bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of two methods for the design of active suspension systems
Authors: De Jager A. G.
Published: July 2007

The design of controllers for active suspension systems can be formulated as an optimal control problem. The main objective of the controller is to isolate parts of the system from vibrations in other parts. Additional constraints are limited suspension travel, limited actuator force and good track‐holding capability. The objective and the constraints can be used in the formulation of an optimality criterion.

Two criteria are examined, with the corresponding LQ and H∞ control design methods. The methods are compared with respect to their ability to generate a controller that achieves the best performance. For the LQ method three controllers with different structures were generated.

To illustrate the use of the design methods, controllers have been designed for a simple but typical suspension system. For this system the controllers based on a quadratic norm perform comparably but the controllers based on output feedback are less robust. The H∞ controller did not perform well for this problem when the same weighting functions were used to generate the controller as for the LQ method. Use of the H∞ design method therefore requires careful tuning of the weighting functions. Use of the standard functions is inappropriate.
Optimal open/closed‐loop control of a rayleigh beam
Authors: Esfandiari Ramin S. , Sadek Ibrahim S.
Published: July 2007

Optimal open/closed‐loop control of a Rayleigh beam relative to a specified performance measure is investigated. A method to suppress the undesired transient beam vibrations is proposed and utilized to obtain numerical results for different problem parameters. With the assumption of a prescribed closed‐loop control law, the Fourier‐type open‐loop optimal control law is derived in closed form through minimization of the performance measure via a calculus‐of‐variations technique. Numerical results presented in graphical form indicate that a feedback control mechanism may be effectively utilized in the presence of an open‐loop control.
Generalized predictive self‐tuning control for tracking a periodic reference signal
Authors: Sakai Hideaki
Published: July 2007

A generalized predictive control scheme for tracking a periodic reference signal, based on the internal model principle, is proposed. Using LQ regulator theory, some stability results are derived. Also, some simulation results for the self‐tuning case are presented to see the effectiveness of the proposed method.
Optimal control of the penicillin G fed‐batch fermentation: An analysis of the model of heijnen et al.
Authors: van Impe Jan F. , Nicolaï Bart M. , Vanrolleghem Peter A. , Spriet Jan A. , De Moor Bart , Vandewalle Joos
Published: July 2007

This paper presents the application of optimal control theory in determining the optimal feed rate profile for the penicillin G fed‐batch fermentation, using a mathematical model based on balancing methods. Since this model does not fulfil all requisites for standard optimal control, we propose a sequence of new models — that converges to the original one in a smooth way — to which the standard techniques are applicable. The unusual optimization of some initial conditions is included. We then state the conjecture that allows us to obtain the optimal control for the original model. The enormous gains in production and the vanishing of the characteristic biphasic behaviour through feed rate profile optimization raise some questions concerning the validity of this model. In this way this optimal control study can prove to be very useful for model discrimination purposes. Furthermore, mathematical and microbial insights lead to the construction of a suboptimal heuristic strategy — which we show to be a limiting case of the optimal scheme — that can serve as a basis for the development of robust, model‐independent, optimal adaptive control schemes.
A numerical algorithm for singular optimal control synthesis using continuation methods
Authors: Chen Yaobin , Huang Jian
Published: July 2007

This paper presents an efficient computational method for the synthesis of singular optimal control problems. The proposed numerical procedure consists of two phases. In the first phase the original singular optimal control problem is converted into a non‐singular one by adding to the performance index a perturbed (or weighted) energy term. The resultant boundary value problem can easily be solved for an appropriately large value of the perturbation parameter. In the second phase the solution obtained from the first phase is refined in a systematic manner based on continuation methods (imbedding methods or homotopy methods) until the optimal (or suboptimal) solution to the original problem is achieved. One of the major advantages of the proposed algorithm is that the resultant two‐point boundary value problem need be solved just once for a properly large perturbation parameter and the refinement of the solution is accomplished by solving a set of initial value problems sequentially and/or in parallel as the perturbation parameter goes to zero. The proposed algorithm is therefore computationally efficient and applicable to a large class of optimal control problems with various boundary conditions (e.g. fixed and free terminal time). The practicability of the method is demonstrated by computer simulations on an example problem.
Public sector capacity reform in Ethiopia: a tale of success in two ministries?
Authors: Mengesha Getachew Hailemariam , Common Richard
Published: July 2007

To enhance the capacity of public institutions in Ethiopia and to create an ideal environment for investment and economic growth, the public sector has gone through a series of reform processes including the civil service. This article attempts to assess the outcomes of the Public Sector Capacity reform, based on a small‐scale survey conducted in two ministries. The survey, which was conducted between March and May in 2005, reveals a notable transformation of service delivery in each organisation. Very high levels of user satisfaction and spectacular improvements in performance were also recorded as a result of the introduction of business process reengineering (BPR). Although the change process in both organisations tended to be sluggish, these improvements appear to be outstanding within the context of Ethiopia's system of public administration. However, one challenge will be for the government to maintain the momentum of reform and to cascade BPR and other elements of the reform to other divisions, departments and work units in the government. Putting in place incentive schemes and an appropriate monitoring system should protect the reform from backsliding. Despite the pessimistic accounts of public sector reform in African countries, this article reveals that there are positive findings of interest to the field of development administration. Copyright © 2007 John Wiley & Sons, Ltd.
Multiscale fiber‐reinforced composites prepared by vacuum‐assisted resin transfer molding
Authors: Song Young Seok
Published: July 2007

