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Showing papers by "University of Manchester published in 2001"


Journal ArticleDOI
Abstract: We describe a new method of matching statistical models of appearance to images. A set of model parameters control modes of shape and gray-level variation learned from a training set. We construct an efficient iterative matching algorithm by learning the relationship between perturbations in the model parameters and the induced image errors.

6,200 citations


Journal ArticleDOI
20 Apr 2001-Science
TL;DR: It is shown that the interaction between human pVHL and a specific domain of the HIF-1α subunit is regulated through hydroxylation of a proline residue by an enzyme the authors have termed Hif-α prolyl-hydroxylase (HIF-PH).
Abstract: Hypoxia-inducible factor (HIF) is a transcriptional complex that plays a central role in the regulation of gene expression by oxygen. In oxygenated and iron replete cells, HIF-alpha subunits are rapidly destroyed by a mechanism that involves ubiquitylation by the von Hippel-Lindau tumor suppressor (pVHL) E3 ligase complex. This process is suppressed by hypoxia and iron chelation, allowing transcriptional activation. Here we show that the interaction between human pVHL and a specific domain of the HIF-1alpha subunit is regulated through hydroxylation of a proline residue (HIF-1alpha P564) by an enzyme we have termed HIF-alpha prolyl-hydroxylase (HIF-PH). An absolute requirement for dioxygen as a cosubstrate and iron as cofactor suggests that HIF-PH functions directly as a cellular oxygen sensor.

5,186 citations


Journal ArticleDOI
TL;DR: In this paper, the effect of residual stresses on fatigue lifetimes and structural integrity are first summarised, followed by the definition and measurement of residual stress, which are characterised according to the characteristic length scale over which they self-equilibrate.
Abstract: Residual stress is that which remains in a body that is stationary and at equilibrium with its surroundings. It can be very detrimental to the performance of a material or the life of a component. Alternatively, beneficial residual stresses can be introduced deliberately. Residual stresses are more difficult to predict than the in-service stresses on which they superimpose. For this reason, it is important to have reliable methods for the measurement of these stresses and to understand the level of information they can provide. In this paper, which is the first part of a two part overview, the effect of residual stresses on fatigue lifetimes and structural integrity are first summarised, followed by the definition and measurement of residual stresses. Different types of stress are characterised according to the characteristic length scale over which they self-equilibrate. By comparing this length to the gauge volume of each technique, the capability of a range of techniques is assessed. In the sec...

1,317 citations


Journal ArticleDOI
TL;DR: A review of trends in employment relations, interdivisional relations, and interfirm relations finds evidence suggesting that the effect of growing knowledge-intensity may indeed be a trend toward greater reliance on trust as mentioned in this paper.
Abstract: Recent conceptualizations of trends in the structure of U.S. industry have focused on the relative importance of markets, hierarchies, and hybrid intermediate forms. This paper advances the discussion by distinguishing three ideal-typical forms of organization and their corresponding coordination mechanisms: market/price, hierarchy/authority, and community/trust. Different institutions combine the three forms/mechanisms in different proportions. Economic and organizational theory have shown that, compared to trust, price and authority are relatively ineffective means of dealing with knowledge-based assets. Therefore, as knowledge becomes increasingly important in our economy, we should expect high-trust institutional forms to proliferate.A review of trends in employment relations, interdivisional relations, and interfirm relations finds evidence suggesting that the effect of growing knowledge-intensity may indeed be a trend toward greater reliance on trust. There is also reason to believe that the form of trust most effective in this context is a distinctively modern kind--"reflective trust"--as opposed to traditionalistic, "blind" trust. Such a trend to reflective trust appears to threaten the privileges of currently dominant social actors, and these actors' resistance, in combination with the complex interdependencies between price, authority, and trust mechanisms, imparts a halting character to the trend. But the momentum of this trend nevertheless appears to be self-reinforcing, which suggests that it may ultimately challenge the foundations of our capitalist form of society while simultaneously creating the foundations of a new, postcapitalist form.

