Ligand 5,10,15,20-Tetra(N-methyl-4-pyridyl)porphine (TMPyP4) Prefers the Parallel Propeller-Type Human Telomeric G-Quadruplex DNA over Its Other Polymorphs

The binding of ligand 5,10,15,20-tetra(N-methyl-4-pyridyl)porphine (TMPyP4) with telomeric and genomic G-quadruplex DNA has been extensively studied. However, a comparative study of interactions of TMPyP4 with different conformations of human telomeric G-quadruplex DNA, namely, parallel propeller-type (PP), antiparallel basket-type (AB), and mixed hybrid-type (MH) G-quadruplex DNA, has not been done. We considered all the possible binding sites in each of the G-quadruplex DNA structures and docked TMPyP4 to each one of them. The resultant most potent sites for binding were analyzed from the mean binding free energy of the complexes. Molecular dynamics simulations were then carried out, and analysis of the binding free energy of the TMPyP4-G-quadruplex complex showed that the binding of TMPyP4 with parallel propeller-type G-quadruplex DNA is preferred over the other two G-quadruplex DNA conformations. The results obtained from the change in solvent excluded surface area (SESA) and solvent accessible surface area (SASA) also support the more pronounced binding of the ligand with the parallel propeller-type G-quadruplex DNA.

Mössbauer effect and electron paramagnetic resonance studies on zinc borate glasses containing transition metal oxides

Studies have been carried out in glasses containing Fe2O3, V2O5, and Fe2O3 + V2O5. Mossbauer studies in the ZnO-B2O3-Fe2O3 system show that iron is present as Fe3+ with tetrahedral coordination and that the isomer shift and the quadrupole splitting decrease with increase of Fe2O3 Content; similarly, the isomer shift and quadrupole splitting are also found to decrease with increasing ZnO. On the other hand, in the Na2O-ZnO-B2O3-Fe2O3 system, the isomer shift increases with Na2O or ZnO while the quadrupole splitting is fairly insensitive. Electron paramagnetic resonance in the ZnO-B2O3-Fe2O3 system shows signals at g = 4.20 and 2.0, whose intensity and linewidth show strong dependence on Fe2O3 content. In the ZnO-B2O3-V2O5 system, electron paramagnetic resonance shows that vanadium is present as the vanadyl complex, and the hyperfine coupling constants, A(parallel-to) and A(perpendicular-to) decrease with increasing V2O5 content; on the other hand, g(parallel-to) decreases and g(perpendicular-to) increases slightly, indicating an increase in tetragonal distortion. Zinc borate glasses containing Fe2O3 + V2O5 do not show the hyperfine structure of V4+ due to the interaction between Fe3+ and V4+

Structural, optical and EPR studies on ZnO:Cu nanopowders prepared via low temperature solution combustion synthesis

Cu (0.1 mol%) doped ZnO nanopowders have been successfully synthesized by a wet chemical method at a relatively low temperature (300 degrees C). Powder X-ray diffraction (PXRD) analysis, scanning electron microscopy (SEM), Transmission electron microscopy (TEM), Fourier transformed infrared (FTIR) spectroscopy, UV-Visible spectroscopy, Photoluminescence (PL) and Electron Paramagnetic Resonance (EPR) measurements were used for characterization. PXRD results confirm that the nanopowders exhibit hexagonal wurtzite structure of ZnO without any secondary phase. The particle size of as-formed product has been calculated by Williamson-Hall (W-H) plots and Scherrer's formula is found to be in the range of similar to 40 nm. TEM image confirms the nano size crystalline nature of Cu doped ZnO. SEM micrographs of undoped and Cu doped ZnO show highly porous with large voids. UV-Vis spectrum showed a red shift in the absorption edge in Cu doped ZnO. PL spectra show prominent peaks corresponding to near band edge UV emission and defect related green emission in the visible region at room temperature and their possible mechanisms have been discussed. The EPR spectrum exhibits a broad resonance signal at g similar to 2.049, and two narrow resonances one at g similar to 1.990 and other at g similar to 1.950. The broad resonance signal at g similar to 2.049 is a characteristic of Cu2+ ion whereas the signal at g similar to 1.990 and g similar to 1.950 can be attributed to ionized oxygen vacancies and shallow donors respectively. The spin concentration (N) and paramagnetic susceptibility (X) have been evaluated and discussed. (C) 2011 Elsevier B. V. All rights reserved.

