Treatment Strategy with Gene Editing for Late-onset Retinal Degeneration Caused by a Founder Variant in C1QTNF5

AbstractPurpose: Genome editing is an emerging group of technologies with the potential to ameliorate dominant, monogenic human diseases such as late-onset retinal degeneration (L-ORD). The goal of this study was to identify disease stages and retinal locations optimal for evaluating the efficacy of a future genome editing trial.Methods: Twenty five L-ORD patients (age range, 33-77 years; median age, 59 years) harboring the founder variant S163R in C1QTNF5 were enrolled from three centers in the United Kingdom and United States. Patients were examined with widefield optical coherence tomography (OCT) and chromatic perimetry under dark-adapted and light-adapted conditions to derive phenomaps of retinal disease. Results were analyzed with a model of a shared natural history of a single delayed exponential across all subjects and all retinal locations.Results: Critical age for the initiation of photoreceptor loss ranged from 48 years at the temporal paramacular retina to 74 years at the inferior midperipheral retina. Subretinal deposits (sRET-Ds) became more prevalent as critical age was approached. Subretinal pigment epithelial deposits (sRPE-Ds) were detectable in the youngest patients showing no other structural or functional abnormalities at the retina. The sRPE-D thickness continuously increased, reaching 25 µm in the extrafoveal retina and 19 µm in the fovea at critical age. Loss of light sensitivity preceded shortening of outer segments and loss of photoreceptors by more than a decade.Conclusions: Retinal regions providing an ideal treatment window exist across all severity stages of L-ORD

Measurement of the p-pbar -> Wgamma + X cross section at sqrt(s) = 1.96 TeV and WWgamma anomalous coupling limits

The WWgamma triple gauge boson coupling parameters are studied using p-pbar -> l nu gamma + X (l = e,mu) events at sqrt(s) = 1.96 TeV. The data were collected with the DO detector from an integrated luminosity of 162 pb^{-1} delivered by the Fermilab Tevatron Collider. The cross section times branching fraction for p-pbar -> W(gamma) + X -> l nu gamma + X with E_T^{gamma} > 8 GeV and Delta R_{l gamma} > 0.7 is 14.8 +/- 1.6 (stat) +/- 1.0 (syst) +/- 1.0 (lum) pb. The one-dimensional 95% confidence level limits on anomalous couplings are -0.88 < Delta kappa_{gamma} < 0.96 and -0.20 < lambda_{gamma} < 0.20.Comment: Submitted to Phys. Rev. D Rapid Communication

Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt{s} = 1.96 TeV using Kinematic Characteristics of Lepton + Jets Events

We present a measurement of the top quark pair ttbar production cross section in ppbar collisions at a center-of-mass energy of 1.96 TeV using 230 pb**{-1} of data collected by the DO detector at the Fermilab Tevatron Collider. We select events with one charged lepton (electron or muon), large missing transverse energy, and at least four jets, and extract the ttbar content of the sample based on the kinematic characteristics of the events. For a top quark mass of 175 GeV, we measure sigma(ttbar) = 6.7 {+1.4-1.3} (stat) {+1.6- 1.1} (syst) +/-0.4 (lumi) pb, in good agreement with the standard model prediction.Comment: submitted to Phys.Rev.Let

Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt(s)=1.96 TeV using Lepton + Jets Events with Lifetime b-tagging

We present a measurement of the top quark pair ($t\bar{t}$) production cross section ($\sigma_{t\bar{t}}$) in $p\bar{p}$ collisions at $\sqrt{s}=1.96$ TeV using 230 pb$^{-1}$ of data collected by the D0 experiment at the Fermilab Tevatron Collider. We select events with one charged lepton (electron or muon), missing transverse energy, and jets in the final state. We employ lifetime-based b-jet identification techniques to further enhance the $t\bar{t}$ purity of the selected sample. For a top quark mass of 175 GeV, we measure $\sigma_{t\bar{t}}=8.6^{+1.6}_{-1.5}(stat.+syst.)\pm 0.6(lumi.)$ pb, in agreement with the standard model expectation.Comment: 7 pages, 2 figures, 3 tables Submitted to Phys.Rev.Let

Search for single top quark production in ppbar collisions at sqrt(s)=1.96 TeV

We present a search for electroweak production of single top quarks in the s-channel and t-channel using neural networks for signal-background separation. We have analyzed 230 pb$^{-1}$ of data collected with the D0 detector at the Fermilab Tevatron Collider at a center-of-mass energy of 1.96 TeV and find no evidence for a single top quark signal. The resulting 95% confidence level upper limits on the single top quark production cross sections are 6.4 pb in the s-channel and 5.0 pb in the t-channel.Comment: 9 pages, 4 figure

Measurement of the WW production cross section in p anti-p collisions at s**(1/2) = 1.96 TeV

We present a measurement of the W boson pair-production cross section in p anti-p collisions at a center-of-mass energy of sqrt{s}=1.96 TeV. The data, collected with the Run II DO detector, correspond to an integrated luminosity of 224-252 pb^-1 depending on the final state (ee, emu or mumu). We observe 25 candidates with a background expectation of 8.1+/-0.6(stat)+/-0.6(syst)+/-0.5(lum) events. The probability for an upward fluctuation of the background to produce the observed signal is 2.3x10^-7, equivalent to 5.2 standard deviations.The measurement yields a cross section of 13.8+4.3/-3.8(stat)+1.2/-0.9(syst)+/-0.9(lum) pb, in agreement with predictions from the standard model.Comment: submitted to PR

Measurement of the Lambda^0_b lifetime in the decay Lambda^0_b -> J/psi Lambda^0 with the D0 Detector

We present measurements of the Lambda^0_b lifetime in the exclusive decay channel Lambda^0_{b}->J/psi Lambda^0, with J/psi to mu+ mu- and Lambda^0 to p pi-, the B^0 lifetime in the decay B^0 -> J/psi K^0_S with J/psi to mu+ mu- and K^0_S to pi+ pi-, and the ratio of these lifetimes. The analysis is based on approximately 250 pb^{-1} of data recorded with the D0 detector in pp(bar) collisions at sqrt{s}=1.96 TeV. The Lambda^0_b lifetime is determined to be tau(Lambda^0_b) = 1.22 +0.22/-0.18 (stat) +/- 0.04 (syst) ps, the B^0 lifetime tau(B^0) = 1.40 +0.11/-0.10 (stat) +/- 0.03 (syst) ps, and the ratio tau(Lambda^0_b)/tau(B^0) = 0.87 +0.17/-0.14 (stat) +/- 0.03 (syst). In contrast with previous measurements using semileptonic decays, this is the first determination of the Lambda^0_b lifetime based on a fully reconstructed decay channel.Comment: 7 pages, 4 figures, Submitted to Physical Review Letters, v2: Added FNAL Pub-numbe

Erratum to Measurement of σ(ppˉ→Z)⋅Br(Z→ττ)\sigma (p \bar p \to Z) \cdot Br(Z \to \tau\tau) at s=\bm{\sqrt{s}=}1.96 TeV, published in Phys. Rev. D {71}, 072004 (2005)

A change in estimated integrated luminosity (from 226 pb$^{-1} to 257 pb$^{-1}$leads to a corrected value for${\sigma (p \bar p \to Z) \cdot}$Br${(Z \to \tau \tau)}$of$209\pm13(stat.)\pm16(syst.)\pm13(lum) pb

The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

Renal cell carcinoma(RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival