Targeting Androgen Receptor Aberrations in Castration-Resistant Prostate Cancer.

Androgen receptor (AR) splice variants (SV) have been implicated in the development of metastatic castration-resistant prostate cancer and resistance to AR targeting therapies, including abiraterone and enzalutamide. Agents targeting AR-SV are urgently needed to test this hypothesis and further improve the outcome of patients suffering from this lethal disease. Clin Cancer Res; 22(17); 4280-2. ©2016 AACRSee related article by Yang et al., p. 4466

Heterogeneous ice nucleation on dust particles sourced from nine deserts worldwide - Part 1: Immersion freezing

Desert dust is one of the most abundant ice nucleating particle types in the atmosphere. Traditionally, clay minerals were assumed to determine the ice nucleation ability of desert dust and constituted the focus of ice nucleation studies over several decades. Recently some feldspar species were identified to be ice active at much higher temperatures than clay minerals, redirecting studies to investigate the contribution of feldspar to ice nucleation on desert dust. However, so far no study has shown the atmospheric relevance of this mineral phase. For this study four dust samples were collected after airborne transport in the troposphere from the Sahara to different locations (Crete, the Peloponnese, Canary Islands, and the Sinai Peninsula). Additionally, 11 dust samples were collected from the surface from nine of the biggest deserts worldwide. The samples were used to study the ice nucleation behavior specific to different desert dusts. Furthermore, we investigated how representative surface-collected dust is for the atmosphere by comparing to the ice nucleation activity of the airborne samples. We used the IMCA-ZINC setup to form droplets on single aerosol particles which were subsequently exposed to temperatures between 233 and 250 K. Dust particles were collected in parallel on filters for offline cold-stage ice nucleation experiments at 253–263 K. To help the interpretation of the ice nucleation experiments the mineralogical composition of the dusts was investigated. We find that a higher ice nucleation activity in a given sample at 253 K can be attributed to the K-feldspar content present in this sample, whereas at temperatures between 238 and 245 K it is attributed to the sum of feldspar and quartz content present. A high clay content, in contrast, is associated with lower ice nucleation activity. This confirms the importance of feldspar above 250 K and the role of quartz and feldspars determining the ice nucleation activities at lower temperatures as found by earlier studies for monomineral dusts. The airborne samples show on average a lower ice nucleation activity than the surface-collected ones. Furthermore, we find that under certain conditions milling can lead to a decrease in the ice nucleation ability of polymineral samples due to the different hardness and cleavage of individual mineral phases causing an increase of minerals with low ice nucleation ability in the atmospherically relevant size fraction. Comparison of our data set to an existing desert dust parameterization confirms its applicability for climate models. Our results suggest that for an improved prediction of the ice nucleation ability of desert dust in the atmosphere, the modeling of emission and atmospheric transport of the feldspar and quartz mineral phases would be key, while other minerals are only of minor importance

3D co-cultures of osteoblasts and endothelial cells in DegraPol foam: Histological and high field MRI analyses of pre-engineered capillary networks in bone grafts

Tissue engineering of bone grafts was addressed in a critical size model on the chick chorioallantoic membrane model (CAM assay), using DegraPol(R) (DP) foam as scaffold material. The scaffolds were seeded with cultures of human osteoblasts (OB) and human en notdo notthelial cells (EC), respectively, or with a co-culture of the two cell types (control: no cells). In vitro samples (7 days cultivation) and ex vivo CAM samples at incubation day 15 (ID 15) were analyzed by high field magnetic resonance imaging (MRI) and histology. The co-culture system performed best with respect to perfusion, as assessed by contrast-enhanced MRI using Gd-DTPA. The scaffold seeded by the co-culture supported an increased vascular ingrowth, which was confirmed by histological analysis. DP foam is a suitable scaffold for bone tissue engineering and the MRI technique allows for non-destructive and quantitative assessment of perfusion capability during early stages of bone forming constructs

Evidence for non-exponential elastic proton proton differential cross-section at low vertical bar t vertical bar and √ s = 8 TeV by TOTEM

The TOTEM experiment has made a precise measurement of the elastic proton proton differential cross-section at the centre-of-mass energy root s = 8 TeV based on a high-statistics data sample obtained with the beta* = 90 m optics. Both the statistical and systematic uncertainties remain below 1%, except for the t-independent contribution from the overall normalisation. This unprecedented precision allows to exclude a purely exponential differential cross-section in the range of four-momentum transfer squared 0.027 <vertical bar t vertical bar <0.2 GeV2 with a significance greater than 7 sigma. Two extended parametrisations, with quadratic and cubic polynomials in the exponent, are shown to be well compatible with the data. Using them for the differential cross-section extrapolation to t = 0, and further applying the optical theorem, yields total cross-section estimates of (101.5 +/- 2.1) mb and (101.9 +/- 2.1) mb, respectively, in agreement with previous TOTEM measurements. (C) 2015 The Authors. Published by Elsevier B.V.Peer reviewe

Tissue engineered cartilage generated from human trachea using DegraPol® scaffold

