Synthesis of a series of diaminobenzo[f]- and diaminobenzo[h]pyrimido[4,5-b]quinolines as 5-deaza tetracyclic nonclassical antifolates

A series of diaminobenzo[f]- and diaminobenzo[h]pyrimido[4,5-b]quinolines 1–11 were designed as 5-deaza tetracyclic nonclassical, lipophilic antifolates. The compounds were designed as conformationally semi-rigid and rigid analogs of 2,4-diamino-6-phenyl- 12 and 2,4-diamino-7-phenylpyrido[2,3-d]pyrimidines 13 and 14 . The target compounds were synthesized by cyclocondensation of chlorovinyl aldehydes obtained from appropriately substituted 1- or 2-tetralone, with 2,4,6-friaminopyrimidine. Compounds 1–11 were evaluated as inhibitors of P. carinii and T. gondii dihydrofolate reductases. These pathogens cause fatal opportunistic infections in AIDS patients. In addition, the selectivity of these agents was evaluated using rat liver dihydrofolate reductase as the mammalian source. In general the benzo[f]pyrimido[4,5-b]quinolines 1–5 were more potent than the corresponding benzo[h]pyrimido[4,5-b]quinoline analogues 6–11 against P. carinii and rat liver dihydrofolate reductase and were equipotent against T. gondii dihydrofolate reductase. Compounds 6–11 were moderately selective towards T. gondii dihydrofolate reductase with IC₅₀S in the 10⁻⁷ M range. In contrast analogues 1–5 lacked selectivity against P. carinii or T. gondii dihydrofolate reductase and were, in general, potent inhibitors of rat liver dihydrofolate reductase with IC₅₀S in the 10⁻⁸ M range. Analogues 1 and 4 were evaluated against a series of tumor cell lines in vitro and were found to have moderate antitumor activity (IC50 10⁻⁶ M). The structure activity/selectivity relationships suggest that benzo[f]pyrimido analogues 1–5 with the phenyl ring substitution in the “upper” portion of the tetracyclic ring are better accommodated within the rat liver (mammalian) dihydrofolate reductase and P. carinii dihydrofolate reductase active sites compared to the benzo[h]pyrimido analogues 6–11 which have the phenyl ring substitution in the “lower” portion of the tetracyclic ring. In contrast T. gondii dihydrofolate reductase does not discriminate between the isomers and binds to both series of compounds with similar affinities.     

Optical Modulation of Azobenzene‐Modified Peptide for Gold Surface Binding

The ability to precisely and remotely modulate reversible binding interactions between biomolecules and abiotic surfaces is appealing for many applications. To achieve this level of control, an azobenzene‐based optical switch is added to nanoparticle‐binding peptides in order to switch peptide conformation and attenuate binding affinity to gold surfaces via binding and dissociation of peptides.     

Electron and positron impact excitation of hydrogen from the initially excited 22S state to 32S and 32P states

The total and differential cross sections for the electron and positron impact excitation of hydrogen from its initially excited metastable 2²S state to 3²S and 3²P states are reported. A distorted-wave approximation theory is used for the calculation. The angular correlation parameters, Ly and alignment angle are also reported for 2²S-3²P excitation. For comparison, similar first Born results are also obtained. Interesting features are noted on comparing our distorted wave results with the first Born results as well as with the other available results forn ²S andn ²P (n=2,3) excitations from the ground 1²S state of hydrogen.     

Laser induced breakdown of Ar,N2 and O2 gases using 1.064, 0.532, 0.355 and 0.266 μm radiation

An experimental investigation of laser-induced breakdown using Nd:YAG laser harmonics for argon, nitrogen and oxygen gases is reported. Pressure dependence as well as wavelength dependence of the breakdown threshold irradianceI _th is investigated. The experimental observations for 1.064 and 0.532 m laser wavelengths are in agreement with theoretical calculations which include the effects of multiphoton ionization and cascade ionization.     

