Structure of Mycobacterium tuberculosis RuvA, a protein involved in recombination

The process of recombinational repair is crucial for maintaining genomic integrity and generating biological diversity. In association with RuvB and RuvC, RuvA plays a central role in processing and resolving Holliday junctions, which are a critical intermediate in homologous recombination. Here, the cloning, purification and structure determination of the RuvA protein from Mycobacterium tuberculosis (MtRuvA) are reported. Analysis of the structure and comparison with other known RuvA proteins reveal an octameric state with conserved subunit-subunit interaction surfaces, indicating the requirement of octamer formation for biological activity. A detailed analysis of plasticity in the RuvA molecules has led to insights into the invariant and variable regions, thus providing a framework for understanding regional flexibility in various aspects of RuvA function.

Tuning the Conductance of Dirac Fermions on the Surface of a Topological Insulator

We study the transport properties of the Dirac fermions with a Fermi velocity v(F) on the surface of a topological insulator across a ferromagnetic strip providing an exchange field J over a region of width d. We show that the conductance of such a junction, in the clean limit and at low temperature, changes from oscillatory to a monotonically decreasing function of d beyond a critical J. This leads to the possible realization of a magnetic switch using these junctions. We also study the conductance of these Dirac fermions across a potential barrier of width d and potential V-0 in the presence of such a ferromagnetic strip and show that beyond a critical J, the criteria of conductance maxima changes from chi = eV(0)d/(h) over barv(F) = n pi to chi = (n + 1/2)pi for integer n. We point out that these novel phenomena have no analogs in graphene and suggest experiments which can probe them.

Microstructural stability and creep in nanocrystals

Microstructural stability is an important consideration during high temperature deformation and processing of nanomaterials. We will address issues relating to triple junctions in limiting grain growth during creep as well as densification. Although early studies on deformation have considered diffusion creep as a possible rate controlling deformation mechanism in nanocrystals, a critical inspection of available data indicates that there is no strong evidence for conventional diffusion creep in such materials. The possibility of diffusion creep by rapid diffusion along triple junctions will be analyzed, and interface controlled diffusion creep will also be discussed critically. It is shown that the critical grain size for dislocation activity is similar to that for occurrence of conventional diffusion creep.

Atomic scale engineering of carbon nanotubes

Carbon nanotubes, seamless cylinders made from carbon atoms, have outstanding characteristics: inherent nano-size, record-high Young’s modulus, high thermal stability and chemical inertness. They also have extraordinary electronic properties: in addition to extremely high conductance, they can be both metals and semiconductors without any external doping, just due to minute changes in the arrangements of atoms. As traditional silicon-based devices are reaching the level of miniaturisation where leakage currents become a problem, these properties make nanotubes a promising material for applications in nanoelectronics. However, several obstacles must be overcome for the development of nanotube-based nanoelectronics. One of them is the ability to modify locally the electronic structure of carbon nanotubes and create reliable interconnects between nanotubes and metal contacts which likely can be used for integration of the nanotubes in macroscopic electronic devices. In this thesis, the possibility of using ion and electron irradiation as a tool to introduce defects in nanotubes in a controllable manner and to achieve these goals is explored. Defects are known to modify the electronic properties of carbon nanotubes. Some defects are always present in pristine nanotubes, and naturally are introduced during irradiation. Obviously, their density can be controlled by irradiation dose. Since different types of defects have very different effects on the conductivity, knowledge of their abundance as induced by ion irradiation is central for controlling the conductivity. In this thesis, the response of single walled carbon nanotubes to ion irradiation is studied. It is shown that, indeed, by energy selective irradiation the conductance can be controlled. Not only the conductivity, but the local electronic structure of single walled carbon nanotubes can be changed by the defects. The presented studies show a variety of changes in the electronic structures of semiconducting single walled nanotubes, varying from individual new states in the band gap to changes in the band gap width. The extensive simulation results for various types of defect make it possible to unequivocally identify defects in single walled carbon nanotubes by combining electronic structure calculations and scanning tunneling spectroscopy, offering a reference data for a wide scientific community of researchers studying nanotubes with surface probe microscopy methods. In electronics applications, carbon nanotubes have to be interconnected to the macroscopic world via metal contacts. Interactions between the nanotubes and metal particles are also essential for nanotube synthesis, as single walled nanotubes are always grown from metal catalyst particles. In this thesis, both growth and creation of nanotube-metal nanoparticle interconnects driven by electron irradiation is studied. Surface curvature and the size of metal nanoparticles is demonstrated to determine the local carbon solubility in these particles. As for nanotube-metal contacts, previous experiments have proved the possibility to create junctions between carbon nanotubes and metal nanoparticles under irradiation in a transmission electron microscope. In this thesis, the microscopic mechanism of junction formation is studied by atomistic simulations carried out at various levels of sophistication. It is shown that structural defects created by the electron beam and efficient reconstruction of the nanotube atomic network, inherently related to the nanometer size and quasi-one dimensional structure of nanotubes, are the driving force for junction formation. Thus, the results of this thesis not only address practical aspects of irradiation-mediated engineering of nanosystems, but also contribute to our understanding of the behaviour of point defects in low-dimensional nanoscale materials.