Giant Magnetoresistance and Related Properties of Rare Earth Manganates and Other Oxide Systems

Giant magnetoresistance (GMR), which was until recently confined to magnetic layered and granular materials, as well as doped magnetic semiconductors, occurs in manganate perovskites of the general formula Ln(1-x)A(x)MnO(3) (Ln = rare earth; A = divalent ion). These manganates are ferromagnetic at or above a certain value of x (or Mn4+ content) and become metallic at temperatures below the curie temperature, T-c. GMR is generally a maximum close to T-c or the insulator-metal (I-M) transition temperature, T-im. The T-c and %MR are markedly affected by the size of the A site cation, [r(A)], thereby affording a useful electronic phase diagram when T-c or T-im is plotted against [r(A)]. We discuss GMR and related properties of manganates in polycrystalline, thin-film, and single-crystal forms and point out certain commonalities and correlations. We also examine some unusual features in the electron-transport properties of manganates, in particular charge-ordering effects. Charge ordering is crucially dependent on [r(A)] or the e(g) band width, and the charge-ordered insulating state transforms to a metallic ferromagnetic state on the application of a magnetic field.

Beyond fractional derivatives: local approximation of other convolution integrals

Dynamic systems involving convolution integrals with decaying kernels, of which fractionally damped systems form a special case, are non-local in time and hence infinite dimensional. Straightforward numerical solution of such systems up to time t needs O(t(2)) computations owing to the repeated evaluation of integrals over intervals that grow like t. Finite-dimensional and local approximations are thus desirable. We present here an approximation method which first rewrites the evolution equation as a coupled in finite-dimensional system with no convolution, and then uses Galerkin approximation with finite elements to obtain linear, finite-dimensional, constant coefficient approximations for the convolution. This paper is a broad generalization, based on a new insight, of our prior work with fractional order derivatives (Singh & Chatterjee 2006 Nonlinear Dyn. 45, 183-206). In particular, the decaying kernels we can address are now generalized to the Laplace transforms of known functions; of these, the power law kernel of fractional order differentiation is a special case. The approximation can be refined easily. The local nature of the approximation allows numerical solution up to time t with O(t) computations. Examples with several different kernels show excellent performance. A key feature of our approach is that the dynamic system in which the convolution integral appears is itself approximated using another system, as distinct from numerically approximating just the solution for the given initial values; this allows non-standard uses of the approximation, e. g. in stability analyses.

Non-linear couette flow with heat transfer using the B-G-K model

In recent years a large number of investigators have devoted their efforts to the study of flow and heat transfer in rarefied gases, using the BGK [1] model or the Boltzmann kinetic equation. The velocity moment method which is based on an expansion of the distribution function as a series of orthogonal polynomials in velocity space, has been applied to the linearized problem of shear flow and heat transfer by Mott-Smith [2] and Wang Chang and Uhlenbeck [3]. Gross, Jackson and Ziering [4] have improved greatly upon this technique by expressing the distribution function in terms of half-range functions and it is this feature which leads to the rapid convergence of the method. The full-range moments method [4] has been modified by Bhatnagar [5] and then applied to plane Couette flow using the B-G-K model. Bhatnagar and Srivastava [6] have also studied the heat transfer in plane Couette flow using the linearized B-G-K equation. On the other hand, the half-range moments method has been applied by Gross and Ziering [7] to heat transfer between parallel plates using Boltzmann equation for hard sphere molecules and by Ziering [83 to shear and heat flow using Maxwell molecular model. Along different lines, a moment method has been applied by Lees and Liu [9] to heat transfer in Couette flow using Maxwell's transfer equation rather than the Boltzmann equation for distribution function. An iteration method has been developed by Willis [10] to apply it to non-linear heat transfer problems using the B-G-K model, with the zeroth iteration being taken as the solution of the collisionless kinetic equation. Krook [11] has also used the moment method to formulate the equivalent continuum equations and has pointed out that if the effects of molecular collisions are described by the B-G-K model, exact numerical solutions of many rarefied gas-dynamic problems can be obtained. Recently, these numerical solutions have been obtained by Anderson [12] for the non-linear heat transfer in Couette flow,

