Effects of solar radiation pressure and Aerodynamic forces on satelliteattitude Dynamics and their utilization for Control: a survey

The environmcnl exerts an important inJuence on the pefirmance of space systems. A brief rel'iew of mo.s/ of the studies, pre.~ented over the past eightem years, relating to the influence ar7d the possible utilization of thc solar radiation pressure &d aero&namic forces, with particular reference to attitude dynamics and control qf satellites is presented here. The semi-passive stabilizers employing rhese forces show p~qmise of long life, low power and economic sjsfems, which though slower in response, compare we1I wit11 the octiw coi~trollers. It is felt that mud more attention is necessary to the actual implema~tution of these ideas and devices: some of which me quite ingenious und unique.

Scroll-Wave Dynamics in Human Cardiac Tissue: Lessons from a Mathematical Model with Inhomogeneities and Fiber Architecture

Cardiac arrhythmias, such as ventricular tachycardia (VT) and ventricular fibrillation (VF), are among the leading causes of death in the industrialized world. These are associated with the formation of spiral and scroll waves of electrical activation in cardiac tissue; single spiral and scroll waves are believed to be associated with VT whereas their turbulent analogs are associated with VF. Thus, the study of these waves is an important biophysical problem. We present a systematic study of the combined effects of muscle-fiber rotation and inhomogeneities on scroll-wave dynamics in the TNNP (ten Tusscher Noble Noble Panfilov) model for human cardiac tissue. In particular, we use the three-dimensional TNNP model with fiber rotation and consider both conduction and ionic inhomogeneities. We find that, in addition to displaying a sensitive dependence on the positions, sizes, and types of inhomogeneities, scroll-wave dynamics also depends delicately upon the degree of fiber rotation. We find that the tendency of scroll waves to anchor to cylindrical conduction inhomogeneities increases with the radius of the inhomogeneity. Furthermore, the filament of the scroll wave can exhibit drift or meandering, transmural bending, twisting, and break-up. If the scroll-wave filament exhibits weak meandering, then there is a fine balance between the anchoring of this wave at the inhomogeneity and a disruption of wave-pinning by fiber rotation. If this filament displays strong meandering, then again the anchoring is suppressed by fiber rotation; also, the scroll wave can be eliminated from most of the layers only to be regenerated by a seed wave. Ionic inhomogeneities can also lead to an anchoring of the scroll wave; scroll waves can now enter the region inside an ionic inhomogeneity and can display a coexistence of spatiotemporal chaos and quasi-periodic behavior in different parts of the simulation domain. We discuss the experimental implications of our study.

The stability of transmembrane helices: A molecular dynamics study on the isolated helices of bacteriorhodopsin

Bacteriorhodopsin (bR) continues to be a proven testing ground for the study of integral membrane proteins (IMPs). It is important to study the stability of the individual helices of bR, as they are postulated to exist as independently stable transmembmne helices (TMHs) and also for their utility as templates for modeling other IMPs with the postulated seven-helix bundle topology. Toward this purpose, the seven helices of bR have been studied by molecular dynamics simulation in this study. The suitability of using the backbone-dependent rotamer library of side-chain conformations arrived at from the data base of globular protein structures in the case TMHs has been tested by another set of ? helix simulations with the side-chain orientations taken from this library. The influence of the residue's net charge oil the helix stability was examined by simulating the helices III, IV, and VI (from both of the above sets of helices) with zero net charge on the side chains. The results of these 20 simulations demonstrate in general the stability of the isolated helices of bR in conformity with the two-stage hypothesis of IMP folding. However, the helices I, II, V, and VII are more stable than the other three helices. The helical nature of certain regions of III, IV, and VI are influenced by factors such as the net charge and orientation of several residues. It is seen that the residues Arg, Lys, Asp, and Glu (charged residues), and Ser, Thr, Gly, and Pro, play a crucial role in the stability of the helices of bR. The backbone-dependent rotamer library for the side chains is found to be suitable for the study of TMHs in IMP. (C) 1996 John Wiley & Sons, Inc.

Structure and dynamics of protein excited states with millisecond lifetimes

An in-depth understanding of biological processes often requires detailed atomic resolution structures of the molecules involved. However in solution where most of these processes occur the conformation of biomolecules like RNA, DNA and proteins is not static but fluctuates. Routinely used structural techniques like X-ray crystallography, NMR spectroscopy and cryo-electron microscopy have almost always been used to determine the structure of the dominant conformation or obtain an average structure of the biomolecule in solution with very little detailed information regarding the dynamics of these molecules in solution. Over the last few years, NMR based methods have been developed to study the dynamics of these biomolecules in solution in a site-specific manner with the aim of generating structures of the different conformations that these molecules can adopt in solution. One powerful technique is the Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion experiment, which can be used to detect and characterize protein excited states that are populated for as less as 0.5% of the time with ∼0.5–10 millisecond lifetimes. Due to recent advances in NMR pulse sequences and labeling methodology, it is now possible to determine the structures of these transiently populated excited states with millisecond lifetimes by obtaining accurate chemical shifts, residual dipolar couplings (RDCs) and residual chemical shift anisotropies (RCSAs) of these excited states. In these excited states the dynamics of some methyl containing residues can also be studied.

