Showing papers by "University of Leeds published in 2004"

Extinction risk from climate change

Abstract: Climate change over the past approximately 30 years has produced numerous shifts in the distributions and abundances of species and has been implicated in one species-level extinction. Using projections of species' distributions for future climate scenarios, we assess extinction risks for sample regions that cover some 20% of the Earth's terrestrial surface. Exploring three approaches in which the estimated probability of extinction shows a power-law relationship with geographical range size, we predict, on the basis of mid-range climate-warming scenarios for 2050, that 15-37% of species in our sample of regions and taxa will be 'committed to extinction'. When the average of the three methods and two dispersal scenarios is taken, minimal climate-warming scenarios produce lower projections of species committed to extinction ( approximately 18%) than mid-range ( approximately 24%) and maximum-change ( approximately 35%) scenarios. These estimates show the importance of rapid implementation of technologies to decrease greenhouse gas emissions and strategies for carbon sequestration.

The present and future role of photodynamic therapy in cancer treatment.

Abstract: It is more than 25 years since photodynamic therapy (PDT) was proposed as a useful tool in oncology, but the approach is only now being used more widely in the clinic. The understanding of the biology of PDT has advanced, and efficient, convenient, and inexpensive systems of light delivery are now available. Results from well-controlled, randomised phase III trials are also becoming available, especially for treatment of non-melanoma skin cancer and Barrett's oesophagus, and improved photosensitising drugs are in development. PDT has several potential advantages over surgery and radiotherapy: it is comparatively non-invasive, it can be targeted accurately, repeated doses can be given without the total-dose limitations associated with radiotherapy, and the healing process results in little or no scarring. PDT can usually be done in an outpatient or day-case setting, is convenient for the patient, and has no side-effects. Two photosensitising drugs, porfirmer sodium and temoporfin, have now been approved for systemic administration, and aminolevulinic acid and methyl aminolevulinate have been approved for topical use. Here, we review current use of PDT in oncology and look at its future potential as more selective photosensitising drugs become available.

Evaluated kinetic and photochemical data for atmospheric chemistry: Volume I - gas phase reactions of O x , HO x , NO x and SO x species

Abstract: . This article, the first in the series, presents kinetic and photochemical data evaluated by the IUPAC Subcommittee on GasKinetic Data Evaluation for Atmospheric Chemistry. It covers the gas phase and photochemical reactions of Ox, HOx, NOx and SOx species, which were last published in 1997, and were updated on the IUPAC website in late 2001. The article consists of a summary sheet, containing the recommended kinetic parameters for the evaluated reactions, and five appendices containing the data sheets, which provide information upon which the recommendations are made.

Silicon Nitride and Related Materials

Abstract: Silicon nitride has been researched intensively, largely in response to the challenge to develop internal combustion engines with hot-zone components made entirely from ceramics. The ceramic engine programs have had only partial success, but this research effort has succeeded in generating a degree of understanding of silicon nitride and of its processing and properties, which in many respects is more advanced than of more widely used technical ceramics. This review examines from the historical standpoint the development of silicon nitride and of its processing into a range of high-grade ceramic materials. The development of understanding of microstructure–property relationships in the silicon nitride materials is also surveyed. Because silicon nitride has close relationships with the SiAlON group of materials, it is impossible to discuss the one without some reference to the other, and a brief mention of the development of the SiAlONs is included for completeness.

Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial

Abstract: Objective To compare the benefits of initiating treatment with methotrexate (MTX) and infliximab (anti–tumor necrosis factor α [anti-TNFα] monoclonal antibody) with those of MTX treatment alone in patients with rheumatoid arthritis (RA) of ≤3 years' duration. Methods RA patients were eligible if they had active disease and no prior treatment with MTX or a TNFα inhibitor. One thousand forty-nine patients were randomly assigned in a 4:5:5 ratio to 3 treatment groups: MTX–placebo, MTX–3 mg/kg infliximab, and MTX–6 mg/kg infliximab. MTX dosages were rapidly escalated to 20 mg/week, and infliximab or placebo infusions were given at weeks 0, 2, and 6, and every 8 weeks thereafter through week 46. Results At week 54, the median percentage of American College of Rheumatology improvement (ACR-N) was higher for the MTX–3 mg/kg infliximab and MTX–6 mg/kg infliximab groups than for the MTX–placebo group (38.9% and 46.7% versus 26.4%, respectively; P < 0.001 for both comparisons). Patients in the MTX–3 mg/kg infliximab and MTX–6 mg/kg infliximab groups also showed less radiographic progression than those receiving MTX alone (mean ± SD changes in van der Heijde modification of the total Sharp score at week 54: 0.4 ± 5.8 and 0.5 ± 5.6 versus 3.7 ± 9.6, respectively; P < 0.001 for each comparison). In addition, physical function improved significantly more in the MTX–3 mg/kg infliximab and MTX–6 mg/kg infliximab groups than in the MTX–placebo group. Infliximab therapy was associated with a significantly higher incidence of serious infections, especially pneumonia. Conclusion For patients with active RA in its early stages, combination therapy with MTX and infliximab provides greater clinical, radiographic, and functional benefits than treatment with MTX alone.

Modified Look-Locker inversion recovery (MOLLI) for high-resolution T1 mapping of the heart

Abstract: A novel pulse sequence scheme is presented that allows the measurement and mapping of myocardial T1 in vivo on a 1.5 Tesla MR system within a single breath-hold. Two major modifications of conventional Look-Locker (LL) imaging are introduced: 1) selective data acquisition, and 2) merging of data from multiple LL experiments into one data set. Each modified LL inversion recovery (MOLLI) study consisted of three successive LL inversion recovery (IR) experiments with different inversion times. We acquired images in late diastole using a single-shot steady-state free-precession (SSFP) technique, combined with sensitivity encoding to achieve a data acquisition window of <200 ms duration. We calculated T1 using signal intensities from regions of interest and pixel by pixel. T1 accuracy at different heart rates derived from simulated ECG signals was tested in phantoms. T1 estimates showed small systematic error for T1 values from 191 to 1196 ms. In vivo T1 mapping was performed in two healthy volunteers and in one patient with acute myocardial infarction before and after administration of Gd-DTPA. T1 values for myocardium and noncardiac structures were in good agreement with values available from the literature. The region of infarction was clearly visualized. MOLLI provides high-resolution T1 maps of human myocardium in native and post-contrast situations within a single breath-hold. Magn Reson Med 52:141–146, 2004. © 2004 Wiley-Liss, Inc.

Predictions and tests of climate‐based hypotheses of broad‐scale variation in taxonomic richness

Abstract: Broad-scale variation in taxonomic richness is strongly correlated with climate. Many mechanisms have been hypothesized to explain these patterns; however, testable predictions that would distinguish among them have rarely been derived. Here, we examine several prominent hypotheses for climate–richness relationships, deriving and testing predictions based on their hypothesized mechanisms. The ‘energy–richness hypothesis’ (also called the ‘more individuals hypothesis’) postulates that more productive areas have more individuals and therefore more species. More productive areas do often have more species, but extant data are not consistent with the expected causal relationship from energy to numbers of individuals to numbers of species. We reject the energy–richness hypothesis in its standard form and consider some proposed modifications. The ‘physiological tolerance hypothesis’ postulates that richness varies according to the tolerances of individual species for different sets of climatic conditions. This hypothesis predicts that more combinations of physiological parameters can survive under warm and wet than cold or dry conditions. Data are qualitatively consistent with this prediction, but are inconsistent with the prediction that species should fill climatically suitable areas. Finally, the ‘speciation rate hypothesis’ postulates that speciation rates should vary with climate, due either to faster evolutionary rates or stronger biotic interactions increasing the opportunity for evolutionary diversification in some regions. The biotic interactions mechanism also has the potential to amplify shallower, underlying gradients in richness. Tests of speciation rate hypotheses are few (to date), and their results are mixed.

