The design and synthesis of redox core-alpha amino acid composites based on thiol-disulfide exchange mechanism and a comparative study of their zinc abstraction potential from [CCXX] boxes in proteins

The design and synthesis of agents that can abstract zinc from their [CCXX] (C=cysteine; X=cysteine/histidine) boxes by thioldisulfide exchange-having as control, the redox parities of the core sulfur ligands of the reagent and the enzyme, has been illustrated, and their efficiency demonstrated by monitoring the inhibition of the transcription of calf thymus DNA by E. coli RNA polymerase, which harbors two zinc atoms in their [CCXX] boxes of which one is exchangeable. Maximum inhibition possible with removal of the exchangeable zinc was seen with redox-sulfanilamide-glutamate composite. In sharp contrast, normal chelating agents (EDTA, phenanthroline) even in a thousand fold excess showed only marginal inhibition, thus supporting an exchange mechanism for the metal removal. (C) 2002 Elsevier Science Ltd. All rights reserved.

Mutagenicity associated with O6-methylguanine-DNA damage and mechanism of nucleotide flipping by AGT during repair

Methylated guanine damage at O6 position (i.e. O6MG) is dangerous due to its mutagenic and carcinogenic character that often gives rise to G:C-A:T mutation. However, the reason for this mutagenicity is not known precisely and has been a matter of controversy. Further, although it is known that O6-alkylguanine-DNA alkyltransferase (AGT) repairs O6MG paired with cytosine in DNA, the complete mechanism of target recognition and repair is not known completely. All these aspects of DNA damage and repair have been addressed here by employing high level density functional theory in gas phase and aqueous medium. It is found that the actual cause of O6MG mediated mutation may arise due to the fact that DNA polymerases incorporate thymine opposite to O6MG, misreading the resulting O6MG:T complex as an A:T base pair due to their analogous binding energies and structural alignments. It is further revealed that AGT mediated nucleotide flipping occurs in two successive steps. The intercalation of the finger residue Arg 128 into the DNA double helix and its interaction with the O6MG: C base pair followed by rotation of the O6MG nucleotide are found to be crucial for the damage recognition and nucleotide flipping.

MFIS and MFS structures using SrBi2Ta2O9 thin films for the FRAM applications

Recently there is an increasing demand and extensive research on high density memories, in particular to the ferroelectric random access memory composed of 1T/1C (1 transistor/1 capacitor) or 2T/2C. FRAM's exhibit fast random acess in read/write mode, non - volatility and low power for good performance. An integration of the ferroelectric on Si is the key importance and in this regard, there had been various models proposed like MFS, MFIS, MFMIS structure etc., Choosing the proper insulator is very essential for the better performance of the device and to exhibit excellent electrical characteristics. ZrTiO4 is a potential candidate because of its excellent thermal stability and lattice match on the Si substrate. SrBi2Ta2O9 and ZrTiO4 thin films were prepared on p - type Si substrate by pulsed excimer laser ablation technique. Optimization of both ZT and SBT thin films in MFS and MFIS structure had been done based on the annealing, oxygen partial pressures and substrate temperatures to have proper texture of the thin films. The dc leakage current, P - E hysteresis, capacitance - voltage and conductance - voltage measurement were carried out. The effect of the frequency dependence on MFIS structure was observed in the C – V curve. It displays a transition of C - V curve from high frequency to low frequency curve on subjection to varied frequencies. Density of interface states has been calculated using Terman and high - low frequency C - V curve. The effect of memory window in the C - V hysteresis were analysed in terms of film thickness and annealing temperatures. DC conduction mechanism were analysed in terms of poole - frenkel, Schottky and space charge limited conduction separately on MFS, MIS structure.

MFIS and MFS structures using SrBi2Ta2O9 thin films for the FRAM applications

Recently there is an increasing demand and extensive research on high density memories, in particular to the ferroelectric random access memory composed of 1T/1C (1 transistor/1 capacitor) or 2T/2C. FRAM's exhibit fast random acess in read/write mode, non - volatility and low power for good performance. An integration of the ferroelectric on Si is the key importance and in this regard, there had been various models proposed like MFS, MFIS, MFMIS structure etc., Choosing the proper insulator is very essential for the better performance of the device and to exhibit excellent electrical characteristics. ZrTiO4 is a potential candidate because of its excellent thermal stability and lattice match on the Si substrate. SrBi2Ta2O9 and ZrTiO4 thin films were prepared on p - type Si substrate by pulsed excimer laser ablation technique. Optimization of both ZT and SBT thin films in MFS and MFIS structure had been done based on the annealing, oxygen partial pressures and substrate temperatures to have proper texture of the thin films. The dc leakage current, P - E hysteresis, capacitance - voltage and conductance - voltage measurement were carried out. The effect of the frequency dependence on MFIS structure was observed in the C – V curve. It displays a transition of C - V curve from high frequency to low frequency curve on subjection to varied frequencies. Density of interface states has been calculated using Terman and high - low frequency C - V curve. The effect of memory window in the C - V hysteresis were analysed in terms of film thickness and annealing temperatures. DC conduction mechanism were analysed in terms of poole - frenkel, Schottky and space charge limited conduction separately on MFS, MIS structure.

