Unzipping and binding of small interfering RNA with single walled carbon nanotube: A platform for small interfering RNA delivery

In an effort to design efficient platform for siRNA delivery, we combine all atom classical and quantum simulations to study the binding of small interfering RNA (siRNA) by pristine single wall carbon nanotube (SWCNT). Our results show that siRNA strongly binds to SWCNT surface via unzipping its base-pairs and the propensity of unzipping increases with the increase in the diameter of the SWCNTs. The unzipping and subsequent wrapping events are initiated and driven by van der Waals interactions between the aromatic rings of siRNA nucleobases and the SWCNT surface. However, molecular dynamics (MD) simulations of double strand DNA (dsDNA) of the same sequence show that the dsDNA undergoes much less unzipping and wrapping on the SWCNT in the simulation time scale of 70 ns. This interesting difference is due to smaller interaction energy of thymidine of dsDNA with the SWCNT compared to that of uridine of siRNA, as calculated by dispersion corrected density functional theory (DFT) methods. After the optimal binding of siRNA to SWCNT, the complex is very stable which serves as one of the major mechanisms of siRNA delivery for biomedical applications. Since siRNA has to undergo unwinding process with the effect of RNA-induced silencing complex, our proposed delivery mechanism by SWCNT possesses potential advantages in achieving RNA interference. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.3682780]

Small-Angle Neutron-Scattering Studies of Mixed Micellar Structures Made of Dimeric Surfactants Having Imidazolium and Ammonium Headgroups

Planar imidazolium cation based gemini surfactants 16-Im-n-Im-16], 2Br(-) (where n = 2, 3, 4, 5, 6, 8, 10, and 12), exhibit different morphologies and internal packing arrangements by adopting different supramolecular assemblies in aqueous media depending on their number of spacer methylene units (CH2)(n). Detailed measurements of the small-angle neutron-scattering (SANS) cross sections from different imidazolium-based surfactant micelles in aqueous media (D2O) are reported. The SANS data, containing the information of aggregation behavior of such surfactants in the molecular level, have been analyzed on the basis of the Hayter and Penfold model for the macro ion solution to compute the interparticle structure factor S(Q) taking into account the screened Coulomb interactions between the dimeric surfactant micelles. The characteristic changes in the SANS spectra of the dimeric surfactant with n = 4 due to variation of temperature have also been investigated. These data are then compared with the SANS characterization data of the corresponding gemini micelles containing tetrahedral ammonium ion based polar headgroups. The critical micellar concentration of each surfactant micelle (cmc) has been determined using pyrene as an extrinsic fluorescence probe. The variation of cmc as a function of spacer chain length has been explained in terms of conformational variation and progressive looping of the spacer into the micellar interior upon increasing the n values. Small-angle neutron-scattering (SANS) cross sections from different mixed micelles composed of surfactants with ammonium headgroups, 16-A(0), 16-Am-n-Am-16], 2Br(-) (where n = 4), 16-I-0, and 16-Im-n-Im-16], 2Br(-) (where n = 4), in aqueous media (D2O) have also been analyzed. The aggregate composition matches with that predicted from the ideal mixing model.

Wheeler-Feynman absorber revisited: a useful technique to calculate decay rates and lifetimes in small scale optical systems

The Wheeler-Feynman (WF) absorber theory of radiation though no more of interest in explaining self interaction of an electron, can be very useful in today's research in small scale optical systems. The significance of the WF absorber is the use of time-symmetrical solution of Maxwell's equations as opposed to only the retarded solution. The radiative coupling of emitters to nano wires in the near field and change in their lifetimes due to small mode volume enclosures have been elucidated with the retarded solutions before. These solutions have also been shown to agree with quantum electrodynamics, thus allowing for classical electromagnetic approaches in such problems. It is here assumed that the radiative coupling of the emitter with a body is in proportion to its contribution to the classical force of radiative reaction as derived in the WF absorber theory. Representing such nano structures as a partial WF absorber acting on the emitter makes the computations considerably easier than conventional electromagnetic solutions for full boundary conditions.

Probing p300/CBP associated Factor (PCAF)-dependent pathways with a small molecule inhibitor

PCAF (KAT2B) belongs to the GNAT family of lysine acetyltransferases (KAT) and specifically acetylates the histone H3K9 residue and several nonhistone proteins. PCAF is also a transcriptional coactivator. Due to the lack of a PCAF KAT-specific small molecule inhibitor, the exclusive role of the acetyltransferase activity of PCAF is not well understood. Here, we report that a natural compound of the hydroxybenzoquinone class, embelin, specifically inhibits H3Lys9 acetylation in mice and inhibits recombinant PCAF-mediated acetylation with near complete specificity in vitro. Furthermore, using embelin, we have identified the gene networks that are regulated by PCAF during muscle differentiation, further highlighting the broader regulatory functions of PCAF in muscle differentiation in addition to the regulation via MyoD acetylation.

