3D QSAR studies of N-4-arylacryloylpiperazin-1-yl-phenyl-oxazolidinones: A novel class of antibacterial agents

Three-dimensional QSAR studies for N-4-arylacryloylpiperazin-1-yl-phenyl-oxazolidinones were conducted using TSAR 3.3. The in vitro activities (MICs) of the compounds against Staphylococcus aureus ATCC 25923 exhibited a strong correlation with the prediction made by the model developed in the present study.

Arabidopsis thaliana J-class heat shock proteins: cellular stress sensors

Plants are sessile organisms that have evolved a variety of mechanisms to maintain their cellular homeostasis under stressful environmental conditions. Survival of plants under abiotic stress conditions requires specialized group of heat shock protein machinery, belonging to Hsp70:J-protein family. These heat shock proteins are most ubiquitous types of chaperone machineries involved in diverse cellular processes including protein folding, translocation across cell membranes, and protein degradation. They play a crucial role in maintaining the protein homeostasis by reestablishing functional native conformations under environmental stress conditions, thus providing protection to the cell. J-proteins are co-chaperones of Hsp70 machine, which play a critical role by stimulating Hsp70s ATPase activity, thereby stabilizing its interaction with client proteins. Using genome-wide analysis of Arabidopsis thaliana, here we have outlined identification and systematic classification of J-protein co-chaperones which are key regulators of Hsp70s function. In comparison with Saccharomyces cerevisiae model system, a comprehensive domain structural organization, cellular localization, and functional diversity of A. thaliana J-proteins have also been summarized. Electronic supplementary material The online version of this article (doi:10.1007/s10142-009-0132-0) contains supplementary material, which is available to authorized users.

A potent nonporphyrin class of photodynamic therapeutic agent: Cellular localisation, cytotoxic potential and influence of hypoxia

We have developed a totally new class of nonporphyrin photodynamic therapeutic agents with a specific focus on two lead candidates azadipyrromethene (ADPM)01 and ADPM06. Confocal laser scanning microscopy imaging showed that these compounds are exclusively localised to the cytosolic compartment, with specific accumulation in the endoplasmic reticulum and to a lesser extent in the mitochondria. Light-induced toxicity assays, carried out over a broad range of human tumour cell lines, displayed EC50 values in the micro-molar range for ADPM01 and nano-molar range for ADPM06, with no discernable activity bias for a specific cell type. Strikingly, the more active agent, ADPM06, even retained significant activity under hypoxic conditions. Both photosensitisers showed low to nondeterminable dark toxicity. Flow cytometric analysis revealed that ADPM01 and ADPM06 were highly effective at inducing apoptosis as a mode of cell death. The photophysical and biological characteristics of these PDT agents suggest that they have potential for the development of new anticancer therapeutics. © 2005 Cancer Research UK.

The curvature invariant for a class of homogeneous operators

For an operator T in the class B-n(), introduced by Cowen and Douglas, the simultaneous unitary equivalence class of the curvature and the covariant derivatives up to a certain order of the corresponding bundle E-T determine the unitary equivalence class of the operator T. In a subsequent paper, the authors ask if the simultaneous unitary equivalence class of the curvature and these covariant derivatives are necessary to determine the unitary equivalence class of the operator T is an element of B-n(). Here we show that some of the covariant derivatives are necessary. Our examples consist of homogeneous operators in B-n(). For homogeneous operators, the simultaneous unitary equivalence class of the curvature and all its covariant derivatives at any point w in the unit disc are determined from the simultaneous unitary equivalence class at 0. This shows that it is enough to calculate all the invariants and compare them at just one point, say 0. These calculations are then carried out in number of examples. One of our main results is that the curvature along with its covariant derivative of order (0, 1) at 0 determines the equivalence class of generic homogeneous Hermitian holomorphic vector bundles over the unit disc.

The Noether-Lefschetz theorem for the divisor class group

Let X be a normal projective threefold over a field of characteristic zero and vertical bar L vertical bar be a base-point free, ample linear system on X. Under suitable hypotheses on (X, vertical bar L vertical bar), we prove that for a very general member Y is an element of vertical bar L vertical bar, the restriction map on divisor class groups Cl(X) -> Cl(Y) is an isomorphism. In particular, we are able to recover the classical Noether-Lefschetz theorem, that a very general hypersurface X subset of P-C(3) of degree >= 4 has Pic(X) congruent to Z.

