Pattern recognition and cellular immune responses to novel Mycobacterium tuberculosis-antigens in individuals from Belarus

Background: Tuberculosis (TB) is an enduring health problem worldwide and the emerging threat of multidrug resistant (MDR) TB and extensively drug resistant (XDR) TB is of particular concern. A better understanding of biomarkers associated with TB will aid to guide the development of better targets for TB diagnosis and for the development of improved TB vaccines. Methods: Recombinant proteins (n = 7) and peptide pools (n = 14) from M. tuberculosis (M.tb) antigens associated with M.tb pathogenicity, modification of cell lipids or cellular metabolism, were used to compare T cell immune responses defined by IFN-gamma production using a whole blood assay (WBA) from i) patients with TB, ii) individuals recovered from TB and iii) individuals exposed to TB without evidence of clinical TB infection from Minsk, Belarus. Results: We identified differences in M.tb target peptide recognition between the test groups, i.e. a frequent recognition of antigens associated with lipid metabolism, e.g. cyclopropane fatty acyl phospholipid synthase. The pattern of peptide recognition was broader in blood from healthy individuals and those recovered from TB as compared to individuals suffering from pulmonary TB. Detection of biologically relevant M.tb targets was confirmed by staining for intracellular cytokines (IL-2, TNF-alpha and IFN-gamma) in T cells from non-human primates (NHPs) after BCG vaccination. Conclusions: PBMCs from healthy individuals and those recovered from TB recognized a broader spectrum of M.tb antigens as compared to patients with TB. The nature of the pattern recognition of a broad panel of M.tb antigens will devise better strategies to identify improved diagnostics gauging previous exposure to M.tb; it may also guide the development of improved TB-vaccines.

PAMAM Dendrimer-Drug Interactions: Effect of pH on the Binding and Release Pattern

Understanding the dendrimer-drug interaction is of great importance to design and optimize the dendrimer-based drug delivery system. Using atomistic molecular dynamics (MD) simulations, we have analyzed the release pattern of four ligands (two soluble drugs, namely, salicylic acid (Sal), L-alanine (Ala), and two insoluble drugs, namely, phenylbutazone (Pbz) and primidone (Prim)), which were initially encapsulated inside the ethylenediamine (EDA) cored polyamidoamine (PAMAM) dendrimer using the docking method. We have computed the potential of mean force (PMF) variation with generation 5 (G5)-PAMAM dendrimer complexed with drug molecules using umbrella sampling. From our calculated PMF values, we observe that soluble drugs (Sal and Ala) have lower energy barriers than insoluble drugs (Pbz and Prim). The order of ease of release pattern for these drugs from G5 protonated PAMAM dendrimer was found to be Ala > Sal > Prim > Pbz. In the case of insoluble drugs (Prim and Pbz), because of larger size, we observe much nonpolar contribution, and thus, their larger energy barriers can be reasoned to van der Waals contribution. From the hydrogen bonding analysis of the four PAMAM drug complexes under study, we found intermolecular hydrogen bonding to show less significant contribution to the free energy barrier. Another interesting feature appears while calculating the PMF profile of G5NP (nonprotonated)-PAMAM Pbz and G5NP (nonprotonated)-PAMAM-Sal complex. The PMF was found to be less when the drug is bound to nonprotonated dendrimer compared to the protonated dendrimer. Our results suggest that encapsulation of the drug molecule into the host PAMAM dendrimer should be carried out at higher pH values (near pH 10). When such complex enters the human body, the pH is around 7.4 and at that physiological pH, the dendrimer holds the drug tightly. Hence the release of drug can occur at a controlled rate into the bloodstream. Thus, our findings provide a microscopic picture of the encapsulation and controlled release of drugs in the case of dendrimer-based host-guest systems.