Molecular insights into the mechanism of phenotypic tolerance to rifampicin conferred on mycobacterial RNA polymerase by MsRbpA

The protein MsRbpA from Mycobacterium smegmatis rescues RNA polymerase (RNAP) from the inhibitory effect of rifampicin (Rif). We have reported previously that MsRbpA interacts with the beta-subunit of RNAP and that the effect of MsRbpA on Rif-resistant (Rif(R)) RNAP is minimal. Here we attempted to gain molecular insights into the mechanism of action of this protein with respect to its role in rescuing RNAP from Rif-mediated transcription inhibition. Our experimental approach comprised multiple-round transcription assays, fluorescence spectroscopy, MS and surface plasmon resonance in order to meet the above objective. Based on our molecular studies we propose here that Rif is released from its binding site in the RNAP-Rif complex in the presence of MsRbpA. Biophysical studies reveal that the location of MsRbpA on RNAP is at the junction of the beta- and beta'-subunits, close to the Rif-binding site and the (i + 1) site on RNAP.

A Flexure-based Deployable Stereo Vision Mechanism and Temperature and Force Sensors for Laparoscopic Tools

This paper presents concepts, designs, and working prototypes of enhanced laparoscopic surgical tools. The enhancements are in equipping the tool with force and temperature sensing as well as image acquisition for stereo vision. Just as the pupils of our eyes are adequately spaced out and the distance between them is adjustable, two minute cameras mounted on a mechanism in our design can be moved closer or farther apart inside the inflated abdomen during the surgery. The cameras are fitted to a deployable mechanism consisting of flexural joints so that they can be inserted through a small incision and then deployed and moved as needed.A temperature sensor and a force sensor are mounted on either of the gripping faces of the surgical grasping tool to measure the temperature and gripping force, which need to be controlled for safe laparoscopic surgery. The sensors are small enough and hence they do not cause interference during surgery and insertion.Prototyping and working of the enhanced laparoscopic tool are presented with details

An Improved Compact Compliant Mechanism for an External Pipe-Crawler

An external pipe-crawling device presented in this paper aids the inspection of pipes in hazardous environments and areas inaccessible to humans. The principal component of our design, which uses inchworm type motion, is a compliant ring mechanism actuated using shape memory alloy (SMA) wire. It was fabricated and tested and was reported in our earlier work. But this device had a drawback of low crawling speed (about 1 mm/min) owing to the delay in heating and cooling of the SMA strips in the linear actuation. Additionally, that design also had the difficulties of mounting on pipes with closed ends, large radial span, and the need for housing for electrical insulation and guiding of the SMA wire. In this paper we present a compact design that overcomes the difficulties of the earlier design. In particular, we present a compact compliant mechanism with two halves so as to enable mounting and un-mounting on any closed or open pipe. Another feature is the presence of insulation and guiding of the SMA wire without housing. This design results in a reduction of the radial span of the ring from 22 mm to 12 mm, and the stiffness of the mechanism and the SMA wire are matched. An SMA helical spring is to used in the place of an SMA strip to increase the crawling speed of the device. A microcontroller-based circuitry is also fitted to cyclically.activate the SMA wires and springs.

A Compliant Mechanism Kit with Flexible Beams and Connectors

We present the concept, prototypes, and an optimal design method for a compliant mechanism kit as a parallel to the kits available for rigid-body mechanisms. The kit consists of flexible beams and connectors that can be easily hand-assembled using snap fits. It enables users, using their creativity and mechanics intuition, to quickly realize a compliant mechanism. The mechanisms assembled in this manner accurately capture the essential behavior of the topology, shape, size and material aspects and thereby can lead the way for a real compliant mechanism for practical use. Also described in this paper are the design of the connector to which flexible beams can be added in eight different directions; and prototyping of the spring steel connectors as well as beams using wire-cut electro discharge machining. It is noted in this paper that the concept of the kit also resolves a discrepancy in the finite element (FE) modeling of beam-based compliant mechanisms. The discrepancy arises when two or more beams are joining at one point and thus leading to increased stiffness. After resolving this discrepancy, this work extends the topology optimization to automatically generate designs that can be assembled with the kit. Thus, the kit and the accompanying analysis and optimal synthesis procedures comprise a self-contained educational as well as a research and pragmatic toolset for compliant mechanisms. The paper also illustrates how human creativity finds new ways of using the kit beyond the original intended use and how it is useful even for a novice to design compliant mechanisms.

