Thermal Lipid Order−Disorder Transitions in Mixtures of Cationic Cholesteryl Lipid Analogues and Dipalmitoyl Phosphatidylcholine Membranes

Two types of cationic cholesteryl amphiphiles, one where the headgroup is attached to the steroid by an ester linkage and the second by an ether linkage, were synthesized. A third type of cholesteryl lipid bearing an oligoethylene glycol segment was also prepared. Each of these synthetic lipids generated vesicle-like aggregates with closed inner aqueous compartments from their aqueous suspensions. We examined their interaction with L-α-dipalmitoyl phosphatidylcholine (DPPC) membranes using fluorescence anisotropy, transmission electron microscopy (TEM), and differential scanning calorimetry (DSC). When included in membranes, the synthetic cholesteryl lipids were found to quench the chain motion of the acyl chains of DPPC. This suggests that these cationic cholesteryl derivatives act as filler molecules despite modification at the headgroup level from the molecular structure of natural cholesterol. Careful analyses of DSC and fluorescence anisotropy data suggest that the nature of perturbation induced by each of these cationic cholesterol derivatives is dependent on the details of their molecular structure and provides significant information on the nature of interaction of these derivatives with phospholipid molecules. In general, amphiphiles that support structured water at the interfacial region tend to rigidify the fluid phase more than others. Importantly, these cholesteryl amphiphiles behave less like cholesterol in that their incorporation in DPPC not only abolishes the phase transition but also depresses the phase transition temperature.

Steady compressible flow of cohesionless granular materials through a wedge-shaped bunker

A continuum model based on the critical-state theory of soil mechanics is used to generate stress, density, and velocity profiles, and to compute discharge rates for the flow of granular material in a mass flow bunker. The bin–hopper transition region is idealized as a shock across which all the variables change discontinuously. Comparison with the work of Michalowski (1987) shows that his experimentally determined rupture layer lies between his prediction and that of the present theory. However, it resembles the former more closely. The conventional condition involving a traction-free surface at the hopper exit is abandoned in favour of an exit shock below which the material falls vertically with zero frictional stress. The basic equations, which are not classifiable under any of the standard types, require excessive computational time. This problem is alleviated by the introduction of the Mohr–Coulomb approximation (MCA). The stress, density, and velocity profiles obtained by integration of the MCA converge to asymptotic fields on moving down the hopper. Expressions for these fields are derived by a perturbation method. Computational difficulties are encountered for bunkers with wall angles θw [gt-or-equal, slanted] 15° these are overcome by altering the initial conditions. Predicted discharge rates lie significantly below the measured values of Nguyen et al. (1980), ranging from 38% at θw = 15° to 59% at θw = 32°. The poor prediction appears to be largely due to the exit condition used here. Paradoxically, incompressible discharge rates lie closer to the measured values. An approximate semi-analytical expression for the discharge rate is obtained, which predicts values within 9% of the exact (numerical) ones in the compressible case, and 11% in the incompressible case. The approximate analysis also suggests that inclusion of density variation decreases the discharge rate. This is borne out by the exact (numerical) results – for the parameter values investigated, the compressible discharge rate is about 10% lower than the incompressible value. A preliminary comparison of the predicted density profiles with the measurements of Fickie et al. (1989) shows that the material within the hopper dilates more strongly than predicted. Surprisingly, just below the exit slot, there is good agreement between theory and experiment.

On the solution of the problem of scattering of surface water waves by a sharp discontinuity in the surface boundary conditions

Closed-form analytical expressions are derived for the reflection and transmission coefficients for the problem of scattering of surface water waves by a sharp discontinuity in the surface-boundary-conditions, for the case of deep water. The method involves the use of the Havelock-type expansion of the velocity potential along with an analysis to solve a Carleman-type singular integral equation over a semi-infinite range. This method of solution is an alternative to the Wiener-Hopf technique used previously.

Theoretical determination of HI vertical scale heights in the dwarf galaxies DDO 154, Ho II, IC 2574 and NGC 2366

In this paper, we model dwarf galaxies as a two-component system of gravitationally coupled stars and atomic hydrogen gas in the external force field of a pseudo-isothermal dark matter halo, and numerically obtain the radial distribution of HI vertical scale heights. This is done for a group of four dwarf galaxies (DDO 154, Ho II, IC 2574 and NGC 2366) for which most necessary input parameters are available from observations. The formulation of the equations takes into account the rising rotation curves generally observed in dwarf galaxies. The inclusion of self-gravity of the gas into the model at par with that of the stars results in scale heights that are smaller than what was obtained by previous authors. This is important as the gas scale height is often used for deriving other physical quantities. The inclusion of gas self-gravity is particularly relevant in the case of dwarf galaxies where the gas cannot be considered a minor perturbation to the mass distribution of the stars. We find that three out of four galaxies studied show a flaring of their HI discs with increasing radius, by a factor of a few within several disc scale lengths. The fourth galaxy has a thick HI disc throughout. This flaring arises as a result of the gas velocity dispersion remaining constant or decreasing only slightly while the disc mass distribution declines exponentially as a function of radius.