Insights to urban dynamics through landscape spatial pattern analysis

Urbanisation is a dynamic complex phenomenon involving large scale changes in the land uses at local levels. Analyses of changes in land uses in urban environments provide a historical perspective of land use and give an opportunity to assess the spatial patterns, correlation, trends, rate and impacts of the change, which would help in better regional planning and good governance of the region. Main objective of this research is to quantify the urban dynamics using temporal remote sensing data with the help of well-established landscape metrics. Bangalore being one of the rapidly urbanising landscapes in India has been chosen for this investigation. Complex process of urban sprawl was modelled using spatio temporal analysis. Land use analyses show 584% growth in built-up area during the last four decades with the decline of vegetation by 66% and water bodies by 74%. Analyses of the temporal data reveals an increase in urban built up area of 342.83% (during 1973-1992), 129.56% (during 1992-1999), 106.7% (1999-2002), 114.51% (2002-2006) and 126.19% from 2006 to 2010. The Study area was divided into four zones and each zone is further divided into 17 concentric circles of 1 km incrementing radius to understand the patterns and extent of the urbanisation at local levels. The urban density gradient illustrates radial pattern of urbanisation for the period 1973-2010. Bangalore grew radially from 1973 to 2010 indicating that the urbanisation is intensifying from the central core and has reached the periphery of the Greater Bangalore. Shannon's entropy, alpha and beta population densities were computed to understand the level of urbanisation at local levels. Shannon's entropy values of recent time confirms dispersed haphazard urban growth in the city, particularly in the outskirts of the city. This also illustrates the extent of influence of drivers of urbanisation in various directions. Landscape metrics provided in depth knowledge about the sprawl. Principal component analysis helped in prioritizing the metrics for detailed analyses. The results clearly indicates that whole landscape is aggregating to a large patch in 2010 as compared to earlier years which was dominated by several small patches. The large scale conversion of small patches to large single patch can be seen from 2006 to 2010. In the year 2010 patches are maximally aggregated indicating that the city is becoming more compact and more urbanised in recent years. Bangalore was the most sought after destination for its climatic condition and the availability of various facilities (land availability, economy, political factors) compared to other cities. The growth into a single urban patch can be attributed to rapid urbanisation coupled with the industrialisation. Monitoring of growth through landscape metrics helps to maintain and manage the natural resources. (C) 2012 Elsevier B.V. All rights reserved.

Dung as a potential medium for inter-sexual chemical signaling in Asian elephants (Elephas maximus)

Chemical signaling is a prominent mode of male-female communication among elephants, especially during their sexually active periods. Studies on the Asian elephant in zoos have shown the significance of a urinary pheromone (Z7-12:Ac) in conveying the reproductive status of a female toward the opposite sex. We investigated the additional possibility of an inter-sexual chemical signal being conveyed through dung. Sixteen semi-captive adult male elephants were presented with dung samples of three female elephants in different reproductive phases. Each male was tested in 3 separate trials, within an interval of 1-3 days. The trials followed a double-blind pattern as the male and female elephants used in the trials were strangers, and the observer was not aware of the reproductive status of females during the period of bioassays. Males responded preferentially (P < 0.005), in terms of higher frequency of sniff, check and place behavior toward the dung of females close to pre-ovulatory period (follicular-phase) as compared to those in post-ovulatory period (luteal-phase). The response toward the follicular phase samples declined over repeated trials though was still significantly higher than the corresponding response toward the non-ovulatory phase in each of the trials performed. This is the first study to show that male Asian elephants were able to distinguish the reproductive phase of the female by possibly detecting a pre-ovulatory pheromone released in dung. (C) 2012 Elsevier B.V. All rights reserved.

A study of epileptogenic network structures in rat hippocampal cultures using first spike latencies during synchronization events

Study of hypersynchronous activity is of prime importance for combating epilepsy. Studies on network structure typically reconstruct the network by measuring various aspects of the interaction between neurons and subsequently measure the properties of the reconstructed network. In sub-sampled networks such methods lead to significant errors in reconstruction. Using rat hippocampal neurons cultured on a multi-electrode array dish and a glutamate injury model of epilepsy in vitro, we studied synchronous activity in neuronal networks. Using the first spike latencies in various neurons during a network burst, we extract various recurring spatio-temporal onset patterns in the networks. Comparing the patterns seen in control and injured networks, we observe that injured networks express a wide diversity in their foci (origin) and activation pattern, while control networks show limited diversity. Furthermore, we note that onset patterns in glutamate injured networks show a positive correlation between synchronization delay and physical distance between neurons, while control networks do not.

