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Showing papers by "University College Dublin published in 2006"


Journal ArticleDOI
30 Mar 2006-Nature
TL;DR: T tandem affinity purification was used to process 4,562 different tagged proteins of the yeast Saccharomyces cerevisiae to identify protein–protein interactions, which will help future studies on individual proteins as well as functional genomics and systems biology.
Abstract: Identification of protein-protein interactions often provides insight into protein function, and many cellular processes are performed by stable protein complexes. We used tandem affinity purification to process 4,562 different tagged proteins of the yeast Saccharomyces cerevisiae. Each preparation was analysed by both matrix-assisted laser desorption/ionization-time of flight mass spectrometry and liquid chromatography tandem mass spectrometry to increase coverage and accuracy. Machine learning was used to integrate the mass spectrometry scores and assign probabilities to the protein-protein interactions. Among 4,087 different proteins identified with high confidence by mass spectrometry from 2,357 successful purifications, our core data set (median precision of 0.69) comprises 7,123 protein-protein interactions involving 2,708 proteins. A Markov clustering algorithm organized these interactions into 547 protein complexes averaging 4.9 subunits per complex, about half of them absent from the MIPS database, as well as 429 additional interactions between pairs of complexes. The data (all of which are available online) will help future studies on individual proteins as well as functional genomics and systems biology.

2,975 citations


Journal ArticleDOI
30 Jun 2006-Science
TL;DR: Evidence on the effects of early environments on child, adolescent, and adult achievement and how early inputs strongly affect the productivity of later inputs is summarized.
Abstract: This paper summarizes evidence on the effects of early environments on child, adolescent, and adult achievement. Life cycle skill formation is a dynamic process in which early inputs strongly affect the productivity of later inputs.

2,882 citations


Journal ArticleDOI
TL;DR: This update to the international guidelines is based primarily on a consensus of opinion rendered by experts in the field and should not be considered to be hard and fast rules.
Abstract: Since the writing of the 1998 guidelines for the selection of candidates for lung transplantation, there has been an increased understanding of the natural history of various lung diseases as well as new treatment strategies developed that may forestall the need for transplantation for certain disorders. This has resulted in several changes to the current strategy for selecting patients for this procedure. The primary goal of this document is to provide up-to-date guidelines to help physicians in the referral and selection process of candidates for lung transplantation. With limited prospective randomized studies to support the recommendations outlined in this document, this update to the international guidelines is based primarily on a consensus of opinion rendered by experts in the field. The bulleted guidelines should therefore not be considered to be hard and fast rules. Because of the potential for long waiting times to transplantation, physicians should err on the side of early referral of their patients to a lung transplant center. © 2006 International Society for Heart and Lung Transplantation.

983 citations


Journal ArticleDOI
22 Sep 2006-Science
TL;DR: The phenotype of the exogenously induced amyloidosis depended on both the host and the source of the agent, suggesting the existence of polymorphic Aβ strains with varying biological activities reminiscent of prion strains.
Abstract: Protein aggregation is an established pathogenic mechanism in Alzheimer's disease, but little is known about the initiation of this process in vivo. Intracerebral injection of dilute, amyloid-beta (Abeta)-containing brain extracts from humans with Alzheimer's disease or beta-amyloid precursor protein (APP) transgenic mice induced cerebral beta-amyloidosis and associated pathology in APP transgenic mice in a time- and concentration-dependent manner. The seeding activity of brain extracts was reduced or abolished by Abeta immunodepletion, protein denaturation, or by Abeta immunization of the host. The phenotype of the exogenously induced amyloidosis depended on both the host and the source of the agent, suggesting the existence of polymorphic Abeta strains with varying biological activities reminiscent of prion strains.

916 citations


Journal ArticleDOI
TL;DR: In this article, the use of multiple proxies and improving understanding of formation mechanisms offers a clear way forward, but the climatological meaning of many speleothem records cannot be interpreted unequivocally; this is particularly so for more subtle shifts and shorter time periods.

