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Showing papers by "University of Bath published in 2003"


Journal ArticleDOI
S. Agostinelli1, John Allison2, K. Amako3, J. Apostolakis4, Henrique Araujo5, P. Arce4, Makoto Asai6, D. Axen4, S. Banerjee7, G. Barrand, F. Behner4, Lorenzo Bellagamba8, J. Boudreau9, L. Broglia10, A. Brunengo8, H. Burkhardt4, Stephane Chauvie, J. Chuma11, R. Chytracek4, Gene Cooperman12, G. Cosmo4, P. V. Degtyarenko13, Andrea Dell'Acqua4, G. Depaola14, D. Dietrich15, R. Enami, A. Feliciello, C. Ferguson16, H. Fesefeldt4, Gunter Folger4, Franca Foppiano, Alessandra Forti2, S. Garelli, S. Gianì4, R. Giannitrapani17, D. Gibin4, J. J. Gomez Y Cadenas4, I. González4, G. Gracia Abril4, G. Greeniaus18, Walter Greiner15, Vladimir Grichine, A. Grossheim4, Susanna Guatelli, P. Gumplinger11, R. Hamatsu19, K. Hashimoto, H. Hasui, A. Heikkinen20, A. S. Howard5, Vladimir Ivanchenko4, A. Johnson6, F.W. Jones11, J. Kallenbach, Naoko Kanaya4, M. Kawabata, Y. Kawabata, M. Kawaguti, S.R. Kelner21, Paul R. C. Kent22, A. Kimura23, T. Kodama24, R. P. Kokoulin21, M. Kossov13, Hisaya Kurashige25, E. Lamanna26, Tapio Lampén20, V. Lara4, Veronique Lefebure4, F. Lei16, M. Liendl4, W. S. Lockman, Francesco Longo27, S. Magni, M. Maire, E. Medernach4, K. Minamimoto24, P. Mora de Freitas, Yoshiyuki Morita3, K. Murakami3, M. Nagamatu24, R. Nartallo28, Petteri Nieminen28, T. Nishimura, K. Ohtsubo, M. Okamura, S. W. O'Neale29, Y. Oohata19, K. Paech15, J Perl6, Andreas Pfeiffer4, Maria Grazia Pia, F. Ranjard4, A.M. Rybin, S.S Sadilov4, E. Di Salvo8, Giovanni Santin27, Takashi Sasaki3, N. Savvas2, Y. Sawada, Stefan Scherer15, S. Sei24, V. Sirotenko4, David J. Smith6, N. Starkov, H. Stoecker15, J. Sulkimo20, M. Takahata23, Satoshi Tanaka30, E. Tcherniaev4, E. Safai Tehrani6, M. Tropeano1, P. Truscott31, H. Uno24, L. Urbán, P. Urban32, M. Verderi, A. Walkden2, W. Wander33, H. Weber15, J.P. Wellisch4, Torre Wenaus34, D.C. Williams, Douglas Wright6, T. Yamada24, H. Yoshida24, D. Zschiesche15 
TL;DR: The Gelfant 4 toolkit as discussed by the authors is a toolkit for simulating the passage of particles through matter, including a complete range of functionality including tracking, geometry, physics models and hits.
Abstract: G eant 4 is a toolkit for simulating the passage of particles through matter. It includes a complete range of functionality including tracking, geometry, physics models and hits. The physics processes offered cover a comprehensive range, including electromagnetic, hadronic and optical processes, a large set of long-lived particles, materials and elements, over a wide energy range starting, in some cases, from 250 eV and extending in others to the TeV energy range. It has been designed and constructed to expose the physics models utilised, to handle complex geometries, and to enable its easy adaptation for optimal use in different sets of applications. The toolkit is the result of a worldwide collaboration of physicists and software engineers. It has been created exploiting software engineering and object-oriented technology and implemented in the C++ programming language. It has been used in applications in particle physics, nuclear physics, accelerator design, space engineering and medical physics.