Low-temperature deformation behaviour of polycrystalline copper

Low-temperature plastic flow in copper was investigated by studying its tensile and creep deformation characteristics. The dependence of the flow stress on temperature and strain rate was used to evaluate the thermal activation energy while the activation area was derived from the change-in-stress creep experiments. A value of 0.6 eV was obtained for the total obstacle energy both in electrolytic and commerical copper. The activation areas in copper of three selected purities fell in the range 1200 to 100 b2. A forest intersection mechanism seems to control the temperature dependent part of the flow stress. The increase in the athermal component of the flow stress with impurity content in copper is attributed to a change in the dislocation density. The investigation also revealed that thermal activation of some attractive junctions also takes place during low-temperature creep. The model of attractive junction formation on a stress decrement during creep, yields a value of 45±10 ergs cm-2 for the stacking fault energy in copper.

Breakdown in p‐n junction diodes made on polycrystalline silicon of large grain size

This communication describes the voltage‐current characteristics in the breakdown region of p‐n junctions made on polycrystalline silicon of large grain size. The observed soft breakdown characteristics have been explained by taking into account the effect of curvature of the junction near the grain boundaries.

Magnetotransport of Dirac fermions on the surface of a topological insulator

We study the properties of Dirac fermions on the surface of a topological insulator in the presence of crossed electric and magnetic fields. We provide an exact solution to this problem and demonstrate that, in contrast to their counterparts in graphene, these Dirac fermions allow relative tuning of the orbital and Zeeman effects of an applied magnetic field by a crossed electric field along the surface. We also elaborate and extend our earlier results on normal-metal-magnetic film-normal metal (NMN) and normal-metal-barrier-magnetic film (NBM) junctions of topological insulators [S. Mondal, D. Sen, K. Sengupta, and R. Shankar, Phys. Rev. Lett. 104, 046403 (2010)]. For NMN junctions, we show that for Dirac fermions with Fermi velocity vF, the transport can be controlled using the exchange field J of a ferromagnetic film over a region of width d. The conductance of such a junction changes from oscillatory to a monotonically decreasing function of d beyond a critical J which leads to the possible realization of magnetic switches using these junctions. For NBM junctions with a potential barrier of width d and potential V-0, we find that beyond a critical J, the criteria of conductance maxima changes from chi=eV(0)d/h upsilon(F)=n pi to chi=(n+1/2)pi for integer n. Finally, we compute the subgap tunneling conductance of a normal-metal-magnetic film-superconductor junctions on the surface of a topological insulator and show that the position of the peaks of the zero-bias tunneling conductance can be tuned using the magnetization of the ferromagnetic film. We point out that these phenomena have no analogs in either conventional two-dimensional materials or Dirac electrons in graphene and suggest experiments to test our theory.

As-deposited near-single crystalline high Tc and Jc superconducting thin films by a pulsed lased deposition process

As-deposited high Tc superconducting Y1Ba2Cu3O7−x films with zero resistance temperatures of similar, equals89 K and critical current densities about 0.7×106 A/cm2 at 77 K have been reproducibly fabricated at a substrate holder temperature at 650°C, using pulsed laser deposition, without post-annealing. One key to these results is the injection of gaseous oxygen into laser produced plume just in front of the target. In this way, the correct amount of oxygen is incorporated into the as-grown film so that post-deposition treatment becomes unnecessary. Axial ion channeling in these as-deposit high Tc superconducting films on (100) SrTiO3 and X-ray photoelectron spectroscopy (XPS) on the film surfaces were performed. Angular yield profile near the film surface for Ba, and the surface peak intensity were measured using 3 MeV He ions. For channeling normal to the substrate a minimum yield of 7%, compared to similar, equals3% for single crystals, was obtained. The results of ion channeling and XPS studies indicate that the as-deposited films have good crystallinity as well as toichiometry to within similar, equals1 nm of the film surface. The in-situ growth of such high Tc and Jc films is an important step in the use of the laser deposition technique to fabricate multilayer structures and the surface perfection is of importance in tunneling devices such as Josephson junctions.

