HISTONE ACETYLTRANSFERASE P300/CBP-ASSOCIATED FACTOR INHIBITION BY QUERCETIN AS ANTICANCER DRUG CANDIDATE WITH IN SILICO AND IN VITRO APPROACH

Objective: The objective of this research was to show quercetin potency to inhibit histone acetyltransferase p300/CBP-associated factor (HAT PCAF) activity. Molecular docking study was used to show inhibition model of quercetin towards HAT PCAF and the kinetic study was used to give the information about inhibition constant (Ki) of quercetin.Methods: Molecular docking simulations between HAT and quercetin were performed using AutoDock Vina, and the results were scored based on its Gibbs free energy change (ΔG) (the most negative ΔG). The kinetic assay of HAT PCAF inhibition by quercetin used fluorometry methods to measure enzyme inhibition by quercetin. Results: Molecular docking showed that quercetin could inhibit HAT PCAF through binding to acetyl-CoA that involved glutamine 525 (Gln525) and cysteine 574 (Cys574) on chain A, and Cys574 and Gln581 on chain B of HAT PCAF. Quercetin also binds to histone active site on HAT PCAF through aspartic acid 610 (Asp610). The kinetic study results showed that quercetin could inhibit histone acetylation based on the fluorescence intensity. Analysis by Dixon plot showed that quercetin competes with histone. Therefore, ithad competitive inhibition. Its Ki value of 9.575 µM. Kinetic study showed the same result as molecular docking study that quercetin had potency as an HAT PCAF inhibitor.Conclusion: The result of this research showed that quercetin had the potency to inhibit HAT PCAF through competition with HAT PCAF substrates. Quercetin could interact with the HAT PCAF active site, thus, lower the HAT PCAF activity. Keywords: Histone acetyltransferase, Quercetin, PCAF, Epigenetic drug, Dockin

XTE J1739-302 as a Supergiant Fast X-ray Transient

XTE J1739-302 is a transient X-ray source with unusually short outbursts, lasting on the order of hours. Here we give a summary of X-ray observations we have made of this object in outburst with the Rossi X-ray Timing Explorer (RXTE) and at a low level of activity with the Chandra X-ray Observatory, as well as observations made by other groups. Visible and infrared spectroscopy of the mass donor of XTE J1739-302 are presented in a companion paper. The X-ray spectrum is hard both at low levels and in outburst, but somewhat variable, and there is strong variability in the absorption column from one outburst to another. Although no pulsation has been observed, the outburst data from multiple observatories show a characteristic timescale for variability on the order of 1500-2000 s. The Chandra localization (right ascension 17h 39m 11.58s, declination -30o 20' 37.6'', J2000) shows that despite being located less than 2 degrees from the Galactic Center and highly absorbed, XTE J1739-302 is actually a foreground object with a bright optical counterpart. The combination of a very short outburst timescale and a supergiant companion is shared with several other recently-discovered systems, forming a class we designate as Supergiant Fast X-ray Transients (SFXTs). Three persistently bright X-ray binaries with similar supergiant companions have also produced extremely short, bright outbursts: Cyg X-1, Vela X-1, and 1E 1145.1-6141.Comment: 16 pages, 7 figures, 2 tables, in press in The Astrophysical Journal; see also the companion paper by Negueruela et a

Diffusion processes on branching Brownian motion

We construct a class of one-dimensional diffusion processes on the particles of branching Brownian motion that are symmetric with respect to the limits of random martingale measures. These measures are associated with the extended extremal process of branching Brownian motion and are supported on a Cantor-like set. The processes are obtained via a time-change of a standard one-dimensional reflected Brownian motion on $\mathbb{R}_+$ in terms of the associated positive continuous additive functionals. The processes introduced in this paper may be regarded as an analogue of the Liouville Brownian motion which has been recently constructed in the context of a Gaussian free field.Comment: 25 pages, 1 figure, published versio

Refined Simulations of the Reaction Front for Diffusion-Limited Two-Species Annihilation in One Dimension

Extensive simulations are performed of the diffusion-limited reaction A$+$B$\to 0$ in one dimension, with initially separated reagents. The reaction rate profile, and the probability distributions of the separation and midpoint of the nearest-neighbour pair of A and B particles, are all shown to exhibit dynamic scaling, independently of the presence of fluctuations in the initial state and of an exclusion principle in the model. The data is consistent with all lengthscales behaving as $t^{1/4}$ as $t\to\infty$. Evidence of multiscaling, found by other authors, is discussed in the light of these findings.Comment: Resubmitted as TeX rather than Postscript file. RevTeX version 3.0, 10 pages with 16 Encapsulated Postscript figures (need epsf). University of Geneva preprint UGVA/DPT 1994/10-85

SECMACE: Scalable and Robust Identity and Credential Management Infrastructure in Vehicular Communication Systems

Several years of academic and industrial research efforts have converged to a common understanding on fundamental security building blocks for the upcoming Vehicular Communication (VC) systems. There is a growing consensus towards deploying a special-purpose identity and credential management infrastructure, i.e., a Vehicular Public-Key Infrastructure (VPKI), enabling pseudonymous authentication, with standardization efforts towards that direction. In spite of the progress made by standardization bodies (IEEE 1609.2 and ETSI) and harmonization efforts (Car2Car Communication Consortium (C2C-CC)), significant questions remain unanswered towards deploying a VPKI. Deep understanding of the VPKI, a central building block of secure and privacy-preserving VC systems, is still lacking. This paper contributes to the closing of this gap. We present SECMACE, a VPKI system, which is compatible with the IEEE 1609.2 and ETSI standards specifications. We provide a detailed description of our state-of-the-art VPKI that improves upon existing proposals in terms of security and privacy protection, and efficiency. SECMACE facilitates multi-domain operations in the VC systems and enhances user privacy, notably preventing linking pseudonyms based on timing information and offering increased protection even against honest-but-curious VPKI entities. We propose multiple policies for the vehicle-VPKI interactions, based on which and two large-scale mobility trace datasets, we evaluate the full-blown implementation of SECMACE. With very little attention on the VPKI performance thus far, our results reveal that modest computing resources can support a large area of vehicles with very low delays and the most promising policy in terms of privacy protection can be supported with moderate overhead.Comment: 14 pages, 9 figures, 10 tables, IEEE Transactions on Intelligent Transportation System

Histone-like TAFs within the PCAF Histone Acetylase Complex

AbstractPCAF histone acetylase plays a role in regulation of transcription, cell cycle progression, and differentiation. Here, we show that PCAF is found in a complex consisting of more than 20 distinct polypeptides. Strikingly, some polypeptides are identical to TBP-associated factors (TAFs), which are subunits of TFIID. Like TFIID, histone fold–containing factors are present within the PCAF complex. The histone H3– and H2B–like subunits within the PCAF complex are identical to those within TFIID, namely, hTAFII31 and hTAFII20/15, respectively. The PCAF complex has a novel histone H4–like subunit with similarity to hTAFII80 that interacts with the histone H3–like domain of hTAFII31. Moreover, the PCAF complex has a novel subunit with WD40 repeats having a similarity to hTAFII100