Cooperative Regulation of NOTCH1 Protein-Phosphatidylinositol 3-Kinase (PI3K) Signaling by NOD1, NOD2, and TLR2 Receptors Renders Enhanced Refractoriness to Transforming Growth Factor-beta (TGF-beta)- or Cytotoxic T-lymphocyte Antigen 4 (CTLA-4)-mediated Impairment of Human Dendritic Cell Maturation

Dendritic cells (DCs) as sentinels of the immune system are important for eliciting both primary and secondary immune responses to a plethora of microbial pathogens. Cooperative stimulation of a complex set of pattern-recognition receptors, including TLR2 and nucleotide-binding oligomerization domain (NOD)-like receptors on DCs, acts as a rate-limiting factor in determining the initiation and mounting of the robust immune response. It underscores the need for ``decoding'' these multiple receptor interactions. In this study, we demonstrate that TLR2 and NOD receptors cooperatively regulate functional maturation of human DCs. Intriguingly, synergistic stimulation of TLR2 and NOD receptors renders enhanced refractoriness to TGF-beta- or CTLA-4-mediated impairment of human DC maturation. Signaling perturbation data suggest that NOTCH1-PI3K signaling dynamics assume critical importance in TLR2- and NOD receptor-mediated surmounting of CTLA-4- and TGF-beta -suppressed maturation of human DCs. Interestingly, the NOTCH1-PI3K signaling axis holds the capacity to regulate DC functions by virtue of PKC delta-MAPK-dependent activation of NF-kappa B. This study provides mechanistic and functional insights into TLR2-and NOD receptor-mediated regulation of DC functions and unravels NOTCH1-PI3K as a signaling cohort for TLR2 and NOD receptors. These findings serve in building a conceptual foundation for the design of improved strategies for adjuvants and immunotherapies against infectious diseases.

Origin of Disk Lopsidedness in Spiral Galaxies

In our work we have used the atomic hydrogen [HΙ] gas distribution in the HΙ 21-cm line emission to study the dark matter halo perturbations. For tHΙs analysis, the 2-D HΙ surface density and velocity maps (arcHΙval) of the galaxies in the Eridanus group (obtained using the GMRT) and in the Ursa Major group (obtained from WSRT) were used. In addition a few HΙckson Compact Groups of galaxies were also studied using the GMRT. The HΙ maps of these galaxies were Fourier analysed to estimate the asymmetry in the distribution and motion of gas. The average asymmetry parameter in the 1.5 to 2.5 K′-band scale lengths was found to be ~ 0.27 for the Eridanus group of galaxies wHΙle it was ~ 0.14 for the Ursa Major group of galaxies. The asymmetries in the distribution of HΙ as a function of Hubble type of galaxies were also studied and was found to be directly correlated with the compactness of the groups. In addition, the trend in the asymmetry as a function of the Hubble type of galaxies was opposite to that seen in the field galaxies, i.e., in the group galaxies, the early type galaxies showed more asymmetry than late type. These two aspects indicated that tidal interactions between the galaxies in a group environment to be the major cause of asymmetries. The observed asymmetry parameters were consistent with recent numerical simulations of asymmetries of gas disk caused by fly-by interactions. We have also estimated the perturbation of dark matter halo using the asymmetry parameter obtained from the Fourier series analysis of the surface density maps.

NETGEM: Network Embedded Temporal GEnerative Model for gene expression data

Background: Temporal analysis of gene expression data has been limited to identifying genes whose expression varies with time and/or correlation between genes that have similar temporal profiles. Often, the methods do not consider the underlying network constraints that connect the genes. It is becoming increasingly evident that interactions change substantially with time. Thus far, there is no systematic method to relate the temporal changes in gene expression to the dynamics of interactions between them. Information on interaction dynamics would open up possibilities for discovering new mechanisms of regulation by providing valuable insight into identifying time-sensitive interactions as well as permit studies on the effect of a genetic perturbation. Results: We present NETGEM, a tractable model rooted in Markov dynamics, for analyzing the dynamics of the interactions between proteins based on the dynamics of the expression changes of the genes that encode them. The model treats the interaction strengths as random variables which are modulated by suitable priors. This approach is necessitated by the extremely small sample size of the datasets, relative to the number of interactions. The model is amenable to a linear time algorithm for efficient inference. Using temporal gene expression data, NETGEM was successful in identifying (i) temporal interactions and determining their strength, (ii) functional categories of the actively interacting partners and (iii) dynamics of interactions in perturbed networks. Conclusions: NETGEM represents an optimal trade-off between model complexity and data requirement. It was able to deduce actively interacting genes and functional categories from temporal gene expression data. It permits inference by incorporating the information available in perturbed networks. Given that the inputs to NETGEM are only the network and the temporal variation of the nodes, this algorithm promises to have widespread applications, beyond biological systems. The source code for NETGEM is available from https://github.com/vjethava/NETGEM

