Curcumin-Arteether Combination Therapy of Plasmodium berghei-Infected Mice Prevents Recrudescence Through Immunomodulation

Earlier studies in this laboratory have shown the potential of artemisinin-curcumin combination therapy in experimental malaria. In a parasite recrudescence model in mice infected with Plasmodium berghei (ANKA), a single dose of alpha, beta-arteether (ART) with three oral doses of curcumin prevented recrudescence, providing almost 95% protection. The parasites were completely cleared in blood with ART-alone (AE) or ART+curcumin (AC) treatments in the short-term, although the clearance was faster in the latter case involving increased ROS generation. But, parasites in liver and spleen were not cleared in AE or AC treatments, perhaps, serving as a reservoir for recrudescence. Parasitemia in blood reached up to 60% in AE-treated mice during the recrudescence phase, leading to death of animals. A transient increase of up to 2-3% parasitemia was observed in AC-treatment, leading to protection and reversal of splenomegaly. A striking increase in spleen mRNA levels for TLR2, IL-10 and IgG-subclass antibodies but a decrease in those for INF gamma and IL-12 was observed in AC-treatment. There was a striking increase in IL-10 and IgG subclass antibody levels but a decrease in INF gamma levels in sera leading to protection against recrudescence. AC-treatment failed to protect against recrudescence in TLR2(-/-) and IL-10(-/-) animals. IL-10 injection to AE-treated wild type mice and AC-treated TLR22/2 mice was able to prolong survival. Blood from the recrudescence phase in AE-treatment, but not from AC-treatment, was able to reinfect and kill naive animals. Sera from the recrudescence phase of AC-treated animals reacted with several parasite proteins compared to that from AE-treated animals. It is proposed that activation of TLR2-mediated innate immune response leading to enhanced IL-10 production and generation of anti-parasite antibodies contribute to protective immunity in AC-treated mice. These results indicate a potential for curcumin-based combination therapy to be tested for prevention of recrudescence in falciparum and relapse in vivax malaria.

Bose-Hubbard model in a strong effective magnetic field: Emergence of a chiral Mott insulator ground state

Motivated by experiments on Josephson junction arrays, and cold atoms in an optical lattice in a synthetic magnetic field, we study the ``fully frustrated'' Bose-Hubbard model with half a magnetic flux quantum per plaquette. We obtain the phase diagram of this model on a two-leg ladder at integer filling via the density matrix renormalization group approach, complemented by Monte Carlo simulations on an effective classical XY model. The ground state at intermediate correlations is consistently shown to be a chiral Mott insulator (CMI) with a gap to all excitations and staggered loop currents which spontaneously break time-reversal symmetry. We characterize the CMI state as a vortex supersolid or an indirect exciton condensate, and discuss various experimental implications.

On the Presumed Kinetic Consequences of Pre-equilibrium. Implications for the Michaelis-Menten Equation

The overall rate equation for a reaction sequence consisting of a pre-equilibrium and rate-determining steps should not be derived on the basis of the concentration of the intermediate product (X). This is apparently indicated by transition state theory (as the path followed to reach the highest energy transition state is irrelevant), but also proved by a straight-forward mathematical approach. The thesis is further supported by the equations of concurrent reactions as applied to the partitioning of X between the two competing routes (reversal of the pre-equilibrium and formation of product). The rate equation may only be derived rigorously on the basis of the law of mass action. It is proposed that the reactants acquire the overall activation energy prior to the pre-equilibrium, thus forming X in a high-energy state en route to the rate-determining transition state. (It is argued that conventional energy profile diagrams are misleading and need to be reinterpreted.) Also, these arguments invalidate the Michaelis-Menten equation of enzyme kinetics, and necessitate a fundamental revision of our present understanding of enzyme catalysis. (The observed ``saturation kinetics'' possibly arises from weak binding of a second molecule of substrate at the active site; analogous conclusions apply to reactions at surfaces).

Junction between surfaces of two topological insulators

We study the properties of a line junction which separates the surfaces of two three-dimensional topological insulators. The velocities of the Dirac electrons on the two surfaces may be unequal and may even have opposite signs. For a time-reversal invariant system, we show that the line junction is characterized by an arbitrary parameter alpha which determines the scattering from the junction. If the surface velocities have the same sign, we show that there can be edge states which propagate along the line junction with a velocity and spin orientation which depend on alpha and the ratio of the velocities. Next, we study what happens if the two surfaces are at an angle phi with respect to each other. We study the scattering and differential conductance through the line junction as functions of phi and alpha. We also find that there are edge states which propagate along the line junction with a velocity and spin orientation which depend on phi. Finally, if the surface velocities have opposite signs, we find that the electrons must transmit into the two-dimensional interface separating the two topological insulators.

