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

Triboson interpretations of the ATLAS diboson excess

The ATLAS excess in fat jet pair production is kinematically compatible with the decay of a heavy resonance into two gauge bosons plus an extra particle. This hypothesis would explain the absence of such a large excess in the analogous CMS analysis of fat dijet final states, as well as the negative results of diboson resonance searches in the semi-leptonic decay modes. If the extra particle is the Higgs boson, this hypothesis might also explain -statistical fluctuations aside- why the CMS search for WH resonances in the semi-leptonic channel finds some excess while in the fully hadronic one it does not have a significant deviation.Comment: LaTeX 17 pages. v2: Enlarged discussion to address CMS WH excess. v3: Added discussion of diboson helicities. Final version to appear in JHE

Lattice Boltzmann methods for global linear instability analysis

Modal global linear instability analysis is performed using, for the first time ever, the lattice Boltzmann method (LBM) to analyze incompressible flows with two and three inhomogeneous spatial directions. Four linearization models have been implemented in order to recover the linearized Navier–Stokes equations in the incompressible limit. Two of those models employ the single relaxation time and have been proposed previously in the literature as linearization of the collision operator of the lattice Boltzmann equation. Two additional models are derived herein for the first time by linearizing the local equilibrium probability distribution function. Instability analysis results are obtained in three benchmark problems, two in closed geometries and one in open flow, namely the square and cubic lid-driven cavity flow and flow in the wake of the circular cylinder. Comparisons with results delivered by classic spectral element methods verify the accuracy of the proposed new methodologies and point potential limitations particular to the LBM approach. The known issue of appearance of numerical instabilities when the SRT model is used in direct numerical simulations employing the LBM is shown to be reflected in a spurious global eigenmode when the SRT model is used in the instability analysis. Although this mode is absent in the multiple relaxation times model, other spurious instabilities can also arise and are documented herein. Areas of potential improvements in order to make the proposed methodology competitive with established approaches for global instability analysis are discussed

On the massive gluon propagator, the PT-BFM scheme and the low-momentum behaviour of decoupling and scaling DSE solutions

We study the low-momentum behaviour of Yang-Mills propagators obtained from Landau-gauge Dyson-Schwinger equations (DSE) in the PT-BFM scheme. We compare the ghost propagator numerical results with the analytical ones obtained by analyzing the low-momentum behaviour of the ghost propagator DSE in Landau gauge, assuming for the truncation a constant ghost-gluon vertex and a simple model for a massive gluon propagator. The asymptotic expression obtained for the regular or decoupling ghost dressing function up to the order ${\cal O}(q^2)$ is proven to fit pretty well the numerical PT-BFM results. Furthermore, when the size of the coupling renormalized at some scale approaches some critical value, the numerical PT-BFM propagators tend to behave as the scaling ones. We also show that the scaling solution, implying a diverging ghost dressing function, cannot be a DSE solution in the PT-BFM scheme but an unattainable limiting case.Comment: 16 pages, 2 figs., 2 tabs (updated version to be published in JHEP

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

Aproximacions demogràfiques per avaluar l’estat de conservació de la baldriga cendrosa Calonectris diomedea i la baldriga balear Puffinus mauretanicus: Demographic approaches for assessing the conservation status of Scopoli’s Shearwater Calonectris diomedea and the Balearic Shearwater Puffinus mauretanicus

In the north-western Mediterranean there are two breeding species of procellariforms from the Procellariidae family: Scopoli’s shearwater Calonectris diomedea and the Balearic shearwater Puffinus mauretanicus. Long-term monitoring carried out in a number of breeding colonies provides enough data to be able to assess the conservation status of both species using demographic approaches that estimate parameters such as survival, recruitment and fertility. This type of approach is recommended because it provides a reliable conservation diagnosis and knowledge of the processes that determine variations in population dynamics. Both species were found to have critically low adult survival rates, unexpected in such long-lived species, which makes these populations unviable under current conditions. This agrees with previous available information on incidental bycatch on fishing gears, and confirms that this threat, together with predation by terrestrial carnivores are of critical concern for the conservation of the populations. The fact that some of the breeding colonies did not show a declining trend indicates that several compensatory mechanisms, such as an immigration rescue effect, may be acting at local level. Nevertheless, all the evidence gathered to date suggests that these compensatory mechanisms are not permanent and that if no action is taken these populations could become extinct. In the case of Scopolis’ shearwater, the global population is much more abundant, so there may be time for mitigation actions to be undertaken. Given the size of the breeding population of Balearic shearwaters, we recommend urgent measures be carried out to reduce adult mortality in this endemic species to prevent its extinction

