Showing papers by "University of Cambridge published in 2002"
TL;DR: Both optimal and suboptimal Bayesian algorithms for nonlinear/non-Gaussian tracking problems, with a focus on particle filters are reviewed.
Abstract: Increasingly, for many application areas, it is becoming important to include elements of nonlinearity and non-Gaussianity in order to model accurately the underlying dynamics of a physical system. Moreover, it is typically crucial to process data on-line as it arrives, both from the point of view of storage costs as well as for rapid adaptation to changing signal characteristics. In this paper, we review both optimal and suboptimal Bayesian algorithms for nonlinear/non-Gaussian tracking problems, with a focus on particle filters. Particle filters are sequential Monte Carlo methods based on point mass (or "particle") representations of probability densities, which can be applied to any state-space model and which generalize the traditional Kalman filtering methods. Several variants of the particle filter such as SIR, ASIR, and RPF are introduced within a generic framework of the sequential importance sampling (SIS) algorithm. These are discussed and compared with the standard EKF through an illustrative example.
11,409 citations
TL;DR: The Cambridge Structural Database now contains data for more than a quarter of a million small-molecule crystal structures, and projections concerning future accession rates indicate that the CSD will contain at least 500,000 crystal structures by the year 2010.
Abstract: The Cambridge Structural Database (CSD) now contains data for more than a quarter of a million small-molecule crystal structures. The information content of the CSD, together with methods for data acquisition, processing and validation, are summarized, with particular emphasis on the chemical information added by CSD editors. Nearly 80% of new structural data arrives electronically, mostly in CIF format, and the CCDC acts as the official crystal structure data depository for 51 major journals. The CCDC now maintains both a CIF archive (more than 73000 CIFs dating from 1996), as well as the distributed binary CSD archive; the availability of data in both archives is discussed. A statistical survey of the CSD is also presented and projections concerning future accession rates indicate that the CSD will contain at least 500000 crystal structures by the year 2010.
9,865 citations
TL;DR: The basics of the suject are looked at, a brief review of the theory is given, examining the strengths and weaknesses of its implementation, and some of the ways simulators approach problems are illustrated through a small case study.
Abstract: First-principles simulation, meaning density-functional theory calculations with plane waves and pseudopotentials, has become a prized technique in condensed-matter theory. Here I look at the basics of the suject, give a brief review of the theory, examining the strengths and weaknesses of its implementation, and illustrating some of the ways simulators approach problems through a small case study. I also discuss why and how modern software design methods have been used in writing a completely new modular version of the CASTEP code.
9,350 citations
TL;DR: In this paper, a selfconsistent density functional method using standard norm-conserving pseudopotentials and a flexible, numerical linear combination of atomic orbitals basis set, which includes multiple-zeta and polarization orbitals, was developed and implemented.
Abstract: We have developed and implemented a selfconsistent density functional method using standard norm-conserving pseudopotentials and a flexible, numerical linear combination of atomic orbitals basis set, which includes multiple-zeta and polarization orbitals. Exchange and correlation are treated with the local spin density or generalized gradient approximations. The basis functions and the electron density are projected on a real-space grid, in order to calculate the Hartree and exchange-correlation potentials and matrix elements, with a number of operations that scales linearly with the size of the system. We use a modified energy functional, whose minimization produces orthogonal wavefunctions and the same energy and density as the Kohn-Sham energy functional, without the need for an explicit orthogonalization. Additionally, using localized Wannier-like electron wavefunctions allows the computation time and memory required to minimize the energy to also scale linearly with the size of the system. Forces and stresses are also calculated efficiently and accurately, thus allowing structural relaxation and molecular dynamics simulations.
8,723 citations
TL;DR: In this paper, the authors describe the deposition methods, deposition mechanisms, characterisation methods, electronic structure, gap states, defects, doping, luminescence, field emission, mechanical properties and some applications of diamond-like carbon.
Abstract: Diamond-like carbon (DLC) is a metastable form of amorphous carbon with significant sp3 bonding. DLC is a semiconductor with a high mechanical hardness, chemical inertness, and optical transparency. This review will describe the deposition methods, deposition mechanisms, characterisation methods, electronic structure, gap states, defects, doping, luminescence, field emission, mechanical properties and some applications of DLCs. The films have widespread applications as protective coatings in areas, such as magnetic storage disks, optical windows and micro-electromechanical devices (MEMs).