Molecular Dynamics of Thermotropic Liquid Crystals: Anomalous relaxation dynamics of calamitic and discotic liquid crystals

Recent optical kerr effect (OKE) studies have demonstrated that orientational relaxation of rod-like nematogens exhibits temporal power law decay at intermediate times not only near the isotropic–nematic (I–N) phase boundary but also in the nematic phase. Such behaviour has drawn an intriguing analogy with supercooled liquids. We have investigated both collective and single-particle orientational dynamics of a family of model system of thermotropic liquid crystals using extensive computer simulations. Several remarkable features of glassy dynamics are on display including non-exponential relaxation, dynamical heterogeneity, and non-Arrhenius temperature dependence of the orientational relaxation time. Over a temperature range near the I–N phase boundary, the system behaves remarkably like a fragile glass-forming liquid. Using proper scaling, we construct the usual relaxation time versus inverse temperature plot and explicitly demonstrate that one can successfully define a density dependent fragility of liquid crystals. The fragility of liquid crystals shows a temperature and density dependence which is remarkably similar to the fragility of glass forming supercooled liquids. Energy landscape analysis of inherent structures shows that the breakdown of the Arrhenius temperature dependence of relaxation rate occurs at a temperature that marks the onset of the growth of the depth of the potential energy minima explored by the system. A model liquid crystal, consisting of disk-like molecules, has also been investigated in molecular dynamics simulations for orientational relaxation along two isobars starting from the high temperature isotropic phase. The isobars have been so chosen that the phase sequence isotropic (I)–nematic (N)–columnar (C) appears upon cooling along one of them and the sequence isotropic (I)–columnar(C) along the other. While the orientational relaxation in the isotropic phase near the I–N phase transition shows a power law decay at short to intermediate times, such power law relaxation is not observed in the isotropic phase near the I–C phase boundary. The origin of the power law decay in the single-particle second-rank orientational time correlation function (OTCF) is traced to the growth of the orientational pair distribution functions near the I–N phase boundary. As the system settles into the nematic phase, the decay of the single-particle second-rank orientational OTCF follows a pattern that is similar to what is observed with calamitic liquid crystals and supercooled molecular liquids.

Advances in the Mathematical Modelling of Hepatitis C Virus Dynamics

Mathematical models have provided key insights into the pathogenesis of hepatitis C virus (HCV) in vivo, suggested predominant mechanism(s) of drug action, explained confounding patterns of viral load changes in HCV infected patients undergoing therapy, and presented a framework for therapy optimization. In this article, I present an overview of the major advances in the mathematical modeling of HCV dynamics.

An Antitubulin Agent BCFMT Inhibits Proliferation of Cancer Cells and Induces Cell Death by Inhibiting Microtubule Dynamics

Using cell based screening assay, we identified a novel anti-tubulin agent (Z)-5-((5-(4-bromo-3-chlorophenyl)furan-2-yl)methylene)-2-thioxothiazoli din-4-one (BCFMT) that inhibited proliferation of human cervical carcinoma (HeLa) (IC50, 7.2 +/- 1.8 mu M), human breast adenocarcinoma (MCF-7) (IC50, 10.0 +/- 0.5 mu M), highly metastatic breast adenocarcinoma (MDA-MB-231) (IC50, 6.0 +/- 1 mu M), cisplatin-resistant human ovarian carcinoma (A2780-cis) (IC50, 5.8 +/- 0.3 mu M) and multi-drug resistant mouse mammary tumor (EMT6/AR1) (IC50, 6.5 +/- 1 mu M) cells. Using several complimentary strategies, BCFMT was found to inhibit cancer cell proliferation at G2/M phase of the cell cycle apparently by targeting microtubules. In addition, BCFMT strongly suppressed the dynamics of individual microtubules in live MCF-7 cells. At its half maximal proliferation inhibitory concentration (10 mu M), BCFMT reduced the rates of growing and shortening phases of microtubules in MCF-7 cells by 37 and 40%, respectively. Further, it increased the time microtubules spent in the pause (neither growing nor shortening detectably) state by 135% and reduced the dynamicity (dimer exchange per unit time) of microtubules by 70%. In vitro, BCFMT bound to tubulin with a dissociation constant of 8.3 +/- 1.8 mu M, inhibited tubulin assembly and suppressed GTPase activity of microtubules. BCFMT competitively inhibited the binding of BODIPY FL-vinblastine to tubulin with an inhibitory concentration (K-i) of 5.2 +/- 1.5 mu M suggesting that it binds to tubulin at the vinblastine site. In cultured cells, BCFMT-treatment depolymerized interphase microtubules, perturbed the spindle organization and accumulated checkpoint proteins (BubR1 and Mad2) at the kinetochores. BCFMT-treated MCF-7 cells showed enhanced nuclear accumulation of p53 and its downstream p21, which consequently activated apoptosis in these cells. The results suggested that BCFMT inhibits proliferation of several types of cancer cells including drug resistance cells by suppressing microtubule dynamics and indicated that the compound may have chemotherapeutic potential.