Globalisation, Economic Geography and the Strategy of Multinational Enterprises

Abstract: The intention of this paper is to review the literature linking ownership and location strategies to economic geography and theories of globalisation and to explore new areas of research. This paper examines globalisation in terms of conflicts between markets and economic management, and suggests that the differential pace of globalisation across markets presents a number of challenges to policy makers in local, national and regional governments, and in international institutions. In examining the changing location and ownership strategies of MNEs, it shows that the increasingly sophisticated decision making of managers in MNEs is slicing the activities of firms more finely and in finding optimum locations for each closely defined activity, they are deepening the international division of labour. Ownership strategies, too, are becoming increasingly complex, leading to a control matrix that runs from wholly owned units via FDI through market relationships such as subcontracting, including joint ventures as options on subsequent decisions in a dynamic pattern. The input of lessons from economic geography is thus becoming more important in understanding the key developments in international business. The consequences of the globalisation of production and consumption represent political challenges, and reaction against these changes has led to a questioning of the effects of global capitalism as well as to its moral basis. These four issues are closely intertwined and present a formidable research agenda to which the international business research community is uniquely fitted to respond.

Improving the quality of reporting in randomised controlled trials.

Abstract: Wound-care journals contain abundant reports of trials, but not all report a satisfactory methodology. Systematic reviews of wound-care trials have highlighted many areas for improvement, and the National Institute for Clinical Excellence (NICE) guidelines recommend that primary research in the field of pressure ulcer prevention should adhere more closely to current methodological standards in terms of conduct and reporting. The CONSORT tool was developed to help achieve these improvements in the design and reporting of randomised controlled trials (RCTs).

Properties and performance of the prototype instrument for the Pierre Auger Observatory

Abstract: Construction of the first stage of the Pierre Auger Observatory has begun. The aim of the Observatory is to collect unprecedented information about cosmic rays above 1018 eV. The first phase of the project, the construction and operation of a prototype system, known as the engineering array, has now been completed. It has allowed all of the sub-systems that will be used in the full instrument to be tested under field conditions. In this paper, the properties and performance of these sub-systems are described and their success illustrated with descriptions of some of the events recorded thus far. © 2003 Elsevier B.V. All rights reserved.

Globalisation, economic geography and the strategy of multinational enterprises

Abstract: The intention of this paper is to review the literature linking ownership and location strategies to economic geography and theories of globalisation and to explore new areas of research. This paper examines globalisation in terms of conflicts between markets and economic management, and suggests that the differential pace of globalisation across markets presents a number of challenges to policy makers in local, national and regional governments, and in international institutions. In examining the changing location and ownership strategies of MNEs, it shows that the increasingly sophisticated decision making of managers in MNEs is slicing the activities of firms more finely and in finding optimum locations for each closely defined activity, they are deepening the international division of labour. Ownership strategies, too, are becoming increasingly complex, leading to a control matrix that runs from wholly owned units via FDI through market relationships such as subcontracting, including joint ventures as options on subsequent decisions in a dynamic pattern. The input of lessons from economic geography is thus becoming more important in understanding the key developments in international business. The consequences of the globalisation of production and consumption represent political challenges, and reaction against these changes has led to a questioning of the effects of global capitalism as well as to its moral basis. These four issues are closely intertwined and present a formidable research agenda to which the international business research community is uniquely fitted to respond.

Variation in wood density determines spatial patterns in Amazonian forest biomass

Abstract: Uncertainty in biomass estimates is one of the greatest limitations to models of carbon flux in tropical forests. Previous comparisons of field-based estimates of the aboveground biomass (AGB) of trees greater than 10cm diameter within Amazonia have been limited by the paucity of data for western Amazon forests, and the use of site-specific methods to estimate biomass from inventory data. In addition, the role of regional variation in stand-level wood specific gravity has not previously been considered. Using data from 56 mature forest plots across Amazonia, we consider the relative roles of species composition (wood specific gravity) and forest structure (basal area) in determining variation in AGB. Mean stand-level wood specific gravity, on a per stem basis, is 15.8% higher in forests in central and eastern, compared with northwestern Amazonia. This pattern is due to the higher diversity and abundance of taxa with high specific gravity values in central and eastern Amazonia, and the greater diversity and abundance of taxa with low specific gravity values in western Amazonia. For two estimates of AGB derived using different allometric equations, basal area explains 51.7% and 63.4%, and stand-level specific gravity 45.4% and 29.7%, of the total variation in AGB. The variation in specific gravity is important because it determines the regional scale, spatial pattern of AGB. When weighting by specific gravity is included, central and eastern Amazon forests have significantly higher AGB than stands in northwest or southwest Amazonia. The regional-scale pattern of species composition therefore defines a broad gradient of AGB across Amazonia.