Surface studies on bimetallic thiocyanate ligand based single crystals of MnHg(SCN)4, CdHg(SCN)4 and ZnCd(SCN)4

Bimetallic SCN ligand based single crystals of manganese mercury thiocyanate (MMTC), cadmium mercury thiocyanate (CMTC) and zinc cadmium thiocyanate (ZCTC) are grown by slow solvent evaporation technique. The growth mechanism and surface features are investigated by optical microscopic techniques such as scanning electron microscopy (SEM) and atomic force microscopy (AFM). The laser induced surface damage measurements were carried out using a Q-switched Nd:YAG laser at 1064 nm with laser beam of 1.0 Hz and pulse duration 25 ps. The laser damage threshold values of MMTC, CMTC and ZCTC are found to be 15.9, 22.9 and 19.7 GW/cm², respectively. The SEM analysis of MMTC reveals the formation of elongated dendrite growth pattern caused by the fluctuations of Mn and Hg metal ligands when thiocyanate (SCN) bridges them. The etching study indicates the occurrence of different types of etch pit patterns like terraced triangles, pillars, pyramids and rods. The AFM images confirm the formation of three major hillocks with cavities in MMTC. The measured roughness values for CMTC crystal are very much lower than that of MMTC.     

High-resolution frequency estimation technique for recovering phase distribution in interferometers

An integral approach to phase measurement is presented. First, the use of a high-resolution technique for the pixelwise detection of phase steps is proposed. Next, the robustness of the algorithm that is developed is improved by incorporation of a denoising procedure during spectral estimation. The pixelwise knowledge of phase steps is then applied to the Vandermonde system of equations for retrieval of phase values at each pixel point. Conceptually, our proposal involves the design of an annihilating filter that has zeros at the frequencies associated with the polynomial that describes the fringe intensity. The parametric estimation of this annihilating filter yields the desired spectral information embedded in the signal, which in our case represents the phase steps. The proposed method offers the advantage of extracting the interference phase of nonsinusoidal waveforms in the presence of miscalibration error of the piezoelectric transducer. In addition, in contrast to previously reported methods, this method does not require the application of selective phase steps between data frames for nonsinusoidal waveforms.     

Three Flavor Neutrino Mixing and Dark Energy Above GUT Scale

Neutrino mixing lead to a non zero contribution to the dark energy of the universe. We assume that the neutrino masses and mixing arise through physics at a scale intermediate between Planck Scale and the electroweak scale. The mechanism of neutrino mixing is a possible candidate to contribute the cosmological dark energy. Quantum gravitational (Planck scale) effects lead to an effective SU(2) _L ×U(1) invariant dimension-5 Lagrangian involving neutrino and Higgs fields, which gives rise to additional terms in neutrino mass matrix. There additional term can be considered to be perturbation of the GUT scale bi-maximal neutrino mass matrix. We assume that the gravitational interaction is flavor. In this paper, we discuss the three flavor neutrino mixing and cosmological dark energy contributes due to Planck scale effects.     

Effect of annular apodization and pupil beam parameter in the focal region of high NA lens

Focusing properties of the radially polarized axisymmetric Bessel-modulated Gaussian beam with quadratic radial dependence (QBG beam) and annular aperture are investigated theoretically by vector diffraction theory. Simulation results show that the intensity distribution in the focal region of the radially polarized axisymmetric QBG beam can be adjusted considerably by small beam parameter (μ) and annular aperture (δ). When μ increases, the focal spot may change to focal hole and changes focal pattern remarkably. On introducing annular aperture, focus can split or extends along the optical axis for different μ. In this paper, we have shown the generation of the focal spot, dark focal spot, focal split and increase in focal depth in the axial direction of the incident beam propagating through the aligned optical system.     

Magnetization transfer and T2 quantitation in normal appearing cortical gray matter and white matter adjacent to focal abnormality in patients with traumatic brain injury

Traumatic brain injury (TBI) is one of the commonest causes of morbidity and mortality in the developed countries with posttraumatic epilepsy and functional disability being its major sequelae. The purpose of this study was to test the hypothesis whether the normal appearing adjacent gray and white matter regions on T2 and T1 weighted magnetization transfer (MT) weighted images show any abnormality on quantitative imaging in patients with TBI. A total of 51 patients with TBI and 10 normal subjects were included in this study. There were significant differences in T2 and MT ratio values of T2 weighted and T1 weighted MT normal appearing gray matter regions adjacent to focal image abnormality compared to normal gray matter regions in the normal individuals as corresponding contralateral regions of the TBI patient's group (p < 0.05). However the adjoining normal appearing white matter quantitative values did not show any significant change compared to the corresponding contralateral normal white matter values. We conclude that quantitative T2 and MT ratio values provide additional abnormality in patients with TBI that is not discernable on conventional T2 weighted and T1 weighted MT imaging especially in gray matter. This additional information may be of value in overall management of these patients with TBI.