Carbon nanotube (CNT)/aramid fiber epoxy composites were produced using a new manufacturing method proposed in this study. The rheological and morphological experiments of the CNT/PEO nanocomposites indicates that the PEO nanocomposites have a good dispersion state of the CNTs. The flexural mechanical properties of the aramid fiber/CNT epoxy composites were measured. The CNTs dispersed in the epoxy resin between the aramid fibers were observed using field emission scanning electron miscroscope (FESEM). It was found that the flexural properties of the multiscale fiber‐reinforced composites were higher than those of aramid fiber/epoxy composites. POLYM. COMPOS., 28:458–461, 2007. © 2007 Society of Plastics Engineers.
Tuning the parameters of the suspension polymerization of styrene, divinylbenzene, and N‐(p‐vinylbenzyl)‐ 4,4‐dimethylazlactone
Authors: Lucchesi Céline , Pascual Sagrario , Jouanneaux Alain , Dujardin Gilles , Fontaine Laurent
Published: July 2007

Azlactone‐functionalized microporous polystyrene resins were synthesized by suspension polymerization of styrene, divinylbenzene and N‐(p‐vinylbenzyl)‐4,4‐dimethylazlactone (VBM). A fractional factorial design of experiments (DOE) has been used to evaluate the influence of several parameters (factors) on the physical and chemical properties (responses) of the resins. Six factors were considered: (i) the organic/aqueous phase ratio, (ii) the amount of the functional monomer N‐(p‐vinylbenzyl)‐4,4‐dimethylazlactone, (iii) the amount of stabilizer, (iv) the amount of initiator, (v) the stirring speed, and (vi) the equilibration time. The process responses were the yield of polymerization, the diameter of the beads and their polydispersity, their swelling ratio in dichloromethane and the accessibility ratio of the immobilized azlactone sites. This methodology enables the determination of an optimal combination of the six factors to synthesize beads in high yield (92%) with remarkable properties for SPOS applications (azlactone sites loading = 1.57 mmol/g, swelling ratio in dichloromethane = 5.0 mL/g and 100% accessibility ratio). © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3677–3686, 2007
Annexin A2/P11 interaction: New insights into annexin A2 tetramer structure by chemical crosslinking, high‐resolution mass spectrometry, and computational modeling
Authors: Schulz Daniela M. , Kalkhof Stefan , Schmidt Andreas , Ihling Christian , Stingl Christoph , Mechtler Karl , Zschörnig Olaf , Sinz Andrea
Published: July 2007

During the past few years, the structural analysis of proteins and protein complexes by chemical crosslinking and mass spectrometry has enjoyed increasing popularity. With this approach we have investigated the quaternary structure of the complex between annexin A2 and p11, which is involved in numerous cellular processes. Although high‐resolution data are available for both interaction partners as well as for the complex between two p11 subunits and two annexin A2 N‐terminal peptides, the structure of the complete annexin A2/p11 heterotetramer has not yet been solved at high resolution. Thus, the quaternary structure of the biologically relevant, membrane‐bound annexin A2/p11 complex is still under discussion, while the existence of a heterotetramer or a heterooctamer is the prevailing opinion. We gained further insight into the spatial organization of the annexin A2/p11 heterotetramer by employing chemical crosslinking combined with high‐resolution mass spectrometry. Furthermore, tandem mass spectrometry served as a tool for an exact localization of crosslinked amino acid residues and for a confirmation of crosslinked product assignment. On the basis of distance constraints from the crosslinking data we derived structural models of the annexin A2/p11 heterotetramer by computational docking with Rosetta. We propose an octameric model for the annexin A2/p11 complex, which exerts annexin A2 function. The proposed structure of the annexin A2/p11 octamer differs from so far suggested models and sheds new light into annexin A2/p11 interaction. Proteins 2007. © 2007 Wiley‐Liss, Inc.
QM/MM linear response method distinguishes ligand affinities for closely related metalloproteins
Authors: Khandelwal Akash , Balaz Stefan
Published: July 2007

