Correction: Usage of Complementary Medicine in Switzerland: Results of the Swiss Health Survey 2012 and Development Since 2007.

[This corrects the article DOI: 10.1371/journal.pone.0141985.]

Correction of aberrant FGFR1 RNA splicing through blocking intronic regulatory elements

Analysis of the human genome has revealed that more than 74% of human genes undergo alternative RNA splicing. Aberrations in alternative RNA splicing have been associated with several human disorders, including cancer. ^ We studied the aberrant expression of alternative RNA splicing isoforms of the Fibroblast Growth Factor Receptor 1 (FGFR1) gene in a human glioblastoma cancer model. Normal glial cells express the FGFR1α, which contains three extracellular domains. In tumors the most abundant isoform is the FGFR1β, which lacks the first extracellular domain due to the skipping of a single exon, termed alpha. The skipping of the α-exon is regulated by two intronic silencing sequences within the precursor mRNA. Since we observed no mutations on these elements in tumor cells, we hypothesized that the over-expression of regulatory proteins that recognize these sequences is responsible for the aberrant expression of splicing isoforms. Hence, we blocked the formation of protein complexes on the ISS using antisense RNA oligonucleotides in vitro. We also evaluated the impact of the ISS antisense oligonucleotides on the endogenous FGFR1 splicing, in a glioblastoma cell model. By targeting intronic regulatory elements we were able to increase the level of alpha exon inclusion up to 90% in glioblastoma cells. The effect was dose dependent, sequence specific and reproducible in glioblastoma and other cancer cells, which also exhibit an alpha exon skipping phenotype. Targeting FGFR1 endogenous ISS1 and ISS2 sequences did not have an additive or synergistic effect, which suggest a regulatory splicing mechanism that requires the interaction of complexes formed on these elements. An increase in the levels of the FGFR1α isoform resulted in a reduction in cell invasiveness. Also, a significant increase in the levels of caspase 3/7 activities, which is indicative of an elevation in apoptosis levels, suggests that expression of FGFR1β might be relevant for tumor survival. These studies demonstrate that it is possible to prevent aberrant expression of exon skipping events through the targeting of intronic regulatory elements, providing an important new therapeutic tool for the correction of human disease caused by alternative RNA splicing. ^

Multiple gradient echo propeller (MGREP) MRI: Technical development and potential applications

The PROPELLER (Periodically Rotated Overlapping Parallel Lines with Enhanced Reconstruction) magnetic resonance imaging (MRI) technique has inherent advantages over other fast imaging methods, including robust motion correction, reduced image distortion, and resistance to off-resonance effects. These features make PROPELLER highly desirable for T2*-sensitive imaging, high-resolution diffusion imaging, and many other applications. However, PROPELLER has been predominantly implemented as a fast spin-echo (FSE) technique, which is insensitive to T2* contrast, and requires time-inefficient signal averaging to achieve adequate signal-to-noise ratio (SNR) for many applications. These issues presently constrain the potential clinical utility of FSE-based PROPELLER. ^ In this research, our aim was to extend and enhance the potential applications of PROPELLER MRI by developing a novel multiple gradient echo PROPELLER (MGREP) technique that can overcome the aforementioned limitations. The MGREP pulse sequence was designed to acquire multiple gradient-echo images simultaneously, without any increase in total scan time or RF energy deposition relative to FSE-based PROPELLER. A new parameter was also introduced for direct user-control over gradient echo spacing, to allow variable sensitivity to T2* contrast. In parallel to pulse sequence development, an improved algorithm for motion correction was also developed and evaluated against the established method through extensive simulations. The potential advantages of MGREP over FSE-based PROPELLER were illustrated via three specific applications: (1) quantitative T2* measurement, (2) time-efficient signal averaging, and (3) high-resolution diffusion imaging. Relative to the FSE-PROPELLER method, the MGREP sequence was found to yield quantitative T2* values, increase SNR by ∼40% without any increase in acquisition time or RF energy deposition, and noticeably improve image quality in high-resolution diffusion maps. In addition, the new motion algorithm was found to improve the performance considerably in motion-artifact reduction. ^ Overall, this work demonstrated a number of enhancements and extensions to existing PROPELLER techniques. The new technical capabilities of PROPELLER imaging, developed in this thesis research, are expected to serve as the foundation for further expanding the scope of PROPELLER applications. ^

J. Ebbeler, Disciplining Christians: Correction and Community in Augustine’s Letters, Oxford University Press, New York 2012, 254 pp. ISBN 9780195372564.