5,400 citations
TL;DR: The authors argue that qualitative researchers should reclaim responsibility for reliability and validity by implementing verification strategies integral and self-correcting during the conduct of inquiry itself, which ensures the attainment of rigor using strategies inherent within each qualitative design, and moves the responsibility for incorporating and maintaining reliability and validation from external reviewers' judgements to the investigators themselves.
Abstract: The rejection of reliability and validity in qualitative inquiry in the 1980s has resulted in an interesting shift for "ensuring rigor" from the investigator’s actions during the course of the research, to the reader or consumer of qualitative inquiry. The emphasis on strategies that are implemented during the research process has been replaced by strategies for evaluating trustworthiness and utility that are implemented once a study is completed. In this article, we argue that reliability and validity remain appropriate concepts for attaining rigor in qualitative research. We argue that qualitative researchers should reclaim responsibility for reliability and validity by implementing verification strategies integral and self-correcting during the conduct of inquiry itself. This ensures the attainment of rigor using strategies inherent within each qualitative design, and moves the responsibility for incorporating and maintaining reliability and validity from external reviewers’ judgements to the investigators themselves. Finally, we make a plea for a return to terminology for ensuring rigor that is used by mainstream science.
4,980 citations
TL;DR: A novel software package called PHENIX (Python-based Hierarchical ENvironment for Integrated Xtallography) is developed, which will provide the necessary algorithms to proceed from reduced intensity data to a refined molecular model and to facilitate structure solution for both the novice and expert crystallographer.
Abstract: Structural genomics seeks to expand rapidly the number of protein structures in order to extract the maximum amount of information from genomic sequence databases. The advent of several large-scale projects worldwide leads to many new challenges in the field of crystallographic macromolecular structure determination. A novel software package called PHENIX (Python-based Hierarchical ENvironment for Integrated Xtallography) is therefore being developed. This new software will provide the necessary algorithms to proceed from reduced intensity data to a refined molecular model and to facilitate structure solution for both the novice and expert crystallographer.
4,201 citations
Book•
01 Jan 2002TL;DR: This presentation discusses Functional Programming in HOL, which aims to provide students with an understanding of the programming language through the lens of Haskell.
Abstract: Elementary Techniques.- 1. The Basics.- 2. Functional Programming in HOL.- 3. More Functional Programming.- 4. Presenting Theories.- Logic and Sets.- 5. The Rules of the Game.- 6. Sets, Functions, and Relations.- 7. Inductively Defined Sets.- Advanced Material.- 8. More about Types.- 9. Advanced Simplification, Recursion, and Induction.- 10. Case Study: Verifying a Security Protocol.
2,964 citations
TL;DR: Two new programs have been developed for searching the Cambridge Structural Database (CSD) and visualizing database entries: ConQuest and Mercury, a high-performance crystal-structure visualizer with extensive facilities for exploring networks of intermolecular contacts.
Abstract: Two new programs have been developed for searching the Cambridge Structural Database (CSD) and visualizing database entries: ConQuest and Mercury The former is a new search interface to the CSD, the latter is a high-performance crystal-structure visualizer with extensive facilities for exploring networks of intermolecular contacts Particular emphasis has been placed on making the programs as intuitive as possible Both ConQuest and Mercury run under Windows and various types of Unix, including Linux
2,689 citations
TL;DR: The evidence presented in this paper suggests that the apparent leveling off of life expectancy in various countries is an artifact of laggards catching up and leaders falling behind, not a sign that life expectancy is approaching its limit.
Abstract: Is human life expectancy approaching its limit? Many--including individuals planning their retirement and officials responsible for health and social policy--believe it is, but the evidence presented in the
Policy Forum
suggests otherwise. For 160 years, best-performance life expectancy has steadily increased by a quarter of a year per year, an extraordinary constancy of human achievement. Mortality experts have repeatedly asserted that life expectancy is close to an ultimate ceiling; these experts have repeatedly been proven wrong. The apparent leveling off of life expectancy in various countries is an artifact of laggards catching up and leaders falling behind.
