrh‐1v1) appears later during embryogenesis. mlrh‐1v2 expression is directed by a new promoter which displays a strong activity in ES cells. The generation of the new transcript is conserved in rats. The identification of novel mlrh‐1 variant and promoter is critical for elucidating LRH‐1 functions in development and adult tissues.
Kinetics of amyloid aggregation of mammal apomyoglobins and correlation with their amino acid sequences
Authors: Vilasi Silvia , Dosi Roberta , Iannuzzi Clara , Malmo Clorinda , Parente Augusto , Irace Gaetano , Sirangelo Ivana
Published: February 2006

In protein deposition disorders, a normally soluble protein is deposited as insoluble aggregates, referred to as amyloid. The intrinsic effects of specific mutations on the rates of protein aggregation and amyloid formation of unfolded polypeptide chains can be correlated with changes in hydrophobicity, propensity to convert α‐helical to β sheet conformation and charge. In this paper, we report the aggregation rates of buffalo, horse and bovine apomyoglobins. The experimental values were compared with the theoretical ones evaluated considering the amino acid differences among the sequences. Our results show that the mutations which play critical roles in the rate‐determining step of apomyoglobin aggregation are those located within the N‐terminal region of the molecule.
Pathogenicity ofSalmonella: SopE‐mediated membrane ruffling is independent of inositol phosphate signals
Authors: Deleu Sandrine , Choi Kuicheon , Reece Jeff M. , Shears Stephen B.
Published: February 2006

Studies [Zhou, D., Chen, L.‐M., Hernandez, L., Shears, S.B., and Galán, J.E. (2001) ASalmonellainositol polyphosphatase acts in conjunction with other bacterial effectors to promote host‐cell actin cytoskeleton rearrangements and bacterial internalization. Mol. Microbiol. 39, 248–259] with engineeredSalmonellamutants showed that deletion ofSopEattenuated the pathogen's ability to deplete host‐cell InsP5and remodel the cytoskeleton. We pursued these observations: In SopE‐transfected host‐cells, membrane ruffling was induced, but SopE did not dephosphorylate InsP5, nor did it recruit PTEN (a cytosolic InsP5phosphatase) for this task. However, PTEN strengthened SopE‐mediated membrane ruffling. We conclude SopE promotes host‐cell InsP5hydrolysis only with the assistance of otherSalmonellaproteins. Our demonstration thatSalmonella‐mediated cytoskeletal modifications are independent of inositolphosphates will focus future studies on elucidating alternate pathogenic consequences of InsP5metabolism, including ion channel conductance and apoptosis.
Mechanisms and strategies to overcome multiple drug resistance in cancer
Authors: Ozben Tomris
Published: February 2006

One of the major problems in chemotherapy is multidrug resistance (MDR) against anticancer drugs. ATP‐binding cassette (ABC) transporters are a family of proteins that mediate MDR via ATP‐dependent drug efflux pumps. Many MDR inhibitors have been identified, but none of them have been proven clinically useful without side effects. Efforts continue to discover not toxic MDR inhibitors which lack pharmacokinetic interactions with anticancer drugs. Novel approaches have also been designed to inhibit or circumvent MDR. In this review, the structure and function of ABC transporters and development of MDR inhibitors are described briefly including various approaches to suppress MDR mechanisms.
Evaluation of Sympathetic Vasomotor Fibres in Carpal Tunnel Syndrome Using Continuous Wave Doppler Ultrasonography
Authors: GALEA L. A. , MERCIECA A. , SCIBERRAS C. , GATT R. , SCHEMBRI M.
Published: February 2006

Sympathetic vasomotor fibres carried by the median nerve and ulnar nerve innervate their respective sensory territories. The sympathetic vasomotor fibres of the median nerve were evaluated in patients with carpal tunnel syndrome and in healthy volunteers using continuous wave Doppler ultrasonography. The pulsatility index of the radialis indicis artery and the radial palmar digital artery of the little finger were measured at baseline and after stimulation. The maximal increase in the pulsatility index of each artery was measured. This was significantly lower for the radialis indicis artery in the CTS group than in the healthy controls. However, there was no significant difference in the maximal increase in pulsatility index of the radial palmar digital artery of the little finger between both groups. Sympathetic vasomotor fibres of the median nerve are affected in carpal tunnel syndrome. Continuous wave Doppler ultrasonography is easy to use and should be investigated further as a possible diagnostic tool for the confirmation of carpal tunnel syndrome.
Utility and Capability
Authors: SUMNER L.W.
Published: February 2006

When Amartya Sen defends his capability theory of well-being he contrasts it with the utility theory advocated by the classical utilitarians, including John Stuart Mill. Yet a closer examination of the two theories reveals that they are much more similar than they appear. Each theory can be interpreted in either a subjective or an objective way. When both are interpreted subjectively the differences between them are slight, and likewise for the objective interpretations. Finally, whatever differences may remain are less important than they might seem, since the two theories are developed by Sen and Mill for different purposes and are in that sense not genuine rivals.
What We Desire, What We Have Reason to Desire, Whatever We Might Desire: Mill and Sen on the Value of Opportunity
Authors: SUGDEN ROBERT
Published: February 2006

I compare Mill's and Sen's accounts of the value of opportunity, focusing on a tension between two ideas they both uphold: that individual freedom is an important component of well-being, and that, because desires can be adaptive, actual desire is not always a good indicator of what will give well-being. The two writers' responses to this tension reflect different understandings of the relationship between freedom and desire. Sen links an individual's well-being to her freedom to choose what she has reason to desire, and looks to a democratic political process for a collective judgement about what it is rational to desire. Mill links the individual's well-being to her freedom to act on her own desires, whatever they may be, within the constraints imposed by a fair initial distribution of resources. He sees no need for collective judgement about what is ultimately valuable in human life. I side with Mill.