Search

A variety of CTLA4-Fc fusion proteins and anti-CTLA4 monoclonal antibody have been approved. Given the shortcomings of macromolecular antibodies, recombinant proteins derived from the tenth unit of human type III fibronectin (FN3) termed monobody were studied as CTLA4 analogs in this study. A peptide EL16 1 derived from CD80-binding domain (MYPPPY motifs) in the complementarity determining region (CDR) 3 of CTLA4 was found to inhibit the interaction of CTLA4 with CD80 significantly. Afterward, the peptide EL16 as well as the CDR1 of CTLA4 which is also critical for its binding to CD80 were grafted onto FN3 and obtained a novel CD80 binding monobody protein CFN13. 2 CFN13 showed 80% binding affinity compared to CTLA4. In addition, to increase the half-life, CFN13 was fused to human IgG1 Fc to generate CFN13-Fc fusion protein. As expected, CFN13-Fc bound to CD80 in a dosage-dependent manner as CFN13 did, and displayed 41.0% and 31.4% inhibition on the interaction of CTLA4-Fc with CD80 at 200 μg/ml and 100 μg/ml respectively. Moreover, peptide EL16 could inhibit CFN13-Fc binding to CD80 significantly, with the inhibition ratio of 64.3% and 52.8% at 100 and 50 μg/ml respectively, indicating that the peptide EL16 and CFN13-Fc shared the similar binding sites with CD80 and the CDR3 motif of CTLA4 contributed more than CDR1 in binding to CD80. In summary, our study provides insights into small molecular analogs of CTLA4. • Peptide EL16 derived from CDR3 loop of CTLA4 inhibited CTLA4/CD80 interaction. • EL16 and CDR1 of CTLA4 were grafted onto FN3, generating a CTLA4 analog CFN13. • CFN13 and CFN13-Fc had high binding affinity to CD80. • CFN13-Fc inhibited CTLA4/CD80 interaction as the peptide EL16 did. • The binding mode of peptide EL16 and CFN13 with CD80 were proposed. [ABSTRACT FROM AUTHOR]

We are interested in approximate Byzantine consensus problem, wherein all the fault-free processes reach consensus asymptotically (approximately in finite time). In particular, we focus on the algorithms under which each process communicates with other processes that are up to l hops away and maintains minimal states across iterations. For a given l , we identify a necessary and sufficient condition on the network structure for the existence of iterative algorithms of interest. Our necessary and sufficient condition generalizes the tight condition identified in prior work for l = 1 . For l ≥ l ⁎ , where l ⁎ is the length of a longest cycle-free path in the given network, our condition is equivalent to the necessary and sufficient conditions for exact consensus in undirected and directed networks both. [ABSTRACT FROM AUTHOR]

1,2-Dichloroethane (1,2-DCA) is a common compound found in groundwater contaminated with organics. This compound is difficult to remove from groundwater and has the potential to inflict significant harm on human health and the environment. This study used sodium persulfate (Na 2 S 2 O 8) activated by sodium hydroxide (NaOH) to remove 1,2-DCA from aqueous solutions. Density functional theory was employed to calculate the potential energy surface of the reactants, intermediates, transient states, and products to thoroughly analyze the degradation pathways. The computations were performed in combination with in situ remediation of a 1,2-DCA plume from a point source to verify the industrial applicability of the technology. The results showed the 1,2-DCA removal efficiency was impacted considerably by the Na 2 S 2 O 8 dosage and the dosing sequence of Na 2 S 2 O 8 and NaOH, with the mean removal ratio reaching 96.24%. A free radical reaction was the main pathway of 1,2-DCA degradation; superoxide radical (O 2 •–) existed stably and played a key role in the reaction, and the main transformation proceeded via a vinyl chloride intermediate. The maximum removal of 1,2-DCA reached 91.79% in the in situ remediation. The developed technology exhibits important advantages in enabling flexible control over chemical dosages, long durations of effective activity, and rapid full-cycle remediation. • SPASH was in situ pilot-scale tested to remediate 1,2-DCA in groundwater. • A free radical reaction was the main pathway of 1,2- DCA degradation. • The transformation involving vinyl chloride comprised the main pathway. • The technology exhibits important advantages in rapid full-cycle remediation. [ABSTRACT FROM AUTHOR]