Showing papers by "University of Cambridge published in 1999"

Measurements of Omega and Lambda from 42 High-Redshift Supernovae

Abstract: We report measurements of the mass density, Omega_M, and cosmological-constant energy density, Omega_Lambda, of the universe based on the analysis of 42 Type Ia supernovae discovered by the Supernova Cosmology Project. The magnitude-redshift data for these SNe, at redshifts between 0.18 and 0.83, are fit jointly with a set of SNe from the Calan/Tololo Supernova Survey, at redshifts below 0.1, to yield values for the cosmological parameters. All SN peak magnitudes are standardized using a SN Ia lightcurve width-luminosity relation. The measurement yields a joint probability distribution of the cosmological parameters that is approximated by the relation 0.8 Omega_M - 0.6 Omega_Lambda ~= -0.2 +/- 0.1 in the region of interest (Omega_M <~ 1.5). For a flat (Omega_M + Omega_Lambda = 1) cosmology we find Omega_M = 0.28{+0.09,-0.08} (1 sigma statistical) {+0.05,-0.04} (identified systematics). The data are strongly inconsistent with a Lambda = 0 flat cosmology, the simplest inflationary universe model. An open, Lambda = 0 cosmology also does not fit the data well: the data indicate that the cosmological constant is non-zero and positive, with a confidence of P(Lambda > 0) = 99%, including the identified systematic uncertainties. The best-fit age of the universe relative to the Hubble time is t_0 = 14.9{+1.4,-1.1} (0.63/h) Gyr for a flat cosmology. The size of our sample allows us to perform a variety of statistical tests to check for possible systematic errors and biases. We find no significant differences in either the host reddening distribution or Malmquist bias between the low-redshift Calan/Tololo sample and our high-redshift sample. The conclusions are robust whether or not a width-luminosity relation is used to standardize the SN peak magnitudes.

Electroluminescence in conjugated polymers

Abstract: Research in the use of organic polymers as the active semiconductors in light-emitting diodes has advanced rapidly, and prototype devices now meet realistic specifications for applications. These achievements have provided insight into many aspects of the background science, from design and synthesis of materials, through materials fabrication issues, to the semiconductor physics of these polymers.

Two-dimensional charge transport in self-organized, high-mobility conjugated polymers

Abstract: Self-organization in many solution-processed, semiconducting conjugated polymers results in complex microstructures, in which ordered microcrystalline domains are embedded in an amorphous matrix1. This has important consequences for electrical properties of these materials: charge transport is usually limited by the most difficult hopping processes and is therefore dominated by the disordered matrix, resulting in low charge-carrier mobilities2 (⩽10-5 cm2 V-1 s-1). Here we use thin-film, field-effect transistor structures to probe the transport properties of the ordered microcrystalline domains in the conjugated polymer poly(3-hexylthiophene), P3HT. Self-organization in P3HT results in a lamella structure with two-dimensional conjugated sheets formed by interchain stacking. We find that, depending on processing conditions, the lamellae can adopt two different orientations—parallel and normal to the substrate—the mobilities of which differ by more than a factor of 100, and can reach values as high as 0.1 cm2 V-1 s-1 (refs 3, 4). Optical spectroscopy of the field-induced charge, combined with the mobility anisotropy, reveals the two-dimensional interchain character of the polaronic charge carriers, which exhibit lower relaxation energies than the corresponding radical cations on isolated one-dimensional chains. The possibility of achieving high mobilities via two-dimensional transport in self-organized conjugated lamellae is important for applications of polymer transistors in logic circuits5 and active-matrix displays4,6.

Information hiding-a survey

Abstract: Information-hiding techniques have recently become important in a number of application areas. Digital audio, video, and pictures are increasingly furnished with distinguishing but imperceptible marks, which may contain a hidden copyright notice or serial number or even help to prevent unauthorized copying directly. Military communications systems make increasing use of traffic security techniques which, rather than merely concealing the content of a message using encryption, seek to conceal its sender, its receiver, or its very existence. Similar techniques are used in some mobile phone systems and schemes proposed for digital elections. Criminals try to use whatever traffic security properties are provided intentionally or otherwise in the available communications systems, and police forces try to restrict their use. However, many of the techniques proposed in this young and rapidly evolving field can trace their history back to antiquity, and many of them are surprisingly easy to circumvent. In this article, we try to give an overview of the field, of what we know, what works, what does not, and what are the interesting topics for research.

Communicating and Mobile Systems: the Pi-Calculus

Abstract: Glossary Part I. Communicating Systems: 1. Introduction 2. Behaviour of automata 3. Sequential processes and bisimulation 4. Concurrent processes and reaction 5. Transitions and strong equivalence 6. Observation equivalence: theory 7. Observation equivalence: examples Part II. The pi-Calculus: 8. What is mobility? 9. The pi-calculus and reaction 10. Applications of the pi-calculus 11. Sorts, objects and functions 12. Commitments and strong bisimulation 13. Observation equivalence and examples 14. Discussion and related work Bibliography Index.

