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.

Luminosity profiles of advanced mergers of galaxies using 2MASS data

A sample of 27 disturbed galaxies that show signs of interaction but have a single nucleus were selected from the Arp and the Arp-Madore catalogues. For these, the Ks band images from the Two Micron All Sky Survey (2MASS) are analysed to obtain their radial luminosity pro�les and other structural parameters. We �nd that in spite of their similar optical appearance, the sample galaxies vary in their dynamical properties, and fall into two distinct classes. The �rst class consists of galaxies which can be described by a single r1=4 law and the second class consists of galaxies that show an outer exponential disk. A few galaxies that have disturbed pro�les cannot be �t into either of the above classes. However, all the galaxies are similar in all other parameters such as the far-infrared colours, the molecular hydrogen content and the central velocity dispersion. Thus, the dynamical parameters of these sets seem to be determined by the ratio of the initial masses of the colliding galaxies. We propose that the galaxies in the �rst class result from a merger of spiral galaxies of equal masses whereas the second class of galaxies results from a merger of unequal mass galaxies. The few objects that do not fall into either category show a disturbed luminosity pro�le and a wandering centre, which is indicative of these being unrelaxed mergers. Of the 27 galaxies in our sample, 9 show elliptical-like pro�les and 13 show an outer exponential. Interestingly, Arp 224, the second oldest merger remnant of the Toomre sequence shows an exponential disk in the outer parts.

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.

Computational and experimental studies of fluid flow and heat transfer in a Calandria based reactor

CFD investigations are carried out to study the heat flux and temperature distribution in the calandria using a 3–Dimensional RANS code. Internal flow computations and experimental studies are carried out for a calandria embedded with a matrix of tubes working together as a reactor. Numerical investigations are carried on the Calandria reactor vessel with horizontal inlets and outlets located on top and the bottom to study the flow pattern and the associated temperature distribution. The computations have been carried out to simulate fluid flow and convective heat transfer for assigned near–to working conditions with different moderator injection rates and reacting heat fluxes. The results of computations provide an estimate of the tolerance bands for safe working limits for the heat dissipation at different working conditions by virtue of prediction of the hot spots in the calandria. The isothermal CFD results are validated by a set of experiments on a specially designed scaled model conducted over a range of flows and simulation parameters. The comparison of CFD results with experiments show good agreement.

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.

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.

Optimal Parameterized Policies for Resource Allocation in Communication Networks

The problem of finding optimal parameterized feedback policies for dynamic bandwidth allocation in communication networks is studied. 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 two different classes of multilevel closed-loop feedback policies for the system and use a two-timescale simultaneous perturbation stochastic approximation (SPSA) algorithm to find optimal policies within each prescribed class. We study the performance of the proposed algorithm on a numerical setting and show performance comparisons of the two optimal multilevel closedloop policies with optimal open loop policies. We observe that closed loop policies of Class B that tune parameters for both the queues and do not have the constraint that the entire bandwidth be used at each instant exhibit the best results overall as they offer greater flexibility in parameter tuning. Index Terms — Resource allocation, dynamic bandwidth allocation in communication networks, two-timescale SPSA algorithm, optimal parameterized policies. I.

Confinement-deconfinement transition and spin correlations in a generalized Kitaev model

We present a spin model, namely, the Kitaev model augmented by a loop term and perturbed by an Ising Hamiltonian, and show that it exhibits both confinement-deconfinement transitions from spin liquid to antiferromagnetic/spin-chain/ferromagnetic phases and topological quantum phase transitions between gapped and gapless spin-liquid phases. We develop a fermionic resonating-valence-bonds (RVB) mean-field theory to chart out the phase diagram of the model and estimate the stability of its spin-liquid phases, which might be relevant for attempts to realize the model in optical lattices and other spin systems. We present an analytical mean-field theory to study the confinement-deconfinement transition for large coefficient of the loop term and show that this transition is first order within such mean-field analysis in this limit. We also conjecture that in some other regimes, the confinement-deconfinement transitions in the model, predicted to be first order within the mean-field theory, may become second order via a defect condensation mechanism. Finally, we present a general classification of the perturbations to the Kitaev model on the basis of their effect on it's spin correlation functions and derive a necessary and sufficient condition, within the regime of validity of perturbation theory, for the spin correlators to exhibit a long-ranged power-law behavior in the presence of such perturbations. Our results reproduce those of Tikhonov et al. [Phys. Rev. Lett. 106, 067203 (2011)] as a special case.