95 research outputs found
Design and Simulation of a Novel Clustering based Fuzzy Controller for DC Motor Speed Control
This research article proposes the speed control of a DC Motor (series as well as shunt motor). The noveltyof this article lies in the application of kernel based hybrid c-means clustering (KPFCM) in the design offuzzy controller for the speed control of DC Motor. The proposed approach provides a mechanism to obtainthe reduced rule set covering the whole input/output space as well as the parameters of membershipfunctions for each input variable. The performance of the proposed clustering based fuzzy logic controlleris compared with that of its corresponding conventional fuzzy logic controller in terms of severalperformance measures such as rise time, peak overshoot, settling time, integral absolute error (IAE) andintegral of time multiplied absolute error (ITAE) and in each case, the proposed scheme shows improvedperformance over its conventional counterpart. Also it shows that the proposed controller scheme givesmuch faster results as it reduces the computational time.Keywords: DC Motor, Fuzzy control, Kernel, Clustering, Validity inde
A 5′-uridine amplifies miRNA/miRNA* asymmetry in Drosophila by promoting RNA-induced silencing complex formation
A 5\u27-uridine Amplifies miRNA/miRNA* Asymmetry in Drosophila by Promoting RNA-induced Silencing Complex Formation
BACKGROUND: MicroRNA (miRNA) are diverse in sequence and have a single known sequence bias: they tend to start with uridine (U).
RESULTS: Our analyses of fly, worm and mouse miRNA sequence data reveal that the 5\u27-U is recognized after miRNA production. Only one of the two strands can be assembled into Argonaute protein from a single miRNA/miRNA* molecule: in fly embryo lysate, a 5\u27-U promotes miRNA loading while decreasing the loading of the miRNA*.
CONCLUSION: We suggest that recognition of the 5\u27-U enhances Argonaute loading by a mechanism distinct from its contribution to weakening base pairing at the 5\u27-end of the prospective miRNA and, as recently proposed in Arabidopsis and in humans, that it improves miRNA precision by excluding incorrectly processed molecules bearing other 5\u27-nt
Discrete time-dependent wave equation for the Schr\"{o}dinger operator with unbounded potential
In this article, we investigate the semiclassical version of the wave
equation for the discrete Schr\"{o}dinger operator,
on the lattice
where is the discrete Laplacian,
and is a non-negative multiplication operator. We prove that
has a purely discrete spectrum when the potential
satisfies the condition as . We also show that
the Cauchy problem with regular coefficients is well-posed in the associated
Sobolev type spaces and very weakly well-posed for distributional coefficients.
Finally, we recover the classical solution as well as the very weak solution in
certain Sobolev type spaces as the limit of the semiclassical parameter
.Comment: 25 page
Conserved chromosome 2q31 conformations are associated with transcriptional regulation of GAD1 GABA synthesis enzyme and altered in prefrontal cortex of subjects with schizophrenia
Little is known about chromosomal loopings involving proximal promoter and distal enhancer elements regulating GABAergic gene expression, including changes in schizophrenia and other psychiatric conditions linked to altered inhibition. Here, we map in human chromosome 2q31 the 3D configuration of 200 kb of linear sequence encompassing the GAD1 GABA synthesis enzyme gene locus, and we describe a loop formation involving the GAD1 transcription start site and intergenic noncoding DNA elements facilitating reporter gene expression. The GAD1-TSS(-50kbLoop) was enriched with nucleosomes epigenetically decorated with the transcriptional mark, histone H3 trimethylated at lysine 4, and was weak or absent in skin fibroblasts and pluripotent stem cells compared with neuronal cultures differentiated from them. In the prefrontal cortex of subjects with schizophrenia, GAD1-TSS(-50kbLoop) was decreased compared with controls, in conjunction with downregulated GAD1 expression. We generated transgenic mice expressing Gad2 promoter-driven green fluorescent protein-conjugated histone H2B and confirmed that Gad1-TSS(-55kbLoop), the murine homolog to GAD1-TSS(-50kbLoop), is a chromosomal conformation specific for GABAergic neurons. In primary neuronal culture, Gad1-TSS(-55kbLoop) and Gad1 expression became upregulated when neuronal activity was increased. We conclude that 3D genome architectures, including chromosomal loopings for promoter-enhancer interactions involved in the regulation of GABAergic gene expression, are conserved between the rodent and primate brain, and subject to developmental and activity-dependent regulation, and disordered in some cases with schizophrenia. More broadly, the findings presented here draw a connection between noncoding DNA, spatial genome architecture, and neuronal plasticity in development and disease
Human-specific histone methylation signatures at transcription start sites in prefrontal neurons
