Mapping Key Residues of ISD11 Critical for NFS1-ISD11 Subcomplex Stability IMPLICATIONS IN THE DEVELOPMENT OF MITOCHONDRIAL DISORDER, COXPD19

Biogenesis of the iron-sulfur (Fe-S) cluster is an indispensable process in living cells. In mammalian mitochondria, the initial step of the Fe-S cluster assembly process is assisted by the NFS1-ISD11 complex, which delivers sulfur to scaffold protein ISCU during Fe-S cluster synthesis. Although ISD11 is an essential protein, its cellular role in Fe-S cluster biogenesis is still not defined. Our study maps the important ISD11 amino acid residues belonging to putative helix 1 (Phe-40), helix 3 (Leu-63, Arg-68, Gln-69, Ile-72, Tyr-76), and C-terminal segment (Leu-81, Glu-84) are critical for in vivo Fe-S cluster biogenesis. Importantly, mutation of these conserved ISD11 residues into alanine leads to its compromised interaction with NFS1, resulting in reduced stability and enhanced aggregation of NFS1 in the mitochondria. Due to altered interaction with ISD11 mutants, the levels of NFS1 and Isu1 were significantly depleted, which affects Fe-S cluster biosynthesis, leading to reduced electron transport chain complex (ETC) activity and mitochondrial respiration. In humans, a clinically relevant ISD11 mutation (R68L) has been associated in the development of a mitochondrial genetic disorder, COXPD19. Our findings highlight that the ISD11 R68A/R68L mutation display reduced affinity to form a stable subcomplex with NFS1, and thereby fails to prevent NFS1 aggregation resulting in impairment of the Fe-S cluster biogenesis. The prime affected machinery is the ETC complex, which showed compromised redox properties, causing diminished mitochondrial respiration. Furthermore, the R68L ISD11 mutant displayed accumulation of mitochondrial iron and reactive oxygen species, leading to mitochondrial dysfunction, which correlates with the phenotype observed in COXPD19 patients.

Disorder, oscillatory dynamics and state switching: the role of c-Myc

In this paper, using the intrinsically disordered oncoprotein Myc as an example, we present a mathematical model to help explain how protein oscillatory dynamics can influence state switching. Earlier studies have demonstrated that, while Myc overexpression can facilitate state switching and transform a normal cell into a cancer phenotype, its downregulation can reverse state-switching. A fundamental aspect of the model is that a Myc threshold determines cell fate in cells expressing p53. We demonstrate that a non-cooperative positive feedback loop coupled with Myc sequestration at multiple binding sites can generate bistable Myc levels. Normal quiescent cells with Myc levels below the threshold can respond to mitogenic signals to activate the cyclin/cdk oscillator for limited cell divisions but the p53/Mdm2 oscillator remains nonfunctional. In response to stress, the p53/Mdm2 oscillator is activated in pulses that are critical to DNA repair. But if stress causes Myc levels to cross the threshold, Myc inactivates the p53/Mdm2 oscillator, abrogates p53 pulses, and pushes the cyclin/cdk oscillator into overdrive sustaining unchecked proliferation seen in cancer. However, if Myc is downregulated, the cyclin/cdk oscillator is inactivated and the p53/Mdm2 oscillator is reset and the cancer phenotype is reversed. (C) 2015 Elsevier Ltd. All rights reserved.

Electric field and temperature dependence of the local structural disorder in the lead-free ferroelectric Na0.5Bi0.5TiO3: An EXAFS study

The complex nature of the structural disorder in the lead-free ferroelectric Na1/2Bi1/2TiO3 has a profound impact on the perceived global structure and polar properties. In this paper, we have investigated the effect of electric field and temperature on the local structure around theBi and Ti atoms using extended x-ray absorption fine structure. Detailed analysis revealed that poling brings about a noticeable change in the bond distances associated with the Bi-coordination sphere, whereas the Ti coordination remains unaffected. We also observed discontinuity in the Bi-O bond lengths across the depolarization temperature of the poled specimen. These results establish that the disappearance of the monoclinic-like (Cc) global distortion, along with the drastic suppression of the short-ranged in-phase octahedral tilt after poling B. N. Rao et al., Phys. Rev. B 88, 224103 (2013)] is a result of the readjustment of theA-O bonds by the electric field, so as to be in conformity with the rhombohedral R3c structure.

