10 research outputs found
Dynamic and Quantitative Method of Analyzing Service Consistency Evolution Based on Extended Hierarchical Finite State Automata
This paper is concerned with the dynamic evolution analysis and quantitative
measurement of primary factors that cause service inconsistency in service-oriented
distributed simulation applications (SODSA). Traditional methods are mostly qualitative
and empirical, and they do not consider the dynamic disturbances among factors in serviceās evolution
behaviors such as producing, publishing, calling, and maintenance. Moreover,
SODSA are rapidly evolving in terms of large-scale, reusable, compositional, pervasive, and flexible features,
which presents difficulties in the usage of traditional analysis methods. To resolve these problems, a novel dynamic
evolution model extended hierarchical service-finite state automata (EHS-FSA) is constructed based on finite state
automata (FSA), which formally depict overall changing processes of service consistency states. And also the service
consistency evolution algorithms (SCEAs) based on EHS-FSA are developed to quantitatively assess
these impact factors. Experimental results show that the bad reusability (17.93% on average) is
the biggest influential factor, the noncomposition of atomic services (13.12%) is
the second biggest one, and the service versionās confusion (1.2%) is
the smallest one. Compared with previous qualitative analysis, SCEAs present good effectiveness
and feasibility. This research can guide the engineers of service consistency technologies toward obtaining a higher level of consistency in SODSA
Pharmaceutical Optimization of Peptide Toxins for Ion Channel Targets: Potent, Selective, and Long-Lived Antagonists of Kv1.3
To
realize the medicinal potential of peptide toxins, naturally
occurring disulfide-rich peptides, as ion channel antagonists, more
efficient pharmaceutical optimization technologies must be developed.
Here, we show that the therapeutic properties of multiple cysteine
toxin peptides can be rapidly and substantially improved by combining
direct chemical strategies with high-throughput electrophysiology.
We applied whole-molecule, brute-force, structureāactivity
analoging to ShK, a peptide toxin from the sea anemone Stichodactyla helianthus that inhibits the voltage-gated
potassium ion channel Kv1.3, to effectively discover critical structural
changes for 15Ć selectivity against the closely related neuronal
ion channel Kv1.1. Subsequent site-specific polymer conjugation resulted
in an exquisitely selective Kv1.3 antagonist (>1000Ć over
Kv1.1)
with picomolar functional activity in whole blood and a pharmacokinetic
profile suitable for weekly administration in primates. The pharmacological
potential of the optimized toxin peptide was demonstrated by potent
and sustained inhibition of cytokine secretion from T cells, a therapeutic
target for autoimmune diseases, in cynomolgus monkeys