Economic analysis of royalactin production under uncertainty: Evaluating the effect of parameter optimization.

Royalactin is a protein with several different potential uses in humans. Research, in insects and in mammalian cells, has shown that it can accelerate cell division and prevent apoptosis. The method of action is through the use of the epidermal growth factor receptor, which is present in humans. Potential use in humans could be to lower cholesterolemic levels in blood, and to elicit similar effects to those seen in bees, e.g., increased lifespan. Mass production of Royalactin has not been accomplished, though a recent article presented a Pichia pastoris fermentation and recovery by aqueous two-phase systems at laboratory scale as a possible basis for production. Economic modelling is a useful tool with which compare possible outcomes for the production of such a molecule and in particular, to locate areas where additional research is needed and optimization may be required. This study uses the BioSolve software to perform an economic analysis on the scale-up of the putative process for Royalactin. The key parameters affecting the cost of production were located via a sensitivity analysis and then evaluated by Monte Carlo analysis. Results show that if titer is not optimized the strategy to maintain a low cost of goods is process oriented. After optimization of this parameter the strategy changes to a product-oriented and the target output becomes the critical parameter determining the cost of goods. This study serves to provide a framework for the evaluation of strategies for future production of Royalactin, by analyzing the factors that influence its cost of manufacture. © 2015 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 2015

UK COVID-19 lockdown: 100 days of air pollution reduction?

On the 23 March 2020, a country-wide COVID-19 lockdown was imposed on the UK. The following 100 days saw anthropogenic movements quickly halt, before slowly easing back to a “new” normality. In this short communication, we use data from official UK air-quality sensors (DEFRA AURN) and the UK Met Office stations to show how lockdown measures affected air quality in the UK. We compare the 100 days post-lockdown (23 March to 30 June 2020) with the same period from the previous 7 years. We find, as shown in numerous studies of other countries, the nitrogen oxides levels across the country dropped substantially (∼ 50%). However, we also find the ozone levels increased (∼ 10%), and the levels of sulphur dioxide more than doubled across the country. These changes, driven by a complex balance in the air chemistry near the surface, may reflect the influence of low humidity as suggested by Met Office data, and potentially, the reduction of nitrogen oxides and their interactions with multiple pollutants

Characterization and optimization of polymer-polymer aqueous two-phase systems for the isolation and purification of CaCo2 cell-derived exosomes

Exosomes are cell-derived vesicles that present attractive characteristics such as nano size and unique structure for their use as drug delivery systems for drug therapy, biomarkers for prognostic, diagnostic and personalized treatments. So far, one of the major challenges for therapeutic applications of exosomes is the development of optimized isolation methods. In this context, aqueous two-phase systems (ATPS) have been used as an alternative method to isolate biological molecules and particles with promising expectations for exosomes. In this work, fractionation of exosomes obtained from CaCo2 cell line and culture media contaminants were individually performed in 20 polymer-polymer ATPS. The effect of design parameters such as polymer composition, molecular weight, and tie-line length (TLL) on polyethylene glycol (PEG)-Dextran, Dextran-Ficoll and PEG-Ficoll systems was studied. After partition analysis, 4 of the 20 systems presented the best exosome fractionation from contaminants under initial conditions, which were optimized via salt addition (NaCl) to a final concentration of 25 mM, to improve collection efficiency. The PEG 10,000 gmol-1 –Dextran 10,000 gmol-1 system at TLL 25% w/w with NaCl, showed the best potential isolation efficiency. Following this proposed strategy, an exosome purification factor of 2 in the top PEG-rich phase can be expected furtherly demonstrating that ATPS have the potential for the selective recovery of these promising nanovesicles

A Preschool Aged Obesity Prevention Project Designed to Increase Moderate to Vigorous Physical Activity

Purpose: The purpose of Juntos Y Saludables (Get Healthy Together [GHT]) is to reduce the prevalence of childhood obesity by focusing on physical activity and healthy eating. GHT is an ongoing project, with phase one of three completed in May 2010.The GHT program was implemented in the Edgewood Independent School District’s Head Start centers located in San Antonio, TX. These centers were selected due to high prevalence of obesity (50%) and diabetes in children and adults living in the community. Method: The gross motor intervention was implemented at two of the three centers. The intervention consisted of teacher training and supplemental gross motor resources (lesson plans and activity resources). The System for Observing Fitness Instruction Time (SOFIT) was used to assess the amount of time spent in moderate to vigorous physical activity (MVPA) and the Learning Accomplishment Profile – 3rd Editions (LAP-3) were used to evaluate the program’s effects on gross motor development. Results: At the start of the project, the two intervention centers were spending eleven minutes (roughly 24%) of their gross motor class period engaged in MVPA while at the end of the program sixteen minutes (roughly 35%) of the time was spent engaged in MVPA. There was an overall increase in physical activity (P\u3c0.001) and MVPA (P\u3c0.019) levels in both intervention and control centers. A similar linear improvement was also observed in the LAP-3 results. At the conclusion of the project, all of the students either met or were above their gross motor developmental ages. Conclusion: Through the implementation of the GHT Gross Motor intervention a significant increase occurred in the student’s gross motor skills and the percentage of time spent in MVPA