ErbB-2 expression and its association with other biological parameters of breast cancer among Indian women

Overexpression of the epidermal growth factor receptor family genes, which include ErbB-1, 2, 3 and 4, has been implicated in a number of cancers. We have studied the extent of ErbB-2 overexpression among Indian women with sporadic breast cancer. Methods: Immmunohistochemistry and genomic polymerase chain reaction (PCR) were used to study the ErbB2 overexpression. ErbB2 status was correlated with other clinico-pathological parameters, including patient survival. Results: ErbB-2 overexpression was detected in 43.2% (159/368) of the cases by immunohistochemistry. For a sub-set of patients (n = 55) for whom total DNA was available, ErbB-2 gene amplification was detected in 25.5% (14/55) of the cases by genomic PCR. While the ErbB2 overexpression was significantly higher in patients with lymphnode (χ2 = 12.06, P≤ 0.001), larger tumor size (χ2 = 8.22, P = 0.042) and ductal carcinoma (χ2 = 15.42, P ≤ 0.001), it was lower in patients with disease-free survival (χ2 = 22.13, P ≤ 0.001). Survival analysis on a sub-set of patients for whom survival data were available (n = 179) revealed that ErbB-2 status (χ2 =25.94, P ≤ 0.001), lymphnode status (χ2 = 12.68, P ≤ 0.001), distant metastasis (χ2 = 19.49, P ≤ 0.001) and stage of the disease (χ2 = 28.04, P ≤0.001) were markers of poor prognosis. Conclusions: ErbB-2 overexpression was significantly greater compared with the Western literature, but comparable to other Indian studies. Significant correlation was found between ErbB-2 status and lymphnode status, tumor size and ductal carcinoma. ErbB-2 status, lymph node status, distant metastasis and stage of the disease were found to be prognostic indicators.

Effect of coordinated ions on structure and flexibility of parallel G-quadruplexes: A molecular dynamics study

ingle tract guanine residues can associate to form stable parallel quadruplex structures in the presence of certain cations. Nanosecond scale molecular dynamics simulations have been performed on fully solvated fibre model of parallel d(G(7)) quadruplex structures with Na+ or K+ ions coordinated in the cavity formed by the O6 atoms of the guanine bases. The AMBER 4.1 force field and Particle Mesh Ewald technique for electrostatic interactions have been used in all simulations. There quadruplex structures are stable during the simulation, with the middle four base tetrads showing root mean square deviation values between 0.5 to 0.8 Angstrom from the initial structure as well the high resolution crystal structure. Even in the absence of any coordinated ion in the initial structure, the G-quadruplex structure remains intact throughout the simulation. During the 1.1 ns MD simulation, one Nai counter ion from the solvent as well as several water molecules enter the central cavity to occupy the empty coordination sites within the parallel quadruplex and help stabilize the structure. Hydrogen bonding pattern depends on the nature of the coordinated ion, with the G-tetrad undergoing local structural variation to accommodate cations of different sizes. in the absence of any coordinated ion. due to strong mutual repulsion, O6 atoms within G-tetrad are forced farther apart from each other, which leads to a considerably different hydrogen bonding scheme within the G-tetrads and very favourable interaction energy between the guanine bases constituting a G-tetrad. However, a coordinated ion between G-tetrads provides extra stacking energy for the G-tetrads and makes the quadruplex structure more rigid. Na+ ions, within the quadruplex cavity, are more mobile than coordinated K+ ions. A number of hydrogen bonded water molecules are observed within the grooves of all quadruplex structures.

