Mycobacterium tuberculosis has diminished capacity to counteract redox stress induced by elevated levels of endogenous superoxide

Mycobacterium tuberculosis (Mtb) has evolved protective and detoxification mechanisms to maintain cytoplasmic redox balance in response to exogenous oxidative stress encountered inside host phagocytes. In contrast, little is known about the dynamic response of this pathogen to endogenous oxidative stress generated within Mtb. Using a noninvasive and specific biosensor of cytoplasmic redox state of Mtb, we for first time discovered a surprisingly high sensitivity of this pathogen to perturbation in redox homeostasis induced by elevated endogenous reactive oxygen species (ROS). We synthesized a series of hydroquinone-based small molecule ROS generators and found that ATD-3169 permeated mycobacteria to reliably enhance endogenous ROS including superoxide radicals. When Mtb strains including multidrug-resistant (MDR) and extensively drug-resistant (XDR) patient isolates were exposed to this compound, a dose-dependent, long-lasting, and irreversible oxidative shift in intramycobacterial redox potential was detected. Dynamic redox potential measurements revealed that Mtb had diminished capacity to restore cytoplasmic redox balance in comparison with Mycobacterium smegmatis (Msm), a fast growing nonpathogenic mycobacterial species. Accordingly, Mtb strains were extremely susceptible to inhibition by ATD-3169 but not Msm, suggesting a functional linkage between dynamic redox changes and survival. Microarray analysis showed major realignment of pathways involved in redox homeostasis, central metabolism, DNA repair, and cell wall lipid biosynthesis in response to ATD-3169, all consistent with enhanced endogenous ROS contributing to lethality induced by this compound. This work provides empirical evidence that the cytoplasmic redox poise of Mtb is uniquely sensitive to manipulation in steady-state endogenous ROS levels, thus revealing the importance of targeting intramycobacterial redox metabolism for controlling TB infection. (C) 2015 The Authors. Published by Elsevier Inc.

Conformal perturbation theory and higher spin entanglement entropy on the torus

We study the free fermion theory in 1+1 dimensions deformed by chemical potentials for holomorphic, conserved currents at finite temperature and on a spatial circle. For a spin-three chemical potential mu, the deformation is related at high temperatures to a higher spin black hole in hs0] theory on AdS(3) spacetime. We calculate the order mu(2) corrections to the single interval Renyi and entanglement entropies on the torus using the bosonized formulation. A consistent result, satisfying all checks, emerges upon carefully accounting for both perturbative and winding mode contributions in the bosonized language. The order mu(2) corrections involve integrals that are finite but potentially sensitive to contact term singularities. We propose and apply a prescription for defining such integrals which matches the Hamiltonian picture and passes several non-trivial checks for both thermal corrections and the Renyi entropies at this order. The thermal corrections are given by a weight six quasi-modular form, whilst the Renyi entropies are controlled by quasi-elliptic functions of the interval length with modular weight six. We also point out the well known connection between the perturbative expansion of the partition function in powers of the spin-three chemical potential and the Gross-Taylor genus expansion of large-N Yang-Mills theory on the torus. We note the absence of winding mode contributions in this connection, which suggests qualitatively different entanglement entropies for the two systems.

Controlled material transport and multidimensional patterning at small length scales using electromigration

Electromigration, mostly known for its damaging effects in microelectronic devices, is basically a material transport phenomenon driven by the electric field and kinetically controlled by diffusion. In this work, we show how controlled electromigration can be used to create scientifically interesting and technologically useful micro-/nano-scale patterns, which are otherwise extremely difficult to fabricate using conventional cleanroom practices, and present a few examples of such patterns. In a solid thin-film structure, electromigration is used to generate pores at preset locations for enhancing the sensitivity of a MEMS sensor. In addition to electromigration in solids, the flow instability associated with the electromigration-induced long-range flow of liquid metals is shown to form numerous structures with high surface area to volume ratio. In very thin solid films on non-conductive substrates, solidification of flow-affected region results in the formation of several features, such as nano-/micro-sized discrete metallic beads, 3D structures consisting of nano-stepped stairs, etc.

