The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers

This review evaluates the role of α-adrenoceptor antagonists as a potential treatment of prostate cancer (PCa). Cochrane, Google Scholar and Pubmed were accessed to retrieve sixty-two articles for analysis. In vitro studies demonstrate that doxazosin, prazosin and terazosin (quinazoline α-antagonists) induce apoptosis, decrease cell growth, and proliferation in PC-3, LNCaP and DU-145 cell lines. Similarly, the piperazine based naftopidil induced cell cycle arrest and death in LNCaP-E9 cell lines. In contrast, sulphonamide based tamsulosin did not exhibit these effects. In vivo data was consistent with in vitro findings as the quinazoline based α-antagonists prevented angiogenesis and decreased tumour mass in mice models of PCa. Mechanistically the cytotoxic and antitumor effects of the α-antagonists appear largely independent of α 1-blockade. The proposed targets include: VEGF, EGFR, HER2/Neu, caspase 8/3, topoisomerase 1 and other mitochondrial apoptotic inducing factors. These cytotoxic effects could not be evaluated in human studies as prospective trial data is lacking. However, retrospective studies show a decreased incidence of PCa in males exposed to α-antagonists. As human data evaluating the use of α-antagonists as treatments are lacking; well designed, prospective clinical trials are needed to conclusively demonstrate the anticancer properties of quinazoline based α-antagonists in PCa and other cancers.     

Slope reliability and back analysis of failure with geotechnical parameters estimated using Bayesian inference

A Bayesian approach is proposed for the inference of the geotechnical parameters used in slope design. The methodology involves the construction of posterior probability distributions that combine prior information on the parameter values with typical data from laboratory tests and site investigations used in design. The posterior distributions are often complex, multidimensional functions whose analysis requires the use of Markov chain Monte Carlo (MCMC) methods. These procedures are used to draw representative samples of the parameters investigated, providing information on their best estimate values, variability and correlations. The paper describes the methodology to define the posterior distributions of the input parameters for slope design and the use of these results for evaluation of the reliability of a slope with the first order reliability method (FORM). The reliability analysis corresponds to a forward stability analysis of the slope where the factor of safety (FS) is calculated with a surrogate model from the more likely values of the input parameters. The Bayesian model is also used to update the estimation of the input parameters based on the back analysis of slope failure. In this case, the condition FS = 1 is treated as a data point that is compared with the model prediction of FS. The analysis requires a sufficient number of observations of failure to outbalance the effect of the initial input parameters. The parameters are updated according to their uncertainty, which is determined by the amount of data supporting them. The methodology is illustrated with an example of a rock slope characterised with a Hoek-Brown rock mass strength. The example is used to highlight the advantages of using Bayesian methods for the slope reliability analysis and to show the effects of data support on the results of the updating process from back analysis of failure.     

Waterborne star-shaped styrene-alkyd resins

Waterborne star-shaped styrene-alkyd resins (SSARs) were synthesized from a branched alkyd resin (AR) and styrene (St) by miniemulsion polymerization. SSARs are an environmentally friendly material. The ratio of AR to St for obtaining SSARs was as follows: 50:50 (SSAR1), 60:40 (SSAR2), 70:30 (SSAR3), and 80:20 (SSAR4). The conversion percentage was directly proportional to St used, and was higher than 94.0 %. Infrared analysis and protonic nuclear magnetic resonance revealed the reaction between AR and St. The synthesis process also leads to the formation of polystyrene and its concentration increases with the concentration of St. The values of the reacted double-bond fractions were higher than 17.80%. The SSARs drop size was bigger than the particle size. The miniemulsion colloidal stability was good at room temperature. The SSARs zeta potential was between −55 and −90 mV. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48386.     

