Investigations of Pyrrole-Imidazole Polyamide Effects on DNA Replication

Pyrrole–Imidazole polyamides are programmable, cell-permeable small molecules that bind in the minor groove of double-stranded DNA sequence-specifically. Polyamide binding has been shown to alter the local helical structure of DNA, disrupt protein-DNA interactions, and modulate endogenous gene expression. Py–Im polyamides targeted to the androgen receptor-DNA interface have been observed to decrease expression of androgen-regulated genes, upregulate p53, and induce apoptosis in a hormone-sensitive prostate cancer cell line. Here we report that androgen response element (ARE)-targeted polyamides induced DNA replication stress in a hormone-insensitive prostate cancer cell line. The ATR checkpoint kinase was activated in response to this stress, causing phosphorylation of MCM2, and FANCD2 was monoubiquitinated. Surprisingly, little single-stranded DNA was exhibited, and the ATR targets RPA2 and Chk1 were not phosphorylated. We conclude that polyamide induces relatively low level replication stress, and suggest inhibition of the replicative helicase as a putative mechanism based on in vitro assays. We also demonstrate polyamide-induced inhibition of DNA replication in cell free extracts from X. laevis oocytes. In this system, inhibition of chromatin decondensation is observed, preventing DNA replication initiation. Finally, we show that Py-Im polyamides targeted to the ARE and ETS binding sequence downregulate AR- and ERG-driven signaling in a prostate cancer cell line harboring the TMPRSS2-ERG fusion. In a mouse xenograft model, ARE-targeted polyamide treatment reduced growth of the tumor.

Magnetic field and pressure effects in a saturated gas laser amplifier

Theoretical and experimental studies of a gas laser amplifier are presented, assuming the amplifier is operating with a saturating optical frequency signal. The analysis is primarily concerned with the effects of the gas pressure and the presence of an axial magnetic field on the characteristics of the amplifying medium. Semiclassical radiation theory is used, along with a density matrix description of the atomic medium which relates the motion of single atoms to the macroscopic observables. A two-level description of the atom, using phenomenological source rates and decay rates, forms the basis of our analysis of the gas laser medium. Pressure effects are taken into account to a large extent through suitable choices of decay rate parameters.

Two methods for calculating the induced polarization of the atomic medium are used. The first method utilizes a perturbation expansion which is valid for signal intensities which barely reach saturation strength, and it is quite general in applicability. The second method is valid for arbitrarily strong signals, but it yields tractable solutions only for zero magnetic field or for axial magnetic fields large enough such that the Zeeman splitting is much larger than the power broadened homogeneous linewidth of the laser transition. The effects of pressure broadening of the homogeneous spectral linewidth are included in both the weak-signal and strong-signal theories; however the effects of Zeeman sublevel-mixing collisions are taken into account only in the weak-signal theory.

The behavior of a He-Ne gas laser amplifier in the presence of an axial magnetic field has been studied experimentally by measuring gain and Faraday rotation of linearly polarized resonant laser signals for various values of input signal intensity, and by measuring nonlinearity - induced anisotropy for elliptically polarized resonant laser signals of various input intensities. Two high-gain transitions in the 3.39-μ region were used for study: a J = 1 to J = 2 (3s₂ → 3p₄) transition and a J = 1 to J = 1 (3s₂ → 3p₂) transition. The input signals were tuned to the centers of their respective resonant gain lines.

The experimental results agree quite well with corresponding theoretical expressions which have been developed to include the nonlinear effects of saturation strength signals. The experimental results clearly show saturation of Faraday rotation, and for the J = 1 t o J = 1 transition a Faraday rotation reversal and a traveling wave gain dip are seen for small values of axial magnetic field. The nonlinearity induced anisotropy shows a marked dependence on the gas pressure in the amplifier tube for the J = 1 to J = 2 transition; this dependence agrees with the predictions of the general perturbational or weak signal theory when allowances are made for the effects of Zeeman sublevel-mixing collisions. The results provide a method for measuring the upper (neon 3s₂) level quadrupole moment decay rate, the dipole moment decay rates for the 3s₂ → 3p₄ and 3s₂ → 3p₂ transitions, and the effects of various types of collision processes on these decay rates.

Effects of density differences on lateral mixing in open-channel flows

This study investigates lateral mixing of tracer fluids in turbulent open-channel flows when the tracer and ambient fluids have different densities. Longitudinal dispersion in flows with longitudinal density gradients is investigated also.

Lateral mixing was studied in a laboratory flume by introducing fluid tracers at the ambient flow velocity continuously and uniformly across a fraction of the flume width and over the entire depth of the ambient flow. Fluid samples were taken to obtain concentration distributions in cross-sections at various distances, x, downstream from the tracer source. The data were used to calculate variances of the lateral distributions of the depth-averaged concentration. When there was a difference in density between the tracer and the ambient fluids, lateral mixing close to the source was enhanced by density-induced secondary flows; however, far downstream where the density gradients were small, lateral mixing rates were independent of the initial density difference. A dimensional analysis of the problem and the data show that the normalized variance is a function of only three dimensionless numbers, which represent: (1) the x-coordinate, (2) the source width, and (3) the buoyancy flux from the source.

