562 research outputs found

    GIFFT: A Fast Solver for Modeling Sources in a Metamaterial Environment of Finite Size

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    Due to the recent explosion of interest in studying the electromagnetic behavior of large (truncated) periodic structures such as phased arrays, frequency-selective surfaces, and metamaterials, there has been a renewed interest in efficiently modeling such structures. Since straightforward numerical analyses of large, finite structures (i.e., explicitly meshing and computing interactions between all mesh elements of the entire structure) involve significant memory storage and computation times, much effort is currently being expended on developing techniques that minimize the high demand on computer resources. One such technique that belongs to the class of fast solvers for large periodic structures is the GIFFT algorithm (Green's function interpolation and FFT), which is first discussed in [1]. This method is a modification of the adaptive integral method (AIM) [2], a technique based on the projection of subdomain basis functions onto a rectangular grid. Like the methods presented in [3]-[4], the GIFFT algorithm is an extension of the AIM method in that it uses basis-function projections onto a rectangular grid through Lagrange interpolating polynomials. The use of a rectangular grid results in a matrix-vector product that is convolutional in form and can thus be evaluated using FFTs. Although our method differs from [3]-[6] in various respects, the primary differences between the AIM approach [2] and the GIFFT method [1] is the latter's use of interpolation to represent the Green's function (GF) and its specialization to periodic structures by taking into account the reusability properties of matrices that arise from interactions between identical cell elements. The present work extends the GIFFT algorithm to allow for a complete numerical analysis of a periodic structure excited by dipole source, as shown in Fig 1. Although GIFFT [1] was originally developed to handle strictly periodic structures, the technique has now been extended to efficiently handle a small number of distinct element types. Thus, in addition to reducing the computational burden associated with large periodic structures, GIFFT now permits modeling these structures with source and defect elements. Relaxing the restriction to strictly identical periodic elements is, of course, useful for practical applications where, for example, a dipole excitation may be of interest or, as is often the case for metamaterials, defective elements are introduced in the structure's fabrication process. The main extensions of the GIFFT method compared to [1] are the following: (1) Both periodic ''background'' and ''source'' or ''defect'' elements are now separately defined in translatable unit cells so that, in the algorithm, mutual electromagnetic interactions can be computed. (2) The near-interaction block matrix must allow for the possibility of ''background-to-source'' or ''background-to-defect'' cell interactions. (3) Matrices representing projections of both ''background and source'' or ''background and defect'' subdomain bases onto the interpolation polynomials must be defined and appropriately selected in forming the matrix-vector product. It is important to note that, although here we consider a metamaterial layer with a dipole-antenna excitation, as per the extended GIFFT algorithm, ''defect'' elements could be considered as well

    Translational Regulation of Utrophin by miRNAs

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    Background Utrophin is the autosomal homolog of dystrophin, the product of the Duchenne Muscular Dystrophy (DMD) locus. Its regulation is of therapeutic interest as its overexpression can compensate for dystrophin's absence in animal models of DMD. The tissue distribution and transcriptional regulation of utrophin have been characterized extensively, and more recently translational control mechanisms that may underlie its complex expression patterns have begun to be identified. Methodology/Principal Findings Using a variety of bioinformatic, molecular and cell biology techniques, we show that the muscle isoform utrophin-A is predominantly suppressed at the translational level in C2C12 myoblasts. The extent of translational inhibition is estimated to be ~99% in C2C12 cells and is mediated by both the 5′- and 3′-UTRs of the utrophin-A mRNA. In this study we identify five miRNAs (let-7c, miR-150, miR-196b, miR-296-5p, miR-133b) that mediate the repression, and confirm repression by the previously identified miR-206. We demonstrate that this translational repression can be overcome by blocking the actions of miRNAs, resulting in an increased level of utrophin protein in C2C12 cells. Conclusions/Significance The present study has identified key inhibitory mechanisms featuring miRNAs that regulate utrophin expression, and demonstrated that these mechanisms can be targeted to increase endogenous utrophin expression in cultured muscle cells. We suggest that miRNA-mediated inhibitory mechanisms could be targeted by methods similar to those described here as a novel strategy to increase utrophin expression as a therapy for DMD

    Dynamics of Co-Transcriptional Pre-mRNA Folding Influences the Induction of Dystrophin Exon Skipping by Antisense Oligonucleotides