Biosorption of Chromium (VI) from Aqueous Solutions onto Fungal Biomass

The biosorption of chromium (VI) on eighteen different natural biosorbents: Natural sediment, chitosan, chitin, Aspergillus flavus I-V, Aspergillus fumigatus I-ll, Helmintosporium sp, Cladosporium sp, Mucor rouxii mutant, M. rouxii IM-80, Mucor sp-I and 2, Candida albicans and Cryptococcus neoformans was studied in this work. It was found that the biomass of C. neoformans, natural sediment, Helmintosporium sp and chitosan was more efficient to remove chromium (VI) (determined spectrophotometrically at 540 nm using diphenylcarbazide as the complexing agent) achieving the. following percentage of removals: 98%, 98% and 63%, respectively. The highest adsorption was obtained with C. neoformans and Helmintosporium sp at pH 2.0 and 4.0 + 0.2, respectively, at 28∘C after 24 hours of incubation, with 0.2 mg/L of cellular biomass

Economic analysis of Uricase production under uncertainty: Contrast of chromatographic purification and aqueous two-phase extraction (with and without PEG recycle)

Uricase is the enzyme responsible for the breakdown of uric acid, the key molecule leading to gout in humans, into allantoin, but it is absent in humans. It has been produced as a PEGylated pharmaceutical where the purification is performed through three sequential chromatographic columns. More recently an aqueous two-phase system (ATPS) was reported that could recover Uricase with high yield and purity. Although the use of ATPS can decrease cost and time, it also generates a large amount of waste. The ability, therefore, to recycle key components of ATPS is of interest. Economic modelling is a powerful tool that allows the bioprocess engineer to compare possible outcomes and find areas where further research or optimization might be required without recourse to extensive experiments and time. This research provides an economic analysis using the commercial software BioSolve of the strategies for Uricase production: chromatographic and ATPS, and includes a third bioprocess that utilises material recycling. The key parameters that affect the process the most were located via a sensitivity analysis and evaluated with a Monte Carlo analysis. Results show that ATPS is far less expensive than chromatography, but that there is an area where the cost of production of both bioprocesses overlap. Furthermore, recycling doesn't impact the cost of production. This study serves to provide a framework for the economic analysis of Uricase production using alternative techniques. This article is protected by copyright. All rights reserved

Estudio de la propagación de estímulos eléctricos en células del sistema nervioso empleando microscopía de fuerza atómica

Las células excitables han sido estudiadas desde un punto de vista eléctrico durante décadas. Actualmente continúan estudiándose intensamente pero ya no sólo por biofísicos y electrofisiólogos; sino también por farmacólogos, neurocientíficos, ingenieros biomédicos, bioquímicos, biólogos moleculares, entre otros. Loa avances más importantes en el estudio de las células excitables ha estado íntimamente relacionado con el desarrollo de nuevas metodologías que van desde la instrumentación y adquisición de señales eléctricas hasta el desarrollo de modelos biológicos apropiados. El trabajo de tesis que se presenta se ubica en este contexto; es decir, mejorar las técnicas tradicionales de adquisición de las señales eléctricas de las células excitables empleando para ello los avances que la nanotecnología nos brinda. Asimismo, mejorar la calidad de las imágenes que es posible obtener con la microscopía de fuerza atómica. Consideramos que los resultados aquí reportados servirán para mejorar la calidad de las mediciones eléctricas de las células y obtener algo que hasta la fecha no había sido posible: la medición simultánea de los potenciales de acción y las corrientes iónicas transmembranales que les dan origen.Excitable cells have been studied for decades from an electrical point of view. Currently, they are still studied intensively not only by biophysicists and electrophysiologists; but also by pharmacologists, neuroscientists, biomedical engineers, biochemicals, molecular biologists, among others. The most important advances in the study of excitable cells have been intimately related to the development of new methodologies ranging from the instrumentation and acquisition of electrical signals to the development of appropriate biological models. The thesis work here presented is located in this context; that is to say, to improve the traditional techniques of acquisition of the electrical signals of the excitable cells using the advances offered by nanotechnology. Additionally, we aim to improve the quality of the images obtained through atomic force microscopy. We believe that the results reported here will serve to improve the quality of the electrical measurements of the cells and to achieve a goal that has remained elusive: the simultaneous measurement of the action potentials and the underlying transmembrane ion currents

The Fermi motion contribution to J/\psi production at the hadron colliders

We investigate the relativistic Fermi motion effect in the case of $J/\psi$ production in various hadron colliders. A light-cone wave function is adopted to represent the $J/\psi$ final state. The change in the confinement parameter which sets a scale for the size of the final state, allows one to see the effect in an explicit manner. While the effect has considerable influence on the fragmentation probabilities and the differential cross sections, the total cross sections are essentially left unchanged. such a feature is in agreement with the momentum sum rule which the fragmentation functions should satisfy.Comment: 10 pages, 4 figures, to appear in Phys. Lett.

Deterministic generation of an on-demand Fock state

We theoretically study the deterministic generation of photon Fock states on-demand using a protocol based on a Jaynes Cummings quantum random walk which includes damping. We then show how each of the steps of this protocol can be implemented in a low temperature solid-state quantum system with a Nitrogen-Vacancy centre in a nano-diamond coupled to a nearby high-Q optical cavity. By controlling the coupling duration between the NV and the cavity via the application of a time dependent Stark shift, and by increasing the decay rate of the NV via stimulated emission depletion (STED) a Fock state with high photon number can be generated on-demand. Our setup can be integrated on a chip and can be accurately controlled.Comment: 13 pages, 9 figure