Symmetrical Bisbenzimidazoles with Benzenediyl Spacer: The Role of the Shape of the Ligand on the Stabilization and Structural Alterations in Telomeric G-Quadruplex DNA and Telomerase Inhibition

The extremities of chromosomes end in a G-rich single-stranded overhang that has been implicated in the onset of the replicate senescence. The repeated sequence forming a G-overhang is able to adopt a four-stranded DNA structure called G-quadruplex, which is a poor substrate for the enzyme telomerase. Small molecule based ligands that selectively stabilize the telomeric G-quadruplex DNA, induce telomere shortening eventually leading to cell death. Herein, we have investigated the G-quadruplex DNA interaction with two isomeric bisbenzimidazole-based compounds that differ in terms of shape (V-shaped angular vs linear).While the linear isomer induced some stabilization of the intramolecular G-quadruplex structure generated in the presence of Na+ the other, having V-shaped central planar core, caused a dramatic structural alteration of the latter, above a threshold concentration. This transition was evident from the pronounced changes observed in the circular dichroism spectra and from the get mobility shift assa involving the G-quadruples DNA. Notably, this angular isomer could also induce the G-quadruplex formation in the absence of any added cation. The ligand-quadruples complexes were investigated by computational molecular modeling, providing further information on structure-activity relationships. Finally, TRAP (telomerase repeat amplification protocol) experiments demonstrated that the angular isomer is selective toward the inhibition of telomerase activity.

Hormones andCuscuta development: In vitro induction of haustoria by cytokinin and its inhibition by other hormones

Cytokinins induced haustoria formation in excised 10-mm segments ofCuscuta vine, the subapical 25-to-50-mm region being most responsive, producing a mean of 4–6 haustoria per segment. The order of effectiveness of cytokinins continuously applied (72 h) was 6-benzylaminopurine (BA) ges isopentenyladenine (iP) Gt zeatin (Z). Ribosides of BA and Z were as effective as the bases, whereas riboside of iP ([9R]iP) was half as effective as iP. Haustoria induction was influenced by weather and seasonal conditions at the time of vine collection; materials obtained on warm, sunny days responded better than those obtained on rainy, cloudy, or cool days. Haustoria were induced equally well all around the segment, and no thigmostimulus was needed for induction. p ]A 10-min pulse of 100 mgrM BA induced half as many haustoria as a 60-min pulse or continuous application of BA. White light inhibited haustoria induction elicited by a short (30-min) pulse of BA, whereas a longer (120-min) BA application overcame this light inhibition. Auxins (IAA or NAA, 1–10 mgrM), gibberellin (GA3, 1–10 mgrM), ethylene (as ethrel, 10–100 mgrM), and abscisic acid (ABA, 100 mgrM) were individually inhibitory (60–80%) with respect to haustoria induction when given continuously with 50 mgrM BA. A 60-min pulse of auxins (10 mgrM), GA3 (100 mgrM), or ethrel (10 mgrM), given at various time intervals during or after a 60-min pulse of 100 mgrM BA, showed that inhibition was maximal (70–95%) between 4 and 16 h of BA application and negligible (GA3) or much reduced (auxin, ethrel) at 20 h, indicating a ldquocommitmentrdquo to haustoria formation by this time.

Effect of coordinated ions on structure and flexiblity of parallel G-quandruplexes: a molecular dynamics study

Single tract guanine residues can associate to form stable parallel quadruplex structures in the presence of certain cations. Nanosecond scale molecular dynamics simulations have been performed on fully solvated fibre model of parallel d(G7) quadruplex structures with Na+ or K+ ions coordinated in the cavity formed by the 06 atoms of the guanine bases. The AMBER 4.1 force field and Particle Mesh Ewald technique for electrostatic interactions have been used in all simulations. These quadruplex structures are stable during the simulation, with the middle four base tetrads showing root mean square deviation values between 0.5 to 0.8 A from the initial structure as well the high resolution crystal structure. Even in the absence of any coordinated ion in the initial structure, the G-quadruplex structure remains intact throughout the simulation. During the 1.1 ns MD simulation, one Na+ counter ion from the solvent as well as several water molecules enter the central cavity to occupy the empty coordination sites within the parallel quadruplex and help stabilize the structure. Hydrogen bonding pattern depends on the nature of the coordinated ion, with the G-tetrad undergoing local structural variation to accommodate cations of different sizes. In the absence of any coordinated ion, due to strong mutual repulsion, 06 atoms within G-tetrad are forced farther apart from each other, which leads to a considerably different hydrogen bonding scheme within the G-tetrads and very favourable interaction energy between the guanine bases constituting a G-tetrad. However, a coordinated ion between G-tetrads provides extra stacking energy for the G-tetrads and makes the quadruplex structure more rigid. Na+ ions, within the quadruplex cavity, are more mobile than coordinated K+ ions. A number of hydrogen bonded water molecules are observed within the grooves of all quadruplex structures

