Interaction of A beta peptide (1-40) with amino acid aluminium complexes: relevance to Alzheimer's disease

A beta (39-43 aminoacid residues) is the principal peptide component of amyloid deposits in Alzheimer's disease (AD). A beta peptide is derived from the amyloid precursor protein (APP) in which mutations give rise to many forms of familial AD. Aluminium is reported to play a key role in inducing conformational change in the synthetic beta-amyloid peptide (1-40)from alpha-helix to beta-pleated sheet, leading to aggregation and fibrillar formation. We have studied the interaction of amino acid-Al complexes such as D-Asp-Al and L-Glu-Al with A beta(1-40) in TFE/buffer (70% TFE and 30% H2O v/v pH 6.7) mixture using CD spectroscopy. The interaction of either of these amino acid complexes with A beta(1-40) results in loss of alpha-helical content and the peptide is more unstructured compared to free Al3+ in the solution. Our data strongly support the idea, that the Al3+ in the form of aminoacid-Al complexes is more effective in inducing random coil conformation in the A beta peptide than the free Al3+ present in the solution.

Unified approach to the constraint counting theory of glasses

An approach to the constraint counting theory of glasses is applied to many glass systems which include an oxide, chalcohalide, and chalcogenides. In this, shifting of the percolation threshold due to noncovalent bonding interactions in a basically covalent network and other recent extensions of the theory appear natural. This is particularly insightful and reveals that the chemical threshold signifies another structural transition along with the rigidity percolation threshold, thus unifying these two seemingly disparate toplogical concepts. [S0163-1829(99)11441-3].

A Complete Characterization of an Optimal Timer Based Selection Scheme

Timer-based mechanisms are often used in several wireless systems to help a given (sink) node select the best helper node among many available nodes. Specifically, a node transmits a packet when its timer expires, and the timer value is a function of its local suitability metric. In practice, the best node gets selected successfully only if no other node's timer expires within a `vulnerability' window after its timer expiry. In this paper, we provide a complete closed-form characterization of the optimal metric-to-timer mapping that maximizes the probability of success for any probability distribution function of the metric. The optimal scheme is scalable, distributed, and much better than the popular inverse metric timer mapping. We also develop an asymptotic characterization of the optimal scheme that is elegant and insightful, and accurate even for a small number of nodes.

On optimal timer-based distributed selection for rate-adaptive multi-user diversity systems

We develop an optimal, distributed, and low feedback timer-based selection scheme to enable next generation rate-adaptive wireless systems to exploit multi-user diversity. In our scheme, each user sets a timer depending on its signal to noise ratio (SNR) and transmits a small packet to identify itself when its timer expires. When the SNR-to-timer mapping is monotone non-decreasing, timers of users with better SNRs expire earlier. Thus, the base station (BS) simply selects the first user whose timer expiry it can detect, and transmits data to it at as high a rate as reliably possible. However, timers that expire too close to one another cannot be detected by the BS due to collisions. We characterize in detail the structure of the SNR-to-timer mapping that optimally handles these collisions to maximize the average data rate. We prove that the optimal timer values take only a discrete set of values, and that the rate adaptation policy strongly influences the optimal scheme's structure. The optimal average rate is very close to that of ideal selection in which the BS always selects highest rate user, and is much higher than that of the popular, but ad hoc, timer schemes considered in the literature.

Geomagnetic Storms Over India: A Close Look at Historic Space Weather at Mumbai

The swirling colors of aurorae, familiar to many in polar communities, can occasionally be seen at middle latitudes in locations such as southern Canada and central Europe. But in rare instances, aurorae can even be seen in the tropics. On 6 February 1872, news of the sighting of one such aurora was carried by the Times of India newspaper. The aurora occurred on 4 February 1872 and, as noted, was also observed over the Middle East.

