Human phosphodiesterase 4D7 (PDE4D7) expression is increased in TMPRSS2-ERG positive primary prostate cancer and independently adds to a reduced risk of post-surgical disease progression

background: There is an acute need to uncover biomarkers that reflect the molecular pathologies, underpinning prostate cancer progression and poor patient outcome. We have previously demonstrated that in prostate cancer cell lines PDE4D7 is downregulated in advanced cases of the disease. To investigate further the prognostic power of PDE4D7 expression during prostate cancer progression and assess how downregulation of this PDE isoform may affect disease outcome, we have examined PDE4D7 expression in physiologically relevant primary human samples. methods: About 1405 patient samples across 8 publically available qPCR, Affymetrix Exon 1.0 ST arrays and RNA sequencing data sets were screened for PDE4D7 expression. The TMPRSS2-ERG gene rearrangement status of patient samples was determined by transformation of the exon array and RNA seq expression data to robust z-scores followed by the application of a threshold >3 to define a positive TMPRSS2-ERG gene fusion event in a tumour sample. results: We demonstrate that PDE4D7 expression positively correlates with primary tumour development. We also show a positive association with the highly prostate cancer-specific gene rearrangement between TMPRSS2 and the ETS transcription factor family member ERG. In addition, we find that in primary TMPRSS2-ERG-positive tumours PDE4D7 expression is significantly positively correlated with low-grade disease and a reduced likelihood of progression after primary treatment. Conversely, PDE4D7 transcript levels become significantly decreased in castration resistant prostate cancer (CRPC). conclusions: We further characterise and add physiological relevance to PDE4D7 as a novel marker that is associated with the development and progression of prostate tumours. We propose that the assessment of PDE4D7 levels may provide a novel, independent predictor of post-surgical disease progression

Estimation of lower-bound K{sub Jc} on pressure vessel steels from invalid data

Statistical methods are currently being introduced into the transition temperature characterization of ferritic steels. Objective is to replace imprecise correlations between empirical impact test methods and universal K{sub Ic} or K{sub Ia} lower-bound curves with direct use of material-specific fracture mechanics data. This paper introduces a computational procedure that couples order statistics, weakest-link statistical theory, and a constraint model to arrive at estimates of lower-bound K{sub Jc} values. All of the above concepts have been used before to meet various objectives. In the present case, scheme is to make a best estimate of lower-bound fracture toughness when resource K{sub Jc} data are too few to use conventional statistical analyses. Utility of the procedure is of greatest value in the middle-to-high toughness part of the transition range where specimen constraint loss and elevated lower-bound toughness interfere with conventional statistical analysis methods

Interplay of Chemical, Electronic, and Structural Effects in the Triple-Conducting BaFeO3-Ba(Zr,Y)O3 Solid Solution

Triple-conducting oxides with mobile protons, oxygen vacancies, and holes are key functional materials for protonic ceramic fuel/electrolysis cells. We comprehensively investigate the Ba(Zr,Y,Fe)O3-delta perovskite solid solution series ranging from electrolyte to electrode-type materials depending on iron content. From thermogravimetry and impedance spectroscopy, the proton and oxygen vacancy concentrations as well as electronic and ionic conductivities are determined. X-ray spectroscopy (Fe K-edge XANES, O K-edge Raman scattering, Fe, Zr, Y K-edge EXAFS) elucidates the finer features of the electronic structure and local distortions. A low Fe content of <= 10% strongly decreases the degree of hydration, while comparably high Fe concentrations of >= 70% are required to obtain an electronic conductivity sufficient for an electrode material. The transport of ionic and electronic carriers is interrelated in a complex way and is closely linked to details of the electronic structure (strength of Fe-O hybridization) and geometrical distortions (Fe-O-Fe and Fe-O-(Zr,Y) buckling). As a result, an optimum combination of proton concentration and electronic conductivity is not obtained in the middle of the solid solution series but rather found for Fe-rich materials with 20-30% doping with oversized, redox-inactive cations. A similar behavior is also expected for related solid solutions between a large-band gap electrolyte and small-band gap redox-active perovskites

Technical Basis for the Master Curve Concept of Fracture Toughness Evaluations in the Transition Range

An American Society for Testing and Materials (ASTM) standard method (E 1921-97) has been developed that exclusively uses fracture mechanics test practices and advanced statistical methods to establish the ductile-to-brittle transition range of fracture toughness for structural steels. The development of suitably accurate analyses had been slowed in the past due to an incomplete understanding of the operational mechanisms that control the fracture toughness behavior of structural steels. New perspectives taken are (1) that dominant linear-elastic conditions need not be rigidly enforced in test specimens and (2) that the effect of weakest-link behavior is defined from local cleavage crack initiators such as precipitates, inclusions, and grain boundary embrittlement; namely, all microstructural features in steel. Statistical models can be built upon such mechanisms that result in defined fracture probability levels and, when coupled to a master curve concept, can more accurately define the true loctition of the ductile-to-brittle transition temperature. An integral part of the ASTM test standard development work has been the production of a supporting technical basis document. This document presents substantial background data and supporting theoretical aspects that have been used to justify the method development. The paper will include some of the salient features presented