Design of selective ligands for closely related targets is becoming one of the most important tasks in the drug development. New tools, more precise than fast scoring functions and less demanding than sophisticated Free Energy Perturbation methods, are necessary to help accomplish this goal. The methods of intermediate complexity, characterizing individual contributions to the binding energy, have been an area of intense research in the past few years. Our recently developed quantum mechanical/molecular mechanical (QM/MM) modification of the Linear Response (LR) method describes the binding free energies as the sum of empirically weighted contributions of the QM/MM interaction energies and solvent‐accessible surface areas for the time‐averaged structures of hydrated complexes, obtained by molecular dynamics (MD) simulations. The method was applied to published data on 27 inhibitors of matrix metalloproteinase‐3 (MMP‐3). The two descriptors explained 90% of variance in the inhibition constants with RMSE of 0.245 log units. The QM/MM treatment is indispensable for characterization of the systems lacking suitable force‐field expressions. In this case, it provided characteristics of H‐bonds of the inhibitors to Glu202, charges of binding site atoms, and accurate coordination geometries of the ligands to catalytic zinc. The geometries were constrained during the MD simulations, which characterized conformational flexibility of the complexes and helped in the elucidation of the binding differences for related compounds. A comparison of the presented QM/MM LR results with those previously published for inhibition of MMP‐9 by the same set of ligands showed that the QM/MM LR approach was able to distinguish subtle differences in binding affinities for MMP‐3 and MMP‐9, which did not exceed one order of magnitude. This precision level makes the approach a useful tool for design of selective ligands to similar targets, because the results can be safely extrapolated to maximize selectivity. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Ureido group containing cyclic dermorphin(1–7) analogues: synthesis, biology and conformation
Authors: Witkowska Ewa , Nowakowski MichaŁ , Oleszczuk Marta , Filip Katarzyna , Ciszewska MaŁgorzata , Chung Nga N. , Schiller Peter W. , Wójcik Jacek , Izdebski Jan
Published: July 2007

Six cyclic peptides related to dermorphin(1–7) have been synthesized. The synthesis of linear peptides containing diamino acid residues in positions 2 and 4 was carried out on a 4‐methylbenzhydrylamine resin, and cyclization was achieved by treatment with bis‐(4‐nitrophenyl)carbonate to form a urea unit. The peptides were tested in the guinea‐pig ileum (GPI) and mouse vas deferens (MVD) assays. Diverse opioid agonist activities were observed, depending on the size of the ring. The results were compared with those obtained earlier for 1–4 dermorphin analogues. The conformations of all six dermorphin analogues were studied. The conformational space of the peptides was examined using the electrostatically driven Monte Carlo method. On the basis of NMR data, an ensemble of conformations was obtained for each peptide. The opioid activity profiles of the compounds are discussed in the light of the structural data. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.
Structure of small II‐VI semiconductor nanoparticles: A new approach based on powder diffraction
Authors: Niederdraenk Franziska , Seufert Knud , Luczak Pawel , Kulkarni Sulabha K. , Chory Christine , Neder Reinhard B. , Kumpf Christian
Published: July 2007

In many cases of nanostructures a better understanding of the optical, electronic, and catalytic properties is hindered by a lack of detailed structural knowledge of sufficient quality. This is in particular true for very small nanoparticles (<5 nm) where quantum confinement effects play a dominant role. We introduce a novel method for the detailed structural analysis of such small nanoparticles, which includes not only the modeling of basic parameters like size, shape, and structure, but also allows to determine impurities and defects (like, e.g., stacking faults), stress and relaxation effects, etc. Distributions of basic parameters as the size distribution are also implemented by enabling ensemble averaging. Different examples obtained from CdS, ZnS and ZnO particles are presented and demonstrate the superiority of the new approach compared to simpler methods. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Comparison of the effect of volume conduction on EEG coherence with the effect of field spread on MEG coherence
Authors: Winter William R. , Nunez Paul L. , Ding Jian , Srinivasan Ramesh
Published: July 2007

We analyzed models of volume conduction and magnetic field spread to account for aspects of spatial structure in electroencephalographic (EEG) and magnetoencephalographic (MEG) coherence. The head volume conduction model consisted of three confocal ellipsoids, representing three layers (brain, skull, and scalp) with different tissue conductivities, while the magnetic field model follows from the Biot–Savart law in a spherically symmetric medium. Source models were constructed based on magnetic resonance imaging data from three subjects, approximating neocortical current source distributions as dipoles oriented perpendicular to the local cortical surface. Assuming that every source is uncorrelated to every other source, coherence between sensors due to volume conduction and field‐spread effects was estimated. Spatial properties of the model coherences were then compared with simultaneously recorded spontaneous EEG and MEG. In both models and experimental data, EEG and MEG coherence was elevated between closely spaced channels. At very large channel separations, the field‐spread effect on MEG coherence appears smaller than the volume conduction effect on EEG coherence. In EEG coherence studies, surface Laplacian methods can be used to remove volume conduction effects. With single‐coil magnetometers, MEG coherences are free of field effects only for sensor pairs separated by more than 20 cm. Model coherences resemble most high‐frequency (e.g. >20 Hz) data; volume conduction and field‐spread effects are independent of frequency, suggesting mostly uncorrelated sources in these bands. High‐frequency EEG and MEG coherence can evidently serve as an estimate of coherence effects due to volume conduction and field effects, when source and head models are not available for individual subjects. Copyright © 2007 John Wiley & Sons, Ltd.
EPR Study of Radicals Generated in Starch by Microwaves or by Conventional Heating
Authors: Dyrek Krystyna , Bidzińska Ewa , Łabanowska Maria , Fortuna Teresa , Przetaczek Izabela , Pietrzyk Sławomir
Published: July 2007

