Androgen Receptor Gene Pathway Upregulation and Radiation Resistance in Oligometastatic Prostate Cancer

Stereotactic ablative body radiotherapy (SABR) is currently used as a salvage intervention for men with oligometastatic prostate cancer (PC), and increasingly so since the results of the Stereotactic Ablative Body Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers (SABR-COMET) trial reported a significant improvement in overall survival with SABR. The addition of androgen deprivation therapy (ADT) to localised prostate radiotherapy improves survival as it sensitises PC to radiotherapy-induced cell death. The importance of the androgen receptor (AR) gene pathway in the development of resistance to radiotherapy is well established. In this review paper, we will examine the data to determine how we can overcome the upregulation of the AR pathway and suggest a strategy for improving outcomes in men with oligometastatic hormone-sensitive PC.     

Design synthesis and structural optimization of a lightweight,monobloc cast iron brake disc with fingered hub

This article focuses on generating a monobloc fingered hub (top-hat) disc design, aiming at reducing disc mass but maintaining rotor thermal capacity, while also improving heat dissipation characteristics. The analyses and tests demonstrated that such a design is possible to achieve, with mass reduction of just over 9%. The activities included research into cast iron modelling, which gave very important insights into the limits of mechanical performance under bending. Initial finite element analyses enabled considerable progress to be made towards establishing a baseline design, but only through shape optimization and topology optimization procedures was the full potential of the design accomplished. Shape optimization facilitated the reduction of maximum principal stress by 32%, considerably improving disc torsional strength with practically no increase in mass. The safety factor in torsion achieved a value of 3.57. Topology optimization provided further, although small, mass reduction (1.5%) while maintaining low stress levels.     

Pressure- and Temperature-Driven Flow Through Triangular and Trapezoidal Microchannels

A detailed study of pressure- and temperature-driven flows through long channels of triangular and trapezoidal cross sections is carried out. Due to the imposed pressure and temperature gradients there is a combined gas flow consisting of a thermal creep flow from the cold toward the hot reservoir and a Poiseuille flow from the high- toward the low-pressure reservoir. The formulation is based on the linearized Shakhov model subject to Maxwell boundary conditions, and it is solved numerically using a finite-difference scheme in the physical space and the discrete velocity method in the molecular velocity space. The results are valid in the whole range of the Knudsen number. In addition to the dimensionless flow rates, a methodology is presented to estimate for a certain set of input data the mass flow rates and the pressure distribution along the channel. Finally, special attention is given to the case of zero net mass flow and to the computation of the coefficient of the thermomolecular pressure difference.     

Non-linear properties of conditional returns under scale mixtures

This article provides a framework for analyzing multifactor financial returns that violate the Gaussian distributional assumption. Analytical expressions are provided for the non-linear regression equation and its prediction error (heteroscedasticity) by modeling the returns of financial assets as scale mixtures of the multivariate normal distribution. The expressions involve conditional moments of the mixing variable. These conditional moments are explicitly derived when the mixing variable belongs to the generalized inverse Gaussian family, of which gamma, inverse gamma and the inverse Gaussian distributions are distinguished members. The derived expressions are non-linear in the parameters and involve the modified Bessel function of the third kind. The effects of the non-linear model, in terms of both the regression equation and heteroscedasticity against the corresponding values for the standard linear regression model, are captured through simulations for the gamma, inverse gamma and inverse Gaussian distributions. The proposed scale mixture models extend the well-known arbitrage pricing theory (APT) in financial modeling to non-Gaussian cases. The methodology is applied to analyze the intra-day log returns quarterly data for DELL and COKE regressed against S&P 500 for the years 1998-2000.     

Bioreactors in Tissue Engineering

Tissue engineering is a promising interdisciplinary scientific field of regenerative medicine. Aiming at the structural and functional restoration of damaged tissues and organs, it possesses a role of significant socioeconomical impact. In the course towards the ultimate goal of artificially constructed natural organs, our knowledge of the elementary constitutive components of living organisms and the intrinsic mechanisms that drive their interactions is greatly enhanced. Bioreactors are valuable tools providing the technological means to investigate fundamental issues for basic research and to improve tissue‐engineering products for clinical applications. They are devices enabling the in vitro simulation of the in vivo biological, physical and mechanical environment of growing tissues. In this review paper, we discuss the general demands defining the design considerations for modern bioreactor systems. These criteria originate from physiological characteristics of the cells and biochemical and mechanical properties of the extracellular matrix (ECM). In this context, we present an overview of the various bioreactor systems dedicated to the study of specific functional tissues developed by numerous research groups.     

Electronic and structural properties of TiB2: Bulk, surface, and nanoscale effects

Titanium diboride (TiB₂), is a widely used hard material that comprises graphene-like layers of B and intercalated Ti atoms. Here we report the results of extensive first-principles calculations on key properties of bulk TiB₂, TiB₂ surfaces, and TiB₂ nanocrystals (NCs). The computational approach is first validated based on the agreement between calculated structural and electronic properties of bulk TiB₂ and available experimental and theoretical data. We then obtain the formation energies for several surface cuts and use these values to construct TiB₂ NCs based on the Wulff theorem. Finally, we demonstrate by studying the adsorption of small molecules that hydrogen and oxygen adatoms can be attached through strongly exothermic chemisorption reactions on TiB₂ surfaces. Likewise, water molecules bind on various TiB₂ surfaces and NC facets, with an energetic preference for the latter. The results are relevant to applications that depend on reactivity-related TiB₂ properties, for example resistance to corrosion and interactions with water-based solutions.     

Effects of subphase pH and temperature on the interfacial behavior of double hydrophilic diblock copolymer PDEGMA-b-PDIPAEMA

The aggregation behavior of two pH- and temperature-responsive diblock copolymers of poly[di-(ethylene glycol) methyl ether methacrylate]-block-poly[2-(diisopropylamino) ethyl methacrylate] (PDEGMA-b-PDIPAEMA) at the air/water interface and the structures of their Langmuir–Blodgett (LB) films were studied by the Langmuir monolayer technique and atomic force microscopy, respectively. At the air/water interface, PDEGMA-b-PDIPAEMA tends to form the core-shell-corona micellar structure composed of a PDIPAEMA main chain core, an amino ethyl ester shell, and a PDEGMA corona. Under acidic, neutral, and alkaline conditions, PDIPAEMA blocks are completely protonated, partially protonated, and completely non-protonated, respectively, and the protonated amino ethyl ester groups are immersed in water before monolayer compression, whereas PDEGMA coronas are adsorbed at the interface. At pH 3, 7, and 10, the limiting areas (A₀) for PDEGMA42%-PDIPAEMA58% (weight percents) and PDEGMA55%-PDIPAEMA45% are 8.2/10.2/14.0 and 6.7/8.3/8.4 nm², respectively. The A₀ values of the former copolymer are larger than those of the latter. This is because the shells in the former copolymer are denser due to the higher polymerization degree of PDIPAEMA blocks, providing greater steric hindrance for PDEGMA coronas and making the latter more extended at the interface. In contrast to other copolymer systems, the effect of temperature on the isotherms of PDEGMA-b-PDIPAEMA is less obvious.