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Showing papers by "Trinity College, Dublin published in 2007"


Journal ArticleDOI
TL;DR: The interpolated Markov model (IMM) DNA discriminator correctly separated 99% of the sequences in a recent genome project that produced a mixture of sequences from the bacterium Prochloron didemni and its sea squirt host, Lissoclinum patella.
Abstract: Motivation: The Glimmer gene-finding software has been successfully used for finding genes in bacteria, archaea and viruses representing hundreds of species. We describe several major changes to the Glimmer system, including improved methods for identifying both coding regions and start codons. We also describe a new module of Glimmer that can distinguish host and endosymbiont DNA. This module was developed in response to the discovery that eukaryotic genome sequencing projects sometimes inadvertently capture the DNA of intracellular bacteria living in the host. Results: The new methods dramatically reduce the rate of false-positive predictions, while maintaining Glimmer's 99% sensitivity rate at detecting genes in most species, and they find substantially more correct start sites, as measured by comparisons to known and well-curated genes. We show that our interpolated Markov model (IMM) DNA discriminator correctly separated 99% of the sequences in a recent genome project that produced a mixture of sequences from the bacterium Prochloron didemni and its sea squirt host, Lissoclinum patella. Availability: Glimmer is OSI Certified Open Source and available at http://cbcb.umd.edu/software/glimmer Contact: adelcher@umiacs.umd.edu

2,738 citations


Journal ArticleDOI
TL;DR: The function of the fifth adaptor, SARM, has been revealed, which negatively regulates TRIF, and it is shown that it acts as a bridging adaptor in the initiation of TLR signalling.
Abstract: Signalling by Toll-like receptors (TLRs) involves five adaptor proteins known as MyD88, MAL, TRIF, TRAM and SARM. Recent insights have revealed additional functions for MyD88 apart from NF-kappaB activation, including activation of the transcription factors IRF1, IRF5 and IRF7, and also a role outside the TLRs in interferon-gamma signalling. Biochemical information on MAL and TRAM has shown that both act as bridging adaptors, with MAL recruiting MyD88 to TLR2 and TLR4, and TRAM recruiting TRIF to TLR4 to allow for IRF3 activation. Finally, the function of the fifth adaptor, SARM, has been revealed, which negatively regulates TRIF. These new insights allow for a detailed description of the function of the five TIR-domain-containing adaptors in the initiation of TLR signalling.

2,474 citations


Journal ArticleDOI
TL;DR: In this paper, the authors construct estimates of external assets and liabilities for 145 countries for 1970-2004, focusing on trends in net and gross external positions, and the composition of international portfolios.

2,030 citations


Journal ArticleDOI
TL;DR: An International Consensus Conference was held in April 2005 to provide recommendations regarding the management of this process and an 11-member international jury answered five pre-defined questions.
Abstract: Weaning covers the entire process of liberating the patient from mechanical support and from the endotracheal tube. Many controversial questions remain concerning the best methods for conducting this process. An International Consensus Conference was held in April 2005 to provide recommendations regarding the management of this process. An 11-member international jury answered five pre-defined questions. 1) What is known about the epidemiology of weaning problems? 2) What is the pathophysiology of weaning failure? 3) What is the usual process of initial weaning from the ventilator? 4) Is there a role for different ventilator modes in more difficult weaning? 5) How should patients with prolonged weaning failure be managed? The main recommendations were as follows. 1) Patients should be categorised into three groups based on the difficulty and duration of the weaning process. 2) Weaning should be considered as early as possible. 3) A spontaneous breathing trial is the major diagnostic test to determine whether patients can be successfully extubated. 4) The initial trial should last 30 min and consist of either T-tube breathing or low levels of pressure support. 5) Pressure support or assist-control ventilation modes should be favoured in patients failing an initial trial/trials. 6) Noninvasive ventilation techniques should be considered in selected patients to shorten the duration of intubation but should not be routinely used as a tool for extubation failure.