Irradiation of starch with microwaves or heating at relatively low temperature (483 K) generates radicals with anisotropic EPR signals (signal I and II) of lorentzian shape and similar g factors (gav=2.006 and 2.007 in X and Q band, respectively). Signal I, exhibiting a doublet hyperfine structure (HFS) with Aav=1.19 mT (X band) and Aav=1.24 mT (Q band), was ascribed to a carbon radical with an unpaired electron localized at C(1) of the glucose unit, from which a hydrogen atom was abstracted. The electron interacts with the nuclear spin of the β‐hydrogen at C(2). Signal II, with g factor values similar to that of signal I but without HFS, was assigned to a radical with unpaired electron localized also at C(1) of the glucose unit from which, however, two hydrogens (α and β) were abstracted from C(1) and C(2), respectively. Signals I and II show different saturation ability in the power range 0.3–30 mW. Radicals generated in the native starch at higher temperature (503 K) exhibit more intensive EPR spectra, with dominating signal II and lower HFS constant of the signal I. The same trend of weakening of the HF interactions is observed for oxidized starch, proving that the β‐hydrogen is abstracted more easily from C(2) at higher temperature. The decay of the radicals generated by microwaves or by heating at 483 K, during storing at 293 K, occurs monotonously, according to a second order kinetics. On the other hand, the radicals formed at higher temperature (503 K) represent nonmonotonous changes with the time of storing at 293 K. Such behavior may be explained assuming nonuniform distribution of thermally generated radicals, which partially do not contribute to the signal intensity leading to the significant broadening of the EPR lines. During relaxation the radicals became better dispersed which makes them active in EPR.
Comparative evaluation of the toxicity and genotoxicity of cadmium in amphibian larvae (Xenopus laevis and Pleurodeles waltl) using the comet assay and the micronucleus test
Authors: Mouchet F. , Gauthier L. , Baudrimont M. , Gonzalez P. , Mailhes C. , Ferrier V. , Devaux A.
Published: July 2007

The toxic and genotoxic potential of Cadmium (CdCl2) were evaluated by the micronucleus test (MNT) and comet assay (CA) using amphibian larvae (Xenopus laevis and Pleurodeles waltl). Acute toxicity results showed that Cd is toxic to Xenopus larvae exposed from 2 to 50 mg/L and to Pleurodeles from 5 to 50 mg/L, depending on the nature of the water (reconstituted water containing mineral salts or mineral water MW (Volvic®)). The MNT results obtained in MW showed that Cd (2 mg/L) is genotoxic to Xenopus, whereas it was not genotoxic to Pleurodeles at all concentrations tested. The CA established that the genotoxicity of Cd to Xenopus and Pleurodeles larvae depends on the concentration, the exposure times, and the comet parameters (Tail DNA, ETM, OTM, and TL). The CA and MNT results were compared for their ability to detect genotoxic effects, considering the concentrations of Cd applied and the exposure time. The CA showed Cd to be genotoxic from the first day of exposure. In amphibians, the CA appears to be a sensitive and suitable method for detecting genotoxicity such as that caused by Cd. © 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 422–435, 2007.
Characteristics of effective summer learning programs in practice
Authors: Bell Susanne R. , Carrillo Natalie
Published: July 2007

The Center for Summer Learning examined various summer program models and found that there are nine characteristics that provide a framework for effective summer programs. In this chapter, the authors demonstrate how effective practices lead to positive results for young people.

The nine characteristics of effective summer learning programs are (1) accelerating learning, (2) youth development, (3) proactive approach to summer learning, (4) leadership, (5) advanced planning, (6) staff development, (7) strategic partnerships, (8) evaluation and commitment to program improvement, and (9) sustainability and cost‐effectiveness. These characteristics are divided into two sections. The first three characteristics address a program's approach to learning. Summer instructional techniques are most effective when academic learning is woven into enrichment activities and youth development. The second section covers program infrastructure to ensure the organization achieves and maintains quality programming. The nine characteristics complement each other to ensure a strong program that works to prevent summer learning loss and narrow the achievement gap.

To demonstrate the variety of high‐quality programs that include the nine characteristics, thirteen program profiles at the conclusion of the chapter each highlight one of the characteristics. These profiles show the various approaches that different summer programs have developed to accelerate academic achievement and promote positive development for young people in their communities.
Monitoring yeast physiology during very high gravity wort fermentations by frequent analysis of gene expression
Authors: Rautio Jari J. , Huuskonen Anne , Vuokko Heikki , Vidgren Virve , Londesborough John
Published: July 2007