18,904 citations


Journal ArticleDOI
17 Jan 2003-Science
TL;DR: In this article, a periodic array of microscopic air holes that run along the entire fiber length are used to guide light by corralling it within a periodic arrays of microscopic holes.
Abstract: Photonic crystal fibers guide light by corralling it within a periodic array of microscopic air holes that run along the entire fiber length Largely through their ability to overcome the limitations of conventional fiber optics—for example, by permitting low-loss guidance of light in a hollow core—these fibers are proving to have a multitude of important technological and scientific applications spanning many disciplines The result has been a renaissance of interest in optical fibers and their uses

3,918 citations


Journal ArticleDOI
TL;DR: Analysis of CA-MRSA isolates from the United States, France, Switzerland, Australia, New Zealand, and Western Samoa indicated distinct genetic backgrounds associated with each geographic origin, although predominantly restricted to the agr3 background.
Abstract: Infections caused by community-acquired (CA)-methicillin-resistant Staphylococcus aureus (MRSA) have been reported worldwide. We assessed whether any common genetic markers existed among 117 CA-MRSA isolates from the United States, France, Switzerland, Australia, New Zealand, and Western Samoa by performing polymerase chain reaction for 24 virulence factors and the methicillinresistance determinant. The genetic background of the strain was analyzed by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). The CAMRSA strains shared a type IV SCCmec cassette and the Panton-Valentine leukocidin locus, whereas the distribution of the other toxin genes was quite specific to the strains from each continent. PFGE and MLST analysis indicated distinct genetic backgrounds associated with each geographic origin, although predominantly restricted to the agr3 background. Within each continent, the genetic background of CA-MRSA strains did not correspond to that of the hospital-acquired MRSA.

1,790 citations


Journal ArticleDOI
TL;DR: In this paper, a review of definitions and classifications of types of risk in supply networks is provided, and a tool is provided and its testing and development in four case studies in the electronics sector is described.

903 citations


Journal ArticleDOI
10 Jul 2003-Nature
TL;DR: The hypothesis that dominance is a by-product of physiology and metabolism rather than the result of selection to mask the deleterious effects of mutations is supported, as it is found that members of large gene families are rarely involved in complexes.
Abstract: According to what we term the balance hypothesis, an imbalance in the concentration of the subcomponents of a protein - protein complex can be deleterious(1). If so, there are two consequences: first, both underexpression and overexpression of protein complex subunits should lower fitness, and second, the accuracy of transcriptional co-regulation of subunits should reflect the deleterious consequences of imbalance. Here we show that all these predictions are upheld in yeast ( Saccharomyces cerevisiae). This supports the hypothesis(2,3) that dominance is a by-product of physiology and metabolism rather than the result of selection to mask the deleterious effects of mutations. Beyond this, single-gene duplication of protein subunits is expected to be harmful, as this, too, leads to imbalance. As then expected, we find that members of large gene families are rarely involved in complexes. The balance hypothesis therefore provides a single theoretical framework for understanding components both of dominance and of gene family size.

819 citations


Journal ArticleDOI
30 Jan 2003-Nature
TL;DR: Three-dimensional analysis of the three-dimensional structure of human testicular ACE shows that it bears little similarity to that of carboxypeptidase A, but instead resembles neurolysin and Pyrococcus furiosus carboxy-zinc metallopeptidases with no detectable sequence similarity to ACE.
Abstract: Angiotensin-converting enzyme (ACE) has a critical role in cardiovascular function by cleaving the carboxy terminal His-Leu dipeptide from angiotensin I to produce a potent vasopressor octapeptide, angiotensin II. Inhibitors of ACE are a first line of therapy for hypertension, heart failure, myocardial infarction and diabetic nephropathy. Notably, these inhibitors were developed without knowledge of the structure of human ACE, but were instead designed on the basis of an assumed mechanistic homology with carboxypeptidase A. Here we present the X-ray structure of human testicular ACE and its complex with one of the most widely used inhibitors, lisinopril (N2-[(S)-1-carboxy-3-phenylpropyl]-L-lysyl-L-proline; also known as Prinivil or Zestril), at 2.0 A resolution. Analysis of the three-dimensional structure of ACE shows that it bears little similarity to that of carboxypeptidase A, but instead resembles neurolysin and Pyrococcus furiosus carboxypeptidase--zinc metallopeptidases with no detectable sequence similarity to ACE. The structure provides an opportunity to design domain-selective ACE inhibitors that may exhibit new pharmacological profiles.

