Design, synthesis, and application of novel triclosan prodrugs as potential antimalarial and antibacterial agents

A number of new triclosan-conjugated analogs bearing biodegradable ester linkage have been synthesized, characterized and evaluated for their antimalarial and antibacterial activities. Many of these compounds exhibit good inhibition against Plasmodium falciparum and Escherichia coli. Among them tertiary amine containing triclosan-conjugated prodrug (5) inhibited both P. falciparum (IC50; 0.62 μM) and E. coli (IC50; 0.26 μM) at lower concentrations as compared to triclosan. Owing to the presence of a cleavable ester moiety, these new prodrugs are hydrolyzed under physiological conditions and parent molecule, triclosan, is released. Further, introduction of tertiary/quaternary functionality increases their cellular uptake. These properties impart them with higher potency to their antimalarial as well as antibacterial activities. The best compound among them 5 shows close to four-fold enhanced activities against P. falciparum and E. coli cultures as compared to triclosan.

Thiourea based novel chromogenic sensor for selective detection of fluoride and cyanide anions in organic and aqueous media

Novel chromogenic thiourea based sensors 4,4'-bis-[3-(4-nitrophenyl) thiourea] diphenyl ether 1 and 4,4'-bis-[3-(4-nitrophenyl) thiourea] diphenyl methane 2 having nitrophenyl group as signaling unit have been synthesized and characterized by spectroscopic techniques and X-ray crystallography. The both sensors show visual detection, UV-vis and NMR spectral changes in presence of fluoride and cyanide anions in organic solvent as well as in aqueous medium. The absorption spectra indicated the formation of complex between host and guest is in 1:2 stoichiometric ratios. (C) 2010 Elsevier B.V. All rights reserved.

Novel fluorescence detection technique for non-contact temperature sensing in microchip PCR

DNA amplification using Polymerase Chain Reaction (PCR) in a small volume is used in Lab-on-a-chip systems involving DNA manipulation. For few microliters of volume of liquid, it becomes difficult to measure and monitor the thermal profile accurately and reproducibly, which is an essential requirement for successful amplification. Conventional temperature sensors are either not biocompatible or too large and hence positioned away from the liquid leading to calibration errors. In this work we present a fluorescence based detection technique that is completely biocompatible and measures directly the liquid temperature. PCR is demonstrated in a 3 ILL silicon-glass microfabricated device using non-contact induction heating whose temperature is controlled using fluorescence feedback from SYBR green I dye molecules intercalated within sensor DNA. The performance is compared with temperature feedback using a thermocouple sensor. Melting curve followed by gel electrophoresis is used to confirm product specificity after the PCR cycles. (c) 2007 Elsevier B.V. All rights reserved.

Splitting Algorithms for Fast Relay Selection: Generalizations, Analysis, and a Unified View

Relay selection for cooperative communications promises significant performance improvements, and is, therefore, attracting considerable attention. While several criteria have been proposed for selecting one or more relays, distributed mechanisms that perform the selection have received relatively less attention. In this paper, we develop a novel, yet simple, asymptotic analysis of a splitting-based multiple access selection algorithm to find the single best relay. The analysis leads to simpler and alternate expressions for the average number of slots required to find the best user. By introducing a new contention load' parameter, the analysis shows that the parameter settings used in the existing literature can be improved upon. New and simple bounds are also derived. Furthermore, we propose a new algorithm that addresses the general problem of selecting the best Q >= 1 relays, and analyze and optimize it. Even for a large number of relays, the scalable algorithm selects the best two relays within 4.406 slots and the best three within 6.491 slots, on average. We also propose a new and simple scheme for the practically relevant case of discrete metrics. Altogether, our results develop a unifying perspective about the general problem of distributed selection in cooperative systems and several other multi-node systems.

Superconductivity from repulsion: a variational view

This letter presents a new class of variational wavefunctions for Fermi systems in any dimension. These wavefunctions introduce correlations between Cooper pairs in different momentum states and the relevant correlations can be computed analytically. At half filling we have a ground state with critical superconducting correlations, that causes negligible increase of the kinetic energy. We find large enhancements in a Cooper-pair correlation function caused purely by the interplay between the uncertainty principle, repulsion and the proximity of half filling. This is surprising since there is no accompanying signature in usual charge and spin response functions, and typifies a novel kind of many-body cooperative behaviour.