1,265 citations


Proceedings ArticleDOI
09 Sep 2007
TL;DR: SimBet Routing is proposed which exploits the exchange of pre-estimated "betweenness' centrality metrics and locally determined social "similarity' to the destination node and outperforms PRoPHET Routing, particularly when the sending and receiving nodes have low connectivity.
Abstract: Message delivery in sparse Mobile Ad hoc Networks (MANETs) is difficult due to the fact that the network graph is rarely (if ever) connected. A key challenge is to find a route that can provide good delivery performance and low end-to-end delay in a disconnected network graph where nodes may move freely. This paper presents a multidisciplinary solution based on the consideration of the so-called small world dynamics which have been proposed for economy and social studies and have recently revealed to be a successful approach to be exploited for characterising information propagation in wireless networks. To this purpose, some bridge nodes are identified based on their centrality characteristics, i.e., on their capability to broker information exchange among otherwise disconnected nodes. Due to the complexity of the centrality metrics in populated networks the concept of ego networks is exploited where nodes are not required to exchange information about the entire network topology, but only locally available information is considered. Then SimBet Routing is proposed which exploits the exchange of pre-estimated "betweenness' centrality metrics and locally determined social "similarity' to the destination node. We present simulations using real trace data to demonstrate that SimBet Routing results in delivery performance close to Epidemic Routing but with significantly reduced overhead. Additionally, we show that SimBet Routing outperforms PRoPHET Routing, particularly when the sending and receiving nodes have low connectivity.

1,232 citations


Journal ArticleDOI
TL;DR: In this article, a new set of independent and dependent variables is introduced to transform the Camassa-Holm equation into a semilinear system, whose solutions are obtained as fixed points of a contractive transformation.
Abstract: This paper develops a new approach in the analysis of the Camassa–Holm equation. By introducing a new set of independent and dependent variables, the equation is transformed into a semilinear system, whose solutions are obtained as fixed points of a contractive transformation. These new variables resolve all singularities due to possible wave breaking. Returning to the original variables, we obtain a semigroup of global solutions, depending continuously on the initial data. Our solutions are conservative, in the sense that the total energy equals a constant, for almost every time.

795 citations


Journal ArticleDOI
TL;DR: In this paper, the authors explore the dynamics of insider research under the headings of access, preunderstanding, role duality, and managing organizational politics, and conclude that insider research can be undertaken within any of the three major research paradigms (positivism, hermeneutics, and action research).
Abstract: Within organizational research, the subject of insider academic research has received relatively little consideration. By insider research, we mean research by complete members of organizational systems in and on their own organizations. Insider research can be undertaken within any of the three major research paradigms—positivism, hermeneutics, and action research—selected and presented in this article. First, we revisit some of the established research paradigms to see what position they might have on insider research. Second, we explore the dynamics of insider research under the headings of access, preunderstanding, role duality, and managing organizational politics. Our conclusion is that within each of the main streams of research, there is no inherent reason why being native is an issue and that the value of insider research is worth reaffirming.

776 citations


Journal ArticleDOI
TL;DR: In this article, the structural chemistry and optical properties of recently synthesized porphyrin derivatives are reviewed for nonlinear optical applications and complement existing studies on phthalocyanines.
Abstract: Porphyrins and phthalocyanines have outstanding chemical and thermal stability. The macrocyclic structure and chemical reactivity of tetrapyrroles offers architectural flexibility and facilitates the tailoring of chemical, physical and optoelectronic parameters. The specific optical properties of the tetrapyrrole macrocycle combined with the synthetic methodologies now available and the already available theoretical and spectroscopic knowledge on their optical behavior make porphyrins a target of choice for this area. They are versatile organic nanomaterials with a rich photochemistry and their excited state properties are easily modulated through conformational design, molecular symmetry, metal complexation, orientation and strength of the molecular dipole moment, size and degree of conjugation of the π-systems, and appropriate donor-acceptor substituents. Here we review the structural chemistry and optical properties of recently synthesized porphyrin derivatives that offer potential for nonlinear optical (NLO) applications and complement existing studies on phthalocyanines. Classes of interest include the classic A4 symmetric tetrapyrroles, while optimized systems include push-pull porphyrins, oligomeric and supramolecular self-assembled systems, films and nanoparticle systems, and highly conjugated porphyrin arrays.

715 citations


Journal ArticleDOI
TL;DR: This paper tested 310,605 SNPs for association in 778 individuals with celiac disease and 1,422 controls, and the most significant finding (rs13119723; P = 2.0 x 10(-7)) was in the KIAA1109-TENR-IL2-IL21 linkage disequilibrium block.
Abstract: We tested 310,605 SNPs for association in 778 individuals with celiac disease and 1,422 controls. Outside the HLA region, the most significant finding (rs13119723; P = 2.0 x 10(-7)) was in the KIAA1109-TENR-IL2-IL21 linkage disequilibrium block. We independently confirmed association in two further collections (strongest association at rs6822844, 24 kb 5' of IL21; meta-analysis P = 1.3 x 10(-14), odds ratio = 0.63), suggesting that genetic variation in this region predisposes to celiac disease.