718 citations


Journal ArticleDOI
01 Aug 2003-Quest
TL;DR: This article examined the influence of experience on coaching practice and found that it is experience and the observation of other coaches that remain the primary sources of knowledge for coaches, despite this, coach education and continuing professional development fail to draw effectively on this experience.
Abstract: Research over the last decade has demonstrated that it is experience and the observation of other coaches that remain the primary sources of knowledge for coaches. Despite this, coach education and continuing professional development fail to draw effectively on this experience. Using the work of Pierre Bourdieu, this paper attempts to understand how the “art of coaching” can be characterized as structured improvisation and how experience is crucial to structuring coaching practice. An examination of current coach education and assessment demonstrates that coaching practice viewed as a composite of knowledge has not specifically addressed the pervasive influence of experience on coaching practice. Drawing on experiences from the educational field, we examine how coach education and continuing professional development can utilize mentoring and critical reflection to situate learning in the practical experience of coaching.

680 citations


Journal ArticleDOI
TL;DR: Examination of the sequence changes at MLST loci during clonal diversification shows that point mutations give rise to new alleles at least 15-fold more frequently than does recombination, which suggests that homologous recombination does contribute toward the evolution of this species over the long term.
Abstract: Staphylococcus aureus is an important human pathogen and represents a growing public health burden owing to the emergence and spread of antibiotic-resistant clones, particularly within the hospital environment. Despite this, basic questions about the evolution and population biology of the species, particularly with regard to the extent and impact of homologous recombination, remain unanswered. We address these issues through an analysis of sequence data obtained from the characterization by multilocus sequence typing (MLST) of 334 isolates of S. aureus, recovered from a well-defined population, over a limited time span. We find no significant differences in the distribution of multilocus genotypes between strains isolated from carriers and those from patients with invasive disease; there is, therefore, no evidence from MLST data, which index variation within the stable “core” genome, for the existence of hypervirulent clones of this pathogen. Examination of the sequence changes at MLST loci during clonal diversification shows that point mutations give rise to new alleles at least 15-fold more frequently than does recombination. This contrasts with the naturally transformable species Neisseria meningitidis and Streptococcus pneumoniae, in which alleles change between 5- and 10-fold more frequently by recombination than by mutation. However, phylogenetic analysis suggests that homologous recombination does contribute toward the evolution of this species over the long term. Finally, we note a striking excess of nonsynonymous substitutions in comparisons between isolates belonging to the same clonal complex compared to isolates belonging to different clonal complexes, suggesting that the removal of deleterious mutations by purifying selection may be relatively slow.

637 citations



Journal ArticleDOI
Geof Wood1
TL;DR: The determining condition for poor people is uncertainty as mentioned in this paper, and the poor have less control over relationships and events around them, and are obliged to live more in the present and to discount the future.

561 citations


Journal ArticleDOI
01 Aug 2003-Pain
TL;DR: The Pain Catastrophizing Scale for Children was adapted for use in children, and its construct and predictive validity was investigated in two studies, revealing that catastrophizing about pain had a unique contribution in predicting pain intensity beyond gender and age.
Abstract: Catastrophizing about pain has emerged as a critical variable in how we understand adjustment to pain in both adults and children. In children, however, current methods of measuring catastrophizing about pain rely on brief subscales of larger coping inventories. Therefore, we adapted the Pain Catastrophizing Scale (Sullivan et al., 1995) for use in children, and investigated its construct and predictive validity in two studies. Study 1 revealed that in a community sample (400 boys, 414 girls; age range between 8 years 9 months and 16 years 5 months) the Pain Catastrophizing Scale for Children (PCS-C) assesses the independent but strongly related dimensions of rumination, magnification and helplessness that are subsumed under the higher-order construct of pain catastrophizing. This three factor structure is invariant across age groups and gender. Study 2 revealed in a clinical sample of children with chronic or recurrent pain (23 girls, 20 boys; age range between 8 years 3 months and 16 years 6 months) that catastrophizing about pain had a unique contribution in predicting pain intensity beyond gender and age, and in predicting disability, beyond gender, age and pain intensity. The function of pain catastrophizing is discussed in terms of the facilitation of escape from pain, and of the communication of distress to significant others.

