Intramodule pressure profiles and protein accumulation during tangential flow filtration.

Tangential flow filtration (TFF) through a 30 kDa nominal molecular weight cut-off (MWCO) ultrafiltration membrane is widely employed to concentrate purified monoclonal antibodies (mAbs) to levels required for their formulation into injectable biologics. While TFF has been used to remove casein from milk for cheese production for over 35 years, and in pharmaceutical manufacture of biotherapeutic proteins for 20 years, the rapid decline in filtration rate (i.e.

pH and excipient profiles during formulation of highly concentrated biotherapeutics using bufferless media.

Several models have been developed to describe the shifts in pH and excipient concentrations seen during diafiltration of monoclonal antibody (mAb) products accounting for both Donnan equilibrium and electroneutrality constraints. However, these models have assumed that the mAb charge is either constant or only a function of pH, assumptions that will not be valid when formulating highly concentrated mAbs using bufferless or low-buffered media due to the change in local H concentration at the protein surface. The objective of this study was to incorporate the effects of both pH and ionic strength on the mAb charge, through the use of a charge regulation model based on the amino acid sequence of the mAb, into an appropriate mass balance model to describe the pH and excipient profiles during diafiltration.

What children do on the Internet: domains visited and their relationship to socio-demographic characteristics and academic performance.

HomeNetToo is a longitudinal field study designed to examine the antecedents and consequences of home Internet use in low-income families. Participants included 140 children, mostly 13-year-old African American (83%) boys (58%), living in single-parent households (75%) where the median annual income was $15,000 (USD). This report focuses on children's Internet activities, socio-demographic characteristics related to their Internet activities, and the relationship between academic performance and Internet activities.

Biochemical characterization of signal peptidase I from gram-positive Streptococcus pneumoniae.

Bacterial signal peptidase I is responsible for proteolytic processing of the precursors of secreted proteins. The enzymes from gram-negative and -positive bacteria are different in structure and specificity. In this study, we have cloned, expressed, and purified the signal peptidase I of gram-positive Streptococcus pneumoniae.