Recovery from DoS Attacks in MIPv6: Modelling and Validation

Denial-of-service (DoS) attacks form a very important category of security threats that are prevalent in MIPv6 (mobile internet protocol version 6) today. Many schemes have been proposed to alleviate such threats, including one of our own [9]. However, reasoning about the correctness of such protocols is not trivial. In addition, new solutions to mitigate attacks may need to be deployed in the network on a frequent basis as and when attacks are detected, as it is practically impossible to anticipate all attacks and provide solutions in advance. This makes it necessary to validate the solutions in a timely manner before deployment in the real network. However, threshold schemes needed in group protocols make analysis complex. Model checking threshold-based group protocols that employ cryptography have not been successful so far. Here, we propose a new simulation based approach for validation using a tool called FRAMOGR that supports executable specification of group protocols that use cryptography. FRAMOGR allows one to specify attackers and track probability distributions of values or paths. We believe that infrastructure such as FRAMOGR would be required in future for validating new group based threshold protocols that may be needed for making MIPv6 more robust.

Compiler Assisted Leakage Energy Optimization for Clustered VLIW Architectures

Miniaturization of devices and the ensuing decrease in the threshold voltage has led to a substantial increase in the leakage component of the total processor energy consumption. Relatively simpler issue logic and the presence of a large number of function units in the VLIW and the clustered VLIW architectures attribute a large fraction of this leakage energy consumption in the functional units. However, functional units are not fully utilized in the VLIW architectures because of the inherent variations in the ILP of the programs. This underutilization is even more pronounced in the context of clustered VLIW architectures because of the contentions for the limited number of slow intercluster communication channels which lead to many short idle cycles.In the past, some architectural schemes have been proposed to obtain leakage energy bene .ts by aggressively exploiting the idleness of functional units. However, presence of many short idle cycles cause frequent transitions from the active mode to the sleep mode and vice-versa and adversely a ffects the energy benefits of a purely hardware based scheme. In this paper, we propose and evaluate a compiler instruction scheduling algorithm that assist such a hardware based scheme in the context of VLIW and clustered VLIW architectures. The proposed scheme exploits the scheduling slacks of instructions to orchestrate the functional unit mapping with the objective of reducing the number of transitions in functional units thereby keeping them off for a longer duration. The proposed compiler-assisted scheme obtains a further 12% reduction of energy consumption of functional units with negligible performance degradation over a hardware-only scheme for a VLIW architecture. The benefits are 15% and 17% in the context of a 2-clustered and a 4-clustered VLIW architecture respectively. Our test bed uses the Trimaran compiler infrastructure.

A general construction of space-time trellis codes for PSK signal sets

The diversity order and coding gain are crucial for the performance of a multiple antenna communication system. It is known that space-time trellis codes (STTC) can be used to achieve these objectives. In particular, we can use STTCs to obtain large coding gains. Many attempts have been made to construct STTCs which achieve full-diversity and good coding gains, though a general method of construction does not exist. Delay diversity code (rate-1) is known to achieve full-diversity, for any number of transmit antennas and any signal set, but does not give a good coding gain. A product distance code based delay diversity scheme (Tarokh, V. et al., IEEE Trans. Inform. Theory, vol.44, p.744-65, 1998) enables one to improve the coding gain and construct STTCs for any given number of states using coding in conjunction with delay diversity; it was stated as an open problem. We achieve such a construction. We assume a shift register based model to construct an STTC for any state complexity. We derive a sufficient condition for this STTC to achieve full-diversity, based on the delay diversity scheme. This condition provides a framework to do coding in conjunction with delay diversity for any signal constellation. Using this condition, we provide a formal rate-1 STTC construction scheme for PSK signal sets, for any number of transmit antennas and any given number of states, which achieves full-diversity and gives a good coding gain.

