890 research outputs found
Cyclic pyrrole-imidazole polyamides targeted to the androgen response element
Hairpin pyrrole−imidazole (Py-Im) polyamides are a class of cell-permeable DNA-binding small molecules that can disrupt transcription factor−DNA binding and regulate endogenous gene expression. The covalent linkage of antiparallel Py-Im ring pairs with an γ-amino acid turn unit affords the classical hairpin Py-Im polyamide structure. Closing the hairpin with a second turn unit yields a cyclic polyamide, a lesser-studied architecture mainly attributable to synthetic inaccessibility. We have applied our methodology for solution-phase polyamide synthesis to cyclic polyamides with an improved high-yield cyclization step. Cyclic 8-ring Py-Im polyamides 1−3 target the DNA sequence 5′-WGWWCW-3′, which corresponds to the androgen response element (ARE) bound by the androgen receptor transcription factor to modulate gene expression. We find that cyclic Py-Im polyamides 1−3 bind DNA with exceptionally high affinities and regulate the expression of AR target genes in cell culture studies, from which we infer that the cycle is cell permeable
Next generation hairpin polyamides with (R)-3,4-diaminobutyric acid turn unit
The characterization of a new class of pyrrole−imidazole hairpin polyamides with β-amino-γ-turn units for recognition of the DNA minor groove is reported. A library of eight hairpins containing (R)- and (S)-3,4-diaminobutyric acid (β-amino-γ-turn) has been synthesized, and the impact of the molecules on DNA-duplex stabilization was studied for comparison with the parent γ-aminobutyric acid (γ-turn) and standard (R)-2,4-diaminobutyric acid (α-amino-γ-turn)-linked eight-ring polyamides. For some, but not all, sequence compositions, melting temperature analyses have revealed that both enantiomeric forms of the β-amino-γ-turn increase the DNA-binding affinity of polyamides relative to the (R)-α-amino-γ-turn. The (R)-β-amine residue may be an attractive alternative for constructing hairpin polyamide conjugates. Biological assays have shown that (R)-β-amino-γ-turn hairpins are able to inhibit androgen receptor-mediated gene expression in cell culture similar to hairpins bearing the standard (R)-α-amino-γ-turn, from which we infer they are cell-permeable
Electron-correlation effects in appearance-potential spectra of Ni
Spin-resolved and temperature-dependent appearance-potential spectra of
ferromagnetic Nickel are measured and analyzed theoretically. The Lander
self-convolution model which relates the line shape to the unoccupied part of
the local density of states turns out to be insufficient. Electron correlations
and orbitally resolved transition-matrix elements are shown to be essential for
a quantitative agreement between experiment and theory.Comment: LaTeX, 6 pages, 2 eps figures included, Phys. Rev. B (in press
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Ruddlesden Popper 2D perovskites as Li-ion battery electrodes
The electrochemical performance of 2-dimensional hybrid perovskite electrodes for Li-ion batteries are investigated using a high-molarity electrolyte. The effect of changing the halide content and layering structure is systematically explored.</p
Water hardness salts on the effectiveness of the fire extinguishing properties of foam have been used for firefighting
Изучалось влияние солей жесткости воды на эффективность огнетушащих свойств пенообразующих составов. В результате проведенного исследования с УПН Майское ПО-6А3F и УПН Снежное ПО-6ТФ установлено, что с увеличением жесткости воды, устойчивость пены снижается. Ее устойчивость зависит от таких факторов, как жесткость воды и заряд активного иона поверхностно активного вещества. Установлено, что с увеличением жесткости воды, увеличивается время тушения пожара и расход огнетушащих средств, для наиболее эффективного пожаротушения рекомендуется использовать воду с УПН Снежное ПО-6ТФ.Studied the effect of water hardness salts on the effectiveness of the fire extinguishing properties of the foam. As a result of the study with UPN may PO-6A3F and UPN Snow PO-6TF found that with increasing water hardness, foam stability decreases. Its stability depends on factors such as water hardness and charge of the active ion of the surfactant. It is established that with increase of water hardness, increasing the extinguishing of the fire and amount of fire extinguishing, for the most effective fire-extinguishing it is recommended to use water with oil treatment IN a Snow-6ТФ
Fluctuations of company yearly profits versus scaled revenue: Fat tail distribution of Levy type
We analyze annual revenues and earnings data for the 500 largest-revenue U.S.
companies during the period 1954-2007. We find that mean year profits are
proportional to mean year revenues, exception made for few anomalous years,
from which we postulate a linear relation between company expected mean profit
and revenue. Mean annual revenues are used to scale both company profits and
revenues. Annual profit fluctuations are obtained as difference between actual
annual profit and its expected mean value, scaled by a power of the revenue to
get a stationary behavior as a function of revenue. We find that profit
fluctuations are broadly distributed having approximate power-law tails with a
Levy-type exponent , from which we derive the associated
break-even probability distribution. The predictions are compared with
empirical data.Comment: 6 pages, 6 figure
Lifetimes of image-potential states on copper surfaces
The lifetime of image states, which represent a key quantity to probe the
coupling of surface electronic states with the solid substrate, have been
recently determined for quantum numbers on Cu(100) by using
time-resolved two-photon photoemission in combination with the coherent
excitation of several states (U. H\"ofer et al, Science 277, 1480 (1997)). We
here report theoretical investigations of the lifetime of image states on
copper surfaces. We evaluate the lifetimes from the knowledge of the
self-energy of the excited quasiparticle, which we compute within the GW
approximation of many-body theory. Single-particle wave functions are obtained
by solving the Schr\"odinger equation with a realistic one-dimensional model
potential, and the screened interaction is evaluated in the random-phase
approximation (RPA). Our results are in good agreement with the experimentally
determined decay times.Comment: 4 pages, 1 figure, to appear in Phys. Rev. Let
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