Cognitive abilities and disorders unique to humans are thought to result from adaptively driven changes in brain transcriptomes, but little is known about the role of cis-regulatory changes affecting transcription start sites (TSS). Here, we mapped in human, chimpanzee, and macaque prefrontal cortex the genome-wide distribution of histone H3 trimethylated at lysine 4 (H3K4me3), an epigenetic mark sharply regulated at TSS, and identified 471 sequences with human-specific enrichment or depletion. Among these were 33 loci selectively methylated in neuronal but not non-neuronal chromatin from children and adults, including TSS at DPP10 (2q14.1), CNTN4 and CHL1 (3p26.3), and other neuropsychiatric susceptibility genes. Regulatory sequences at DPP10 and additional loci carried a strong footprint of hominid adaptation, including elevated nucleotide substitution rates and regulatory motifs absent in other primates (including archaic hominins), with evidence for selective pressures during more recent evolution and adaptive fixations in modern populations. Chromosome conformation capture at two neurodevelopmental disease loci, 2q14.1 and 16p11.2, revealed higher order chromatin structures resulting in physical contact of multiple human-specific H3K4me3 peaks spaced 0.5-1 Mb apart, in conjunction with a novel cis-bound antisense RNA linked to Polycomb repressor proteins and downregulated DPP10 expression. Therefore, coordinated epigenetic regulation via newly derived TSS chromatin could play an important role in the emergence of human-specific gene expression networks in brain that contribute to cognitive functions and neurological disease susceptibility in modern day humans
Functions of PIWI proteins in spermatogenesis
Recently, a significant understanding of the molecular mechanisms regulating spermatogenesis has been achieved utilizing small RNA molecules (small RNAs), including small interfering RNAs (siRNAs), microRNAs (miRNAs), and Piwi-interacting RNAs (piRNAs) which emerged as important regulators of gene expression at the post-transcriptional or translation level. piRNAs are only present in pachytene spermatocytes and round spermatids, whereas miRNAs are expressed abundantly in male germ cells throughout spermatogenesis. This review is aimed at providing a glimpse of piRNAs and their interacting family proteins such as PIWIL1, PIWIL2, and PIWIL4 in spermatogenesis
A-RAF Kinase Functions in ARF6 Regulated Endocytic Membrane Traffic
BACKGROUND: RAF kinases direct ERK MAPK signaling to distinct subcellular compartments in response to growth factor stimulation. METHODOLOGY/PRINCIPAL FINDINGS: Of the three mammalian isoforms A-RAF is special in that one of its two lipid binding domains mediates a unique pattern of membrane localization. Specific membrane binding is retained by an N-terminal fragment (AR149) that corresponds to a naturally occurring splice variant termed DA-RAF2. AR149 colocalizes with ARF6 on tubular endosomes and has a dominant negative effect on endocytic trafficking. Moreover actin polymerization of yeast and mammalian cells is abolished. AR149/DA-RAF2 does not affect the internalization step of endocytosis, but trafficking to the recycling compartment. CONCLUSIONS/SIGNIFICANCE: A-RAF induced ERK activation is required for this step by activating ARF6, as A-RAF depletion or inhibition of the A-RAF controlled MEK-ERK cascade blocks recycling. These data led to a new model for A-RAF function in endocytic trafficking
GEP100/Arf6 Is Required for Epidermal Growth Factor-Induced ERK/Rac1 Signaling and Cell Migration in Human Hepatoma HepG2 Cells
BACKGROUND: Epidermal growth factor (EGF) signaling is implicated in the invasion and metastasis of hepatoma cells. However, the signaling pathways for EGF-induced motility of hepatoma cells remain undefined. METHODOLOGY/PRINCIPAL FINDINGS: We found that EGF dose-dependently stimulated the migration of human hepatoma cells HepG2, with the maximal effect at 10 ng/mL. Additionally, EGF increased Arf6 activity, and ectopic expression of Arf6 T27N, a dominant negative Arf6 mutant, largely abolish EGF-induced cell migration. Blocking GEP100 with GEP100 siRNA or GEP100-△PH, a pleckstrin homology (PH) domain deletion mutant of GEP100, blocked EGF-induced Arf6 activity and cell migration. EGF also increased ERK and Rac1 activity. Ectopic expression GEP100 siRNA, GEP100-△PH, or Arf6-T27N suppressed EGF-induced ERK and Rac1 activity. Furthermore, blocking ERK signaling with its inhibitor U0126 remarkably inhibited both EGF-induced Rac1 activation as well as cell migration, and ectopic expression of inactive mutant form of Rac1 (Rac1-T17N) also largely abolished EGF-induced cell migration. CONCLUSIONS/SIGNIFICANCE: Taken together, this study highlights the function of the PH domain of GEP100 and its regulated Arf6/ERK/Rac1 signaling cascade in EGF-induced hepatoma cell migration. These findings could provide a rationale for designing new therapy based on inhibition of hepatoma metastasis
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