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.     

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.     

BRCA Mutations in Prostate Cancer: Assessment,Implications and Treatment Considerations

Prostate cancer ranks fifth in cancer-related mortality in men worldwide. DNA damage is implicated in cancer and DNA damage response (DDR) pathways are in place against this to maintain genomic stability. Impaired DDR pathways play a role in prostate carcinogenesis and germline or somatic mutations in DDR genes have been found in both primary and metastatic prostate cancer. Among these, BRCA mutations have been found to be especially clinically relevant with a role for germline or somatic testing. Prostate cancer with DDR defects may be sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors which target proteins in a process called PARylation. Initially they were used to target BRCA-mutated tumor cells in a process of synthetic lethality. However, recent studies have found potential for PARP inhibitors in a variety of other genetic settings. In this review, we explore the mechanisms of DNA repair, potential for genomic analysis of prostate cancer and therapeutics of PARP inhibitors along with their safety profile.     

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.     

Aging of packaging films in the marine environment

The present article examines the aging behavior in the marine environment of some representative flexible plastic packaging films including supermarket plastic bags made of low‐density polyethylene (LDPE), polyethylene terephthalate (PET) films, polyamide–polyethylene (PAPE) films and films made of a material under the commercial name Mater‐Bi®. The effect of aging was studied by Fourier transform infrared spectroscopy, differential scanning calorimetry, and tension including creep‐recovery tests. The polyethylene films were not hydrolytically degraded during aging in seawater, and the polyethylene chains did not undergo any substantial chain scission. The PET films after exposure for 8 months in seawater did not suffer any substantial degradation, and the PET chains were plasticized by the absorbed water. After prolonged exposure to seawater (12 months), the PET films started to degrade. The PAPE film underwent extensive chemical and structural changes during aging in seawater as result of plasticization and hydrolysis of the polyamide (PA) component in combination with an eventual loosening of the tie layer. Mater‐Bi® film underwent a severe deterioration during aging in seawater due to the hydrolysis of the starch and polycaprolactone components. All films exhibited a marked degradation of their tensile properties after exposure to accelerating aging conditions under UV radiation. POLYM. ENG. SCI., 59:E432–E441, 2019. © 2019 Society of Plastics Engineers     

Utilization of different tall oils for improving the water resistance of cellulosic fibers

This study was conducted to assess the effect of the pulping by-products crude tall oil (CTO), distilled tall oil (DTO), and tall oil fatty acid (TOFA) on dynamic water vapor sorption behavior, interfiber strength, and thermal stability of cellulosic paper-sheets. The results were compared against those obtained in cellulose papers treated with the conventional petroleum-derived hydrophobic agent hydrowax and in untreated ones. The tall oil treatments caused strong reduction in equilibrium moisture content of the paper-sheets during adsorption and desorption runs. The same trend was noticed for the hydrowax-treated papers, however, it was less pronounced than the CTO-treated and DTO-treated samples in the relative humidity range of 75–95%. The sorption hysteresis was considerably decreased after the treatments. The ultimate dry-tensile strengths of the paper-sheets were significantly reduced by TOFA and hydrowax treatments, while CTO and DTO showed comparable strength as that of untreated control. The ultimate wet-strengths of the paper-sheets were improved after the treatments. The thermal stability of the specimens was improved by the tall oil treatments, and the hydrowax-treated samples illustrated lower degradation temperature than the untreated control. The results are promising for the use of tall oils as alternative hydrophobic agents of cellulosic fiber-based products, such as wood panels and paper packaging. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47303.     

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.