Towards maximum acceleration of monoclonal antibody development: Leveraging transposase-mediated cell line generation to enable GMP manufacturing within 3 months using a stable pool.

In recent years, acceleration of development timelines has become a major focus within the biopharmaceutical industry to bring innovative therapies faster to patients. However, in order to address a high unmet medical need even faster further acceleration potential has to be identified to transform "speed-to-clinic" concepts into "warp-speed" development programs. Recombinant Chinese hamster ovary (CHO) cell lines are the predominant expression system for monoclonal antibodies (mAbs) and are routinely generated by random transgene integration (RTI) of the genetic information into the host cell genome.

Accuracy of fully automated oscillometric central aortic blood pressure measurement techniques.

Background: Central aortic blood pressure (cBP) is a valuable predictor of cardiovascular risk. The lack of fully automated measurement devices impeded an implementation in daily clinical practice so far. The present study compares two novel automated oscillometric devices with invasively measured cBP.

Hemodynamics of paradoxical severe aortic stenosis: insight from a pressure-volume loop analysis.

Background: Controversy exists about the pathophysiology of different hemodynamic subgroups of AS. In particular, the mechanism of the paradoxical low-flow, low-gradient (PLFLG) AS with preserved ejection fraction (EF) is unclear.

Methods: A total of 41 patients with severe, symptomatic AS were divided into the following 4 subgroups based on the echocardiographically determined hemodynamics: (1) normal-flow, high-gradient (NFHG) AS; (2) low-flow, high-gradient AS; (3) paradoxical low-flow, low-gradient (PLFLG) AS with preserved EF and (4) low-flow, low-gradient (LFLG) AS with reduced EF.

CpG-methylation regulates a class of Epstein-Barr virus promoters.

DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian gene regulation. In general, cytosine-phosphatidyl-guanosine (CpG)-methylated promoters are transcriptionally repressed and nuclear proteins such as MECP2, MBD1, MBD2, and MBD4 bind CpG-methylated DNA and contribute to epigenetic silencing. Methylation of viral DNA also regulates gene expression of Epstein-Barr virus (EBV), which is a model of herpes virus latency.

AP-1 homolog BZLF1 of Epstein-Barr virus has two essential functions dependent on the epigenetic state of the viral genome.

EBV, a member of the herpes virus family, is a paradigm for human tumor viruses and a model of viral latency amenable for study in vitro. It induces resting human B lymphocytes to proliferate indefinitely in vitro and initially establishes a strictly latent infection in these cells. BZLF1, related to the cellular activating protein 1 (AP-1) family of transcription factors, is the viral master gene essential and sufficient to mediate the switch to induce the EBV lytic phase in latently infected B cells.