668 citations


Journal ArticleDOI
TL;DR: There is a pressing need for careful consideration of benefits and side effects of the use of nanoparticles in medicine, and a balanced update of these exciting pharmacological and potentially toxicological developments is provided.
Abstract: Nanoparticles are tiny materials (<1000 nm in size) that have specific physicochemical properties different to bulk materials of the same composition and such properties make them very attractive for commercial and medical development. However, nanoparticles can act on living cells at the nanolevel resulting not only in biologically desirable, but also in undesirable effects. In contrast to many efforts aimed at exploiting desirable properties of nanoparticles for medicine, there are limited attempts to evaluate potentially undesirable effects of these particles when administered intentionally for medical purposes. Therefore, there is a pressing need for careful consideration of benefits and side effects of the use of nanoparticles in medicine. This review article aims at providing a balanced update of these exciting pharmacological and potentially toxicological developments. The classes of nanoparticles, the current status of nanoparticle use in pharmacology and therapeutics, the demonstrated and potential toxicity of nanoparticles will be discussed.

643 citations


Journal ArticleDOI
TL;DR: It is shown that the common filaggrin (FLG) null mutations that cause ichthyosis vulgaris and predispose to eczema and secondary allergic diseases are ancestral variants carried on conserved haplotypes, and a strategy for full sequencing of this large, highly repetitive gene is reported.
Abstract: We recently reported two common filaggrin (FLG) null mutations that cause ichthyosis vulgaris and predispose to eczema and secondary allergic diseases. We show here that these common European mutations are ancestral variants carried on conserved haplotypes. To facilitate comprehensive analysis of other populations, we report a strategy for full sequencing of this large, highly repetitive gene, and we describe 15 variants, including seven that are prevalent. All the variants are either nonsense or frameshift mutations that, in representative cases, resulted in loss of filaggrin production in the epidermis. In an Irish case-control study, the five most common European mutations showed a strong association with moderate-to-severe childhood eczema (chi2 test: P = 2.12 x 10(-51); Fisher's exact test: heterozygote odds ratio (OR) = 7.44 (95% confidence interval (c.i.) = 4.9-11.3), and homozygote OR = 151 (95% c.i. = 20-1,136)). We found three additional rare null mutations in this case series, suggesting that the genetic architecture of filaggrin-related atopic dermatitis consists of both prevalent and rare risk alleles.

Journal ArticleDOI
TL;DR: Findings indicate that gene expression in cytologically normal large-airway epithelial cells can serve as a lung cancer biomarker, potentially owing to a cancer-specific airway-wide response to cigarette smoke.
Abstract: Lung cancer is the leading cause of death from cancer in the US and the world 1 . The high mortality rate (80–85% within 5 years) results, in part, from a lack of effective tools to diagnose the disease at an early stage 2–4 . Given that cigarette smoke creates a field of injury throughout the airway 5–11 , we sought to determine if gene expression in histologically normal large-airway epithelial cells obtained at bronchoscopy from smokers with suspicion of lung cancer could be used as a lung cancer biomarker. Using a training set (n ¼ 77) and gene-expression profiles from Affymetrix HG-U133A microarrays, we identified an 80-gene biomarker that distinguishes smokers with and without lung cancer. We tested the biomarker on an independent test set (n ¼ 52), with an accuracy of 83% (80% sensitive, 84% specific), and on an additional validation set independently obtained from five medical centers (n ¼ 35). Our biomarker had B90% sensitivity for stage 1 cancer across all subjects. Combining cytopathology of lower airway cells obtained at bronchoscopy with the biomarker yielded 95% sensitivity and a 95% negative predictive value. These findings indicate that gene expression in cytologically normal large-airway epithelial cells can serve as a lung cancer biomarker, potentially owing to a cancer-specific airway-wide response to cigarette smoke.