736 citations


Journal ArticleDOI
23 Jan 2006
TL;DR: The various methods that can be used to induce faults in semiconductors and exploit such errors maliciously are covered and a series of countermeasures to thwart these attacks are described.
Abstract: The effect of faults on electronic systems has been studied since the 1970s when it was noticed that radioactive particles caused errors in chips. This led to further research on the effect of charged particles on silicon, motivated by the aerospace industry, which was becoming concerned about the effect of faults in airborne electronic systems. Since then various mechanisms for fault creation and propagation have been discovered and researched. This paper covers the various methods that can be used to induce faults in semiconductors and exploit such errors maliciously. Several examples of attacks stemming from the exploiting of faults are explained. Finally a series of countermeasures to thwart these attacks are described.

690 citations


Journal ArticleDOI
TL;DR: The current state of autonomic communications research is surveyed and significant emerging trends and techniques are identified.
Abstract: Autonomic communications seek to improve the ability of network and services to cope with unpredicted change, including changes in topology, load, task, the physical and logical characteristics of the networks that can be accessed, and so forth. Broad-ranging autonomic solutions require designers to account for a range of end-to-end issues affecting programming models, network and contextual modeling and reasoning, decentralised algorithms, trust acquisition and maintenance---issues whose solutions may draw on approaches and results from a surprisingly broad range of disciplines. We survey the current state of autonomic communications research and identify significant emerging trends and techniques.

690 citations


Journal ArticleDOI
TL;DR: It is hypothesized that hypoxia releases repression of NFκB activity through decreased PHD-dependent hydroxylation of IKKβ, an event that may contribute to tumor development and progression through amplification of tumorigenic signaling pathways.
Abstract: Hypoxia is a feature of the microenvironment of a growing tumor. The transcription factor NFκB is activated in hypoxia, an event that has significant implications for tumor progression. Here, we demonstrate that hypoxia activates NFκB through a pathway involving activation of IκB kinase-β (IKKβ) leading to phosphorylation-dependent degradation of IκBα and liberation of NFκB. Furthermore, through increasing the pool and/or activation potential of IKKβ, hypoxia amplifies cellular sensitivity to stimulation with TNFα. Within its activation loop, IKKβ contains an evolutionarily conserved LxxLAP consensus motif for hydroxylation by prolyl hydroxylases (PHDs). Mimicking hypoxia by treatment of cells with siRNA against PHD-1 or PHD-2 or the pan-prolyl hydroxylase inhibitor DMOG results in NFκB activation. Conversely, overexpression of PHD-1 decreases cytokine-stimulated NFκB reporter activity, further suggesting a repressive role for PHD-1 in controlling the activity of NFκB. Hypoxia increases both the expression and activity of IKKβ, and site-directed mutagenesis of the proline residue (P191A) of the putative IKKβ hydroxylation site results in a loss of hypoxic inducibility. Thus, we hypothesize that hypoxia releases repression of NFκB activity through decreased PHD-dependent hydroxylation of IKKβ, an event that may contribute to tumor development and progression through amplification of tumorigenic signaling pathways.

676 citations


Journal ArticleDOI
TL;DR: Bilateral flickering stimuli were presented simultaneously and continuously over entire trial blocks, such that externally evoked alpha desynchronization is equated in precue baseline and postcue intervals and suggests that alpha synchronization reflects an active attentional suppression mechanism, rather than a passive one reflecting "idling" circuits.
Abstract: Human electrophysiological (EEG) studies have demonstrated the involvement of alpha band (8- to 14-Hz) oscillations in the anticipatory biasing of attention. In the context of visual spatial attent...

667 citations


Journal ArticleDOI
TL;DR: In this article, the authors examined the properties of instrumental variables applied to models with essential heterogeneity, that is, models where responses to interventions are heterogeneous and agents adopt treatments (participate in programs) with at least partial knowledge of their idiosyncratic response.
Abstract: This paper examines the properties of instrumental variables (IV) applied to models with essential heterogeneity, that is, models where responses to interventions are heterogeneous and agents adopt treatments (participate in programs) with at least partial knowledge of their idiosyncratic response. We analyze two-outcome and multiple-outcome models, including ordered and unordered choice models. We allow for transition-specific and general instruments. We generalize previous analyses by developing weights for treatment effects for general instruments. We develop a simple test for the presence of essential heterogeneity. We note the asymmetry of the model of essential heterogeneity: outcomes of choices are heterogeneous in a general way; choices are not. When both choices and outcomes are permitted to be symmetrically heterogeneous, the method of IV breaks down for estimating treatment parameters.

