Vector and Cell Line Engineering Technologies Toward Recombinant Protein Expression in Mammalian Cell Lines

The rapid growth of global biopharmaceutical market in the recent years has been a good indication of its significance in biotechnology industry. During a long period of time in recombinant protein production from 1980s, optimizations in both upstream and downstream processes were launched. In this regard, one of the most promising strategies is expression vector engineering technology based on incorporation of DNA opening elements found in the chromatin border regions of vectors as well as targeting gene integration. Along with these approaches, cell line engineering has revealed convenient outcomes in isolating high-producing clones. According to the fact that more than 50% of the approved therapeutic proteins is being manufactured in mammalian cell lines, in this review, we focus on several approaches and developments in vector and cell line engineering technologies in mammalian cell culture.     

Highly effective and regioselective Michael addition of indoles to α,β-unsaturated ketones promoted by pentafluorophenylammonium triflate

A simple, inexpensive, environmentally friendly and efficient route for Michael addition of indoles to α,β-unsaturated ketones using pentafluorophenylammonium triflate (PFPAT) as a catalyst is described. Various indole derivatives were synthesized in good to excellent yields. The preparation of PFPAT catalyst from simple and readily available starting materials makes this method more affordable.     

Health-based pharmaceutical pay-for-performance risk-sharing agreements

Many new drugs, such as biologics and cancer drugs, are very costly. However, their effectiveness outside of clinical trial settings is often uncertain at the time they gain market approval. This uncertainty may reflect a lack of real-world outcomes data, as opposed to clinical trials data, for a typical patient population. A risk-sharing agreement is a contract between a drug manufacturer and a healthcare payer to help manage uncertainties regarding the cost and effectiveness of those drugs. In this paper, we model a risk-sharing agreement in which a proportion of total sales is rebated. We model disease progression using a continuous time Markov chain with uncertain transition rates. We examine the performance of this risk-sharing agreement from the manufacturer’s perspective and investigate the conditions under which the manufacturer will make a profit. We illustrate with a numerical model parameterized using data from a Phase 2 clinical trial of an oncology drug that was subjected to a risk-sharing agreement in the UK.     

Preservation theorems in linear continuous logic

Linear continuous logic is the fragment of continuous logic obtained by restricting connectives to addition and scalar multiplications. Most results in the full continuous logic have a counterpart in this fragment. In particular a linear form of the compactness theorem holds. We prove this variant and use it to deduce some basic preservation theorems.     

A new direction in design and manufacture of co-sensitized dye solar cells: Toward concurrent optimization of power conversion efficiency and durability

A novel methodology was implemented in the present study to concurrently control power conversion efficiency (η) and durability (D) of co-sensitized dye solar cells. Applying response surface methodology (RSM) and Desirability Function (DF), the main influential assembling (dye volume ratio and anti-aggregation agent concentration) and operational (performance temperature) parameters were systematically changed to probe their main and interactive effects on the η and D responses. Individual optimization based on RSM elucidated that D can be solely controlled by changing the ratio of vat-based organic photosensitizers, whereas η takes both effects of dye volume ratio and anti-aggregation concentration into account. Among the studied factors, the performance temperature played the most vital role in η and D regulation. In particular, however, multi-objective optimization by DF explored the degree to which one should be careful about manipulation of assembling and operational parameters in the way maximization of performance of a co-sensitized dye solar cell.     

A digital pseudo-random number generator based on sawtooth chaotic map with a guaranteed enhanced period

Nonlinear Dynamics - We investigate tunneling behavior between two bright solitons in a Bose–Einstein condensate with attractive contact interactions between atoms. The explicit tunneling...