Cationic lipid-based nanoparticles mediate functional delivery of acetate to tumor cells in vivo leading to significant anticancer effects

Metabolic reengineering using nanoparticle delivery represents an innovative therapeutic approach to normalizing the deregulation of cellular metabolism underlying many diseases, including cancer. Here, we demonstrated a unique and novel application to the treatment of malignancy using a short-chain fatty acid (SCFA)-encapsulated lipid-based delivery system – liposome-encapsulated acetate nanoparticles for cancer applications (LITA-CAN). We assessed chronic in vivo administration of our nanoparticle in three separate murine models of colorectal cancer. We demonstrated a substantial reduction in tumor growth in the xenograft model of colorectal cancer cell lines HT-29, HCT-116 p53+/+ and HCT-116 p53-/-. Nanoparticle-induced reductions in histone deacetylase gene expression indicated a potential mechanism for these anti-proliferative effects. Together, these results indicated that LITA-CAN could be used as an effective direct or adjunct therapy to treat malignant transformation in vivo

Spectral ergodicity and normal modes in ensembles of sparse matrices

We investigate the properties of sparse matrix ensembles with particular regard for the spectral ergodicity hypothesis, which claims the identity of ensemble and spectral averages of spectral correlators. An apparent violation of the spectral ergodicity is observed. This effect is studied with the aid of the normal modes of the random matrix spectrum, which describe fluctuations of the eigenvalues around their average positions. This analysis reveals that spectral ergodicity is not broken, but that different energy scales of the spectra are examined by the two averaging techniques. Normal modes are shown to provide a useful complement to traditional spectral analysis with possible applications to a wide range of physical systems.Comment: 22 pages, 15 figure

Background Independent Quantum Mechanics and Gravity

We argue that the demand of background independence in a quantum theory of gravity calls for an extension of standard geometric quantum mechanics. We discuss a possible kinematical and dynamical generalization of the latter by way of a quantum covariance of the state space. Specifically, we apply our scheme to the problem of a background independent formulation of Matrix Theory.Comment: 9 pages, LaTe

Unconventional decay law for excited states in closed many-body systems

We study the time evolution of an initially excited many-body state in a finite system of interacting Fermi-particles in the situation when the interaction gives rise to the ``chaotic'' structure of compound states. This situation is generic for highly excited many-particle states in quantum systems, such as heavy nuclei, complex atoms, quantum dots, spin systems, and quantum computers. For a strong interaction the leading term for the return probability $W(t)$ has the form $W(t)\simeq \exp (-\Delta_E^2t^2)$ with $\Delta_E^2$ as the variance of the strength function. The conventional exponential linear dependence $W(t)=C\exp (-\Gamma t)$ formally arises for a very large time. However, the prefactor $C$ turns out to be exponentially large, thus resulting in a strong difference from the conventional estimate for $W(t)$.Comment: RevTex, 4 pages including 1 eps-figur

Electronic excitations and the tunneling spectra of metallic nanograins

Tunneling-induced electronic excitations in a metallic nanograin are classified in terms of {\em generations}: subspaces of excitations containing a specific number of electron-hole pairs. This yields a hierarchy of populated excited states of the nanograin that strongly depends on (a) the available electronic energy levels; and (b) the ratio between the electronic relaxation rate within the nano-grain and the bottleneck rate for tunneling transitions. To study the response of the electronic energy level structure of the nanograin to the excitations, and its signature in the tunneling spectrum, we propose a microscopic mean-field theory. Two main features emerge when considering an Al nanograin coated with Al oxide: (i) The electronic energy response fluctuates strongly in the presence of disorder, from level to level and excitation to excitation. Such fluctuations produce a dramatic sample dependence of the tunneling spectra. On the other hand, for excitations that are energetically accessible at low applied bias voltages, the magnitude of the response, reflected in the renormalization of the single-electron energy levels, is smaller than the average spacing between energy levels. (ii) If the tunneling and electronic relaxation time scales are such as to admit a significant non-equilibrium population of the excited nanoparticle states, it should be possible to realize much higher spectral densities of resonances than have been observed to date in such devices. These resonances arise from tunneling into ground-state and excited electronic energy levels, as well as from charge fluctuations present during tunneling.Comment: Submitted to the Physical Review

Universal Correlations of Coulomb Blockade Conductance Peaks and the Rotation Scaling in Quantum Dots