Interface Diffusion and Compatibility of (Ba,La)FeO3−δ Perovskite Electrodes in Contact with Barium Zirconate and Ceria

Ba1-x La (x) FeO3-delta perovskites (BLF) capable of conducting electrons, protons, and oxygen ions are promising oxygen electrodes for efficient solid oxide cells (fuel cells or electrolyzers), an integral part of prospected large-scale power-to-gas energy storage systems. We investigated the compatibility of BLF with lanthanum content between 5 and 50%, in contact with oxide-ion-conducting Ce0.8Gd0.2O2-delta and proton-conducting Ba-Zr0.825Y0.175O3-delta electrolytes, annealing the electrode-electrolyte bilayers at high temperature to simulate thermal stresses of fabrication and prolonged operation. By employing both bulk X-ray diffraction and synchrotron X-ray microspectroscopy, we present a space-resolved picture of the interaction between electrode and electrolyte as what concerns cation interdiffusion, exsolution, and phase stability. We found that the phase stability of BLF in contact with other phases is correlated with the Goldschmidt tolerance factor, in turn determined by the La/Ba ratio, and appropriate doping strategies with oversized cations (Zn2+, Y3+) could improve structural stability. While extensive reactivity and/or interdiffusion was often observed, we put forward that most products of interfacial reactions, including proton-conducting Ba-(Ce,Gd)-O3-delta and mixed-conducting (Ba,La)-(Fe,Zr,Y)-O3-delta, may not be very detrimental for practical cell operation

Applications of energy-release-rate techniques to part-through cracks in experimental pressure vessels

In nonlinear applications of computational fracture mechanics, energy release rate techniques are used increasingly for computing stress intensity parameters of crack configurations. Recently, deLorenzi used the virtual-crack-extension method to derive an analytical expression for the energy release rate that is better suited for three-dimensional calculations than the well-known J-integral. Certain studies of fracture phenomena, such as pressurized-thermal-shock of cracked structures, require that crack tip parameters be determined for combined thermal and mechanical loads. A method is proposed here that modifies the isothermal formulation of deLorenzi to account for thermal strains in cracked bodies. This combined thermo-mechanical formulation of the energy release rate is valid for general fracture, including nonplanar fracture, and applies to thermo-elastic as well as deformation plasticity material models. Two applications of the technique are described here. In the first, semi-elliptical surface cracks in an experimental test vessel are analyzed under elastic-plastic conditions using the finite element method. The second application is a thick-walled test vessel subjected to combined pressure and thermal shock loadings

Adaptive Optics for Astronomy

Adaptive Optics is a prime example of how progress in observational astronomy can be driven by technological developments. At many observatories it is now considered to be part of a standard instrumentation suite, enabling ground-based telescopes to reach the diffraction limit and thus providing spatial resolution superior to that achievable from space with current or planned satellites. In this review we consider adaptive optics from the astrophysical perspective. We show that adaptive optics has led to important advances in our understanding of a multitude of astrophysical processes, and describe how the requirements from science applications are now driving the development of the next generation of novel adaptive optics techniques.Comment: to appear in ARA&A vol 50, 201

Test of 6-inch-thick pressure vessels. Series 2. Intermediate test vessels V-3, V-4, and V-6

The second series of intermediate vessel tests were crack initiation fracture tests of 6-in.-thick 39-in.-OD steel vessels with sharp surface flaws approximately 2$sup 1$/$sub 2$ in. deep by 8 in. long in the longitudinal weld seams of the test cylinders. Fracture was initiated by means of hydraulic pressurization. One vessel was tested at each of three temperatures: 75, 130, and 190$sup 0$F. Pretest analyses were made to predict the failure pressures and strains. Fracture toughness data obtained by equivalent-energy analysis of precracked Charpy-V tests and compact-tension specimen tests were used in the fracture analyses. The vessels behaved generally as had been expected. Posttest fracture analyses were also performed for each vessel. Detailed discussions of the fracture analysis methods developed in support of the vessel tests described are included. 34 references. (auth

Number partitioning as random energy model

Number partitioning is a classical problem from combinatorial optimisation. In physical terms it corresponds to a long range anti-ferromagnetic Ising spin glass. It has been rigorously proven that the low lying energies of number partitioning behave like uncorrelated random variables. We claim that neighbouring energy levels are uncorrelated almost everywhere on the energy axis, and that energetically adjacent configurations are uncorrelated, too. Apparently there is no relation between geometry (configuration) and energy that could be exploited by an optimization algorithm. This ``local random energy'' picture of number partitioning is corroborated by numerical simulations and heuristic arguments.Comment: 8+2 pages, 9 figures, PDF onl