Analysis of water-soluble vitamins in biopharma raw materials by electrophoresis micro-chips with contactless conductivity detection

Detailed information concerning the composition of the raw materials employed in the production of biologics is important for the efficient control and optimization of bioprocesses. The analytical methods used in these applications must be simple and fast as well as be easily transferable from one site to another. In that context, microchip‐based electrophoresis represents a promising tool for application in the analysis of raw materials in biologics. Using electrophoresis micro‐chips, analysis times can be reduced to seconds and high separation efficiencies can be achieved using extremely low volume samples, minimal reagent consumption and waste generation, low cost/disposability, portability and ease of mass‐production [1]. Additionally the use of Capacitively Coupled Contactless Conductivity Detection (C4D) offers a rather simple and yet sensitive method for detection of ionic species. Recently, C4D has gained much popularity as on‐chip detection in electrophoresis micro‐chips [2]. The main reason for this is that there is no physical contact of the detection electrodes with the electrolyte solution. Therefore, the integration of this detection mode within the analytical system is rather simple. Furthermore, the background noise is significantly reduced leading to lower detection limits than the conventional contact conductivity detection. Vitamins are present at very low concentrations in biopharma raw materials and are usually determined using HPLC and CE methods [3]. Electrophoresis micro‐chips are a very good alternative to these techniques due to the shorter analysis time and yet very good resolution, among others. In this paper, we present the application of electrophoresis micro‐chips with C4D detection to the analysis of water‐soluble vitamins in raw materials used for the production of biologics in bioreactors. For that purpose, hybrid PDMS/glass chips were fabricated by using standard photolithographic techniques (Figure 1). The chip structure contains an extremely long channel of 101 mm (50 x 50 μm width x depth). Figure 2 shows the setup used for vitamins detection

Solutions of the divergence and Korn inequalities on domains with an external cusp

This paper deals with solutions of the divergence for domains with external cusps. It is known that the classic results in standard Sobolev spaces, which are basic in the variational analysis of the Stokes equations, are not valid for this class of domains. For some bounded domains $\Omega\subset{\mathbb R}^n$ presenting power type cusps of integer dimension $m\le n-2$, we prove the existence of solutions of the equation ${div}{\bf u}=f$ in weighted Sobolev spaces, where the weights are powers of the distance to the cusp. The results obtained are optimal in the sense that the powers cannot be improved. As an application, we prove existence and uniqueness of solutions of the Stokes equations in appropriate spaces for cuspidal domains. Also, we obtain weighted Korn type inequalities for this class of domains

On the weighted fractional Poincare-type inequalities

Weighted fractional Poincare-type inequalities are proved on John domains whenever the weights defined on the domain depend on the distance to the boundary and to an arbitrary compact set in the boundary of the domain.Peer reviewe

Analysis of biopharma raw materials by electrophoresis microchips with contactless conductivity detection

Detailed information concerning the composition of the raw materials employed in the production of biologics is important for the efficient control and optimization of bioprocesses. We demonstrate the application of electrophoresis microchips with capacitively-coupled contactless conductivity detection (C4D) to the analysis of wa-ter-soluble vitamins and metal cations in raw material solutions that are subse-quently fed into bioreactors for the production of biologics

SDN-AAA: Towards the standard management of AAA infrastructures

Software Defined Networking (SDN) is a widely deployed technology enabling the agile and flexible management of networks and services. This paradigm represents an appropriate candidate to address the dynamic and secure management of large and complex Authentication, Authorization and Accounting (AAA) infrastructures. In those infrastructures, there are several nodes which must exchange information securely to interconnect different realms. This article describes a novel SDN-based framework with a data model-driven approach following the standard YANG, named SDN-AAA, which can be used to dynamically manage routing and security configuration in AAA scenarios.Comment: 7 pages, 5 figure

Exceso de mortalidad, esperanza de vida y años de vida perdidos por COVID en España

Se presenta el estudio sobre cuál ha sido el impacto de la Covid-19 en la población española, analizando tres indicadores: mortalidad, esperanza de vida y años perdidos. Las conclusiones del estudio son: 1. La COVID-19 tuvo efectos directos e indirectos sobre el exceso de mortalidad y sobre la mortalidad prematura; 2. Los métodos del exceso de muertes y la mortalidad prematura por grupos de edad, sexos y regiones, junto con las tendencias de periodo y estacionales, ayudan a conocer el impacto en la salud de factores que afectan a la salud pública; 3. Las diferencias de impacto de la COVID-19 entre comunidades autónomas han de suponer un primer paso para evaluar las políticas sanitariasN

Propuestas para un real decreto de comités de ética de la investigación

Propuestas para un real decreto de comités de ética de la investigación, Fernando García López. Centro Nacional de Epidemiología. Presidente del CEI del Instituto de Salud Carlos III.N

Pautas éticas en vigilancia epidemiológica y en brotes epidémicos infecciosos

Definición de vigilancia de la salud pública. El estudio de sífilis de Tuskegee. Hitos en la ética de la investgación en seres humanos. Consideraciones éticas fundamentales para la vigilancia en salud pública. Las pautas de la OMS sobre la ética en la vigilancia de la salud pública. Cuestiones éticas en los brotes infecciosos principios éticos más relevantes. Las obligaciones de los gobiernos y de la comunidad internacional. Obligación de asegurar la protección y los derechos de los participantes. Intercambio de datos, almacenamiento de muestras y propuestas.N

Dietary micronutrients intake and plasma fibrinogen levels in the general adult population.

Plasma fibrinogen predicts cardiovascular and nonvascular mortality. However, there is limited population-based evidence on the association between fibrinogen levels and dietary intakes of micronutrients possibly associated with inflammation status. Data were taken from the ENRICA study, conducted with 10,808 individuals representative of the population of Spain aged ≥ 18 years. Nutrient intake (vitamin A, carotenoids, vitamin B6, vitamin C, vitamin D, vitamin E, magnesium, selenium, zinc and iron) was estimated with a validated diet history, and plasma fibrinogen was measured under appropriate quality checks. Statistical analyses were performed with linear regression and adjusted for main confounders. The geometric means of fibrinogen (g/L) across increasing quintiles of nutrient intake were 3.22, 3.22, 3.22, 3.16, and 3.19 (p-trend = 0.030) for vitamin E; 3.23, 3.22, 3.20, 3.19, and 3.19 (p-trend = 0.047) for magnesium; and 3.24, 3.22, 3.19, 3.21, and 3.19 (p-trend = 0.050) for iron. These inverse associations were more marked in participants with abdominal obesity and aged ≥ 60 years, but lost statistical significance after adjustment for other nutrients. Although dietary intakes of vitamin E, magnesium and iron were inversely associated with fibrinogen levels, clinical implications of these findings are uncertain since these results were of very small magnitude and mostly explained by intake levels of other nutrients.This work has been funded by State Secretary of R + D + I and FEDER/FSE FIS grants (F.R.A., grant 16/609 and 19/319; E.L.G., grant 16/1512); and the JPI HDHL-SALAMANDER project (F.R.A., grant APCIN 2016-145). The funders had no role in the design, analysis or writing of this workS