A simplified set of equations of motion for a fluid with a horizontal density gradient was integrated to give an expression for the density-induced velocity distribution. The dispersion coefficient due to this velocity distribution was also obtained. Using this dispersion coefficient in an analysis for predicting lateral mixing rates in the experiments of this investigation gave only qualitative agreement with the data. However, predicted longitudinal salinity distributions in an idealized laboratory estuary agree well with published data.

XPM-induced pulse compression in birefringent dispersion decreasing fiber

The pulse compression induced by cross-phase modulation in birefringent dispersion decreasing fiber is discussed theoretically by solving the coupled Schrodinger equations which include the contribution of the high-order non-linear effects, and third-order dispersion. In particular, it is found that a high quality compressed signal pulse can be obtained by a pump pulse of low intense through the technique. The dependence of optimum compression on the non-linear factor N, time delay tau(d) and the dispersive ratio f is also discussed in detail. (c) 2005 Elsevier B.V. All rights reserved.

Effects produced in GaAs by MeV ion bombardment

Presented in the first part of this thesis is work performed on the ionizing energy beam induced adhesion enhancement of thin (~ 500 Angstrom) Au films on GaAs substrates. The ionizing beam, employed in the present thesis, is the MeV ions (i.e., ¹⁶O, ¹⁹F, and ³⁵Cl), with energies between 1 and 20 MeV. Using the "Scratch" test for adhesion measurement, and ESCA for chemical analysis of the film-substrate interface, the native oxide layer at the interface is shown to play an important role in the adhesion enhancement by the ionizing radiation. A model is discussed which explains the experimental data on the the dependence of adhesion enhancement on the energy which was deposited into electronic processes at the interface. The ESCA data indicate that the chemical bonds (or compounds), which are responsible for the increase in the thin film adherence, are hydroxides rather than oxides.

In the second part of the thesis we present a research performed on the radiation damage in GaAs crystals produced by MeV ions. Lattice parameter dilatation in the surface layers of the GaAs crystals becomes saturated after a high dose bombardment at room temperature. The strain produced by nuclear collisions is shown to relax partially due to electronic excitation (with a functional dependence on the nuclear and electronic stopping power of bombarding ions). Data on the GaAs and GaP crystals suggest that low temperature recovery stage defects produce major crystal distortion. The x-ray rocking curve technique with a dynamical diffraction theory analysis provides the depth distribution of the strain and damage in the MeV ion bombarded crystals.

Primary and secondary threshold intensities of ultraviolet-laser-induced domain nucleation in nearly stoichiometric LiTaO3

The primary and secondary threshold intensities of ultraviolet-laser-induced preferential domain nucleation in nearly stoichiometric LiTaO3 is observed. The primary threshold is the minimum intensity to achieve the instantaneous preferential domain nucleation within the focus by the combined action of irradiation and electric fields. The secondary threshold is the minimum intensity to achieve the memory effect without any irradiation within the original focus. The space charge field created by the photoionization carriers is thought to be responsible for the instantaneous effect. The explanation based on the formation and transformation of extrinsic defect is presented for the memory effect. (c) 2008 American Institute of Physics.

Effects of magnetostriction and superlattice formation in ferromagnetic thin films

The contribution to the magnetic uniaxial perpendicular anisotropy which arises from substrate constraint through magnetostrictive effects has been measured in Ni-Fe and Ni-Co thin films evaporated on substrates at room temperature. This was accomplished by measuring the perpendicular anisotropy before and after removal of the film from the substrate. Data are given for the fcc crystal structure regions of both alloy systems, but data for Ni-Co include compositions with less than 60% Ni which have a small percentage of the hcp phase mixed with the fcc phase. The constraint contribution to the perpendicular anisotropy correlates well with the value of the bulk magnetostriction constant using the equation ∆K_˔=3/2λ_sσ. Measured values of isotropic stress for films thicker than 600 Å were 1.6 x 10¹⁰ dyn/cm². In films less than 600 Å thick the isotropic stress decreased with decreasing thickness. After removal of the films from the substrates, the measured perpendicular anisotropy deviated from the expected geometrical shape anisotropy near pure Ni in both alloys. This indicates that additional significant sources of anisotropy exist at these compositions.

The effect of substrate constraint on the crystalline anisotropy K₁ of Ni-Fe epitaxial films has been studied by use of a film removal technique, which involves the evaporation of an epitaxial layer of LiF on MgO, the epitaxial growth of the metallic film on the LiF, and the stripping of the film with water soluble tape. Films ranging in composition from 50% to 100% Ni have been studied. For compositions below 90% Ni the experimental values agree reasonably well with the first order theoretical prediction, ∆K₁=[-9/4(C₁₁-C₁₂)λ² 100+9/2C₄₄λ²111].