The Self and Autobiographical Memory: Correspondence and Coherence

Abstract: A modified version of Conway and Pleydell-Pearce's Self Memory System (SMS) account of autobiographical memory and the self is introduced. Modifications include discussion of a fundamental tension between adaptive correspondence (experience-near sensory-perceptual records of goal activity) and self-coherence (a more abstracted and conceptually-rich long-term store of conceptual and remembered knowledge). This tension is examined in relation to each SMS component—the episodic memory system, long-term self, and the working self. The long-term self, a new aspect of the model, consists of the interaction of the autobiographical knowledge base and the conceptual self. The working self, depending on goal activity status, mediates between episodic memory and the long-term self. Applications of the SMS to personality and clinical psychology are provided through analysis of self-defining memories and adult attachment categories, as well as case histories of traumatic memory. The SMS's role in imagination ...

The equilibrative nucleoside transporter family, SLC29.

Abstract: The human SLC29 family of proteins contains four members, designated equilibrative nucleoside transporters (ENTs) because of the properties of the first-characterised family member, hENT1. They belong to the widely-distributed eukaryotic ENT family of equilibrative and concentrative nucleoside/nucleobase transporters and are distantly related to a lysosomal membrane protein, CLN3, mutations in which cause neuronal ceroid lipofuscinosis. A predicted topology of 11 transmembrane helices with a cytoplasmic N-terminus and an extracellular C-terminus has been experimentally confirmed for hENT1. The best-characterised members of the family, hENT1 and hENT2, possess similar broad substrate specificities for purine and pyrimidine nucleosides, but hENT2 in addition efficiently transports nucleobases. The ENT3 and ENT4 isoforms have more recently also been shown to be genuine nucleoside transporters. All four isoforms are widely distributed in mammalian tissues, although their relative abundance varies: ENT2 is particularly abundant in skeletal muscle. In polarised cells ENT1 and ENT2 are found in the basolateral membrane and, in tandem with concentrative transporters of the SLC28 family, may play a role in transepithelial nucleoside transport. The transporters play key roles in nucleoside and nucleobase uptake for salvage pathways of nucleotide synthesis, and are also responsible for the cellular uptake of nucleoside analogues used in the treatment of cancers and viral diseases. In addition, by regulating the concentration of adenosine available to cell surface receptors, they influence many physiological processes ranging from cardiovascular activity to neurotransmission.

Genetics and Cytogenetics of Multiple Myeloma A Workshop Report

Abstract: Much has been learned regarding the biology and clinical implications of genetic abnormalities in multiple myeloma. Because of recent advances in the field, an International Workshop was held in Paris in february of 2003. This summary describes the consensus recommendations arising from that meeting with special emphasis on novel genetic observations. For instance, it is increasingly clear that translocations involving the immunoglobin heavy-chain locus are important for the pathogenesis of one-half of patients. As a corollary, it also clear that the remaining patients, lacking IgH translocations, have hyperdiploidy as the hallmark of their disease. Several important genetic markers are associated with a shortened survival such as chromosome 13 monosomy, hypodiploidy, and others. The events leading the transformation of the monoclonal gammopathy of undetermined significance (MGUS) to myeloma are still unclear. One of the few differential genetic lesions between myeloma and MGUS is the presence of ras mutations in the latter. Gene expression platforms are capable of detecting many of the genetic aberrations found in the clonal cells of myeloma. Areas in need of further study were identified. The study of the genetic aberrations will likely form the platform for targeted therapy for the disease.

New insights into magnetic derivatives for structural mapping

Abstract: Magnetic and gravity derivatives can be likened to seismic attributes in that they can help define/estimate the physical properties of the source structure causing the anomaly. This contribution looks at the tilt derivative, first reported in 1994 and more recently used to derive the local wavenumber (1997). We will show that the combination of the tilt derivative and its total horizontal derivative are highly suitable for mapping shallow basement structure and mineral exploration targets and that they have distinct advantages over many conventional derivatives. We provide the simple theory behind the derivatives, use a range of simple 2D models to illustrate their response, and apply them to mapping a mineral target in Namibia.