Local Structural Differences in Homologous Proteins: Specificities in Different SCOP Classes

The constant increase in the number of solved protein structures is of great help in understanding the basic principles behind protein folding and evolution. 3-D structural knowledge is valuable in designing and developing methods for comparison, modelling and prediction of protein structures. These approaches for structure analysis can be directly implicated in studying protein function and for drug design. The backbone of a protein structure favours certain local conformations which include alpha-helices, beta-strands and turns. Libraries of limited number of local conformations (Structural Alphabets) were developed in the past to obtain a useful categorization of backbone conformation. Protein Block (PB) is one such Structural Alphabet that gave a reasonable structure approximation of 0.42 angstrom. In this study, we use PB description of local structures to analyse conformations that are preferred sites for structural variations and insertions, among group of related folds. This knowledge can be utilized in improving tools for structure comparison that work by analysing local structure similarities. Conformational differences between homologous proteins are known to occur often in the regions comprising turns and loops. Interestingly, these differences are found to have specific preferences depending upon the structural classes of proteins. Such class-specific preferences are mainly seen in the all-beta class with changes involving short helical conformations and hairpin turns. A test carried out on a benchmark dataset also indicates that the use of knowledge on the class specific variations can improve the performance of a PB based structure comparison approach. The preference for the indel sites also seem to be confined to a few backbone conformations involving beta-turns and helix C-caps. These are mainly associated with short loops joining the regular secondary structures that mediate a reversal in the chain direction. Rare beta-turns of type I' and II' are also identified as preferred sites for insertions.

Si isotope variability in Proterozoic cherts

We report Si-isotopic compositions of 75 sedimentologically and petrographically characterized chert samples with ages ranging from similar to 2600 to 750 Ma using multi-collector inductively coupled plasma mass spectrometry. delta Si-30 values of the cherts analyzed in this study show a similar to 7 parts per thousand range, from -4.29 to +2.85. This variability can be explained in part by (1) simple mixing of silica derived from continental (higher delta Si-30) and hydrothermal (lower delta Si-30) sources, (2) multiple mechanisms of silica precipitation and (3) Rayleigh-type fractionations within pore waters of individual basins. We observe similar to 3 parts per thousand variation in peritidal cherts from a single Neoproterozoic sedimentary basin (Spitsbergen). This variation can be explained by Rayleigh-type fractionation during precipitation from silica-saturated porewaters. In some samples, post-dissolution and reprecipitation of silica could have added to this effect. Our data also indicate that peritidal cherts are enriched in the heavier isotopes of Si whereas basinal cherts associated with banded iron formations (BIF) show lower delta Si-30. This difference could partly be due to Si being derived from hydrothermal sources in BIFs. We postulate that the difference in delta Si-30 between non-BIF and BIF cherts is consistent with the contrasting genesis of these deposits. Low delta Si-30 in BIF is consistent with laboratory experiments showing that silica adsorbed onto Fe-hydroxide particles preferentially incorporates lighter Si isotopes. Despite large intrabasinal variation and environmental differences, the data show a clear pattern of secular variation. Low delta Si-30 in Archean cherts is consistent with a dominantly hydrothermal source of silica to the oceans at that time. The monotonically increasing delta Si-30 from 3.8 to 1.5 Ga appears to reflect a general increase in continental versus hydrothermal sources of Si in seawater, as well as the preferential removal of lighter Si isotopes during silica precipitation in iron-associated cherts from silica-saturated seawater. The highest delta Si-30 values are observed in 1.5 Ga peritidal cherts; in part, these enriched values could reflect increasing sequestration of light silica during soil-forming processes, thus, delivering relatively heavy dissolved silica to the oceans from continental sources. The causes behind the reversal in trend towards lower delta Si-30 in cherts younger than 1.5 Ga old are less clear. Cherts deposited 1800-1900 Ma are especially low delta Si-30, a possible indication of transiently strong hydrothermal input at this time. (C) 2012 Elsevier Ltd. All rights reserved.

