Showing papers by "University of Cambridge published in 2006"

Raman spectrum of graphene and graphene layers.

Abstract: Graphene is the two-dimensional building block for carbon allotropes of every other dimensionality We show that its electronic structure is captured in its Raman spectrum that clearly evolves with the number of layers The D peak second order changes in shape, width, and position for an increasing number of layers, reflecting the change in the electron bands via a double resonant Raman process The G peak slightly down-shifts This allows unambiguous, high-throughput, nondestructive identification of graphene layers, which is critically lacking in this emerging research area

Multiferroic and magnetoelectric materials

Abstract: A ferroelectric crystal exhibits a stable and switchable electrical polarization that is manifested in the form of cooperative atomic displacements. A ferromagnetic crystal exhibits a stable and switchable magnetization that arises through the quantum mechanical phenomenon of exchange. There are very few 'multiferroic' materials that exhibit both of these properties, but the 'magnetoelectric' coupling of magnetic and electrical properties is a more general and widespread phenomenon. Although work in this area can be traced back to pioneering research in the 1950s and 1960s, there has been a recent resurgence of interest driven by long-term technological aspirations.

Mercury: visualization and analysis of crystal structures

Abstract: Since its original release, the popular crystal structure visualization program Mercury has undergone continuous further development. Comparisons between crystal structures are facilitated by the ability to display multiple structures simultaneously and to overlay them. Improvements have been made to many aspects of the visual display, including the addition of depth cueing, and highly customizable lighting and background effects. Textual and numeric data associated with structures can be shown in tables or spreadsheets, the latter opening up new ways of interacting with the visual display. Atomic displacement ellipsoids, calculated powder diffraction patterns and predicted morphologies can now be shown. Some limited molecular-editing capabilities have been added. The object-oriented nature of the C++ libraries underlying Mercury makes it easy to re-use the code in other applications, and this has facilitated three-dimensional visualization in several other programs produced by the Cambridge Crystallographic Data Centre.

Protein Misfolding, Functional Amyloid, and Human Disease

Abstract: Peptides or proteins convert under some conditions from their soluble forms into highly ordered fibrillar aggregates. Such transitions can give rise to pathological conditions ranging from neurodegenerative disorders to systemic amyloidoses. In this review, we identify the diseases known to be associated with formation of fibrillar aggregates and the specific peptides and proteins involved in each case. We describe, in addition, that living organisms can take advantage of the inherent ability of proteins to form such structures to generate novel and diverse biological functions. We review recent advances toward the elucidation of the structures of amyloid fibrils and the mechanisms of their formation at a molecular level. Finally, we discuss the relative importance of the common main-chain and side-chain interactions in determining the propensities of proteins to aggregate and describe some of the evidence that the oligomeric fibril precursors are the primary origins of pathological behavior.

Machine learning for high-speed corner detection

Abstract: Where feature points are used in real-time frame-rate applications, a high-speed feature detector is necessary. Feature detectors such as SIFT (DoG), Harris and SUSAN are good methods which yield high quality features, however they are too computationally intensive for use in real-time applications of any complexity. Here we show that machine learning can be used to derive a feature detector which can fully process live PAL video using less than 7% of the available processing time. By comparison neither the Harris detector (120%) nor the detection stage of SIFT (300%) can operate at full frame rate. Clearly a high-speed detector is of limited use if the features produced are unsuitable for downstream processing. In particular, the same scene viewed from two different positions should yield features which correspond to the same real-world 3D locations [1]. Hence the second contribution of this paper is a comparison corner detectors based on this criterion applied to 3D scenes. This comparison supports a number of claims made elsewhere concerning existing corner detectors. Further, contrary to our initial expectations, we show that despite being principally constructed for speed, our detector significantly outperforms existing feature detectors according to this criterion.

Structure and function of matrix metalloproteinases and TIMPs

Abstract: Matrix metalloproteinases (MMPs), also called matrixins, function in the extracellular environment of cells and degrade both matrix and non-matrix proteins. They play central roles in morphogenesis, wound healing, tissue repair and remodelling in response to injury, e.g. after myocardial infarction, and in progression of diseases such as atheroma, arthritis, cancer and chronic tissue ulcers. They are multi-domain proteins and their activities are regulated by tissue inhibitors of metalloproteinases (TIMPs). This review introduces the members of the MMP family and discusses their domain structure and function, proenyme activation, the mechanism of inhibition by TIMPs and their significance in physiology and pathology.

