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Understanding enhanced mechanical stability of DNA in the presence of intercalated anticancer drug: Implications for DNA associated processes
No full textMost of the anticancer drugs bind to double-stranded DNA (dsDNA) by intercalative-binding mode. Although experimental studies have become available recently, a molecular-level understanding of the interactions between the drug and dsDNA that lead to the stability of the intercalated drug is lacking. Of particular interest are the modifications of the mechanical properties of dsDNA observed in experiments. The latter could affect many biological functions, such as DNA transcription and replication. Here, we probe, via all-atom molecular dynamics (MD) simulations, the change in the mechanical properties of intercalated drug-DNA complexes for two intercalators, daunomycin and ethidium. We find that, upon drug intercalation, the stretch modulus of DNA increases significantly, whereas its persistence length and bending modulus decrease. Steered MD simulations reveal that it requires higher forces to stretch the intercalated dsDNA complexes than the normal dsDNA. Adopting various pulling protocols to study force-induced DNA melting, we find that the dissociation of dsDNA becomes difficult in the presence of intercalators. The results obtained here provide a plausible mechanism of function of the anticancer drugs, i.e., via altering the mechanical properties of DNA. We also discuss long-time consequences of using these drugs, which require further in vivo investigations
characterization of symmetric points in l(p)(n)-spaces
No full textWe characterize the left-symmetric points as well as the right-symmetric points in the sense of Birkhoff-James orthogonality, of the Banach spaces ln p (1 = p=8). As an application of our study, we produce an elementary proof of the well-known result: T is an isometry on ln p (p = 1, 2,8) if and only if T is a signed permutation. This illustrates the pivotal role played by the set of left-symmetric points in determining the isometry group of a given Banach space
Destabilization of Insulin Hexamer in Water-Ethanol Binary Mixture
No full textWe report combined experimental and simulation studies which reveal that the structural integrity of insulin hexamer, the storehouse of the important hormone in our body, is compromised by the interactions with ethanol. X-ray crystal structures suggest that ethanol replaces water molecules inside the insulin hexamer cavity. At the maximum physiologically tolerable concentration of ethanol (similar to 0.6% v/v), molecular dynamics simulations show that ethanol molecules get exchanged between the bulk and the cavity with a free energy cost of similar to 5 kcal mol(-1). However, biological time scales are orders of magnitude longer than that achievable by molecular dynamics simulations. Hence, to accelerate the process we investigate insulin hexamer in similar to 30% v/v ethanol concentration. We find that the entrance and exit of ethanol from the hexamer cavity lead to the modification of atomic contacts in the protein. This causes large-scale fluctuations that force the protein out of its native state free energy minimum. Structural perturbations are also observed at lower ethanol concentration. The computational findings are consistent with dynamic light scattering experiments that suggest an abrupt reduction in the population of insulin hexamers at a critical ethanol concentration. The structural changes triggered by interaction of ethanol with the insulin hexamer are likely to represent a general dynamic event of amphiphilic cosolvent induced changes in macromolecular assemblies with the consequent effects on cellular homeostasis
A review on the conservation genetic studies of Indian amphibians and their implications on developing strategies for conservation(dagger)
No full textAmphibians show a very high level of diversity and endemism and are facing global declines from the past few decades. Studies have shown that the molecular tools can be helpful in their conservation efforts. In India, more than 80% of amphibians are endemic and most show a narrow range of distribution. Most of the Indian amphibians lack information on their genetic diversity. In this study, we review the overall trend on amphibian studies in India with the specific focus on conservation genetics. Overall, of the 173 studies, only 14 dealt with the conservation of amphibians through genetic tools and five studies estimated the genetic diversity or gene structure. Here, we discuss the gaps and provide future directions on how genetic studies can be helpful in Indian amphibian conservation
Stiffness based technique to probe cyclic damage accumulation in micro-structurally graded bond coats viamicro-beam bending tests
No full textThis paper highlights a novel technique to delineate the fatigue response of different regions within thin microstructurally graded platinum nickel aluminide bond coats. Notched clamped beam structures fabricated from distinct microstructural zones of these coatings are subjected to programmed cyclic bending using the nano-indentation system. A methodical approach is established herein to quantify the cyclic damage preceding crack pop-in by using the cyclic stiffness of the beam as an indicator to mark failure. Preliminary results from these tests show that there is a characteristic change in the stiffness of the beam before a crack pop-in event occurs and different regions within the coating show different stiffening characteristics. Factors affecting the measured stiffness such as offsets in the loading position and blunting of the notch tip have been estimated using the finite element method. A graded flow stress model has been proposed and implemented in FEM to quantify the local flow stress changes accompanying the measured rise in stiffness. Electron transparent foils lifted off from the notched region of the beam post-testing suggests that the cyclic stiffening of the beams occurs due to dislocation hardening in the plastically deformed region close to the notch tip. Toughening mechanisms active in the crack wake have thus been investigated and correlated to the measured cyclic stiffness