Impact of glycosylation on stability, structure and unfolding of soybean agglutinin (SBA): an insight from thermal perturbation molecular dynamics simulations

Glycosylation has been recognized as one of the most prevalent and complex post-translational modifications of proteins involving numerous enzymes and substrates. Its effect on the protein conformational transitions is not clearly understood yet. In this study, we have examined the effect of glycosylation on protein stability using molecular dynamics simulation of legume lectin soybean agglutinin (SBA). Its glycosylated moiety consists of high mannose type N-linked glycan (Man(9)GlcNAc(2)). To unveil the structural perturbations during thermal unfolding of these two forms, we have studied and compared them to the experimental results. From the perspective of dynamics, our simulations revealed that the nonglycosylated monomeric form is less stable than corresponding glycosylated form at normal and elevated temperatures. Moreover, at elevated temperature thermal destabilization is more prominent in solvent exposed loops, turns and ends of distinct beta sheets. SBA maintains it folded structure due to some important saltbridges, hydrogen bonds and hydrophobic interactions within the protein. The reducing terminal GlcNAc residues interact with the protein residues VAL161, PRO182 and SER225 via hydrophobic and via hydrogen bonding with ASN 9 and ASN 75. Our simulations also revealed that single glycosylation (ASN75) has no significant effect on corresponding cis peptide angle orientation. This atomistic description might have important implications for understanding the functionality and stability of Soybean agglutinin.

Origin of nonlinearity and plausible turbulence by hydromagnetic transient growth in accretion disks: Faster growth rate than magnetorotational instability

We investigate the evolution of hydromagnetic perturbations in a small section of accretion disks. It is known that molecular viscosity is negligible in accretion disks. Hence, it has been argued that a mechanism, known as magnetorotational instability (MRI), is responsible for transporting matter in the presence of a weak magnetic field. However, there are some shortcomings, which question the effectiveness of MRI. Now the question arises, whether other hydromagnetic effects, e.g., transient growth (TG), can play an important role in bringing nonlinearity into the system, even at weak magnetic fields. In addition, it should be determined whether MRI or TG is primarily responsible for revealing nonlinearity in order to make the flow turbulent. Our results prove explicitly that the flows with a high Reynolds number (Re), which is the case for realistic astrophysical accretion disks, exhibit nonlinearity via TG of perturbation modes faster than that by modes producing MRI. For a fixed wave vector, MRI dominates over transient effects only at low Re, lower than the value expected to be in astrophysical accretion disks, and low magnetic fields. This calls into serious question the (overall) persuasiveness of MRI in astrophysical accretion disks.

Ultra-sensitive pressure dependence of bandgap of rutile-GeO2 revealed by many body perturbation theory

The reported values of bandgap of rutile GeO2 calculated by the standard density functional theory within local-density approximation (LDA)/generalized gradient approximation (GGA) show a wide variation (similar to 2 eV), whose origin remains unresolved. Here, we investigate the reasons for this variation by studying the electronic structure of rutile-GeO2 using many-body perturbation theory within the GW framework. The bandgap as well as valence bandwidth at Gamma-point of rutile phase shows a strong dependence on volume change, which is independent of bandgap underestimation problem of LDA/GGA. This strong dependence originates from a change in hybridization among O-p and Ge-(s and p) orbitals. Furthermore, the parabolic nature of first conduction band along X-Gamma-M direction changes towards a linear dispersion with volume expansion. (C) 2015 AIP Publishing LLC.

Ultra-small sulphur nanoparticles configured inside a flexible organic mixed conducting network as a cathode for lithium-sulphur batteries

The major challenges in Li-S batteries are the formation of soluble polysulphides during the reversible conversion of S-8 <-> Li2S, large changes in sulphur particle volume during lithiation and extremely poor charge transport in sulphur. We demonstrate here a novel and simple strategy to overcome these challenges towards practical realization of a stable high performance Li-S battery. For the first time, a strategy is developed which does away with the necessity of pre-fabricated high surface area hollow-structured adsorbates and also multiple nontrivial synthesis steps related to sulphur loading inside such adsorbates. A lithiated polyethylene glycol (PEG) based surfactant tethered on ultra-small sulphur nanoparticles and wrapped up with polyaniline (PAni) (abbreviated as S-MIEC) is demonstrated here as an exceptional cathode for Li-S batteries. The PEG and PAni network around the sulphur nanoparticles serves as an efficient flexible trap for sulphur and polysulphides and also provides distinct pathways for electrons (through PAni) and ions (through PEG) during battery operation. Contrary to the cathodes demonstrated based on various carbon-sulphur composites, the mixed conducting S-MIEC showed an extremely high loading of 75%. The S-MIEC exhibited a stable capacity of nearly 900 mA h g(-1) at the end of 100 cycles at a 1C current rate.

pi-Electron rich small molecule sensors for the recognition of nitroaromatics

Selective and discriminative detection of -NO2 containing high energy organic compounds such as picric acid (PA), 2,4,6-trinitrotoluene (TNT) and dinitrotoluene (DNT) has become a challenging task due to concerns over national security, criminal investigations and environment protections. Among various known detection methods, fluorescence techniques have gained special attention in recent time. A wide variety of fluorescent chemosensors have been developed for nitroaromatic explosive detection. In this review article, we provide an overview of the recent developments made in small molecule-based turn-off fluorescent sensors for nitroaromatic explosives with special focus on organic and H-bonded supramolecular sensors. The fluorescent sensors discussed in this review are classified and organized according to their functionality and their recognition of nitroaromatics by fluorescence quenching.

