Co-evolution of specific amino acid in sigma 1.2 region and nucleotide base in the discriminator to act as sensors of small molecule effectors of transcription initiation in mycobacteria

The transcription from rrn and a number of other promoters is regulated by initiating ribonucleotides (iNTPs) and guanosine tetra/penta phosphate (p)ppGpp], either by strengthening or by weakening of the RNA polymerase (RNAP)-promoter interactions during initiation. Studies in Escherichia coli revealed the importance of a sequence termed discriminator, located between -10 and the transcription start site of the responsive promoters in this mode of regulation. Instability of the open complex at these promoters is attributed to the lack of stabilizing interactions between the suboptimal discriminator and the 1.2 region of sigma 70 (Sig70) in RNAP holoenzyme. We demonstrate a different pattern of interaction between the promoters and sigma A (SigA) of Mycobacterium tuberculosis to execute similar regulation. Instead of cytosine and methionine, thymine at three nucleotides downstream to -10 element and leucine 232 in SigA are found to be essential for iNTPs and pppGpp mediated response at the rrn and gyr promoters of the organism. The specificity of the interaction is substantiated by mutational replacements, either in the discriminator or in SigA, which abolish the nucleotide mediated regulation in vitro or in vivo. Specific yet distinct bases and the amino acids appear to have co-evolved' to retain the discriminator-sigma 1.2 region regulatory switch operated by iNTPs/pppGpp during the transcription initiation in different bacteria.

A Hardware Grid Simulator to Test Grid-Connected Inverter Systems.

Grid-connected systems when put to use at the site would experience scenarios like voltage sag, voltage swell, frequency deviations and unbalance which are common in the real world grid. When these systems are tested at laboratory, these scenarios do not exist and an almost stiff voltage source is what is usually seen. But, to qualify the grid-connected systems to operate at the site, it becomes essential to test them under the grid conditions mentioned earlier. The grid simulator is a hardware that can be programmed to generate some of the typical conditions experienced by the grid-connected systems at site. It is an inverter that is controlled to act like a voltage source in series with a grid impedance. The series grid impedance is emulated virtually within the inverter control rather than through physical components, thus avoiding the losses and the need for bulky reactive components. This paper describes the design of a grid simulator. Control implementation issues are highlighted in the experimental results.

Orthogonal biofunctionalization of magnetic nanoparticles via ``clickable'' poly(ethylene glycol) silanes: a ``universal ligand'' strategy to design stealth and target-specific nanocarriers

The present work demonstrates a novel strategy to synthesize orthogonally bio-engineered magnetonanohybrids (MNPs) through the design of versatile, biocompatible linkers whose structure includes: (i) a robust anchor to bind with metal-oxide surfaces; (ii) tailored surface groups to act as spacers and (iii) a general method to implement orthogonal functionalizations of the substrate via ``click chemistry''. Ligands that possess the synthetic generality of features (i)-(iii) are categorized as ``universal ligands''. Herein, we report the synthesis of a novel, azido-terminated poly(ethylene glycol) (PEG) silane that can easily self-assemble on MNPs through hetero-condensation between surface hydroxyl groups and the silane end of the ligand, and simultaneously provide multiple clickable sites for high density, chemoselective bio-conjugation. To establish the universal-ligand-strategy, we clicked alkyl-functionalized folate onto the surface of PEGylated MNPs. By further integrating a near-infrared fluorescent (NIRF) marker (Alexa-Fluor 647) with MNPs, we demonstrated their folate-receptor mediated internalization inside cancer cells and subsequent translocation into lysosomes and mitochondria. Ex vivo NIRF imaging established that the azido-PEG-silane developed in course of the study can effectively reduce the sequestration of MNPs by macrophage organs (viz. liver and spleen). These folate-PEG-MNPs were not only stealth and noncytotoxic but their dual optical and magnetic properties aided in tracking their whereabouts through combined magnetic resonance and optical imaging. Together, these results provided a strong motivation for the future use of the ``universal ligand'' strategy towards development of ``smart'' nanohybrids for theragnostic applications.