Journal ArticleDOI
TL;DR: This paper argues for an understanding of language Learner autonomy in which the development of learner autonomy and the growth of target language proficiency are mutually supporting and fully integrated with each other.
Abstract: The concept of learner autonomy is often applied to the process and content of language learning but not specifically to its intended outcome, the development of proficiency in a second or foreign language. Against this tendency, the present paper argues for an understanding of language learner autonomy in which the development of learner autonomy and the growth of target language proficiency are mutually supporting and fully integrated with each other. It further argues that only on the basis of such an understanding can learner autonomy move to the centre of language teaching theory and practice. The paper begins by considering the origins of the universally accepted definition of learner autonomy, ‘the ability to take charge of one's own learning’. It then briefly reviews social-psychological and cognitive evidence in favour of promoting learner autonomy before discussing constructivist theories of pedagogy and their implications for a theory of language learner autonomy. From this it derives three fun...

Journal ArticleDOI
TL;DR: In this article, it was shown that in a solitary water wave each particle is transported in the wave direction but slower than the wave speed, while all particles located ahead of the wave crest are lifted, while those behind it experience a downward motion, with the particle trajectory having asymptotic height above the flat bed.
Abstract: Analyzing a free boundary problem for harmonic functions in an infinite planar domain, we prove that in a solitary water wave each particle is transported in the wave direction but slower than the wave speed. As the solitary wave propagates, all particles located ahead of the wave crest are lifted, while those behind it experience a downward motion, with the particle trajectory having asymptotically the same height above the flat bed.

Journal ArticleDOI
TL;DR: In this paper, a case-control study of 6,106 individuals from the UK, Vietnam and several African countries with invasive pneumococcal disease, bacteremia, malaria and tuberculosis was conducted.
Abstract: Toll-like receptors (TLRs) and members of their signaling pathway are important in the initiation of the innate immune response to a wide variety of pathogens. The adaptor protein Mal (also known as TIRAP), encoded by TIRAP (MIM 606252), mediates downstream signaling of TLR2 and TLR4 (refs. 4-6). We report a case-control study of 6,106 individuals from the UK, Vietnam and several African countries with invasive pneumococcal disease, bacteremia, malaria and tuberculosis. We genotyped 33 SNPs, including rs8177374, which encodes a leucine substitution at Ser180 of Mal. We found that heterozygous carriage of this variant associated independently with all four infectious diseases in the different study populations. Combining the study groups, we found substantial support for a protective effect of S180L heterozygosity against these infectious diseases (N = 6,106; overall P = 9.6 x 10(-8)). We found that the Mal S180L variant attenuated TLR2 signal transduction.

Book
01 Jan 2007
TL;DR: The Theory of Critical Distance Theories of Fracture (TCD) is a group of theories used for predicting the effects of notches and other stress-concentration features as mentioned in this paper.
Abstract: This paper summarises the keynote talk opening the session on ‘Critical Distance Theories of Fracture’; my aim is to describe the methodology used, to demonstrate its applicability in predicting experimental data on fracture and fatigue, to discuss the fundamental basis of the theory and, to suggest areas for future work in this field. The Theory of Critical Distances (TCD) is the name which I have given to a group of theories used for predicting the effects of notches and other stress-concentration features. These theories have a long history, but currently they are being investigated by only a small number of researchers worldwide. This is a pity, because the TCD is capable of accurate predictions in a wide variety of situations. The essential elements are an elastic stress analysis and a material-dependent critical distance, a parameter which we call L. The value of L can be written in terms of other material parameters as: $$ L = \frac{1} {\pi }\left( {\frac{{K_c }} {{\sigma _o }}} \right)^2 $$ (1)

Journal ArticleDOI
21 Sep 2007-Immunity
TL;DR: It is reported that Th2 cytokines affect autophagy in macrophages and their ability to control intracellular M. tuberculosis and a mechanism through which Th1-Th2 polarization differentially affects the immune control of intrACEllular pathogens.

Journal ArticleDOI
TL;DR: It is demonstrated that domestic pigs of Near Eastern ancestry were definitely introduced into Europe during the Neolithic (potentially along two separate routes), reaching the Paris Basin by at least the early 4th millennium B.C.
Abstract: The Neolithic Revolution began 11,000 years ago in the Near East and preceded a westward migration into Europe of distinctive cultural groups and their agricultural economies, including domesticated animals and plants. Despite decades of research, no consensus has emerged about the extent of admixture between the indigenous and exotic populations or the degree to which the appearance of specific components of the "Neolithic cultural package" in Europe reflects truly independent development. Here, through the use of mitochondrial DNA from 323 modern and 221 ancient pig specimens sampled across western Eurasia, we demonstrate that domestic pigs of Near Eastern ancestry were definitely introduced into Europe during the Neolithic (potentially along two separate routes), reaching the Paris Basin by at least the early 4th millennium B.C. Local European wild boar were also domesticated by this time, possibly as a direct consequence of the introduction of Near Eastern domestic pigs. Once domesticated, European pigs rapidly replaced the introduced domestic pigs of Near Eastern origin throughout Europe. Domestic pigs formed a key component of the Neolithic Revolution, and this detailed genetic record of their origins reveals a complex set of interactions and processes during the spread of early farmers into Europe.