Lessons from the Genome Sequence of Neurospora crassa: Tracing the Path from Genomic Blueprint to Multicellular Organism

Abstract: We present an analysis of over 1,100 of the approximately 10,000 predicted proteins encoded by the genome sequence of the filamentous fungus Neurospora crassa. Seven major areas of Neurospora genomics and biology are covered. First, the basic features of the genome, including the automated assembly, gene calls, and global gene analyses are summarized. The second section covers components of the centromere and kinetochore complexes, chromatin assembly and modification, and transcription and translation initiation factors. The third area discusses genome defense mechanisms, including repeat induced point mutation, quelling and meiotic silencing, and DNA repair and recombination. In the fourth section, topics relevant to metabolism and transport include extracellular digestion; membrane transporters; aspects of carbon, sulfur, nitrogen, and lipid metabolism; the mitochondrion and energy metabolism; the proteasome; and protein glycosylation, secretion, and endocytosis. Environmental sensing is the focus of the fifth section with a treatment of two-component systems; GTP-binding proteins; mitogen-activated protein, p21-activated, and germinal center kinases; calcium signaling; protein phosphatases; photobiology; circadian rhythms; and heat shock and stress responses. The sixth area of analysis is growth and development; it encompasses cell wall synthesis, proteins important for hyphal polarity, cytoskeletal components, the cyclin/cyclin-dependent kinase machinery, macroconidiation, meiosis, and the sexual cycle. The seventh section covers topics relevant to animal and plant pathogenesis and human disease. The results demonstrate that a large proportion of Neurospora genes do not have homologues in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe. The group of unshared genes includes potential new targets for antifungals as well as loci implicated in human and plant physiology and disease.

Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism

Abstract: In the RAS (renin–angiotensin system), Ang I (angiotensin I) is cleaved by ACE (angiotensin-converting enzyme) to form Ang II (angiotensin II), which has effects on blood pressure, fluid and electrolyte homoeostasis. We have examined the kinetics of angiotensin peptide cleavage by full-length human ACE, the separate N- and C-domains of ACE, the homologue of ACE, ACE2, and NEP (neprilysin). The activity of the enzyme preparations was determined by active-site titrations using competitive tight-binding inhibitors and fluorogenic substrates. Ang I was effectively cleaved by NEP to Ang (1–7) (kcat/Km of 6.2×105 M−1·s−1), but was a poor substrate for ACE2 (kcat/Km of 3.3×104 M−1·s−1). Ang (1–9) was a better substrate for NEP than ACE (kcat/Km of 3.7×105 M−1·s−1 compared with kcat/Km of 6.8×104 M−1·s−1). Ang II was cleaved efficiently by ACE2 to Ang (1–7) (kcat/Km of 2.2×106 M−1·s−1) and was cleaved by NEP (kcat/Km of 2.2×105 M−1·s−1) to several degradation products. In contrast with a previous report, Ang (1–7), like Ang I and Ang (1–9), was cleaved with a similar efficiency by both the N- and C-domains of ACE (kcat/Km of 3.6×105 M−1·s−1 compared with kcat/Km of 3.3×105 M−1·s−1). The two active sites of ACE exhibited negative co-operativity when either Ang I or Ang (1–7) was the substrate. In addition, a range of ACE inhibitors failed to inhibit ACE2. These kinetic data highlight that the flux of peptides through the RAS is complex, with the levels of ACE, ACE2 and NEP dictating whether vasoconstriction or vasodilation will predominate.

Genic capture and resolving the lek paradox

Abstract: The genic capture hypothesis offers a resolution to the question of how genetic variation in male sexually selected traits is maintained in the face of strong female preferences. The hypothesis is that male display traits are costly to produce and hence depend upon overall condition, which itself is dependent upon genes at many loci. Few attempts have been made to test the assumptions and predictions of the genic capture hypothesis rigorously and, in particular, little attention has been paid to determining the genetic basis of condition. Such tests are crucial to our understanding of the maintenance of genetic variation and in the evaluation of recent models that propose a role for sexual selection in the maintenance of sex. Here, we review approaches to testing the link between genetically determined condition and levels of sexual trait expression and consider the probable importance of deleterious mutations.