Rule-based modelling of iron homeostasis in tuberculosis

To establish itself within the host system, Mycobacterium tuberculosis (Mtb) has formulated various means of attacking the host system. One such crucial strategy is the exploitation of the iron resources of the host system. Obtaining and maintaining the required concentration of iron becomes a matter of contest between the host and the pathogen, both trying to achieve this through complex molecular networks. The extent of complexity makes it important to obtain a systems perspective of the interplay between the host and the pathogen with respect to iron homeostasis. We have reconstructed a systems model comprising 92 components and 85 protein-protein or protein-metabolite interactions, which have been captured as a set of 194 rules. Apart from the interactions, these rules also account for protein synthesis and decay, RBC circulation and bacterial production and death rates. We have used a rule-based modelling approach, Kappa, to simulate the system separately under infection and non-infection conditions. Various perturbations including knock-outs and dual perturbation were also carried out to monitor the behavioral change of important proteins and metabolites. From this, key components as well as the required controlling factors in the model that are critical for maintaining iron homeostasis were identified. The model is able to re-establish the importance of iron-dependent regulator (ideR) in Mtb and transferrin (Tf) in the host. Perturbations, where iron storage is increased, appear to enhance nutritional immunity and the analysis indicates how they can be harmful for the host. Instead, decreasing the rate of iron uptake by Tf may prove to be helpful. Simulation and perturbation studies help in identifying Tf as a possible drug target. Regulating the mycobactin (myB) concentration was also identified as a possible strategy to control bacterial growth. The simulations thus provide significant insight into iron homeostasis and also for identifying possible drug targets for tuberculosis.

Linear stability, transient growth and the role of viscosity stratification in compressible Couette flow

Linear stability and the nonmodal transient energy growth in compressible plane Couette flow are investigated for two prototype mean flows: (a) the uniform shear flow with constant viscosity, and (b) the nonuniform shear flow with stratified viscosity. Both mean flows are linearly unstable for a range of supersonic Mach numbers (M). For a given M, the critical Reynolds number (Re) is significantly smaller for the uniform shear flow than its nonuniform shear counterpart; for a given Re, the dominant instability (over all streamwise wave numbers, α) of each mean flow belongs to different modes for a range of supersonic M. An analysis of perturbation energy reveals that the instability is primarily caused by an excess transfer of energy from mean flow to perturbations. It is shown that the energy transfer from mean flow occurs close to the moving top wall for “mode I” instability, whereas it occurs in the bulk of the flow domain for “mode II.” For the nonmodal transient growth analysis, it is shown that the maximum temporal amplification of perturbation energy, Gmax, and the corresponding time scale are significantly larger for the uniform shear case compared to those for its nonuniform counterpart. For α=0, the linear stability operator can be partitioned into L∼L̅ +Re2 Lp, and the Re-dependent operator Lp is shown to have a negligibly small contribution to perturbation energy which is responsible for the validity of the well-known quadratic-scaling law in uniform shear flow: G(t∕Re)∼Re2. In contrast, the dominance of Lp is responsible for the invalidity of this scaling law in nonuniform shear flow. An inviscid reduced model, based on Ellingsen-Palm-type solution, has been shown to capture all salient features of transient energy growth of full viscous problem. For both modal and nonmodal instability, it is shown that the viscosity stratification of the underlying mean flow would lead to a delayed transition in compressible Couette flow.

Zero momentum gluons and the total pp and pbarp cross-sections

We describe a QCD motivated model for total cross-sections which uses the eikonal representation and incorporates QCD mini-jets to drive the rise with energy of the cross-section, while the impact parameter distribution is obtained through the Fourier transform of the transverse momentum distribution of soft gluons emitted in the parton-parton interactions giving rise to mini-jets in the final state. A singular but integral expression for the running coupling constant in the infrared region is part of this model.

