Technical Progress on the Ares I-X Flight Test

Ares I-X will be NASA's first test flight for a new human-rated launch vehicle since 1981, and the team is well on its way toward completing the vehicle's design and hardware fabrication for an April 2009 launch. This uncrewed suborbital development test flight gives NASA its first opportunities to: gather critical data about the flight dynamics of the integrated launch vehicle; understand how to control its roll during flight; better characterize the stage separation environments during future flight; and demonstrate the first stage recovery system. The Ares I-X Flight Test Vehicle (FTV) incorporates a mix of flight and mockup hardware. It is powered by a four-segment solid rocket booster, and will be modified to include a fifth, spacer segment; the upper stage, Orion crew exploration vehicle, and launch abort system are simulator hardware to make the FTV aerodynamically similar to the same size, shape, and weight of Ares I. The Ares IX first stage includes an existing Shuttle solid rocket motor and thrust vector control system controlled by an Ascent Thrust Vector Controller (ATVC) designed and built by Honeywell International. The avionics system will be tested in a dedicated System Integration Laboratory located at Lockheed Martin Space Systems (LMSS) in Denver, Colorado. The Upper Stage Simulator (USS) is made up of cylindrical segments that will be stacked and integrated at Kennedy Space Center (KSC) for launch. Glenn Research Center is already building these segments, along with their internal access structures. The active Roll Control System (RoCS) includes two thruster units harvested from Peacekeeper missiles. Duty cycle testing for RoCS was conducted, and fuel tanking and detanking tests will occur at KSC in early 2008. This important flight will provide valuable experience for the ground operations team in integrating, stacking, and launching Ares I. Data from Ares I-X will ensure the safety and reliability of America's newest launch vehicle

Hypoxia alters the epigenetic profile in cultured human placental trophoblasts

The mechanisms by which the placenta adapts to exogenous stimuli to create a stable and healthy environment for the growing fetus are not well known. Low oxygen tension influences placental function, and is associated with preeclampsia, a condition displaying altered development of placental trophoblast. We hypothesized that oxygen tension affects villous trophoblast by modulation of gene expression through DNA methylation. We used the Infinium HumanMethylation450 BeadChip array to compare the DNA methylation profile of primary cultures of human cytotrophoblasts and syncytiotrophoblasts under < 1%, 8% and 20% oxygen levels. We found no effect of oxygen tension on average DNA methylation for either cell phenotype, but a set of loci became hypermethylated in cytotrophoblasts exposed for 24 h to < 1% oxygen, as compared with those exposed to 8% or 20% oxygen. Hypermethylation with low oxygen tension was independently confirmed by bisulfite-pyrosequencing in a subset of functionally relevant genes including CD59, CFB, GRAM3 and ZNF217. Intriguingly, 70 out of the 147 CpGs that became hypermethylated in < 1% oxygen overlapped with CpG sites that became hypomethylated upon differentiation of cytotrophoblasts into syncytiotrophoblasts. Furthermore, the preponderance of altered sites was located at AP-1 binding sites. We suggest that AP-1 expression is triggered by hypoxia and interacts with DNA methyltransferases (DNMTs) to target methylation at specific sites in the genome, thus causing suppression of the associated genes that are responsible for differentiation of villous cytotrophoblast to syncytiotrophoblast

Concurrent prescribing of opioids with other sedating medications after cancer diagnosis: a population-level analysis

Purpose: Cancer is a major reason for concurrent prescription of opioids with other sedating medications—particularly benzodiazepines and gabapentinoids—yet population-based assessments of the extent and predictors of concurrent prescribing among clinically and demographically diverse patients with cancer are lacking. Methods: We conducted a retrospective cohort study of patients with non-metastatic cancer using North Carolina cancer registry data linked with Medicare and private insurance claims (2013–2016). We used modified Poisson regression to assess associations of patient characteristic with adjusted relative risk (aRR) of new concurrent prescribing of opioids with benzodiazepines or gabapentinoids after diagnosis. Results: Overall, 15% of patients were concurrently prescribed opioids with benzodiazepines or gabapentinoids. Characteristics independently associated with an increased risk of concurrent prescribing included cancer type (e.g., aRR cervical vs. colorectal cancer: 1.55, 95% CI: 1.12–2.14); prior use of opioids (aRR: 2.43, 95% CI:2.21–2.67), benzodiazepines (aRR: 4.08, 95% CI: 3.72–4.48), or gabapentinoids (3.82, 95% CI: 3.31–4.39), and premorbid mental health conditions, including substance use disorder (aRR: 1.27, 95% CI: 1.05–1.54). Black and Hispanic patients were less likely to experience concurrent prescribing (aRR, Black vs. White: 0.35, 95% CI: 0.15–0.83; aRR, Hispanic vs. White: 0.75, 95% CI: 0.66–0.85). Conclusion: Approximately 1 in 7 patients with cancer was concurrently prescribed opioids with other sedating medications. Associations between patient characteristics and risk of concurrent prescribing highlight predictors of concurrent prescribing and suggest a rationale for systematic assessment of substance use history at diagnosis. Future research could explore inequitable pain and symptom management and investigate risk of adverse medication-related events

Exact Hypersurface-Homogeneous Solutions in Cosmology and Astrophysics

A framework is introduced which explains the existence and similarities of most exact solutions of the Einstein equations with a wide range of sources for the class of hypersurface-homogeneous spacetimes which admit a Hamiltonian formulation. This class includes the spatially homogeneous cosmological models and the astrophysically interesting static spherically symmetric models as well as the stationary cylindrically symmetric models. The framework involves methods for finding and exploiting hidden symmetries and invariant submanifolds of the Hamiltonian formulation of the field equations. It unifies, simplifies and extends most known work on hypersurface-homogeneous exact solutions. It is shown that the same framework is also relevant to gravitational theories with a similar structure, like Brans-Dicke or higher-dimensional theories.Comment: 41 pages, REVTEX/LaTeX 2.09 file (don't use LaTeX2e !!!) Accepted for publication in Phys. Rev.

MET-receptor targeted fluorescent imaging and spectroscopy to detect multifocal papillary thyroid cancer

Purpose: Multifocal disease in PTC is associated with an increased recurrence rate. Multifocal disease (MD) is underdiagnosed with the current gold standard of pre-operative ultrasound staging. Here, we evaluate the use of EMI-137 targeted molecular fluorescence-guided imaging (MFGI) and spectroscopy as a tool for the intra-operative detection of uni- and multifocal papillary thyroid cancer (PTC) aiming to improve disease staging and treatment selection. Methods: A phase-1 study (NCT03470259) with EMI-137 was conducted to evaluate the possibility of detecting PTC using MFGI and quantitative fiber-optic spectroscopy. Results: Fourteen patients underwent hemi- or total thyroidectomy (TTX) after administration of 0.09 mg/kg (n = 1), 0.13 mg/kg (n = 8), or 0.18 mg/kg (n = 5) EMI-137. Both MFGI and spectroscopy could differentiate PTC from healthy thyroid tissue after administration of EMI-137, which binds selectively to MET in PTC. 0.13 mg/kg was the lowest dosage EMI-137 that allowed for differentiation between PTC and healthy thyroid tissue. The smallest PTC focus detected by MFGI was 1.4 mm. MFGI restaged 80% of patients from unifocal to multifocal PTC compared to ultrasound. Conclusion: EMI-137-guided MFGI and spectroscopy can be used to detect multifocal PTC. This may improve disease staging and treatment selection between hemi- and total thyroidectomy by better differentiation between unifocal and multifocal disease. Trial registration: NCT03470259.</p

Photoproduction of D∗±D^{*\pm} mesons associated with a leading neutron

The photoproduction of $D^{*\pm} (2010)$ mesons associated with a leading neutron has been observed with the ZEUS detector in $ep$ collisions at HERA using an integrated luminosity of 80 pb$^{-1}$. The neutron carries a large fraction, {$x_L>0.2$}, of the incoming proton beam energy and is detected at very small production angles, {$\theta_n<0.8$ mrad}, an indication of peripheral scattering. The $D^*$ meson is centrally produced with pseudorapidity {$|\eta| 1.9$ GeV}, which is large compared to the average transverse momentum of the neutron of 0.22 GeV. The ratio of neutron-tagged to inclusive $D^*$ production is $8.85\pm 0.93({\rm stat.})^{+0.48}_{-0.61}({\rm syst.})\%$ in the photon-proton center-of-mass energy range {$130 <W<280$ GeV}. The data suggest that the presence of a hard scale enhances the fraction of events with a leading neutron in the final state.Comment: 28 pages, 4 figures, 2 table

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

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