Journal ArticleDOI
TL;DR: In this article, the surface energies of the adhesive, substrate and interface between them determine the extent of wetting or spreading at equilibrium, and the extent to which the relationships, appropriate for plane surfaces, may be modified to take into account interfacial roughness.

Journal ArticleDOI
TL;DR: It is inferred that MRSA has emerged at least 20 times upon acquisition of the methicillin resistance determinant, which is carried on a mobile genetic element called the staphylococcal cassette chromosome mec (SCCmec).
Abstract: Five major lineages of methicillin-resistant Staphylococcus aureus (MRSA) have evolved since the introduction of methicillin for the treatment of infections caused by penicillin-resistant S. aureus in 1959. The clones of these lineages are responsible for the vast majority of hospital-acquired MRSA disease globally. We have constructed high-resolution evolutionary models for each lineage using a parsimony approach with 15 partial gene sequences from 147 geographically diverse isolates. On the basis of these models, we infer that MRSA has emerged at least 20 times upon acquisition of the methicillin resistance determinant, which is carried on a mobile genetic element called the staphylococcal cassette chromosome mec (SCCmec). The acquisition of SCCmec by sensitive clones was four times more common than the replacement of one SCCmec with another. Notably, SCCmec type IV was found in twice as many clones as any other SCCmec type, and it is this SCCmec type which is commonly found in clones from patients with community-acquired MRSA disease. Our findings suggest that most clones of MRSA arise by the acquisition of SCCmec type IV by methicillin-sensitive isolates.

Journal ArticleDOI
19 Sep 2003-Science
TL;DR: The cancellation of the soliton self-frequency shift in a silica-core photonic crystal fiber with a negative dispersion slope is reported and may find applications in the development of a family of optical parametric amplifiers.
Abstract: We report the cancellation of the soliton self-frequency shift in a silica-core photonic crystal fiber with a negative dispersion slope. Numerical and experimental results show that stabilization of the soliton wavelength is accompanied by exponential amplification of the red-shifted Cherenkov radiation emitted by the soliton. The spectral recoil from the radiation acts on the soliton to compensate for the Raman frequency shift. This phenomenon may find applications in the development of a family of optical parametric amplifiers.

Journal ArticleDOI
31 Jul 2003-Nature
TL;DR: This work reports on spectral broadening of 100-fs pulses in PCFs with anomalously flat CD profiles, showing how, through appropriate choice of CD, nonlinearities can be efficiently harnessed to generate laser light at new wavelengths.
Abstract: Photonic crystal fibres (PCFs) offer greatly enhanced design freedom compared to standard optical fibres. For example, they allow precise control of the chromatic dispersion (CD) profile—the frequency dependence of propagation speed—over a broad wavelength range. This permits studies of nonlinear pulse propagation in previously inaccessible parameter regimes. Here we report on spectral broadening of 100-fs pulses in PCFs with anomalously flat CD profiles. Maps of the spectral and spatio-temporal behaviour as a function of power show that dramatic conversion (to both longer and shorter wavelengths) can occur in remarkably short lengths of fibre, depending on the magnitude and shape of the CD profile. Because the PCFs used are single-mode at all wavelengths, the light always emerges in a fundamental guided mode. Excellent agreement is obtained between the experimental results and numerical solutions of the nonlinear wave equation, indicating that the underlying processes can be reliably modelled. These results show how, through appropriate choice of CD, nonlinearities can be efficiently harnessed to generate laser light at new wavelengths.

