New limits on a cosmological constant from statistics of gravitational lensing

We present new limits on cosmological parameters from the statistics of gravitational lensing, based on the recently revised knowledge of the luminosity function and internal dynamics of E/S0 galaxies that are essential in lensing high-redshift QSOs. We find that the lens models using updated Schechter parameters for such galaxies, derived from the recent redshift surveys combined with morphological classification, are found to give smaller lensing probabilities than earlier calculated. Inconsistent adoption of these parameters from a mixture of various galaxy surveys gives rise to systematic biases in the results. We also show that less compact dwarf-type galaxies which largely dominate the faint part of the Schechter-form luminosity function contribute little to lensing probabilities, so that earlier lens models overestimate incidents of small separation lenses. Applications of the lens models to the existing lens surveys indicate that reproduction of both the lensing probability of optical sources and the image separations of optical and radio lenses is significantly improved in the revised lens models. The likelihood analyses allow us to conclude that a flat universe with Omega=0.3(+0.2-0.1) and Omega+Lambda=1 is most preferable, and a matter-dominated flat universe with Lambda=0 is ruled out at 98 % confidence level. These new limits are unaffected by inclusion of uncertainties in the lens properties.Comment: 30 pages, 9 ps figures, AASTeX, ApJ in pres

Boolean analysis identifies CD38 as a biomarker of aggressive localized prostate cancer.

The introduction of serum Prostate Specific Antigen (PSA) testing nearly 30 years ago has been associated with a significant shift towards localized disease and decreased deaths due to prostate cancer. Recognition that PSA testing has caused over diagnosis and over treatment of prostate cancer has generated considerable controversy over its value, and has spurred efforts to identify prognostic biomarkers to distinguish patients who need treatment from those that can be observed. Recent studies show that cancer is heterogeneous and forms a hierarchy of tumor cell populations. We developed a method of identifying prostate cancer differentiation states related to androgen signaling using Boolean logic. Using gene expression data, we identified two markers, CD38 and ARG2, that group prostate cancer into three differentiation states. Cancers with CD38-, ARG2- expression patterns, corresponding to an undifferentiated state, had significantly lower 10-year recurrence-free survival compared to the most differentiated group (CD38+ARG2+). We carried out immunohistochemical (IHC) staining for these two markers in a single institution (Stanford; n = 234) and multi-institution (Canary; n = 1326) cohorts. IHC staining for CD38 and ARG2 in the Stanford cohort demonstrated that combined expression of CD38 and ARG2 was prognostic. In the Canary cohort, low CD38 protein expression by IHC was significantly associated with recurrence-free survival (RFS), seminal vesicle invasion (SVI), extra-capsular extension (ECE) in univariable analysis. In multivariable analysis, ARG2 and CD38 IHC staining results were not independently associated with RFS, overall survival, or disease-specific survival after adjusting for other factors including SVI, ECE, Gleason score, pre-operative PSA, and surgical margins

State of Utah Space Environment & Contamination Study (SUSpECS) MISSE-6 Payload to Investigate Their Effects on Electron Emission and Resistivity of Spacecraft Materials

A study of the effects of prolonged exposure to the space environment and of charge-enhanced contamination on the electron emission and resistivity of spacecraft materials, the State of Utah Space Environment & Contamination Study (SUSpECS), is planned for flight aboard the MISSE-6 payload. The Materials International Space Station Experiment (MISSE-6) program is designed to characterize the performance of candidate new space materials over the course of approximately four to eight month exposure periods on-orbit on the International Space Station, with a target flight date of mid-2006. The study is conducted by the Utah State University Materials Physics Group, in cooperation with the USU Get-Away Special Program and ATK Thiokol. Electron emission and transport properties of materials are key in determining the likelihood of deleterious spacecraft charging effects and are essential parameters in modeling these effects with engineering tools like NASCAP-2K code. While preliminary ground-based studies have shown that contamination can lead to catastrophic charging effects under certain circumstances, little direct information is presently available on the effects of sample deterioration and contamination on emission properties for materials flown in space. Approximately 40 samples will be mounted on panels on both the ram and wake sides of the ISS. They have been carefully chosen to provide needed information for different ongoing studies and a broad cross-section of prototypical materials used on the exteriors of spacecrafts. Much of the pre-flight testing has already been done in conjunction with previous studies through the NASA Space Environments and Effects Program and other projects. The materials will be tested for resistivity and dielectric strength, and for electron-, ion-, and photon-induced electron emission yield curves and emission spectra. Characterization measurements include optical and electron microscopy, reflection spectroscopy, resistivity and Auger electron spectroscopy. In addition, studies of the service life of composite and ceramic materials of the ATK Thermal Protection Systems and Lightweight Structure System

