The potential of antisense oligonucleotide therapies for inherited childhood lung diseases

Antisense oligonucleotides are an emerging therapeutic option to treat diseases with known genetic origin. In the age of personalised medicines, antisense oligonucleotides can sometimes be designed to target and bypass or overcome a patient’s genetic mutation, in particular those lesions that compromise normal pre-mRNA processing. Antisense oligonucleotides can alter gene expression through a variety of mechanisms as determined by the chemistry and antisense oligomer design. Through targeting the pre-mRNA, antisense oligonucleotides can alter splicing and induce a specific spliceoform or disrupt the reading frame, target an RNA transcript for degradation through RNaseH activation, block ribosome initiation of protein translation or disrupt miRNA function. The recent accelerated approval of eteplirsen (renamed Exondys 51™) by the Food and Drug Administration, for the treatment of Duchenne muscular dystrophy, and nusinersen, for the treatment of spinal muscular atrophy, herald a new and exciting era in splice-switching antisense oligonucleotide applications to treat inherited diseases. This review considers the potential of antisense oligonucleotides to treat inherited lung diseases of childhood with a focus on cystic fibrosis and disorders of surfactant protein metabolism

An Exact Diagonalization Demonstration of Incommensurability and Rigid Band Filling for N Holes in the t-J Model

We have calculated S(q) and the single particle distribution function for N holes in the t - J model on a non--square sqrt{8} X sqrt{32} 16--site lattice with periodic boundary conditions; we justify the use of this lattice in compariosn to those of having the full square symmetry of the bulk. This new cluster has a high density of vec k points along the diagonal of reciprocal space, viz. along k = (k,k). The results clearly demonstrate that when the single hole problem has a ground state with a system momentum of vec k = (pi/2,pi/2), the resulting ground state for N holes involves a shift of the peak of the system's structure factor away from the antiferromagnetic state. This shift effectively increases continuously with N. When the single hole problem has a ground state with a momentum that is not equal to k = (pi/2,pi/2), then the above--mentioned incommensurability for N holes is not found. The results for the incommensurate ground states can be understood in terms of rigid--band filling: the effective occupation of the single hole k = (pi/2,pi/2) states is demonstrated by the evaluation of the single particle momentum distribution function . Unlike many previous studies, we show that for the many hole ground state the occupied momentum states are indeed k = (+/- pi/2,+/- pi/2) states.Comment: Revtex 3.0; 23 pages, 1 table, and 13 figures, all include

Spin dependence in high pT2p^{2}_{T} elastic pp and np scattering

Using the polarized proton capability of the Argonne ZGS the authors recently made 90 degrees /sub cm/ measurements of elastic pp scattering from 6 to 11.75 GeV/c, determining the parallel and anti- parallel pure initial spin state cross sections and the associated spin-spin parameter A/sub nn/ with the spins normal to the scattering plane. They find that the parallel to anti-parallel cross section ratio rises dramatically from 1.2+or-.06 at p/sub t//sup 2/=3.3 (GeV /c)/sup 2/ to 3.2+or-.4 at 4.8 (GeV/c)/sup 2/, similar to the p/sub T //sup 2/ dependence previously observed at the fixed laboratory momentum of 11.75 GeV/c. They have also extended the measurements at 6 GeV/c and find that A/sub nn/ has a small but sharp rise at 90 degrees /sub cm/. In addition a month of 12 GeV/c polarized deuteron acceleration in the ZGS enabled them to measure two A/sub nn/ at two points at 6 GeV/c for np elastic scattering: A/sub nn/=-.17+or-.04 at p/sub T//sup 2/=.8, A/sub nn/=-.19+or-.05 at P/sub T//sup 2/=1.0. These values are opposite in sign from the pp results at the same momentum. (4 refs)

Creation and impact of containment units with high-risk zones during the coronavirus disease 2019 (COVID-19) pandemic

Background: The rapid spread of coronavirus disease 2019 (COVID-19) required swift preparation to protect healthcare personnel (HCP) and patients, especially considering shortages of personal protective equipment (PPE). Due to the lack of a pre-existing biocontainment unit, we needed to develop a novel approach to placing patients in isolation cohorts while working with the pre-existing physical space. Objectives: To prevent disease transmission to non–COVID-19 patients and HCP caring for COVID-19 patients, to optimize PPE usage, and to provide a comfortable and safe working environment. Methods: An interdisciplinary workgroup developed a combination of approaches to convert existing spaces into COVID-19 containment units with high-risk zones (HRZs). We developed standard workflow and visual management in conjunction with updated staff training and workflows. The infection prevention team created PPE standard practices for ease of use, conservation, and staff safety. Results: The interventions resulted in 1 possible case of patient-to-HCP transmission and zero cases of patient-to-patient transmission. PPE usage decreased with the HRZ model while maintaining a safe environment of care. Staff on the COVID-19 units were extremely satisfied with PPE availability (76.7%) and efforts to protect them from COVID-19 (72.7%). Moreover, 54.8% of HCP working in the COVID-19 unit agreed that PPE monitors played an essential role in staff safety. Conclusions: The HRZ model of containment unit is an effective method to prevent the spread of COVID-19 with several benefits. It is easily implemented and scaled to accommodate census changes. Our experience suggests that other institutions do not need to modify existing physical structures to create similarly protective spaces

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters