Ligand-modulated Parallel Mechanical Unfolding Pathways of Maltose-binding Proteins

Protein folding and unfolding are complex phenomena, and it is accepted that multidomain proteins generally follow multiple pathways. Maltose-binding protein (MBP) is a large (a two-domain, 370-amino acid residue) bacterial periplasmic protein involved in maltose uptake. Despite the large size, it has been shown to exhibit an apparent two-state equilibrium unfolding in bulk experiments. Single-molecule studies can uncover rare events that are masked by averaging in bulk studies. Here, we use single-molecule force spectroscopy to study the mechanical unfolding pathways of MBP and its precursor protein (preMBP) in the presence and absence of ligands. Our results show that MBP exhibits kinetic partitioning on mechanical stretching and unfolds via two parallel pathways: one of them involves a mechanically stable intermediate (path I) whereas the other is devoid of it (path II). The apoMBP unfolds via path I in 62% of the mechanical unfolding events, and the remaining 38% follow path II. In the case of maltose-bound MBP, the protein unfolds via the intermediate in 79% of the cases, the remaining 21% via path II. Similarly, on binding to maltotriose, a ligand whose binding strength with the polyprotein is similar to that of maltose, the occurrence of the intermediate is comparable (82% via path I) with that of maltose. The precursor protein preMBP also shows a similar behavior upon mechanical unfolding. The percentages of molecules unfolding via path I are 53% in the apo form and 68% and 72% upon binding to maltose and maltotriose, respectively, for preMBP. These observations demonstrate that ligand binding can modulate the mechanical unfolding pathways of proteins by a kinetic partitioning mechanism. This could be a general mechanism in the unfolding of other large two-domain ligand-binding proteins of the bacterial periplasmic space.

Wave dispersion in a cellular composite with modulated microstructure

In this paper we report a modeling technique and analysis of wave dispersion in a cellular composite laminate with spatially modulated microstructure, which can be modeled by parameterization and homogenization in an appropriate length scale. Higher order beam theory is applied and the system of wave equations are derived. Homogenization of these equations are carried out in the scale of wavelength and frequency of the individual wave modes. Smaller scale scattering below the order of cell size are filtered out in the present approach. The longitudinal dispersion relations for different values of a modulation parameter are analyzed which indicates the existence of stop and pass band patterns. Dispersion relations for flexural-shear case are also analyzed which indicates a tendency toward forming the stop and pass bands for increasing values of a shear stiffness modulation parameter. The effect the phase angle (θ) of the incident wave indicates the existence more number of alternative stop bands and pass bands for θ = 45°.

Novel Switching Sequences for a Space-Vector-Modulated Three-Level Inverter

A three-level inverter produces six active vectors, each of normalized magnitudes 1, 0.866, and 0.5, besides a zero vector. The vectors of relative length 0.5 are termed pivot vectors.The three nearest voltage vectors are usually used to synthesize the reference vector. In most continuous pulsewidth-modulation(PWM) schemes, the switching sequence begins from a pivot vector and ends with the same pivot vector. Thus, the pivot vector is applied twice in a subcycle or half-carrier cycle. This paper proposes and investigates alternative switching sequences, which use the pivot vector only once but employ one of the other two vectors twice within the subcycle. The total harmonic distortion(THD) in the fundamental line current pertaining to these novel sequences is studied theoretically as well as experimentally over the whole range of modulation. Compared with centered space vector PWM, two of the proposed sequences lead to reduced THD at high modulation indices at a given average switching frequency.

Measurement of Electron Spin Lifetime and Optical Orientation Efficiency in Germanium Using Electrical Detection of Radio Frequency Modulated Spin Polarization

We propose and demonstrate a technique for electrical detection of polarized spins in semiconductors in zero applied magnetic fields. Spin polarization is generated by optical injection using circularly polarized light which is modulated rapidly using an electro-optic cell. The modulated spin polarization generates a weak time-varying magnetic field which is detected by a sensitive radio-frequency coil. Using a calibrated pickup coil and amplification electronics, clear signals were obtained for bulk GaAs and Ge samples from which an optical spin orientation efficiency of 4.8% could be determined for Ge at 1342 nm excitation wavelength. In the presence of a small external magnetic field, the signal decayed according to the Hanle effect, from which a spin lifetime of 4.6 +/- 1.0 ns for electrons in bulk Ge at 127 K was extracted.