Bose-Einstein condensation of exciton polaritons

Abstract: Phase transitions to quantum condensed phases—such as Bose–Einstein condensation (BEC), superfluidity, and superconductivity—have long fascinated scientists, as they bring pure quantum effects to a macroscopic scale. BEC has, for example, famously been demonstrated in dilute atom gas of rubidium atoms at temperatures below 200 nanokelvin. Much effort has been devoted to finding a solid-state system in which BEC can take place. Promising candidate systems are semiconductor microcavities, in which photons are confined and strongly coupled to electronic excitations, leading to the creation of exciton polaritons. These bosonic quasi-particles are 109 times lighter than rubidium atoms, thus theoretically permitting BEC to occur at standard cryogenic temperatures. Here we detail a comprehensive set of experiments giving compelling evidence for BEC of polaritons. Above a critical density, we observe massive occupation of the ground state developing from a polariton gas at thermal equilibrium at 19 K, an increase of temporal coherence, and the build-up of long-range spatial coherence and linear polarization, all of which indicate the spontaneous onset of a macroscopic quantum phase. Bose–Einstein condensation (BEC), a form of matter first postulated in 1924, has famously been demonstrated in dilute atomic gases at ultra-low temperatures. Much effort is now being devoted to exploring solid-state systems in which BEC can occur. In theory semiconductor microcavities, where photons are confined and coupled to electronic excitations leading to the creation of polaritons, could allow BEC at standard cryogenic temperatures. Kasprzak et al. now present experiments in which polaritons are excited in such a microcavity. Above a critical polariton density, spontaneous onset of a macroscopic quantum phase occurs, indicating a solid-state BEC. BEC should also be possible at higher temperatures if coupling of light with solid excitations is sufficiently strong. Demokritov et al. have achieved just that, BEC at room temperature in a gas of magnons, which are a type of magnetic excitation. This paper presents a comprehensive set of experiments in which polaritons are excited in a semiconductor microcavity. Above a critical density of polaritons, massive occupation of the ground state at 19 K is observed and various pieces of experimental evidence point to a spontaneous onset of a macroscopic quantum phase.

Notch signalling: a simple pathway becomes complex

Abstract: A small number of signalling pathways are used iteratively to regulate cell fates, cell proliferation and cell death in development. Notch is the receptor in one such pathway, and is unusual in that most of its ligands are also transmembrane proteins; therefore signalling is restricted to neighbouring cells. Although the intracellular transduction of the Notch signal is remarkably simple, with no secondary messengers, this pathway functions in an enormous diversity of developmental processes and its dysfunction is implicated in many cancers.

A Resilient, Low-Frequency, Small-World Human Brain Functional Network with Highly Connected Association Cortical Hubs

Abstract: Small-world properties have been demonstrated for many complex networks. Here, we applied the discrete wavelet transform to functional magnetic resonance imaging (fMRI) time series, acquired from healthy volunteers in the resting state, to estimate frequency-dependent correlation matrices characterizing functional connectivity between 90 cortical and subcortical regions. After thresholding the wavelet correlation matrices to create undirected graphs of brain functional networks, we found a small-world topology of sparse connections most salient in the low-frequency interval 0.03–0.06 Hz. Global mean path length (2.49) was approximately equivalent to a comparable random network, whereas clustering (0.53) was two times greater; similar parameters have been reported for the network of anatomical connections in the macaque cortex. The human functional network was dominated by a neocortical core of highly connected hubs and had an exponentially truncated power law degree distribution. Hubs included recently evolved regions of the heteromodal association cortex, with long-distance connections to other regions, and more cliquishly connected regions of the unimodal association and primary cortices; paralimbic and limbic regions were topologically more peripheral. The network was more resilient to targeted attack on its hubs than a comparable scale-free network, but about equally resilient to random error. We conclude that correlated, low-frequency oscillations in human fMRI data have a small-world architecture that probably reflects underlying anatomical connectivity of the cortex. Because the major hubs of this network are critical for cognition, its slow dynamics could provide a physiological substrate for segregated and distributed information processing.

