Engineering a mammalian super producer

Mammalian cells are the preferred host for the manufacture of a wide range of biopharmaceuticals, but production costs are high owing to low productivity. A range of rational engineering strategies have been pursued in order to increase volumetric product titres from mammalian cells, such as delaying apoptosis, manipulation of the cell cycle, and improving metabolism and protein processing. Unfortunately, outcomes from these strategies have been mixed, with few instances where significant improvements in product yield have been achieved. This article reviews and contrasts many of the engineering strategies attempted to date, highlighting the variability and context specificity in outcome. The paper argues that this is a reflection of the complexity of mammalian cells, and that a deeper understanding of the biology underpinning protein production for biotechnological purposes is required. Copyright © 2011 Society of Chemical Industry     

Synthetic and Biological Studies of Sesquiterpene Polygodial: Activity of 9‐Epipolygodial against Drug‐Resistant Cancer Cells

Polygodial, a terpenoid dialdehyde isolated from Polygonum hydropiper L., is a known agonist of the transient receptor potential vanilloid 1 (TRPV1). In this investigation a series of polygodial analogues were prepared and investigated for TRPV1‐agonist and anticancer activities. These experiments led to the identification of 9‐epipolygodial, which has antiproliferative potency significantly exceeding that of polygodial. 9‐Epipolygodial was found to maintain potency against apoptosis‐resistant cancer cells as well as those displaying the multidrug‐resistant (MDR) phenotype. In addition, the chemical feasibility for the previously proposed mechanism of action of polygodial, involving the formation of a Paal–Knorr pyrrole with a lysine residue on the target protein, was demonstrated by the synthesis of a stable polygodial pyrrole derivative. These studies reveal rich chemical and biological properties associated with polygodial and its direct derivatives. These compounds should inspire further work in this area aimed at the development of new pharmacological agents, or the exploration of novel mechanisms of covalent modification of biological molecules with natural products.     

Porphyrin polymers and organic frameworks

The versatility of porphyrins as optoelectronic or catalytic units makes them attractive elements for inclusion in functional materials. Polymers that include porphyrins have been created with a wide variety of structures and used in a wide range of applications. This review covers recent developments in the synthesis, characterization and applications of polymeric materials in which porphyrins are key components of the repeat units, including the rapidly growing area of metal–organic frameworks and related covalent organic frameworks. © 2015 Society of Chemical Industry     

Towards Efficient Nonenzymatic DNA Ligation: Comparing Key Parameters for Maximizing Ligation Rates and Yields with Carbodiimide Activation**

Chemical ligation is an important tool for the generation of synthetic DNA structures, which are used for a wide range of applications. Surprisingly, reported chemical ligation yields can range from 30 to 95 % for the same chemical activating agent and comparable DNA structures. We report a systematic study of DNA ligation by using a well-defined bimolecular test system and a water-soluble carbodiimide (EDC) as a phosphate-activating agent. Our results emphasize the interplay between template-substrate complex stability and the rates of the chemical steps of ligation, with 3′ phosphate substrates providing yields near 100 % after 24 hours for particularly favorable reaction conditions. Ligation rates are also shown to be sensitive to the identity of the base pairs flanking a nick site, with as much as threefold variation. Finally, the observation that DNA substrates are modified by EDC at rates that can be comparable with ligation rates emphasizes the importance of considering side reactions when designing protocols to maximize ligation yields.     

Effect of network mesh size and swelling to the drug delivery from pH responsive hydrogels

pH responsive hydrogels are ideal platforms for numerous therapeutic delivery applications, including oral delivery, as they are capable of overcoming the many barriers that must be considered when creating an effective drug delivery system. Understanding of the innate hydrogel network structure and its swelling behavior at environmentally relevant conditions is vital for designing hydrogel network capable of effective controlled drug release. Herein, we explored how to expand traditional techniques of swelling and pore characterization to gain better insight into the performance of anionic microparticles composed of the poly(methyl methacrylate-co-acrylic acid) with varying molar percentage of 10, 20, and 30 mol% of MMA, for controlled release of low-molecular-weight drugs. By evaluating these carrier systems at environmental conditions, we can observe changes in swelling and pore size of the anionic hydrogel networks as a function of MMA, which was then correlated with the release profiles of the small-molecular-weight drug sodium nitrate. With the correlation of the swelling behavior of the networks and the release profiles, we demonstrated how the expansion of swelling parameters at relevant pH values provides further incite for evaluating for the optimal blend for controlled release. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48767.     

Mixed modifier effect in Na2O·K2O·CaO aluminosilicate glasses: Pairwise and ternary interactions

The mixed modifier effect (MME) is one of the most challenging puzzles in the field of oxide glasses, as there exists no universal quantitative theoretical model for accurately describing and predicting the nonlinear deviation of property values. In this paper, pairwise and ternary interactions are examined experimentally to understand the MME in a series of aluminosilicate glasses. By keeping the glass network former concentration constant and adjusting the molar ratios of three network modifiers (Na₂O, K₂O, and CaO), the MMEs in glass transition temperature (T_g), Vickers hardness (H_v), and activation energy (E_a) for aqueous dissolution for each modifier cation are investigated. We examine whether a pairwise interaction model is sufficient, or if ternary interactions also need to be included to predict the MME in these aluminosilicate glass systems. This work reveals that the pairwise model can be used to predict the MME for T_g in complex multiple-modifier glass systems using only two-body interaction factors. However, ternary mixed-modifier interactions are present in other properties such as H_v and E_a.     

Performance characteristics of an axial-flow gas induction impeller

Power number, pressure coefficient, and induced gas flow rate of a novel axial-flow gas induction impeller with large openings for gas flow are reported. The effects of rotational speed, impeller diameter, submergence, and pumping mode are considered in turbulent operation. The pressure coefficient is measured using the reduction in pressure at speeds below the minimum induction speed as well as from the minimum induction speed. The minimum induction speed approach consistently yields lower pressure coefficient values, indicating the existence of impeller exit losses that are required to force gas from the centre of the impeller into the liquid. The induced gas flow rate is modelled using two approaches. The first approach relates the gas flow rate to the available pressure difference, and in this case, the relation is found to be strongly affected by impeller diameter. The second approach is a literature model that likens the induction process to water jet injection. While this approach appears promising, flow measurement device pressure losses make it difficult to definitively evaluate this method.     

Effect of a lattice distortion strategy on the phase transition and properties in KNN-based ceramics

High performance lead-free piezoelectric ceramics are of great importance to the sustainable development of the environment. To obtain excellent comprehensive performance KNN-based lead-free piezoelectric ceramics, a lattice distortion strategy combined with domain configuration was designed in (1 − x)K_0.5Na_0.5Nb_0.95Sb_0.05O₃–xCaHfO₃ ((1 − x)KNNS–xCH) system by introduced Ca²⁺ into the A-site and Hf⁴⁺ into the B-site. The results demonstrated that the rhombohedral–orthorhombic–tetragonal polymorphic phase boundary (PPB) was constructed in 0.02 ≤ x ≤ 0.04 and significant lattice distortion occurred in R- and T-phase. Moreover, the 0.97KNNS–0.03CH sample exhibited excellent electrical performance (e.g., k_p ∼ 43.8%, d^*₃₃ ∼ 478.6 pm/V, and d₃₃ ∼ 392 pC/N) together with a high Curie temperature (T_C ∼ 295°C) profited from the PPB and domain configurations. The ceramics also showed the optimal thermal stability, which was beneficial to promote the development of KNN-based ceramics.