Effect of silica fume on mechanical properties of high-strength concrete

Abstract: This paper presents the results of experimental work on short- and long-term mechanical properties of high-strength concrete containing different levels of silica fume. The aim of the study was to investigate the effects of binder systems containing different levels of silica fume on fresh and mechanical properties of concrete. The work focused on concrete mixes having a fixed water/binder ratio of 0.35 and a constant total binder content of 500 kg/m3. The percentages of silica fume that replaced cement in this research were: 0%, 6%, 10% and 15%. Apart from measuring the workability of fresh concrete, the mechanical properties evaluated were: development of compressive strength; secant modulus of elasticity; strain due to creep, shrinkage, swelling and moisture movement. The results of this research indicate that as the proportion of silica fume increased, the workability of concrete decreased but its short-term mechanical properties such as 28-day compressive strength and secant modulus improved. Also the percentages of silica fume replacement did not have a significant influence on total shrinkage; however, the autogenous shrinkage of concrete increased as the amount of silica fume increased. Moreover, the basic creep of concrete decreased at higher silica fume replacement levels. Drying creep (total creep − basic creep) of specimens was negligible in this investigation. The results of swelling tests after shrinkage and creep indicate that increasing the proportion of silica fume lowered the amount of expansion. Because the existing models for predicting creep and shrinkage were inaccurate for high-strength concrete containing silica fume, alternative prediction models are presented here.

Fungal cell wall chitinases and glucanases.

Abstract: The fungal cell wall is a complex structure composed of chitin, glucans and other polymers, and there is evidence of extensive cross-linking between these components. The wall structure is highly dynamic, changing constantly during cell division, growth and morphogenesis. Hydrolytic enzymes, closely associated with the cell wall, have been implicated in the maintenance of wall plasticity and may have roles during branching and cross-linking of polymers. Most fungal cell wall hydrolases identified to date have chitinase or glucanase activity and this short article reviews the apparent functions of these enzymes in unicellular and filamentous fungi, and the mechanisms that regulate enzyme activity in yeasts.

Reproductive biology: delivering spermatozoan RNA to the oocyte.

Abstract: Even though the genetic fingerprint of human sperm has been defined, its role in orchestrating fertilization and the development of the early embryo remains vague. Here we show that human male gametes pass over more to the oocyte than just the haploid male genome--paternal messenger RNAs are also delivered to the egg at fertilization. If these transcripts, previously thought to be left-overs from spermatogenesis, are important in early development, our findings may have implications for the success of somatic-cell nuclear transfer in cloning technology and the identification of components leading to unexplained male-factor infertility.

Postweaning exposure to aflatoxin results in impaired child growth: a longitudinal study in Benin, West Africa.

Abstract: Aflatoxins are dietary contaminants that are hepatocarcinogenic and immunotoxic and cause growth retardation in animals, but there is little evidence concerning the latter two parameters in exposed human populations. Aflatoxin exposure of West African children is known to be high, so we conducted a longitudinal study over an 8-month period in Benin to assess the effects of exposure on growth. Two hundred children 16-37 months of age were recruited from four villages, two with high and two with low aflatoxin exposure (50 children per village). Serum aflatoxin-albumin (AF-alb) adducts, anthropometric parameters, information on food consumption, and various demographic data were measured at recruitment (February) and at two subsequent time points (June and October). Plasma levels of vitamin A and zinc were also measured. AF-alb adducts increased markedly between February and October in three of the four villages, with the largest increases in the villages with higher exposures. Children who were fully weaned at recruitment had higher AF-alb than did those still partially breast-fed (p < 0.0001); the major weaning food was a maize-based porridge. There was no association between AF-alb and micronutrient levels, suggesting that aflatoxin exposure was not accompanied by a general nutritional deficiency. There was, however, a strong negative correlation (p < 0.0001) between AF-alb and height increase over the 8-month follow-up after adjustment for age, sex, height at recruitment, socioeconomic status, village, and weaning status; the highest quartile of AF-alb was associated with a mean 1.7 cm reduction in growth over 8 months compared with the lowest quartile. This study emphasizes the association between aflatoxin and stunting, although the underlying mechanisms remain unclear. Aflatoxin exposure during the weaning period may be critical in terms of adverse health effects in West African children, and intervention measures to reduce exposure merit investigation.