Ultrasound-modulated optical tomography: recovery of amplitude of vibration in the insonified region from boundary measurement of light correlation

We address a certain inverse problem in ultrasound-modulated optical tomography: the recovery of the amplitude of vibration of scatterers [p(r)] in the ultrasound focal volume in a diffusive object from boundary measurement of the modulation depth (M) of the amplitude autocorrelation of light [phi(r, tau)] traversing through it. Since M is dependent on the stiffness of the material, this is the precursor to elasticity imaging. The propagation of phi(r, tau) is described by a diffusion equation from which we have derived a nonlinear perturbation equation connecting p(r) and refractive index modulation [Delta n(r)] in the region of interest to M measured on the boundary. The nonlinear perturbation equation and its approximate linear counterpart are solved for the recovery of p(r). The numerical results reveal regions of different stiffness, proving that the present method recovers p(r) with reasonable quantitative accuracy and spatial resolution. (C) 2011 Optical Society of America

High sensitivity detection of radio-frequency modulated magnetic moment in semiconductors

An experimental setup has been realized to measure weak magnetic moments which can be modulated at radio frequencies (similar to 1-5 MHz). Using an optimized radio-frequency (RF) pickup coil and lock-in amplifier, an experimental sensitivity of 10(-15) Am(2) corresponding to 10(-18) emu has been demonstrated with a 1 s time constant. The detection limit at room temperature is 9.3 x 10(-16) Am(2)/root Hz limited by Johnson noise of the coil. The setup has been used to directly measure the magnetic moment due to a small number (similar to 7 x 10(8)) of spin polarized electrons generated by polarization modulated optical radiation in GaAs and Ge. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3654229]

Ultrasound modulated optical tomography: Young's modulus of the insonified region from measurement of natural frequency of vibration

We demonstrate a method to recover the Young's modulus (E) of a tissue-mimicking phantom from measurements of ultrasound modulated optical tomography (UMOT). The object is insonified by a dualbeam, confocal ultrasound transducer (US) oscillating at frequencies f(0) and f(0) + Delta f and the variation of modulation depth (M) in the autocorrelation of light traversed through the focal region of the US transducer against Delta f is measured. From the dominant peaks observed in the above variation, the natural frequencies of the insonified region associated with the vibration along the US transducer axis are deduced. A consequence of the above resonance is that the speckle fluctuation at the resonance frequency has a higher signal-to-noise to ratio (SNR). From these natural frequencies and the associated eigenspectrum of the oscillating object, Young's modulus (E) of the material in the focal region is recovered. The working of this method is confirmed by recovering E in the case of three tissue-mimicking phantoms of different elastic modulus values. (C) 2011 Optical Society of America

Input voltage modulated high voltage DC power supply topology for pulsed load applications

High voltage power supplies for radar applications are investigated which are subjected to pulsed load with stringent specifications. In the proposed solution, power conversion is done in two stages. A low power-high frequency converter modulates the input voltage of a high power-low frequency converter. This method satisfies all the performance specifications and takes care of the critical aspects of HV transformer.

Seismic hazard map of Coimbatore using subsurface fault rupture

This study presents the future seismic hazard map of Coimbatore city, India, by considering rupture phenomenon. Seismotectonic map for Coimbatore has been generated using past earthquakes and seismic sources within 300 km radius around the city. The region experienced a largest earthquake of moment magnitude 6.3 in 1900. Available earthquakes are divided into two categories: one includes events having moment magnitude of 5.0 and above, i.e., damaging earthquakes in the region and the other includes the remaining, i.e., minor earthquakes. Subsurface rupture character of the region has been established by considering the damaging earthquakes and total length of seismic source. Magnitudes of each source are estimated by assuming the subsurface rupture length in terms of percentage of total length of sources and matched with reported earthquake. Estimated magnitudes match well with the reported earthquakes for a RLD of 5.2% of the total length of source. Zone of influence circles is also marked in the seismotectonic map by considering subsurface rupture length of fault associated with these earthquakes. As earthquakes relive strain energy that builds up on faults, it is assumed that all the earthquakes close to damaging earthquake have released the entire strain energy and it would take some time for the rebuilding of strain energy to cause a similar earthquake in the same location/fault. Area free from influence circles has potential for future earthquake, if there is seismogenic source and minor earthquake in the last 20 years. Based on this rupture phenomenon, eight probable locations have been identified and these locations might have the potential for the future earthquakes. Characteristic earthquake moment magnitude (M-w) of 6.4 is estimated for the seismic study area considering seismic sources close to probable zones and 15% increased regional rupture character. The city is divided into several grid points at spacing of 0.01 degrees and the peak ground acceleration (PGA) due to each probable earthquake is calculated at every grid point in city by using the regional attenuation model. The maximum of all these eight PGAs is taken for each grid point and the final PGA map is arrived. This map is compared to the PGA map developed based on the conventional deterministic seismic hazard analysis (DSHA) approach. The probable future rupture earthquakes gave less PGA than that of DSHA approach. The occurrence of any earthquake may be expected in near future in these eight zones, as these eight places have been experiencing minor earthquakes and are located in well-defined seismogenic sources.