MPK-09, a small molecule inspired from bioactive styryllactone restores the wild-type function of mutant p53

In the search for more efficacious and less toxic cancer drugs, the tumor suppressor p53 protein has long been a desirable therapeutic target. In the recent past, few independent studies have demonstrated that the antitumor activity of wild-type p53 can be restored in cancer cells harboring mutant form of p53 using small molecule activators. In this study, we describe a novel small molecule MPK-09, which is selective and highly potent against allele specific p53 mutations mainly, R175H, R249S, R273H, R273C, and E285K. Except E285K, all other mutations tested are among the six ``hot spot'' p53 mutations reported in majority of human cancer. Furthermore, our study conclusively demonstrates that the apoptotic activity of the small molecule MPK-09 against cancer cells harboring R273C and E285K mutations is due to restoration of the wild-type conformation to the corresponding mutant form of p53.

Formation flying of small satellites using suboptimal MPSP guidance

Using the recently developed model predictive static programming (MPSP), a suboptimal guidance logic is presented in this paper for formation flying of small satellites. Due to the inherent nature of the problem formulation, MPSP does not require the system dynamics to be linearized. The proposed guidance scheme is valid both for high eccentricity chief satellite orbits as well as large separation distance between chief and deputy satellites. Moreover, since MPSP poses the desired conditions as a set of `hard constraints', the final accuracy level achieved is very high. The proposed guidance scheme has been tested successfully for a variety of initial conditions and for a variety of formation commands as well. Comparison with standard Linear Quadratic Regulator (LQR) solution (which serves as a guess solution for MPSP) and another nonlinear controller, State Dependent Riccati Equation (SDRE) reveals that MPSP guidance achieves the objective with higher accuracy and with lesser amount of control usage as well.

Fracture Testing at Small-Length Scales: From Plasticity in Si to Brittleness in Pt

The field of micro-/nano-mechanics of materials has been driven, on the one hand by the development of ever smaller structures in devices, and, on the other, by the need to map property variations in large systems that are microstructurally graded. Observations of `smaller is stronger' have also brought in questions of accompanying fracture property changes in the materials. In the wake of scattered articles on micro-scale fracture testing of various material classes, this review attempts to provide a holistic picture of the current state of the art. In the process, various reliable micro-scale geometries are shown, challenges with respect to instrumentation to probe ever smaller length scales are discussed and examples from recent literature are put together to exhibit the expanse of unusual fracture response of materials, from ductility in Si to brittleness in Pt. Outstanding issues related to fracture mechanics of small structures are critically examined for plausible solutions.

Molecular Cage Impregnated Palladium Nanoparticles: Efficient, Additive-Free Heterogeneous Catalysts for Cyanation of Aryl Halides

Two shape-persistent covalent cages (CC1(r) and CC2(r)) have been devised from triphenyl amine-based trialdehydes and cyclohexane diamine building blocks utilizing the dynamic imine chemistry followed by imine bond reduction. The cage compounds have been characterized by several spectroscopic techniques which suggest that CC1(r) and CC2(r) are 2+3] and 8+12] self-assembled architectures, respectively. These state-of-the-art molecules have a porous interior and stable aromatic backbone with multiple palladium binding sites to engineer the controlled synthesis and stabilization of ultrafine palladium nanoparticles (PdNPs). As-synthesized cage-embedded PdNPs have been characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and powder X-ray diffraction (PXRD). Inductively coupled plasma optical emission spectrometry reveals that Pd@CC1(r) and Pd@CC2(r) have 40 and 25 wt% palladium loading, respectively. On the basis of TEM analysis, it has been estimated that as small as similar to 1.8 nm PdNPs could be stabilized inside the CC1(r), while larger CC2(r) could stabilize similar to 3.7 nm NPs. In contrast, reduction of palladium salts in the absence of the cages form structure less agglomerates. The well-dispersed cage-embedded NPs exhibit efficient catalytic performance in the cyanation of aryl halides under heterogeneous, additive-free condition. Moreover, these materials have excellent stability and recyclability without any agglomeration of PdNPs after several cycles.

A NOTE ON SMALL GAPS BETWEEN NONZERO FOURIER COEFFICIENTS OF CUSP FORMS

It is shown that there are infinitely many primitive cusp forms f of weight 2 with the property that for all X large enough, every interval (X, X + cX(1/4)), where c > 0 depends only on the form, contains an integer n such that the n-th Fourier coefficient of f is nonzero.