2,462 citations
TL;DR: This finding provides added evidence that avoidance of protein aggregation is crucial for the preservation of biological function and suggests common features in the origins of this family of protein deposition diseases.
Abstract: A range of human degenerative conditions, including Alzheimer's disease, light-chain amyloidosis and the spongiform encephalopathies, is associated with the deposition in tissue of proteinaceous aggregates known as amyloid fibrils or plaques. It has been shown previously that fibrillar aggregates that are closely similar to those associated with clinical amyloidoses can be formed in vitro from proteins not connected with these diseases, including the SH3 domain from bovine phosphatidyl-inositol-3'-kinase and the amino-terminal domain of the Escherichia coli HypF protein. Here we show that species formed early in the aggregation of these non-disease-associated proteins can be inherently highly cytotoxic. This finding provides added evidence that avoidance of protein aggregation is crucial for the preservation of biological function and suggests common features in the origins of this family of protein deposition diseases.
10 Dec 2002
TL;DR: Algorithms developed by the author for recognizing persons by their iris patterns have now been tested in many field and laboratory trials, producing no false matches in several million comparison tests.
Abstract: The principle that underlies the recognition of persons by their iris patterns is the failure of a test of statistical independence on texture phase structure as encoded by multiscale quadrature wavelets. The combinatorial complexity of this phase information across different persons spans about 249 degrees of freedom and generates a discrimination entropy of about 3.2 bits/mm/sup 2/ over the iris, enabling real-time decisions about personal identity with extremely high confidence. Algorithms first described by the author in 1993 have now been tested in several independent field trials and are becoming widely licensed. This presentation reviews how the algorithms work and presents the results of 9.1 million comparisons among different eye images acquired in trials in Britain, the USA, Korea, and Japan.
TL;DR: A monolithic terahertz injection laser that is based on interminiband transitions in the conduction band of a semiconductor (GaAs/AlGaAs) heterostructure is reported, which is very promising for extending the present laser concept to continuous-wave and high-temperature operation, which would lead to implementation in practical photonic systems.
Abstract: Semiconductor devices have become indispensable for generating electromagnetic radiation in everyday applications. Visible and infrared diode lasers are at the core of information technology, and at the other end of the spectrum, microwave and radio-frequency emitters enable wireless communications. But the terahertz region (1-10 THz; 1 THz = 10(12) Hz) between these ranges has remained largely underdeveloped, despite the identification of various possible applications--for example, chemical detection, astronomy and medical imaging. Progress in this area has been hampered by the lack of compact, low-consumption, solid-state terahertz sources. Here we report a monolithic terahertz injection laser that is based on interminiband transitions in the conduction band of a semiconductor (GaAs/AlGaAs) heterostructure. The prototype demonstrated emits a single mode at 4.4 THz, and already shows high output powers of more than 2 mW with low threshold current densities of about a few hundred A cm(-2) up to 50 K. These results are very promising for extending the present laser concept to continuous-wave and high-temperature operation, which would lead to implementation in practical photonic systems.
TL;DR: In this article, the authors take the regulation of identity as a focus for examining organizational control and consider how employees are enjoined to develop self-images and work orientations that are deemed congruent with managerially defined objectives.
Abstract: This paper takes the regulation of identity as a focus for examining organizational control. It considers how employees are enjoined to develop self-images and work orientations that are deemed congruent with managerially defined objectives. This focus on identity extends and deepens themes developed within other analyses of normative control. Empirical materials are deployed to illustrate how managerial intervention operates, more or less intentionally and in/effectively, to influence employees' self-constructions in terms of coherence, distinctiveness and commitment. The processual nature of such control is emphasized, arguing that it exists in tension with other intra. and extra-organizational claims upon employees' sense of identity in a way that can open a space for forms of micro-emancipation. (Less)
TL;DR: It is demonstrated that CSPGs are important inhibitory molecules in vivo and suggested that their manipulation will be useful for treatment of human spinal injuries.