Journal ArticleDOI
TL;DR: In this article, a life story of a professional soccer coach is used to understand the dynamic social construction of coaching knowledge in a highly challenging, competitive environment, and the role of coach education programs in the development of knowledge.
Abstract: The purpose of this paper is to provide an in-depth understanding of some of the ways in which one elite soccer coach has constructed, and continues to construct, his professional knowledge. By adopting a life-story approach the paper problematises the predominant rationality of much existing coaching research and questions the role of coach education programmes in the development of coaching knowledge. To accomplish this, the paper focuses on the life events of Steve Harrison, a 48-year-old professional soccer coach who currently works at Middlesborough Football Club. Specifically, it illustrates some of the dimensions of the dynamic social construction of coaching knowledge in a highly challenging, competitive environment. The paper is organised into three sections. In the first section, a rationale for a focus on coaches' knowledge is followed by a brief overview of the life-story method as used in this study. Second, Steve's story is presented, drawing upon excerpts from field-notes, interview transcr...

Journal ArticleDOI
TL;DR: A multilocus sequence typing (MLST) scheme has been developed for the unambiguous characterization of encapsulated and noncapsulated Haemophilus influenzae isolates, finding significant congruence between many of the trees reconstructed from the sequences of the seven individual loci.
Abstract: A multilocus sequence typing (MLST) scheme has been developed for the unambiguous characterization of encapsulated and noncapsulated Haemophilus influenzae isolates The sequences of internal fragments of seven housekeeping genes were determined for 131 isolates, comprising a diverse set of 104 serotype a, b, c, d, e, and f isolates and 27 noncapsulated isolates Many of the encapsulated isolates had previously been characterized by multilocus enzyme electrophoresis (MLEE), and the validity of the MLST scheme was established by the very similar clustering of isolates obtained by these methods Isolates of serotypes c, d, e, and f formed monophyletic groups on a dendrogram constructed from the differences in the allelic profiles of the isolates, whereas there were highly divergent lineages of both serotype a and b isolates Noncapsulated isolates were distinct from encapsulated isolates and, with one exception, were within two highly divergent clusters The relationships between the major lineages of encapsulated H influenzae inferred from MLEE data could not be discerned on a dendrogram constructed from differences in the allelic profiles, but were apparent on a tree reconstructed from the concatenated nucleotide sequences Recombination has not therefore completely eliminated phylogenetic signal, and in support of this, for encapsulated isolates, there was significant congruence between many of the trees reconstructed from the sequences of the seven individual loci Congruence was less apparent for noncapsulated isolates, suggesting that the impact of recombination is greater among noncapsulated than encapsulated isolates The H influenzae MLST scheme is available at wwwmlstnet, it allows any isolate to be compared with those in the MLST database, and (for encapsulated isolates) it assigns isolates to their phylogenetic lineage, via the Internet

Journal ArticleDOI
TL;DR: In this article, the authors studied the hole transport phase in a solid-state dye-sensitized solar cells employing spiro-MeOTAD [2,2‘7,7‘-tetrakis(N,N-di-p-methoxyphenyl-amine)-9,9‘ -spirobifluorene] as a hole-transportation phase.
Abstract: Solid-state dye-sensitized solar cells employing spiro-MeOTAD [2,2‘7,7‘-tetrakis(N,N-di-p-methoxyphenyl-amine)-9,9‘-spirobifluorene] as a hole transport phase were studied by intensity modulated photocurrent spectroscopy (IMPS) and intensity modulated photovoltage spectroscopy (IMVS) over a wide range of illumination intensity. The IMPS and IMVS responses provide information about charge transport and electron−hole recombination, respectively. For the range of light intensities investigated, the dynamic photocurrent response appears to be limited by the transport of electrons in the nanocrystalline TiO2 film rather than by the transport of holes in the spiro-MeOTAD. The diffusion length of electrons in the TiO2 was found to be 4.4 × 10-4 cm. This value was almost independent of light intensity as a consequence of the fact that the electron diffusion coefficient and the rate constant for electron−hole recombination both increase in the same way with light intensity (proportional to I00.64).

Journal ArticleDOI
TL;DR: It is shown that a biological feature of bacterial infections can lead to the opposite prediction: a positive correlation between relatedness and virulence.
Abstract: Kin selection theory predicts that the damage to a host resulting from parasite infection (parasite virulence) will be negatively correlated to the relatedness between parasites within the host. This occurs because a lower relatedness leads to greater competition for host resources, which favours rapid growth to achieve greater relative success within the host, and that higher parasite growth rate leads to higher virulence. We show that a biological feature of bacterial infections can lead to the opposite prediction: a positive correlation between relatedness and virulence. This occurs because a high relatedness can favour greater (cooperative) production of molecules that scavenge iron (siderophores), which results in higher growth rates and virulence. More generally, the same underlying idea can predict a positive relationship between relatedness and virulence in any case where parasites can cooperate to increase their growth rate; other examples include immune suppression and the production of biofilms to aid colonization.