How to run a campaign: Optimal control of SIS and SIR information epidemics

Information spreading in a population can be modeled as an epidemic. Campaigners (e.g., election campaign managers, companies marketing products or movies) are interested in spreading a message by a given deadline, using limited resources. In this paper, we formulate the above situation as an optimal control problem and the solution (using Pontryagin's Maximum Principle) prescribes an optimal resource allocation over the time of the campaign. We consider two different scenarios-in the first, the campaigner can adjust a direct control (over time) which allows her to recruit individuals from the population (at some cost) to act as spreaders for the Susceptible-Infected-Susceptible (SIS) epidemic model. In the second case, we allow the campaigner to adjust the effective spreading rate by incentivizing the infected in the Susceptible-Infected-Recovered (SIR) model, in addition to the direct recruitment. We consider time varying information spreading rate in our formulation to model the changing interest level of individuals in the campaign, as the deadline is reached. In both the cases, we show the existence of a solution and its uniqueness for sufficiently small campaign deadlines. For the fixed spreading rate, we show the effectiveness of the optimal control strategy against the constant control strategy, a heuristic control strategy and no control. We show the sensitivity of the optimal control to the spreading rate profile when it is time varying. (C) 2014 Elsevier Inc. All rights reserved.

A quinazoline derivative as quick-response red-shifted reporter for nanomolar Al3+ and applicable to living cell staining

A newly synthesized and structurally characterized quinazoline derivative (L) has been shown to act as a quick-response chemosensor for Al3+ with a high selectivity over other metal ions in water-DMSO. In the presence of Al3+, L shows a red-shifted ratiometric enhancement in fluorescence as a result of internal charge transfer and chelation-enhanced fluorescence through the inhibition of a photo-induced electron transfer mechanism. This probe detects Al3+ at concentrations as low as 1.48 nM in 100 mM HEPES buffer (DMSO-water, 1 : 9 v/v) at biological pH with a very short response time (15-20 s). L was applied to biological imaging to validate its utility as a fluorescent probe for monitoring Al3+ ions in living cells, illustrating its value in practical environmental and biological systems.

Males and females of the social wasp Ropalidia marginata do not differ in their cuticular hydrocarbon profiles and do not seem to use any long-distance volatile mate attraction cues

Sex pheromones are vital in communication between individuals belonging to opposite sexes and form an integral part of the reproductive biology of various species. Among insects, sexual dimorphism in CHCs has been reported from diverse taxa spanning seven different orders, and thereby CHCs have been implicated as sex pheromones. Because males and females of the primitively eusocial wasp Ropalidia marginata touch each other with their antennae during mating, before engaging in sperm transfer, a sex pheromone that is perceived via contact chemosensation through the antennae can possibly exist in this species. Since CHCs have been implied as sex pheromones in various insects (including hymenopterans), and since sexual dimorphism of CHCs should be an obligatory prerequisite for them to act as sex pheromones, we investigated whether males and females of R. marginata differ in their CHC profiles. We found only nonvolatile CHCs, and our results show absence of sexual dimorphism in CHCs, suggesting that CHCs do not function as sex pheromone in this species. A behavioral assay failed to show presence of mate attraction at a distance, thereby showing the absence of volatile long-distance mate attraction cues (that may originate from sources other than and in addition to CHCs).

Iron(II) and iron(III) complexes of 2,4-dithiobiuret

Ferrous and ferric complexes of 2,4-dithiobiuret (Dtb) of the type Fe(Dtb)m Xn where m, n = 1-3, and X = CI–, Br–, I– and SO 4 2– , and a neutral Fe(Dtb-H)2 complex have been synthesized and characterised by elemental analyses, magnetic susceptibility, i.r., electronic and Mössbauer spectroscopic studies. From its i.r. spectrum Dtb was found to act as a S,S-coordinating bidentate chelate. The magnetic moment, electronic and Massbauer spectra are consistent with a low spin distorted octahedral structure for the ferric complexes and a high spin form for ferrous complexes.