Molecular probe dynamics reveals suppression of ice-like regions in strongly confined supercooled water

The structure of the hydrogen bond network is a key element for understanding water's thermodynamic and kinetic anomalies. While ambient water is strongly believed to be a uniform, continuous hydrogen-bonded liquid, there is growing consensus that supercooled water is better described in terms of distinct domains with either a low-density ice-like structure or a high-density disordered one. We evidenced two distinct rotational mobilities of probe molecules in interstitial supercooled water of polycrystalline ice Banerjee D, et al. (2009) ESR evidence for 2 coexisting liquid phases in deeply supercooled bulk water. Proc Natl Acad Sci USA 106: 11448-11453]. Here we show that, by increasing the confinement of interstitial water, the mobility of probe molecules, surprisingly, increases. We argue that loose confinement allows the presence of ice-like regions in supercooled water, whereas a tighter confinement yields the suppression of this ordered fraction and leads to higher fluidity. Compelling evidence of the presence of ice-like regions is provided by the probe orientational entropy barrier which is set, through hydrogen bonding, by the configuration of the surrounding water molecules and yields a direct measure of the configurational entropy of the same. We find that, under loose confinement of supercooled water, the entropy barrier surmounted by the slower probe fraction exceeds that of equilibrium water by the melting entropy of ice, whereas no increase of the barrier is observed under stronger confinement. The lower limit of metastability of supercooled water is discussed.

Dynamics and Regulation of RecA Polymerization and De-Polymerization on Double-Stranded DNA

The RecA filament formed on double-stranded (ds) DNA is proposed to be a functional state analogous to that generated during the process of DNA strand exchange. RecA polymerization and de-polymerization on dsDNA is governed by multiple physiological factors. However, a comprehensive understanding of how these factors regulate the processes of polymerization and de-polymerization of RecA filament on dsDNA is still evolving. Here, we investigate the effects of temperature, pH, tensile force, and DNA ends (in particular ssDNA overhang) on the polymerization and de-polymerization dynamics of the E. coli RecA filament at a single-molecule level. Our results identified the optimal conditions that permitted spontaneous RecA nucleation and polymerization, as well as conditions that could maintain the stability of a preformed RecA filament. Further examination at a nano-meter spatial resolution, by stretching short DNA constructs, revealed a striking dynamic RecA polymerization and de-polymerization induced saw-tooth pattern in DNA extension fluctuation. In addition, we show that RecA does not polymerize on S-DNA, a recently identified novel base-paired elongated DNA structure that was previously proposed to be a possible binding substrate for RecA. Overall, our studies have helped to resolve several previous single-molecule studies that reported contradictory and inconsistent results on RecA nucleation, polymerization and stability. Furthermore, our findings also provide insights into the regulatory mechanisms of RecA filament formation and stability in vivo.

Spiral-Wave Dynamics in a Mathematical Model of Human Ventricular Tissue with Myocytes and Fibroblasts

Cardiac fibroblasts, when coupled functionally with myocytes, can modulate the electrophysiological properties of cardiac tissue. We present systematic numerical studies of such modulation of electrophysiological properties in mathematical models for (a) single myocyte-fibroblast (MF) units and (b) two-dimensional (2D) arrays of such units; our models build on earlier ones and allow for zero-, one-, and two-sided MF couplings. Our studies of MF units elucidate the dependence of the action-potential (AP) morphology on parameters such as E-f, the fibroblast resting-membrane potential, the fibroblast conductance G(f), and the MF gap-junctional coupling G(gap). Furthermore, we find that our MF composite can show autorhythmic and oscillatory behaviors in addition to an excitable response. Our 2D studies use (a) both homogeneous and inhomogeneous distributions of fibroblasts, (b) various ranges for parameters such as G(gap), G(f), and E-f, and (c) intercellular couplings that can be zero-sided, one-sided, and two-sided connections of fibroblasts with myocytes. We show, in particular, that the plane-wave conduction velocity CV decreases as a function of G(gap), for zero-sided and one-sided couplings; however, for two-sided coupling, CV decreases initially and then increases as a function of G(gap), and, eventually, we observe that conduction failure occurs for low values of G(gap). In our homogeneous studies, we find that the rotation speed and stability of a spiral wave can be controlled either by controlling G(gap) or E-f. Our studies with fibroblast inhomogeneities show that a spiral wave can get anchored to a local fibroblast inhomogeneity. We also study the efficacy of a low-amplitude control scheme, which has been suggested for the control of spiral-wave turbulence in mathematical models for cardiac tissue, in our MF model both with and without heterogeneities.