1,265 citations


Journal ArticleDOI
TL;DR: In this article, the synthesis and study of so-called "nanoparticles" with diameters in the range of 1−20 nm, has become a major interdisciplinary area of research over the past 10 years.
Abstract: The synthesis and study of so-called “nanoparticles”, particles with diameters in the range of 1−20 nm, has become a major interdisciplinary area of research over the past 10 years. Semiconductor nanoparticles promise to play a major role in several new technologies. The intense interest in this area derives from their unique chemical and electronic properties, which gives rise to their potential use in the fields of nonlinear optics, luminescence, electronics, catalysis, solar energy conversion, and optoelectronics, as well as other areas. The small dimensions of these particles result in different physical properties from those observed in the corresponding macrocrystalline, “bulk”, material. As particle sizes become smaller, the ratio of surface atoms to those in the interior increase, leading to the surface properties playing an important role in the properties of the material. Semiconductor nanoparticles also exhibit a change in their electronic properties relative to that of the bulk material; as th...

1,213 citations


Journal ArticleDOI
28 Dec 2001-Cell
TL;DR: Analysis of clock proteins in m CRY-deficient mice shows that the mCRYs are necessary for stabilizing phosphorylated mPER2 and for the nuclear accumulation of mPER1, mper2, and CKIepsilon, and provides in vivo evidence that casein kinase I delta is a second clock relevant kinase.

1,114 citations


Journal ArticleDOI
TL;DR: ETS-domain transcription-factor networks represent a model for how combinatorial gene expression is achieved and a complex series of inter and intramolecular interactions, and signalling pathways impinge on these proteins to further regulate their action.
Abstract: ETS-domain transcription-factor networks represent a model for how combinatorial gene expression is achieved. These transcription factors interact with a multitude of co-regulatory partners to elicit gene-specific responses and drive distinct biological processes. These proteins are controlled by a complex series of inter and intramolecular interactions, and signalling pathways impinge on these proteins to further regulate their action.

1,042 citations


Journal ArticleDOI
TL;DR: It is demonstrated how the intracellular concentrations of metabolites can reveal phenotypes for proteins active in metabolic regulation, and this approach to functional analysis, using comparative metabolomics, is called FANCY—an abbreviation for functional analysis by co-responses in yeast.
Abstract: A large proportion of the 6,000 genes present in the genome of Saccharomyces cerevisiae, and of those sequenced in other organisms, encode proteins of unknown function. Many of these genes are "silent," that is, they show no overt phenotype, in terms of growth rate or other fluxes, when they are deleted from the genome. We demonstrate how the intracellular concentrations of metabolites can reveal phenotypes for proteins active in metabolic regulation. Quantification of the change of several metabolite concentrations relative to the concentration change of one selected metabolite can reveal the site of action, in the metabolic network, of a silent gene. In the same way, comprehensive analyses of metabolite concentrations in mutants, providing "metabolic snapshots," can reveal functions when snapshots from strains deleted for unstudied genes are compared to those deleted for known genes. This approach to functional analysis, using comparative metabolomics, we call FANCY—an abbreviation for functional analysis by co-responses in yeast.

1,014 citations


Journal ArticleDOI
TL;DR: In this paper, the authors argue that any understanding of the global economy must be sensitive to four considerations: (a) conceptual categories and labels carry with them the dis- cursive power to shape material processes; (b) multiple scales of analysis must be incorporated in recognition of the contemporary'relativization of scale'; (c) no single institutional or organizational locus of analysis should be privileged; and (d) extrapolations from specific case studies and instances must be treated with caution.
Abstract: A vast and continually expanding literature on economic globalization continues to generate a miasma of conflicting viewpoints and alternative discourses. This article argues that any understanding of the global economy must be sensitive to four considerations: (a) conceptual categories and labels carry with them the dis- cursive power to shape material processes; (b) multiple scales of analysis must be incorporated in recognition of the contemporary 'relativization of scale'; (c) no single institutional or organizational locus of analysis should be privileged; and (d) extrapolations from specific case studies and instances must be treated with caution, but this should not preclude the option of discussing the global economy, and power relations within it, as a structural whole. This paper advocates a network method- ology as a potential framework to incorporate these concerns. Such a methodology requires us to identify actors in networks, their ongoing relations and the structural outcomes of these relations. Networks thus become the foundational unit of analysis for our understanding of the global economy, rather than individuals, firms or nation states. In presenting this argument we critically examine two examples of network methodology that have been used to provide frameworks for analysing the global economy: global commodity chains and actor-network theory. We suggest that while they fall short of fulfilling the promise of a network methodology in some respects, they do provide indications of the utility of such a methodology as a basis for under- standing the global economy.

