Medium development strategies and scale down models for a high density high productivity cell line

Medium Development at Regeneron continues to enhance fed batch culture productivity. These efforts have been enabled through the development of high throughput scale down models in shake flasks and the ambr® 250. Design of Experiment (DOE) approaches have been applied to optimize the operating conditions in the small scale models leading to performance for growth and titer that match benchtop bioreactor with no off-set. The development of these representative scale down models and our approach to medium development will be described. A medium development case study will be presented from a recent Regeneron fed batch process with a cell line achieving high cell densities and depleting the culture of key amino acids. The traditional medium development approach of supplementing the culture with the depleted nutrients was unsuccessful: high amino acid consumption rates required large amounts of amino acids resulting in significantly increased culture osmolality and reduced productivity. Leveraging high throughput culture systems and multifactor DOEs, multiple medium composition factors in combination were rapidly evaluated. Mathematical models relating medium input factors to process outputs are generated that allow for process optimization. Using this approach, a new feeding strategy was developed that limits increases in osmolality and yields titers approaching 10g/L in both the scale down systems and a process that has been implemented for clinical scale manufacturing of a monoclonal antibody

Measurements of eye lens doses in interventional cardiology using OSL and electronic dosemeters

The purpose of this paper is to test the appropriateness of OSL and electronic dosemeters to estimate eye lens doses at interventional cardiology environment. Using TLD as reference detectors, personal dose equivalent was measured in phantoms and during clinical procedures. For phantom measurements, OSL dose values resulted in an average difference of 215% vs. TLD. Tests carried out with other electronic dosemeters revealed differences up to +/- 20% versus TLD. With dosemeters positioned outside the goggles and when TLD doses were > 20 mu Sv, the average difference OSL vs. TLD was 29%. Eye lens doses of almost 700 mu Sv per procedure were measured in two cases out of a sample of 33 measurements in individual clinical procedures, thus showing the risk of high exposure to the lenses of the eye when protection rules are not followed. The differences found between OSL and TLD are acceptable for the purpose and range of doses measured in the survey.Postprint (published version

Advanced characterization and optical simulation for the design of solar selective coatings based on carbon: transition metal carbide nanocomposites

Solar selective coatings based on carbon transition metal carbide nanocomposite absorber layers were designed. Pulsed filtered cathodic arc was used for depositing amorphous carbon:metal carbide (a-C:MeC, Me = V, Mo) thin films. Composition and structure of the samples were characterized by ion beam analysis, X-ray diffraction, Raman spectroscopy, and transmission electron microscopy. The optical properties were determined by ellipsometry and spectrophotometry. Three effective medium approximations (EMA), namely Maxwell-Garnett, Bruggeman, and Bergman, were applied to simulate the optical behaviour of the nanocomposite thin films. Excellent agreement was achieved between simulated and measured reflectance spectra in the entire wavelength range by using the Bergman approach, where in-depth knowledge of the nanocomposite thin film microstructure is included. The reflectance is shown to be a function of the metal carbide volume fraction and its degree of percolation, but not dependent on whether the nanocomposite microstructure is homogeneous or a self-organized multilayer. Solar selective coatings based on an optimized a-C:MeC absorber layer were designed exhibiting a maximum solar absorptance of 96% and a low thermal emittance of ~5% and 15% at 25 and 600 °C, respectively. The results of this study can be considered as a predictive design tool for nanomaterial-based optical coatings in general

Quantum kinetic Ising models

We introduce a quantum generalization of classical kinetic Ising models, described by a certain class of quantum many body master equations. Similarly to kinetic Ising models with detailed balance that are equivalent to certain Hamiltonian systems, our models reduce to a set of Hamiltonian systems determining the dynamics of the elements of the many body density matrix. The ground states of these Hamiltonians are well described by matrix product, or pair entangled projected states. We discuss critical properties of such Hamiltonians, as well as entanglement properties of their low energy states.Comment: 20 pages, 4 figures, minor improvements, accepted in New Journal of Physic

DIAGNÓSTICO DE INDICADORES DE CALIDAD FÍSICO-QUÍMICA DEL AGUA EN AFLUENTES DEL RÍO ATOYAC - DIAGNOSIS OF INDICATORS OF PHYSICAL-CHEMICAL QUALITY OF WATER IN AFFLUENTS OF THE ATOYAC RIVER

