Mining large-scale response networks reveals `topmost activities' in Mycobacterium tuberculosis infection

Mycobacterium tuberculosis owes its high pathogenic potential to its ability to evade host immune responses and thrive inside the macrophage. The outcome of infection is largely determined by the cellular response comprising a multitude of molecular events. The complexity and inter-relatedness in the processes makes it essential to adopt systems approaches to study them. In this work, we construct a comprehensive network of infection-related processes in a human macrophage comprising 1888 proteins and 14,016 interactions. We then compute response networks based on available gene expression profiles corresponding to states of health, disease and drug treatment. We use a novel formulation for mining response networks that has led to identifying highest activities in the cell. Highest activity paths provide mechanistic insights into pathogenesis and response to treatment. The approach used here serves as a generic framework for mining dynamic changes in genome-scale protein interaction networks.

Wafer scale fabrication of porous three-dimensional plasmonic metamaterials for the visible region: chiral and beyond

We report on a wafer scale fabrication method of a three-dimensional plasmonic metamaterial with strong chiroptical response in the visible region of the electromagnetic spectrum. The system was comprised of metallic nanoparticles arranged in a helical fashion, with high degree of flexibility over the choice of the underlying material, as well as their geometrical parameters. This resulted in exquisite control over the chiroptical properties, most importantly the spectral signature of the circular dichroism. In spite of the large variability in the arrangement, as well as the size and shape of the constituent nanoparticles, the average chiro-optical response of the material remained uniform across the wafer, thus confirming the suitability of this system as a large area chiral metamaterial. By simply heating the substrate for a few minutes, the geometrical properties of the nanoparticles could be altered, thus providing an additional handle towards tailoring the spectral response of this novel material.

Interplay Between Optimal Selection Scheme, Selection Criterion, and Discrete Rate Adaptation in Opportunistic Wireless Systems

An opportunistic, rate-adaptive system exploits multi-user diversity by selecting the best node, which has the highest channel power gain, and adapting the data rate to selected node's channel gain. Since channel knowledge is local to a node, we propose using a distributed, low-feedback timer backoff scheme to select the best node. It uses a mapping that maps the channel gain, or, in general, a real-valued metric, to a timer value. The mapping is such that timers of nodes with higher metrics expire earlier. Our goal is to maximize the system throughput when rate adaptation is discrete, as is the case in practice. To improve throughput, we use a pragmatic selection policy, in which even a node other than the best node can be selected. We derive several novel, insightful results about the optimal mapping and develop an algorithm to compute it. These results bring out the inter-relationship between the discrete rate adaptation rule, optimal mapping, and selection policy. We also extensively benchmark the performance of the optimal mapping with several timer and opportunistic multiple access schemes considered in the literature, and demonstrate that the developed scheme is effective in many regimes of interest.

Scale-dependent relationships between tree species richness and ecosystem function in forests

1. The relationship between species richness and ecosystem function, as measured by productivity or biomass, is of long-standing theoretical and practical interest in ecology. This is especially true for forests, which represent a majority of global biomass, productivity and biodiversity. 2. Here, we conduct an analysis of relationships between tree species richness, biomass and productivity in 25 forest plots of area 8-50ha from across the world. The data were collected using standardized protocols, obviating the need to correct for methodological differences that plague many studies on this topic. 3. We found that at very small spatial grains (0.04ha) species richness was generally positively related to productivity and biomass within plots, with a doubling of species richness corresponding to an average 48% increase in productivity and 53% increase in biomass. At larger spatial grains (0.25ha, 1ha), results were mixed, with negative relationships becoming more common. The results were qualitatively similar but much weaker when we controlled for stem density: at the 0.04ha spatial grain, a doubling of species richness corresponded to a 5% increase in productivity and 7% increase in biomass. Productivity and biomass were themselves almost always positively related at all spatial grains. 4. Synthesis. This is the first cross-site study of the effect of tree species richness on forest biomass and productivity that systematically varies spatial grain within a controlled methodology. The scale-dependent results are consistent with theoretical models in which sampling effects and niche complementarity dominate at small scales, while environmental gradients drive patterns at large scales. Our study shows that the relationship of tree species richness with biomass and productivity changes qualitatively when moving from scales typical of forest surveys (0.04ha) to slightly larger scales (0.25 and 1ha). This needs to be recognized in forest conservation policy and management.

