Synthesis and evaluation of the biological activity of N `-2-oxo-1,2 dihydro-3H-indol-3-ylidene] benzohydrazides as potential anticancer agents

New N'-2-oxo-1,2-dihydro-3H-indol-3-ylidene]benzohydrazide derivatives were synthesized and evaluated for their cytotoxic properties against murine leukemia, L1210, human leukemia, REH and K562, human T-cell leukemia, CEM and human cervix carcinoma, HeLa cells. Among the tested compounds, the 3,4,5-trimethoxy-N'-5-methyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene]ben zohydrazide derivative (5t) emerged as the most potent inhibitor against all the tumor cell lines evaluated. To investigate the mechanism of action, 5t was further studied by cell cycle analysis, mitochondrial membrane potential analysis, DNA fragmentation and Annexin V-FITC flow cytometric analysis, which suggested that 5t was able to induce apoptosis at submicromolar range.

Maximum group velocity in a one-dimensional model with a sinusoidally varying staggered potential

We use Floquet theory to study the maximum value of the stroboscopic group velocity in a one-dimensional tight-binding model subjected to an on-site staggered potential varying sinusoidally in time. The results obtained by numerically diagonalizing the Floquet operator are analyzed using a variety of analytical schemes. In the low-frequency limit we use adiabatic theory, while in the high-frequency limit the Magnus expansion of the Floquet Hamiltonian turns out to be appropriate. When the magnitude of the staggered potential is much greater or much less than the hopping, we use degenerate Floquet perturbation theory; we find that dynamical localization occurs in the former case when the maximum group velocity vanishes. Finally, starting from an ``engineered'' initial state where the particles (taken to be hard-core bosons) are localized in one part of the chain, we demonstrate that the existence of a maximum stroboscopic group velocity manifests in a light-cone-like spreading of the particles in real space.

Outer Bounds on the Secrecy Rate of the 2-User Symmetric Deterministic Interference Channel with Transmitter Cooperation

This paper derives outer bounds for the 2-user symmetric linear deterministic interference channel (SLDIC) with limited-rate transmitter cooperation and perfect secrecy constraints at the receivers. Five outer bounds are derived, under different assumptions of providing side information to receivers and partitioning the encoded message/output depending on the relative strength of the signal and the interference. The usefulness of these outer bounds is shown by comparing the bounds with the inner bound on the achievable secrecy rate derived by the authors in a previous work. Also, the outer bounds help to establish that sharing random bits through the cooperative link can achieve the optimal rate in the very high interference regime.

Symmetric Supercapacitor Based on Reduced Graphene Oxide in Non-Aqueous Electrolyte

Reduced graphene oxide (RGO) is prepared by thermal exfoliation of graphite oxide in air. Symmetric RGO/RGO supercapacitors are constructed in a non-aqueous electrolyte and characterized. The values of energy density are 44 Wh kg(-1) and 15 Wh kg(-1), respectively at 0.15 and 8.0 kW kg(-1). The symmetric supercapacitor exhibits stable charge/discharge cycling tested up to 3000 cycles. The low-temperature thermal exfoliation approach is convenient for mass production of RGO at low cost and it can be used as electrode material for energy storage applications. (c) The Author(s) 2015. Published by ECS. All rights reserved.

Inner Bound on the GDOF of the K-User MIMO Gaussian Symmetric Interference Channel

The K-user multiple input multiple output (MIMO) Gaussian symmetric interference channel where each transmitter has M antennas and each receiver has N antennas is studied from a generalized degrees of freedom (GDOF) perspective. An inner bound on the GDOF is derived using a combination of techniques such as treating interference as noise, zero forcing (ZF) at the receivers, interference alignment (IA), and extending the Han-Kobayashi (HK) scheme to K users, as a function of the number of antennas and the log INR/log SNR level. Several interesting conclusions are drawn from the derived bounds. It is shown that when K > N/M + 1, a combination of the HK and IA schemes performs the best among the schemes considered. When N/M < K <= N/M + 1, the HK-scheme outperforms other schemes and is found to be GDOF optimal in many cases. In addition, when the SNR and INR are at the same level, ZF-receiving and the HK-scheme have the same GDOF performance.