Micro-satellite angular rate estimation using second-order sliding mode observer

Development of computationally efficient and accurate attitude rate estimation algorithm using low-cost commercially available star sensor arrays and processing unit for micro-satellite mission is presented. Our design reduces the computational load of least square (LS)-based rate estimation method while maintaining the same accuracy compared to other rate estimation approaches. Furthermore, rate estimation accuracy is improved by using recently developed fast and accurate second-order sliding mode observer (SOSMO) scheme. It also gives robust estimation in the presence of modeling uncertainties, unknown disturbances, and measurement noise. Simulation study shows that rate estimation accuracy achieved by our LS-based method is comparable with other methods for a typical commercially available star sensor array. The robustness analysis of SOSMO with respect to measurement noise is also presented in this paper. Simulation test bench for a practical scenario of satellite rate estimation uses moment-of-inertia variation and environmental disturbances affecting a typical micro-satellite at 500km circular orbit. Comparison studies of SOSMO with 1-SMO and pseudo-linear Kalman filter show that satisfactory estimation accuracy is achieved by SOSMO.

A C-0 Interior Penalty Method for a Fourth-order Variational Inequality of the Second Kind

In this article, we propose a C-0 interior penalty ((CIP)-I-0) method for the frictional plate contact problem and derive both a priori and a posteriori error estimates. We derive an abstract error estimate in the energy norm without additional regularity assumption on the exact solution. The a priori error estimate is of optimal order whenever the solution is regular. Further, we derive a reliable and efficient a posteriori error estimator. Numerical experiments are presented to illustrate the theoretical results. (c) 2015Wiley Periodicals, Inc.

Evaluation and Minimization of Low-Order Harmonic Torque in Low-Switching-Frequency Inverter-Fed Induction Motor Drives

A low-order harmonic pulsating torque is a major concern in high-power drives, high-speed drives, and motor drives operating in an overmodulation region. This paper attempts to minimize the low-order harmonic torques in induction motor drives, operated at a low pulse number (i.e., a low ratio of switching frequency to fundamental frequency), through a frequency domain (FD) approach as well as a synchronous reference frame (SRF) based approach. This paper first investigates FD-based approximate elimination of harmonic torque as suggested by classical works. This is then extended into a procedure for minimization of low-order pulsating torque components in the FD, which is independent of machine parameters and mechanical load. Furthermore, an SRF-based optimal pulse width modulation (PWM) method is proposed to minimize the low-order harmonic torques, considering the motor parameters and load torque. The two optimal methods are evaluated and compared with sine-triangle (ST) PWM and selective harmonic elimination (SHE) PWM through simulations and experimental studies on a 3.7-kW induction motor drive. The SRF-based optimal PWM results in marginally better performance than the FD-based one. However, the selection of optimal switching angle for any modulation index (M) takes much longer in case of SRF than in case of the FD-based approach. The FD-based optimal solutions can be used as good starting solutions and/or to reasonably restrict the search space for optimal solutions in the SRF-based approach. Both of the FD-based and SRF-based optimal PWM methods reduce the low-order pulsating torque significantly, compared to ST PWM and SHE PWM, as shown by the simulation and experimental results.

Integrals of motion for one-dimensional Anderson localized systems

Anderson localization is known to be inevitable in one-dimension for generic disordered models. Since localization leads to Poissonian energy level statistics, we ask if localized systems possess `additional' integrals of motion as well, so as to enhance the analogy with quantum integrable systems. We answer this in the affirmative in the present work. We construct a set of nontrivial integrals of motion for Anderson localized models, in terms of the original creation and annihilation operators. These are found as a power series in the hopping parameter. The recently found Type-1 Hamiltonians, which are known to be quantum integrable in a precise sense, motivate our construction. We note that these models can be viewed as disordered electron models with infinite-range hopping, where a similar series truncates at the linear order. We show that despite the infinite range hopping, all states but one are localized. We also study the conservation laws for the disorder free Aubry-Andre model, where the states are either localized or extended, depending on the strength of a coupling constant. We formulate a specific procedure for averaging over disorder, in order to examine the convergence of the power series. Using this procedure in the Aubry-Andre model, we show that integrals of motion given by our construction are well-defined in localized phase, but not so in the extended phase. Finally, we also obtain the integrals of motion for a model with interactions to lowest order in the interaction.