Evaluation of Suitable Locations for Generation Expansion in Restructured Power Systems: A Novel Concept of T-index Thukaram

In developing countries, a high rate of growth in the demand for electric energy is felt, and so the addition of new generating units becomes inevitable. In deregulated power systems, private generating stations are encouraged to add new generations. Some of the factors considered while placing a new generating unit are: availability of esources, ease of transmitting power, distance from the load centre, etc. Finding the most appropriate locations for generation expansion can be done by running repeated power flows and carrying system studies like analyzing the voltage profile, voltage stability, loss analysis, etc. In this paper a new methodology is proposed which will mainly consider the existing network topology. A concept of T-index is introduced in this paper, which considers the electrical distances between generator and load nodes. This index is used for ranking the most significant new generation expansion locations and also indicates the amount of permissible generations that can be installed at these new locations. This concept facilitates for the medium and long term planning of power generation expansions within the available transmission corridors. Studies carried out on an EHV equivalent 10-bus system and IEEE 30 bus systems are presented for illustration purposes.

Novel De-Acylative Ring Opening of 3-Acetyl and 3-Bromo Acetyl Coumarins

Reaction of 3-acetyl and 3-bromoacetyl coumarins with hydrazine hydrate has resulted in the ring opening of the coumarin moiety. The reaction was attempted with a view to obtain some new pyridazinones and pyrazolones. The reaction did not proceed via the expected pathway instead led to the formation of salicyl azines, the structure of which has been confirmed by single crystal X-ray studies.

A novel piezoelectric ZnO nanogenerator on flexible metal alloy substrate

In this paper, we report a novel piezoelectric ZnO nanogenerator on flexible metal alloy substrate (Phynox alloy) for energy harvesting and sensing applications. The vertically aligned ZnO nanowires are sandwiched between Au electrodes. The aligned growth of ZnO nanowires have been successfully synthesized on Au coated metal alloy substrate by hydrothermal method at low temperature (95 +/- 1 degrees C). The as-synthesized vertically aligned ZnO nanowires were characterized using FE-SEM. Further, PMMA is spin coated over the aligned ZnO nanowires for the purpose of their long term stability. The fabricated nanogenerator is of size 30mm x 6mm. From energy harvesting point of view, the response of the nanogenerator due to finger tip impacts ranges from 0.9 V to 1.4V. Also for sensing application, the maximum output voltage response of the nanogenerator is found to be 2.86V due to stainless steel (SS) ball impact and 0.92 V due to plastic ball impact.

A novel adeno-associated virus serotype (AAV)-8 capsid mutant improves human coagulation factor IX expression in vivo

Recombinant AAV-8 vectors have shown significant promise for hepatic gene therapy of hemophilia B. However, the theme of AAV vector dose dependent immunotoxicity seen with AAV2 vectors earlier seem to re-emerge with AAV8 vectors as well. It is therefore important to develop novel AAV8 vectors that provide enhanced gene expression at significantly less vector doses. We hypothesized that AAV8 during its intracellular trafficking, are targeted for destruction in the cytoplasm by the host-cellular kinase/ubiquitination/proteasomal degradation machinery and modification of specific serine/threonine kinase or ubiquitination targets on AAV8 capsid (Fig.1A) may improve its transduction efficiency. To test this, point mutations at specific serine (S)/threonine (T) > alanine (A) or lysine (K)>arginine (R) residues were generated on AAV8 capsid. scAAV8-EGFP vectors containing the wild-type (WT) and each one of the 5 S/T/K-mutant(S276A, S501A, S671A, T251A and K137R) capsids were evaluated for their liver transduction efficiency at a dose of 5 X 1010 vgs/ animal in C57BL/6 mice in vivo. The best performing mutant was found to be the K137R vector in terms of either the gene expression (46-fold) or the vector copy numbers in the hepatocytes (22-fold) compared to WT-AAV8 (Fig.1B). The K137R-AAV8 vector that showed significantly decreased ubiquitination of the viral capsid had reduced activation of markers of innate immune response [IL-6, IL-12, tumor necrosis factor α, Kupffer cells and TLR-9]. In addition, animals injected with the K137R mutant also demonstrated decreased (2-fold) levels of cross-neutralizing antibodies when compared to animals that received the WT-AAV8 vector. To study further the utility of the novel AAV8-K137R mutant in a therapeutic setting, we delivered human coagulation factor IX (h.FIX) under the control of liver specific promoters (LP1 or hAAT) at two different doses (2.5x10^10 and 1x10^11 vgs per mouse) in 8-12 weeks old male C57BL/6 mice. As can be seen in Fig.1C/D, the circulating levels of h.FIX were higher in all the K137R-AAV8 treated groups as compared to the WT-AAV8 treated groups either at 2 weeks (62% vs 37% for hAAT constructs and 47% vs 21% for LP1 constructs) or 4 weeks (78% vs 56% for hAAT constructs and 64% vs 30% for LP1 constructs) post hepatic gene transfer. These studies demonstrate the feasibility of the use of this novel vector for potential gene therapy of hemophilia B.