A unified view of the Apriori-based algorithms for frequent episode discovery

Frequent episode discovery framework is a popular framework in temporal data mining with many applications. Over the years, many different notions of frequencies of episodes have been proposed along with different algorithms for episode discovery. In this paper, we present a unified view of all the apriori-based discoverymethods for serial episodes under these different notions of frequencies. Specifically, we present a unified view of the various frequency counting algorithms. We propose a generic counting algorithm such that all current algorithms are special cases of it. This unified view allows one to gain insights into different frequencies, and we present quantitative relationships among different frequencies.Our unified view also helps in obtaining correctness proofs for various counting algorithms as we show here. It also aids in understanding and obtaining the anti-monotonicity properties satisfied by the various frequencies, the properties exploited by the candidate generation step of any apriori-based method. We also point out how our unified view of counting helps to consider generalization of the algorithm to count episodes with general partial orders.

Opportunistic Scheduling in Cellular Systems in the Presence of Noncooperative Mobiles

A central scheduling problem in wireless communications is that of allocating resources to one of many mobile stations that have a common radio channel. Much attention has been given to the design of efficient and fair scheduling schemes that are centrally controlled by a base station (BS) whose decisions depend on the channel conditions reported by each mobile. The BS is the only entity taking decisions in this framework. The decisions are based on the reports of mobiles on their radio channel conditions. In this paper, we study the scheduling problem from a game-theoretic perspective in which some of the mobiles may be noncooperative or strategic, and may not necessarily report their true channel conditions. We model this situation as a signaling game and study its equilibria. We demonstrate that the only Perfect Bayesian Equilibria (PBE) of the signaling game are of the babbling type: the noncooperative mobiles send signals independent of their channel states, the BS simply ignores them, and allocates channels based only on the prior information on the channel statistics. We then propose various approaches to enforce truthful signaling of the radio channel conditions: a pricing approach, an approach based on some knowledge of the mobiles' policies, and an approach that replaces this knowledge by a stochastic approximations approach that combines estimation and control. We further identify other equilibria that involve non-truthful signaling.

Sensitivity of nucleation phenomena on range of interaction potential

Theoretical and computational investigations of nucleation have been plagued by the sensitivity of the phase diagram to the range of the interaction potential. As the surface tension depends strongly on the range of interaction potential and as the classical nucleation theory (CNT) predicts the free energy barrier to be directly proportional to the cube of the surface tension, one expects a strong sensitivity of nucleation barrier to the range of the potential; however, CNT leaves many aspects unexplored. We find for gas-liquid nucleation in Lennard-Jones system that on increasing the range of interaction the kinetic spinodal (KS) (where the mechanism of nucleation changes from activated to barrierless) shifts deeper into the metastable region. Therefore the system remains metastable for larger value of supersaturation and this allows one to explore the high metastable region without encountering the KS. On increasing the range of interaction, both the critical cluster size and pre-critical minima in the free energy surface of kth largest cluster, at respective kinetic spinodals, shift towards smaller cluster size. In order to separate surface tension contribution to the increase in the barrier from other non-trivial factors, we introduce a new scaling form for surface tension and use it to capture both the temperature and the interaction range dependence of surface tension. Surprisingly, we find only a weak non-trivial contribution from other factors to the free energy barrier of nucleation. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.3685835]

A unified view of the apriori-based algorithms for frequent episode discovery

Frequent episode discovery framework is a popular framework in temporal data mining with many applications. Over the years, many different notions of frequencies of episodes have been proposed along with different algorithms for episode discovery. In this paper, we present a unified view of all the apriori-based discovery methods for serial episodes under these different notions of frequencies. Specifically, we present a unified view of the various frequency counting algorithms. We propose a generic counting algorithm such that all current algorithms are special cases of it. This unified view allows one to gain insights into different frequencies, and we present quantitative relationships among different frequencies. Our unified view also helps in obtaining correctness proofs for various counting algorithms as we show here. It also aids in understanding and obtaining the anti-monotonicity properties satisfied by the various frequencies, the properties exploited by the candidate generation step of any apriori-based method. We also point out how our unified view of counting helps to consider generalization of the algorithm to count episodes with general partial orders.