654 citations


Journal ArticleDOI
TL;DR: The finding of seven missense mutations in 15 individuals, of whom four had familial ALS and 11 apparently 'sporadic' ALS, provides further evidence that variations in hypoxia-inducible genes have an important role in motor neuron degeneration.
Abstract: We recently identified angiogenin (ANG) as a candidate susceptibility gene for amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized by adult-onset loss of motor neurons. We now report the finding of seven missense mutations in 15 individuals, of whom four had familial ALS and 11 apparently 'sporadic' ALS. Our findings provide further evidence that variations in hypoxia-inducible genes have an important role in motor neuron degeneration.

Journal ArticleDOI
TL;DR: The hypothesis that diffusible oligomers of Aβ initiate a synaptic dysfunction that may be an early event in AD is supported and specific assemblies, particularly timers of naturally secreted Aβ oligomers are potent and selective inhibitors of certain forms of hippocampal LTP.
Abstract: The accumulation of amyloid beta-protein (Abeta) in brain regions serving memory and cognition is a central pathogenic feature of Alzheimer's disease (AD) We have shown that small soluble oligomers of human Abeta that are naturally secreted by cultured cells inhibit hippocampal long-term potentiation (LTP) in vitro and in vivo and transiently impair the recall of a complex learned behaviour in rats These results support the hypothesis that diffusible oligomers of Abeta initiate a synaptic dysfunction that may be an early event in AD We now report detailed electrophysiological analyses that define conditions under which acute application of soluble Abeta inhibits hippocampal synaptic plasticity in wild-type mice To ascertain which Abeta assemblies contribute to the impairment of LTP, we fractionated oligomers by size-exclusion chromatography and found that Abeta trimers fully inhibit LTP, whereas dimers and tetramers have an intermediate potency Natural Abeta oligomers are sensitive to heat denaturation, primarily inhibit the induction phase of LTP, and cause a sustained impairment of LTP even after extensive washout We observed no effects of Abeta oligomers on presynaptic vesicle release LTP in juvenile mice is resistant to the effects of Abeta oligomers, as is brain-derived-neurotrophic-factor-induced LTP in adult hippocampus We conclude that specific assemblies, particularly timers, of naturally secreted Abeta oligomers are potent and selective inhibitors of certain forms of hippocampal LTP

Journal ArticleDOI
TL;DR: The authors formulates hypotheses and reports on individual attitudes towards immigration based on data for 24 countries on socioeconomic position, sociodemographic characteristics and political attitudes, and suggests that a range of other economic and cultural factors influence attitudes toward immigration.

Journal ArticleDOI
TL;DR: M-Coffee is a meta-method for assembling multiple sequence alignments (MSA) by combining the output of several individual methods into one single MSA that is robust to variations in the choice of constituent methods and reasonably tolerant to duplicate MSAs.
Abstract: We introduce M-Coffee, a meta-method for assembling multiple sequence alignments (MSA) by combining the output of several individual methods into one single MSA. M-Coffee is an extension of T-Coffee and uses consistency to estimate a consensus alignment. We show that the procedure is robust to variations in the choice of constituent methods and reasonably tolerant to duplicate MSAs. We also show that performances can be improved by carefully selecting the constituent methods. M-Coffee outperforms all the individual methods on three major reference datasets: HOMSTRAD, Prefab and Balibase. We also show that on a case-by-case basis, M-Coffee is twice as likely to deliver the best alignment than any individual method. Given a collection of pre-computed MSAs, M-Coffee has similar CPU requirements to the original T-Coffee. M-Coffee is a freeware open-source package available from http://www.tcoffee.org/.

Journal ArticleDOI
TL;DR: The fifth mammalian TIR adaptor SARM is a negative regulator of Toll-like receptor signaling, and 'knockdown' of endogenous SARM expression by interfering RNA led to enhanced TRIF-dependent cytokine and chemokine induction.
Abstract: Toll-like receptors discriminate between different pathogen-associated molecules and activate signaling cascades that lead to immune responses. The specificity of Toll-like receptor signaling occurs by means of adaptor proteins containing Toll-interleukin 1 receptor (TIR) domains. Activating functions have been assigned to four TIR adaptors: MyD88, Mal, TRIF and TRAM. Here we characterize a fifth TIR adaptor, SARM, as a negative regulator of TRIF-dependent Toll-like receptor signaling. Expression of SARM blocked gene induction 'downstream' of TRIF but not of MyD88. SARM associated with TRIF, and 'knockdown' of endogenous SARM expression by interfering RNA led to enhanced TRIF-dependent cytokine and chemokine induction. Thus, the fifth mammalian TIR adaptor SARM is a negative regulator of Toll-like receptor signaling.