Management of the COPD patient with comorbidities: an experts recommendation document

Background: Chronic obstructive pulmonary disease (COPD) is associated with multiple comorbidities, which impact negatively on patients and are often underdiagnosed, thus lacking a proper management due to the absence of clear guidelines. Purpose: To elaborate expert recommendations aimed to help healthcare professionals to provide the right care for treating COPD patients with comorbidities. Methods: A modified RAND-UCLA appropriateness method consisting of nominal groups to draw up consensus recommendations (6 Spanish experts) and 2-Delphi rounds to validate them (23 Spanish experts) was performed. Results: A panel of Spanish internal medicine experts reached consensus on 73 recommendations and 81 conclusions on the clinical consequences of the presence of comorbidities. In general, the experts reached consensus on the issues raised with regard to cardiovascular comorbidity and metabolic disorders. Consensus was reached on the use of selective serotonin reuptake inhibitors in cases of depression and the usefulness of referring patients with anxiety to respiratory rehabilitation programmes. The results also showed consensus on the usefulness of investigating the quality of sleep, the treatment of pain with opioids and the evaluation of osteoporosis by lateral chest radiography. Conclusion: This study provides conclusions and recommendations that are intended to improve the management of the complexity of patients with COPD and important comorbidities, usually excluded from clinical trials. Keywords: chronic obstructive pulmonary disease, COPD, comorbidities, modified RANDUCLA, Delphi techniqu

Gluon mass through ghost synergy

In this work we compute, at the 'one-loop-dressed' level, the nonperturbative contribution of the ghost loops to the self-energy of the gluon propagator, in the Landau gauge. This is accomplished within the PT-BFM formalism, which guarantees the gauge-invariance of the emerging answer. In particular, the contribution of the ghost-loops is automatically transverse, by virtue of the QED-like Ward identities satisfied in this framework. Using as nonperturbative input the available lattice data for the ghost dressing function, we show that the ghost contributions have a rather sizable effect on the overall shape of the gluon propagator, both for d=3,4. Then, by exploiting a recently introduced dynamical equation for the effective gluon mass, whose solutions depend crucially on the characteristics of the gluon propagator at intermediate energies, we show that if the ghost loops are removed from the gluon propagator then the gluon mass vanishes. These findings strongly suggest that, at least at the level of the Schwinger-Dyson equations, the effects of gluons and ghosts are inextricably connected, and must be combined suitably in order to reproduce the results obtained in the recent lattice simulations

Two- and three-point functions in two-dimensional Landau-gauge Yang-Mills theory: Continuum results

We investigate the Dyson-Schwinger equations for the gluon and ghost propagators and the ghost-gluon vertex of Landau-gauge gluodynamics in two dimensions. While this simplifies some aspects of the calculations as compared to three and four dimensions, new complications arise due to a mixing of different momentum regimes. As a result, the solutions for the propagators are more sensitive to changes in the three-point functions and the ansaetze used for them at the leading order in a vertex a expansion. Here, we therefore go beyond this common truncation by including the ghost-gluon vertex self-consistently for the first time, while using a model for the three-gluon vertex which reproduces the known infrared asymptotics and the zeros at intermediate momenta as observed on the lattice. A separate computation of the three-gluon vertex from the results is used to confirm the stability of this behavior a posteriori. We also present further arguments for the absence of the decoupling solution in two dimensions. Finally, we show how in general the infrared exponent kappa of the scaling solutions in two, three and four dimensions can be changed by allowing an angle dependence and thus an essential singularity of the ghost-gluon vertex in the infrared.Comment: 24 pages; added references, improved choices of parameters for vertex models; identical to version published in JHE

Bounds and Decays of New Heavy Vector-like Top Partners

We study the phenomenology of new heavy vector-like fermions that couple to the third generation quarks via Yukawa interactions, covering all the allowed representations under the standard model gauge groups. We first review tree and loop level bounds on these states. We then discuss tree level decays and loop-induced decays to photon or gluon plus top. The main decays at tree level are to W b and/or Z and Higgs plus top via the new Yukawa couplings. The radiative loop decays turn out to be quite close to the naive estimate: in all cases, in the allowed perturbative parameter space, the branching ratios are mildly sensitive on the new Yukawa couplings and small. We therefore conclude that the new states can be observed at the LHC and that the tree level decays can allow to distinguish the different representations. Moreover, the observation of the radiative decays at the LHC would suggest a large Yukawa coupling in the non-perturbative regime.Comment: 32 pages, 2 tables, 10 figure