Mass Spectrometry-Based Systems Approach for Identification of Inhibitors of Plasmodium falciparum Fatty Acid Synthase{triangledown}

The emergence of strains of Plasmodium falciparum resistant to the commonly used antimalarials warrants the development of new antimalarial agents. The discovery of type II fatty acid synthase (FAS) in Plasmodium distinct from the FAS in its human host (type I FAS) opened up new avenues for the development of novel antimalarials. The process of fatty acid synthesis takes place by iterative elongation of butyryl-acyl carrier protein (butyryl-ACP) by two carbon units, with the successive action of four enzymes constituting the elongation module of FAS until the desired acyl length is obtained. The study of the fatty acid synthesis machinery of the parasite inside the red blood cell culture has always been a challenging task. Here, we report the in vitro reconstitution of the elongation module of the FAS of malaria parasite involving all four enzymes, FabB/F (β-ketoacyl-ACP synthase), FabG (β-ketoacyl-ACP reductase), FabZ (β-ketoacyl-ACP dehydratase), and FabI (enoyl-ACP reductase), and its analysis by matrix-assisted laser desorption-time of flight mass spectrometry (MALDI-TOF MS). That this in vitro systems approach completely mimics the in vivo machinery is confirmed by the distribution of acyl products. Using known inhibitors of the enzymes of the elongation module, cerulenin, triclosan, NAS-21/91, and (–)-catechin gallate, we demonstrate that accumulation of intermediates resulting from the inhibition of any of the enzymes can be unambiguously followed by MALDI-TOF MS. Thus, this work not only offers a powerful tool for easier and faster throughput screening of inhibitors but also allows for the study of the biochemical properties of the FAS pathway of the malaria parasite.

Mass Spectrometry-Based Systems Approach for Identification of Inhibitors of Plasmodium falciparum Fatty Acid Synthase{triangledown}

The emergence of strains of Plasmodium falciparum resistant to the commonly used antimalarials warrants the development of new antimalarial agents. The discovery of type II fatty acid synthase (FAS) in Plasmodium distinct from the FAS in its human host (type I FAS) opened up new avenues for the development of novel antimalarials. The process of fatty acid synthesis takes place by iterative elongation of butyryl-acyl carrier protein (butyryl-ACP) by two carbon units, with the successive action of four enzymes constituting the elongation module of FAS until the desired acyl length is obtained. The study of the fatty acid synthesis machinery of the parasite inside the red blood cell culture has always been a challenging task. Here, we report the in vitro reconstitution of the elongation module of the FAS of malaria parasite involving all four enzymes, FabB/F (β-ketoacyl-ACP synthase), FabG (β-ketoacyl-ACP reductase), FabZ (β-ketoacyl-ACP dehydratase), and FabI (enoyl-ACP reductase), and its analysis by matrix-assisted laser desorption-time of flight mass spectrometry (MALDI-TOF MS). That this in vitro systems approach completely mimics the in vivo machinery is confirmed by the distribution of acyl products. Using known inhibitors of the enzymes of the elongation module, cerulenin, triclosan, NAS-21/91, and (–)-catechin gallate, we demonstrate that accumulation of intermediates resulting from the inhibition of any of the enzymes can be unambiguously followed by MALDI-TOF MS. Thus, this work not only offers a powerful tool for easier and faster throughput screening of inhibitors but also allows for the study of the biochemical properties of the FAS pathway of the malaria parasite.

Biological and materials properties of various cholesterol based systems

Liposomes composed of cationic lipids have become very popular gene delivery vehicles. A great deal of research is being pursued to make efficient vectors by varying their molecular architecture. Cholesterol being ubiquitous component in most of the animal cell membranes is increasingly being used as a hydrophobic segment of synthetic cationic lipids. In this review we describe various cholesterol based cationic lipids and focus on the effect of modifying various structural segments like linker and the head group of the cationic lipids on gene transfection efficiency with a special emphasis on the importance of ether linkage between cholesteryl backbone and the polar head group. Interaction of cationic cholesteryl lipids with dipalmitylphosphatidycholine membranes is also discussed here. Apart from cholesterol being an attractive scaffold in the drug/gene delivery vehicles, certain cholesteryl derivatives have also been shown to be attractive room temperature liquid-crystalline materials.

Representation of evidence: An approach to uncertainty handling in knowledge-based systems

Many knowledge based systems (KBS) transform a situation information into an appropriate decision using an in built knowledge base. As the knowledge in real world situation is often uncertain, the degree of truth of a proposition provides a measure of uncertainty in the underlying knowledge. This uncertainty can be evaluated by collecting `evidence' about the truth or falsehood of the proposition from multiple sources. In this paper we propose a simple framework for representing uncertainty in using the notion of an evidence space.