Exploring Transfer Learning Approaches for Head Pose Classification from Multi-view Surveillance Images

Head pose classification from surveillance images acquired with distant, large field-of-view cameras is difficult as faces are captured at low-resolution and have a blurred appearance. Domain adaptation approaches are useful for transferring knowledge from the training (source) to the test (target) data when they have different attributes, minimizing target data labeling efforts in the process. This paper examines the use of transfer learning for efficient multi-view head pose classification with minimal target training data under three challenging situations: (i) where the range of head poses in the source and target images is different, (ii) where source images capture a stationary person while target images capture a moving person whose facial appearance varies under motion due to changing perspective, scale and (iii) a combination of (i) and (ii). On the whole, the presented methods represent novel transfer learning solutions employed in the context of multi-view head pose classification. We demonstrate that the proposed solutions considerably outperform the state-of-the-art through extensive experimental validation. Finally, the DPOSE dataset compiled for benchmarking head pose classification performance with moving persons, and to aid behavioral understanding applications is presented in this work.

VIRTUAL VIEW SYNTHESIS BY NON-LOCAL MEANS FILTERING USING TEMPORAL DATA

A novel algorithm for Virtual View Synthesis based on Non-Local Means Filtering is presented in this paper. Apart from using the video frames from the nearby cameras and the corresponding per-pixel depth map, this algorithm also makes use of the previously synthesized frame. Simple and efficient, the algorithm can synthesize video at any given virtual viewpoint at a faster rate. In the process, the quality of the synthesized frame is not compromised. Experimental results prove the above mentioned claim. The subjective and objective quality of the synthesized frames are comparable to the existing algorithms.

Insulin-Like Growth Factor System in Cancer: Novel Targeted Therapies

Insulin-like growth factors (IGFs) are essential for growth and survival that suppress apoptosis and promote cell cycle progression, angiogenesis, and metastatic activities in various cancers. The IGFs actions are mediated through the IGF-1 receptor that is involved in cell transformation induced by tumour. These effects depend on the bioavailability of IGFs, which is regulated by IGF binding proteins (IGFBPs). We describe here the role of the IGF system in cancer, proposing new strategies targeting this system. We have attempted to expand the general viewpoint on IGF-1R, its inhibitors, potential limitations of IGF-1R, antibodies and tyrosine kinase inhibitors, and IGFBP actions. This review discusses the emerging view that blocking IGF via IGFBP is a better option than blocking IGF receptors. This can lead to the development of novel cancer therapies.

Novel Design of Honeycombs Using a Seamless Combination of Auxetic and Conventional Cores Toward Phononic Band Gap Engineering

A novel design for the geometric configuration of honeycombs using a seamless combination of auxetic and conventional cores- elements with negative and positive Possion ratios respectively, has been presented. The proposed design has been shown to generate a superior band gap property while retaining all major advantages of a purely conventional or purely auxetic honeycomb structure. Seamless combination ensures that joint cardinality is also retained. Several configurations involving different degree of auxeticity and different proportions auxetic and conventional elements have been analyzed. It has been shown that the preferred configurations open up wide and clean band gap at a significantly lower frequency ranges compared to their pure counterparts. In view of existence of band gaps being desired feature for the phononic applications, reported results might be appealing. Use of such design may enable superior vibration control as well. Proposed configurations can be made isovolumic and iso-weight giving designers a fairer ground of applying such configurations without significantly changing size and weight criteria.