Propensity to Form Amyloid Fibrils Is Encoded as Excitations in the Free Energy Landscape of Monomeric Proteins

Protein aggregation, linked to many of diseases, is initiated when monomers access rogue conformations that are poised to form amyloid fibrils. We show, using simulations of src SH3 domain, that mechanical force enhances the population of the aggregation-prone (N*) states, which are rarely populated under force free native conditions but are encoded in the spectrum of native fluctuations. The folding phase diagrams of SH3 as a function of denaturant concentration (C]), mechanical force (f), and temperature exhibit an apparent two-state behavior, without revealing the presence of the elusive N* states. Interestingly, the phase boundaries separating the folded and unfolded states at all C] and f fall on a master curve, which can be quantitatively described using an analogy to superconductors in a magnetic field. The free energy profiles as a function of the molecular extension (R), which are accessible in pulling experiments, (R), reveal the presence of a native-like N* with a disordered solvent-exposed amino-terminal beta-strand. The structure of the N* state is identical with that found in Fyn SH3 by NMR dispersion experiments. We show that the timescale for fibril formation can be estimated from the population of the N* state, determined by the free energy gap separating the native structure and the N* state, a finding that can be used to assess fibril forming tendencies of proteins. The structures of the N* state are used to show that oligomer formation and likely route to fibrils occur by a domain-swap mechanism in SH3 domain. (C) 2014 Elsevier Ltd. All rights reserved.

Noise Detected NMR Spectroscopy

Spin noise phenomenon was predicted way back in 1946. However, experimental investigations regarding spin noise became possible only recently with major technological improvements in NMR hardware. These experiments have several potential novel applications and also demand refinements in the existing theoretical framework to explain the phenomenon. Elegance of noise spectroscopy in gathering information about the properties of a system lies in the fact that it does not require external perturbation, and the system remains in thermal equilibrium. Spin noise is intrinsic magnetic fluctuations, and both longitudinal and transverse components have been detected independently in many systems. Detection of fluctuating longitudinal magnetization leads to field of Magnetic Resonance Force Microscopy (MRFM) that can efficiently probe very few spins even down to the level of single spin utilizing ultrasensitive cantilevers. Transverse component of spin noise, which can simultaneously monitor different resonances over a given frequency range enabling one to distinguish between different chemical environments, has also received considerable attention, and found many novel applications. These experiments demand a detailed understanding of the underlying spin noise phenomenon in order to perform perturbation-free magnetic resonance and widen the highly promising application area. Detailed investigations of noise magnetization have been performed recently using force microscopy on equilibrium ensemble of paramagnetic alkali atoms. It was observed that random fluctuations generate spontaneous spin coherences which has similar characteristics as generated by macroscopic magnetization of polarized ensemble in terms of precession and relaxation properties. Several other intrinsic properties like g-factors, isotope-abundance ratios, hyperfine splitting, spin coherence lifetimes etc. also have been achieved without having to excite the sample. In contrast to MRFM-approaches, detection of transverse spin noise also offers novel applications, attracting considerable attention. This has unique advantage as different resonances over a given frequency range enable one to distinguish between different chemical environments. Since these noise signatures scale inversely with sample size, these approaches lead to the possibility of non-perturbative magnetic resonance of small systems down to nano-scale. In this review, these different approaches will be highlighted with main emphasis on transverse spin noise investigations.

Solid-state optical absorption from optimally tuned time-dependent range-separated hybrid density functional theory

We present a framework for obtaining reliable solid-state charge and optical excitations and spectra from optimally tuned range-separated hybrid density functional theory. The approach, which is fully couched within the formal framework of generalized Kohn-Sham theory, allows for the accurate prediction of exciton binding energies. We demonstrate our approach through first principles calculations of one- and two-particle excitations in pentacene, a molecular semiconducting crystal, where our work is in excellent agreement with experiments and prior computations. We further show that with one adjustable parameter, set to produce the known band gap, this method accurately predicts band structures and optical spectra of silicon and lithium fluoride, prototypical covalent and ionic solids. Our findings indicate that for a broad range of extended bulk systems, this method may provide a computationally inexpensive alternative to many-body perturbation theory, opening the door to studies of materials of increasing size and complexity.