1,007 citations


Journal ArticleDOI
TL;DR: Evidence for the contribution of cytokines to acute neurodegeneration is reviewed, focusing primarily on interleukin 1, tumour necrosis factor-α (TNFα) and transforming growth factor-β (TGFβ).
Abstract: Cytokines have been implicated as mediators and inhibitors of diverse forms of neurodegeneration. They are induced in response to brain injury and have diverse actions that can cause, exacerbate, mediate and/or inhibit cellular injury and repair. Here we review evidence for the contribution of cytokines to acute neurodegeneration, focusing primarily on interleukin 1 (IL-1), tumour necrosis factor-α (TNFα) and transforming growth factor-β (TGFβ). TGFβ seems to exert primarily neuroprotective actions, whereas TNFα might contribute to neuronal injury and exert protective effects. IL-1 mediates ischaemic, excitotoxic and traumatic brain injury, probably through multiple actions on glia, neurons and the vasculature. Understanding cytokine action in acute neurodegeneration could lead to novel and effective therapeutic strategies, some of which are already in clinical trials.

1,002 citations


Journal ArticleDOI
TL;DR: Vascular endothelial growth factor (VEGF) is a secreted mitogen highly specific for cultured endothelial cells and plays a central role in both angiogenesis and vasculogenesis, most notably the neovascularisation of growing tumours.
Abstract: Vascular endothelial growth factor (VEGF) is a secreted mitogen highly specific for cultured endothelial cells. In vivo VEGF induces microvascular permeability and plays a central role in both angiogenesis and vasculogenesis. VEGF is a promising target for therapeutic intervention in certain pathological conditions that are angiogenesis dependent, most notably the neovascularisation of growing tumours. Through alternative mRNA splicing, a single gene gives rise to several distinct isoforms of VEGF, which differ in their expression patterns as well as their biochemical and biological properties. Two VEGF receptor tyrosine kinases (VEGFRs) have been identified, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1). VEGFR-2 seems to mediate almost all observed endothelial cell responses to VEGF, whereas roles for VEGFR-1 are more elusive. VEGFR-1 might act predominantly as a ligand-binding molecule, sequestering VEGF from VEGFR-2 signalling. Several isoform-specific VEGF receptors exist that modulate VEGF activity. Neuropilin-1 acts as a co-receptor for VEGF(165), enhancing its binding to VEGFR-2 and its bioactivity. Heparan sulphate proteoglycans (HSPGs), as well as binding certain VEGF isoforms, interact with both VEGFR-1 and VEGFR-2. HSPGs have a wide variety of functions, such as the ability to partially restore lost function to damaged VEGF(165) and thereby prolonging its biological activity.

Journal ArticleDOI
TL;DR: The application of automated electron backscatter diffraction (EBSD) in the scanning electron microscope, to the quantitative analysis of grain and subgrain structures is discussed and compared with conventional methods of quantitative metallography.
Abstract: The application of automated Electron Backscatter Diffraction (EBSD) in the scanning electron microscope, to the quantitative analysis of grain and subgrain structures is discussed and compared with conventional methods of quantitative metallography. It is shown that the technique has reached a state of maturity such that linescans and maps can routinely be obtained and analysed using commercially available equipment and that EBSD in a Field Emission SEM (FEGSEM) allows quantitative analysis of grain/subgrains as small as ∼0.2 μm. EBSD can often give more accurate measurements of grain and subgrain size than conventional imaging methods, often in comparable times. Subgrain/cell measurements may be made more easily than in the TEM although the limited angular resolution of EBSD may be problematic in some cases. Additional information available from EBSD and not from conventional microscopy, gives a new dimension to quantitative metallography. Texture and its correlation with grain or subgrain size, shape and position are readily measured. Boundary misorientations, which are readily obtainable from EBSD, enable the distribution of boundary types to be determined and CSL boundaries can be identified and measured. The spatial distribution of Stored Energy in a sample and the amount of Recrystallization may also be measured by EBSD methods.

Journal ArticleDOI
TL;DR: Evidence for the continuity of psychotic symptoms with normal experiences is reviewed, focusing on the symptoms of hallucinations and delusions, and the theoretical and treatment implications of such a continuum are discussed.