Journal ArticleDOI
TL;DR: In this paper, the authors present both a critique of the neo-liberal model of marketised education and a challenge to academics to work as public intellectuals both individually and with civil society organisations to develop a counter-hegemonic discourse to the Neo-Liberalism for higher education.
Abstract: This article is based on a keynote paper presented to the European Conference on Educational Research (ECER), University College Dublin, 5-9 September 2005. The massification of education in European countries over the last 100 years has produced cultures and societies that have benefited greatly from state investment in education. To maintain this level of social and economic development that derives from high quality education requires continual state investment. With the rise of the New Right, neo-liberal agenda, there is an attempt to offload the cost of education, and indeed other public services such as housing, transport, care services etc., on to the individual. There is an increasing attempt to privatise public services, including education, so that citizens will have to buy them at market value rather than have them provided by the state. Europe is no exception to this trend of neo-liberalisation. Recent Organisation for Economic Cooperation and Development (OECD) reports, including one on higher education in Ireland, (2004), concentrate strongly on the role of education in servicing the economy to the neglect of its social and developmental responsibilities. The view that education is simply another market commodity has become normalised in policy and public discourses. Schools run purely as businesses are a growing phenomenon within and without Europe, and there is an increasing expectation in several countries that schools will supplement their income from private sources, even though they are within the state sector. In this article, the writer presents both a critique of the neo-liberal model of marketised education and a challenge to academics to work as public intellectuals both individually and with civil society organisations to develop a counter- hegemonic discourse to neo-liberalism for higher education.

Journal ArticleDOI
TL;DR: This work has constructed robust phylogenies for fungi based on whole genome analysis that provide strong support for the classification of phyla, sub-phyla, classes and orders.
Abstract: To date, most fungal phylogenies have been derived from single gene comparisons, or from concatenated alignments of a small number of genes. The increase in fungal genome sequencing presents an opportunity to reconstruct evolutionary events using entire genomes. As a tool for future comparative, phylogenomic and phylogenetic studies, we used both supertrees and concatenated alignments to infer relationships between 42 species of fungi for which complete genome sequences are available. A dataset of 345,829 genes was extracted from 42 publicly available fungal genomes. Supertree methods were employed to derive phylogenies from 4,805 single gene families. We found that the average consensus supertree method may suffer from long-branch attraction artifacts, while matrix representation with parsimony (MRP) appears to be immune from these. A genome phylogeny was also reconstructed from a concatenated alignment of 153 universally distributed orthologs. Our MRP supertree and concatenated phylogeny are highly congruent. Within the Ascomycota, the sub-phyla Pezizomycotina and Saccharomycotina were resolved. Both phylogenies infer that the Leotiomycetes are the closest sister group to the Sordariomycetes. There is some ambiguity regarding the placement of Stagonospora nodurum, the sole member of the class Dothideomycetes present in the dataset. Within the Saccharomycotina, a monophyletic clade containing organisms that translate CTG as serine instead of leucine is evident. There is also strong support for two groups within the CTG clade, one containing the fully sexual species Candida lusitaniae, Candida guilliermondii and Debaryomyces hansenii, and the second group containing Candida albicans, Candida dubliniensis, Candida tropicalis, Candida parapsilosis and Lodderomyces elongisporus. The second major clade within the Saccharomycotina contains species whose genomes have undergone a whole genome duplication (WGD), and their close relatives. We could not confidently resolve whether Candida glabrata or Saccharomyces castellii lies at the base of the WGD clade. We have constructed robust phylogenies for fungi based on whole genome analysis. Overall, our phylogenies provide strong support for the classification of phyla, sub-phyla, classes and orders. We have resolved the relationship of the classes Leotiomyctes and Sordariomycetes, and have identified two classes within the CTG clade of the Saccharomycotina that may correlate with sexual status.

