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.

Self-organization of multiple components in a steroidal hydrogel matrix: design, construction and studies on novel tunable luminescent gels and xerogels

The present work combines two rapidly growing research areas-functional supramolecular gels and lanthanide based hybrid materials. Facile hydrogel formation from several lanthanide(III) cholates has been demonstrated. The morphological and mechanical properties of these cholate gels were investigated by TEM and rheology. The hydrogel matrix was subsequently utilized for the sensitization of Tb(III) by doping a non-coordinating chromophore, 2,3-dihydroxynaphthalene (DHN), at micromolar concentrations. In the mixed gels of Tb(III)-Eu(III), an energy transfer pathway was found to operate from Tb(III) to Eu(III) and by utilizing this energy transfer, tunable multiple-color luminescent hydrogels were obtained. The emissive properties of the hydrogels were also retained in the xerogels and their suspensions in n-hexane were used for making luminescent coating on glass surface.

Novel Algorithm for estimation of Swell Pressure of Fine Grained Soils Based on Diffuse Double Layer (DDL) Theory

Use of engineered landfills for the disposal of industrial wastes is currently a common practice. Bentonite is attracting a greater attention not only as capping and lining materials in landfills but also as buffer and backfill materials for repositories of high-level nuclear waste around the world. In the design of buffer and backfill materials, it is important to know the swelling pressures of compacted bentonite with different electrolyte solutions. The theoretical studies on swell pressure behaviour are all based on Diffuse Double Layer (DDL) theory. To establish a relation between the swell pressure and void ratio of the soil, it is necessary to calculate the mid-plane potential in the diffuse part of the interacting ionic double layers. The difficulty in these calculations is the elliptic integral involved in the relation between half space distance and mid plane potential. Several investigators circumvented this problem using indirect methods or by using cumbersome numerical techniques. In this work, a novel approach is proposed for theoretical estimations of swell pressures of fine-grained soil from the DDL theory. The proposed approach circumvents the complex computations in establishing the relationship between mid-plane potential and diffused plates’ distances in other words, between swell pressure and void ratio.

On a Novel Geometric Representation of Rotation

This paper presents a novel method of representing rotation and its application to representing the ranges of motion of coupled joints in the human body, using planar maps. The present work focuses on the viability of this representation for situations that relied on maps on a unit sphere. Maps on a unit sphere have been used in diverse applications such as Gauss map, visibility maps, axis-angle and Euler-angle representations of rotation etc. Computations on a spherical surface are difficult and computationally expensive; all the above applications suffer from problems associated with singularities at the poles. There are methods to represent the ranges of motion of such joints using two-dimensional spherical polygons. The present work proposes to use multiple planar domain “cube” instead of a single spherical domain, to achieve the above objective. The parameterization on the planar domains is easy to obtain and convert to spherical coordinates. Further, there is no localized and extreme distortion of the parameter space and it gives robustness to the computations. The representation has been compared with the spherical representation in terms of computational ease and issues related to singularities. Methods have been proposed to represent joint range of motion and coupled degrees of freedom for various joints in digital human models (such as shoulder, wrist and fingers). A novel method has been proposed to represent twist in addition to the existing swing-swivel representation.

Synthesis and Antileukemic Activity of Novel 4-(3-(Piperidin-4-yl) Propyl)Piperidine Derivatives

To explore the anticancer effect associated with the piperidine framework, several (substituted phenyl) {4-[3-(piperidin-4-yl)propyl]piperidin-1-yl} methanone derivatives 3(a-i) were synthesized. Variation in the functional group at N-terminal of the piperidine led to a set of compounds bearing amide moiety. Their chemical structures were confirmed by (1)H NMR, IR and mass spectra analysis. Among these, compounds 3a, 3d and 3e were endowed with antiproliferative activity. The most active compound among this series was 3a with nitro and fluoro substitution on the phenyl ring of aryl carboxamide moiety, which inhibited the growth of human leukemia cells (K562 and Reh) at low concentration. Comparison with other derivative (3h) results shown by LDH assay, cell cycle analysis and DNA fragmentation suggested that 3a is more potent to induce apoptosis.

Analysis of a Novel MOEM Race Track Resontor based Vibration Sensor

In this paper we analyze a novel Micro Opto Electro Mechanical Systems (MOEMS) race track resonator based vibration sensor. In this vibration sensor the straight portion of a race track resonator is located at the foot of the cantilever beam with proof mass. As the beam deflects due to vibration, stress induced refractive change in the waveguide located over the beam lead to the wavelength shift providing the measure of vibration. A wavelength shift of 3.19 pm/g in the range of 280 g for a cantilever beam of 1750μm×450m×20μmhas been obtained. The maximum acceleration (breakdown) for these dimensions is 2900g when a safety factor of 2 is taken into account. Since the wavelength of operation is around 1.55μm hybrid integration of source and detector is possible on the same substrate. Also it is less amenable to noise as wavelength shift provides the sensor signal. This type of sensors can be used for aerospace application and other harsh environments with suitable design.

Continous Time Sigma-Delta Modulator Employing a Novel Comparator Architecture

A novel comparator architecture is proposed for speed operation in low voltage environment. Performance comparison with a conventional regenerative comparator shows a speed-up of 41%. The proposed comparator is embedded in a continuous time sigma-delta ADC so as to reduce the quantizer delay and hence minimizes the excess loop delay problem. A performance enhancement of 1dB in the dynamic range of the ADC is achieved with this new comparator. We have implemented this ADC in a standard single-poly 8-Metal 0.13 mum UMC process. The entire system operates at 1.2 V supply providing a dynamic range of 32 dB consuming 720 muW of power and occupies an area of 0.1 mm2.