Synthetic long non-coding RNAs [SINEUPs] rescue defective gene expression in vivo

Non-coding RNAs provide additional regulatory layers to gene expression as well as the potential to being exploited as therapeutic tools. Non-coding RNA-based therapeutic approaches have been attempted in dominant diseases, however their use for treatment of genetic diseases caused by insufficient gene dosage is currently more challenging. SINEUPs are long antisense non-coding RNAs that up-regulate translation in mammalian cells in a gene-specific manner, although, so far evidence of SINEUP efficacy has only been demonstrated in in vitro systems. We now show that synthetic SINEUPs effectively and specifically increase protein levels of a gene of interest in vivo. We demonstrated that SINEUPs rescue haploinsufficient gene dosage in a medakafish model of a human disorder leading to amelioration of the disease phenotype. Our results demonstrate that SINEUPs act through mechanisms conserved among vertebrates and that SINEUP technology can be successfully applied in vivo as a new research and therapeutic tool for gene-specific up-regulation of endogenous functional proteins

Signals for strange quark contributions to the neutrino (antineutrino) scattering in quasi-elastic region

Strange quark contributions to the neutrino (antineutrino) scattering are investigated on the elastic neutrino-nucleon scattering and the neutrino-nucleus scattering for 12C target in the quasi-elastic region on the incident energy of 500 MeV, within the framework of a relativistic single particle model. For the neutrino-nucleus scattering, the effects of final state interaction for the knocked-out nucleon are included by a relativistic optical potential. In the cross sections we found some cancellations of the strange quark contributions between the knocked-out protons and neutrons. Consequently, the asymmetries between the incident neutrino and antineutrino which is the ratio of neutral current to charged current, and the difference between the asymmetries are shown to be able to yield more feasible quantities for the strangeness effects. In order to explicitly display importance of the cancellations, results of the exclusive reaction 16O(\nu, \nu' p) are additionally presented for detecting the strangeness effects.Comment: 14 pages, 8 figures, submitted to Phys. Lett.

Evaluation of analytical performance and comparison of clinical results of the new generation method AccuTnI+3 for the measurement of cardiac troponin I using both patients and quality control plasma samples

The study aims are to evaluate the analytical performance and the clinical results of the chemiluminescent Access AccuTnI+3 immunoassay for the determination of cardiac troponin I (cTnI)with DxI 800 and Access2 platforms and to compare the clinical results obtained with this method with those of three cTnI immunoassays, recently introduced in the European market. The limits of blank (LoB), detection (LoD), and quantitation (LoQ) at 20% CV and 10% CV were 4.5 ng/L and 10.9 ng/L, 17.1 and 30.4 ng/L, respectively. The results of STAT Architect high Sensitive TnI (Abbott Diagnostics), ADVIA Centaur Troponin I Ultra (Siemens Healthcare Diagnostics), ST AIA-Pack cTnI third generation (Tosoh Bioscience), and Access AccuTnI + 3 (Beckman Coulter Diagnostics) showed very close correlations (R ranging from 0.901 to 0.994) in 122 samples of patients admitted to the emergency department. However, on average there was a difference up to 2.4-fold between the method measuring the highest (ADVIA method) and lowest cTnI values (AccuTnI + 3 method). The consensus mean values between methods ranged from 6.2% to 29.6% in 18 quality control samples distributed in an external quality control study (cTnI concentrations ranging from 29.3 ng/L to 1557.5 ng/L). In conclusion, the results of our analytical evaluation concerning the AccuTnI + 3 method, using the DxI platform, are well in agreement with those suggested by the manufacturer as well as those reported by some recent studies using the Access2 platform. Our results confirm that the AccuTnI + 3 method for the Access2 and DxI 800 platforms is a clinically usable method for cTnI measurement

Cardiac resynchronization therapy after coronary sinus lead extraction: feasibility and mid-term outcome of transvenous reimplantation in a tertiary referral centre

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Neutrino tomography - Learning about the Earth's interior using the propagation of neutrinos

Because the propagation of neutrinos is affected by the presence of Earth matter, it opens new possibilities to probe the Earth's interior. Different approaches range from techniques based upon the interaction of high energy (above TeV) neutrinos with Earth matter, to methods using the MSW effect on the neutrino oscillations of low energy (MeV to GeV) neutrinos. In principle, neutrinos from many different sources (sun, atmosphere, supernovae, beams etc.) can be used. In this talk, we summarize and compare different approaches with an emphasis on more recent developments. In addition, we point out other geophysical aspects relevant for neutrino oscillations.Comment: 22 pages, 9 figures. Proceedings of ``Neutrino sciences 2005: Neutrino geophysics'', December 14-16, 2005, Honolulu, USA. Minor changes, some references added. Final version to appear in Earth, Moon, and Planet

Hemodynamic and EEG Time-Courses During Unilateral Hand Movement in Patients with Cortical Myoclonus. An EEG-fMRI and EEG-TD-fNIRS Study.