We show that the parametric correlations of the conductance peak amplitudes of a chaotic or weakly disordered quantum dot in the Coulomb blockade regime become universal upon an appropriate scaling of the parameter. We compute the universal forms of this correlator for both cases of conserved and broken time reversal symmetry. For a symmetric dot the correlator is independent of the details in each lead such as the number of channels and their correlation. We derive a new scaling, which we call the rotation scaling, that can be computed directly from the dot's eigenfunction rotation rate or alternatively from the conductance peak heights, and therefore does not require knowledge of the spectrum of the dot. The relation of the rotation scaling to the level velocity scaling is discussed. The exact analytic form of the conductance peak correlator is derived at short distances. We also calculate the universal distributions of the average level width velocity for various values of the scaled parameter. The universality is illustrated in an Anderson model of a disordered dot.Comment: 35 pages, RevTex, 6 Postscript figure

Statistics of pre-localized states in disordered conductors

The distribution function of local amplitudes of single-particle states in disordered conductors is calculated on the basis of the supersymmetric $\sigma$-model approach using a saddle-point solution of its reduced version. Although the distribution of relatively small amplitudes can be approximated by the universal Porter-Thomas formulae known from the random matrix theory, the statistics of large amplitudes is strongly modified by localization effects. In particular, we find a multifractal behavior of eigenstates in 2D conductors which follows from the non-integer power-law scaling for the inverse participation numbers (IPN) with the size of the system. This result is valid for all fundamental symmetry classes (unitary, orthogonal and symplectic). The multifractality is due to the existence of pre-localized states which are characterized by power-law envelopes of wave functions, $|\psi_t(r)|^2\propto r^{-2\mu}$, $\mu <1$. The pre-localized states in short quasi-1D wires have the power-law tails $|\psi (x)|^2\propto x^{-2}$, too, although their IPN's indicate no fractal behavior. The distribution function of the largest-amplitude fluctuations of wave functions in 2D and 3D conductors has logarithmically-normal asymptotics.Comment: RevTex, 17 twocolumn pages; revised version (several misprint corrected

Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group

Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P&lt;5 × 10−8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis

Molecular structure and developmental expression of zebrafish atp2a genes

[[abstract]]We isolated two atp2a genes, atp2a1 and atp2a2a, from embryonic zebrafish. Amino acid sequences deduced from zebrafish atp2a genes are aligned with orthologue proteins from other species, the results showed that they share high percentage of identities (82%–94%) and acidic pIs (5.03–5.33). Whole mount in situ hybridization experiments showed that atp2a1 and atp2a2a are maternal inherited genes which can be detected at 1-cell stage embryos and express in the entire animal pole from 6 hours post-fertilization (hpf) to 12 hpf. At the later stages (48–96 hpf), expression of atp2a1 was restricted in head and trunk muscles as well as in some neurons. In contrast to the strongly expression of atp2a1 in head muscle, expression of atp2a2a was detected in head muscle in a fainter manner. In addition, transcripts of atp2a2a were observed in the developing heart during early cardiogenesis. The present studies not only help us to comparatively analyze atp2a genes across species, but also provide useful information about expressions during early embryogenesis that will help in further investigations of functional studies of Atp2a in the future.[[incitationindex]]SCI[[booktype]]紙

Comparison of the high energy models for neutral meson photoproduction and the related hadronic processes

To critically compare the Michigan and Argonne models we perform simultaneus fits to the high-energy data for [pi]0 and [nu] photoproduction together with that for the related hadronic vector meson production reactions, in particular that for [pi]+n --&gt; [omega]p. Thus all constraints on these models are considered simultaneously. Particular attention is given to the strength of absoptive cuts in both models, and to the role of the B-meson exchange in filling dips in the Argonne model. We find that the [varrho]-Pomeron cuts (i.e. cuts associated with large helicity flip at the N vertex) are essential to introducing unnatural parity exchange in the Michigan model, and that the B-meson contribution is incapable of filling unwanted dips which appear in any model with nonsense wrong signature zeros as required by exchange degeneracy. The flip and non-flip [varrho] and [omega] coupling strengths at the N vertex are determined. Predictions are made for various polarization asymmetries for [gamma]p --&gt; [pi]0p and [gamma]p --&gt; [eta]p. The differential cross section for KL0p --&gt; KS0p is calculated and compared with the existing data.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33569/1/0000070.pd