Chemistry and biology of DNA methyltransferases

Recognition of a specific DNA sequence by a protein is probably the best example of macromolecular interactions leading to various events. It is a prerequisite to understanding the basis of protein-DNA interactions to obtain a better insight into fundamental processes such as transcription, replication, repair, and recombination. DNA methyltransferases with varying sequence specificities provide an excellent model system for understanding the molecular mechanism of specific DNA recognition. Sequence comparison of cloned genes, along with mutational analyses and recent crystallographic studies, have clearly defined the functions of various conserved motifs. These enzymes access their target base in an elegant manner by flipping it out of the DNA double helix. The drastic protein-induced DNA distortion, first reported for HhaI DNA methyltransferase, appears to be a common mechanism employed by various proteins that need to act on bases. A remarkable feature of the catalytic mechanism of DNA (cytosine-5) methyltransferases is the ability of these enzymes to induce deamination of the target cytosine in the absence of S-adenosyl-L-methionine or its analogs. The enzyme-catalyzed deamination reaction is postulated to be the major cause of mutational hotspots at CpG islands responsible for various human genetic disorders. Methylation of adenine residues in Escherichia coli is known to regulate various processes such as transcription, replication, repair, recombination, transposition, and phage packaging.

Rationalizing the effects of amino acid side chain, pyridine, and imidazole on the assembly and reversible disassembly of a octanuclear Cu(III) complex

This paper reports the observation of a reversible disassembly process for a previously reported octanuclear Cu(II) complex with imidazole. To identify the factors responsible for the process, five Cu(II) complexes of different nuclearity with different amino acid-derived tetradentate ligands were structurally characterized. The results show that the coordination geometry preference of Cu(II), the tendency of imidazole to act as in-plane ligand, and H-bonding played important role in the formation and disassembly of the octanuclear complex. A general scheme describing the effect of different amino acid side arms, solvents, and exogenous ligands on the nuclearity of the Cu(II) complexes has been presented. The crystals of the complexes also showed formation of multifaceted networks in the resulting complexes.

4,4′-Bipyridyl complexes of iron: Magnetic, Mössbauer and other spectroscopic studies

4,4prime-Bipyridyl (4,4prime-bipy) complexes of ferrous salts of the Fe(4,4prime-bipy)x(anion)y type (where x or y=1 or 2) and of ferric salts of the Fe(4,4prime-bipy)m(anion)n type (where m=1 or 2 and n=3) have been synthesised. Elemental analyses, i.r. and electronic spectra, magnetic and Mössbauer studies have been performed to characterize the complexes. 4,4prime-Bipy and some anions are inferred to act as bridging ligands. The magnetic moments, electronic and Mössbauer spectra suggest that the complexes are of high spin type with distorted octahedral structures. The value of the isomer shift and quadrupole splitting are discussed in terms of bonding of the ligand and anions.

Probing Fluorine Interactions in a Polyhydroxylated Environment: Conservation of a C-F center dot center dot center dot H-C Recognition Motif in Presence of O-H center dot center dot center dot O Hydrogen Bonds

Three conformationally locked fluorinated polycyclitols have been specially crafted on a rigid trans-decalin backbone, employing a surprisingly facile pyridine-poly(hydrogen fluoride)-mediated stereospecific epoxide ring opening as the key reaction. Molecula design of the three fluorinated probes under study focused on providing an efficient platform for (a) evaluating the ability of covalently bonded fluorine, vis-a-vis the isosteric hydroxy group, to act as a H-bond acceptor and (b) examining the possibility for an organic fluorine moiety, placed suitably in a spatially invariant position, to engage an 1,3-diaxial OH functionality in a purported intramolecular O-H center dot center dot center dot F hydrogen bond. The present endeavour reveals that C(sp(3))-F center dot center dot center dot H-C(sp(3)) hydrogen bonds, though weak and lesser investigated, can indeed be observed and supramolecular recognition motifs, involving such interactions, can be conserved even in crystal structures laden with stronger O-H center dot center dot center dot O hydrogen bonds.