Brewer's yeast experiences constantly changing environmental conditions during wort fermentation. Cells can rapidly adapt to changing surroundings by transcriptional regulation. Changes in genomic expression can indicate the physiological condition of yeast in the brewing process. We monitored, using the transcript analysis with aid of affinity capture (TRAC) method, the expression of some 70 selected genes relevant to wort fermentation at high frequency through 9–10 day fermentations of very high gravity wort (25°P) by an industrial lager strain. Rapid changes in expression occurred during the first hours of fermentations for several genes, e.g. genes involved in maltose metabolism, glycolysis and ergosterol synthesis were strongly upregulated 2–6 h after pitching. By the time yeast growth had stopped (72 h) and total sugars had dropped by about 50%, most selected genes had passed their highest expression levels and total mRNA was less than half the levels during growth. There was an unexpected upregulation of some genes of oxygen‐requiring pathways during the final fermentation stages. For five genes, expression of both the Saccharomyces cerevisiae and S. bayanus components of the hybrid lager strain were determined. Expression profiles were either markedly different (ADH1, ERG3) or very similar (MALx1, ILV5, ATF1) between these two components. By frequent analysis of a chosen set of genes, TRAC provided a detailed and dynamic picture of the physiological state of the fermenting yeast. This approach offers a possible way to monitor and optimize the performance of yeast in a complex process environment. Copyright © 2007 John Wiley & Sons, Ltd.
Comparative genomics of the environmental stress response in ascomycete fungi
Authors: Gasch Audrey P.
Published: July 2007

Unicellular fungi thrive in diverse niches around the world, and many of these niches present unique and stressful challenges that must be contended with by their inhabitants. Numerous studies have investigated the genomic expression responses to environmental stress in ‘model’ ascomycete fungi, including Saccharomyces cerevisiae, Candida albicans and Schizosaccharomyces pombe. This review presents a comparative‐genomics perspective on the environmental stress response, a common response to diverse stresses. Implications for the role of this response, based on its presence or absence in fungi from disparate ecological niches, are discussed. Copyright © 2007 John Wiley & Sons, Ltd.
A2 and A4 Flexor Pulley Biomechanical Analysis: Comparison among Gender and Digit
Authors: Mallo Gregory Charles , Sless Yury , Hurst Lawrence C. , Wilson Kevin
Published: July 2007

Rock climbing has become increasingly more popular in the USA over the past two decades. Accordingly, with increased participation comes an increase in climbing-related injuries. Rooks et al noted that three-quarters of elite and recreational climbers will suffer upper extremity injuries, approximately 60% involving the hand or wrist and 40% divided evenly between the shoulder and elbow. Most of these injures will be strains, microtrauma, and tendonitis; however, 30–50% represent trauma to the proximal interphalangeal region. The purpose of this study was to investigate the biomechanical properties of the A2 and A4 pulley and compare biomechanical properties among gender and digit. A specially designed materials testing machine, shown in the included figure, measured maximum breaking load, displacement and stiffness of the A2 and A4 pulleys of ten cadaveric hands using an S hook to apply a steady force until complete pulley rupture. The A2 and A4 biomechanical properties of breaking load, displacement, and stiffness did not significantly differ among the index, middle, ring, and little fingers. Additionally, there was no significant difference in A2 or A4 pulley biomechanics between male and female specimens. The A2 and A4 pulleys among differing digits and genders have similar biomechanical properties in regards to maximum breaking load, displacement, and stiffness.
Phenology, nectar production and visitation behaviour of bats on the flowers of the bromeliad Werauhia gladioliflora in a Costa Rican lowland rain forest
Authors: Tschapka Marco , von Helversen Otto
Published: July 2007

We studied the interaction between the bromeliad Werauhia gladioliflora and its flower visitors in the Caribbean lowland forest of Costa Rica, in order to quantify the mutual benefits to both partners. Over 6 y, the bromeliads flowered mainly between October and December; with an individual inflorescence flowering for an average of 34 d (n = 233 inflorescences). The bromeliad showed a flexible breeding system with autogamy occurring in addition to cross-pollination. Exclusive pollinators were small nectar-feeding bats (Phyllostomidae: Glossophaginae). The average volume of nectar produced per flower was 1.1 ml (n = 25 flowers). The main visitor was the bat Glossophaga commissarisi, which approached the flowers exclusively using hovering flight. Visitation by bats, measured by infrared light sensors, occurred throughout the night with an activity peak after midnight. Median hovering duration of the bats at the flowers was 320 ms (n = 1246 visits). Hourly mean of hovering duration was negatively correlated with hourly nectar secretion rate. The flower visitation behaviour of a bat over the night seems to be shaped by a combination of intrinsic physiological factors and by nectar availability. Size of both flowers and visitors make Werauhia gladioliflora a very accessible system for quantification of factors affecting evolution of bat–plant interactions.
Adaptive function of drip tips: a test of the epiphyll hypothesis in Psychotria marginata and Faramea occidentalis (Rubiaceae)
Authors: Burd Martin
Published: July 2007