A Novel Monte-Carlo-Sampling-Based Receiver for Large-Scale Uplink Multiuser MIMO Systems

In this paper, we propose low-complexity algorithms based on Monte Carlo sampling for signal detection and channel estimation on the uplink in large-scale multiuser multiple-input-multiple-output (MIMO) systems with tens to hundreds of antennas at the base station (BS) and a similar number of uplink users. A BS receiver that employs a novel mixed sampling technique (which makes a probabilistic choice between Gibbs sampling and random uniform sampling in each coordinate update) for detection and a Gibbs-sampling-based method for channel estimation is proposed. The algorithm proposed for detection alleviates the stalling problem encountered at high signal-to-noise ratios (SNRs) in conventional Gibbs-sampling-based detection and achieves near-optimal performance in large systems with M-ary quadrature amplitude modulation (M-QAM). A novel ingredient in the detection algorithm that is responsible for achieving near-optimal performance at low complexity is the joint use of a mixed Gibbs sampling (MGS) strategy coupled with a multiple restart (MR) strategy with an efficient restart criterion. Near-optimal detection performance is demonstrated for a large number of BS antennas and users (e. g., 64 and 128 BS antennas and users). The proposed Gibbs-sampling-based channel estimation algorithm refines an initial estimate of the channel obtained during the pilot phase through iterations with the proposed MGS-based detection during the data phase. In time-division duplex systems where channel reciprocity holds, these channel estimates can be used for multiuser MIMO precoding on the downlink. The proposed receiver is shown to achieve good performance and scale well for large dimensions.

Role of the cloud adjustment time scale in simulation of the interannual variability of Indian summer monsoon

The simulation of precipitation in a general circulation model relying on relaxed mass flux cumulus parameterization scheme is sensitive to cloud adjustment time scale (CATS). In this study, the frequency of the dominant intra-seasonal mode and interannual variability of Indian summer monsoon rainfall (ISMR) simulated by an atmospheric general circulation model is shown to be sensitive to the CATS. It has been shown that a longer CATS of about 5 h simulates the spatial distribution of the ISMR better. El Nio Southern Oscillation-ISMR relationship is also sensitive to CATS. The equatorial Indian Ocean rainfall and ISMR coupling is sensitive to CATS. Our study suggests that a careful choice of CATS is necessary for adequate simulation of spatial pattern as well as interannual variation of Indian summer monsoon precipitation.

Small-scale mechanical testing of materials

Small-scale mechanical testing of materials has gained prominence in the last decade or so due to the continuous miniaturization of components and devices in everyday application. This review describes the various micro-fabrication processes associated with the preparation of miniaturized specimens, geometries of test specimens and the small scale testing techniques used to determine the mechanical behaviour of materials at the length scales of a few hundred micro-meters and below. This is followed by illustrative examples in a selected class of materials. The choice of the case studies is based on the relevance of the materials used in today's world: evaluation of mechanical properties of thermal barrier coatings (TBCs), applied for enhanced high temperature protection of advanced gas turbine engine components, is essential since its failure by fracture leads to the collapse of the engine system. Si-based substrates, though brittle, are indispensible for MEMS/NEMS applications. Biological specimens, whose response to mechanical loads is important to ascertain their role in diseases and to mimic their structure for attaining high fracture toughness and impact resistance. An insight into the mechanisms behind the observed size effects in metallic systems can be exploited to achieve excellent strength at the nano-scale. A future outlook of where all this is heading is also presented.

A novel MCMC algorithm for near-optimal detection in large-scale uplink mulituser MIMO systems

In this paper, we propose a low-complexity algorithm based on Markov chain Monte Carlo (MCMC) technique for signal detection on the uplink in large scale multiuser multiple input multiple output (MIMO) systems with tens to hundreds of antennas at the base station (BS) and similar number of uplink users. The algorithm employs a randomized sampling method (which makes a probabilistic choice between Gibbs sampling and random sampling in each iteration) for detection. The proposed algorithm alleviates the stalling problem encountered at high SNRs in conventional MCMC algorithm and achieves near-optimal performance in large systems with M-QAM. A novel ingredient in the algorithm that is responsible for achieving near-optimal performance at low complexities is the joint use of a randomized MCMC (R-MCMC) strategy coupled with a multiple restart strategy with an efficient restart criterion. Near-optimal detection performance is demonstrated for large number of BS antennas and users (e.g., 64, 128, 256 BS antennas/users).