Multimodal human brain mapping has been proposed as an integrated approach capable of improving the recognition of the cortical correlates of specific neurological functions. We used simultaneous EEG-fMRI (functional magnetic resonance imaging) and EEG-TD-fNIRS (time domain functional near-infrared spectroscopy) recordings to compare different hemodynamic methods with changes in EEG in ten patients with progressive myoclonic epilepsy and 12 healthy controls. We evaluated O(2)Hb, HHb and Blood oxygen level-dependent (BOLD) changes and event-related desynchronization/synchronization (ERD/ERS) in the alpha and beta bands of all of the subjects while they performed a simple motor task. The general linear model was used to obtain comparable fMRI and TD-fNIRS activation maps. We also analyzed cortical thickness in order to evaluate any structural changes. In the patients, the TD-NIRS and fMRI data significantly correlated and showed a significant lessening of the increase in O(2)Hb and the decrease in BOLD. The post-movement beta rebound was minimal or absent in patients. Cortical thickness was moderately reduced in the motor area of the patients and correlated with the reduction in the hemodynamic signals. The fMRI and TD-NIRS results were consistent, significantly correlated and showed smaller hemodynamic changes in the patients. This finding may be partially attributable to mild cortical thickening. However, cortical hyperexcitability, which is known to generate myoclonic jerks and probably accounts for the lack of EEG beta-ERS, did not reflect any increased energy requirement. We hypothesize that this is due to a loss of inhibitory neuronal components that typically fire at high frequencies

Working Group Report: Neutrino and Astroparticle Physics

This is the report of neutrino and astroparticle physics working group at WHEPP-8. We present the discussions carried out during the workshop on selected topics in the above fields and also indicate progress made subsequently. The neutrino physics subgroup studied the possibilites of constraining neutrino masses, mixing and CPT violation in lepton sector from future experiments. Neutrino mass models in the context of abelian horizontal symmetries, warped extra dimensions and in presence of triplet Higgs were studied. Effect of threshold corrections on radiative magnification of mixing angles was investigated. The astroparticle physics subgroup focused on how various particle physics inputs affect the CMBR fluctuation spectrum, and on brane cosmology. This report also contains an introduction on how to use the publicly available code CMBFAST to calculate the CMBR fluctuations.Comment: Prepared for the 8th Workshop on High-Energy Physics Phenomenology (WHEPP-8), IIT Mumbai, India, 5-16 Jan 200

Acellular dermal matrix and coronally advanced flap or tunnel technique in the treatment of multiple adjacent gingival recessions. A 12-year follow-up from a randomized clinical trial

AimTo evaluate the long-term outcomes of Acellular Dermal Matrix (ADM) with Coronally Advanced Flap (CAF) or Tunnel technique (TUN) in the treatment of multiple adjacent gingival recessions (MAGRs).Material and methodsNineteen of the original 24 patients contributing to a total number of 33 sites for CAF and 34 for TUN were available for the 12 years follow-up examination. Recession depth, mean root coverage (mRC), keratinized tissue width (KTW), gingival thickness (GT) were evaluated and compared with baseline values and 6-months results. Regression analysis was performed to identify factors related to the stability of the gingival margin.ResultsA highly significant drop in mRC was observed for both groups from the 6 months timepoint to the 12 years recall (p  .05). KTW - 2 mm and GT - 1.2 mm at 6-months were two predictors for stability of the gingival margin (p = .03 and p = .01, respectively).ConclusionsA significant relapse of the gingival margin of MAGRs treated with CAF or TUN + ADM was observed after 12 years.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151340/1/jcpe13163_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151340/2/jcpe13163.pd

Comparison of large-angle production of charged pions with incident protons on cylindrical long and short targets

The HARP collaboration has presented measurements of the double-differential pi+/pi- production cross-section in the range of momentum 100 MeV/c <= p 800 MeV/c and angle 0.35 rad <= theta <= 2.15 rad with proton beams hitting thin nuclear targets. In many applications the extrapolation to long targets is necessary. In this paper the analysis of data taken with long (one interaction length) solid cylindrical targets made of carbon, tantalum and lead is presented. The data were taken with the large acceptance HARP detector in the T9 beam line of the CERN PS. The secondary pions were produced by beams of protons with momenta 5 GeV/c, 8 GeV/c and 12 GeV/c. The tracking and identification of the produced particles were performed using a small-radius cylindrical time projection chamber (TPC) placed inside a solenoidal magnet. Incident protons were identified by an elaborate system of beam detectors. Results are obtained for the double-differential yields per target nucleon d2 sigma / dp dtheta. The measurements are compared with predictions of the MARS and GEANT4 Monte Carlo simulations.Comment: 43 pages, 20 figure

Large-angle production of charged pions by 3 GeV/c - 12 GeV/c protons on carbon, copper and tin targets

A measurement of the double-differential $\pi^{\pm}$ production cross-section in proton--carbon, proton--copper and proton--tin collisions in the range of pion momentum 100 \MeVc \leq p < 800 \MeVc and angle 0.35 \rad \le \theta <2.15 \rad is presented. The data were taken with the HARP detector in the T9 beam line of the CERN PS. The pions were produced by proton beams in a momentum range from 3 \GeVc to 12 \GeVc hitting a target with a thickness of 5% of a nuclear interaction length. The tracking and identification of the produced particles was done using a small-radius cylindrical time projection chamber (TPC) placed in a solenoidal magnet. An elaborate system of detectors in the beam line ensured the identification of the incident particles. Results are shown for the double-differential cross-sections at four incident proton beam momenta (3 \GeVc, 5 \GeVc, 8 \GeVc and 12 \GeVc)