Drip tips are thought to resist the growth of epiphyllous fungi, lichens, bryophytes and algae on leaf surfaces by promoting the drainage of water following rain. This hypothesis was tested by altering the tip of one leaf in each of 50 pairs of opposite leaves on plants of each of two woody species in the understorey of Barro Colorado Island, Panama. After 11 mo in situ, there were no statistical differences between the mean epiphyll cover on leaves with and leaves without drip tips. Epiphyll cover was, however, strongly correlated between the opposite leaves at a node, even though one had a drip tip and the other had the tip removed. This correlation could be due to small-scale heterogeneity of insolation, temperature and humidity in the crowns of plants. A relationship between epiphyll cover and growth of the branch containing the leaves provides qualitative support for this interpretation. It seems clear that drip tips do not have a large, consistent, easily detectable effect on epiphyll cover. However, because of the tiny cost of drip tips, reductions in epiphyll growth that are small and transitory and occur in only a portion of a plant's leaves may provide sufficient advantage to explain the evolution of drip tips. No experiment to date has been capable of detecting such effects.
Domains and directionality in the evolution of German final fortition
Authors: Iverson Gregory K. , Salmons Joseph C.
Published: July 2007

Laryngeal realism (Honeybone 2005) holds that thoroughly voiced stops in a language like Dutch will be represented phonologically with the feature [voice], leaving the voiceless unaspirated stops laryngeally neutral, whereas the typically aspirated stops of a language like German are marked with the feature [spread glottis], rendering the passively voiced stops in this language neutral. These two languages also merge laryngeal oppositions in final environments, Dutch undergoing final devoicing but German final fortition. We apply the findings of Evolutionary Phonology (Blevins 2004, 2006b) to these distinctions in final laryngeal neutralisation, underscoring that the evolutionary approach to phonological alternation allows for non-assimilatory feature addition as well as loss. We examine in particular the known history of final fortition in German and find that the reference standard form of the language has evolved an alignment condition to the effect that a fortified syllable edge must match up with the morpheme edge.
Understanding near mergers: the case of morphological tone in Cantonese
Authors: Yu Alan C. L.
Published: July 2007

A growing body of work on exemplar-based theories of learning suggests the possibility of formal models of phonological representation which will offer deeper explanations of basic phonological properties than current models allow. The main purpose of this paper is to shed light on near merger, a recalcitrant problem in sound change and in phonological theory, with this newer perspective, through a case study of tonal near merger in Cantonese.
Consumer preferences for front-of-pack calories labelling
Authors: van Kleef Ellen , van Trijp Hans , Paeps Frederic , Fernández-Celemín Laura
Published: July 2007

Objective

In light of the emerging obesity pandemic, front-of-pack calories labels may be an important tool to assist consumers in making informed healthier food choices. However, there is little prior research to guide key decisions on whether caloric content should be expressed in absolute terms or relative to recommended daily intake, whether it should be expressed in per serving or per 100 g and whether the information should be further brought alive for consumers in terms of what the extra calorie intake implies in relation to activity levels. The present study aimed at providing more insight into consumers’ appreciation of front-of-pack labelling of caloric content of food products and their specific preferences for alternative execution formats for such information in Europe.

Design

For this purpose, eight executions of front-of-pack calorie flags were designed and their appeal and information value were extensively discussed with consumers through qualitative research in four different countries (Germany, The Netherlands, France and the UK).

Results

The results show that calories are well-understood and that participants were generally positive about front-of-pack flags, particularly when flags are uniform across products. The most liked flags are the simpler flags depicting only the number of calories per serving or per 100 g, while more complex flags including references to daily needs or exercise and the flag including a phrase referring to balanced lifestyle were least preferred. Some relevant differences between countries were observed. Although participants seem to be familiar with the notion of calories, they do not seem to fully understand how to apply them.

Conclusion

From the results, managerial implications for the design and implementation of front-of-pack calorie labelling as well as important directions for future research are discussed.
Patient reactions to hospital choice in Norway, Denmark, and Sweden
Authors: VRANGBÆK KARSTEN , ØSTERGREN KATARINA , BIRK HANS OKKELS , WINBLAD ULRIKA
Published: July 2007

This article is a comparative study of three Scandinavian countries – Norway, Denmark, and Sweden – all of which have provided the individual patient with extensive rights to choose the hospital where he/she wishes to receive treatment. In the paper, we present an analysis of the utilization of the opportunity to choose between hospitals in these three countries. The analysis addresses two questions: (i) How many patients are exercising the right to choose between hospitals in these countries and who is making use of this opportunity? (ii) How can we explain the observed utilization pattern? The results of the study reveal clear similarities between the three countries and suggest that few patients have actually chosen their hospital. However, a gradual increase can be observed over the years. Few formal, legislative, or economic barriers exist for patients. Instead, limited knowledge amongst patients regarding reforms, combined with insufficient support from GPs and limited information, can explain why few patients choose to receive care outside of their local region.
The American right-wing policy agenda
Authors: JOST TIMOTHY STOLTZFUS
Published: July 2007

Right-wing health policy is alive and well in the United States. Pro-business and libertarian health policy advocacy groups, generously funded by right-wing foundations (and, in some instances, by the health care industry), produce a continuous stream of press releases, policy-statements, books, articles, and symposia, as well as testimony before legislative and administrative bodies. Their positions are taken very seriously by the American media, who make certain that right-wing policy experts are represented in any discussion of current health policy issues.
Organizational innovations and health care decentralization: a perspective from Spain
Authors: LÓPEZ-CASASANOVAS GUILLEM
Published: July 2007