Journal ArticleDOI
TL;DR: In this article, a simple analytical model is developed to calculate load factors associated with various collapse mechanisms of wall assemblies, and vulnerability functions are derived to quantify reduction in vulnerability associated with strengthening implementations for different typologies.
Abstract: In historic city centers the mitigation of seismic risk is dependent on the possibility of implementing strengthening programs. Given the cultural and economic value attached to the historic structures, however, interventions should be tailored to suit aesthetic and structural requirements of each building type, and provide sufficient reliability of performance in future earthquakes. A simple analytical model is developed to calculate load factors associated with various collapse mechanisms of wall assemblies, and vulnerability functions are derived. An application shows the capability of the procedure to quantify reduction in vulnerability associated with strengthening implementations for different typologies. [DOI: 10.1193/1.1599896]

Journal ArticleDOI
TL;DR: It is considered that the conversion of liver to pancreas could be the basis of a new type of therapy for insulin-dependent diabetes.

Journal ArticleDOI
TL;DR: This research empirically investigates co-opetition, management of knowledge sharing and the role of IS in the context of small and medium-sized enterprises (SMEs) in the U.K.
Abstract: Co-opetition, simultaneous cooperation and competition, is a recent phenomenon. Co-opetition entails sharing knowledge that may be a key source of competitive advantage. Yet, the knowledge gained by cooperation may also be used for competition. However, there is little investigation of how this problem may be modelled and, hence, managed. A game-theoretic framework for analysing interorganisational knowledge sharing under co-opetition and guidelines for the management of explicit knowledge predicated on coordination and control theory has been proposed, but remains untested. This research empirically investigates these issues in the context of small and medium-sized enterprises (SMEs). SMEs provide an interesting setting as they are knowledge generators, but are poor at knowledge exploitation. The paper uses data from U.K. SMEs to investigate co-opetition, management of knowledge sharing and the role of IS.

Journal ArticleDOI
TL;DR: In this article, the authors examine and evaluate methods and assumptions used by the economic studies and compare ex-ante models and forecasts with the ex-post approach to improve the information available to policy makers and potential future hosts of Summer Olympics and other mega-events.
Abstract: As the Summer Olympics are growing with larger media coverage and sponsorship, host cities have started to attach great importance to the tourism and other likely economic effects that occur by staging such a special event As a result, a number of studies have been conducted to consider the various economic implications on the hosts This paper examines and evaluates methods and assumptions used by the economic studies It also compares ex-ante models and forecasts with the ex-post approach The aim is to improve the information available to policy makers and potential future hosts of Summer Olympics and other mega-events Copyright © 2003 John Wiley & Sons, Ltd

Journal ArticleDOI
TL;DR: In this article, the role of HR policies and processes as facilitators of the social capital that interconnects knowledge by focusing on the needs of knowledge workers is highlighted, and a detailed study of a single case is presented.
Abstract: Knowledge-intensive firms need to share knowledge held by employees if they are to gain the most from their intellectual capital and compete effectively in the marketplace. Sharing and integrating knowledge within the organisation depends partly on building social capital. However, there are obstacles to this integration because knowledge is often distributed throughout the organisation. This article draws on a detailed study of a single case to examine the ways in which HR policies and processes contribute to overcoming these barriers to sharing knowledge. We highlight the role of HR policies and processes as facilitators of the social capital that interconnects knowledge by focusing on the needs of knowledge workers.