A TEM study on TiB2-20%MoSi2 composite: Microstructure development and densification mechanism

We report the results of transmission electron microscopy (TEM) study, carried out on a hot-pressed TiB2-20 wt.%MoSi2 composite. One of the important microstructural observations includes the detection of crystalline TiSi2 at triple grain junctions. The densification mechanism is discussed, based on experimental observations and thermodynamic analysis

Macroscopic model of city traffic using bond graph modelling

Modelling of city traffic involves capturing of all the dynamics that exist in real-time traffic. Probabilistic models and queuing theory have been used for mathematical representation of the traffic system. This paper proposes the concept of modelling the traffic system using bond graphs wherein traffic flow is based on energy conservation. The proposed modelling approach uses switched junctions to model complex traffic networks. This paper presents the modelling, simulation and experimental validation aspects.

Effect of wall thickness on the end corrections of the extended inlet and outlet of a double-tuned expansion chamber

Simple expansion chambers, the simplest of the muffler configurations, have very limited practical application due to the presence of periodic troughs in the transmission loss spectrum which drastically lower the overall transmission loss of the muffler. Tuned extended inlet and outlet can be designed to nullify three-fourths of these troughs, making use of the plane wave theory. These cancellations would not occur unless one altered the geometric lengths for the extended tube in order to incorporate the effect of evanescent higher-order modes (multidimensional effect) through end corrections or lumped inertance approximation at the area discontinuities or junctions. End corrections of the extended inlet and outlet have been studied by several researchers. However the effect of wall thickness of the inlet/outlet duct on end correction has not been studied explicitly. This has significant effect on the tuning of an extended inlet/outlet expansion chamber. It is investigated here experimentally as well as numerically (through use of 3-D FEM software) for stationary medium. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.

CA/TG sequence at the 5' end of oligo(A)-tracts strongly modulates DNA curvature

An analysis of the base pair doublet geometries in available crystal structures indicates that the often reported intrinsic curvature of DNA containing oligo-(d(A).d(T)) tracts may also depend on the nature of the flanking sequences. The presence of CA/TG doublet in particular at the 5' end of these tracts is expected to enhance their intrinsic bending property. To test this proposition, three oligonucleotides, d(GAAAAACCCCCC), d(CCCCCCAAAAAG), d(GAAAAATTTTTC), and their complementary sequences were synthesized to study the effect of various flanking sequences, at the 5' and 3' ends of the A-tracts, on the curvature of DNA in solution. An analysis of the polyacrylamide gel electrophoretic mobilities of these sequences under different conditions of salts and temperatures (below their melting points) clearly showed that the oligomer with CA/TG sequence in the center was always more retarded than the oligomer with AC/GT sequence, as well as the oligomer with AT/AT sequence. Hydroxyl radical probing of the sequences with AC/GT and CA/TG doublet junctions gives a similar cutting pattern in the A-tracts, which is quite different from that in the C-tracts, indicating that the oligo(A)-tracts have similar structures in the two oligomers. KMnO4 probing shows that the oligomer with a CA/TG doublet junction forms a kink that is responsible for its inherent curvature and unusual electrophoretic mobility. UV melting shows a reduced thermal stability of the duplex with CA/TG doublet junction, and circular dichroism (CD) studies indicate that a premelting transition occurs in the oligomer with CA/TG doublet step before global melting but not in the oligomer with AC/GT doublet step, which may correspond to thermally induced unbending of the oligomer. These observations indicate that the CA/TG doublet junction at the 5' end of the oligo(A)-tract has a crucial role in modulating the overall curvature in DNA.

Literature Review: Investigating Drug Transport at the Blood-Brain Barrier and the Effects of P-glycoprotein on the Brain Distribution of Drugs.