Recent policy developments in public health care systems lead to a greater diversity in health care. Decentralization, either geographically or at an institutional level, is the key force, because it encourages innovation and local initiatives in health care provision. The devolution of responsibilities allows for a sort of ‘deconstruction’ of the status quo by changing both organizational forms and service provision. The new organizations enjoy greater freedom in the way they pay their staff, and are judged according to the results. These organizations may retain financial surpluses, develop ‘spin-off’ companies, and commission a range of specialized services (such as Diagnostic and Treatment Centres in UK) from providers outside the institutional setting in order to have more access to capital markets. However, this diversity may generate a feeling of a lack of commitment to a national health service and ultimately a loss of social cohesion. Through fiscal decentralization to regional authorities or planned delegation of financial agreements to providers, financial incentives are more explicit and may seem to place profit making above a commitment to better health care. An evaluation of the ‘myths and realities’ of the decentralization process is needed. Here, I offer an assessment of the ‘pros’ and ‘cons’ of the health care decentralization process in Spain, drawing on the experience of regional reforms from the pioneering organizational innovations implemented in Catalonia in 1981, up to the currently observed dispersion of health care spending per capita across the regions.
Supplementary health insurance as a tool for risk-selection in mandatory basic health insurance markets
Authors: PAOLUCCI FRANCESCO , SCHUT ERIK , BECK KONSTANTIN , GREß STEFAN , VAN DE VOORDE CARINE , ZMORA IRIT
Published: July 2007

As the share of supplementary health insurance (SI) in health care finance is likely to grow, SI may become an increasingly attractive tool for risk-selection in basic health insurance (BI). In this paper, we develop a conceptual framework to assess the probability that insurers will use SI for favourable risk-selection in BI. We apply our framework to five countries in which risk-selection via SI is feasible: Belgium, Germany, Israel, the Netherlands, and Switzerland. For each country, we review the available evidence of SI being used as selection device. We find that the probability that SI is and will be used for risk-selection substantially varies across countries. Finally, we discuss several strategies for policy makers to reduce the chance that SI will be used for risk-selection in BI markets.
Post‐ischemic treatment with erythropoietin or carbamylated erythropoietin reduces infarction and improves neurological outcome in a rat model of focal cerebral ischemia
Authors: Wang Y , Zhang Z G , Rhodes K , Renzi M , Zhang R L , Kapke A , Lu M , Pool C , Heavner G , Chopp M
Published: July 2007

Background and purpose:

Recombinant human erythropoietin (rhEPO; Epoetin‐α; PROCRIT™) has been shown to exert neuroprotective and restorative effects in a variety of CNS injury models. However, limited information is available regarding the dose levels required for these beneficial effects or the neuronal responses that may underlie them. Here we have investigated the dose‐response to rhEPO and compared the effects of rhEPO with those of carbamylated rhEPO (CEPO) in a model of cerebral stroke in rats.

Experimental approach:

Rats subjected to embolic middle cerebral artery occlusion (MCAo) were treated with rhEPO or CEPO, starting at 6 h and repeated at 24 and 48 h, after MCAo. Cerebral infarct volumes were assessed at 28 days and neurological impairment at 7, 14, 21 and 28 days, post‐MCAo.

Key results:

rhEPO at dose levels of 500, 1150 or 5000 IU kg−1 or CEPO at a dose level of 50 μg kg−1 significantly reduced cortical infarct volume and reduced neurologic impairment. All doses of rhEPO, but not CEPO, produced a transient increase in haematocrit, while rhEPO and CEPO substantially reduced the number of apoptotic cells and activated microglia in the ischemic boundary region.

Conclusions and implications:

These data indicate that rhEPO and CEPO have anti‐inflammatory and anti‐apoptotic effects, even with administration at 6 h following embolic MCAo in rats. Taken together, these actions of rhEPO and CEPO are likely to contribute to their reduction of neurologic impairment following cerebral ischemia.

British Journal of Pharmacology (2007) 151, 1377–1384; doi:10.1038/sj.bjp.0707285
Specificity of the ecto‐ATPase inhibitor ARL 67156 on human and mouse ectonucleotidases
Authors: Lévesque S A , Lavoie É G , Lecka J , Bigonnesse F , Sévigny J
Published: July 2007

Background and purpose:

ARL 67156, 6‐N,N‐Diethyl‐D‐β‐γ‐dibromomethylene adenosine triphosphate, originally named FPL 67156, is the only commercially available inhibitor of ecto‐ATPases. Since the first report on this molecule, various ectonucleotidases responsible for the hydrolysis of ATP at the cell surface have been cloned and characterized. In this work, we identified the ectonucleotidases inhibited by ARL 67156.

Experimental approach:

The effect of ARL 67156 on recombinant NTPDase1, 2, 3 & 8 (mouse and human), NPP1, NPP3 and ecto‐5′‐nucleotidase (human) have been evaluated. The inhibition of the activity of NTPDases (using the following substrates: ATP, ADP, UTP), NPPs (pnp‐TMP, Ap3A) and ecto‐5′‐nucleotidase (AMP) was measured by colorimetric or HPLC assays.