Conformational Polymorphism in G-tetraplex Structures: Strand Reversal by Base Flipover or Sugar Flipover

Guanine rich sequences adopt a variety of four stranded structures, which differ in strand orientation and conformation about the glycosidic bond even though they are all stabilised by Hoogsteen hydrogen bonded guanine tetrads. Detailed model building and molecular mechanics calculations have been carried out to investigate various possible conformations of guanines along a strand and different possible orientations of guanine strands in a G-tetraplex structure. It is found that for an oligo G stretch per se, a parallel four stranded structure with all guanines in anti conformation is favoured over other possible tetraplex structures. Hence an alternating syn-anti arrangement of guanines along a strand is likely to occur only in folded back tetraplex structures with antiparallel G strands. Our study provides a theoretical rationale for the observed alternation of glycosidic conformation and the inverted stacking arrangement arising from base flipover, in antiparallel G-tetraplex structures and also highlights the various structural features arising due to different types of strand orientations. The molecular mechanics calculations help in elucidating the various interactions which stabilize different G-tetraplex structures and indicate that screening of phosphate charge by counterions could have a dramatic effect on groove width in these four stranded structures.

A Thermodynamic Proposal for the Exposition of Critically and other Subtle Features in Self-Deflagrating Ammonium Perchlorate Systems

A first comprehensive investigation on the deflagration of ammonium perchlorate (AP) in the subcritical regime, below the low pressure deflagration limit (LPL, 2.03 MPa) christened as regime I$^{\prime}$, is discussed by using an elegant thermodynamic approach. In this regime, deflagration was effected by augmenting the initial temperature (T$_{0}$) of the AP strand and by adding fuels like aliphatic dicarboxylic acids or polymers like carboxy terminated polybutadiene (CTPB). From this thermodynamic model, considering the dependence of burning rate ($\dot{r}$) on pressure (P) and T$_{0}$, the true condensed (E$_{\text{s,c}}$) and gas phase (E$_{\text{s,g}}$) activation energies, just below and above the surface respectively, have been obtained and the data clearly distinguishes the deflagration mechanisms in regime I$^{\prime}$ and I (2.03-6.08 MPa). Substantial reduction in the E$_{\text{s,c}}$ of regime I$^{\prime}$, compared to that of regime I, is attributed to HClO$_{4}$ catalysed decomposition of AP. HClO$_{4}$ formation, which occurs only in regime I$^{\prime}$, promotes dent formation on the surface as revealed by the reflectance photomicrographs, in contrast to the smooth surface in regime I. The HClO$_{4}$ vapours, in regime I$^{\prime}$, also catalyse the gas phase reactions and thus bring down the E$_{\text{s,g}}$ too. The excess heat transferred on to the surface from the gas phase is used to melt AP and hence E$_{\text{s,c}}$, in regime I, corresponds to the melt AP decomposition. It is consistent with the similar variation observed for both the melt layer thickness and $\dot{r}$ as a function of P. Thermochemical calculations of the surface heat release support the thermodynamic model and reveal that the AP sublimation reduces the required critical exothermicity of 1108.8 kJ kg$^{-1}$ at the surface. It accounts for the AP not sustaining combustion in the subcritical regime I$^{\prime}$. Further support for the model comes from the temperature-time profiles of the combustion train of AP. The gas and condensed phase enthalpies, derived from the profile, give excellent agreement with those computed thermochemically. The $\sigma _{\text{p}}$ expressions derived from this model establish the mechanistic distinction of regime I$^{\prime}$ and I and thus lend support to the thermodynamic model. On comparing the deflagration of strand against powder AP, the proposed thermodynamic model correctly predicts that the total enthalpy of the condensed and gas phases remains unaltered. However, 16% of AP particles undergo buoyant lifting into the gas phase in the `free board region' (FBR) and this renders the demarcation of the true surface difficult. It is found that T$_{\text{s}}$ lies in the FBR and due to this, in regime I$^{\prime}$, the E$_{\text{s,c}}$ of powder AP matches with the E$_{\text{s,g}}$ of the pellet. The model was extended to AP/dicarboxylic acids and AP/CTPB mixture. The condensed ($\Delta $H$_{1}$) and gas phase ($\Delta $H$_{2}$) enthalpies were obtained from the temperature profile analyses which fit well with those computed thermochemically. The $\Delta $H$_{1}$ of the AP/succinic acid mixture was found just at the threshold of sustaining combustion. Indeed the lower homologue malonic acid, as predicted, does not sustain combustion. In vaporizable fuels like sebacic acid the E$_{\text{s,c}}$ in regime I$^{\prime}$, understandably, conforms to the AP decomposition. However, the E$_{\text{s,c}}$ in AP/CTPB system corresponds to the softening of the polymer which covers AP particles to promote extensive condensed phase reactions. The proposed thermodynamic model also satisfactorily explains certain unique features like intermittent, plateau and flameless combustion in AP/ polymeric fuel systems.

