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

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

A new discrete dipole kernel for quantitative susceptibility mapping

PURPOSE: Most approaches for quantitative susceptibility mapping (QSM) are based on a forward model approximation that employs a continuous Fourier transform operator to solve a differential equation system. Such formulation, however, is prone to high-frequency aliasing. The aim of this study was to reduce such errors using an alternative dipole kernel formulation based on the discrete Fourier transform and discrete operators. METHODS: The impact of such an approach on forward model calculation and susceptibility inversion was evaluated in contrast to the continuous formulation both with synthetic phantoms and in vivo MRI data. RESULTS: The discrete kernel demonstrated systematically better fits to analytic field solutions, and showed less over-oscillations and aliasing artifacts while preserving low- and medium-frequency responses relative to those obtained with the continuous kernel. In the context of QSM estimation, the use of the proposed discrete kernel resulted in error reduction and increased sharpness. CONCLUSION: This proof-of-concept study demonstrated that discretizing the dipole kernel is advantageous for QSM. The impact on small or narrow structures such as the venous vasculature might by particularly relevant to high-resolution QSM applications with ultra-high field MRI - a topic for future investigations. The proposed dipole kernel has a straightforward implementation to existing QSM routines

Chaos around Holographic Regge Trajectories

Using methods of Hamiltonian dynamical systems, we show analytically that a dynamical system connected to the classical spinning string solution holographically dual to the principal Regge trajectory is non-integrable. The Regge trajectories themselves form an integrable island in the total phase space of the dynamical system. Our argument applies to any gravity background dual to confining field theories and we verify it explicitly in various supergravity backgrounds: Klebanov-Strassler, Maldacena-Nunez, Witten QCD and the AdS soliton. Having established non-integrability for this general class of supergravity backgrounds, we show explicitly by direct computation of the Poincare sections and the largest Lyapunov exponent, that such strings have chaotic motion.Comment: 28 pages, 5 figures. V3: Minor changes complying to referee's suggestions. Typos correcte

Enrichment of trace elements in the clay size fraction of mining soils

Reactive waste dumps with sulfide minerals pro- 14 mote acid mine drainage (AMD), which results in water and 15 soil contamination by metals and metalloids. In these systems, 16 contamination is regulated by many factors, such as mineral- 17 ogical composition of soil and the presence of sorption sites 18 on specific mineral phases. So, the present study dedicates 19 itself to understanding the distribution of trace elements in 20 different size fractions (<2-mm and <2-μm fractions) of min- 21 ing soils and to evaluate the relationship between chemical 22 and mineralogical composition. Cerdeirinha and Penedono, 23 located in Portugal, were the waste dumps under study. The 24 results revealed that the two waste dumps have high degree of 25 contamination by metals and arsenic and that these elements 26 are concentrated in the clay size fraction. Hence, the higher 27 degree of contamination by toxic elements, especially arsenic 28 in Penedono as well as the role of clay minerals, jarosite, and 29 goethite in retaining trace elements has management implica- 30 tions. Such information must be carefully thought in the reha- 31 bilitation projects to be planned for both waste dumps

W+W-, WZ and ZZ production in the POWHEG BOX

We present an implementation of the vector boson pair production processes ZZ, W+W- and W Z within the POWHEG framework, which is a method that allows the interfacing of NLO calculations to shower Monte Carlo programs. The implementation is built within the POWHEG BOX package. The Z/\gamma^* interference, as well as singly resonant contributions, are properly included. We also considered interference terms arising from identical leptons in the final state. As a result, all contributions leading to the desired four-lepton system have been included in the calculation, with the sole exception of the interference between ZZ and W+W- in the production of a pair of same-flavour, oppositely charged fermions and a pair of neutrinos, which we show to be fully negligible. Anomalous trilinear couplings can be also set in the program, and we give some examples of their effect at the LHC. We have made the relevant code available at the POWHEG BOX web site.Comment: 20 pages, 9 figures, 2 tables. Minor corrections and updated references in revised versio

Joint data imputation and mechanistic modelling for simulating heart-brain interactions in incomplete datasets

The use of mechanistic models in clinical studies is limited by the lack of multi-modal patients data representing different anatomical and physiological processes. For example, neuroimaging datasets do not provide a sufficient representation of heart features for the modeling of cardiovascular factors in brain disorders. To tackle this problem we introduce a probabilistic framework for joint cardiac data imputation and personalisation of cardiovascular mechanistic models, with application to brain studies with incomplete heart data. Our approach is based on a variational framework for the joint inference of an imputation model of cardiac information from the available features, along with a Gaussian Process emulator that can faithfully reproduce personalised cardiovascular dynamics. Experimental results on UK Biobank show that our model allows accurate imputation of missing cardiac features in datasets containing minimal heart information, e.g. systolic and diastolic blood pressures only, while jointly estimating the emulated parameters of the lumped model. This allows a novel exploration of the heart-brain joint relationship through simulation of realistic cardiac dynamics corresponding to different conditions of brain anatomy

Confusion after spine injury: cerebral fat embolism after traumatic rupture of a Tarlov cyst: Case report

<p>Abstract</p> <p>Background</p> <p>Acute low back pain is a very common symptom and reason for many medical consultations. In some unusual circumstances it could be linked to a rare aetiology.</p> <p>Case presentation</p> <p>We report a 70-year-old man with an 8-month history of left posterior thigh and leg pain who had sudden confusion after a fall from standing. It was due to cerebral fat embolism suspected by computed tomography scan, later confirmed by brain magnetic resonance imaging (MRI). A spinal MRI scan was then performed and revealed a sacral fracture which drained into an unknown perineurial cyst (Tarlov cyst). Under medical observation the patient fully recovered within three weeks.</p> <p>Conclusions</p> <p>Sacral perineurial cysts are rare, however they remain a potential cause of lumbosacral radiculopathy.</p