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    Antisense oligonucleotides (AONs) mediated exon skipping offers potential therapy for Duchenne muscular dystrophy. However, the identification of effective AON target sites remains unsatisfactory for lack of a precise method to predict their binding accessibility. This study demonstrates the importance of co-transcriptional pre-mRNA folding in determining the accessibility of AON target sites for AON induction of selective exon skipping in DMD. Because transcription and splicing occur in tandem, AONs must bind to their target sites before splicing factors. Furthermore, co-transcriptional pre-mRNA folding forms transient secondary structures, which redistributes accessible binding sites. In our analysis, to approximate transcription elongation, a “window of analysis” that included the entire targeted exon was shifted one nucleotide at a time along the pre-mRNA. Possible co-transcriptional secondary structures were predicted using the sequence in each step of transcriptional analysis. A nucleotide was considered “engaged” if it formed a complementary base pairing in all predicted secondary structures of a particular step. Correlation of frequency and localisation of engaged nucleotides in AON target sites accounted for the performance (efficacy and efficiency) of 94% of 176 previously reported AONs. Four novel insights are inferred: (1) the lowest frequencies of engaged nucleotides are associated with the most efficient AONs; (2) engaged nucleotides at 3′ or 5′ ends of the target site attenuate AON performance more than at other sites; (3) the performance of longer AONs is less attenuated by engaged nucleotides at 3′ or 5′ ends of the target site compared to shorter AONs; (4) engaged nucleotides at 3′ end of a short target site attenuates AON efficiency more than at 5′ end

    Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

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    The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

    Rationale, design and conduct of a comprehensive evaluation of a school-based peer-led anti-smoking intervention in the UK: the ASSIST cluster randomised trial [ISRCTN55572965]

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    BACKGROUND: To date, no school-based intervention has been proven to be effective in preventing adolescent smoking, despite continuing concern about smoking levels amongst young people in the United Kingdom. Although formal teacher-led smoking prevention interventions are considered unlikely to be effective, peer-led approaches to reducing smoking have been proposed as potentially valuable. METHODS/DESIGN: ASSIST (A Stop Smoking in Schools Trial) is a comprehensive, large-scale evaluation to rigorously test whether peer supporters in Year 8 (age 11–12) can be recruited and trained to effect a reduction in smoking uptake among their fellow students. The evaluation is employing a cluster randomised controlled trial (RCT) design with secondary school as the unit of randomisation, and is being undertaken in 59 schools in South East Wales and the West of England. Embedded within the trial are an economic evaluation of the intervention costs, a process evaluation to provide detailed information on how the intervention was delivered and received, and an analysis of social networks to consider whether such a peer group intervention could work amongst schoolchildren in this age group. Schools were randomised to either continue with normal smoking education (n = 29 schools, 5562 students), or to do so and additionally receive the ASSIST intervention (n = 30 schools, 5481 students). No schools withdrew once the trial had started, and the intervention was successfully implemented in all 30 schools, with excellent participation rates from the peer supporters. The primary outcome is regular (weekly) smoking, validated by salivary cotinine, and this outcome has been obtained for 94.4%, 91.0% and 95.6% of eligible students at baseline, immediate post-intervention, and one-year follow-up respectively. DISCUSSION: Comprehensive evaluations of complex public health interventions of this scale and nature are rare in the United Kingdom. This paper demonstrates the feasibility of conducting cluster RCTs of complex public health interventions in schools, and how the rigour of such designs can be maximised both by thorough implementation of the protocol and by broadening the scope of questions addressed in the trial by including additional evaluative components

    Investigating concordance in diabetes diagnosis between primary care charts (electronic medical records) and health administrative data: a retrospective cohort study

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    <p>Abstract</p> <p>Background</p> <p>Electronic medical records contain valuable clinical information not readily available elsewhere. Accordingly, they hold important potential for contributing to and enhancing chronic disease registries with the goal of improving chronic disease management; however a standard for diagnoses of conditions such as diabetes remains to be developed. The purpose of this study was to establish a validated electronic medical record definition for diabetes.</p> <p>Methods</p> <p>We constructed a retrospective cohort using health administrative data from the Institute for Clinical Evaluative Sciences Ontario Diabetes Database linked with electronic medical records from the Deliver Primary Healthcare Information Project using data from 1 April 2006 - 31 March 2008 (N = 19,443). We systematically examined eight definitions for diabetes diagnosis, both established and proposed.</p> <p>Results</p> <p>The definition that identified the highest number of patients with diabetes (N = 2,180) while limiting to those with the highest probability of having diabetes was: individuals with ≥2 abnormal plasma glucose tests, or diabetes on the problem list, or insulin prescription, or ≥2 oral anti-diabetic agents, or HbA1c ≥6.5%. Compared to the Ontario Diabetes Database, this definition identified 13% more patients while maintaining good sensitivity (75%) and specificity (98%).</p> <p>Conclusions</p> <p>This study establishes the feasibility of developing an electronic medical record standard definition of diabetes and validates an algorithm for use in this context. While the algorithm may need to be tailored to fit available data in different electronic medical records, it contributes to the establishment of validated disease registries with the goal of enhancing research, and enabling quality improvement in clinical care and patient self-management.</p

    Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

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    The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

    X-ray emission from the Sombrero galaxy: discrete sources

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    We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres

    Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

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    The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO
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