Suite of tools for statistical N-gram language modeling for pattern mining in whole genome sequences

Genome sequences contain a number of patterns that have biomedical significance. Repetitive sequences of various kinds are a primary component of most of the genomic sequence patterns. We extended the suffix-array based Biological Language Modeling Toolkit to compute n-gram frequencies as well as n-gram language-model based perplexity in windows over the whole genome sequence to find biologically relevant patterns. We present the suite of tools and their application for analysis on whole human genome sequence.

A study of epileptogenic network structures in rat hippocampal cultures using first spike latencies during synchronization events

Study of hypersynchronous activity is of prime importance for combating epilepsy. Studies on network structure typically reconstruct the network by measuring various aspects of the interaction between neurons and subsequently measure the properties of the reconstructed network. In sub-sampled networks such methods lead to significant errors in reconstruction. Using rat hippocampal neurons cultured on a multi-electrode array dish and a glutamate injury model of epilepsy in vitro, we studied synchronous activity in neuronal networks. Using the first spike latencies in various neurons during a network burst, we extract various recurring spatio-temporal onset patterns in the networks. Comparing the patterns seen in control and injured networks, we observe that injured networks express a wide diversity in their foci (origin) and activation pattern, while control networks show limited diversity. Furthermore, we note that onset patterns in glutamate injured networks show a positive correlation between synchronization delay and physical distance between neurons, while control networks do not.

Spatial Modulation and Space Shift Keying in Single Carrier Communication

Spatial modulation (SM) and space shift keying (SSK) are relatively new modulation techniques which are attractive in multi-antenna communications. Single carrier (SC) systems can avoid the peak-to-average power ratio (PAPR) problem encountered in multicarrier systems. In this paper, we study SM and SSK signaling in cyclic-prefixed SC (CPSC) systems on MIMO-ISI channels. We present a diversity analysis of MIMO-CPSC systems under SSK and SM signaling. Our analysis shows that the diversity order achieved by (n(t), n(r)) SSK scheme and (n(t), n(r), Theta(M)) SM scheme in MIMO-CPSC systems under maximum-likelihood (ML) detection is n(r), where n(t), n(r) denote the number of transmit and receive antennas and Theta(M) denotes the modulation alphabet of size M. Bit error rate (BER) simulation results validate this predicted diversity order. Simulation results also show that MIMO-CPSC with SM and SSK achieves much better performance than MIMO-OFDM with SM and SSK.

Increasing System Capacity in Uplink Multiuser MIMO Using Sparsity Exploiting Receiver

In multiuser communication on the uplink, all subscribed users may not be active simultaneously. This leads to sparsity in the activity pattern in the users' transmissions, which can be exploited in the multiuser MIMO receiver at the base station (BS). Because of no transmissions from inactive users, joint detection at the BS has to consider an augmented signal set that includes zero. In this paper, we propose a receiver that exploits this inactivity-induced sparsity and considers the zero-augmented signal set. The proposed receiver is based on Markov Chain Monte Carlo techniques. Near-optimal performance and increased system capacity (in terms of number of users in the system) are demonstrated. For example, a multiuser MIMO system with N = 32 receive antennas at the BS and an user activity factor of 0.2 supports 51 uplink users meeting a QoS of 10(-3) coded bit error rate.