Objective: To date numerous attempts have been undertaken to conquer the challenging problem of reconstructing long segmental tracheal defects, as yet without lasting success. Recently, employing concepts of tissue engineering in animals, cartilage-like constructs were transplanted in vivo. However, both the feasibility of fabricating tracheal replacements and the use of human tracheal chondrocytes (HTC) for tissue engineering are still under investigation. In this study, we optimized isolation and cultivation techniques for human tracheal cartilage, assessing the feasibility of seeding these cells onto a novel, three-dimensional (3-D) polyester-urethane polymer (DegraPol®). Methods: Human tracheal cartilage was harvested from the trachea of lung donors, digested in 0.3% collagenase II, and the condrocytes serially passaged every 7-9 days. Cells were also cultivated over agar plate during the total 6-8 weeks expansion phase. Thereafter, chondrocytes were seeded onto DegraPol® (pore sizes 150-200 μm) with a seeding density of 2.4×107/ml, and chondrocyte-polymer constructs maintained during in vitro static culture. Results: HTC displayed stable proliferation kinetics in monolayer culture with positive expression of collagen type II. Following polymer seeding, both cellular proliferation and extracellular matrix (ECM) production, as measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and glycosaminoglycan assays, continued over extended culture. Active growth of HTC on DegraPol® was further demonstrated by Alcian blue staining, with the histomorphological appearance of the construct resembling that of native cartilage. Scanning electron microscopy showed chondrocyte growth and ECM synthesis both on the surface and inside the porous scaffold, with a dense cell layer on the surface of the scaffold and a lower cell distribution in the scaffold's interior. Conclusions: The harvested chondrocytes from human trachea cartilage expand well in vitro and possess the ability to form new cartilage-like tissue when seeded onto DegraPol® matrix. However, improved culture conditions are needed to permit cellular growth throughout cell-polymer construct

First measurement of elastic, inelastic and total cross-section at √s = 13TeV by TOTEM and overview of cross-section data at LHC energies : TOTEM Collaboration

The TOTEM collaboration has measured the proton- proton total cross section at v s = 13 TeV with a luminosity- independent method. Using dedicated ss * = 90m beam optics, the Roman Pots were inserted very close to the beam. The inelastic scattering rate has been measured by the T1 and T2 telescopes during the same LHC fill. After applying the optical theorem the total proton- proton cross section is stot = (110.6 +/- 3.4) mb, well in agreement with the extrapolation from lower energies. This method also allows one to derive the luminosity- independent elastic and inelastic cross sections: sel = (31.0 +/- 1.7) mband sinel = (79.5 +/- 1.8) mb.Peer reviewe

MONTE CARLO SIMULATION OF ORANGE JUICE PECTINMETHYLESTERASE (PME) INACTIVATION BY COMBINED PROCESSES OF HIGH HYDROSTATIC PRESSURE (HHP) AND TEMPERATURE

The variability effect of kinetic data was investigated by simulating orange juice pectinmethylesterase (PME) inactivation with combined processes of high hydrostatic pressure-temperature (100-500 MPa; 20-40°C), applying the Monte Carlo method. Parameters from an Eyring-Arrheniius model that predicts the kinetic inactivation constant (k) as a function of both pressure and temperature were found reported in literature and considered for the analysis. The kinetic analysis was carried out with both Monte Carlo simulations and the traditional deterministic approach, which only considers mean values and does not take into account data variability. Simulations with the Monte Carlo method demonstrated that residual PME activity predicted with deterministic calculations greatly differed from those obtained through confidence intervals of simulated probabilistic distributions. Mean values overrated residual enzyme activity from 4% to ≈2,800% when compared to the 95% confidence intervals generated with the Monte Carlo method. This divergence augmented as both applied pressure and temperature levels increased. Similar risk analysis projects can be further developed to establish the foundations for future food processing regulations of enzymatic control.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Universidad Autónoma Metropolitana Unidad Iztapalapa and can be found at: http://www.redalyc.org/revista.oa?id=620.Keywords: Process simulation, High hydrostatic pressure (HHP), Orange juice, Pectinmethylesterase (PME), Monte CarloKeywords: Process simulation, High hydrostatic pressure (HHP), Orange juice, Pectinmethylesterase (PME), Monte Carl

Identification of plasma lipid biomarkers for prostate cancer by lipidomics and bioinformatics

Background: Lipids have critical functions in cellular energy storage, structure and signaling. Many individual lipid molecules have been associated with the evolution of prostate cancer; however, none of them has been approved to be used as a biomarker. The aim of this study is to identify lipid molecules from hundreds plasma apparent lipid species as biomarkers for diagnosis of prostate cancer. Methodology/Principal Findings: Using lipidomics, lipid profiling of 390 individual apparent lipid species was performed on 141 plasma samples from 105 patients with prostate cancer and 36 male controls. High throughput data generated from lipidomics were analyzed using bioinformatic and statistical methods. From 390 apparent lipid species, 35 species were demonstrated to have potential in differentiation of prostate cancer. Within the 35 species, 12 were identified as individual plasma lipid biomarkers for diagnosis of prostate cancer with a sensitivity above 80%, specificity above 50% and accuracy above 80%. Using top 15 of 35 potential biomarkers together increased predictive power dramatically in diagnosis of prostate cancer with a sensitivity of 93.6%, specificity of 90.1% and accuracy of 97.3%. Principal component analysis (PCA) and hierarchical clustering analysis (HCA) demonstrated that patient and control populations were visually separated by identified lipid biomarkers. RandomForest and 10-fold cross validation analyses demonstrated that the identified lipid biomarkers were able to predict unknown populations accurately, and this was not influenced by patient's age and race. Three out of 13 lipid classes, phosphatidylethanolamine (PE), ether-linked phosphatidylethanolamine (ePE) and ether-linked phosphatidylcholine (ePC) could be considered as biomarkers in diagnosis of prostate cancer. Conclusions/Significance: Using lipidomics and bioinformatic and statistical methods, we have identified a few out of hundreds plasma apparent lipid molecular species as biomarkers for diagnosis of prostate cancer with a high sensitivity, specificity and accuracy