Journal ArticleDOI
TL;DR: A comprehensive list of caspase substrates is compiled and a searchable web resource is described which contains information pertaining to all currently known caspases which contains some of the unresolved issues relating to casp enzyme-dependent events in apoptosis and inflammation.
Abstract: Apoptosis is coordinated by members of the caspase family of aspartic acid-specific proteases. Other members of this protease family also play essential roles in inflammation where they participate in the maturation of pro-inflammatory cytokines. To date, almost 400 substrates for the apoptosis-associated caspases have been reported and there are likely to be hundreds more yet to be discovered. Thus, the fraction of the proteome that is degraded (the degradome) by caspases during the demolition phase of apoptosis appears to be quite substantial. Despite this, we still know surprisingly little concerning how caspases provoke some of the signature events in apoptosis, such as membrane phosphatidylserine externalization, cellular retraction, chromatin condensation and apoptotic body production. The inflammatory caspases appear to be much more specific proteases than those involved in apoptosis and only two confirmed substrates for these proteases have been described to date. Here, we have compiled a comprehensive list of caspase substrates and describe a searchable web resource (The Casbah; www.casbah.ie) which contains information pertaining to all currently known caspase substrates. We also discuss some of the unresolved issues relating to caspase-dependent events in apoptosis and inflammation.

Journal ArticleDOI
TL;DR: An original method for grading the colours between different images or shots is proposed using an original and parameter free algorithm that is able to transform any N-dimensional probability density function into another one.

Journal ArticleDOI
TL;DR: Comp comparative analyses are revealing the evolutionary processes that occur as multiple related genomes diverge from a shared polyploid ancestor, and in individual genomes that underwent several successive rounds of duplication.

Journal ArticleDOI
26 Nov 2007-Trials
TL;DR: Commentary article concerning problems associated with the standardisation of clinical trials and systematic reviews.
Abstract: Commentary article concerning problems associated with the standardisation of clinical trials and systematic reviews.

Journal ArticleDOI
TL;DR: Carbon mitigation by the energy crop, Miscanthus is shown to have an important role in climate change mitigation and can be a source of concern for policymakers and scientists.
Abstract: Clifton-Brown, J. C., Breuer, J., Jones, M. B. (2007). Carbon mitigation by the energy crop, Miscanthus. Global Change Biology. 13 (11), 2296-2307 Sponsorship: EU JOUB-0069 / AIR-CT92-0294 RAE2008

Journal ArticleDOI
TL;DR: The OmpA outer membrane protein of Escherichia coli and other enterobacteria is a multifaceted protein that can function as an adhesin and invasin, participate in biofilm formation, act as both an immune target and evasin, and serves as a receptor for several bacteriophages.
Abstract: The OmpA outer membrane protein of Escherichia coli and other enterobacteria is a multifaceted protein. This protein is expressed to very high levels and ompA is tightly regulated at the posttranscriptional level. It can function as an adhesin and invasin, participate in biofilm formation, act as both an immune target and evasin, and serves as a receptor for several bacteriophages. Many of these properties are due to four short protein loops that emanate from the protein to the outside of the cell. Herein it is described how the structure of this protein relates to its many functions.