Proceedings ArticleDOI
25 Jun 2006
TL;DR: A selection of strategies for addressing the implications of diagonal dominance for unsupervised kernel methods in the task of document clustering are proposed, and their effectiveness in producing more accurate and stable clusterings is evaluated.
Abstract: In supervised kernel methods, it has been observed that the performance of the SVM classifier is poor in cases where the diagonal entries of the Gram matrix are large relative to the off-diagonal entries. This problem, referred to as diagonal dominance, often occurs when certain kernel functions are applied to sparse high-dimensional data, such as text corpora. In this paper we investigate the implications of diagonal dominance for unsupervised kernel methods, specifically in the task of document clustering. We propose a selection of strategies for addressing this issue, and evaluate their effectiveness in producing more accurate and stable clusterings.

Journal ArticleDOI
S. Schael1, R. Barate, R. Bruneliere, I. De Bonis  +1279 moreInstitutions (141)
TL;DR: In this paper, four LEP collaborations, ALEPH, DELPHI, L3 and OPAL, have searched for the neutral Higgs bosons which are predicted by the minimal supersymmetric standard model (MSSM).
Abstract: The four LEP collaborations, ALEPH, DELPHI, L3 and OPAL, have searched for the neutral Higgs bosons which are predicted by the Minimal Supersymmetric standard model (MSSM). The data of the four collaborations are statistically combined and examined for their consistency with the background hypothesis and with a possible Higgs boson signal. The combined LEP data show no significant excess of events which would indicate the production of Higgs bosons. The search results are used to set upper bounds on the cross-sections of various Higgs-like event topologies. The results are interpreted within the MSSM in a number of “benchmark” models, including CP-conserving and CP-violating scenarios. These interpretations lead in all cases to large exclusions in the MSSM parameter space. Absolute limits are set on the parameter cosβ and, in some scenarios, on the masses of neutral Higgs bosons.

Journal ArticleDOI
TL;DR: The results of this study show that the performance of a patient adaptable classifier increases with the amount of training of the system on the local record and the performance can be significantly boosted with a small amount of adaptation.
Abstract: An adaptive system for the automatic processing of the electrocardiogram (ECG) for the classification of heartbeats into one of the five beat classes recommended by ANSI/AAMI EC57:1998 standard is presented. The heartbeat classification system processes an incoming recording with a global-classifier to produce the first set of beat annotations. An expert then validates and if necessary corrects a fraction of the beats of the recording. The system then adapts by first training a local-classifier using the newly annotated beats and combines this with the global-classifier to produce an adapted classification system. The adapted system is then used to update beat annotations. The results of this study show that the performance of a patient adaptable classifier increases with the amount of training of the system on the local record. Crucially, the performance of the system can be significantly boosted with a small amount of adaptation even when all beats used for adaptation are from a single class. This study illustrates the ability to provide highly beneficial automatic arrhythmia monitoring and is an improvement on previously reported results for automated heartbeat classification systems

Journal ArticleDOI
TL;DR: In this article, the relative potential of various technologies for the confirmation of food authenticity and quality are discussed in terms of their potential ease of application in an industrial setting, and the use of specific techniques with chemometric analysis for the classification of food samples based on quality attributes is also included in this review.
Abstract: The relative potential of various technologies for the confirmation of food authenticity and quality are discussed. Techniques that have found new applications in the field of quality assurance since 2001 are discussed in terms of their potential ease of application in an industrial setting. The use of specific techniques with chemometric analysis for the classification of food samples based on quality attributes is also included in this review. The techniques discussed are spectroscopy (UV, NIR, MIR, visible, Raman), isotopic analysis, chromatography, electronic nose, polymerase chain reaction, enzyme-linked immunosorbent assay and thermal analysis.