Design of symmetric TIM barrel proteins from first principles

Background: Computational protein design is a rapidly maturing field within structural biology, with the goal of designing proteins with custom structures and functions. Such proteins could find widespread medical and industrial applications. Here, we have adapted algorithms from the Rosetta software suite to design much larger proteins, based on ideal geometric and topological criteria. Furthermore, we have developed techniques to incorporate symmetry into designed structures. For our first design attempt, we targeted the (alpha/beta)(8) TIM barrel scaffold. We gained novel insights into TIM barrel folding mechanisms from studying natural TIM barrel structures, and from analyzing previous TIM barrel design attempts. Methods: Computational protein design and analysis was performed using the Rosetta software suite and custom scripts. Genes encoding all designed proteins were synthesized and cloned on the pET20-b vector. Standard circular dichroism and gel chromatographic experiments were performed to determine protein biophysical characteristics. 1D NMR and 2D HSQC experiments were performed to determine protein structural characteristics. Results: Extensive protein design simulations coupled with ab initio modeling yielded several all-atom models of ideal, 4-fold symmetric TIM barrels. Four such models were experimentally characterized. The best designed structure (Symmetrin-1) contained a polar, histidine-rich pore, forming an extensive hydrogen bonding network. Symmetrin-1 was easily expressed and readily soluble. It showed circular dichroism spectra characteristic of well-folded alpha/beta proteins. Temperature melting experiments revealed cooperative and reversible unfolding, with a T-m of 44 degrees C and a Gibbs free energy of unfolding (Delta G degrees) of 8.0 kJ/mol. Urea denaturing experiments confirmed these observations, revealing a C-m of 1.6 M and a Delta G degrees of 8.3 kJ/mol. Symmetrin-1 adopted a monomeric conformation, with an apparent molecular weight of 32.12 kDa, and displayed well resolved 1D-NMR spectra. However, the HSQC spectrum revealed somewhat molten characteristics. Conclusions: Despite the detection of molten characteristics, the creation of a soluble, cooperatively folding protein represents an advancement over previous attempts at TIM barrel design. Strategies to further improve Symmetrin-1 are elaborated. Our techniques may be used to create other large, internally symmetric proteins.

Isotopic fractionation in proteins as a measure of hydrogen bond length

If a deuterated molecule containing strong intramolecular hydrogen bonds is placed in a hydrogenated solvent, it may preferentially exchange deuterium for hydrogen. This preference is due to the difference between the vibrational zero-point energy for hydrogen and deuterium. It is found that the associated fractionation factor (I) is correlated with the strength of the intramolecular hydrogen bonds. This correlation has been used to determine the length of the H-bonds (donor-acceptor separation) in a diverse range of enzymes and has been argued to support the existence of short low-barrier H-bonds. Starting with a potential energy surface based on a simple diabatic state model for H-bonds, we calculate (I) as a function of the proton donor-acceptor distance R. For numerical results, we use a parameterization of the model for symmetric 0-H. ``.0 bonds R. H. McKenzie, Chem. Phys. Lett. 535, 196 (2012)]. We consider the relative contributions of the 0-H stretch vibration, O-H bend vibrations (both in plane and out of plane), tunneling splitting effects at finite temperature, and the secondary geometric isotope effect. We compare our total (I) as a function of R with NMR experimental results for enzymes, and in particular with an earlier model parametrization (D(R), used previously to determine bond lengths. (C) 2015 AIP Publishing LLC.