Designing carboxymethyl cellulose based layer-by-layer capsules as a carrier for protein delivery

Stable hollow microcapsules composed of sodium carboxymethyl cellulose (CMC) and poly (allylamine hydrochloride) (PAH) were produced by layer-by-layer adsorption of polyelectrolytes onto CaCO 3 microparticles. Subsequently the core was removed by addition of chelating agents for calcium ions. Zeta potential studies showed charge reversal with deposition of successive polyelectrolyte layers, indicating that the alternate electrostatic adsorption of polyelectrolytes of opposite charge was successfully achieved. The size and surface morphology of the capsules was characterized by various microscopy techniques. The pH responsive loading behavior was elucidated by confocal laser scanning microscopy (CLSM) studies using fluorescence labeled dextran (FITC-dextran) and labeled BSA (FITC-BSA). CLSM images confirmed the open (pH ≤ 6) and closed state (pH ≥ 7) of the capsules. A model drug bovine serum albumin (BSA) was spontaneously loaded below its isoelectric point into hollow microcapsules, where BSA is positively charged. The loading of the BSA into the microcapsules was found to be dependent on the feeding concentration and pH of the medium. 65 of the loaded BSA was released over 7h of which about 34 was released in the first hour. These findings demonstrate that (CMC/PAH) 2 hollow capsules can be further exploited as a potential drug delivery system.

Continuum theory of edge states of topological insulators: variational principle and boundary conditions

We develop a continuum theory to model low energy excitations of a generic four-band time reversal invariant electronic system with boundaries. We propose a variational energy functional for the wavefunctions which allows us to derive natural boundary conditions valid for such systems. Our formulation is particularly suited for developing a continuum theory of the protected edge/surface excitations of topological insulators both in two and three dimensions. By a detailed comparison of our analytical formulation with tight binding calculations of ribbons of topological insulators modelled by the Bernevig-Hughes-Zhang (BHZ) Hamiltonian, we show that the continuum theory with a natural boundary condition provides an appropriate description of the low energy physics.

Sharp raman anomalies and broken adiabaticity at a pressure induced transition from band to topological insulator in Sb2Se3

The nontrivial electronic topology of a topological insulator is thus far known to display signatures in a robust metallic state at the surface. Here, we establish vibrational anomalies in Raman spectra of the bulk that signify changes in electronic topology: an E-g(2) phonon softens unusually and its linewidth exhibits an asymmetric peak at the pressure induced electronic topological transition (ETT) in Sb2Se3 crystal. Our first-principles calculations confirm the electronic transition from band to topological insulating state with reversal of parity of electronic bands passing through a metallic state at the ETT, but do not capture the phonon anomalies which involve breakdown of adiabatic approximation due to strongly coupled dynamics of phonons and electrons. Treating this within a four-band model of topological insulators, we elucidate how nonadiabatic renormalization of phonons constitutes readily measurable bulk signatures of an ETT, which will facilitate efforts to develop topological insulators by modifying a band insulator. DOI: 10.1103/PhysRevLett.110.107401

Chiral Mott insulator with staggered loop currents in the fully frustrated Bose-Hubbard model

Motivated by experiments on Josephson junction arrays in a magnetic field and ultracold interacting atoms in an optical lattice in the presence of a ``synthetic'' orbital magnetic field, we study the ``fully frustrated'' Bose-Hubbard model and quantum XY model with half a flux quantum per lattice plaquette. Using Monte Carlo simulations and the density matrix renormalization group method, we show that these kinetically frustrated boson models admit three phases at integer filling: a weakly interacting chiral superfluid phase with staggered loop currents which spontaneously break time-reversal symmetry, a conventional Mott insulator at strong coupling, and a remarkable ``chiral Mott insulator'' (CMI) with staggered loop currents sandwiched between them at intermediate correlation. We discuss how the CMI state may be viewed as an exciton condensate or a vortex supersolid, study a Jastrow variational wave function which captures its correlations, present results for the boson momentum distribution across the phase diagram, and consider various experimental implications of our phase diagram. Finally, we consider generalizations to a staggered flux Bose-Hubbard model and a two-dimensional (2D) version of the CMI in weakly coupled ladders.

Transport across a junction of topological insulators and a superconductor

We study transport across a line junction lying between two orthogonal topological insulator surfaces and a superconductor which can have either s-wave (spin-singlet) or p-wave (spin-triplet) pairing symmetry. The junction can have three time-reversal invariant barriers on three sides. We compute the charge and the spin conductance across such a junction and study their behaviors as a function of the bias voltage applied across the junction and the three parameters used to characterize the barrier. We find that the presence of topological insulators and a superconductor leads to both Dirac- and Schrodinger-like features in charge and spin conductances. We discuss the effect of bound states on the superconducting side of the barrier on the conductance; in particular, we show that for triplet p-wave superconductors, such a junction may be used to determine the spin state of its Cooper pairs. Our study reveals that there is a nonzero spin conductance for some particular spin states of the triplet Cooper pairs; this is an effect of the topological insulators which break the spin rotation symmetry. Finally, we find an unusual satellite peak (in addition to the usual zero bias peak) in the spin conductance for p-wave symmetry of the superconductor order parameter.