Fuzzy Logic-Based Approaches in Water Resource System Modelling

Recent research in modelling uncertainty in water resource systems has highlighted the use of fuzzy logic-based approaches. A number of research contributions exist in the literature that deal with uncertainty in water resource systems including fuzziness, subjectivity, imprecision and lack of adequate data. This chapter presents a broad overview of the fuzzy logic-based approaches adopted in addressing uncertainty in water resource systems modelling. Applications of fuzzy rule-based systems and fuzzy optimisation are then discussed. Perspectives on the scope for further research are presented.

A Microprocessor-Based Scheme for Testing Protective Relays

This paper presents a general hardware scheme for testing protective relays using microprocessor based systems. The microprocessor simulates the relaying signals for test purpose and monitors the relay performance. Based on the proposed hardware, a teat procedure for directional overcurrent relays is presented in detail. Typical test results of various routine tests conducted on a commercial single phase directional over-current relay clearly demonstrate the efficacy of the proposed technique for conducting tests on commercial relays.

A questioning based method to automatically acquire expert assembly diagnostic knowledge

In the domain of manual mechanical assembly, expert knowledge is an important means of supporting assembly planning that leads to fewer issues during actual assembly. Knowledge based systems can be used to provide assembly planners with expert knowledge as advice. However, acquisition of knowledge remains a difficult task to automate, while manual acquisition is tedious, time-consuming, and requires engagement of knowledge engineers with specialist knowledge to understand and translate expert knowledge. This paper describes the development, implementation and preliminary evaluation of a method that asks a series of questions to an expert, so as to automatically acquire necessary diagnostic and remedial knowledge as rules for use in a knowledge based system for advising assembly planners diagnose and resolve issues. The method, called a questioning procedure, organizes its questions around an assembly situation which it presents to the expert as the context, and adapts its questions based on the answers it receives from the expert. (C) 2014 Elsevier Ltd. All rights reserved.

Linear filtering in DCT IV/DST IV and MDCT/MDST domain

In this paper, expressions for convolution multiplication properties of DCT IV and DST IV are derived starting from equivalent DFT representations. Using these expressions methods for implementing linear filtering through block convolution in the DCT IV and DST IV domain are proposed. Techniques developed for DCT IV and DST IV are further extended to MDCT and MDST where the filter implementation is near exact for symmetric filters and approximate for non-symmetric filters. No additional overlapping is required for implementing the symmetric filtering in the MDCT domain and hence the proposed algorithm is computationally competitive with DFT based systems. Moreover, inherent 50% overlap between the adjacent frames used for MDCT/MDST domain reduces the blocking artifacts due to block processing or quantization. The techniques are computationally efficient for symmetric filters and provides a new alternative to DFT based convolution.

Charge transport in transparent conductors: A comparison

A comparative investigation of charge transport properties is presented, for polymeric [poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)], single-wall carbon nanotube (SWNT) and inorganic (indium tin oxide, ITO), transparent conducting electrodes. The polymeric and nanotube systems show hopping transport at low temperatures, in contrast with the disordered-metal transport in ITO. The low temperature magnetotransport (up to 11 T) and high electric-field transport (up to 500 V/cm) indicate the significant role of nanoscopic scale disorder for charge transport in polymer and nanotube based systems. The results show that characteristic length scales like localization length correlates with the nanomorphology in these systems. Further, the high frequency conductivity measurements (up to 30 MHz) in PEDOT:PSS and SWNT follow the extended pair approximation model [σ(ω)=σ(0)[1+(ω/ω0)s].

ICI-ISI mitigation in cooperative SFBC-OFDM with carrier frequency offset

Synchronization issues pose a big challenge in cooperative communications. The benefits of cooperative diversity could be easily undone by improper synchronization. The problem arises because it would be difficult, from a complexity perspective, for multiple transmitting nodes to synchronize to a single receiver. For OFDM based systems, loss of performance due to imperfect carrier synchronization is severe, since it results in inter-carrier interference (ICI). The use of space-time/space-frequency codes from orthogonal designs are attractive for cooperative encoding. But orthogonal designs suffer from inter-symbol interference (ISI) due to the violation of quasi-static assumption, which can arise due to frequency- or time-selectivity of the channel. In this paper, we are concerned with combating the effects of i) ICI induced by carrier frequency offsets (CFO), and ii) ISI induced by frequency selectivity of the channel, in a cooperative communication scheme using space-frequency block coded (SFBC) OFDM. Specifically, we present an iterative interference cancellation (IC) algorithm to combat the ISI and ICI effects. The proposed algorithm could be applied to any orthogonal or quasi-orthogonal designs in cooperative SFBC OFDM schemes.

Decision support requirements for intelligent operation of southern grid in India

Control centers (CC) play a very important role in power system operation. An overall view of the system with information about all existing resources and needs is implemented through SCADA (Supervisory control and data acquisition system) and an EMS (energy management system). As advanced technologies have made their way into the utility environment, the operators are flooded with huge amount of data. The last decade has seen extensive applications of AI techniques, knowledge-based systems, Artificial Neural Networks in this area. This paper focuses on the need for development of an intelligent decision support system to assist the operator in making proper decisions. The requirements for realization of such a system are recognized for the effective operation and energy management of the southern grid in India The application of Petri nets leading to decision support system has been illustrated considering 24 bus system that is a part of southern grid.