Compositionally modulated Pb(Mg1/3Nb2/3)O-3-PbTiO3 relaxor thin films deposited by pulsed excimer laser ablation technique

Thin films of (1-x)Pb(Mg1/3Nb2/3)O-3 - xPbTiO(3) (x = 0.1 to 0.3)(PMN-PT) were deposited on the platinum coated silicon substrate by pulsed excimer laser ablation technique. A template layer of LaSr0.5Co0.5O3 (LSCO) was deposited on platinum substrate prior to the deposition of PMN-PT thin films. The composition and the structure of the films were modulated via proper variation of the deposition parameter such as substrate temperature, laser fluence and thickness of the template layers. We observed the impact of the thickness of LSCO template layer on the orientation of the films. A room temperature dielectric constant varying from 2000 to 4500 was noted for different composition of the films. The dielectric properties of the films were studied over the frequency range of 100 Hz - 100 kHz over a wide range of temperatures. The films exhibited the relaxor- type behavior that was characterized by the frequency dispersion of the temperature of dielectric constant maxima (T-m) and also diffuse phase transition. C1 Indian Inst Sci, Mat Res Ctr, Bangalore, Karnataka 560012 India.

Compositionally and structurally modulated Pb(Mg1/3Nb2/3)O3-PbTiO3 relaxor thin films for microactuator application

Thin films of (1-x)Pb(Mg1/3Nb2/3)O3-xPbTiO3(x = 0.1 to 0.3) (PMN-PT) were successfully grown on the platinum coated silicon substrate by pulsed excimer laser ablation technique. A thin template layer of LaSr0.5Co0.5O3 (LSCO) was deposited on platinum substrate prior to the deposition of PMN-PT thin films. The composition and the structure of the films were modulated via proper variation of the deposition parameter such as substrate temperature, laser fluence and thickness of the template layers. We observed the impact of the thickness of LSCO template layer on the orientation of the films. The crystallographic structure and compositional variation were confirmed with x-ray diffraction and energy diffraction x-ray (EDX) analysis. A room temperature dielectric constant varying from 2000 to 4500 was noted for different composition of the films. The dielectric properties of the films were studied over the frequency range of 100 Hz - 100 kHz over a wide range of temperatures. The films exhibited the relaxor-type behavior that was characterized by the frequency dispersion of the temperature of dielectric constant maxima (Tm) and also diffuse phase transition. This relaxor nature in PMN-PT thin films was attributed to freezing of the dipole moment, which takes place below a certain temperature. This phenomenon was found to be very similar to spin glass system, where spins are observed to freeze after certain temperature.

Learning polyhedral classifiers using logistic function

In this paper we propose a new algorithm for learning polyhedral classifiers. In contrast to existing methods for learning polyhedral classifier which solve a constrained optimization problem, our method solves an unconstrained optimization problem. Our method is based on a logistic function based model for the posterior probability function. We propose an alternating optimization algorithm, namely, SPLA1 (Single Polyhedral Learning Algorithm1) which maximizes the loglikelihood of the training data to learn the parameters. We also extend our method to make it independent of any user specified parameter (e.g., number of hyperplanes required to form a polyhedral set) in SPLA2. We show the effectiveness of our approach with experiments on various synthetic and real world datasets and compare our approach with a standard decision tree method (OC1) and a constrained optimization based method for learning polyhedral sets.

Pricing Defaultable Bonds in a Markov Modulated Market

We address the problem of pricing defaultable bonds in a Markov modulated market. Using Merton's structural approach we show that various types of defaultable bonds are combination of European type contingent claims. Thus pricing a defaultable bond is tantamount to pricing a contingent claim in a Markov modulated market. Since the market is incomplete, we use the method of quadratic hedging and minimal martingale measure to derive locally risk minimizing derivative prices, hedging strategies and the corresponding residual risks. The price of defaultable bonds are obtained as solutions to a system of PDEs with weak coupling subject to appropriate terminal and boundary conditions. We solve the system of PDEs numerically and carry out a numerical investigation for the defaultable bond prices. We compare their credit spreads with some of the existing models. We observe higher spreads in the Markov modulated market. We show how business cycles can be easily incorporated in the proposed framework. We demonstrate the impact on spreads of the inclusion of rare states that attempt to capture a tight liquidity situation. These states are characterized by low risk-free interest rate, high payout rate and high volatility.