Dynein-Dynactin Complex Is Essential for Dendritic Restriction of TM1-Containing Drosophila Dscam

BACKGROUND: Many membrane proteins, including Drosophila Dscam, are enriched in dendrites or axons within neurons. However, little is known about how the differential distribution is established and maintained. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated the mechanisms underlying the dendritic targeting of Dscam[TM1]. Through forward genetic mosaic screens and by silencing specific genes via targeted RNAi, we found that several genes, encoding various components of the dynein-dynactin complex, are required for restricting Dscam[TM1] to the mushroom body dendrites. In contrast, compromising dynein/dynactin function did not affect dendritic targeting of two other dendritic markers, Nod and Rdl. Tracing newly synthesized Dscam[TM1] further revealed that compromising dynein/dynactin function did not affect the initial dendritic targeting of Dscam[TM1], but disrupted the maintenance of its restriction to dendrites. CONCLUSIONS/SIGNIFICANCE: The results of this study suggest multiple mechanisms of dendritic protein targeting. Notably, dynein-dynactin plays a role in excluding dendritic Dscam, but not Rdl, from axons by retrograde transport

Defining a standard set of patient-centered outcomes for men with localized prostate cancer

Background Value-based health care has been proposed as a unifying force to drive improved outcomes and cost containment. Objective To develop a standard set of multidimensional patient-centered health outcomes for tracking, comparing, and improving localized prostate cancer (PCa) treatment value. Design, setting, and participants We convened an international working group of patients, registry experts, urologists, and radiation oncologists to review existing data and practices. Outcome measurements and statistical analysis The group defined a recommended standard set representing who should be tracked, what should be measured and at what time points, and what data are necessary to make meaningful comparisons. Using a modified Delphi method over a series of teleconferences, the group reached consensus for the Standard Set. Results and limitations We recommend that the Standard Set apply to men with newly diagnosed localized PCa treated with active surveillance, surgery, radiation, or other methods. The Standard Set includes acute toxicities occurring within 6 mo of treatment as well as patient-reported outcomes tracked regularly out to 10 yr. Patient-reported domains of urinary incontinence and irritation, bowel symptoms, sexual symptoms, and hormonal symptoms are included, and the recommended measurement tool is the Expanded Prostate Cancer Index Composite Short Form. Disease control outcomes include overall, cause-specific, metastasis-free, and biochemical relapse-free survival. Baseline clinical, pathologic, and comorbidity information is included to improve the interpretability of comparisons. Conclusions We have defined a simple, easily implemented set of outcomes that we believe should be measured in all men with localized PCa as a crucial first step in improving the value of care. Patient summary Measuring, reporting, and comparing identical outcomes across treatments and treatment centers will provide patients and providers with information to make informed treatment decisions. We defined a set of outcomes that we recommend being tracked for every man being treated for localized prostate cancer

First measurement of the muon neutrino charged current single pion production cross section on water with the T2K near detector

The T2K off-axis near detector, ND280, is used to make the first differential cross section measurements of muon neutrino charged current single positive pion production on a water target at energies ∼0.8 GeV. The differential measurements are presented as a function of the muon and pion kinematics, in the restricted phase space defined by pπþ > 200 MeV=c, pμ > 200 MeV=c, cosðθπþ Þ > 0.3 and cosðθμÞ > 0.3. The total flux integrated νμ charged current single positive pion production cross section on water in the restricted phase space is measured to be hσiϕ ¼ 4.25 0.48ðstatÞ 1.56ðsystÞ × 10−40 cm2=nucleon. The total cross section is consistent with the NEUT prediction (5.03 × 10−40 cm2=nucleon) and 2σ lower than the GENIE prediction (7.68 × 10−40 cm2=nucleon). The differential cross sections are in good agreement with the NEUT generator. The GENIE simulation reproduces well the shapes of the distributions, but overestimates the overall cross section normalization

Updated T2K measurements of muon neutrino and antineutrino disappearance using 1.5 x 10(21) protons on target