In order to compare the magnetic properties of epitaxial thin films more completely with the properties of bulk single crystals, Ni-Fe films ranging in composition from 60% to 90% Ni, which were evaporated epitaxially on (100) MgO substrates, have been subsequently annealed at 400°C in a vacuum of less than 10^-7 Torr to form the ordered Ni₃Fe structure near the 75% composition. This ordered structure has been confirmed by electron diffraction.

The saturation magnetization at Ni₃Fe increased about 6% with ordering which is in good agreement with previous bulk data. Measurements of the magnetocrystalline anisotropy energy K₁ for the epitaxial films show the same large changes with ordering as observed in bulk single crystal samples. In the (001) plane the magnetostriction constants ^λ100, ^λ111 are directly related to the induced anisotropy due to a uniform uniaxial strain in the [100] and [110] directions respectively. Assuming that the elastic constants of a film are the same as in bulk material and are unchanged by ordering, the changes in strain sensitivity with ordering for the epitaxial films are found to be in good agreement with values predicted from bulk data. The exchange constant A as measured by ferromagnetic resonance has been measured at the Ni₃Fe composition and found to increase 25% with ordering. This seems to indicate a significant increase in the Curie temperature which has only been inferred indirectly for bulk material.

Laser diode array side-pumped acousto-optic induced unidirectional operation Q-switched Nd : YAG slab ring laser

A laser-diode array (LDA) side-pumped Nd:YAG slab ring laser is described that incorporates a prism-shaped acousto-optic modulator to enforce unidirectional operation and Q-switching. When pumped by the maximum power of 50 W, Q-switched energies of 3.6 mJ and 50 ns duration, corresponding to a peak power of 72 kW, are obtained. (C) 1999 Society of Photo-Optical Instrumentation Engineers. [S0091-3286(99)01306-9].

Laser-induced changes on the complex refractive indices of phase-change thin film

The refractive indices of crystalline phase-change films are usually obtained by thermal-induced crystallization. However, this is not accurate, because the crystallization of phase-change film in rewritable optical disks is laser induced. In this study, we use the initializer to crystallize the phase-change films. The dependence of the refractive index n and the extinction coefficient k of the phase-change films on the initialization conditions are studied. Remarkable changes of the refractive indices (especially k) are found when the initialization laser power density is 6.63 mW/mum(2) and the initialization velocity is 4.0 m/s. At the same time, the structure changes of the phase-change films are also studied. This dependence is explained by the structure change of the films. These results are significant in improving the accuracy of optical design and the thermal simulation of phase-change optical disks, as well as in the study of phase-change optical disks at shorter wavelengths. (C) 2003 Society of Photo-Optical Instrumentation Engineers.

Thermal and thermal-optical effects in high-power photonic crystal fiber lasers

A series-parallel model is introduced to calculate the effective thermal conductivities of hollow claddings of photonic crystal fibers ( PCFs ). The temperature distribution and thermal-optical properties of PCF lasers are studied by solving the heat transfer equations. The average power scaling of the PCF lasers in respect of the thermal effects is also discussed. (c) 2006 Society of Photo-Optical Instrumentation Engineers.

Thermal and thermal-optical effects in high-power photonic crystal fiber lasers

A series-parallel model is introduced to calculate the effective thermal conductivities of hollow claddings of photonic crystal fibers ( PCFs ). The temperature distribution and thermal-optical properties of PCF lasers are studied by solving the heat transfer equations. The average power scaling of the PCF lasers in respect of the thermal effects is also discussed. (c) 2006 Society of Photo-Optical Instrumentation Engineers.

Effect of PbO on precipitation of laser-induced gold nanoparticles inside silicate glasses

We report on three-dimensional precipitation of Au nanoparticles in gold ions-doped silicate glasses by a femtosecond laser irradiation and further annealing. Experimental results show that PbO addition plays the double roles of inhibiting hole-trapped centers generation and promoting formation and growth of gold nanoparticles. Additionally, glass containing PbO shows an increased non-linear absorption after femtosecond laser irradiation and annealing. The observed phenomena are significant for applications such as fabrications of three-dimensional multi-colored images inside transparent materials and three-dimensional optical memory, and integrated micro-optical switches. (c) 2007 Elsevier B.V. All rights reserved.

Effects of thermal treatment on broadband near-infrared emission from Bi-doped chalcohalide glasses

GeGaSKBr glass with Bi ions as emission centers were fabricated. An intense emission centered at around 1230 nm with the width of more than 175 nm was observed by 808 nm photo-excitation of the glass. Lower quenching rate and thermal treatment promote micro-crystallization process, thus strengthening the emission. Crown Copyright (c) 2008 Published by Elsevier Ltd. All rights reserved.