Abstract: The inability of axons to regenerate after a spinal cord injury in the adult mammalian central nervous system (CNS) can lead to permanent paralysis. At sites of CNS injury, a glial scar develops, containing extracellular matrix molecules including chondroitin sulphate proteoglycans (CSPGs). CSPGs are inhibitory to axon growth in vitro, and regenerating axons stop at CSPG-rich regions in vivo. Removing CSPG glycosaminoglycan (GAG) chains attenuates CSPG inhibitory activity. To test the functional effects of degrading chondroitin sulphate (CS)-GAG after spinal cord injury, we delivered chondroitinase ABC (ChABC) to the lesioned dorsal columns of adult rats. We show that intrathecal treatment with ChABC degraded CS-GAG at the injury site, upregulated a regeneration-associated protein in injured neurons, and promoted regeneration of both ascending sensory projections and descending corticospinal tract axons. ChABC treatment also restored post-synaptic activity below the lesion after electrical stimulation of corticospinal neurons, and promoted functional recovery of locomotor and proprioceptive behaviours. Our results demonstrate that CSPGs are important inhibitory molecules in vivo and suggest that their manipulation will be useful for treatment of human spinal injuries.
TL;DR: In this paper, the authors proposed a method for matching the next-to-leading order (NLO) calculation of a given QCD process with a parton shower Monte Carlo (MC) simulation.
Abstract: We propose a method for matching the next-to-leading order (NLO) calculation of a given QCD process with a parton shower Monte Carlo (MC) simulation. The method has the following features: fully exclusive events are generated, with hadronization according to the MC model; total exclusive rates are accurate to NLO; NLO results for distributions are recovered upon expansion in ?s; hard emissions are treated as in NLO computations while soft/collinear emissions are handled by the MC simulation, with the same logarithmic accuracy as the MC; and matching between the hard- and soft/collinear-emission regions is smooth. A fraction of events with negative weight is generated, but unweighting remains possible with reasonable efficiency. The method is clarified using a simple toy model, and illustrated by application to the hadroproduction of W+W? pairs.
TL;DR: The basolateral amygdala (BLA) appears to be required for a Pavlovian conditioned stimulus to gain access to the current value of the specific unconditioned stimulus (US) that it predicts, while the central nucleus of the amygdala acts as a controller of brainstem arousal and response systems, and subserves some forms of stimulus-response Pavlovia conditioning.
TL;DR: Although there was substantial heterogeneity among studies (especially for antisocial personality disorder), only a small proportion was explained by differences in prevalence rates between detainees and sentenced inmates.
TL;DR: Some recent examples where dynamic covalent chemistry has been demonstrated are shown to emphasise the basic concepts of this area of science.
Abstract: Dynamic covalent chemistry relates to chemical reactions carried out reversibly under conditions of equilibrium control. The reversible nature of the reactions introduces the prospects of "error checking" and "proof-reading" into synthetic processes where dynamic covalent chemistry operates. Since the formation of products occurs under thermodynamic control, product distributions depend only on the relative stabilities of the final products. In kinetically controlled reactions, however, it is the free energy differences between the transition states leading to the products that determines their relative proportions. Supramolecular chemistry has had a huge impact on synthesis at two levels: one is noncovalent synthesis, or strict self-assembly, and the other is supramolecular assistance to molecular synthesis, also referred to as self-assembly followed by covalent modification. Noncovalent synthesis has given us access to finite supermolecules and infinite supramolecular arrays. Supramolecular assistance to covalent synthesis has been exploited in the construction of more-complex systems, such as interlocked molecular compounds (for example, catenanes and rotaxanes) as well as container molecules (molecular capsules). The appealing prospect of also synthesizing these types of compounds with complex molecular architectures using reversible covalent bond forming chemistry has led to the development of dynamic covalent chemistry. Historically, dynamic covalent chemistry has played a central role in the development of conformational analysis by opening up the possibility to be able to equilibrate configurational isomers, sometimes with base (for example, esters) and sometimes with acid (for example, acetals). These stereochemical "balancing acts" revealed another major advantage that dynamic covalent chemistry offers the chemist, which is not so easily accessible in the kinetically controlled regime: the ability to re-adjust the product distribution of a reaction, even once the initial products have been formed, by changing the reaction's environment (for example, concentration, temperature, presence or absence of a template). This highly transparent, yet tremendously subtle, characteristic of dynamic covalent chemistry has led to key discoveries in polymer chemistry. In this review, some recent examples where dynamic covalent chemistry has been demonstrated are shown to emphasise the basic concepts of this area of science.