Small-World Brain Networks

Abstract: Many complex networks have a small-world topology characterized by dense local clustering or cliquishness of connections between neighboring nodes yet a short path length between any (distant) pair of nodes due to the existence of relatively few long-range connections. This is an attractive model for the organization of brain anatomical and functional networks because a small-world topology can support both segregated/specialized and distributed/integrated information processing. Moreover, small-world networks are economical, tending to minimize wiring costs while supporting high dynamical complexity. The authors introduce some of the key mathematical concepts in graph theory required for small-world analysis and review how these methods have been applied to quantification of cortical connectivity matrices derived from anatomical tract-tracing studies in the macaque monkey and the cat. The evolution of small-world networks is discussed in terms of a selection pressure to deliver cost-effective information-processing systems. The authors illustrate how these techniques and concepts are increasingly being applied to the analysis of human brain functional networks derived from electroencephalography/magnetoencephalography and fMRI experiments. Finally, the authors consider the relevance of small-world models for understanding the emergence of complex behaviors and the resilience of brain systems to pathological attack by disease or aberrant development. They conclude that small-world models provide a powerful and versatile approach to understanding the structure and function of human brain systems.

The Supernova Legacy Survey: Measurement of Omega_M, Omega_Lambda,and w from the First Year Data Set

Abstract: We present distance measurements to 71 high redshift type Ia supernovae discovered during the first year of the 5-year Supernova Legacy Survey (SNLS). These events were detected and their multi-color light-curves measured using the MegaPrime/MegaCam instrument at the Canada-France-Hawaii Telescope (CFHT), by repeatedly imaging four one-square degree fields in four bands. Follow-up spectroscopy was performed at the VLT, Gemini and Keck telescopes to confirm the nature of the supernovae and to measure their redshift. With this data set, we have built a Hubble diagram extending to z = 1, with all distance measurements involving at least two bands. Systematic uncertainties are evaluated making use of the multiband photometry obtained at CFHT. Cosmological fits to this first year SNLS Hubble diagram give the following results: {Omega}{sub M} = 0.263 {+-} 0.042 (stat) {+-} 0.032 (sys) for a flat {Lambda}CDM model; and w = -1.023 {+-} 0.090 (stat) {+-} 0.054 (sys) for a flat cosmology with constant equation of state w when combined with the constraint from the recent Sloan Digital Sky Survey measurement of baryon acoustic oscillations.

Doing interpretive research

Abstract: Interpretive research in information systems (IS) is now a well-established part of the field. However, there is a need for more material on how to carry out such work from inception to publication. I published a paper a decade ago (Walsham, 1995) which addressed the nature of interpretive IS case studies and methods for doing such research. The current paper extends this earlier contribution, with a widened scope of all interpretive research in IS, and through further material on carrying out fieldwork, using theory and analysing data. In addition, new topics are discussed on constructing and justifying a research contribution, and on ethical issues and tensions in the conduct of interpretive work. The primary target audience for the paper is less-experienced IS researchers, but I hope that the paper will also stimulate reflection for the more-experienced IS researcher and be of relevance to interpretive researchers in other social science fields.

Consensus statement on management of intersex disorders

Abstract: The birth of an intersex child prompts a long-term management strategy that involves a myriad of professionals working with the family. There has been progress in diagnosis, surgical techniques, understanding psychosocial issues and in recognizing and accepting the place of patient advocacy. The Lawson Wilkins Paediatric Endocrine Society (LWPES) and the European Society for Paediatric Endocrinology (ESPE) considered it timely to review the management of intersex disorders from a broad perspective, to review data on longer term outcome and to formulate proposals for future studies. The methodology comprised establishing a number of working groups whose membership was drawn from 50 international experts in the field. The groups prepared prior written responses to a defined set of questions resulting from an evidence based review of the literature. At a subsequent gathering of participants, a framework for a consensus document was agreed. This paper constitutes its final form.

Global biodiversity conservation priorities.