Key results:

ARL 67156 was a weak competitive inhibitor of human NTPDase1, NTPDase3 and NPP1 with Ki of 11±3, 18±4 and 12±3 μM, respectively. At concentrations used in the literature (50–100 μM), ARL 67156 partially but significantly inhibited the mouse and human forms of these enzymes. NTPDase2, NTPDase8, NPP3 and ecto‐5′‐nucleotidase activities were less affected. Importantly, ARL 67156 was not hydrolysed by either human NTPDase1, 2, 3, 8, NPP1 or NPP3.

Conclusions and implications:

In cell environments where NTPDase1, NTPDase3, NPP1 or mouse NTPDase8 are present, ARL 67156 would prolong the effect of endogenously released ATP on P2 receptors. However, it does not block any ectonucleotidases efficiently when high concentrations of substrates are present, such as in biochemical, pharmacological or P2X7 assays. In addition, ARL 67156 is not an effective inhibitor of NTPDase2, human NTPDase8, NPP3 and ecto‐5′‐nucleotidase.

British Journal of Pharmacology (2007) 152, 141–150; doi:10.1038/sj.bjp.0707361
α1‐Adrenoceptors and ejaculatory function
Authors: Michel M C
Published: July 2007

The abnormal ejaculation of semen is a typical but infrequent side effect of someα1‐adrenoceptor antagonists, particularly those with selectivity forα1A‐adrenoceptors such as silodosin or tamsulosin. Recent clinical studies suggest that this represents a relative anejaculation rather than a retrograde ejaculation. An elegant study in this issue of the journal usingα1Asingle andα1A/B/Dtriple knock‐out mice reports a similar phenomenon in rodents. Using a multi‐disciplinary approach, the reduced ejaculation and related male infertility is shown to be caused by an impaired function of the vas deferens rather than by alterations in sperm formation, number or function. Similarities and differences between mouse and human data are discussed, particularly why a complete inhibition of all threeα1‐adrenoceptor subtypes has the strongest effects in mice whereas apparently onlyα1A‐adrenoceptor‐selective drugs impair ejaculatory function in humans.

British Journal of Pharmacology(2007)152, 289–290; doi:10.1038/sj.bjp.0707369; published online 2 July 2007
Origin and evolution of high throughput screening
Authors: Pereira D A , Williams J A
Published: July 2007

This article reviews the origin and evolution of high throughput screening (HTS) through the experience of an individual pharmaceutical company, revealing some of the mysteries of the early stages of drug discovery to the wider pharmacology audience. HTS in this company (Pfizer, Groton, USA) had its origin in natural products screening in 1986, by substituting fermentation broths with dimethyl sulphoxide solutions of synthetic compounds, using 96‐well plates and reduced assay volumes of 50‐100μl. A nominal 30mM source compound concentration provided high μM assay concentrations. Starting at 800 compounds each week, the process reached a steady state of 7200 compounds per week by 1989. Screening in the Applied Biotechnology and Screening Group was centralized with screens operating in lock‐step to maximize efficiency. Initial screens were full files run in triplicate. Autoradiography and image analysis were introduced for 125I receptor ligand screens. Reverse transcriptase (RT) coupled with quantitative PCR and multiplexing addressed several targets in a single assay. By 1992 HTS produced ‘hits’ as starting matter for approximately 40% of the Discovery portfolio. In 1995, the HTS methodology was expanded to include ADMET targets. ADME targets required each compound to be physically detected leading to the development of automated high throughput LC‐MS. In 1996, 90 compounds/week were screened in microsomal, protein binding and serum stability assays. Subsequently, the mutagenic Ames assay was adapted to a 96‐well plate liquid assay and novel algorithms permitted automated image analysis of the micronucleus assay. By 1999 ADME HTS was fully integrated into the discovery cycle.

British Journal of Pharmacology (2007) 152, 53–61; doi:10.1038/sj.bjp.0707373
Telomerase and its potential for therapeutic intervention
Authors: Phatak P , Burger A M
Published: July 2007

Telomerase and telomeres are attractive targets for anticancer therapy. This is supported by the fact that the majority of human cancers express the enzyme telomerase which is essential to maintain their telomere length and thus, to ensure indefinite cell proliferation – a hallmark of cancer. Tumours have relatively shorter telomeres compared to normal cell types, opening the possibility that human cancers may be considerably more susceptible to killing by agents that inhibit telomere replication than normal cells. Advances in the understanding of the regulation of telomerase activity and the telomere structure, as well as the identification of telomerase and telomere associated binding proteins have opened new avenues for therapeutic intervention. Here, we review telomere and telomerase biology and the various approaches which have been developed to inhibit the telomere/telomerase complex over the past decade. They include inhibitors of the enzyme catalytic subunit and RNA component, agents that target telomeres, telomerase vaccines and drugs targeting binding proteins. The emerging role of telomerase in cancer stem cells and the implications for cancer therapy are also discussed.

British Journal of Pharmacology (2007) 152, 1003–1011; doi:10.1038/sj.bjp.0707374; published online 2 July 2007