Effect of nanofiller on fibre laser drilling quality of carbon fibre reinforced polymer composite laminates
No full textLaser machining of carbon fibre reinforced polymer composites is a challenging task due to a significant difference between physical and thermal properties of the constituent materials, i.e. polymer matrix and carbon fibres. This results in extended heat-affected zone (HAZ), taper kerf and poor surface finishing. This paper focuses on an investigation, attempting to minimise the divergence in the decomposition temperature of carbon fibres and epoxy resin by adding multi-walled carbon nanotubes in polymer matrix as a secondary reinforcement. High thermal conductivity of multi-walled carbon nanotubes increases the thermal diffusivity of polymer matrix, which in turn reduces the matrix recession. In addition, laser power and scan speed was also considered as an input parameter and their influence on output responses such as HAZ, taper angle and surface roughness has been studied. To analyse the effect of multi-walled carbon nanotubes on the resultant thermal damage, an innovative technique, i.e. scanning acoustic microscopy was used. This technique provides a ply-by-ply damage analysis. C-scans of the top and bottom surface of the machined holes in the composite were also carried out. Further, micrographs of the holes were taken to analyse the quality of the holes using field-emission scanning electron microscope. The obtained results indicated that HAZ, taper angle and surface roughness of holes decreased by similar to 30%, similar to 47% and similar to 43%, respectively, with 1.5 wt% multi-walled carbon nanotubes doped carbon fibre reinforced polymer laminates, when compared with the results obtained from experiments with neat carbon fibre reinforced polymer composite laminates
Vibration analysis of magneto-flexo-electrically actuated porous rotary nanobeams considering thermal effects via nonlocal strain gradient elasticity theory
No full textIn this article the frequency response of magneto-flexo-electric rotary porous (MFERP) nanobeams subjected to thermal loads has been investigated through nonlocal strain gradient elasticity theory. A quasi-3D beam model beam theory is used for the expositions of the displacement components. With the aid of Hamilton's principle, the governing equations of MFERP nanobeams are obtained. Further, administrating an analytical solution the frequency problem of MFERP nanobeams are solved. In addition the numerical examples are also provided to evaluate the effect of nonlocal strain gradient parameter, hygro thermo environment, flexoelectric effect, in-plane magnet field, volume fraction of porosity and angular velocity on the dimensionless eigen frequency
A finite element-based assessment of free vibration behaviour of circular and annular magneto-electro-elastic plates using higher order shear deformation theory
No full textIn this article, the free vibration behaviour of circular and annular magneto-electro-elastic plates has been investigated under the framework of higher order shear deformation theory. The three-dimensional finite element formulation has been derived with the aid of Hamilton's principle by taking into account the coupling between elastic, electric and magnetic properties. The equations of motion are solved using condensation technique. Furthermore, the credibility of proposed finite element formulation has been validated using COMSOL software and also by comparing the results with previously published articles. Special attention has also been paid to assess the influence of parameters such as coupling effect, stacking sequences and inner-to-outer diameter ratio. The numerical results reveal that the coupled natural frequencies of the annular magneto-electro-elastic plates vary significantly with the circular hole dimensions incorporated. The circular and annular plates are considered as one of the prominent structural components in various engineering and industrial application. Therefore, the proposed finite element formulation and the results presented in this article can serve as benchmark solutions for the design and analysis of smart sensors and actuators
On Differential Torsion Theories and Rings with Several Objects
No full textLet R be a small preadditive category, viewed as a ``ring with several objects.'' A right R-module is an additive functor from R-op to the category Ab of abelian groups. We show that every hereditary torsion theory on the category (R-op, Ab) of right R-modules must be dioerential
Local projection stabilization with discontinuous Galerkin method in time applied to convection dominated problems in time-dependent domains
No full textThis paper presents the numerical analysis of a stabilized finite element scheme with discontinuous Galerkin (dG) discretization in time for the solution of a transient convection-diffusion-reaction equation in time-dependent domains. In particular, the local projection stabilization and the higher order dG time stepping scheme are used for convection dominated problems. Further, an arbitrary Lagrangian-Eulerian formulation is used to handle the time-dependent domain. The stability and error estimates are given for the proposed numerical scheme. The validation of the proposed local projection stabilization scheme with higher order dG time discretization is demonstrated with appropriate numerical examples