No abstract

Site-specific chemical conjugation of proteins can enhance their therapeutic and diagnostic utility but has seldom been applied to CRISPR-Cas9, which is a rapidly growing field with great therapeutic potential. The low efficiency of homology-directed repair remains a major hurdle in CRISPR-Cas9–mediated precise genome editing, which is limited by low concentration of donor DNA template at the cleavage site. In this study, we have developed methodology to site-specifically conjugate oligonucleotides to recombinant Cas9 protein containing a genetically encoded noncanonical amino acid with orthogonal chemical reactivity. The Cas9-oligonucleotide conjugates recruited an unmodified donor DNA template to the target site through base pairing, markedly increasing homology-directed repair efficiency in both human cell culture and mouse zygotes. These chemically modified Cas9 mutants provide an additional tool, one that is complementary to chemically modified nucleic acids, for improving the utility of CRISPR-Cas9–based genome-editing systems.

No abstract

By applying the time-delay control theory to a TCP/RED dynamic model, this note establishes some explicit conditions under which the TCP/RED system is stable in terms of the average queue length. Then, the stability region is discussed. Finally, the results are illustrated by using 2 simulations, which demonstrates that it is able to choose an appropriate control parameter max of RED based on the stability conditions derived in this note, to achieve satisfactory network performance. It is found, by comparison, that this improved performance is better than that of three other typical active queue management (AQM) schemes-the random exponential marking (REM), proportional-integral (PI) controller, and adaptive virtual queue (AVQ) schemes.Index Terms-Active queue management (AQM), random early detection (RED), stability, time-delay control.

No abstract

No abstract

No abstract

Introducing the Internet into process control systems has brought a lot of benefits and some difficulties to control engineers as well. The major challenge of Internet-based process control systems is how to deal with Internet time delay and data loss. This paper analyses Internet communication features and proposes a control structure with a variable sampling time to overcome the Internet transmission delay. In order to take advantage of the structure fully and attack the major difficulties, two compensation elements have been designed and implemented in the system. These two compensators are located in the feedback and feedforward channels in the architecture respectively. Our simulation and experimental results illustrate that the control structure and two compensation elements can efficiently deal with the Internet time delay and data loss. Our simulation results also show that the time delay and data loss in the feedforward channel seem to cause more serious influence on the control performance and is more difficult to be compensated for.