Helix-sheet interconversion in a synthetic pore lining peptide derived from a designed ion channel

We have designed a four-helix protein that is expected to tetramerize in the membrane to form an ion channel with a structurally well defined pore. A synthetic peptide corresponding to the channel lining helix facilitates ion transport across liposomal membranes and largely helical in membranes. Detailed circular dichroism studies of the peptide in methanol, water and methanal-water mixtures reveal that it is helical in methanol, beta-structured in 97.5% water and a combination of these two structures at intermediate compositions of methanol and water. A fluorescence resonance energy transfer study of the peptide shows that the peptide is monomeric in methanol but undergoes extensive anti-parallel aggregation in aqueous solution.

Liquefaction And Pore Water Pressure Generation In Sand - A Cyclic Strain Approach

This paper presents the results of laboratory investigation carried out on Ahmedabad sand on the liquefaction and pore water pressure generation during strain controled cyclic loading. Laboratory experiments were carried out on representative natural sand samples (base sand) collected from earthquake-affected area of Ahmedabad City of Gujarat State in India. A series of strain controled cyclic triaxial tests were carried out on isotropically compressed samples to study the influence of different parameters such as shear strain amplitude, initial effective confining pressure, relative density and percentage of non-plastic fines on the behavior of liquefaction and pore water pressure generation. It has been observed from the laboratory investigation that the potential for liquefaction of the sandy soils depends on the shear strain amplitude, initial relative density, initial effective confining pressure and non-plastic fines. In addition, an empirical relationship between pore pressure ratio and cycle ratio independent of the number of cycles of loading, relative density, confining pressure, amplitude of shear strain and non-plastic fines has been proposed.

Use of narrow-pore filters in He II transfer devices - new results

With the aim of finding simple methods for the fabrication of He II refilling devices, He II flow has been studied through filters made from various fine powders (oxides and metals, grain sizes in the range 0.05–2 μm) by compacting them under pressure. The results obtained for the different states of He II flow, especially in the “breakthrough” and “easy flow” range, are explained by the fountain effect, He II hydrodynamics and the choking effect. According to the results, pressedpowder filters can be classified into three groups with different flow characteristics, of which the “good transfer filters” with a behaviour neatly described by simple theory are suitable for use in He II refilling devices.

Multiresolution Area-based Fractal Dimension Estimation of Signals Applied to EEG Data

In this paper, we present an approach to estimate fractal complexity of discrete time signal waveforms based on computation of area bounded by sample points of the signal at different time resolutions. The slope of best straight line fit to the graph of log(A(rk)A / rk(2)) versus log(l/rk) is estimated, where A(rk) is the area computed at different time resolutions and rk time resolutions at which the area have been computed. The slope quantifies complexity of the signal and it is taken as an estimate of the fractal dimension (FD). The proposed approach is used to estimate the fractal dimension of parametric fractal signals with known fractal dimensions and the method has given accurate results. The estimation accuracy of the method is compared with that of Higuchi's and Sevcik's methods. The proposed method has given more accurate results when compared with that of Sevcik's method and the results are comparable to that of the Higuchi's method. The practical application of the complexity measure in detecting change in complexity of signals is discussed using real sleep electroencephalogram recordings from eight different subjects. The FD-based approach has shown good performance in discriminating different stages of sleep.

Signal Characterization using Fractal Dimension

Fractal Dimensions (FD) are popular metrics for characterizing signals. They are used as complexity measuresin signal analysis applications in various fields. However, proper interpretation of such analyses has not been thoroughly addressed. In this paper, we study the effect of various signal properties on FD and interpret results in terms of classical signal processing concepts such as amplitude, frequency,number of harmonics, noise power and signal bandwidth. We have used Higuchi’s method for estimating FDs. This study helps in gaining a better understanding of the FD complexity measure for various signal parameters. Our results indicate that FD is a useful metric in estimating various signal properties. As an application of the FD measure in real world scenario, the FD is used as a feature in discriminating seizures from seizure free intervals in intracranial EEG data recordings and the FD feature has given good discrimination performance.

Complexity analysis of EEG in patients with schizophrenia using fractal dimension

We computed Higuchi's fractal dimension (FD) of resting, eyes closed EEG recorded from 30 scalp locations in 18 male neuroleptic-naive, recent-onset schizophrenia (NRS) subjects and 15 male healthy control (HC) subjects, who were group-matched for age. Schizophrenia patients showed a diffuse reduction of FD except in the bilateral temporal and occipital regions, with the reduction being most prominent bifrontally. The positive symptom (PS) schizophrenia subjects showed FD values similar to or even higher than HC in the bilateral temporo-occipital regions, along with a co-existent bifrontal FD reduction as noted in the overall sample of NRS. In contrast, this increase in FD values in the bilateral temporo-occipital region was absent in the negative symptom (NS) subgroup. The regional differences in complexity suggested by these findings may reflect the aberrant brain dynamics underlying the pathophysiology of schizophrenia and its symptom dimensions. Higuchi's method of measuring FD directly in the time domain provides an alternative for the more computationally intensive nonlinear methods of estimating EEG complexity.

