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

CPS Based Liquid Metal Divertor Target for EU-DEMO

AbstractPower exhaust is a key mission in the roadmap to the realization of a future fusion reactor. Among the different solutions, the use of liquid metals as plasma facing materials are of interest due to their potential increased lifetime. Several liquid metal limiters have been successfully tested in the Frascati Tokamak Upgrade over the last 10 years. Liquid materials such as lithium and tin have been investigated using capillary porous systems (CPSs), and their impact on plasma performance has been explored. From such experience, a liquid metal divertor (LMD) concept design, CPS-based, is here proposed. Tin has been preferred as plasma facing material. The proposed LMD would operate, in low evaporative regime, with matching heat exhausting capabilities to those of the baseline ITER-like divertor. Continuous refilling of the CPS is guaranteed with a reservoir at the back of the unit, where the metal is kept liquid through a gas heating circuit. The study has been carried out using ANSYS and the thermal results will be shown. All the design choices are compatible with the current materials and the constraints adopted for the DEMO W divertor. Using such configuration, thermal loads up to 20 MW/m2 are exhausted while keeping the surface temperature below 1250 °C. The design foresees values of pressure, temperature and flow rate of the water coolant in the same range expected for the W DEMO divertor, thus facilitating the integration of such solution in the current cassette design. Technological and practical aspects are addressed, i.e. tin corrosion and CPS wettability. Possible solutions to prevent tin corrosion, and its compatibility with structural materials, will be outlined

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

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

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 $\alpha \simeq 1.7$, from which we derive the associated break-even probability distribution. The predictions are compared with empirical data.Comment: 6 pages, 6 figure

Single-cell analysis reveals individual spore responses to simulated space vacuum

Outer space is a challenging environment for all forms of life, and dormant spores of bacteria have been frequently used to study the survival of terrestrial life in a space journey. Previous work showed that outer space vacuum alone can kill bacterial spores. However, the responses and mechanisms of resistance of individual spores to space vacuum are unclear. Here, we examined spores’ molecular changes under simulated space vacuum (~10−5 Pa) using micro-Raman spectroscopy and found that this vacuum did not cause significant denaturation of spore protein. Then, live-cell microscopy was developed to investigate the temporal events during germination, outgrowth, and growth of individual Bacillus spores. The results showed that after exposure to simulated space vacuum for 10 days, viability of spores of two Bacillus species was reduced up to 35%, but all spores retained their large Ca2 +-dipicolinic acid depot. Some of the killed spores did not germinate, and the remaining germinated but did not proceed to vegetative growth. The vacuum treatment slowed spore germination, and changed average times of all major germination events. In addition, viable vacuum-treated spores exhibited much greater sensitivity than untreated spores to dry heat and hyperosmotic stress. Among spores’ resistance mechanisms to high vacuum, DNA-protective α/β−type small acid-soluble proteins, and non- homologous end joining and base excision repair of DNA played the most important roles, especially against multiple cycles of vacuum treatment. Overall, these results give new insight into individual spore’s responses to space vacuum and provide new techniques for microorganism analysis at the single-cell level

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 $n\le 6$ 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

Microwave Assisted Synthesis of Py-Im Polyamides

Microwave synthesis was utilized to rapidly build Py-Im polyamides in high yields and purity using Boc-protection chemistry on Kaiser oxime resin. A representative polyamide targeting the 5′-WGWWCW-3′ (W = A or T) subset of the consensus Androgen and Glucocorticoid Response Elements was synthesized in 56% yield after 20 linear steps and HPLC purification. It was confirmed by Mosher amide derivatization of the polyamide that a chiral α-amino acid does not racemize after several additional coupling steps