Accelerate cell culture development using the modular automated sampling technology (MASTTM) platform in an integrated bioprocess lab environment

Biopharmaceutical companies are continually striving to fundamentally understand and optimize cellular performance within their bioreactors. While on-line process analytical technology (PAT) tools like dielectric and Raman spectroscopy are helping to provide insight into cell processes that impact titer and antibody quality, the integration of these data with off-line measurements such as cell density, viability, titer and glycosylation remains an elusive goal. Bend Research Inc., in collaboration with Lilly, Pfizer and other major biopharmaceutical companies, is advancing the Modular Automated Sampling Technology (MASTTM) platform and integrating this system with automated analytical and data retrieval systems. This approach allows application of novel experimental methods providing greater insight into the bioreactor environment. In this process, aseptically collected bioreactor samples are delivered to multiple analytical devices with resulting data being automatically retrieved and curated. This data is presented at a graphical user interface (GUI) for real-time data analysis and predictive model development. Early studies with the MAST sample delivery system coupled with our data-processing software increased system observability and real-time process understanding by the end user. This presentation describes how Bend Research has used the MAST platform as a cornerstone of an integrated lab environment. We will describe how the MAST system works and the features that set it apart from other autosampling solutions. Applications will be presented where MAST facilitated the use novel development approaches yielding enhance process understanding From this new level of insight into the bioreactor, scientists can obtain enhanced data-driven guidance for key activities like optimizing process operation. With this new technology, the bioprocess industry can make major advances toward advanced real-time testing, predictive control, and overall enhanced bioprocess design and operation

Glutamate, N-acetyl aspartate and psychotic symptoms in chronic ketamine users

Rationale: Ketamine, a non-competitive NMDA receptor antagonist, induces acute effects resembling the positive, negative and cognitive symptoms of schizophrenia. Chronic use has been suggested to lead to persistent schizophrenia-like neurobiological changes. Objectives: This study aims to test the hypothesis that chronic ketamine users have changes in brain neurochemistry and increased subthreshold psychotic symptoms compared to matched poly-drug users. Methods: Fifteen ketamine users and 13 poly-drug users were included in the study. Psychopathology was assessed using the Comprehensive Assessment of At-Risk Mental State. Creatine-scaled glutamate (Glu/Cr), glutamate + glutamine (Glu + Gln/Cr) and N-acetyl aspartate (NAA/Cr) were measured in three brain regions—anterior cingulate, left thalamus and left medial temporal cortex using proton magnetic resonance spectroscopy. Results: Chronic ketamine users had higher levels of subthreshold psychotic symptoms (p < 0.005, Cohen’s d = 1.48) and lower thalamic NAA/Cr (p < 0.01, d = 1.17) compared to non-users. There were no differences in medial temporal cortex or anterior cingulate NAA/Cr or in Glu/Cr or Glu + Gln/Cr in any brain region between the two groups. In chronic ketamine users, CAARMS severity of abnormal perceptions was directly correlated with anterior cingulate Glu/Cr (p < 0.05, r = 0.61—uncorrected), but NAA/Cr was not related to any measures of psychopathology. Conclusions: The finding of lower thalamic NAA/Cr in chronic ketamine users may be secondary to the effects of ketamine use compared to other drugs of abuse and resembles previous reports in individuals at genetic or clinical risk of schizophrenia

Did a Switch in Time Save Nine?

Franklin Delano Roosevelt’s court-packing plan of 1937 and the “switch in time that saved nine” animate central questions of law, politics, and history. Did Supreme Court Justice Roberts abruptly switch votes in 1937 to avert a showdown with Roosevelt? Scholars disagree vigorously about whether Roberts’s transformation was gradual and anticipated or abrupt and unexpected. Using newly collected data of votes from the 1931–1940 terms, we contribute to the historical understanding of this episode by providing the first quantitative evidence of Roberts’s transformation. Applying modern measurement methods, we show that Roberts shifted sharply to the left in the 1936 term. The shift appears sudden and temporary. The duration of Roberts’s shift, however, is in many ways irrelevant, as the long-term transformation of the Court is overwhelmingly attributable to Roosevelt’s appointees