Journal ArticleDOI
TL;DR: In this article, the authors summarise a number of international research projects being undertaken to understand the mechanical properties of natural cellulose fibres and composite materials, in particular the use of novel techniques, such as Raman spectroscopy, synchrotron x-ray and half-fringe photoelastic methods of measuring the physical and micromechanical properties.
Abstract: The following paper summarises a number of international research projects being undertaken to understand the mechanical properties of natural cellulose fibres and composite materials. In particular the use of novel techniques, such as Raman spectroscopy, synchrotron x-ray and half-fringe photoelastic methods of measuring the physical and micromechanical properties of cellulose fibres is reported. Current single fibre testing procedures are also reviewed with emphasis on the end-use in papermaking. The techniques involved in chemically modifying fibres to improve interfacial adhesion in composites are also reviewed, and the use of novel fibre sources such as bacterial and animal cellulose. It is found that there is overlap in current international research into this area, and that there are complementary approaches and therefore further combining of these may make further progress possible. In particular a need to measure locally the adhesion properties and deformation processes of fibres in composites, with different chemical treatments, ought to be a focus of future research.

Journal ArticleDOI
TL;DR: It is argued that biases in this cycle cause negative events to be attributed to external agents and hence contribute to the building of a paranoid world view, and a new integrative model is proposed that builds on this work.

Journal ArticleDOI
TL;DR: The findings suggest that attempts to exploit the association between cervical neoplasia and HPV infection to improve effectiveness of cervical screening programmes might be undermined by the limited inferences that can be drawn from the characterisation of a woman's HPV status at a single point in time, and the short lead time gained by its detection.

Journal ArticleDOI
TL;DR: Preliminary case-control evidence suggests that the quest for dietary and pharmacological means of modifying serum PON1 activity may allow the oxidant model of atherosclerosis to be tested in clinical trials.
Abstract: —There is considerable evidence that the antioxidant activity of high density lipoprotein (HDL) is largely due to the paraoxonase-1 (PON1) located on it. Experiments with transgenic PON1 knockout mice indicate the potential for PON1 to protect against atherogenesis. This protective effect of HDL against low density lipoprotein (LDL) lipid peroxidation is maintained longer than is the protective effect of antioxidant vitamins and could thus be more important. There is evidence that the genetic polymorphisms of PON1 least able to protect LDL against lipid peroxidation are overrepresented in coronary heart disease, particularly in association with diabetes. However, these polymorphisms explain only part of the variation in serum PON1 activity; thus, a more critical test of the hypothesis is likely to be whether low serum PON1 activity is associated with coronary heart disease. Preliminary case-control evidence suggests that this is indeed the case and, thus, that the quest for dietary and pharmacolog...

Journal ArticleDOI
TL;DR: This article surveys various complexity and expressiveness results on different forms of logic programming, in particular, propositional logic programming and datalog, but it also mentions general logic programming with function symbols.
Abstract: This article surveys various complexity and expressiveness results on different forms of logic programming. The main focus is on decidable forms of logic programming, in particular, propositional logic programming and datalog, but we also mention general logic programming with function symbols. Next to classical results on plain logic programming (pure Horn clause programs), more recent results on various important extensions of logic programming are surveyed. These include logic programming with different forms of negation, disjunctive logic programming, logic programming with equality, and constraint logic programming.

Journal ArticleDOI
TL;DR: The results show that markers vary in accuracy, with sentence repetition (a previously unused marker) proving to be the most useful and being able to identify the majority of children whose current language status falls in the normal range despite a history of SLI.
Abstract: In this study 160 children, aged 11 years with a definite history of specific language impairment (SLI), completed four tasks that could be potential positive psycholinguistic markers for this impairment: a third person singular task, a past tense task, a nonword repetition task, and a sentence repetition task. This allowed examination of more than one type of marker simultaneously, facilitating both comparisons between markers and also evaluation of combinations of markers in relation to identifying SLI. The study also provided data regarding the markers in relation to nonverbal IQ, made use of new normative data on all tasks, and examined marker accuracy in relation to current language status. The results show that markers vary in accuracy, with sentence repetition (a previously unused marker) proving to be the most useful. This psycholinguistic marker shows high levels of sensitivity (90%), specificity (85%), and overall accuracy (88%), as well as being able to identify the majority of children whose current language status falls in the normal range despite a history of SLI.

Journal ArticleDOI
TL;DR: In this paper, the effect of the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer was investigated using a multivariate analysis.
Abstract: Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras incolorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P=0.004, HR 1.3) and overall survival (P=0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P=0.008, HR 1.5, overall survival P=0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P=0.46, HR 1.12, overall survival P=0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer. ⌐ 2001 Cancer Research Campaign.