Journal ArticleDOI
21 Dec 2006-Nature
TL;DR: Zhang et al. as discussed by the authors reported that GRB 060614 was not accompanied by supernova emission down to limits hundreds of times fainter than the archetypal supernova SN 1998bw that accompanied GRB 980425, and faintter than any type Ic supernova ever observed.
Abstract: The tidy classification system that divided γ-ray bursts (GRBs) into long-duration busts (lasting more than two seconds) and short may have had its day. The final nail in its coffin may be GRB 060614. Discovered on 14 June 2006 by the Burst Alert Telescope on-board the Swift satellite, this burst was long, at 102 seconds, but as reported in a clutch of papers in this issue, it has a number of properties, including the absence of an accompanying supernova, that were previously considered diagnostic of a 'short' GRB. The hunt is now on for a classification system to take account of the diversity now apparent in GRBs. In the accompanying News & Views, Bing Zhang suggests that the answer may be to adopt a Type I/Type II classification similar to that used for supernovae. GRB 060505 and GRB 060614 were not accompanied by supernova emission down to limits hundreds of times fainter than the archetypal SN 1998bw that accompanied GRB 980425, and fainter than any type Ic supernova ever observed. It is now accepted that long-duration γ-ray bursts (GRBs) are produced during the collapse of a massive star1,2. The standard ‘collapsar’ model3 predicts that a broad-lined and luminous type Ic core-collapse supernova accompanies every long-duration GRB4. This association has been confirmed in observations of several nearby GRBs5–9. Here we report that GRB 060505 (ref. 10) and GRB 060614 (ref. 11) were not accompanied by supernova emission down to limits hundreds of times fainter than the archetypal supernova SN 1998bw that accompanied GRB 980425, and fainter than any type Ic supernova ever observed12. Multi-band observations of the early afterglows, as well as spectroscopy of the host galaxies, exclude the possibility of significant dust obscuration and show that the bursts originated in actively star-forming regions. The absence of a supernova to such deep limits is qualitatively different from all previous nearby long-duration GRBs and suggests a new phenomenological type of massive stellar death.

Journal ArticleDOI
TL;DR: In this article, the authors proposed a new model to assess cultural distance and psychic distance separately, based on survey data of more than 300 managers, and showed that both concepts are conceptually different and that psychic distance is determined by cultural distance.
Abstract: Cultural distance and psychic distance are two concepts that are widely used in the international business literature. A large number of studies use both concepts interchangeably with no clear distinction between them. The authors propose a new model to assess cultural distance and psychic distance separately. Through the use of survey data of more than 300 managers, this article shows that both concepts are conceptually different and that psychic distance is determined by cultural distance and the individual values of the managers.

Journal ArticleDOI
V. M. Abazov1, Brad Abbott2, M. Abolins3, Bobby Samir Acharya4  +814 moreInstitutions (74)
TL;DR: The D0 experiment enjoyed a very successful data-collection run at the Fermilab Tevatron collider between 1992 and 1996 as discussed by the authors, and the detector has been upgraded to take advantage of improvements to the Tevoton and to enhance its physics capabilities.
Abstract: The D0 experiment enjoyed a very successful data-collection run at the Fermilab Tevatron collider between 1992 and 1996. Since then, the detector has been upgraded to take advantage of improvements to the Tevatron and to enhance its physics capabilities. We describe the new elements of the detector, including the silicon microstrip tracker, central fiber tracker, solenoidal magnet, preshower detectors, forward muon detector, and forward proton detector. The uranium/liquid-argon calorimeters and central muon detector, remaining from Run I, are discussed briefly. We also present the associated electronics, triggering, and data acquisition systems, along with the design and implementation of software specific to D0.

Journal ArticleDOI
TL;DR: The extensive adaptive radiation in echolocation call design is shaped largely by ecology, showing how perceptual challenges imposed by the environment can often override phylogenetic constraints.
Abstract: Recent molecular phylogenies have changed our perspective on the evolution of echolocation in bats. These phylogenies suggest that certain bats with sophisticated echolocation (e.g. horseshoe bats) share a common ancestry with non-echolocating bats (e.g. Old World fruit bats). One interpretation of these trees presumes that laryngeal echolocation (calls produced in the larynx) probably evolved in the ancestor of all extant bats. Echolocation might have subsequently been lost in Old World fruit bats, only to evolve secondarily (by tongue clicking) in this family. Remarkable acoustic features such as Doppler shift compensation, whispering echolocation and nasal emission of sound each show multiple convergent origins in bats. The extensive adaptive radiation in echolocation call design is shaped largely by ecology, showing how perceptual challenges imposed by the environment can often override phylogenetic constraints.