Delay optimal scheduling of a discrete-time batch service queue for point-to-point channel code rate selection

We consider the problem of characterizing the minimum average delay, or equivalently the minimum average queue length, of message symbols randomly arriving to the transmitter queue of a point-to-point link which dynamically selects a (n, k) block code from a given collection. The system is modeled by a discrete time queue with an IID batch arrival process and batch service. We obtain a lower bound on the minimum average queue length, which is the optimal value for a linear program, using only the mean (λ) and variance (σ2) of the batch arrivals. For a finite collection of (n, k) codes the minimum achievable average queue length is shown to be Θ(1/ε) as ε ↓ 0 where ε is the difference between the maximum code rate and λ. We obtain a sufficient condition for code rate selection policies to achieve this optimal growth rate. A simple family of policies that use only one block code each as well as two other heuristic policies are shown to be weakly optimal in the sense of achieving the 1/ε growth rate. An appropriate selection from the family of policies that use only one block code each is also shown to achieve the optimal coefficient σ2/2 of the 1/ε growth rate. We compare the performance of the heuristic policies with the minimum achievable average queue length and the lower bound numerically. For a countable collection of (n, k) codes, the optimal average queue length is shown to be Ω(1/ε). We illustrate the selectivity among policies of the growth rate optimality criterion for both finite and countable collections of (n, k) block codes.

A multi-level multi-scale approach to study essential genes in Mycobacterium tuberculosis

Background: The set of indispensable genes that are required by an organism to grow and sustain life are termed as essential genes. There is a strong interest in identification of the set of essential genes, particularly in pathogens, not only for a better understanding of the pathogen biology, but also for identifying drug targets and the minimal gene set for the organism. Essentiality is inherently a systems property and requires consideration of the system as a whole for their identification. The available experimental approaches capture some aspects but each method comes with its own limitations. Moreover, they do not explain the basis for essentiality in most cases. A powerful prediction method to recognize this gene pool including rationalization of the known essential genes in a given organism would be very useful. Here we describe a multi-level multi-scale approach to identify the essential gene pool in a deadly pathogen, Mycobacterium tuberculosis. Results: The multi-level workflow analyses the bacterial cell by studying (a) genome-wide gene expression profiles to identify the set of genes which show consistent and significant levels of expression in multiple samples of the same condition, (b) indispensability for growth by using gene expression integrated flux balance analysis of a genome-scale metabolic model, (c) importance for maintaining the integrity and flow in a protein-protein interaction network and (d) evolutionary conservation in a set of genomes of the same ecological niche. In the gene pool identified, the functional basis for essentiality has been addressed by studying residue level conservation and the sub-structure at the ligand binding pockets, from which essential amino acid residues in that pocket have also been identified. 283 genes were identified as essential genes with high-confidence. An agreement of about 73.5% is observed with that obtained from the experimental transposon mutagenesis technique. A large proportion of the identified genes belong to the class of intermediary metabolism and respiration. Conclusions: The multi-scale, multi-level approach described can be generally applied to other pathogens as well. The essential gene pool identified form a basis for designing experiments to probe their finer functional roles and also serve as a ready shortlist for identifying drug targets.

Self-assembly of discrete metallamacrocycles employing half-sandwich octahedral diruthenium(II) building units and imidazole-based ligands