Journal ArticleDOI
TL;DR: In this paper, the authors examine the enablers and strategic blockages in pursuing mass customisation, via a mapping process, and reveal reasons why some firms remain unable to devise and implement manufacturing strategies.
Abstract: This paper is based on longitudinal case studies of research into strategy formulation within six plants from large firms – three in the car industry and three from the computer industry – that have embarked on mass customisation. The core theme of this paper is that, in spite of the increasing attention given to manufacturing strategy from the seminal work of Skinner through to the plethora of articles in recent times, little is mentioned about its application to paradigms of agility or mass customisation. As a consequence firms attempt to become agile and to pursue mass customisation without appreciating the contribution of plant‐specific manufacturing strategies that might enable them to achieve these aspirations. We examine the enablers and strategic blockages in pursuing mass customisation, via a mapping process, and reveal reasons why some firms remain unable to devise and implement manufacturing strategies.

Journal ArticleDOI
TL;DR: Modulation instability at high frequencies has been demonstrated in the normal dispersion regime by use of a photonic crystal fiber that provides efficient conversion of red pump light into blue and near-infrared light.
Abstract: Modulation instability at high frequencies has been demonstrated in the normal dispersion regime by use of a photonic crystal fiber. This fiber-optic parametric generator provides efficient conversion of red pump light into blue and near-infrared light.

Journal ArticleDOI
TL;DR: The structural features of current inhibitors are discussed and how next-generation ACE inhibitors could be designed by using the three-dimensional molecular structure of human testis ACE are outlined.
Abstract: Current-generation angiotensin-converting enzyme (ACE) inhibitors are widely used for cardiovascular diseases, including high blood pressure, heart failure, heart attack and kidney failure, and have combined annual sales in excess of US $6 billion. However, the use of these ACE inhibitors, which were developed in the late 1970s and early 1980s, is hampered by common side effects. Moreover, we now know that ACE actually consists of two parts (called the N- and C-domains) that have different functions. Therefore, the design of specific domain-selective ACE inhibitors is expected to produce next-generation drugs that might be safer and more effective. Here we discuss the structural features of current inhibitors and outline how next-generation ACE inhibitors could be designed by using the three-dimensional molecular structure of human testis ACE. The ACE structure provides a unique opportunity for rational drug design, based on a combination of in silico modelling using existing inhibitors as scaffolds and iterative lead optimization to drive the synthetic chemistry.

Journal ArticleDOI
TL;DR: It is shown that the tail of the frog tadpole, comprising spinal cord, muscle, and notochord, regenerates following partial amputation, except for a "refractory period" between stages 45 and 47, when tails heal over without regeneration.

Journal ArticleDOI
TL;DR: The results indicate that changes in GRB10 dosage could, in at least some cases, account for the severe growth retardation that is characteristic of Silver–Russell syndrome and provides evidence that imprinting acts on at least two major fetal growth axes in a manner consistent with parent–offspring conflict theory.
Abstract: To investigate the function of the Grb10 adapter protein, we have generated mice in which the Grb10 gene was disrupted by a gene-trap insertion. Our experiments confirm that Grb10 is subject to genomic imprinting with the majority of Grb10 expression arising from the maternally inherited allele. Consistent with this, disruption of the maternal allele results in overgrowth of both the embryo and placenta such that mutant mice are at birth approximately 30% larger than normal. This observation establishes that Grb10 is a potent growth inhibitor. In humans, GRB10 is located at chromosome 7p11.2-p12 and has been associated with Silver-Russell syndrome, in which approximately 10% of those affected inherit both copies of chromosome 7 from their mother. Our results indicate that changes in GRB10 dosage could, in at least some cases, account for the severe growth retardation that is characteristic of Silver-Russell syndrome. Because Grb10 is a signaling protein capable of interacting with tyrosine kinase receptors, we tested genetically whether Grb10 might act downstream of insulin-like growth factor 2, a paternally expressed growth-promoting gene. The result indicates that Grb10 action is essentially independent of insulin-like growth factor 2, providing evidence that imprinting acts on at least two major fetal growth axes in a manner consistent with parent-offspring conflict theory.

Journal ArticleDOI
TL;DR: In this article, the authors describe the underlying principles of action research as: (1) grounded in lived experience, (2) developed in partnership, (3) addressing significant problems, and (4) worki...
Abstract: In this overview the authors describe the underlying principles of action research as: (1) grounded in lived experience, (2) developed in partnership, (3) addressing significant problems, (4) worki...