Abstract: The location of and threats to biodiversity are distributed unevenly, so prioritization is essential to minimize biodiversity loss. To address this need, biodiversity conservation organizations have proposed nine templates of global priorities over the past decade. Here, we review the concepts, methods, results, impacts, and challenges of these prioritizations of conservation practice within the theoretical irreplaceability/vulnerability framework of systematic conservation planning. Most of the templates prioritize highly irreplaceable regions; some are reactive (prioritizing high vulnerability), and others are proactive (prioritizing low vulnerability). We hope this synthesis improves understanding of these prioritization approaches and that it results in more efficient allocation of geographically flexible conservation funding.

Path dependence and regional economic evolution

Abstract: In recent years, economic geographers have seized on the concepts of `path dependence' and `lock-in' as key ingredients in constructing an evolutionary approach to their subject. However, they have tended to invoke these notions without proper examination of the ongoing discussion and debate devoted to them within evolutionary economics and elsewhere. Our aim in this paper, therefore, is, first, to highlight some of the unresolved issues that surround these concepts, and, second, to explore their usefulness for understanding the evolution of the economic landscape and the process of regional development. We argue that in many important aspects, path dependence and `lock-in' are place-dependent processes, and as such require geographical explanation. However, the precise meaning of regional `lock-in', we contend, is unclear, and little is known about why it is that some regional economies become locked into development paths that lose dynamism, whilst other regional economies seem able to avoid this danger and in effect are able to `reinvent' themselves through successive new paths or phases of development. The issue of regional path creation is thus equally important, but has been rarely discussed. We conclude that whilst path dependence is an important feature of the economic landscape, the concept requires further elaboration if it is to function as a core notion in an evolutionary economic geography.

A Century of Alzheimer's Disease

Abstract: One hundred years ago a small group of psychiatrists described the abnormal protein deposits in the brain that define the most common neurodegenerative diseases Over the past 25 years, it has become clear that the proteins forming the deposits are central to the disease process Amyloid-β and tau make up the plaques and tangles of Alzheimer's disease, where these normally soluble proteins assemble into amyloid-like filaments Tau inclusions are also found in a number of related disorders Genetic studies have shown that dysfunction of amyloid-β or tau is sufficient to cause dementia The ongoing molecular dissection of the neurodegenerative pathways is expected to lead to a true understanding of disease pathogenesis

Risk of dementia in diabetes mellitus: a systematic review

Abstract: The relation between diabetes and major types of dementia is controversial. This systematic review examines the incidence of dementia in people with diabetes mellitus. We identified 14 eligible longitudinal population-based studies of variable methodological quality. The incidence of "any dementia" was higher in individuals with diabetes than in those without diabetes in seven of ten studies reporting this aggregate outcome. This high risk included both Alzheimer's disease and vascular dementia (eight of 13 studies and six of nine studies respectively). Detailed data on modulating and mediating effects of glycaemic control, microvascular complications, and comorbidity (eg, hypertension and stroke) were generally absent. The findings of mechanistic studies suggest that vascular disease and alterations in glucose, insulin, and amyloid metabolism underlie the pathophysiology, but which of these mechanisms are clinically relevant is unclear. Further high quality studies need to be initiated, with objective diabetes assessment, together with reliable methods to establish the contribution of vascular disease and other comorbidity to dementia.

The Addenbrooke's Cognitive Examination Revised (ACE-R): a brief cognitive test battery for dementia screening

Abstract: There is a clear need for brief, but sensitive and specific, cognitive screening instruments as evidenced by the popularity of the Addenbrooke's Cognitive Examination (ACE). Objectives We aimed to validate an improved revision (the ACE-R) which incorporates five sub-domain scores (orientation/attention, memory, verbal fluency, language and visuo-spatial). Methods Standard tests for evaluating dementia screening tests were applied. A total of 241 subjects participated in this study (Alzheimer's disease = 67, frontotemporal dementia = 55, dementia of Lewy Bodies = 20; mild cognitive impairment–MCI = 36; controls = 63). Results Reliability of the ACE-R was very good (alpha coefficient = 0.8). Correlation with the Clinical Dementia Scale was significant (r = −0.321, p < 0.001). Two cut-offs were defined (88: sensitivity = 0.94, specificity = 0.89; 82: sensitivity = 0.84, specificity = 1.0). Likelihood ratios of dementia were generated for scores between 88 and 82: at a cut-off of 82 the likelihood of dementia is 100:1. A comparison of individual age and education matched groups of MCI, AD and controls placed the MCI group performance between controls and AD and revealed MCI patients to be impaired in areas other than memory (attention/orientation, verbal fluency and language). Conclusions The ACE-R accomplishes standards of a valid dementia screening test, sensitive to early cognitive dysfunction. Copyright © 2006 John Wiley & Sons, Ltd.