Gelation of gellan – A review

Gellan is an anionic extracellular bacterial polysaccharide discovered in 1978. Acyl groups present in the native polymer are removed by alkaline hydrolysis in normal commercial production, giving the charged tetrasaccharide repeating sequence: → 3)-β-d-Glcp-(1 → 4)-β-d-GlcpA-(1 → 4)-β-d-Glcp-(1 → 4)-α-l-Rhap-(1 →. Deacylated gellan converts on cooling from disordered coils to 3-fold double helices. The coil–helix transition temperature (T_m) is raised by salt in the way expected from polyelectrolyte theory: equivalent molar concentrations of different monovalent cations (Group I and Me₄N⁺) cause the same increase in T_m; there is also no selectivity between different divalent (Group II) cations, but divalent cations cause greater elevation of T_m than monovalent. Cations present as counterions to the charged groups of the polymer have the same effect as those introduced by addition of salt. Increasing polymer concentration raises T_m because of the consequent increase in concentration of the counterions, but the concentration of polymer chains themselves does not affect T_m. Gelation occurs by aggregation of double helices. Aggregation stabilises the helices to temperatures higher than those at which they form on cooling, giving thermal hysteresis between gelation and melting. Melting of aggregated and non-aggregated helices can be seen as separate thermal and rheological processes. Reduction in pH promotes aggregation and gelation by decreasing the negative charge on the polymer and thus decreasing electrostatic repulsion between the helices. Group I cations decrease repulsion by binding to the helices in specific coordination sites around the carboxylate groups of the polymer. Strength of binding increases with increasing ionic size (Li⁺ < Na⁺ < K⁺ < Rb⁺ < Cs⁺); the extent of aggregation and effectiveness in promoting gel formation increase in the same order. Me₄N⁺ cations, which cannot form coordination complexes, act solely by non-specific screening of electrostatic repulsion, and give gels only at very high concentration (above ∼0.6 M). At low concentrations of monovalent cations, ordered gellan behaves like a normal polymer solution; as salt concentration is increased there is then a region where fluid “weak gels” are formed, before the cation concentration becomes sufficient to give true, self-supporting gels. Aggregation and consequent gelation with Group II cations occurs by direct site-binding of the divalent ions between gellan double helices. High concentrations of salt or acid cause excessive aggregation, with consequent reduction in gel strength. Maximum strength with divalent cations comes at about stoichiometric equivalence to the gellan carboxylate groups. Much higher concentrations of monovalent cations are required to attain maximum gel strength. The content of divalent cations in commercial gellan is normally sufficient to give cohesive gels at polymer concentrations down to ∼0.15 wt %. Gellan gels are very brittle, and have excellent flavour release. The networks are dynamic: gellan gels release polymer chains when immersed in water and show substantial recovery from mechanical disruption or expulsion of water by slow compression. High concentrations of sugar (∼70 wt % and above) inhibit aggregation and give sparingly-crosslinked networks which vitrify on cooling. Gellan forms coupled networks with konjac glucomannan and tamarind xyloglucan, phase-separated networks with kappa carrageenan and calcium alginate, interpenetrating networks with agarose and gelling maltodextrin, and complex coacervates with gelatin under acidic conditions. Native gellan carries acetyl and l-glyceryl groups at, respectively, O(6) and O(2) of the 3-linked glucose residue in the tetrasaccharide repeat unit. The presence of these substituents does not change the overall double helix structure, but has profound effects on gelation. l-Glyceryl groups stabilise the double helix by forming additional hydrogen bonds within and between the two strands, giving higher gelation temperatures, but abolish the binding site for metal ions by changing the orientation of the adjacent glucuronate residue and its carboxyl group. The consequent loss of cation-mediated aggregation reduces gel strength and brittleness, and eliminates thermal hysteresis. Aggregation is further inhibited by acetyl groups located on the periphery of the double helix. Gellan with a high content of residual acyl groups is available commercially as “high acyl gellan”. Mixtures of high acyl and deacylated gellan form interpenetrating networks, with no double helices incorporating strands of both types. Gellan has numerous existing and potential practical applications in food, cosmetics, toiletries, pharmaceuticals and microbiology.     

Microstructure and multifunctional properties of liquid + polymer bicomponent structural electrolytes: Epoxy gels and porous monoliths

Multifunctional structural batteries and supercapacitors have the potential to improve performance and efficiency in advanced lightweight systems. A critical requirement is a structural electrolyte with superior multifunctional performance. We present here structural electrolytes prepared by the integration of liquid electrolytes with structural epoxy networks. Two distinct approaches were investigated: direct blending of an epoxy resin with a poly(ethylene‐glycol) (PEG)‐ or propylene carbonate (PC)‐based liquid electrolyte followed by in‐situ cure of the resin; and formation of a porous neat epoxy sample followed by backfill with a PC‐based electrolyte. The results show that in situ cure of the electrolytes within the epoxy network does not lead to good multifunctional performance due to a combination of plasticization of the structural network and limited percolation of the liquid network. In contrast, addition of a liquid electrolyte to a porous monolith results in both good stiffness and high ionic conductivity that approach multifunctional goals. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42681.     

MoO2 Diffusion in Aluminosilicate Glass

A diffusion couple of an oxidized molybdenum disk and a glass cylinder was used to measure the solubiiity and effective binary diffusion coefficient of MoO₂ in a non-alkali aluminosilicate glass. At 1400°C, the solubility limit was 8.4 mol%; the value of the diffusion coefficient (4.1 × 10⁻¹⁶ m²/s) was significantly lower than that estimated from the Stokes-Einstein relation.