Journal ArticleDOI
01 Mar 2007-Geology
TL;DR: In this paper, the authors present paleotemperature estimates from foraminifer isotopes and the membrane lipids of marine Crenarcheota from new drill cores in Tanzania that indicate a warm and generally stable tropical climate over this period.
Abstract: Earth's climate cooled from a period of extreme warmth in the early Eocene Epoch (ca. 50 Ma) to the early Oligocene (ca. 33 Ma), when a large ice cap first appeared on Antarctica. Evidence from the planktonic foraminifer oxygen isotope record in deep-sea cores has suggested that tropical sea-surface temperatures declined by 5-10 degrees over this interval, eventually becoming much cooler than modern temperatures. Here we present paleotemperature estimates from foraminifer isotopes and the membrane lipids of marine Crenarcheota from new drill cores in Tanzania that indicate a warm and generally stable tropical climate over this period. We reinterpret the previously published isotope records in the light of comparative textural analysis of the deep-sea foraminifer shells, which shows that in contrast to the Tanzanian material, they have been diagenetically recrystallized. We suggest that increasingly severe alteration of the deep-sea plankton shells through the Eocene produced a diagenetic overprint on their oxygen isotope ratios that imparts the false appearance of a tropical sea-surface cooling trend. This implies that the long-term Eocene climatic cooling trend occurred mainly at the poles and had little effect at lower latitudes.

Journal ArticleDOI
TL;DR: In this paper, Ding et al. investigated macroeconomic influences on gold using the asymmetric power GARCH model (APGARCH) of [Ding, Z., Granger, C.W.J., Engle, R.F., 1993.

Journal ArticleDOI
TL;DR: It is hypothesised that methylol cross-links between RNA and protein which occur during tissue processing inhibit the yield of total RNA, however, small RNA molecules appear to be less affected by this process and are recovered more easily in the extraction process.
Abstract: Archival formalin-fixed paraffin-embedded (FFPE) tissues have limited utility in applications involving analysis of gene expression due to mRNA degradation and modification during fixation and processing. This study analyzed 160 miRNAs in paired snap frozen and FFPE cells to investigate if miRNAs may be successfully detected in archival specimens. Our results show that miRNA extracted from FFPE blocks was successfully amplified using Q-RT-PCR. The levels of expression of miRNA detected in total RNA extracted from FFPE were higher than that extracted from snap frozen cells when the quantity of total RNA was identical. This phenomenon is most likely explained by the fact that larger numbers of FFPE cells were required to generate equivalent quantities of total RNA than their snap frozen counterparts. We hypothesise that methylol cross-links between RNA and protein which occur during tissue processing inhibit the yield of total RNA. However, small RNA molecules appear to be less affected by this process and are recovered more easily in the extraction process. In general miRNAs demonstrated reliable expression levels in FFPE compared with snap frozen paired samples, suggesting these molecules might prove to be robust targets amenable to detection in archival material in the molecular pathology setting.

Journal ArticleDOI
TL;DR: The work that has been done to understand how cracks form and grow in bone, and how they can be detected and repaired in a timely manner is reviewed.
Abstract: Our bones are full of cracks, which form and grow as a result of daily loading activities Bone is the major structural material in our bodies Although weaker than many engineering materials, it has one trick that keeps it ahead - it can repair itself Small cracks, which grow under cyclic stresses by the mechanism of fatigue, can be detected and removed before they become long enough to be dangerous This article reviews the work that has been done to understand how cracks form and grow in bone, and how they can be detected and repaired in a timely manner This is truly an interdisciplinary research field, requiring the close cooperation of materials scientists, biologists and engineers

Journal ArticleDOI
TL;DR: The data suggest that the ACC might participate in both preconscious and conscious error detection and that cortical arousal provides a necessary setting condition for error awareness.
Abstract: Error-processing research has demonstrated that the brain uses a specialized neural network to detect errors during task performance but the brain regions necessary for conscious awareness of an error are poorly understood. In the present study we show that two well-known error-related event-related potential (ERP) components, the error-related negativity (ERN) and error positivity (Pe) have a differential relationship with awareness during performance of a manual response inhibition task optimized to examine error awareness. While the ERN was unaffected by the participants’ conscious experience of errors, the Pe was only seen when participants were aware of committing an error. Source localization of these components indicated that the ERN was generated by a caudal region of the anterior cingulate cortex (ACC) while the Pe was associated with contributions from a more anterior ACC region and the posterior cingulate–precuneus. Tonic EEG measures of cortical arousal were correlated with individual rates of error awareness and showed a specific relationship with the amplitude of the Pe. The latter finding is consistent with evidence that the Pe represents a P3-like facilitation of information processing modulated by subcortical arousal systems. Our data suggest that the ACC might participate in both preconscious and conscious error detection and that cortical arousal provides a necessary setting condition for error awareness. These findings may be particularly important in the context of clinical studies in which a proper understanding of self-monitoring deficits requires an explicit measurement of error awareness.