Journal ArticleDOI
04 Dec 2006
TL;DR: In this paper, a new representation of the Volterra series is proposed, which is derived from a previously introduced modified VOLTERRA series, but adapted to the discrete time domain and reformulated in a novel way.
Abstract: A new representation of the Volterra series is proposed, which is derived from a previously introduced modified Volterra series, but adapted to the discrete time domain and reformulated in a novel way. Based on this representation, an efficient model-pruning approach, called dynamic deviation reduction, is introduced to simplify the structure of Volterra-series-based RF power amplifier behavioral models aimed at significantly reducing the complexity of the model, but without incurring loss of model fidelity. Both static nonlinearities and different orders of dynamic behavior can be separately identified and the proposed representation retains the important property of linearity with respect to series coefficients. This model can, therefore, be easily extracted directly from the measured time domain of input and output samples of an amplifier by employing simple linear system identification algorithms. A systematic mathematical derivation is presented, together with validation of the proposed method using both computer simulation and experiment

Journal ArticleDOI
TL;DR: A case for the recent convergent evolution of a lighter pigmentation phenotype in Europeans and East Asians is supported by the testing for the presence of positive directional selection in 6 pigmentation genes using an empirical F(ST) approach and a role for MATP in determining normal skin pigmentation variation using admixture mapping methods.
Abstract: Human skin pigmentation shows a strong positive correlation with ultraviolet radiation intensity, suggesting that variation in skin color is, at least partially, due to adaptation via natural selection. We investigated the evolution of pigmentation variation by testing for the presence of positive directional selection in 6 pigmentation genes using an empirical F(ST) approach, through an examination of global diversity patterns of these genes in the Centre d'Etude du Polymorphisme Humain (CEPH)-Diversity Panel, and by exploring signatures of selection in data from the International HapMap project. Additionally, we demonstrated a role for MATP in determining normal skin pigmentation variation using admixture mapping methods. Taken together (with the results of previous admixture mapping studies), these results point to the importance of several genes in shaping the pigmentation phenotype and a complex evolutionary history involving strong selection. Polymorphisms in 2 genes, ASIP and OCA2, may play a shared role in shaping light and dark pigmentation across the globe, whereas SLC24A5, MATP, and TYR have a predominant role in the evolution of light skin in Europeans but not in East Asians. These findings support a case for the recent convergent evolution of a lighter pigmentation phenotype in Europeans and East Asians.

Journal ArticleDOI
TL;DR: An empirical study in which some of the most commonly used feature selection methods are compared to 9 publicly available datasets, and it is reported that the choice of feature selection method, the number of genes in the genelist, the numbers of cases and the noise in the dataset, substantially influence classification success.
Abstract: Numerous feature selection methods have been applied to the identification of differentially expressed genes in microarray data. These include simple fold change, classical t-statistic and moderated t-statistics. Even though these methods return gene lists that are often dissimilar, few direct comparisons of these exist. We present an empirical study in which we compare some of the most commonly used feature selection methods. We apply these to 9 publicly available datasets, and compare, both the gene lists produced and how these perform in class prediction of test datasets.

Journal ArticleDOI
TL;DR: In this article, the adsorption characteristics of P-adsorption on the dewatered alum sludge were identified as a function of pH and ion strengths in solution.

Journal ArticleDOI
TL;DR: An empirical equation is defined that expresses the pK(a) as a function of electrostatic potential, hydrogen bonds and accessible surface area and reaches a high overall jack-knifed accuracy, and is fast enough to be used during a molecular dynamics simulation.
Abstract: pK(a) calculations for macromolecules are normally performed by solving the Poisson-Boltzmann equation, accounting for the different dielectric constants of solvent and solute, as well as the ionic strength. Despite the large number of successful applications, there are some situations where the current algorithms are not suitable: (1) large scale, high-throughput analysis which requires calculations to be completed within a fraction of a second, e.g. when permanently monitoring pK(a) shifts during a molecular dynamics simulation; (2) prediction of pK(a)s in periodic boundaries, e.g. when reconstructing entire protein crystal unit cells from PDB files, including the correct protonation patterns at experimental pH. Such in silico crystals are needed by 'self-parameterizing' molecular dynamics force fields like YASARA YAMBER, that optimize their parameters while energy-minimizing high-resolution protein crystals. To address both problems, we define an empirical equation that expresses the pK(a) as a function of electrostatic potential, hydrogen bonds and accessible surface area. The electrostatic potential is evaluated by Ewald summation, which captures periodic crystal environments and the uncertainty in atom positions using Gaussian charge densities. The empirical proportionality constants are derived from 217 experimentally determined pK(a)s, and despite its simplicity, this pK(a) calculation method reaches a high overall jack-knifed accuracy, and is fast enough to be used during a molecular dynamics simulation. A reliable null-model to judge pK(a) prediction accuracies is also presented.