Journal ArticleDOI
TL;DR: The results indicate that the superficial zone of OA cartilage specimens, which is characterized by fibrillations, chondrocyte clusters, and degenerative matrix changes, contains a variable proportion of cells that immunostain for IL-1beta, TNFalpha, and 6 different MMPs.
Abstract: Objective To examine by immunohistochemistry the relative distributions of 6 matrix metalloproteinases (MMPs 1, 2, 3, 8, 9, and 13) and the 2 proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) in osteoarthritic (OA) cartilage compared with normal, age-matched articular cartilage. Methods Articular cartilage samples were obtained from the tibial plateau of OA knees removed at arthroplasty and from normal, nonarthritic, knees obtained at autopsy. Specimens were promptly fixed in Carnoy's fixative, processed, embedded in paraffin, sectioned, and examined by immunohistochemistry for MMP and cytokine production. In addition, human articular chondrocytes (HAC) were treated in vitro with either IL-1β, TNFα, or phorbol myristate acetate (PMA) to assess their potential to produce each of the MMPs, as determined by Western blotting and gelatin zymography. Results Immunodetection of the collagenases (MMPs 1, 8, and 13) and stromelysin 1 (MMP-3) was demonstrated in a proportion of chondrocytes in the superficial zone of almost all of the OA specimens that had degenerative matrix changes. The gelatinases (MMPs 2 and 9) were also demonstrated by immunohistochemistry but were not so prominent. IL-1β– and TNFα-positive chondrocytes were also observed in a proportion of cells in the superficial zones of OA specimens. Much less immunostaining for MMPs and cytokines was observed in the deep zone of all OA specimens, where the cartilage matrix and chondrocyte morphology appeared normal. In contrast, full-thickness normal cartilage specimens showed virtually no immunostaining for these MMPs or cytokines. Confirmation that chondrocytes can produce these 6 MMPs was obtained from HAC cultures treated with either IL-1β, TNFα, or PMA; conditioned medium from activated HAC contained all the MMPs demonstrated by immunohistochemistry. Dual immunolocalization studies of OA cartilage specimens demonstrated the coexpression of IL-1 with MMP-8 by individual chondrocytes in situ. Conclusion These results indicate that the superficial zone of OA cartilage specimens, which is characterized by fibrillations, chondrocyte clusters, and degenerative matrix changes, contains a variable proportion of cells that immunostain for IL-1β, TNFα, and 6 different MMPs. These observations support the concept that cytokine–MMP associations reflect a modified chondrocyte phenotype and an intrinsic process of cartilage degradation in OA.

Journal ArticleDOI
TL;DR: A generalised and extended decision matrix is constructed and rule and utility based techniques are developed for transforming various types of information within the matrix for aggregating attributes via ER that are equivalent with regard to underlying utility and rational in terms of preserving the features of original assessments.

Journal ArticleDOI
TL;DR: In this paper, a cognitive approach to the understanding of psychotic symptoms that focuses on the interpretation of intrusions into awareness is outlined, and the literature is reviewed and found to be compatible with such a model and the clinical implications are discussed.
Abstract: A cognitive approach to the understanding of psychotic symptoms that focuses on the interpretation of intrusions into awareness is outlined. It is argued that many positive psychotic symptoms (such as hallucinations and delusions) can be conceptualized as intrusions into awareness or culturally unacceptable interpretations of such intrusions, and that it is the interpretation of these intrusions that causes the associated distress and disability. It is also argued that the nature of these interpretations is affected by faulty self and social knowledge and that both the intrusions and their interpretations are maintained by mood, physiology, and cognitive and behavioural responses (including selective attention, safety behaviours and counterproductive control strategies). The literature is reviewed and found to be compatible with such a model and the clinical implications are discussed.

Journal ArticleDOI
TL;DR: The survey is proving to be extremely successful, with more than 600 pulsars discovered so far as discussed by the authors, and the number of newly discovered pulsars tend to be young, distant and of high radio luminosity, which is a valuable sample for studies of pulsar emission properties, the Galactic distribution and evolution of pulsars, and as probes of interstellar medium properties.
Abstract: limiting flux density of the survey is about 0.2 mJy. At shorter or longer periods or higher dispersions, the sensitivity is reduced. Timing observations are carried out for pulsars discovered in the survey for 12‐18 months after confirmation to obtain accurate positions, spin parameters, dispersion measures, pulse shapes and mean flux densities. The survey is proving to be extremely successful, with more than 600 pulsars discovered so far. We expect that, when complete, this one survey will come close to finding as many pulsars as all previous pulsar surveys put together. The newly discovered pulsars tend to be young, distant and of high radio luminosity. They will form a valuable sample for studies of pulsar emission properties, the Galactic distribution and evolution of pulsars, and as probes of interstellar medium properties. This paper reports the timing and pulse shape parameters for the first 100 pulsars timed at Parkes, including three pulsars with periods of less than 100 ms which are members of binary systems. These results are briefly compared with the parameters of the previously known population.