Equimolar combination of a series of binuclear half-sandwich p-cymene ruthenium(II) building units Ru-2(mu-eta(4)-C2O4)(MeOH)(2)(eta(6)-p-cymene)(2)](OTf)(2) 1a](OTf)(2), Ru-2(mu-eta(4)-N,N'-diphenyloxamidato)( MeOH)(2)(eta(6)-p-cymene)(2)](OTf)(2) 1b](OTf)(2) and Ru-2(mu-eta(4)-C6H2O4)(MeOH)(2)(eta(6)-p-cymene)(2)](OTf)(2) 1c](OTf)(2) separately with imidazole-based ditopic ligands (L-1-L-2) in methanol yielded a series of tetranuclear metallamacrocycles 2-7](OTf)(4), respectively L-1 = 1,4-bis(imidazole-1-yl)benzene; L-2 = 4,4'-bis(imidazole-1-yl)biphenyl; OTf- = O3SCF3-]. Similarly, the reaction of Ru-2(mu-eta(4)-C2O4)(MeOH)(2)(eta(6)-p-cymene)2](OTf)(2) 1a](OTf)(2) with a triazine-based tritopic ligand 1,3,5-tris(imidazole-1-yl) triazine (L3) in 3: 2 M ratio afforded an unexpected tetranuclear macrocycle 8](OTf)(4) instead of an expected trigonal prismatic cage 8a](OTf)(6). All the self-assembled macrocycles 2-8](OTf)(4) were isolated in moderate to high yields and were fully characterized by multinuclear H-1, F-19] NMR, IR and electrospray ionization mass spectrometry (ESI-MS). In addition, X-ray diffraction study on the single crystals of 3](OTf)(4) and 8](OTf)(4) also indicated the formation 2 + 2] self-assembled macrocycles. Despite the possibility of formation of different conformational isomeric macrocycles (syn-and anti) and polymeric product due to free rotation of ligand sites of imidazole linkers, the selective formation of single conformational isomer (anti) as the only product is quite interesting. Furthermore, the photo-and electrochemical properties of these assemblies have been studied using UV/Vis absorption and cyclic voltammetry analysis. (c) 2013 Elsevier B.V. All rights reserved.

Three-Dimensional Study of Natural Convection in a Horizontal Channel With Discrete Heaters on One of Its Vertical Walls

Three-dimensional natural convection in a horizontal channel with an array of discrete flush-mounted heaters on one of its vertical walls is numerically studied. Effects of thermal conductivities of substrate and heaters and convection on outer sides of the channel walls on heat transfer are examined. The substrate affects heat transfer in a wider range of thermal conductivities than do the heaters. At lower heater thermal conductivities a higher heat portion is transferred by direct convection from the heaters to the adjacent coolant. However, higher substrate conductivity is associated with higher heat portion transferred through the substrate. The innermost heater column is found to become the hottest heater column due to the lower coolant accessibility. The heat transfer in the channel is strongly influenced by convection on the outer sides of the channel walls. Correlations are presented for dimensionless temperature maximum and average Nusselt number.

Large-Scale Elastic Net Regularized Linear Classification SVMs and Logistic Regression

Elastic Net Regularizers have shown much promise in designing sparse classifiers for linear classification. In this work, we propose an alternating optimization approach to solve the dual problems of elastic net regularized linear classification Support Vector Machines (SVMs) and logistic regression (LR). One of the sub-problems turns out to be a simple projection. The other sub-problem can be solved using dual coordinate descent methods developed for non-sparse L2-regularized linear SVMs and LR, without altering their iteration complexity and convergence properties. Experiments on very large datasets indicate that the proposed dual coordinate descent - projection (DCD-P) methods are fast and achieve comparable generalization performance after the first pass through the data, with extremely sparse models.

Cubic Sieve Congruence of the Discrete Logarithm Problem, and fractional part sequences

The Cubic Sieve Method for solving the Discrete Logarithm Problem in prime fields requires a nontrivial solution to the Cubic Sieve Congruence (CSC) x(3) equivalent to y(2)z (mod p), where p is a given prime number. A nontrivial solution must also satisfy x(3) not equal y(2)z and 1 <= x, y, z < p(alpha), where alpha is a given real number such that 1/3 < alpha <= 1/2. The CSC problem is to find an efficient algorithm to obtain a nontrivial solution to CSC. CSC can be parametrized as x equivalent to v(2)z (mod p) and y equivalent to v(3)z (mod p). In this paper, we give a deterministic polynomial-time (O(ln(3) p) bit-operations) algorithm to determine, for a given v, a nontrivial solution to CSC, if one exists. Previously it took (O) over tilde (p(alpha)) time in the worst case to determine this. We relate the CSC problem to the gap problem of fractional part sequences, where we need to determine the non-negative integers N satisfying the fractional part inequality {theta N} < phi (theta and phi are given real numbers). The correspondence between the CSC problem and the gap problem is that determining the parameter z in the former problem corresponds to determining N in the latter problem. We also show in the alpha = 1/2 case of CSC that for a certain class of primes the CSC problem can be solved deterministically in <(O)over tilde>(p(1/3)) time compared to the previous best of (O) over tilde (p(1/2)). It is empirically observed that about one out of three primes is covered by the above class. (C) 2013 Elsevier B.V. All rights reserved.