Emerging trends at the interface of chemistry and biology: Applications to the design of human therapeutics

This article describes recent developments in the design and implementation of various strategies towards the development of novel therapeutics using first principles from biology and chemistry. Strategies for multi-target therapeutics and network analysis with a focus on cancer and HIV are discussed. Methods for gene and siRNA delivery are presented along with challenges and opportunities for siRNA therapeutics. Advances in protein design methodology and screening are described, with a focus on their application to the design of antibody based therapeutics. Future advances in this area relevant to vaccine design are also mentioned.

Fracture behavior of concrete–concrete interface using acoustic emission technique

The fracture behavior of concrete–concrete interface is characterized using acoustic emission (AE). Beams of different sizes having jointed interface between two different strengths of concrete are tested. The results of load, displacement, CMOD, AE-events and AE-energy are analyzed. The width of fracture process zone and damage zone are computed using AE-data and are found to be independent of size. It is observed that, as the difference in compressive strength of concrete on either side of interface increases, the load carrying capacity, number of AE-events, AE-energy, width of fracture process zone and damage zone decreases.

Dynamic programming based optimum non-uniform samples for speech reconstruction and coding

Non-uniform sampling of a signal is formulated as an optimization problem which minimizes the reconstruction signal error. Dynamic programming (DP) has been used to solve this problem efficiently for a finite duration signal. Further, the optimum samples are quantized to realize a speech coder. The quantizer and the DP based optimum search for non-uniform samples (DP-NUS) can be combined in a closed-loop manner, which provides distinct advantage over the open-loop formulation. The DP-NUS formulation provides a useful control over the trade-off between bitrate and performance (reconstruction error). It is shown that 5-10 dB SNR improvement is possible using DP-NUS compared to extrema sampling approach. In addition, the close-loop DP-NUS gives a 4-5 dB improvement in reconstruction error.

A generalized Linear Programming based approach to optimal divisible load scheduling

In this paper we propose a general Linear Programming (LP) based formulation and solution methodology for obtaining optimal solution to the load distribution problem in divisible load scheduling. We exploit the power of the versatile LP formulation to propose algorithms that yield exact solutions to several very general load distribution problems for which either no solutions or only heuristic solutions were available. We consider both star (single-level tree) networks and linear daisy chain networks, having processors equipped with front-ends, that form the generic models for several important network topologies. We consider arbitrary processing node availability or release times and general models for communication delays and computation time that account for constant overheads such as start up times in communication and computation. The optimality of the LP based algorithms is proved rigorously.

Protein Block Expert (PBE): a web-based protein structure analysis server using a structural alphabet

Encoding protein 3D structures into 1D string using short structural prototypes or structural alphabets opens a new front for structure comparison and analysis. Using the well-documented 16 motifs of Protein Blocks (PBs) as structural alphabet, we have developed a methodology to compare protein structures that are encoded as sequences of PBs by aligning them using dynamic programming which uses a substitution matrix for PBs. This methodology is implemented in the applications available in Protein Block Expert (PBE) server. PBE addresses common issues in the field of protein structure analysis such as comparison of proteins structures and identification of protein structures in structural databanks that resemble a given structure. PBE-T provides facility to transform any PDB file into sequences of PBs. PBE-ALIGNc performs comparison of two protein structures based on the alignment of their corresponding PB sequences. PBE-ALIGNm is a facility for mining SCOP database for similar structures based on the alignment of PBs. Besides, PBE provides an interface to a database (PBE-SAdb) of preprocessed PB sequences from SCOP culled at 95% and of all-against-all pairwise PB alignments at family and superfamily levels. PBE server is freely available at http://bioinformatics.univ-reunion.fr/ PBE/.

Second order cone programming approaches for handling missing and uncertain data

We propose a novel second order cone programming formulation for designing robust classifiers which can handle uncertainty in observations. Similar formulations are also derived for designing regression functions which are robust to uncertainties in the regression setting. The proposed formulations are independent of the underlying distribution, requiring only the existence of second order moments. These formulations are then specialized to the case of missing values in observations for both classification and regression problems. Experiments show that the proposed formulations outperform imputation.

A mathematical programming approach to optimal Markovian switching of Poisson arrival streams to queueing systems

Motivated by certain situations in manufacturing systems and communication networks, we look into the problem of maximizing the profit in a queueing system with linear reward and cost structure and having a choice of selecting the streams of Poisson arrivals according to an independent Markov chain. We view the system as a MMPP/GI/1 queue and seek to maximize the profits by optimally choosing the stationary probabilities of the modulating Markov chain. We consider two formulations of the optimization problem. The first one (which we call the PUT problem) seeks to maximize the profit per unit time whereas the second one considers the maximization of the profit per accepted customer (the PAC problem). In each of these formulations, we explore three separate problems. In the first one, the constraints come from bounding the utilization of an infinite capacity server; in the second one the constraints arise from bounding the mean queue length of the same queue; and in the third one the finite capacity of the buffer reflect as a set of constraints. In the problems bounding the utilization factor of the queue, the solutions are given by essentially linear programs, while the problems with mean queue length constraints are linear programs if the service is exponentially distributed. The problems modeling the finite capacity queue are non-convex programs for which global maxima can be found. There is a rich relationship between the solutions of the PUT and PAC problems. In particular, the PUT solutions always make the server work at a utilization factor that is no less than that of the PAC solutions.