Inverse density dependence and the Allee effect

Abstract: The Allee effect describes a scenario in which populations at low numbers are affected by a positive relationship between population growth rate and density, which increases their likelihood of extinction The importance of this dynamic process in ecology has been under-appreciated and recent evidence now suggests that it might have an impact on the population dynamics of many plant and animal species Studies of the causal mechanisms generating Allee effects in small populations could provide a key to understanding their dynamics

Early development and fitness in birds and mammals

Abstract: Conditions experienced during early development affect survival and reproductive performance in many bird and mammal species. Factors affecting early development can therefore have an important influence both on the optimization of life histories and on population dynamics. The understanding of these evolutionary and dynamic consequences is just starting to emerge.

Quality control by DNA repair.

Abstract: Faithful maintenance of the genome is crucial to the individual and to species. DNA damage arises from both endogenous sources such as water and oxygen and exogenous sources such as sunlight and tobacco smoke. In human cells, base alterations are generally removed by excision repair pathways that counteract the mutagenic effects of DNA lesions. This serves to maintain the integrity of the genetic information, although not all of the pathways are absolutely error-free. In some cases, DNA damage is not repaired but is instead bypassed by specialized DNA polymerases.

The anatomy of a context-aware application

Abstract: We describe a sensor-driven, or sentient, platform for context-aware computing that enables applications to follow mobile users as they move around a building. The platform is particularly suitable for richly equipped, networked environments. The only item a user is required to carry is a small sensor tag, which identifies them to the system and locates them accurately in three dimensions. The platform builds a dynamic model of the environment using these location sensors and resource information gathered by telemetry software, and presents it in a form suitable for application programmers. Use of the platform is illustrated through a practical example, which allows a user's current working desktop to follow them as they move around the environment.

Social intelligence in the normal and autistic brain: an fMRI study.

Abstract: There is increasing support for the existence of 'social intelligence' [Humphrey (1984) Consciousness Regained], independent of general intelligence. Brothers et al. 1990) J. Cog. Neurosci., 4, 107-118] proposed a network of neural regions that comprise the 'social brain': the orbito-frontal cortex (OFC), superior temporal gyrus (STG) and amygdala. We tested Brothers' theory by examining both normal subjects as well as patients with high-functioning autism or Asperger syndrome (AS), who are well known to have deficits in social intelligence, and perhaps deficits in amygdala function [Bauman & Kemper (1988) J. Neuropath. Exp. Neurol., 47, 369]. We used a test of judging from the expressions of another person's eyes what that other person might be thinking or feeling. Using functional magnetic resonance imaging (fMRI) we confirmed Brothers' prediction that the STG and amygdala show increased activation when using social intelligence. Some areas of the prefrontal cortex also showed activation. In contrast, patients with autism or AS activated the fronto-temporal regions but not the amygdala when making mentalistic inferences from the eyes. These results provide support for the social brain theory of normal function, and the amygdala theory of autism.

The Resurrecting Duckling: Security Issues for Ad-hoc Wireless Networks

Abstract: In the near future, many personal electronic devices will be able to communicate with each other over a short range wireless channel. We investigate the principal security issues for such an environment. Our discussion is based on the concrete example of a thermometer that makes its readings available to other nodes over the air. Some lessons learned from this example appear to be quite general to ad-hoc networks, and rather different from what we have come to expect in more conventional systems: denial of service, the goals of authentication, and the problems of naming all need re-examination. We present the resurrecting duckling security policy model, which describes secure transient association of a device with multiple serialised owners.

Dominant negative mutations in human PPARγ associated with severe insulin resistance, diabetes mellitus and hypertension

Abstract: Thiazolidinediones are a new class of antidiabetic agent that improve insulin sensitivity and reduce plasma glucose and blood pressure in subjects with type 2 diabetes. Although these agents can bind and activate an orphan nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARgamma), there is no direct evidence to conclusively implicate this receptor in the regulation of mammalian glucose homeostasis. Here we report two different heterozygous mutations in the ligand-binding domain of PPARgamma in three subjects with severe insulin resistance. In the PPARgamma crystal structure, the mutations destabilize helix 12 which mediates transactivation. Consistent with this, both receptor mutants are markedly transcriptionally impaired and, moreover, are able to inhibit the action of coexpressed wild-type PPARgamma in a dominant negative manner. In addition to insulin resistance, all three subjects developed type 2 diabetes mellitus and hypertension at an unusually early age. Our findings represent the first germline loss-of-function mutations in PPARgamma and provide compelling genetic evidence that this receptor is important in the control of insulin sensitivity, glucose homeostasis and blood pressure in man.