Conformational polymorphism in G-tetraplex structures: strand reversal by base flipover or sugar flipover

Guanlne rich sequences adopt a variety of four stranded structures, which differ in strand orientation and conformation about the glycosldic bond even though they are all stabilised by Hoogsteen hydrogen bonded guanlne tetrads. Detailed model building and molecular mechanics calculations have been carried out to investigate various possible conformations of guanlnes along a strand and different possible orientations of guanlne strands In a G-tetraplex structure. It is found that for an ollgo G stretch per se, a parallel four stranded structure with all guanines In anti conformation is favoured over other possible tetraplex structures. Hence an alternating syn-anti arrangement of guanlnes along a strand is likely to occur only in folded back tetraplex structures with antiparallel G strands. Our study provides a theoretical rationale for the observed alternation of glycosldic conformation and the inverted stacking arrangement arising from base filpover, In antlparallel G-tetraplex structures and also highlights the various structural features arising due to different types of strand orientations. The molecular mechanics calculations help in elucidating the various interactions which stabilize different G-tetraplex structures and indicate that screening of phosphate charge by counterions could have a dramatic effect on groove width in these four stranded structures.

Needleless Vaccine Delivery Using Micro-Shock Waves

Shock waves are one of the most efficient mechanisms of energy dissipation observed in nature. In this study, utilizing the instantaneous mechanical impulse generated behind a micro-shock wave during a controlled explosion, a novel nonintrusive needleless vaccine delivery system has been developed. It is well-known that antigens in the epidermis are efficiently presented by resident Langerhans cells, eliciting the requisite immune response, making them a good target for vaccine delivery. Unfortunately, needle-free devices for epidermal delivery have inherent problems from the perspective of the safety and comfort of the patient. The penetration depth of less than 100 mu m in the skin can elicit higher immune response without any pain. Here we show the efficient utilization of our needleless device (that uses micro-shock waves) for vaccination. The production of liquid jet was confirmed by high-speed microscopy, and the penetration in acrylamide gel and mouse skin was observed by confocal microscopy. Salmonella enterica serovar Typhimurium vaccine strain pmrG-HM-D (DV-STM-07) was delivered using our device in the murine salmonellosis model, and the effectiveness of the delivery system for vaccination was compared with other routes of vaccination. Vaccination using our device elicits better protection and an IgG response even at a lower vaccine dose (10-fold less) compared to other routes of vaccination. We anticipate that our novel method can be utilized for effective, cheap, and safe vaccination in the near future.