Communication: Evidence of dynamic heterogeneity in glassy polymer monolayers from interface microrheology measurements

We have developed a novel nanoparticle tracking based interface microrheology technique to perform in situ studies on confined complex fluids. To demonstrate the power of this technique, we show, for the first time, how in situ glass formation in polymers confined at air-water interface can be directly probed by monitoring variation of the mean square displacement of embedded nanoparticles as a function of surface density. We have further quantified the appearance of dynamic heterogeneity and hence vitrification in polymethyl methacrylate monolayers above a certain surface density, through the variation of non-Gaussian parameter of the probes. (C) 2010 American Institute of Physics. [doi:10.1063/1.3471584].

Urban ecosystem services at the plant-soil interface

Continuing urbanization is a crucial driver of land transformation, having widespread impacts on virtually all ecosystems. Terrestrial ecosystems, including disturbed ones, are dependent on soils, which provide a multitude of ecosystem services. As soils are always directly and/or indirectly impacted through land transformation, land cover change causes soil change. Knowledge of ecosystem properties and functions in soils is increasing in importance as humans continue to concentrate into already densely-populated areas. Urban soils often have hampered functioning due to various disturbances resulting from human activity. Innovative solutions are needed to bring the lacking ecosystem services and quality of life to these urban environments. For instance, the ecosystem services of the urban green infrastructure may be substantially improved through knowledge of their functional properties. In the research forming this thesis, the impacts of four plant species (Picea abies, Calluna vulgaris, Lotus corniculatus and Holcus lanatus) on belowground biota and regulatory ecosystem services were investigated in two different urban soil types. The retention of inorganic nitrogen and phosphorus in the plant-soil system, decomposition of plant litter, primary production, and the degradation of polycyclic aromatic hydrocarbons (PAHs) were examined in the field and under laboratory conditions. The main objective of the research was to determine whether the different plant species (representing traits with varying litter decomposability) will give rise to dissimilar urban belowground communities with differing ecological functions. Microbial activity as well as the abundance of nematodes and enchytraeid worm biomass was highest below the legume L. corniculatus. L. corniculatus and the grass H. lanatus, producing labile or intermediate quality litter, enhanced the proportion of bacteria in the soil rhizosphere, while the recalcitrant litter-producing shrub C. vulgaris and the conifer P. abies stimulated the growth of fungi. The loss of nitrogen from the plant-soil system was small for H. lanatus and the combination of C. vulgaris + P. abies, irrespective of their energy channel composition. These presumably nitrogen-conservative plant species effectively diminished the leaching losses from the plant-soil systems with all the plant traits present. The laboratory experiment revealed a difference in N allocation between the plant traits: C. vulgaris and P. abies sequestered significantly more N in aboveground shoots in comparison to L. corniculatus and H. Lanatus. Plant rhizosphere effects were less clear for phosphorus retention, litter decomposition and the degradation of PAH compounds. This may be due to the relatively short experimental durations, as the maturation of the plant-soil system is likely to take a considerably longer time. The empirical studies of this thesis demonstrated that the soil communities rapidly reflect changes in plant coverage, and this has consequences for the functionality of soils. The energy channel composition of soils can be manipulated through plants, which was also supported by the results of the separate meta-analysis conducted in this thesis. However, further research is needed to understand the linkages between the biological community properties and ecosystem services in strongly human-modified systems.

Nonlinear programming solutions for controlling the vibration pattern of stretched strings

The problem of controlling the vibration pattern of a driven string is considered. The basic question dealt with here is to find the control forces which reduce the energy of vibration of a driven string over a prescribed portion of its length while maintaining the energy outside that length above a desired value. The criterion of keeping the response outside the region of energy reduction as close to the original response as possible is introduced as an additional constraint. The slack unconstrained minimization technique (SLUMT) has been successfully applied to solve the above problem. The effect of varying the phase of the control forces (which results in a six-variable control problem) is then studied. The nonlinear programming techniques which have been effectively used to handle problems involving many variables and constraints therefore offer a powerful tool for the solution of vibration control problems.