The blood-brain barrier (BBB) is a unique barrier that strictly regulates the entry of endogenous substrates and xenobiotics into the brain. This is due to its tight junctions and the array of transporters and metabolic enzymes that are expressed. The determination of brain concentrations in vivo is difficult, laborious and expensive which means that there is interest in developing predictive tools of brain distribution. Predicting brain concentrations is important even in early drug development to ensure efficacy of central nervous system (CNS) targeted drugs and safety of non-CNS drugs. The literature review covers the most common current in vitro, in vivo and in silico methods of studying transport into the brain, concentrating on transporter effects. The consequences of efflux mediated by p-glycoprotein, the most widely characterized transporter expressed at the BBB, is also discussed. The aim of the experimental study was to build a pharmacokinetic (PK) model to describe p-glycoprotein substrate drug concentrations in the brain using commonly measured in vivo parameters of brain distribution. The possibility of replacing in vivo parameter values with their in vitro counterparts was also studied. All data for the study was taken from the literature. A simple 2-compartment PK model was built using the Stella™ software. Brain concentrations of morphine, loperamide and quinidine were simulated and compared with published studies. Correlation of in vitro measured efflux ratio (ER) from different studies was evaluated in addition to studying correlation between in vitro and in vivo measured ER. A Stella™ model was also constructed to simulate an in vitro transcellular monolayer experiment, to study the sensitivity of measured ER to changes in passive permeability and Michaelis-Menten kinetic parameter values. Interspecies differences in rats and mice were investigated with regards to brain permeability and drug binding in brain tissue. Although the PK brain model was able to capture the concentration-time profiles for all 3 compounds in both brain and plasma and performed fairly well for morphine, for quinidine it underestimated and for loperamide it overestimated brain concentrations. Because the ratio of concentrations in brain and blood is dependent on the ER, it is suggested that the variable values cited for this parameter and its inaccuracy could be one explanation for the failure of predictions. Validation of the model with more compounds is needed to draw further conclusions. In vitro ER showed variable correlation between studies, indicating variability due to experimental factors such as test concentration, but overall differences were small. Good correlation between in vitro and in vivo ER at low concentrations supports the possibility of using of in vitro ER in the PK model. The in vitro simulation illustrated that in the simulation setting, efflux is significant only with low passive permeability, which highlights the fact that the cell model used to measure ER must have low enough paracellular permeability to correctly mimic the in vivo situation.

CA\TG Sequence at the 5'end of Oligo(A)-tracts Strongly Modulates DNA Curvature

An analysis of the base pair doublet geometries in available crystal structures indicates that the often reported intrinsic curvature of DNA containing oligo-(d(A).d(T)) tracts may also depend on the nature of the flanking sequences. The presence of CA/TG doublet in particular at the 5' end of these tracts is expected to enhance their intrinsic bending property. To test this proposition, three oligonucleotides, d(GAAAAACCCCCC), d(CCCCCCAAAAAG), d(GAAAAATTTTTC), and their complementary sequences were synthesized to study the effect of various flanking sequences, at the 5' and 3' ends of the A-tracts, on the curvature of DNA in solution. An analysis of the polyacrylamide gel electrophoretic mobilities of these sequences under different conditions of salts and temperatures (below their melting points) clearly showed that the oligomer with CA/TG sequence in the center was always more retarded than the oligomer with AC/GT sequence, as well as the oligomer with AT/AT sequence. Hydroxyl radical probing of the sequences with AC/GT and CA/TG doublet junctions gives a similar cutting pattern in the A-tracts, which is quite different from that in the C-tracts, indicating that the oligo(A)-tracts have similar structures in the two oligomers. KMnO4 probing shows that the oligomer with a CA/TG doublet junction forms a kink that is responsible for its inherent curvature and unusual electrophoretic mobility. UV melting shows a reduced thermal stability of the duplex with CA/TG doublet junction, and circular dichroism (CD) studies indicate that a premelting transition occurs in the oligomer with CA/TG doublet step before global melting but not in the oligomer with AC/GT doublet step, which may correspond to thermally induced unbending of the oligomer. These observations indicate that the CA/TG doublet junction at the 5' end of the oligo(A)-tract has a crucial role in modulating the overall curvature in DNA.

Efficiency of nonhomologous DNA end joining varies among somatic tissues, despite similarity in mechanism

Failure to repair DNA double-strand breaks (DSBs) can lead to cell death or cancer. Although nonhomologous end joining (NHEJ) has been studied extensively in mammals, little is known about it in primary tissues. Using oligomeric DNA mimicking endogenous DSBs, NHEJ in cell-free extracts of rat tissues were studied. Results show that efficiency of NHEJ is highest in lungs compared to other somatic tissues. DSBs with compatible and blunt ends joined without modifications, while noncompatible ends joined with minimal alterations in lungs and testes. Thymus exhibited elevated joining, followed by brain and spleen, which could be correlated with NHEJ gene expression. However, NHEJ efficiency was poor in terminally differentiated organs like heart, kidney and liver. Strikingly, NHEJ junctions from these tissues also showed extensive deletions and insertions. Hence, for the first time, we show that despite mode of joining being generally comparable, efficiency of NHEJ varies among primary tissues of mammals.