Exploring the potential of adjunct therapy in tuberculosis

A critical unmet need for treatment of drug-resistant tuberculosis (TB) is to find novel therapies that are efficacious, safe, and shorten the duration of treatment. Drug discovery approaches for TB primarily target essential genes of the pathogen Mycobacterium tuberculosis (Mtb) but novel strategies such as host-directed therapies and nonmicrobicidal targets are necessary to bring about a paradigm shift in treatment. Drugs targeting the host pathways and nonmicrobicidal proteins can be used only in conjunction with existing drugs as adjunct therapies. Significantly, host-directed adjunct therapies have the potential to decrease duration of treatment, as they are less prone to drug resistance, target the immune responses, and act via novel mechanism of action. Recent advances in targeting host-pathogen interactions have implicated pathways such as eicosanoid regulation and angiogenesis. Furthermore, several approved drugs such as metformin and verapamil have been identified that appear suitable for repurposing for the treatment of TB. These findings and the challenges in the area of host- and/or pathogen-directed adjunct therapies and their implications for TB therapy are discussed.

Average Overlap for Clustering Incomplete Data using Symmetric Non-Negative Matrix Factorization

Clustering techniques which can handle incomplete data have become increasingly important due to varied applications in marketing research, medical diagnosis and survey data analysis. Existing techniques cope up with missing values either by using data modification/imputation or by partial distance computation, often unreliable depending on the number of features available. In this paper, we propose a novel approach for clustering data with missing values, which performs the task by Symmetric Non-Negative Matrix Factorization (SNMF) of a complete pair-wise similarity matrix, computed from the given incomplete data. To accomplish this, we define a novel similarity measure based on Average Overlap similarity metric which can effectively handle missing values without modification of data. Further, the similarity measure is more reliable than partial distances and inherently possesses the properties required to perform SNMF. The experimental evaluation on real world datasets demonstrates that the proposed approach is efficient, scalable and shows significantly better performance compared to the existing techniques.

An Open-End winding IM drive with Multilevel 12-sided Polygonal Vectors with Symmetric Triangles

Multilevel inverters with hexagonal voltage space vector structures have improved performance of induction motor drives compared to that of the two level inverters. Further reduction in the torque ripple on the motor shaft is possible by using multilevel dodecagonal (12-sided polygon) voltage space vector structures. The advantages of dodecagonal voltage space vector based PWM techniques are the complete elimination of fifth and seventh harmonics in phase voltages for the full modulation range and the extension of linear modulation range. This paper proposes an inverter circuit topology capable of generating multilevel dodecagonal voltage space vectors with symmetric triangles, by cascading two asymmetric three level inverters with isolated H-Bridges. This is made possible by proper selection of DC link voltages and the selection of resultant switching states for the inverters. In this paper, a simple PWM timing calculation method is proposed. Experimental results have also been presented in this paper to validate the proposed concept.

A method for coupling the phase-field model based on a grand-potential formalism to thermodynamic databases

In this paper we derive an approach for the effective utilization of thermodynamic data in phase-field simulations. While the most widely used methodology for multi-component alloys is following the work by Eiken et al. (2006), wherein, an extrapolative scheme is utilized in conjunction with the TQ interface for deriving the driving force for phase transformation, a corresponding simplistic method based on the formulation of a parabolic free-energy model incorporating all the thermodynamics has been laid out for binary alloys in the work by Folch and Plapp (2005). In the following, we extend this latter approach for multi-component alloys in the framework of the grand-potential formalism. The coupling is applied for the case of the binary eutectic solidification in the Cr-Ni alloy and two-phase solidification in the ternary eutectic alloy (Al-Cr-Ni). A thermodynamic justification entails the basis of the formulation and places it in context of the bigger picture of Integrated Computational Materials Engineering. (C) 2015 Elsevier Ltd. All rights reserved.

An automatic algorithm for mixed mode crack growth rate based on drop potential method

A new automatic algorithm for the assessment of mixed mode crack growth rate characteristics is presented based on the concept of an equivalent crack. The residual ligament size approach is introduced to implementation this algorithm for identifying the crack tip position on a curved path with respect to the drop potential signal. The automatic algorithm accounting for the curvilinear crack trajectory and employing an electrical potential difference was calibrated with respect to the optical measurements for the growing crack under cyclic mixed mode loading conditions. The effectiveness of the proposed algorithm is confirmed by fatigue tests performed on ST3 steel compact tension-shear specimens in the full range of mode mixities from pure mode Ito pure mode II. (C) 2015 Elsevier Ltd. All rights reserved.