Sequential Monte Carlo samplers

Abstract: Summary. We propose a methodology to sample sequentially from a sequence of probability distributions that are defined on a common space, each distribution being known up to a normalizing constant. These probability distributions are approximated by a cloud of weighted random samples which are propagated over time by using sequential Monte Carlo methods. This methodology allows us to derive simple algorithms to make parallel Markov chain Monte Carlo algorithms interact to perform global optimization and sequential Bayesian estimation and to compute ratios of normalizing constants. We illustrate these algorithms for various integration tasks arising in the context of Bayesian inference.

The roles of intracellular protein-degradation pathways in neurodegeneration

Abstract: Many late-onset neurodegenerative diseases, including Parkinson's disease and Huntington's disease, are associated with the formation of intracellular aggregates by toxic proteins. It is therefore crucial to understand the factors that regulate the steady-state levels of these 'toxins', at both the synthetic and degradation stages. The degradation pathways acting on such aggregate-prone cytosolic proteins include the ubiquitin-proteasome system and macroautophagy. Dysfunction of the ubiquitin-proteasome or macroautophagy pathways might contribute to the pathology of various neurodegenerative conditions. However, enhancing macroautophagy with drugs such as rapamycin could offer a tractable therapeutic strategy for a number of these diseases.

Evaluated kinetic and photochemical data for atmospheric chemistry: Volume IV – gas phase reactions of organic halogen species

Abstract: This article, the fourth in the series, presents kinetic and photochemical data sheets evaluated by the IUPAC Subcommittee on Gas Kinetic Data Evaluation for Atmospheric Chemistry. It covers the gas phase and photochemical reactions of organic halogen species, which were last published in 1997, and were updated on the IUPAC website in 2006/07. The article consists of a summary sheet, containing the recommended kinetic parameters for the evaluated reactions, and four appendices containing the data sheets, which provide information upon which the recommendations are made.

High dielectric constant gate oxides for metal oxide Si transistors

Abstract: The scaling of complementary metal oxide semiconductor transistors has led to the silicon dioxide layer, used as a gate dielectric, being so thin (14?nm) that its leakage current is too large It is necessary to replace the SiO2 with a physically thicker layer of oxides of higher dielectric constant (?) or 'high K' gate oxides such as hafnium oxide and hafnium silicate These oxides had not been extensively studied like SiO2, and they were found to have inferior properties compared with SiO2, such as a tendency to crystallize and a high density of electronic defects Intensive research was needed to develop these oxides as high quality electronic materials This review covers both scientific and technological issues?the choice of oxides, their deposition, their structural and metallurgical behaviour, atomic diffusion, interface structure and reactions, their electronic structure, bonding, band offsets, electronic defects, charge trapping and conduction mechanisms, mobility degradation and flat band voltage shifts The oxygen vacancy is the dominant electron trap It is turning out that the oxides must be implemented in conjunction with metal gate electrodes, the development of which is further behind Issues about work function control in metal gate electrodes are discussed

An SCN9A channelopathy causes congenital inability to experience pain

Abstract: The complete inability to sense pain in an otherwise healthy individual is a very rare phenotype. In three consanguineous families from northern Pakistan, we mapped the condition as an autosomal-recessive trait to chromosome 2q24.3. This region contains the gene SCN9A, encoding the alpha-subunit of the voltage-gated sodium channel, Na(v)1.7, which is strongly expressed in nociceptive neurons. Sequence analysis of SCN9A in affected individuals revealed three distinct homozygous nonsense mutations (S459X, I767X and W897X). We show that these mutations cause loss of function of Na(v)1.7 by co-expression of wild-type or mutant human Na(v)1.7 with sodium channel beta(1) and beta(2) subunits in HEK293 cells. In cells expressing mutant Na(v)1.7, the currents were no greater than background. Our data suggest that SCN9A is an essential and non-redundant requirement for nociception in humans. These findings should stimulate the search for novel analgesics that selectively target this sodium channel subunit.

Detecting Awareness in the Vegetative State

Abstract: We used functional magnetic resonance imaging to demonstrate preserved conscious awareness in a patient fulfilling the criteria for a diagnosis of vegetative state. When asked to imagine playing tennis or moving around her home, the patient activated predicted cortical areas in a manner indistinguishable from that of healthy volunteers.

Behavioral Theories and the Neurophysiology of Reward

Abstract: The functions of rewards are based primarily on their effects on behavior and are less directly governed by the physics and chemistry of input events as in sensory systems. Therefore, the investigation of neural mechanisms underlying reward functions requires behavioral theories that can conceptualize the different effects of rewards on behavior. The scientific investigation of behavioral processes by animal learning theory and economic utility theory has produced a theoretical framework that can help to elucidate the neural correlates for reward functions in learning, goal-directed approach behavior, and decision making under uncertainty. Individual neurons can be studied in the reward systems of the brain, including dopamine neurons, orbitofrontal cortex, and striatum. The neural activity can be related to basic theoretical terms of reward and uncertainty, such as contiguity, contingency, prediction error, magnitude, probability, expected value, and variance.

Results from the International Conference of Experts on Intra-abdominal Hypertension and Abdominal Compartment Syndrome. II. Recommendations.

Abstract: Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) have been increasingly recognized in the critically ill over the past decade. In the absence of consensus definitions and treatment guidelines the diagnosis and management of IAH and ACS remains variable from institution to institution. An international consensus group of multidisciplinary critical care specialists convened at the second World Congress on Abdominal Compartment Syndrome to develop practice guidelines for the diagnosis, management, and prevention of IAH and ACS. Prior to the conference the authors developed a blueprint for consensus definitions and treatment guidelines which were refined both during and after the conference. The present article is the second installment of the final report from the 2004 International ACS Consensus Definitions Conference and is endorsed by the World Society of the Abdominal Compartment Syndrome. The prevalence and etiological factors for IAH and ACS are reviewed. Evidence-based medicine treatment guidelines are presented to facilitate the diagnosis and management of IAH and ACS. Recommendations to guide future studies are proposed. These definitions, guidelines, and recommendations, based upon current best evidence and expert opinion are proposed to assist clinicians in the management of IAH and ACS as well as serve as a reference for future clinical and basic science research.

TextonBoost : joint appearance, shape and context modeling for multi-class object recognition and segmentation

Abstract: This paper proposes a new approach to learning a discriminative model of object classes, incorporating appearance, shape and context information efficiently. The learned model is used for automatic visual recognition and semantic segmentation of photographs. Our discriminative model exploits novel features, based on textons, which jointly model shape and texture. Unary classification and feature selection is achieved using shared boosting to give an efficient classifier which can be applied to a large number of classes. Accurate image segmentation is achieved by incorporating these classifiers in a conditional random field. Efficient training of the model on very large datasets is achieved by exploiting both random feature selection and piecewise training methods. High classification and segmentation accuracy are demonstrated on three different databases: i) our own 21-object class database of photographs of real objects viewed under general lighting conditions, poses and viewpoints, ii) the 7-class Corel subset and iii) the 7-class Sowerby database used in [1]. The proposed algorithm gives competitive results both for highly textured (e.g. grass, trees), highly structured (e.g. cars, faces, bikes, aeroplanes) and articulated objects (e.g. body, cow).

Giant Electrocaloric Effect in Thin-Film PbZr0.95Ti0.05O3

Abstract: An applied electric field can reversibly change the temperature of an electrocaloric material under adiabatic conditions, and the effect is strongest near phase transitions. We demonstrate a giant electrocaloric effect (0.48 kelvin per volt) in 350-nanometer PbZr 0.95 Ti 0.05 O 3 films near the ferroelectric Curie temperature of 222°C. A large electrocaloric effect may find application in electrical refrigeration.