Development of an N-1 perfusion process and optimized scale-down models for implementation in a platform CHO cell culture manufacturing process

The use of N-1 perfusion, coupled with high-inoculum fed batch in CHO cell culture manufacturing processes, has been shown to increase volumetric productivity and shorten the duration of the fed-batch production phase. Implementation of N-1 perfusion as part of a platform process requires the ability to screen multiple clones and to optimize media and process parameters in a high-throughput manner. We have developed an N-1 perfusion process, along with a series of scale-down models for N-1 perfusion using shake flasks, cell culture tubes, and deep-well plates. Process parameters for scale-down models were optimized to maximize comparability of growth profiles and cell culture performance relative to 5L N-1 perfusion bioreactors. Scale-down models were used to inoculate fed-batch experiments in Ambr15 micro-bioreactors at high seeding density, in order to compare growth and productivity profiles to those observed in 5L bench scale bioreactors. Multiple cell lines derived from different CHO hosts were evaluated in order to verify the robustness of the scale-down models. Results demonstrated that cell growth and viability in the optimized scale-down models were comparable to those observed in 5L N-1 perfusion bioreactors. Furthermore, growth, productivity, and product quality profiles from high-inoculum fed-batch experiments were comparable regardless of inoculum source. Optimized scale down models of N-1 perfusion, coupled with Ambr15 fed-batch production micro-bioreactors, have now been integrated into a high-throughput and robust workflow to enable DOE and screening experiments for clone selection, media development and parameter optimization in a platform N-1 perfusion process for monoclonal antibody manufacturing

Psychiatric comorbidities among people with epilepsy: A population-based assessment in disadvantaged communities

Psychiatric disorders are frequent among people with epilepsy but often under-recognized. The diagnosis and treatment of these disorders in low- and low-middle-income countries (LMICs) are challenging. METHODS: This cross-sectional survey included people recruited during a community epilepsy screening program involving 59,509 individuals from poor communities in Ludhiana in Northwest India. Adults (age ≥18 years) with confirmed epilepsy on antiseizure medications were screened for depression and anxiety using the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and Generalized Anxiety Disorder-7 (GAD-7) twice over two years of follow-up. They were later interviewed for symptoms using the Brief Psychiatric Rating Scale, which was then confirmed by assessments by an experienced psychiatrist. RESULTS: Of the 240 people with confirmed epilepsy, 167 (70%) were adults, of whom, 116 (70%) eventually participated in the study. The NDDI-E with a cut-off of 15 identified depression in 14 (12%) of 116 people after one year of follow-up and 17 (15%) at two years. The GAD-7 using a cut-off of 6 identified 22 (19%) at one year and 32 (28%) with anxiety at two years. The area under the curves for NDDI-E was estimated as 0.62 (95%CI, 0.51-0.73; SE: 0.06; p = 0.04) and for GAD-7 as 0.62 (95%CI, 0.46-0.78; SE: 0.08; p = 0.12). Brief Psychiatric Rating Scale identified 63 (54%) people with psychiatric symptoms, for whom, a psychiatric diagnosis was confirmed in 60 (52%). A psychiatric diagnosis was associated with education below high school [Odds Ratio (OR): 2.59, 95%CI, 1.12-5.1; p = 0.03], later age of seizure onset (OR, 1.05, 95%CI: 1.0-1.10; p = 0.04), seizure frequency of at least one/year at enrolment (OR, 2.36, 95%CI: 1.0-5.58; p = 0.05) and the use of clobazam (OR, 5.09, 95%CI, 1.40-18.42; p = 0.01). CONCLUSION: Depression and anxiety are common in people with epilepsy. Our findings underscore the low yields of screening instruments, NDDI-E and GAD-7, and comparatively better professionally-administered diagnostic assessments in resource-limited settings in LMICs. Moreover, previously established cut-offs do not apply to the community studied

Extended Hückel Theory for Quantum Transport in Magnetic Tunnel Junctions

Abstract-Spin-resolved conductivities in magnetic tunnel junctions are calculated using a semiempirical tight-binding model and non-equilibrium Green's functions. The performance of half-metallic electrodes is studied by comparing conventional Fe-MgO-Fe structures to Co2FeAl-MgO-Co2FeAl structures. The results show higher tunneling magnetoresistance and resistancearea product for Co2FeAl devices across a wide bias range

Scintillation Properties of Eu2+-Activated Barium Fluoroiodide

The scintillation properties of powders and single-crystals of BaFI doped with Eu2+ are presented. Single crystals were grown by the vertical Bridgman technique. Under optical and X-ray excitation, the samples exhibit a narrow E2+ 5d-4f transition emission centered at 405 nm. The scintillation light output is estimated to be 55,000+-5,000 photons/MeV at 662 keV with 85percent of the light decaying within 600 ns. An energyresolution of 8.5percent full width at half maximum (FWHM) has been achieved using this scintillator for 662 keV excitation (137Cs source) at room temperature

An Empirical Approach To Solving The General Utility Problem In Speedup Learning

Many recent approaches to avoiding the utility problem in speedup learning (the eventual degradation of performance due to increasing amounts of learned problem-solver control knowledge) rely on sophisticated utility measures and significant numbers of training problems to accurately estimate the utility of control knowledge. Empirical results presented here and elsewhere indicate that a simple selection strategy of retaining all control rules derived from a training problem solution quickly defines an efficient set of control knowledge from few training problems. This simple selection strategy provides a low-cost alternative to example-intensive approaches for improving the speed of a problem solver. Experimentation illustrates the existence of a minimum (representing least cost) in the learning curve which is reached after a few training examples. Stress is placed on controlling the amount of learned knowledge as opposed to which knowledge. An attempt is also made to relate domain ch..

Evaluation of salivary chromium levels among patients undergoing fixed orthodontic treatment

Aims: The present study was conducted for evaluation of salivary chromium levels among patients undergoing fixed orthodontic treatment. Materials & method: 20 patients who presented to the orthodontic clinic were selected. The salivary samples were taken from the patients in following stages: before appliance placement, one month, and 4 months following appliance placement. The salivary samples were collected in a plastic tube and were stored in the freezer before analysis. The samples were then transferred to the laboratory, and the amounts of metals were determined by graphite furnace atomic absorption spectrometry with an autosampler. Each sample was analyzed three times, and the average was reported. All the results were recorded and analysed by SPSS software. Results: Mean salivary chromium levels before appliance placement; one month after appliance placement and four months after appliance placement was 2.5 μg/L, 3.9 μg/L and 2.9 μg/L respectively. Significant results were obtained while comparing the alteration in salivary chromium levels. Significant results were obtained while comparing the salivary chromium levels at different time intervals. Conclusion: Corrosion of fixed orthodontic appliances leads to elevated salivary chromium levels early after the initiation of orthodontic treatment