Fracture Testing at Small-Length Scales: From Plasticity in Si to Brittleness in Pt

The field of micro-/nano-mechanics of materials has been driven, on the one hand by the development of ever smaller structures in devices, and, on the other, by the need to map property variations in large systems that are microstructurally graded. Observations of `smaller is stronger' have also brought in questions of accompanying fracture property changes in the materials. In the wake of scattered articles on micro-scale fracture testing of various material classes, this review attempts to provide a holistic picture of the current state of the art. In the process, various reliable micro-scale geometries are shown, challenges with respect to instrumentation to probe ever smaller length scales are discussed and examples from recent literature are put together to exhibit the expanse of unusual fracture response of materials, from ductility in Si to brittleness in Pt. Outstanding issues related to fracture mechanics of small structures are critically examined for plausible solutions.

Tailoring of Electronic Structure and Thermoelectric Properties of a Topological Crystalline Insulator by Chemical Doping

Topological crystalline insulators (TCIs) are a new quantum state of matter in which linearly dispersed metallic surface states are protected by crystal mirror symmetry. Owing to its vanishingly small bulk band gap, a TCI like Pb0.6Sn0.4Te has poor thermoelectric properties. Breaking of crystal symmetry can widen the band gap of TCI. While breaking of mirror symmetry in a TCI has been mostly explored by various physical perturbation techniques, chemical doping, which may also alter the electronic structure of TCI by perturbing the local mirror symmetry, has not yet been explored. Herein, we demonstrate that Na doping in Pb0.6Sn0.4Te locally breaks the crystal symmetry and opens up a bulk electronic band gap, which is confirmed by direct electronic absorption spectroscopy and electronic structure calculations. Na doping in Pb0.6Sn0.4Te increases p-type carrier concentration and suppresses the bipolar conduction (by widening the band gap), which collectively gives rise to a promising zT of 1 at 856 K for Pb0.58Sn0.40Na0.02Te. Breaking of crystal symmetry by chemical doping widens the bulk band gap in TCI, which uncovers a route to improve TCI for thermoelectric applications.

Small-Signal Stability Analysis of an Open-Loop Induction Motor Drive Including the Effect of Inverter Deadtime

This paper demonstrates light-load instability in a 100-kW open-loop induction motor drive on account of inverter deadtime. An improved small-signal model of an inverter-fed induction motor is proposed. This improved model is derived by linearizing the nonlinear dynamic equations of the motor, which include the inverter deadtime effect. Stability analysis is carried out on the 100-kW415-V three-phase induction motor considering no load. The analysis brings out the region of instability of this motor drive on the voltage versus frequency (V-f) plane. This region of light-load instability is found to expand with increase in inverter deadtime. Subharmonic oscillations of significant amplitude are observed in the steady-state simulated and measured current waveforms, at numerous operating points in the unstable region predicted, confirming the validity of the stability analysis. Furthermore, simulation and experimental results demonstrate that the proposed model is more accurate than an existing small-signal model in predicting the region of instability.

Perturbation of nucleo-cytoplasmic transport affects size of nucleus and nucleolus in human cells

Size regulation of human cell nucleus and nucleolus are poorly understood subjects. 3D reconstruction of live image shows that the karyoplasmic ratio (KR) increases by 30-80% in transformed cell lines compared to their immortalized counterpart. The attenuation of nucleo-cytoplasmic transport causes the KR value to increase by 30-50% in immortalized cell lines. Nucleolus volumes are significantly increased in transformed cell lines and the attenuation of nucleo-cytoplasmic transport causes a significant increase in the nucleolus volume of immortalized cell lines. A cytosol and nuclear fraction swapping experiment emphasizes the potential role of unknown cytosolic factors in nuclear and nucleolar size regulation.

A NOTE ON SMALL GAPS BETWEEN NONZERO FOURIER COEFFICIENTS OF CUSP FORMS

It is shown that there are infinitely many primitive cusp forms f of weight 2 with the property that for all X large enough, every interval (X, X + cX(1/4)), where c > 0 depends only on the form, contains an integer n such that the n-th Fourier coefficient of f is nonzero.