The performance measurement revolution: why now and what next?

Abstract: Asks why business performance measurement has become so topical, so recently. Argues that there are seven main reasons: the changing nature of work; increasing competition; specific improvement initiatives; national and international quality awards; changing organisational roles; changing external demands; and the power of information technology. Evidence to support this assertion is drawn from the academic and practitioner literatures, interviews and discussions with people specialising in the field and a broad review of the current state‐of‐the‐art in business performance measurement. Presents a framework onto which current research in business performance measurement can be mapped and identifies areas which require further work.

Single-Domain Circular Nanomagnets

Abstract: The magnetic properties of deep submicron circular nanomagnets fabricated by high-resolution electron beam lithography from Supermalloy $({\mathrm{Ni}}_{80}{\mathrm{Fe}}_{14}{\mathrm{Mo}}_{5})$ have been studied as a function of both diameter (500--55 nm) and thickness (6--15 nm). A high sensitivity magneto-optical method has been used to measure the hysteresis loops of these nanomagnets. An experimental phase diagram in diameter and thickness has thus been produced which identifies a vortex phase and a single-domain phase. The two phases agree well with micromagnetic theory.

Attention and executive deficits in Alzheimer's disease: A critical review

Abstract: In this review we summarize the progress that has been made in the research on attentional and executive deficits in Alzheimer's disease. Like memory, attention is now recognized as consisting of subtypes that differ in their function and anatomical basis. We base our review upon a classification of three subtypes of attention: selective, sustained and divided. This model derives from lesion studies, animal electrophysiological recordings and functional imaging. We examine how these subcomponents of attention can be reconciled with neuropsychological models of attentional control, particularly the Supervisory Attentional System and the Central Executive System of Shallice and Baddeley, respectively. We also discuss the relationship of attention to the concept of executive function. Current evidence suggests that after an initial amnesic stage in Alzheimer's disease, attention is the first non-memory domain to be affected, before deficits in language and visuospatial functions. This is consistent with the possibility that difficulties with activities of daily living, which occur in even mildly demented patients, may be related to attentional deficits. It appears that divided attention and aspects of selective attention, such as set-shifting and response selection, are particularly vulnerable while sustained attention is relatively preserved in the early stages. The phenomenon of cognitive slowing in Alzheimer's disease and normal ageing emphasizes the need to discriminate quantitative changes in attention dysfunction from qualitative changes which may be specifically related to the disease process. The neuropathological basis of these attentional deficits remains unsettled, with two competing hypotheses: spread of pathology from the medial temporal to basal forebrain structures versus corticocortical tract disconnection. Finally we discuss the difficulties of comparing evidence across studies and look at the implications for the design of future studies and future directions that may be fruitful in the research on attention in Alzheimer's disease.

The DNA sequence of human chromosome 22

Abstract: Knowledge of the complete genomic DNA sequence of an organism allows a systematic approach to defining its genetic components. The genomic sequence provides access to the complete structures of all genes, including those without known function, their control elements, and, by inference, the proteins they encode, as well as all other biologically important sequences. Furthermore, the sequence is a rich and permanent source of information for the design of further biological studies of the organism and for the study of evolution through cross-species sequence comparison. The power of this approach has been amply demonstrated by the determination of the sequences of a number of microbial and model organisms. The next step is to obtain the complete sequence of the entire human genome. Here we report the sequence of the euchromatic part of human chromosome 22. The sequence obtained consists of 12 contiguous segments spanning 33.4 megabases, contains at least 545 genes and 134 pseudogenes, and provides the first view of the complex chromosomal landscapes that will be found in the rest of the genome.

Recognition of Faux Pas by Normally Developing Children and Children with Asperger Syndrome or High-Functioning Autism

Abstract: Most theory of mind (ToM) tests are designed for subjects with a mental age of 4-6 years. There are very few ToM tests for subjects who are older or more able than this. We report a new test of ToM, designed for children 7-11 years old. The task involves recognizing faux pas. Study 1 tested 7-9, and 11-year-old normal children. Results showed that the ability to detect faux pas developed with age and that there was a differential developmental profile between the two sexes (female superiority). Study 2 tested children with Asperger syndrome (AS) or high-functioning autism (HFA), selected for being able to pass traditional 4- to 6-year level (first- and second-order) false belief tests. Results showed that whereas normal 9- to 11-year-old children were skilled at detecting faux pas, children with AS or HFA were impaired on this task. Study 3 reports a refinement in the test, employing control stimuli. This replicated the results from Study 2. Some patients with AS or HFA were able to recognize faux pas but still produced them. Future research should assess faux pas production.