Inhibition of Human Two-Pore Domain K+ Channel TREK1 by Local Anesthetic Lidocaine: Negative Cooperativity and Half-of-Sites Saturation Kinetics

TWIK-related K+ channel TREK1, a background leak K+ channel, has been strongly implicated as the target of several general and local anesthetics. Here, using the whole-cell and single-channel patch-clamp technique, we investigated the effect of lidocaine, a local anesthetic, on the human (h) TREK1 channel heterologously expressed in human embryonic kidney 293 cells by an adenoviral-mediated expression system. Lidocaine, at clinical concentrations, produced reversible, concentration-dependent inhibition of hTREK1 current, with IC50 value of 180 mu M, by reducing the single-channel open probability and stabilizing the closed state. We have identified a strategically placed unique aromatic couplet (Tyr352 and Phe355) in the vicinity of the protein kinase A phosphorylation site, Ser348, in the C-terminal domain (CTD) of hTREK1, that is critical for the action of lidocaine. Furthermore, the phosphorylation state of Ser348 was found to have a regulatory role in lidocaine-mediated inhibition of hTREK1. It is interesting that we observed strong intersubunit negative cooperativity (Hill coefficient = 0.49) and half-of-sites saturation binding stoichiometry (half-reaction order) for the binding of lidocaine to hTREK1. Studies with the heterodimer of wild-type (wt)-hTREK1 and Delta 119 C-terminal deletion mutant (hTREK1(wt)-Delta 119) revealed that single CTD of hTREK1 was capable of mediating partial inhibition by lidocaine, but complete inhibition necessitates the cooperative interaction between both the CTDs upon binding of lidocaine. Based on our observations, we propose a model that explains the unique kinetics and provides a plausible paradigm for the inhibitory action of lidocaine on hTREK1.

Influence of surface chemistry of mesoporous alumina with wide pore distribution on controlled drug release

The crucial role of the drug carrier surface chemical moeities on the uptake and in vitro release of drug is discussed here in a systematic manner. Mesoporous alumina with a wide pore size distribution (2-7 nm) functionalized with various hydrophilic and hydrophobic surface chemical groups was employed as the carrier for delivery of the model drug ibuprofen. Surface functionalization with hydrophobic groups resulted in low degree of drug loading (approximately 20%) and fast rate of release (85% over a period of 5 h) whereas hydrophilic groups resulted in a significantly higher drug payloads (21%-45%) and slower rate of release (12%-40% over a period of 5 h). Depending on the chemical moiety, the diffusion controlled (proportional to time(-0.5)) drug release was additionally observed to be dependent on the mode of arrangement of the functional groups on the alumina surface as well as on the pore characteristics of the matrix. For all mesoporous alumina systems the drug dosages were far lower than the maximum recommended therapeutic dosages (MRTD) for oral delivery. We envisage that the present study would aid in the design of delivery systems capable of sustained release of multiple drugs.

Geometric Representation of Graphs in Low Dimension Using Axis Parallel Boxes

An axis-parallel k-dimensional box is a Cartesian product R-1 x R-2 x...x R-k where R-i (for 1 <= i <= k) is a closed interval of the form [a(i), b(i)] on the real line. For a graph G, its boxicity box(G) is the minimum dimension k, such that G is representable as the intersection graph of (axis-parallel) boxes in k-dimensional space. The concept of boxicity finds applications in various areas such as ecology, operations research etc. A number of NP-hard problems are either polynomial time solvable or have much better approximation ratio on low boxicity graphs. For example, the max-clique problem is polynomial time solvable on bounded boxicity graphs and the maximum independent set problem for boxicity d graphs, given a box representation, has a left perpendicular1 + 1/c log n right perpendicular(d-1) approximation ratio for any constant c >= 1 when d >= 2. In most cases, the first step usually is computing a low dimensional box representation of the given graph. Deciding whether the boxicity of a graph is at most 2 itself is NP-hard. We give an efficient randomized algorithm to construct a box representation of any graph G on n vertices in left perpendicular(Delta + 2) ln nright perpendicular dimensions, where Delta is the maximum degree of G. This algorithm implies that box(G) <= left perpendicular(Delta + 2) ln nright perpendicular for any graph G. Our bound is tight up to a factor of ln n. We also show that our randomized algorithm can be derandomized to get a polynomial time deterministic algorithm. Though our general upper bound is in terms of maximum degree Delta, we show that for almost all graphs on n vertices, their boxicity is O(d(av) ln n) where d(av) is the average degree.