Synthesis of new 4-isopropylthiazole hydrazide analogs and some derived clubbed triazole, oxadiazole ring systems - A novel class of potential antibacterial, antifungal and antitubercular agents

In the present study a series of 4-isopropylthiazole-2-carbohydrazide analogs, derived clubbed oxadiazole-thiazole and triazole-thiazole derivatives have been synthesized and characterized by IR, H-1 NMR, C-13 NMR, elemental and mass spectral analyses. The synthesized compounds were evaluated for their preliminary in vitro antibacterial, antifungal and antitubercular activity against Mycobacterium tuberculosis H(37)Rv strain by broth dilution assay method. The synthesized compounds 7a, 7b, 7d and 4 showed an antitubercular efficacy considerably greater than that of the parent 4-isopropyl-1,3-thiazole-2-carbohydrazide 1, suggesting that the substituted 4-isopropylthiazole-2-carbohydrazide moiety plays an important role in enhancing the antitubercular properties of this class of compounds. Compounds 2c, 3, 4, 6d, 7a and 7b exhibited good or moderate antibacterial and antifungal activity. Compounds 4 and 7b showed appreciable cytotoxicity at a concentration of 250 mu M.

Synthesis and Evaluation of a Novel Class of G-Quadruplex-Stabilizing Small Molecules Based on the 1,3-Phenylene-Bis(piperazinyl benzimidazole) System

Achieving stabilization of telomeric DNA in G-quadruplex conformation by Various organic compounds has been an important goal for the medicinal chemists seeking to develop new anticancer agents. Several compounds are known to stabilize G-quadruplexes. However, relatively few are known to induce their formation and/or alter the topology, of the preformed quadruplex DNA. Herein, four compounds having the 1,3-phenylene-bis(piperazinyl benzimidazole) unit as a basic skeleton have been synthesized, and their interactions with the 24-mer telomeric DNA sequences from Tetrahymena thermophilia d(T(2)G(4))(4) have been investigated using high-resolution techniques Such as circular dichroism (CD) spectropolarimetry, CD melting, emission spectroscopy, and polyacrylamide gel electrophoresis. The data obtained, in the presence of one of three ions (Li+, Na+, or K+), indicate that all the new compounds have a high affinity for G-quadruplex DNA, and the strength of the binding with G-quadruplex depends on (1) phenyl ring substitution, (ii) the piperazinyl side chain, and (iii) the type of monovalent cation present in the buffer. Results further Suggest that these compounds are able to abet the conversion of the Intramolecular quadruplex into parallel stranded intermolecular G-quadruplex DNA. Notably, these compounds are also capable of inducing and stabilizing the parallel stranded quadruplex from randomly structured DNA in the absence of any stabilizing cation. The kinetics of the structural changes Induced by these compounds could be followed by recording the changes in the CD signal as a function of time. The implications of the findings mentioned above are discussed in this paper.

R1STM: One-class support tensor machine with randomised kernel

Identifying unusual or anomalous patterns in an underlying dataset is an important but challenging task in many applications. The focus of the unsupervised anomaly detection literature has mostly been on vectorised data. However, many applications are more naturally described using higher-order tensor representations. Approaches that vectorise tensorial data can destroy the structural information encoded in the high-dimensional space, and lead to the problem of the curse of dimensionality. In this paper we present the first unsupervised tensorial anomaly detection method, along with a randomised version of our method. Our anomaly detection method, the One-class Support Tensor Machine (1STM), is a generalisation of conventional one-class Support Vector Machines to higher-order spaces. 1STM preserves the multiway structure of tensor data, while achieving significant improvement in accuracy and efficiency over conventional vectorised methods. We then leverage the theory of nonlinear random projections to propose the Randomised 1STM (R1STM). Our empirical analysis on several real and synthetic datasets shows that our R1STM algorithm delivers comparable or better accuracy to a state-of-the-art deep learning method and traditional kernelised approaches for anomaly detection, while being approximately 100 times faster in training and testing.

Shortcomings of discontinuous-pressure finite element methods on a class of transient problems

Past studies that have compared LBB stable discontinuous- and continuous-pressure finite element formulations on a variety of problems have concluded that both methods yield Solutions of comparable accuracy, and that the choice of interpolation is dictated by which of the two is more efficient. In this work, we show that using discontinuous-pressure interpolations can yield inaccurate solutions at large times on a class of transient problems, while the continuous-pressure formulation yields solutions that are in good agreement with the analytical Solution.