TL;DR: It is suggested that two neglected dimensions for understanding human sex differences are 'empathising' and 'systemising', which can be considered as an extreme of the normal male profile of autism.
TL;DR: In this paper, a rapid binary-evolution algorithm was proposed to model the formation and evolution of binary systems, including all aspects of single-star evolution, features such as mass transfer, mass accretion, common envelope evolution, collisions, supernova kicks and angular momentum loss mechanisms.
Abstract: We present a rapid binary-evolution algorithm that enables modelling of even the most complex binary systems. In addition to all aspects of single-star evolution, features such as mass transfer, mass accretion, common-envelope evolution, collisions, supernova kicks and angular momentum loss mechanisms are included. In particular, circularization and synchronization of the orbit by tidal interactions are calculated for convective, radiative and degenerate damping mechanisms. We use this algorithm to study the formation and evolution of various binary systems. We also investigate the effect that tidal friction has on the outcome of binary evolution. Using the rapid binary code, we generate a series of large binary populations and evaluate the formation rate of interesting individual species and events. By comparing the results for populations with and without tidal friction, we quantify the hitherto ignored systematic effect of tides and show that modelling of tidal evolution in binary systems is necessary in order to draw accurate conclusions from population synthesis work. Tidal synchronism is important but, because orbits generally circularize before Roche lobe overflow, the outcome of the interactions of systems with the same semilatus rectum is almost independent of eccentricity. It is not necessary to include a distribution of eccentricities in population synthesis of interacting binaries; however, the initial separations should be distributed according to the observed distribution of semilatera recta rather than periods or semimajor axes.
International Agency for Research on Cancer1, University of Texas Health Science Center at San Antonio2, Aarhus University3, Institut Gustave Roussy4, Harvard University5, National and Kapodistrian University of Athens6, University of Turin7, Utrecht University8, University of Tromsø9, Lund University10, Umeå University11, University of Cambridge12, University of Oxford13
TL;DR: The present paper provides a description of theEPIC study, with the aim of simplifying reference to it in future papers reporting substantive or methodological studies carried out in the EPIC cohort.
Abstract: The European Prospective Investigation into Cancer and Nutrition (EPIC) is an ongoing multi-centre prospective cohort study designed to investigate the relationship between nutrition and cancer, with the potential for studying other diseases as well. The study currently includes 519 978 participants (366 521 women and 153 457 men, mostly aged 35-70 years) in 23 centres located in 10 European countries, to be followed for cancer incidence and cause-specific mortality for several decades. At enrollment, which took place between 1992 and 2000 at each of the different centres, information was collected through a non-dietary questionnaire on lifestyle variables and through a dietary questionnaire addressing usual diet. Anthropometric measurements were performed and blood samples taken, from which plasma, serum, red cells and buffy coat fractions were separated and aliquoted for long-term storage, mostly in liquid nitrogen. To calibrate dietary measurements, a standardised, computer-assisted 24-hour dietary recall was implemented at each centre on stratified random samples of the participants, for a total of 36 900 subjects. EPIC represents the largest single resource available today world-wide for prospective investigations on the aetiology of cancers (and other diseases) that can integrate questionnaire data on lifestyle and diet, biomarkers of diet and of endogenous metabolism (e.g. hormones and growth factors) and genetic polymorphisms. First results of case-control studies nested within the cohort are expected early in 2003. The present paper provides a description of the EPIC study, with the aim of simplifying reference to it in future papers reporting substantive or methodological studies carried out in the EPIC cohort.
TL;DR: What is known about the biological functions of the BRCA proteins is examined and how their disruption can induce susceptibility to specific types of cancer is asked.
TL;DR: The mature ECM is thus inhibitory for experience-dependent plasticity, and degradation of CSPGs reactivates cortical plasticity.