Nonadiabatic charge pumping by oscillating potentials in one dimension: Results for infinite system and finite ring

We study charge pumping when a combination of static potentials and potentials oscillating with a time period T is applied in a one-dimensional system of noninteracting electrons. We consider both an infinite system using the Dirac equation in the continuum approximation and a periodic ring with a finite number of sites using the tight-binding model. The infinite system is taken to be coupled to reservoirs on the two sides which are at the same chemical potential and temperature. We consider a model in which oscillating potentials help the electrons to access a transmission resonance produced by the static potentials and show that nonadiabatic pumping violates the simple sin phi rule which is obeyed by adiabatic two-site pumping. For the ring, we do not introduce any reservoirs, and we present a method for calculating the current averaged over an infinite time using the time evolution operator U(T) assuming a purely Hamiltonian evolution. We analytically show that the averaged current is zero if the Hamiltonian is real and time-reversal invariant. Numerical studies indicate another interesting result, namely, that the integrated current is zero for any time dependence of the potential if it is applied to only one site. Finally we study the effects of pumping at two sites on a ring at resonant and nonresonant frequencies, and show that the pumped current has different dependences on the pumping amplitude in the two cases.

The hardness of approximating the boxicity, cubicity and threshold dimension of a graph

A k-dimensional box is the Cartesian product R-1 X R-2 X ... X R-k where each R-i is a closed interval on the real line. The boxicity of a graph G, denoted as box(G), is the minimum integer k such that G can be represented as the intersection graph of a collection of k-dimensional boxes. A unit cube in k-dimensional space or a k-cube is defined as the Cartesian product R-1 X R-2 X ... X R-k where each R-i is a closed interval oil the real line of the form a(i), a(i) + 1]. The cubicity of G, denoted as cub(G), is the minimum integer k such that G can be represented as the intersection graph of a collection of k-cubes. The threshold dimension of a graph G(V, E) is the smallest integer k such that E can be covered by k threshold spanning subgraphs of G. In this paper we will show that there exists no polynomial-time algorithm for approximating the threshold dimension of a graph on n vertices with a factor of O(n(0.5-epsilon)) for any epsilon > 0 unless NP = ZPP. From this result we will show that there exists no polynomial-time algorithm for approximating the boxicity and the cubicity of a graph on n vertices with factor O(n(0.5-epsilon)) for any epsilon > 0 unless NP = ZPP. In fact all these hardness results hold even for a highly structured class of graphs, namely the split graphs. We will also show that it is NP-complete to determine whether a given split graph has boxicity at most 3. (C) 2010 Elsevier B.V. All rights reserved.

Spin-1 Kitaev model in one dimension

We study a one-dimensional version of the Kitaev model on a ring of size N, in which there is a spin S > 1/2 on each site and the Hamiltonian is J Sigma(nSnSn+1y)-S-x. The cases where S is integer and half-odd integer are qualitatively different. We show that there is a Z(2)-valued conserved quantity W-n for each bond (n, n + 1) of the system. For integer S, the Hilbert space can be decomposed into 2N sectors, of unequal sizes. The number of states in most of the sectors grows as d(N), where d depends on the sector. The largest sector contains the ground state, and for this sector, for S=1, d=(root 5+1)/2. We carry out exact diagonalization for small systems. The extrapolation of our results to large N indicates that the energy gap remains finite in this limit. In the ground-state sector, the system can be mapped to a spin-1/2 model. We develop variational wave functions to study the lowest energy states in the ground state and other sectors. The first excited state of the system is the lowest energy state of a different sector and we estimate its excitation energy. We consider a more general Hamiltonian, adding a term lambda Sigma W-n(n), and show that this has gapless excitations in the range lambda(c)(1)<=lambda <=lambda(c)(2). We use the variational wave functions to study how the ground-state energy and the defect density vary near the two critical points lambda(c)(1) and lambda(c)(2).

Signal characterization using fractal dimension

Fractal Dimensions (FD) are one of the popular measures used for characterizing signals. They have been used as complexity measures of signals in various fields including speech and biomedical applications. However, proper interpretation of such analyses has not been thoroughly addressed. In this paper, we study the effect of various signal properties on FD and interpret results in terms of classical signal processing concepts such as amplitude, frequency, number of harmonics, noise power and signal bandwidth. We have used Higuchi's method for estimating FDs. This study may help in gaining a better understanding of the FD complexity measure itself, and for interpreting changing structural complexity of signals in terms of FD. Our results indicate that FD is a useful measure in quantifying structural changes in signal properties.