We report measurements by the T2K experiment of the parameters $\theta_{23}$ and $\Delta m^{2}_{32}$ governing the disappearance of muon neutrinos and antineutrinos in the three flavor neutrino oscillation model. Utilizing the ability of the experiment to run with either a mainly neutrino or a mainly antineutrino beam, the parameters are measured separately for neutrinos and antineutrinos. Using $7.482 \times 10^{20}$ POT in neutrino running mode and $7.471 \times 10^{20}$ POT in antineutrino mode, T2K obtained, $\sin^{2}(\theta_{23})=0.51^{+0.08}_{-0.07}$ and $\Delta m^{2}_{32} = 2.53^{+0.15}_{-0.13} \times 10^{-3}$eV$^{2}$/c$^{4}$ for neutrinos, and $\sin^{2}({\overline{\theta}}_{23})=0.42^{+0.25}_{-0.07}$ and ${\Delta\overline{m}^2}_{32} = 2.55^{+0.33}_{-0.27} \times 10^{-3}$eV$^{2}$/c$^{4}$ for antineutrinos (assuming normal mass ordering). No significant differences between the values of the parameters describing the disappearance of muon neutrinos and antineutrinos were observed.Comment: 8 pages, 2 figure

Search for Lorentz and CPT violation using sidereal time dependence of neutrino flavor transitions over a short baseline

A class of extensions of the Standard Model allows Lorentz and CPT violations, which can be identified by the observation of sidereal modulations in the neutrino interaction rate. A search for such modulations was performed using the T2K on-axis near detector. Two complementary methods were used in this study, both of which resulted in no evidence of a signal. Limits on associated Lorentz and CPT-violating terms from the Standard Model extension have been derived by taking into account their correlations in this model for the first time. These results imply such symmetry violations are suppressed by a factor of more than 10 20 at the GeV scale

Measurement of the single pi(0) production rate in neutral current neutrino interactions on water

The single π0 production rate in neutral current neutrino interactions on water in a neutrino beam with a peak neutrino energy of 0.6 GeV has been measured using the PØD, one of the subdetectors of the T2K near detector. The production rate was measured for data taking periods when the PØD contained water (2.64×10(20) protons-on-target) and also periods without water (3.49×10(20) protons-on-target). A measurement of the neutral current single π0 production rate on water is made using appropriate subtraction of the production rate with water in from the rate with water out of the target region. The subtraction analysis yields 106 ± 41 ± 69 signal events where the uncertainties are statistical (stat.) and systematic (sys.) respectively. This is consistent with the prediction of 157 events from the nominal simulation. The measured to expected ratio is 0.68 ± 0.26 (stat) ± 0.44 (sys) ± 0.12 (flux). The nominal simulation uses a flux integrated cross section of 7.63×10(−39)cm(2) per nucleon with an average neutrino interaction energy of 1.3 GeV

First Measurement of the Muon Neutrino Charged Current Single Pion Production Cross Section on Water with the T2K Near Detector

The T2K off-axis near detector, ND280, is used to make the first differential cross section measurements of muon neutrino charged current single positive pion production on a water target at energies ${\sim}0.8$ GeV. The differential measurements are presented as a function of muon and pion kinematics, in the restricted phase-space defined by $p_{\pi^+}>200$MeV/c, $p_{\mu^-}>200$MeV/c, $\cos \theta_{\pi^+}>0.3$ and $\cos \theta_{\mu^-}>0.3$. The total flux integrated $\nu_\mu$ charged current single positive pion production cross section on water in the restricted phase-space is measured to be $\langle\sigma\rangle_\phi=4.25\pm0.48 (\mathrm{stat})\pm1.56 (\mathrm{syst})\times10^{-40} \mathrm{cm}^{2}/\mathrm{nucleon}$. The total cross section is consistent with the NEUT prediction ($5.03\times10^{-40} \mathrm{cm}^{2}/\mathrm{nucleon}$) and 2$\sigma$ lower than the GENIE prediction ($7.68\times10^{-40} \mathrm{cm}^{2}/\mathrm{nucleon}$). The differential cross sections are in good agreement with the NEUT generator. The GENIE simulation reproduces well the shapes of the distributions, but over-estimates the overall cross section normalization

Measurement of Coherent pi(+) Production in Low Energy Neutrino-Carbon Scattering

International audienceWe report the first measurement of the flux-averaged cross section for charged current coherent π+ production on carbon for neutrino energies less than 1.5 GeV to a restricted final state phase space region in the T2K near detector, ND280. Comparisons are made with predictions from the Rein-Sehgal coherent production model and the model by Alvarez-Ruso {\it et al.}, the latter representing the first implementation of an instance of the new class of microscopic coherent models in a neutrino interaction Monte Carlo event generator. This results contradicts the null results reported by K2K and SciBooNE in a similar neutrino energy region