Abstract: In young animals, monocular deprivation leads to an ocular dominance shift, whereas in adults after the critical period there is no such shift. Chondroitin sulphate proteoglycans (CSPGs) are components of the extracellular matrix (ECM) inhibitory for axonal sprouting. We tested whether the developmental maturation of the ECM is inhibitory for experience-dependent plasticity in the visual cortex. The organization of CSPGs into perineuronal nets coincided with the end of the critical period and was delayed by dark rearing. After CSPG degradation with chondroitinase-ABC in adult rats, monocular deprivation caused an ocular dominance shift toward the nondeprived eye. The mature ECM is thus inhibitory for experience-dependent plasticity, and degradation of CSPGs reactivates cortical plasticity.
TL;DR: It is concluded that at most one massive metal-free star forms per pregalactic halo, consistent with recent abundance measurements of metal-poor galactic halo stars.
Abstract: We describe results from a fully self-consistent three-dimensional hydrodynamical simulation of the formation of one of the first stars in the Universe. In current models of structure formation, dark matter initially dominates, and pregalactic objects form because of gravitational instability from small initial density perturbations. As they assemble via hierarchical merging, primordial gas cools through ro-vibrational lines of hydrogen molecules and sinks to the center of the dark matter potential well. The high-redshift analog of a molecular cloud is formed. As the dense, central parts of the cold gas cloud become self-gravitating, a dense core of approximately 100 M (where M is the mass of the Sun) undergoes rapid contraction. At particle number densities greater than 10(9) per cubic centimeter, a 1 M protostellar core becomes fully molecular as a result of three-body H2 formation. Contrary to analytical expectations, this process does not lead to renewed fragmentation and only one star is formed. The calculation is stopped when optical depth effects become important, leaving the final mass of the fully formed star somewhat uncertain. At this stage the protostar is accreting material very rapidly (approximately 10(-2) M year-1). Radiative feedback from the star will not only halt its growth but also inhibit the formation of other stars in the same pregalactic object (at least until the first star ends its life, presumably as a supernova). We conclude that at most one massive (M 1 M) metal-free star forms per pregalactic halo, consistent with recent abundance measurements of metal-poor galactic halo stars.
University of Cambridge1, Conservation International2, University of East Anglia3, University of Maryland Center for Environmental Science4, University of Pittsburgh5, Royal Society for the Protection of Birds6, World Conservation Monitoring Centre7, University of British Columbia8, University of Washington9, Stanford University10
TL;DR: It is estimated that the overall benefit:cost ratio of an effective global program for the conservation of remaining wild nature is at least 100:1.
Abstract: On the eve of the World Summit on Sustainable Development, it is timely to assess progress over the 10 years since its predecessor in Rio de Janeiro. Loss and degradation of remaining natural habitats has continued largely unabated. However, evidence has been accumulating that such systems generate marked economic benefits, which the available data suggest exceed those obtained from continued habitat conversion. We estimate that the overall benefit:cost ratio of an effective global program for the conservation of remaining wild nature is at least 100:1.
TL;DR: The wide range of phenotypic abnormalities seen in the leptin-deficient ob/ob mouse and their reversibility by leptin administration provide compelling evidence for the existence of multiple physiological functions of this hormone in rodents.
Abstract: The wide range of phenotypic abnormalities seen in the leptin-deficient ob/ob mouse and their reversibility by leptin administration provide compelling evidence for the existence of multiple physiological functions of this hormone in rodents. In contrast, information regarding the roles of this hormone in humans is limited. Three morbidly obese children, who were congenitally deficient in leptin, were treated with daily subcutaneous injections of recombinant human leptin for up to 4 years with sustained, beneficial effects on appetite, fat mass, hyperinsulinemia, and hyperlipidemia. Leptin therapy resulted in a rapid and sustained increase in plasma thyroid hormone levels and, through its age-dependent effects on gonadotropin secretion, facilitated appropriately timed pubertal development. Leptin deficiency was associated with reduced numbers of circulating CD4+ T cells and impaired T cell proliferation and cytokine release, all of which were reversed by recombinant human leptin administration. The subcutaneous administration of recombinant human leptin has major and sustained beneficial effects on the multiple phenotypic abnormalities associated with congenital human leptin deficiency.