Self-organized criticality in dynamics without branching

We demonstrate the phenomenon of self-organized criticality (SOC) in a simple random walk model described by a random walk of a myopic ant, i.e., a walker who can see only nearest neighbors. The ant acts on the underlying lattice aiming at uniform digging, i.e., reduction of the height profile of the surface but is unaffected by the underlying lattice. In one, two, and three dimensions we have explored this model and have obtained power laws in the time intervals between consecutive events of "digging." Being a simple random walk, the power laws in space translate to power laws in time. We also study the finite size scaling of asymptotic scale invariant process as well as dynamic scaling in this system. This model differs qualitatively from the cascade models of SOC.

Shock propagation in gas dynamics: explicit form of higher order compatibility conditions

With the use of tensor analysis and the method of singular surfaces, an infinite system of equations can be derived to study the propagation of curved shocks of arbitrary strength in gas dynamics. The first three of these have been explicitly given here. This system is further reduced to one involving scalars only. The choice of dependent variables in the infinite system is quite important, it leads to coefficients free from singularities for all values of the shock strength.

Experiments on a plume with off-source heating: Implications for cloud fluid dynamics

We report here on a series of laboratory experiments on plumes, undertaken with the object of simulating the effect of the heat release that occurs in clouds on condensation of water vapor. The experimental technique used for this purpose relies on ohmic heating generated in an electrically conducting plume fluid subjected to a suitable alternating voltage across specified axial stations in the plume flow [Bhat et al., 1989]. The present series of experiments achieves a value of the Richardson number that is toward the lower end of the range that characteristics cumulus clouds. It is found that the buoyancy enhancement due to heating disrupts the eddy structures in the flow and reduces the dilution owing to entrainment of ambient fluid that would otherwise have occurred in the central region of the plume. Heating also reduces the spread rate of the plume, but as it accelerates the flow as well, the overall specific mass flux in the plume does not show a very significant change at the heat input employed in the experiment. However, there is some indication that the entrainment rate (proportional to the streamwise derivative of the mass flux) is slightly higher immediately after heat injection and slightly lower farther downstream. The measurements support a previous proposal for a cloud scenario [Bhat and Narasimha, 1996] and demonstrate how fresh insights into certain aspects of the fluid dynamics of clouds may be derived from the experimental techniques employed here.

Cell Dynamics of Model Proteins

We design rapidly folding sequences by assigning the strongest couplings to the contacts present in a target native state in a two dimensional model of heteropolymers. The pathways to folding and their dependence on the temperature are illustrated via a mapping of the dynamics into motion within the space of the maximally compact cells.

Dynamics of ribonuclease A and ribonuclease S: Computational and experimental studies

RNase S is a complex consisting of two proteolytic fragments of RNase A: the S peptide (residues 1-20) and S protein (residues 21-124). RNase S and RNase A have very similar X-ray structures and enzymatic activities. previous experiments have shown increased rates of hydrogen exchange and greater sensitivity to tryptic cleavage for RNase S relative to RNase A. It has therefore been asserted that the RNase S complex is considerably more dynamically flexible than RNase A. In the present study we examine the differences in the dynamics of RNaseS and RNase A computationally, by MD simulations, and experimentally, using trypsin cleavage as a probe of dynamics. The fluctuations around the average solution structure during the simulation were analyzed by measuring the RMS deviation in coordinates. No significant differences between RNase S and RNase A dynamics were observed in the simulations. We were able to account for the apparent discrepancy between simulation and experiment by a simple model, According to this model, the experimentally observed differences in dynamics can be quantitatively explained by the small amounts of free S peptide and S protein that are present in equilibrium with the RNase S complex. Thus, folded RNase A and the RNase S complex have identical dynamic behavior, despite the presence of a break in polypeptide chain between residues 20 and 21 in the latter molecule. This is in contrast to what has been widely believed for over 30 years about this important fragment complementation system.