Review of Geohazard Warning Systems toward Development of a Popular Usage Geohazard Warning Communication System

The advent and evolution of geohazard warning systems is a very interesting study. The two broad fields that are immediately visible are that of geohazard evaluation and subsequent warning dissemination. Evidently, the latter field lacks any systematic study or standards. Arbitrarily organized and vague data and information on warning techniques create confusion and indecision. The purpose of this review is to try and systematize the available bulk of information on warning systems so that meaningful insights can be derived through decidable flowcharts, and a developmental process can be undertaken. Hence, the methods and technologies for numerous geohazard warning systems have been assessed by putting them into suitable categories for better understanding of possible ways to analyze their efficacy as well as shortcomings. By establishing a classification scheme based on extent, control, time period, and advancements in technology, the geohazard warning systems available in any literature could be comprehensively analyzed and evaluated. Although major advancements have taken place in geohazard warning systems in recent times, they have been lacking a complete purpose. Some systems just assess the hazard and wait for other means to communicate, and some are designed only for communication and wait for the hazard information to be provided, which usually is after the mishap. Primarily, systems are left at the mercy of administrators and service providers and are not in real time. An integrated hazard evaluation and warning dissemination system could solve this problem. Warning systems have also suffered from complexity of nature, requirement of expert-level monitoring, extensive and dedicated infrastructural setups, and so on. The user community, which would greatly appreciate having a convenient, fast, and generalized warning methodology, is surveyed in this review. The review concludes with the future scope of research in the field of hazard warning systems and some suggestions for developing an efficient mechanism toward the development of an automated integrated geohazard warning system. DOI: 10.1061/(ASCE)NH.1527-6996.0000078. (C) 2012 American Society of Civil Engineers.

Pattern clustering using cooperative game theory

In this paper, we approach the classical problem of clustering using solution concepts from cooperative game theory such as Nucleolus and Shapley value. We formulate the problem of clustering as a characteristic form game and develop a novel algorithm DRAC (Density-Restricted Agglomerative Clustering) for clustering. With extensive experimentation on standard data sets, we compare the performance of DRAC with that of well known algorithms. We show an interesting result that four prominent solution concepts, Nucleolus, Shapley value, Gately point and \tau-value coincide for the defined characteristic form game. This vindicates the choice of the characteristic function of the clustering game and also provides strong intuitive foundation for our approach.

Efficient Regular Expression Pattern Matching for Network Intrusion Detection Systems using Modified Word-based Automata

Network Intrusion Detection Systems (NIDS) intercept the traffic at an organization's network periphery to thwart intrusion attempts. Signature-based NIDS compares the intercepted packets against its database of known vulnerabilities and malware signatures to detect such cyber attacks. These signatures are represented using Regular Expressions (REs) and strings. Regular Expressions, because of their higher expressive power, are preferred over simple strings to write these signatures. We present Cascaded Automata Architecture to perform memory efficient Regular Expression pattern matching using existing string matching solutions. The proposed architecture performs two stage Regular Expression pattern matching. We replace the substring and character class components of the Regular Expression with new symbols. We address the challenges involved in this approach. We augment the Word-based Automata, obtained from the re-written Regular Expressions, with counter-based states and length bound transitions to perform Regular Expression pattern matching. We evaluated our architecture on Regular Expressions taken from Snort rulesets. We were able to reduce the number of automata states between 50% to 85%. Additionally, we could reduce the number of transitions by a factor of 3 leading to further reduction in the memory requirements.

Multiple transmitter localization and communication footprint identification using sparse reconstruction techniques

This paper considers the problem of identifying the footprints of communication of multiple transmitters in a given geographical area. To do this, a number of sensors are deployed at arbitrary but known locations in the area, and their individual decisions regarding the presence or absence of the transmitters' signal are combined at a fusion center to reconstruct the spatial spectral usage map. One straightforward scheme to construct this map is to query each of the sensors and cluster the sensors that detect the primary's signal. However, using the fact that a typical transmitter footprint map is a sparse image, two novel compressive sensing based schemes are proposed, which require significantly fewer number of transmissions compared to the querying scheme. A key feature of the proposed schemes is that the measurement matrix is constructed from a pseudo-random binary phase shift applied to the decision of each sensor prior to transmission. The measurement matrix is thus a binary ensemble which satisfies the restricted isometry property. The number of measurements needed for accurate footprint reconstruction is determined using compressive sampling theory. The three schemes are compared through simulations in terms of a performance measure that quantifies the accuracy of the reconstructed spatial spectral usage map. It is found that the proposed sparse reconstruction technique-based schemes significantly outperform the round-robin scheme.