Journal ArticleDOI
TL;DR: In this paper, the authors discuss the impact of workplace transitions on employee well-being, focusing on four issues that are current concerns for organizations and workforce; job insecurity, work hours, control at work, and managerial style.
Abstract: Over the last 40 years, major changes have taken place in the workplace. The growth in the use of information technology at work, the globalization of many industries, organizational restructuring, changes in work contracts and worktime scheduling have radically transformed the nature of work in many organizations. The workforce itself is also diversifying, with an increase in female participation, a growing number of dual-earner couples and older workers. The present paper discusses the impact of these workplace transitions on employee well-being. We focus on four issues that are current concerns for organizations and the workforce; job insecurity, work hours, control at work, and managerial style. For each topic, recent research is presented, with suggestions for future research and recommendations for practitioners working in the organizations of today. The paper concludes with some final considerations for researchers and practitioners that may benefit both employee well-being and organizational effectiveness.

Journal ArticleDOI
22 Feb 2001-Nature
TL;DR: A role is demonstrated for the Ets1 and Ets2 transcription factors based on their ability to activate the p16INK4a promoter through an ETS-binding site and their patterns of expression during the lifespan of human diploid fibroblasts.
Abstract: The p16INK4a cyclin-dependent kinase inhibitor is implicated in replicative senescence, the state of permanent growth arrest provoked by cumulative cell divisions or as a response to constitutive Ras-Raf-MEK signalling in somatic cells Some contribution to senescence presumably underlies the importance of p16INK4a as a tumour suppressor but the mechanisms regulating its expression in these different contexts remain unknown Here we demonstrate a role for the Ets1 and Ets2 transcription factors based on their ability to activate the p16INK4a promoter through an ETS-binding site and their patterns of expression during the lifespan of human diploid fibroblasts The induction of p16INK4a by Ets2, which is abundant in young human diploid fibroblasts, is potentiated by signalling through the Ras-Raf-MEK kinase cascade and inhibited by a direct interaction with the helix-loop-helix protein Id1 (ref 11) In senescent cells, where the Ets2 levels and MEK signalling decline, the marked increase in p16INK4a expression is consistent with the reciprocal reduction of Id1 and accumulation of Ets1

Journal ArticleDOI
TL;DR: People who showed more demanding challenging behavior were more likely to need greater levels of assistance in eating, dressing and washing, be incontinent and have more restricted expressive and receptive communication.

Journal ArticleDOI
TL;DR: The role of regulation and the use of synthetic agrochemicals, the desired degree of self reliance of agricultural systems, and the scale of production and trade in agricultural goods are all considered in the context of this discussion of sustainability as mentioned in this paper.

Journal ArticleDOI
12 Jan 2001-Cell
TL;DR: It is reported that XRCC1 interacts with human polynucleotide kinase in addition to its established interactions with DNA polymerase-beta and DNA ligase III, which identifies a novel pathway for mammalian single-strand break repair and demonstrates a concerted role for XR CCP and PNK in the initial step of processing damaged DNA ends.

Proceedings ArticleDOI
03 Jul 2001
TL;DR: The Active Shape Model essentially matches a model to boundaries in an image, and the Active Appearance Model finds model parameters which synthesize a complete image which is as similar as possible to the target image.
Abstract: Statistical models of shape and appearance are powerful tools for interpreting medical images. We assume a training set of images in which corresponding landmark points have been marked on every image. From this data we can compute a statistical model of the shape variation, a model of the texture variation and a model of the correlations between shape and texture. With enough training examples such models should be able to synthesize any image of normal anatomy. By finding the parameters which optimize the match between a synthesized model image and a target image we can locate all the structures represented by the model. Two approaches to the matching will be described. The Active Shape Model essentially matches a model to boundaries in an image. The Active Appearance Model finds model parameters which synthesize a complete image which is as similar as possible to the target image. By using a difference decomposition approach the current difference between target image and synthesized model image can be used to update the model parameters, leading to rapid matching of complex models. We will demonstrate the application of such models to a variety of different problems.