MnFe2O4-Fe3O4 core-shell nanoparticles as a potential contrast agent for magnetic resonance imaging

In recent years, magnetic core-shell nanoparticles have received widespread attention due to their unique properties that can be used for various applications. We introduce here a magnetic core-shell nanoparticle system for potential application as a contrast agent in magnetic resonance imaging (MRI). MnFe2O4-Fe3O4 core-shell nanoparticles were synthesized by the wet-chemical synthesis method. Detailed structural and compositional charaterization confirmed the formation of a core-shell microstructure for the nanoparticles. Magnetic charaterization revealed the superparamagnetic nature of the as-synthesized core-shell nanoparticles. Average size and saturation magnetization values obtained for the as-synthesized core-shell nanoparticle were 12.5 nm and 69.34 emu g(-1) respectively. The transverse relaxivity value of the water protons obtained in the presence of the core-shell nanoparticles was 184.1 mM(-1) s(-1). To investigate the effect of the core-shell geometry towards enhancing the relaxivity value, transverse relaxivity values were also obtained in the presence of separately synthesized single phase Fe3O4 and MnFe2O4 nanoparticles. Average size and saturation magnetization values for the as-synthesized Fe3O4 nanoparticles were 12 nm and 65.8 emu g(-1) respectively. Average size and saturation magnetization values for the MnFe2O4 nanoparticles were 9 nm and 61.5 emu g(-1) respectively. The transverse relaxivity value obtained in the presence of single phase Fe3O4 and MnFe2O4 nanoparticles was 96.6 and 83.2 mM(-1) s(-1) respectively. All the nanoparticles (core-shell and single phase) were coated with chitosan by a surfactant exchange reaction before determining the relaxivity values. For similar nanoparticle sizes and saturation magnetization values, the highest value of the transverse relaxivity in the case of core-shell nanoparticles clearly illustrated that the difference in the magnetic nature of the core and shell phases in the core-shell nanoparticles creates greater magnetic inhomogeneity in the surrounding medium yielding a high value for proton relaxivity. The MnFe2O4-Fe3O4 core-shell nanoparticles exhibited extremely low toxicity towards the MCF-7 cell line. Taken together, this opens up new avenues for the use of core-shell nanoparticles in MRI.

Baryon squishing in synthetic dimensions by effective SU(M) gauge fields

The ``synthetic dimension'' proposal A. Celi et al., Phys. Rev. Lett. 112, 043001 (2014)] uses atoms with M internal states (''flavors'') in a one-dimensional (1D) optical lattice, to realize a hopping Hamiltonian equivalent to the Hofstadter model (tight-binding model with a given magnetic flux per plaquette) on an M-sites-wide square lattice strip. We investigate the physics of SU(M) symmetric interactions in the synthetic dimension system. We show that this system is equivalent to particles with SU(M) symmetric interactions] experiencing an SU(M) Zeeman field at each lattice site and a non-Abelian SU(M) gauge potential that affects their hopping. This equivalence brings out the possibility of generating nonlocal interactions between particles at different sites of the optical lattice. In addition, the gauge field induces a flavor-orbital coupling, which mitigates the ``baryon breaking'' effect of the Zeeman field. For M particles, concomitantly, the SU(M) singlet baryon which is site localized in the usual 1D optical lattice, is deformed to a nonlocal object (''squished baryon''). We conclusively demonstrate this effect by analytical arguments and exact (numerical) diagonalization studies. Our study promises a rich many-body phase diagram for this system. It also uncovers the possibility of using the synthetic dimension system to laboratory realize condensed-matter models such as the SU(M) random flux model, inconceivable in conventional experimental systems.