19,561 research outputs found
Retraction and Generalized Extension of Computing with Words
Fuzzy automata, whose input alphabet is a set of numbers or symbols, are a
formal model of computing with values. Motivated by Zadeh's paradigm of
computing with words rather than numbers, Ying proposed a kind of fuzzy
automata, whose input alphabet consists of all fuzzy subsets of a set of
symbols, as a formal model of computing with all words. In this paper, we
introduce a somewhat general formal model of computing with (some special)
words. The new features of the model are that the input alphabet only comprises
some (not necessarily all) fuzzy subsets of a set of symbols and the fuzzy
transition function can be specified arbitrarily. By employing the methodology
of fuzzy control, we establish a retraction principle from computing with words
to computing with values for handling crisp inputs and a generalized extension
principle from computing with words to computing with all words for handling
fuzzy inputs. These principles show that computing with values and computing
with all words can be respectively implemented by computing with words. Some
algebraic properties of retractions and generalized extensions are addressed as
well.Comment: 13 double column pages; 3 figures; to be published in the IEEE
Transactions on Fuzzy System
Insights into the Mutation-Induced HHH Syndrome from Modeling Human Mitochondrial Ornithine Transporter-1
Human mitochondrial ornithine transporter-1 is reported in coupling with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, which is a rare autosomal recessive disorder. For in-depth understanding of the molecular mechanism of the disease, it is crucially important to acquire the 3D structure of human mitochondrial ornithine transporter-1. Since no such structure is available in the current protein structure database, we have developed it via computational approaches based on the recent NMR structure of human mitochondrial uncoupling protein (Berardi MJ, Chou JJ, et al. Nature 2011, 476:109ā113). Subsequently, we docked the ligand L-ornithine into the computational structure to search for the favorable binding mode. It was observed that the binding interaction for the most favorable binding mode is featured by six remarkable hydrogen bonds between the receptor and ligand, and that the most favorable binding mode shared the same ligand-binding site with most of the homologous mitochondrial carriers from different organisms, implying that the ligand-binding sites are quite conservative in the mitochondrial carriers family although their sequences similarity is very low with 20% or so. Moreover, according to our structural analysis, the relationship between the disease-causing mutations of human mitochondrial ornithine transporter-1 and the HHH syndrome can be classified into the following three categories: (i) the mutation occurs in the pseudo-repeat regions so as to change the region of the protein closer to the mitochondrial matrix; (ii) the mutation is directly affecting the substrate binding pocket so as to reduce the substrate binding affinity; (iii) the mutation is located in the structural region closer to the intermembrane space that can significantly break the salt bridge networks of the protein. These findings may provide useful insights for in-depth understanding of the molecular mechanism of the HHH syndrome and developing effective drugs against the disease
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