Encapsulation of cobalt phthalocyanine in zeolite-Y: Evidence for nonplanar geometry

Cobalt (11) phthalocyanine (CoPc) molecules have been encapsulated within the supercage of zeolite-Y. The square-planar complex, being larger than the almost spherical cage, is forced to adopt a distorted geometry on encapsulation. A comparative spectroscopic and magnetic investigation of CoPc encapsulated in zeolite-Y and in the unencapsulated state is reported. These results supported by molecular modeling have been used to understand the nature and extent of the loss of planarity of CoPc on encapsulation. The encapsulated molecule is shown to be the trans-diprotonated species in which the center of inversion is lost due to distortions required to accommodate the square complex within the zeolite. Encapsulation also leads to an enhancement of the magnetic moment of the CoPc. This is shown to be a consequence of the nonplanar geometry of the encapsulated molecule resulting in an excited high-spin state being thermally accessible.

Multi-Armed Bandit Mechanisms for Multi-Slot Sponsored Searth Auctions

In pay-per click sponsored search auctions which are currently extensively used by search engines, the auction for a keyword involves a certain number of advertisers (say k) competing for available slots (say m) to display their ads. This auction is typically conducted for a number of rounds (say T). There are click probabilities mu_ij associated with agent-slot pairs. The search engine's goal is to maximize social welfare, for example, the sum of values of the advertisers. The search engine does not know the true value of an advertiser for a click to her ad and also does not know the click probabilities mu_ij s. A key problem for the search engine therefore is to learn these during the T rounds of the auction and also to ensure that the auction mechanism is truthful. Mechanisms for addressing such learning and incentives issues have recently been introduced and would be referred to as multi-armed-bandit (MAB) mechanisms. When m = 1,characterizations for truthful MAB mechanisms are available in the literature and it has been shown that the regret for such mechanisms will be O(T^{2/3}). In this paper, we seek to derive a characterization in the realistic but nontrivial general case when m > 1 and obtain several interesting results.

Non-Gaussianity and direction-dependent systematics in HST Key Project data

Two new statistics, namely Delta(chi 2) and Delta(chi), based on the extreme value theory, were derived by Gupta et al. We use these statistics to study the direction dependence in the HST Key Project data, which provides one of the most precise measurements of the Hubble constant. We also study the non-Gaussianity in this data set using these statistics. Our results for Delta(chi 2) show that the significance of direction-dependent systematics is restricted to well below the 1 sigma confidence limit; however, the presence of non-Gaussian features is subtle. On the other hand, the Delta(chi). statistic, which is more sensitive to direction dependence, shows direction dependence systematics to be at a slightly higher confidence level, and the presence of non-Gaussian features at a level similar to the Delta(chi 2) statistic.

The biological and structural characterization of Mycobacterium tuberculosis UvrA provides novel insights into its mechanism of action

Mycobacterium tuberculosis is an extremely well adapted intracellular human pathogen that is exposed to multiple DNA damaging chemical assaults originating from the host defence mechanisms. As a consequence, this bacterium is thought to possess highly efficient DNA repair machineries, the nucleotide excision repair (NER) system amongst these. Although NER is of central importance to DNA repair in M. tuberculosis, our understanding of the processes in this species is limited. The conserved UvrABC endonuclease represents the multi-enzymatic core in bacterial NER, where the UvrA ATPase provides the DNA lesion-sensing function. The herein reported genetic analysis demonstrates that M. tuberculosis UvrA is important for the repair of nitrosative and oxidative DNA damage. Moreover, our biochemical and structural characterization of recombinant M. tuberculosis UvrA contributes new insights into its mechanism of action. In particular, the structural investigation reveals an unprecedented conformation of the UvrB-binding domain that we propose to be of functional relevance. Taken together, our data suggest UvrA as a potential target for the development of novel anti-tubercular agents and provide a biochemical framework for the identification of small-molecule inhibitors interfering with the NER activity in M. tuberculosis.