Evaluation of Raman spectroscopy for online monitoring of cell culture product quality

Recent years have shown an increase in the development and application of Raman spectroscopy for process monitoring and control in the biopharmaceutical industry. While Raman spectroscopy has been successfully used to predict concentration of cell counts and conventional metabolites, limited work has been presented on its capability to measure product titer and quality. Here, we present results using Raman spectroscopy to obtain online predictions of CHO antibody titer, charge variants, size variants, and glycan species across several products and cell lines. Products assessed include standard antibodies and complex molecular formats

Impact of multimorbidity count on all-cause mortality and glycaemic outcomes in people with type 2 diabetes: a systematic review protocol

Introduction: Type 2 diabetes (T2D) is a leading health priority worldwide. Multimorbidity (MM) is a term describing the co-occurrence of two or more chronic diseases or conditions. The majority of people living with T2D have MM. The relationship between MM and mortality and glycaemia in people with T2D is not clear. Methods and analysis: Medline, Embase, Cumulative Index of Nursing and Allied Health Complete, The Cochrane Library, and SCOPUS will be searched with a prespecified search strategy. The searches will be limited to quantitative empirical studies in English with no restriction on publication date. One reviewer will perform title screening and two review authors will independently screen the abstract and full texts using Covidence software, with disagreements adjudicated by a third reviewer. Data will be extracted using a using a Population, Exposure, Comparator and Outcomes framework. Two reviewers will independently extract data and undertake the risk of bias (quality) assessment. Disagreements will be resolved by consensus. A narrative synthesis of the results will be conducted and meta-analysis considered if appropriate. Quality appraisal will be undertaken using the Newcastle-Ottawa quality assessment scale and the quality of the cumulative evidence of the included studies will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. This protocol was prepared in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines to ensure the quality of our review. Ethics and dissemination: This review will synthesise the existing evidence about the impact of MM on mortality and glycaemic outcomes in people living with T2D and increase our understanding of this subject and will inform future practice and policy. Findings will be disseminated via conference presentations, social media and peer-reviewed publication

Process intensification: Case study with a CHO-based monoclonal antibody production process

Standard platform technologies for cell culture processing provide simple and robust strategies to meet rapid timelines for early process development and ease of manufacturing. However, when there is a need to achieve high antibody titers due to high product demand, both culture media and feed strategies must be customized for specific cell lines. Two case studies will describe the strategies employed as part of a process intensification effort to overcome the limitations of a platform Phase III cell culture process. The first case study will demonstrate an intensified fed-batch process development effort performed to maximize production of a CHO-based monoclonal antibody, while maintaining product quality comparability with the original Phase III process. The second case study will describe the evaluation of a concentrated fed-batch process using alternating tangential flow filtration to retain the protein in the bioreactor, and achieve even higher titers in support of the high product demand forecast. These case studies will show that the intensified fed-batch process improved titers by 50%, and the concentrated fed-batch process improved titers by 100% relative to the fed-batch platform

Paraphyly of organelle DNAs in Cycas Sect. Asiorientales due to ancient ancestral polymorphisms

<p>Abstract</p> <p>Background</p> <p>This study addresses the apportionment of genetic diversity between <it>Cycas revoluta </it>and <it>C. taitungensis</it>, species that constitute the section <it>Asiorientales </it>and represent a unique, basal lineage of the Laurasian genus <it>Cycas</it>. Fossil evidence indicates divergence of the section from the rest of <it>Cycas </it>at least 30 million years ago. Geographically, <it>C. taitungensis </it>is limited to Taiwan whereas <it>C. revoluta </it>is found in the Ryukyu Archipelago and on mainland China.</p> <p>Results</p> <p>The phylogenies of ribosomal ITS region of mtDNA and the intergenic spacer between <it>atp</it>B and <it>rbc</it>L genes of cpDNA were reconstructed. Phylogenetic analyses revealed paraphyly of both loci in the two species and also in the section <it>Asiorientales</it>. The lack of reciprocal monophyly between these long isolated sections is likely due to persistent shared ancestral polymorphisms. Molecular dating estimated that mt- and cp DNA lineages coalesced to the most recent common ancestors (TMRCA) about 327 (mt) and 204 MYA (cp), corresponding with the divergence of cycad sections in the Mesozoic.</p> <p>Conclusion</p> <p>Fates of newly derived mutations of cycads follow Klopfstein et al.'s surfing model where the majority of new mutations do not spread geographically and remain at low frequencies or are eventually lost by genetic drift. Only successful 'surfing mutations' reach very high frequencies and occupy a large portion of a species range. These mutations exist as dominant cytotypes across populations and species. Geographical subdivision is lacking in both species, even though recurrent gene flow by both pollen and seed is severely limited. In total, the contrasting levels between historical and ongoing gene flow, large population sizes, a long lifespan, and slow mutation rates in both organelle DNAs have all likely contributed to the unusually long duration of paraphyly in cycads.</p

Bioimpedance-derived membrane capacitance: Clinically relevant sources of variability, precision, and reliability

Membrane capacitance (

Clinical Follow‐up of Parkinson’s Disease With Newly Prescribed Quetiapine

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162820/2/mds28193_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162820/1/mds28193.pd

Origin and Dynamics of the Mutually Inclined Orbits of Upsilon Andromedae c and d

We evaluate the orbital evolution and several plausible origins scenarios for the mutually inclined orbits of Upsilon Andromedae c and d. These two planets have orbital elements that oscillate with large amplitudes and lie close to the stability boundary. This configuration, and in particular the observed mutual inclination, demands an explanation. The planetary system may be influenced by a nearby low-mass star, Upsilon And B, which could perturb the planetary orbits, but we find it cannot modify two coplanar orbits into the observed mutual inclination of ~30 deg. However, it could incite ejections or collisions between planetary companions that subsequently raise the mutual inclination to >30 deg. Our simulated systems with large mutual inclinations tend to be further from the stability boundary than Upsilon And, but we are able to produce similar systems. We conclude that scattering is a plausible mechanism to explain the observed orbits of Upsilon And c and d, but we cannot determine whether the scattering was caused by instabilities among the planets themselves or by perturbations from Upsilon And B. We also develop a procedure to quantitatively compare numerous properties of the observed system to our numerical models. Although we only implement this procedure to Upsilon And, it may be applied to any exoplanetary system.Comment: 19 pages, 5 figures, accepted to Astrophysical Journa

The effects of monetary policy on real estate investment in China: a regional perspective

Monetary policy on real estate investment in China has had varying impacts across the country due to regional differences. A supply-determined model is used to measure the policy effects on property investment volume based on a set of regional data from 2003 to 2010. This research yields several important findings contributing to an understanding of uneven policy effects on the unbalanced regional markets. Firstly, it is revealed that the eastern coastal provinces in China have a higher dependence on bank loans for housing investment than that of the other inland provinces. Secondly, this research has disentangled the specific transmission channels of monetary policy in the property market. Bank loan supply, instead of interest rates, would be a potentially effective policy tool for the government in making property market adjustment. Thirdly, the eastern coastal provinces are more sensitive in their responses to the changes of monetary stances than the other non-coastal central and western provinces. Therefore, the government must take note of the significant heterogeneity arising from the regional differences in estimating the policy impacts, although monetary policy is uniformly employed in the nation most of the time