Synthesis and bioassay of a new class of heterocycles pyrrolyl oxadiazoles/thiadiazoles/triazoles

A new class of heterocycles pyrrolyl thiadiazoles, pyrrolyl oxadiazoles and pyrrolyl triazoles were prepared from arylsulfonylethenesulfonylacetic acid methyl ester and tested for their antimicrobial and cytotoxic activities. (C) 2008 Elsevier Masson SAS. All rights reserved.

Facile one-pot synthesis of thio and selenourea derivatives: A new class of potent urease inhibitors

A facile, one-pot synthesis of thio and selenourea derivatives from amines using tetrathiomolybdate 1 and tetraseleno-tungstate 2 as sulfur and selenium transfer reagents, respectively, is reported. The compounds were tested for their activity as urease inhibitors and some of the compounds showed potent activity in the nanomolar range towards jack bean urease. (C) 2007 Elsevier Ltd. All rights reserved.

Time and Energy Complexity of Distributed Computation of a Class of Functions in Wireless Sensor Networks

We consider a scenario in which a wireless sensor network is formed by randomly deploying n sensors to measure some spatial function over a field, with the objective of computing a function of the measurements and communicating it to an operator station. We restrict ourselves to the class of type-threshold functions (as defined in the work of Giridhar and Kumar, 2005), of which max, min, and indicator functions are important examples: our discussions are couched in terms of the max function. We view the problem as one of message-passing distributed computation over a geometric random graph. The network is assumed to be synchronous, and the sensors synchronously measure values and then collaborate to compute and deliver the function computed with these values to the operator station. Computation algorithms differ in (1) the communication topology assumed and (2) the messages that the nodes need to exchange in order to carry out the computation. The focus of our paper is to establish (in probability) scaling laws for the time and energy complexity of the distributed function computation over random wireless networks, under the assumption of centralized contention-free scheduling of packet transmissions. First, without any constraint on the computation algorithm, we establish scaling laws for the computation time and energy expenditure for one-time maximum computation. We show that for an optimal algorithm, the computation time and energy expenditure scale, respectively, as Theta(radicn/log n) and Theta(n) asymptotically as the number of sensors n rarr infin. Second, we analyze the performance of three specific computation algorithms that may be used in specific practical situations, namely, the tree algorithm, multihop transmission, and the Ripple algorithm (a type of gossip algorithm), and obtain scaling laws for the computation time and energy expenditure as n rarr infin. In particular, we show that the computation time for these algorithms scales as Theta(radicn/lo- g n), Theta(n), and Theta(radicn log n), respectively, whereas the energy expended scales as , Theta(n), Theta(radicn/log n), and Theta(radicn log n), respectively. Finally, simulation results are provided to show that our analysis indeed captures the correct scaling. The simulations also yield estimates of the constant multipliers in the scaling laws. Our analyses throughout assume a centralized optimal scheduler, and hence, our results can be viewed as providing bounds for the performance with practical distributed schedulers.

Synthesis and Characterization of a Class of Donor-Acceptor Conjugated Molecules: Experiments and Theoretical Calculations

A class of conjugated molecules containing donor (thiophene) and acceptor (malononitrile) is synthesized by Knoevenagel condensation reaction between 2-(2,6-dimethy1-4H-pyran-4-ylidene) malononitrile and thiophene carbaldehyde containing two and three thiophene units. The resulting molecules are characterized by H-1 and C-13 NMR. We have performed UV-vis absorption, fluorescence, and cyclic voltammetry measurements on these materials. The spectroscopic and electrochemical measurements proved beyond doubt that these materials possess lowexcitation gap and are suitable for being an active material in various electronic devices. We have also performed electronic structure calculations using density functional theory (DFT) and INDO/SCI methods to characterize the ground and excited states of this class of molecules. These donor-acceptor molecules show a strong charge transfercharacter that increases with the increase in the number of thiophene rings coupled to the malononitrile acceptor moiety. We have also calculated the pi-coherence length, Stoke's shift, and effect of solvents on excited states for this class of molecules, Our theoretical values agree well with experimental results.