TL;DR: Almost one fourth of patients with apparently sporadic pheochromocytoma may be carriers of mutations; routine analysis for mutations of RET, VHL, SDHD, and SDHB is indicated to identify pheosene-associated syndromes that would otherwise be missed.
Abstract: Background The group of susceptibility genes for pheochromocytoma that included the proto-oncogene RET (associated with multiple endocrine neoplasia type 2 [MEN-2]) and the tumor-suppressor gene VHL (associated with von Hippel–Lindau disease) now also encompasses the newly identified genes for succinate dehydrogenase subunit D (SDHD) and succinate dehydrogenase subunit B (SDHB), which predispose carriers to pheochromocytomas and glomus tumors. We used molecular tools to classify a large cohort of patients with pheochromocytoma with respect to the presence or absence of mutations of one of these four genes and to investigate the relevance of genetic analyses to clinical practice. Methods Peripheral blood from unrelated, consenting registry patients with pheochromocytoma was tested for mutations of RET, VHL, SDHD, and SDHB. Clinical data at first presentation and follow-up were evaluated. Results Among 271 patients who presented with nonsyndromic pheochromocytoma and without a family history of the disease,...
TL;DR: The monoaminergic and cholinergic systems appear to play separable roles in different aspects of performance controlled by the 5CSRTT, in neural systems centred on the prefrontal cortex, cingulate cortex and striatum.
Abstract:
Rationale. The developmental history and application of the 5-choice serial reaction time task (5CSRTT) for measuring effects of drugs and other manipulations on attentional performance (and stimulus control) in rats is reviewed.
Objectives. The 5CSRTT has been used for measuring effects of systemic drug treatments and also central manipulations such as neurochemical lesions on various aspects of attentional control, including sustained, selective and divided attention – and is relevant to the definition of neural systems of attention and applications to human disorders such as attention deficit/hyperactivity disorder (ADHD) and Alzheimer's disease.
Methods. The 5CSRTT is implemented in a specially designed operant chamber with multiple response locations ('nine-hole box') using food reinforcers to maintain performance on baseline sessions (about 100 trials) at criterion levels of accuracy and trials completed. The 5CSRTT can be used for measuring various aspects of attentional control over performance with its main measures of accuracy, premature responding, correct response latencies and latency to collect earned food pellets.
Results. The data reviewed include studies mainly of systemic and intra-cerebral effects of adrenoceptor, dopamine receptor, serotoninergic receptor and cholinergic receptor agents. These are compared with investigations of effects of selective chemical neurotoxins and excitotoxins applied to discrete parts of the forebrain, in order to define the neural and neurochemical substrates of attentional function. Furthermore, these results are integrated with findings from in vivo microdialysis in freely moving rats or metabolic studies.
Conclusions. The monoaminergic and cholinergic systems appear to play separable roles in different aspects of performance controlled by the 5CSRTT, in neural systems centred on the prefrontal cortex, cingulate cortex and striatum. These conclusions are considered in the methodological and theoretical context of other psychopharmacological studies of attention in animals and humans.
TL;DR: It is demonstrated that atherosclerotic plaque inflammation can be imaged with 18 FDG-PET, and that symptomatic, unstable plaques accumulate more 18FDG than asymptomatic lesions.
Abstract: Background— Atherosclerotic plaque rupture is usually a consequence of inflammatory cell activity within the plaque. Current imaging techniques provide anatomic data but no indication of plaque inflammation. The glucose analogue [18F]-fluorodeoxyglucose (18FDG) can be used to image inflammatory cell activity non-invasively by PET. In this study we tested whether 18FDG-PET imaging can identify inflammation within carotid artery atherosclerotic plaques. Methods and Results— Eight patients with symptomatic carotid atherosclerosis were imaged using 18FDG-PET and co-registered CT. Symptomatic carotid plaques were visible in 18FDG-PET images acquired 3 hours post-18FDG injection. The estimated net 18FDG accumulation rate (plaque/integral plasma) in symptomatic lesions was 27% higher than in contralateral asymptomatic lesions. There was no measurable 18FDG uptake into normal carotid arteries. Autoradiography of excised plaques confirmed accumulation of deoxyglucose in macrophage-rich areas of the plaque. Conclus...