Reversing Blood Flows Act through klf2a to Ensure Normal Valvulogenesis in the Developing Heart

Heart valve anomalies are some of the most common congenital heart defects, yet neither the genetic nor the epigenetic forces guiding heart valve development are well understood. When functioning normally, mature heart valves prevent intracardiac retrograde blood flow; before valves develop, there is considerable regurgitation, resulting in reversing (or oscillatory) flows between the atrium and ventricle. As reversing flows are particularly strong stimuli to endothelial cells in culture, an attractive hypothesis is that heart valves form as a developmental response to retrograde blood flows through the maturing heart. Here, we exploit the relationship between oscillatory flow and heart rate to manipulate the amount of retrograde flow in the atrioventricular (AV) canal before and during valvulogenesis, and find that this leads to arrested valve growth. Using this manipulation, we determined that klf2a is normally expressed in the valve precursors in response to reversing flows, and is dramatically reduced by treatments that decrease such flows. Experimentally knocking down the expression of this shear-responsive gene with morpholine antisense oligonucleotides (MOs) results in dysfunctional valves. Thus, klf2a expression appears to be necessary for normal valve formation. This, together with its dependence on intracardiac hemodynamic forces, makes klf2a expression an early and reliable indicator of proper valve development. Together, these results demonstrate a critical role for reversing flows during valvulogenesis and show how relatively subtle perturbations of normal hemodynamic patterns can lead to both major alterations in gene expression and severe valve dysgenesis

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

Gene expression response in target organ and whole blood varies as a function of target organ injury phenotype

Histopathology, clinical chemistry, hematology and gene expression data were collected from the rat liver and blood after treatment with eight known hepatotoxins

Pharmacogenetics of telatinib, a VEGFR-2 and VEGFR-3 tyrosine kinase inhibitor, used in patients with solid tumors

Purpose Telatinib is an orally active small-molecule tyrosine kinase inhibitor of kinase insert domain receptor (KDR; VEGFR-2) and fms-related tyrosine kinase 4 (FLT4; VEGFR-3). This study aims at the identification of relationships between single nucleotide polymorphisms (SNPs) in genes encoding for transporter proteins and pharmacokinetic parameters in order to clarify the significant interpatient variability in drug exposure. In addition, the potential relationship between target receptor polymorphisms and toxicity of telatinib is explored. Methods Blood samples from 33 patients enrolled in a phase I dose-escalation study of telatinib were analyzed. For correlation with dose normalized AUC(0–12), ATP-binding cassette (ABC) B1 (ABCB1), ABCC1, and ABCG2 were the genes selected. For correlation with telatinib toxicity, selected genes were the drug target genes KDR and FLT4. Results No association between dose normalized AUC(0–12) and drug transporter protein polymorphisms was observed. In addition, no association between toxicity and KDR or FLT4 genotype or haplotype was seen. Conclusions Our pharmacogenetic analysis could not reveal a correlation between relevant gene polymorphisms and clinical and pharmacokinetic observations of telatinib

Ingestion of marine debris by Wedge-tailed Shearwaters ( Ardenna pacifica ) on Lord Howe Island, Australia during 2005–2018

publisher: Elsevier articletitle: Ingestion of marine debris by Wedge-tailed Shearwaters (Ardenna pacifica) on Lord Howe Island, Australia during 2005–2018 journaltitle: Marine Pollution Bulletin articlelink: https://doi.org/10.1016/j.marpolbul.2018.06.023 content_type: article copyright: © 2018 Elsevier Ltd. All rights reserved.The attached document is the authors’ submitted version of the journal article. You are advised to consult the publisher’s version if you wish to cite from it

VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma

Inactivation of the von Hippel-Lindau (VHL) E3 ubiquitin ligase protein is a hallmark of clear cell renal cell carcinoma (ccRCC). Identifying how pathways affected by VHL loss contribute to ccRCC remains challenging. We used a genome-wide in vitro expression strategy to identify proteins that bind VHL when hydroxylated. Zinc fingers and homeoboxes 2 (ZHX2) was found as a VHL target, and its hydroxylation allowed VHL to regulate its protein stability. Tumor cells from ccRCC patients with VHL loss-of-function mutations usually had increased abundance and nuclear localization of ZHX2. Functionally, depletion of ZHX2 inhibited VHL-deficient ccRCC cell growth in vitro and in vivo. Mechanistically, integrated chromatin immunoprecipitation sequencing and microarray analysis showed that ZHX2 promoted nuclear factor κB activation. These studies reveal ZHX2 as a potential therapeutic target for ccRCC