Foaming of slags under dynamic conditions

Slag foaming under dynamic conditions has been studied in laboratory scale to examine the influence of properties commonly used to describe the foaminess and foam stability of slags under steady-state conditions. Synthetically produced slags with compositions relevant to tool steel and stainless steel production were studied through X-ray equipment in measurements simulating the dynamic conditions found in real processes. It is found that the dynamic systems display a more complex behavior than systems Under steady state. Traditional theories for foaming do not seem to be valid for slag foaming under dynamic conditions. The foam displays a fluctuating behavior, which the presently available models are not able to take into account. The concept of a foaming index does not seem to be applicable, resulting in the need for alternative models.

Synthesis, Structure and Optical Studies of a Family of Three-Dimensional Rare-Earth Aminoisophthalates M(mu(2)-OH)(C8H5NO4)] (M = Y3+, La3+, Pr3+, Nd3+, Sm3+, Eu3+, Gd3+, Dy3+, and Er3+)

A hydrothermal reaction of the acetate salts of the rare-earths, 5-aminoisophthalic acid (H(2)AIP), and NaOH at 150 degrees C for 3 days gave rise to a new family of three-dimensional rare-earth aminoisophthalates, M(mu(2)-OH)(C8H5NO4)] M = Y3+ (I), La3+ (II), Pr3+ (III), Nd3+ (IV), Sm3+ (V), Eu3+ (VI), Gd3+ (VII), Dy3+ (VIII), and Er3+ (IX)]. The structures contain M-O(H)-M chains connected by AIP anions. The AIP ions are connected to five metal centers and each metal center is connected with five AIP anions giving rise to a unique (5,5) net. To the best of our knowledge, this is the first observation of a (5,5) net in metal-organic frameworks that involve rare-earth elements. The doping of Eu3+/(3+) ions in place of Y3+/ La3+ in the parent structures gave rise to characteristic metal-centered emission (red = Eu3+, green = Tb3+). Life-time studies indicated that the excited emission states in the case of Eu3+ (4 mol-% doped) are in the range 0.287-0.490 ms and for Tb3+ (4 mol-% doped) are in the range of 1.265-1.702 ms. The Nd3+-containing compound exhibits up-conversion behavior based on two-photon absorption when excited using lambda = 580 nm.

Model-theoretic approach to clustering

The paper deals with a model-theoretic approach to clustering. The approach can be used to generate cluster description based on knowledge alone. Such a process of generating descriptions would be extremely useful in clustering partially specified objects. A natural byproduct of the proposed approach is that missing values of attributes of an object can be estimated with ease in a meaningful fashion. An important feature of the approach is that noisy objects can be detected effectively, leading to the formation of natural groups. The proposed algorithm is applied to a library database consisting of a collection of books.

A Strategy for Conserving the Biodiversity of the Uttara Kannada District in South India

Taking the various values ascribed to biodiversity as its point of departure rather many years ago, the present study aims at deriving a conservation strategy for Uttara Kannada. This hilly district, with the highest proportion of its area under forests in South India, is divided into five ecological zones: coastal, northern evergreen, southern evergreen, moist deciduous, and dry deciduous. The heavily-populated coastal zone includes mangrove forests and estuarine wetlands. The evergreen forests are particularly rich in the diversity of plant species which they support - including wild relatives of a number of cultivated plants. They also serve a vital function in watershed conservation. The moist deciduous forests are rich in bird species; both moist and dry deciduous forests include a number of freshwater ponds and lakes that support a high diversity of aquatic birds.Reviewing the overall distribution of biodiversity, we identify specific localities - including estuaries, evergreen forests, and moist deciduous forests - which should be set aside as Nature reserves. These larger reserves must be complemented by a network of traditionally-protected sacred groves and sacred trees that are distributed throughout the district and that protect today, for instance, the finest surviving stand of dipterocarp trees.We also spell out the necessary policy-changes in overall development strategy that should stem the ongoing decimation of biodiversity. These include (1) revitalizing community-based systems of sustainable management of village forests and protection of sacred groves and trees; (2) reorienting the usage-pattern of reserve forests from production of a limited variety of timber and softwood species for industrial consumers, to production of a larger diversity of non-wood forest produce of commercial value to support the rural economy; (3) utilizing marginal lands under private ownership for generating industrial wood supplies; and (4) provision of incentives for in situ maintenance of land-races of cultivated plants - especially evergreen, fruit-yielding trees - by the local people.It is proposed that this broad framework be now taken to the local communities, and that an action-plan be developed on the basis of inputs provided - and initiatives taken - by them.