Suppression Of Barkhausen Noise Due To Exchange Biasing In Fe-FeMn Bilalayers

Exchange biased Fe(FM)-FeMn(AFM) bilayers were grown by pulsed laser ablation in UHV and probed by SQUID magnetometer and planar Hall effect measurements. A suppression of barkhausen avalanches was observed during the switching of the bilayer when compared to that of pure Fe, which is indicative of a change in the reversal mechanism.

Refining sub-solidus phase relations in the systems CaO-RuO2-SiO2 and CaO-RuO2-V2O5

Sub-solidus phase relations in the ternary systems CaO-RuO2-SiO2 and CaO-RuO2-V2O5 have been refined using thermodynamic data on calcium ruthenates, silicates and vanadates. Tie lines are established by considering Gibbs energy change for exchange reactions. Quaternary oxides have not been detected in these systems. Because of the relatively large entropy associated with phase transition of Ca2SiO4 from olivine to alpha' structure at 1120 K, reversal of one tie line is seen in the system CaO-RuO2-SiO2 between 950 and 1230 K. There is no change in sub-solidus phase relation as a function of temperature in the system CaO-RuO2-V2O5. Since vanadium can exist in several lower oxidation states, the computed sub-solidus phase relations are valid only at high oxygen partial pressures. There is fair agreement between the computed phase diagram and the limited experimental information available for CaO-deficient compositions in the literature. (C) 2013 Elsevier Ltd. All rights reserved.

The effect of Sb on the electrical and magnetic properties of Ni-Zn ferrites prepared by sol-gel autocombustion method

Polycrystalline Ni-Zn ferrites with a well-defined composition of Ni0.4Zn0.6Fe2-xSbxO4 synthesized using sol-gel method. Morphological characterizations on the prepared samples were performed by high resolution transmission electron and field emission scanning electron microscopy. The powders were densified using microwave sintering method. The room temperature complex permittivity (epsilon' and epsilon aEuro(3)) and permeability (mu' and mu aEuro(3)) were measured over a wide frequency range from 1 MHz-1.8 GHz. The real part of permittivity varies as `x' concentration increases and the resonance frequency was observed at much higher frequencies and there is a significant decrease in the loss factor (tan delta). The electrical resistivity and permeability of NiZn ferrites increased with an increase of Sb content. As the concentration of `x' increases from 0 to 0.08 the saturation magnetisation decreases. The saturation magnetization (M-s) a parts per thousand aEuro parts per thousand 52.211 A.m(2)/Kg for x = 0 at room temperature. The room temperature electro paramagnetic resonance (EPR) were studied.

Floquet generation of Majorana end modes and topological invariants

We show how Majorana end modes can be generated in a one-dimensional system by varying some of the parameters in the Hamiltonian periodically in time. The specific model we consider is a chain containing spinless electrons with a nearest-neighbor hopping amplitude, a p-wave superconducting term, and a chemical potential; this is equivalent to a spin-1/2 chain with anisotropic XY couplings between nearest neighbors and a magnetic field applied in the (z) over cap direction. We show that varying the chemical potential (or magnetic field) periodically in time can produce Majorana modes at the ends of a long chain. We discuss two kinds of periodic driving, periodic delta-function kicks, and a simple harmonic variation with time. We discuss some distinctive features of the end modes such as the inverse participation ratio of their wave functions and their Floquet eigenvalues which are always equal to +/- 1 for time-reversal-symmetric systems. For the case of periodic delta-function kicks, we use the effective Hamiltonian of a system with periodic boundary conditions to define two topological invariants. The first invariant is a well-known winding number, while the second invariant has not appeared in the literature before. The second invariant is more powerful in that it always correctly predicts the numbers of end modes with Floquet eigenvalues equal to + 1 and -1, while the first invariant does not. We find that the number of end modes can become very large as the driving frequency decreases. We show that periodic delta-function kicks in the hopping and superconducting terms can also produce end modes. Finally, we study the effect of electron-phonon interactions (which are relevant at finite temperatures) and a random noise in the chemical potential on the Majorana modes.