Overcoming the ‘value‐action gap’ in environmental policy: Tensions between national policy and local experience

Abstract: This paper is concerned with debates over the implementation of sustainability objectives. In particular, it focuses on policies that address the ‘value‐action gap’ in environmental policy. Using evidence from the author's research connected with the UK Going for Green Sustainable Communities Project in Huntingdonshire, the paper highlights the tensions between national policies that are based on an ‘information deficit’ model of participation, and local research and experience that posits a more complex relationship between individuals and institutions. While this suggests the need to develop more differentiated policies based on the restructuring of socioeconomic and political institutions, the paper warns against knee‐jerk calls for more local, community or public participation which simply replace one set of generalised appeals with another. The paper concludes that greater emphasis must be placed on the negotiation of partnerships that are more sensitive to local diversity, and which involve...

Mechanical and Chemical Unfolding of a Single Protein: A Comparison

Abstract: Is the mechanical unraveling of protein domains by atomic force microscopy (AFM) just a technological feat or a true measurement of their unfolding? By engineering a protein made of tandem repeats of identical Ig modules, we were able to get explicit AFM data on the unfolding rate of a single protein domain that can be accurately extrapolated to zero force. We compare this with chemical unfolding rates for untethered modules extrapolated to 0 M denaturant. The unfolding rates obtained by the two methods are the same. Furthermore, the transition state for unfolding appears at the same position on the folding pathway when assessed by either method. These results indicate that mechanical unfolding of a single protein by AFM does indeed reflect the same event that is observed in traditional unfolding experiments. The way is now open for the extensive use of AFM to measure folding reactions at the single-molecule level. Single-molecule AFM recordings have the added advantage that they define the reaction coordinate and expose rare unfolding events that cannot be observed in the absence of chemical denaturants.

Characterization of progressive motor deficits in mice transgenic for the human Huntington's disease mutation.

Abstract: Transgenic mice expressing exon 1 of the human Huntington’s disease (HD) gene carrying a 141–157 CAG repeat (line R6/2) develop a progressive neurological phenotype with motor symptoms resembling those seen in HD. We have characterized the motor deficits in R6/2 mice using a battery of behavioral tests selected to measure motor aspects of swimming, fore- and hindlimb coordination, balance, and sensorimotor gating [swimming tank, rotarod, raised beam, fore- and hindpaw footprinting, and acoustic startle/prepulse inhibition (PPI)]. Behavioral testing was performed on female hemizygotic R6/2 transgenic mice (n = 9) and female wild-type littermates (n = 22) between 5 and 14 weeks of age. Transgenic mice did not show an overt behavioral phenotype until around 8 weeks of age. However, as early as 5–6 weeks of age they had significant difficulty swimming, traversing the narrowest square (5 mm) raised beam, and maintaining balance on the rotarod at rotation speeds of 33–44 rpm. Furthermore, they showed significant impairment in prepulse inhibition (an impairment also seen in patients with HD). Between 8 and 15 weeks, R6/2 transgenic mice showed a progressive deterioration in performance on all of the motor tests. Thus R6/2 mice show measurable deficits in motor behavior that begin subtly and increase progressively until death. Our data support the use of R6/2 mice as a model of HD and indicate that they may be useful for evaluating therapeutic strategies for HD, particularly those aimed at reducing the severity of motor symptoms or slowing the course of the disease.

Global optimization of clusters, crystals, and biomolecules

Abstract: Finding the optimal solution to a complex optimization problem is of great importance in many fields, ranging from protein structure prediction to the design of microprocessor circuitry. Some recent progress in finding the global minima of potential energy functions is described, focusing on applications of the simple "basin-hopping" approach to atomic and molecular clusters and more complicated hypersurface deformation techniques for crystals and biomolecules. These methods have produced promising results and should enable larger and more complex systems to be treated in the future.

Regulation of p53 in response to DNA damage

Abstract: Activation of p53 can occur in response to a number of cellular stresses, including DNA damage, hypoxia and nucleotide deprivation. Several forms of DNA damage have been shown to activate p53, including those generated by ionising radiation (IR), radio-mimetic drugs, ultraviolet light (UV) and chemicals such as methyl methane sulfonate (MMS). Under normal conditions, p53 levels are maintained at a low state by virtue of the extremely short-half life of the polypeptide. In addition to this, p53 normally exists in an largely inactive state that is relatively inefficient at binding to DNA and activating transcription. Activation of p53 in response to DNA damage is associated with a rapid increase in its levels and with an increased ability of p53 to bind DNA and mediate transcriptional activation. This then leads to the activation of a number of genes whose products trigger cell-cycle arrest, apoptosis, or DNA repair. Recent work has suggested that this regulation is brought about largely through DNA damage triggering a series of phosphorylation, de-phosphorylation and acetylation events on the p53 polypeptide. Here, we discuss the nature of these modifications, the enzymes that bring them about, and how changes in p53 modification lead to p53 activation.