Fil: Correa, Soledad. Universidad Nacional de Rosario

Early Cenozoic Atlantic and Pacific benthic foraminiferal isotopes from 12 sites

Oxygen and carbon isotope records are important tools used to reconstruct past ocean and climate conditions, with those of benthic foraminifera providing information on the deep oceans. Reconstructions are complicated by interspecies isotopic offsets that result from microhabitat preferences (carbonate precipitation in isotopically distinct environments) and vital effects (species-specific metabolic variation in isotopic fractionation). We provide correction factors for early Cenozoic benthic foraminifera commonly used for isotopic measurements (Cibicidoides spp., Nuttallides truempyi, Oridorsalis spp., Stensioina beccariiformis, Hanzawaia ammophila, and Bulimina spp.), showing that most yield reliable isotopic proxies of environmental change. The statistical methods and larger data sets used in this study provide more robust correction factors than do previous studies. Interspecies isotopic offsets appear to have changed through the Cenozoic, either (1) as a result of evolutionary changes or (2) as an artifact of different statistical methods and data set sizes used to determine the offsets in different studies. Regardless of the reason, the assumption that isotopic offsets have remained constant through the Cenozoic has introduced an 1-2°C uncertainty into deep sea paleotemperature calculations. In addition, we compare multiple species isotopic data from a western North Atlantic section that includes the Paleocene-Eocene thermal maximum to determine the most reliable isotopic indicator for this event. We propose that Oridorsalis spp. was the most reliable deepwater isotopic recorder at this location because it was best able to withstand the harsh water conditions that existed at this time; it may be the best recorder at other locations and for other extreme events also.

Correction of systematic errors in Wide Area Multilateration

This work presents a method to estimate and correct slow time-dependent position errors due to non perfect ground station synchronization and tropospheric propagation. It uses opportunity traffic emissions, i.e. signals transmitted from the aircrafts within the coverage zone. This method is used to overcome the difficulty of installing reference beacons simultaneously visible by all the base stations in a given Wide Area Multilateration (WAM) system.

Fast Correction of Tiled Display Systems on Planar Surfaces

A method for fast colour and geometric correction of a tiled display system is presented in this paper. Such kind of displays are a common choice for virtual reality applications and simulators, where a high resolution image is required. They are the cheapest and more flexible alternative for large image generation but they require a precise geometric and colour correction. The purpose of the proposed method is to correct the projection system as fast as possible so in case the system needs to be recalibrated it doesn’t interfere with the normal operation of the simulator or virtual reality application. This technique makes use of a single conventional webcam for both geometric and photometric correction. Some previous assumptions are made, like planar projection surface and negligibleintra-projector colour variation and black-offset levels. If these assumptions hold true, geometric and photometric seamlessness can be achievedfor this kind of display systems. The method described in this paper is scalable for an undefined number of projectors and completely automatic.

Tiled Projector Displays Correction for Dark Scenes in Railway Simulators

Tiled projector displays are a common choice for training simulators, where a high resolution output image is required. They are cheap for the resolution that they can reach and can be configured in many different ways. Nevertheless, such kinds of displays require geometric and color correction so that the composite image looks seamless. Display correction is an even bigger challenge when the projected images include dark scenes combined with brighter scenes. This is usually a problem for railway simulators when the train is positioned inside a tunnel and the black offset effect becomes noticeable. In this paper, a method for fast photometric and geometric correction of tiled display systems where dark and bright scenes are combined is presented. The image correction is carried out in two steps. First, geometric alignment and overlapping areas attenuation for brighter scenes is applied. Second, in the event of being inside a tunnel, the brightness of the scene is increased in certain areas using light sources in order to create the impression of darkness but minimizing the effect of the black offset

Quantitative evaluation of artifact removal in real magnetoencephalogram signals with blind source separation

The magnetoencephalogram (MEG) is contaminated with undesired signals, which are called artifacts. Some of the most important ones are the cardiac and the ocular artifacts (CA and OA, respectively), and the power line noise (PLN). Blind source separation (BSS) has been used to reduce the influence of the artifacts in the data. There is a plethora of BSS-based artifact removal approaches, but few comparative analyses. In this study, MEG background activity from 26 subjects was processed with five widespread BSS (AMUSE, SOBI, JADE, extended Infomax, and FastICA) and one constrained BSS (cBSS) techniques. Then, the ability of several combinations of BSS algorithm, epoch length, and artifact detection metric to automatically reduce the CA, OA, and PLN were quantified with objective criteria. The results pinpointed to cBSS as a very suitable approach to remove the CA. Additionally, a combination of AMUSE or SOBI and artifact detection metrics based on entropy or power criteria decreased the OA. Finally, the PLN was reduced by means of a spectral metric. These findings confirm the utility of BSS to help in the artifact removal for MEG background activity.

Correction of one unstable embankment in Spain

During the years 1992-1996 a climatic change took place in the Iberian Peninsula, changing from dry years to humid years, giving place to numerous and abundant rainfalls that, in the zone of Andalusia caused enough problems in embankments of the roads.