Generalized asymptotic expansions for the wavenumbers in infinite flexible in vacuo orthotropic cylindrical shells

Analytical expressions are found for the wavenumbers and resonance frequencies in flexible, orthotropic shells using the asymptotic methods. These expressions are valid for arbitrary circumferential orders n. The Donnell-Mushtari shell theory is used to model the dynamics of the cylindrical shell. Initially, an in vacuo cylindrical isotropic shell is considered and expressions for all the wavenumbers (bending, near-field bending, longitudinal and torsional) are found. Subsequently, defining a suitable orthotropy parameter epsilon, the problem of wave propagation in an orthotropic shell is posed as a perturbation on the corresponding problem for an isotropic shell. Asymptotic expressions for the wavenumbers in the in vacuo orthotropic shell are then obtained by treating epsilon as an expansion parameter. In both cases (isotropy and orthotropy), a frequency-scaling parameter (eta) and Poisson's ratio (nu) are used to find elegant expansions in the different frequency regimes. The asymptotic expansions are compared with numerical solutions in each of the cases and the match is found to be good. The main contribution of this work lies in the extension of the existing literature by developing closed-form expressions for wavenumbers with arbitrary circumferential orders n in the case of both, isotropic and orthotropic shells. Finally, we present natural frequency expressions in finite shells (isotropic and orthotropic) for the axisymmetric mode and compare them with numerical and ANSYS results. Here also, the comparison is found to be good. (C) 2011 Elsevier Ltd. All rights reserved.

High-rate analysis of channel-optimized vector quantization

High-rate analysis of channel-optimized vector quantizationThis paper considers the high-rate performance of channel optimized source coding for noisy discrete symmetric channels with random index assignment. Specifically, with mean squared error (MSE) as the performance metric, an upper bound on the asymptotic (i.e., high-rate) distortion is derived by assuming a general structure on the codebook. This structure enables extension of the analysis of the channel optimized source quantizer to one with a singular point density: for channels with small errors, the point density that minimizes the upper bound is continuous, while as the error rate increases, the point density becomes singular. The extent of the singularity is also characterized. The accuracy of the expressions obtained are verified through Monte Carlo simulations.

Analog/RF Built-in-Self-Test Subsystem for a Mobile Broadcast Video Receiver in 65-nm CMOS

A built-in-self-test (BIST) subsystem embedded in a 65-nm mobile broadcast video receiver is described. The subsystem is designed to perform analog and RF measurements at multiple internal nodes of the receiver. It uses a distributed network of CMOS sensors and a low bandwidth, 12-bit A/D converter to perform the measurements with a serial bus interface enabling a digital transfer of measured data to automatic test equipment (ATE). A perturbation/correlation based BIST method is described, which makes pass/fail determination on parts, resulting in significant test time and cost reduction.

Stochastic Algorithms for Discrete Parameter Simulation Optimization

We present two efficient discrete parameter simulation optimization (DPSO) algorithms for the long-run average cost objective. One of these algorithms uses the smoothed functional approximation (SFA) procedure, while the other is based on simultaneous perturbation stochastic approximation (SPSA). The use of SFA for DPSO had not been proposed previously in the literature. Further, both algorithms adopt an interesting technique of random projections that we present here for the first time. We give a proof of convergence of our algorithms. Next, we present detailed numerical experiments on a problem of admission control with dependent service times. We consider two different settings involving parameter sets that have moderate and large sizes, respectively. On the first setting, we also show performance comparisons with the well-studied optimal computing budget allocation (OCBA) algorithm and also the equal allocation algorithm. Note to Practitioners-Even though SPSA and SFA have been devised in the literature for continuous optimization problems, our results indicate that they can be powerful techniques even when they are adapted to discrete optimization settings. OCBA is widely recognized as one of the most powerful methods for discrete optimization when the parameter sets are of small or moderate size. On a setting involving a parameter set of size 100, we observe that when the computing budget is small, both SPSA and OCBA show similar performance and are better in comparison to SFA, however, as the computing budget is increased, SPSA and SFA show better performance than OCBA. Both our algorithms also show good performance when the parameter set has a size of 10(8). SFA is seen to show the best overall performance. Unlike most other DPSO algorithms in the literature, an advantage with our algorithms is that they are easily implementable regardless of the size of the parameter sets and show good performance in both scenarios.

An algorithm for dynamic optimal bandwidth allocation in communication networks

We study the problem of optimal bandwidth allocation in communication networks. We consider a queueing model with two queues to which traffic from different competing flows arrive. The queue length at the buffers is observed every T instants of time, on the basis of which a decision on the amount of bandwidth to be allocated to each buffer for the next T instants is made. We consider a class of closed-loop feedback policies for the system and use a twotimescale simultaneous perturbation stochastic approximation(SPSA) algorithm to find an optimal policy within the prescribed class. We study the performance of the proposed algorithm on a numerical setting. Our algorithm is found to exhibit good performance.