Equivalent circuit parameters of the film-covered magnesium/electrolyte interface in Mg/MnO2 dry cells from transient and ac impedance measurements

The electrochemical properties of the film-covered anode/solution interface in the magnesium/ manganese dioxide dry cell have been evaluated. The most plausible electrical equivalent circuit description of the Mg/solution interface with the passive film intact, has been identified. These results are based on the analysis of ac impedance and voltage transient measurements made on the dry cell under conditions which cause no damage to the protective passive film on the anode. The study demonstrates the complementary character of impedance and transient measurements when widely different frequency ranges are sampled in each type of investigation. The values and temperature dependence of the anode-film resistance, film capacitance, double-layer capacitance and charge-transfer resistance of the film-covered magnesium/solution interface have been determined. The magnitude of these values and its implications in understanding the important performance aspects of the magnesium/manganese dioxide dry cell are discussed. The study may be extended, in principle, to Li, Al and Ca batteries.

Equivalent circuit parameters of the film-covered magnesium/electrolyte interface in Mg/MnO2 dry cells from transient and ac impedance measurements

The electrochemical properties of the film-covered anode/solution interface in the magnesium/ manganese dioxide dry cell have been evaluated. The most plausible electrical equivalent circuit description of the Mg/solution interface with the passive film intact, has been identified. These results are based on the analysis of ac impedance and voltage transient measurements made on the dry cell under conditions which cause no damage to the protective passive film on the anode. The study demonstrates the complementary character of impedance and transient measurements when widely different frequency ranges are sampled in each type of investigation. The values and temperature dependence of the anode-film resistance, film capacitance, double-layer capacitance and charge-transfer resistance of the film-covered magnesium/solution interface have been determined. The magnitude of these values and its implications in understanding the important performance aspects of the magnesium/manganese dioxide dry cell are discussed. The study may be extended, in principle, to Li, Al and Ca batteries.

Electromagnetic wave propagation at the interface between two polar semiconductors

The interface between two polar semiconductors can support three types of phonon-plasmon-polariton modes propagating in three well-defined frequency windows ??1?[min(?1,?3),?R1], ??2?[max(?2,?4),?R2], and ??3?[min(?2,?4),?R3]. The limiting frequencies ?1,2,3,4 are defined by ?1(?)=0, ?2(?)=0, and ?R1,2,3 by ?1(?)+?2(?)=0, where ?i(?) are dielectric functions of the two media with i=1,2. The dispersion, decay distances, and polarization of the three modes are discussed. The variation of the limiting frequencies with the interface plasma parameter ???p22/?p12 reveals an interesting feature in the dispersion characteristics of these modes. For the interfaces for which the bulk coupled phonon-plasmon frequencies of medium 1 are greater than the LO frequency or are less than the TO frequency of medium 2, there exist two values of ?=?1 and ?2(interface modes defined by ??1 and ??3 propagate with constant frequencies equal to the bulk coupled phonon-plasmon frequencies of medium 1, i.e., without showing any dispersion.

Ordered Ports – a Language Concept for High-level Distributed Programming

A new language concept for high-level distributed programming is proposed. Programs are organised as a collection of concurrently executing processes. Some of these processes, referred to as liaison processes, have a monitor-like structure and contain ports which may be invoked by other processes for the purposes of synchronisation and communication. Synchronisation is achieved by conditional activation of ports and also through port control constructs which may directly specify the execution ordering of ports. These constructs implement a path-expression-like mechanism for synchronisation and are also equipped with options to provide conditional, non-deterministic and priority ordering of ports. The usefulness and expressive power of the proposed concepts are illustrated through solutions of several representative programming problems. Some implementation issues are also considered.

Effects of Parasitics and Interface Traps on Ballistic Nanowire FET in the Ultimate Quantum Capacitance Limit

In this paper, we focus on the performance of a nanowire field-effect transistor in the ultimate quantum capacitance limit (UQCL) (where only one subband is occupied) in the presence of interface traps (D-it), parasitic capacitance (C-L), and source/drain series resistance (R-s,R-d), using a ballistic transport model and compare the performance with its classical capacitance limit (CCL) counterpart. We discuss four different aspects relevant to the present scenario, namely: 1) gate capacitance; 2) drain-current saturation; 3) subthreshold slope; and 4) scaling performance. To gain physical insights into these effects, we also develop a set of semianalytical equations. The key observations are as follows: 1) A strongly energy-quantized nanowire shows nonmonotonic multiple-peak C-V characteristics due to discrete contributions from individual subbands; 2) the ballistic drain current saturates better in the UQCL than in the CCL, both in the presence and absence of D-it and R-s,R-d; 3) the subthreshold slope does not suffer any relative degradation in the UQCL compared to the CCL, even with Dit and R-s,R-d; 4) the UQCL scaling outperforms the CCL in the ideal condition; and 5) the UQCL scaling is more immune to R-s,R-d, but the presence of D-it and C-L significantly degrades the scaling advantages in the UQCL.