Mooij correlation in disordered metals

We point out that the Mooij correlation follows naturally from a dynamically disordered tight-binding Hamiltonian with random modulations of both the diagonal and the off-diagonal matrix elements which are known to act in opposition. The dynamic disorder is treated exactly while the static disorder is incorporated approximately as an effective additional time-dependent disorder affecting the diffusive electron. Such a time translation of static disorder is known to manifest itself in certain limits as a renormalization of the diffusion coefficient. The calculated conductivity exhibits the Mooij correlation at high temperatures, where quantum coherence associated with the static disorder can be ignored.

Structural studies of analgesics and their interactions. XII. Structure and interactions of anti-inflammatory fenamates. A concerted crystallographic and theoretical conformational study

A theoretical conformational analysis of fenamates, which are N-arylated derivatives of anthranilic acid or 2-aminonicotinic acid with different substituents on the aryl (phenyl) group, is reported. The analysis of these analgesics, which are believed to act through the inhibition of prostaglandin biosynthesis, was carried out using semi-empirical potential functions. The results and available crystallographic observations have been critically examined in terms of their relevance to drug action. Crystallographic studies of these drugs and their complexes have revealed that the fenamate molecules share a striking invariant feature, namely, the sixmembered ring bearing the carboxyl group is coplanar with the carboxyl group and the bridging imino group,the coplanarity being stabilized by resonance interactions and an internal hydrogen bond between the imino and carboxyl groups. The results of the theoretical analysis provide a conformational rationale for the observed invariant coplanarity. The second sixmembered ring, which provides hydrophobicity in a substantial part of the molecule, has limited conformational flexibility in meclofenamic, mefenamic and flufenamic acids. Comparison of the conformational energy maps of these acids shows that they could all assume the same conformation when bound to the relevant enzyme. The present study provides a structural explanation for the difference in the activity of niflumic acid, which can assume a conformation in which the whole molecule is nearly planar. The main role of the carboxyl group appears to be to provide a site for intermolecular interactions in addition to helping in stabilizing the invariant coplanar feature and providing hydrophilicity at one end of the molecule. The fenamates thus provide a good example of conformation- dependent molecular asymmetry.

Modelling, Design and Analysis of Low Frequency Platform for Attenuating Micro-Vibration in Spacecraft

One of the most important factors that affect the pointing of precision payloads and devices in space platforms is the vibration generated due to static and dynamic unbalanced forces of rotary equipments placed in the neighborhood of payload. Generally, such disturbances are of low amplitude, less than 1 kHz, and are termed as ‘micro-vibrations’. Due to low damping in the space structure, these vibrations have long decay time and they degrade the performance of payload. This paper addresses the design, modeling and analysis of a low frequency space frame platform for passive and active attenuation of micro-vibrations. This flexible platform has been designed to act as a mount for devices like reaction wheels, and consists of four folded continuous beams arranged in three dimensions. Frequency and response analysis have been carried out by varying the number of folds, and thickness of vertical beam. Results show that lower frequencies can be achieved by increasing the number of folds and by decreasing the thickness of the blade. In addition, active vibration control is studied by incorporating piezoelectric actuators and sensors in the dynamic model. It is shown using simulation that a control strategy using optimal control is effective for vibration suppression under a wide variety of loading conditions.

The Design and Construction of Synthetic Protein Mimics

A strategy for the modular construction of synthetic protein mimics based on the ability non-protein amino acids to act as stereochemical directors of polypeptide chain folding, is described. The use of alpha-aminoisobutyric acid (Aib) to construct stereochemically rigid helices has been exemplified by crystallographic and spectroscopic studies of several apolar peptides, ranging in length from seven to sixteen residues. The problem of linker design in elaborating alpha,alpha motifs has been considered. Analysis of protein crystal structure data provides a guide to choosing linking sequences. Attempts at constructing linked helical motifs using linking Gly-Pro segments have been described. The use of flexible linkers, like epsilon-aminocaproic acid has been examined and the crystallographic and solution state analysis of a linked helix motif has been presented. The use of bulky sidechain modifications on a helical scaffold, as a means of generating putative binding sites has been exemplified by a crystal structure of a peptide packed in a parallel zipper arrangement.