En la Región de Texmelucan, Pue., las principales fuentes de agua para riego provienen del deshielo de los volcanes y de pozos profundos; estas fuentes satisfacen las necesidades de agua del área agrícola de Texmelucan y sus alrededores. Sin embargo, alrededor de 350 productores también emplean aguas residuales para regar sus cultivos. Se evaluaron algunos parámetros que inciden en la calidad físico-química del agua cuando se utiliza con fines de riego (pH, CE, Ca2+, Mg2+, K+, PO42-, SO42-, CO32-, HCO3-, Na+, B y Cl-). Se realizó un muestreo aleatorio en 28 puntos, en afluentes del cauce del Río Atoyac, donde se tomaron muestras de agua para realizar el análisis físico-químico correspondiente. Los resultados muestran que la CE osciló entre 0 y 0.875 dS m-1; el 64.28% correspondió a aguas de baja salinidad y bajo contenido de sodio (clase C1S1), el 28.57% a aguas con salinidad media y bajo contenido de sodio (clase C2S1) y el 7.15% a aguas de salinidad alta y bajo contenido de sodio (clase C3S1). En promedio, el Ca (0.98 meq L-1) y Mg (1.11 meq L-1) estuvieron presentes en mayor concentración, lo que modificó favorablemente los valores de la relación de adsorción de sodio (RAS). Los iones bicarbonato (HCO3-) en el agua presentaron una media de 1.83 meq L-1. La concentración de Cl-, HCO3-, CO3-2, B y SO4-2 no ha afectado a los cultivos establecidos y la concentración de PO42- es un aporte significativo a los cultivos. Estos resultados indican que la región de Texmelucan, Pue., tiene agua apta para el riego desde el punto de vista físico-químico; sin considerar el contenido de metales pesados ni análisis biológicos de la misma

Acute Kidney Injury in Pregnancy: The Need for Higher Awareness. A Pragmatic Review Focused on What Could Be Improved in the Prevention and Care of Pregnancy-Related AKI, in the Year Dedicated to Women and Kidney Diseases

Pregnancy-related acute kidney injury (pAKI), preeclampsia (PE), and the hypertensive disorders of pregnancy are closely related conditions, which are, in turn, frequently linked to pre-existing and often non-diagnosed chronic kidney disease (CKD). The current literature and research mainly underline the effects of pregnancy complications on the offspring; this review strongly emphasizes the maternal health as well. These conditions not only negatively affect pregnancy outcomes, but have a relevant effect on the future health of affected mothers and their children. Therefore, dedicated diagnostic and follow-up programs are needed, for optimizing materno-foetal health and reducing the impact of pregnancy-related problems in the mothers and in the new generations. This narrative review, performed on the occasion of the 2018 World Kidney Day dedicated to women's health, focuses on three aspects of the problem. Firstly, the risk of AKI in the hypertensive disorders of pregnancy (the risk is the highest in developing countries; however PE is the main cause of pregnancy related AKI worldwide). Secondly, the effect of AKI and the hypertensive disorders of pregnancy on the development of CKD in the mother and offspring: long-term risks are increased; the entity and the trajectories are still unknown. Thirdly, the role of CKD in the pathogenesis of AKI and the hypertensive disorders of pregnancy: CKD is a major risk factor and the most important element in the differential diagnosis; pregnancy is a precious occasion for early diagnosis of CKD. Higher awareness on the importance of AKI in pregnancy is needed to improve short and long term outcomes in mothers and children

Magnetothermodynamics of BPS baby skyrmions

The magnetothermodynamics of skyrmion type matter described by the gauged BPS baby Skyrme model at zero temperature is investigated. We prove that the BPS property of the model is preserved also for boundary conditions corresponding to an asymptotically constant magnetic field. The BPS bound and the corresponding BPS equations saturating the bound are found. Further, we show that one may introduce pressure in the gauged model by a redefinition of the superpotential. Interestingly, this is related to non-extremal type solutions in the so-called fake supersymmetry method. Finally, we compute the equation of state of magnetized BSP baby skyrmions inserted into an external constant magnetic field $H$ and under external pressure $P$, i.e., $V=V(P,H)$, where $V$ is the "volume" (area) occupied by the skyrmions. We show that the BPS baby skyrmions form a ferromagnetic medium.Comment: Latex, 39 pages, 14 figures. v2: New results and references added, physical interpretation partly change