Pluronic copolymer encapsulated SCR7 as a potential anticancer agent

Nonhomologous end joining (NHEJ) of DNA double strand breaks (DSBs) inside cells can be selectively inhibited by 5,6-bis-(benzylideneamino)-2-mercaptopyrimidin-4-ol (SCR7) which possesses anticancer properties. The hydrophobicity of SCR7 decreases its bioavailability which is a major setback in the utilization of this compound as a therapeutic agent. In order to circumvent the drawback of SCR7, we prepared a polymer encapsulated form of SCR7. The physical interaction of SCR7 and Pluronic (R) copolymer is evident from different analytical techniques. The in vitro cytotoxicity of the drug formulations is established using the MTT assay.

Suppression of protein aggregation by gold nanoparticles: a new way to store and transport proteins

Suppression of the aggregation of proteins has tremendous implications in biology and medicine. In the pharmaceuticals industry, aggregation of therapeutically important proteins and peptides while stored, reduces the efficacy and promptness of action leading to, in many instances, intoxication of the patient by the aggregate. Here we report the effect of gold nanoparticles (Au-NPs) in preventing the thermal and chemical aggregation of two unrelated proteins of different size, alcohol dehydrogenase (ADH, 84 kDa) and insulin (6 kDa), respectively, in physiological pH. Our principal observation is that there is a significant reduction (up to 95%) in the extent of aggregation of ADH and insulin in the presence of gold nanoparticles (Au-NPs). Aggregation of these proteins at micromolar concentration is prevented using nanomolar or less amounts of gold nanoparticles which is remarkable since chaperones which prevent such aggregation in vivo are required in micromolar quantity. The prevention of aggregation of these two different proteins under two different denaturing environments has established the role of Au-NPs as a protein aggregation prevention agent. The extent of prevention increases rapidly with the increase in the size of the gold nanoparticles. Protein molecules get physisorbed on the gold nanoparticle surface and thus become inaccessible by the denaturing agent in solution. This adsorption of proteins on AuNPs has been established by a variety of techniques and assays.

Multi-agent Reinforcement Learning for Traffic Signal Control

Optimal control of traffic lights at junctions or traffic signal control (TSC) is essential for reducing the average delay experienced by the road users amidst the rapid increase in the usage of vehicles. In this paper, we formulate the TSC problem as a discounted cost Markov decision process (MDP) and apply multi-agent reinforcement learning (MARL) algorithms to obtain dynamic TSC policies. We model each traffic signal junction as an independent agent. An agent decides the signal duration of its phases in a round-robin (RR) manner using multi-agent Q-learning with either is an element of-greedy or UCB 3] based exploration strategies. It updates its Q-factors based on the cost feedback signal received from its neighbouring agents. This feedback signal can be easily constructed and is shown to be effective in minimizing the average delay of the vehicles in the network. We show through simulations over VISSIM that our algorithms perform significantly better than both the standard fixed signal timing (FST) algorithm and the saturation balancing (SAT) algorithm 15] over two real road networks.

Accurate Indoor Positioning of Firefighters using Dual Foot-mounted Inertial Sensors and Inter-agent Ranging

A real-time cooperative localization system, utilizing dual foot-mounted low-cost inertial sensors and RF-based inter-agent ranging, has been developed. Scenario-based tests have been performed, using fully-equipped firefighters mimicking a search operation in a partly smoke-filled environment, to evaluate the performance of the TOR (Tactical lOcatoR) system. The performed tests included realistic firefighter movements and inter-agent distances, factors that are crucial in order to provide realistic evaluations of the expected performance in real-world operations. The tests indicate that the TOR system may be able to provide a position accuracy of approximately two to three meters during realistic firefighter operations, with only two smoke diving firefighters and one supervising firefighter within range.

Application of principal component analysis to gas sensing characteristics of Cr0.8Fe0.2NbO4 thick film array

The transient changes in resistances of Cr0.8Fe0.2NbO4 thick film sensors towards specified concentrations of H-2, NH3, acetonitrile, acetone, alcohol, cyclohexane and petroleum gas at different operating temperatures were recorded. The analyte-specific characteristics such as slopes of the response and retrace curves, area under the curve and sensitivity deduced from the transient curve of the respective analyte gas have been used to construct a data matrix. Principal component analysis (PCA) was applied to this data and the score plot was obtained. Distinguishing one reducing gas from the other is demonstrated based on this approach, which otherwise is not possible by measuring relative changes in conductivity. This methodology is extended for three Cr0.8Fe0.2NbO4 thick film sensor array operated at different temperatures. (C) 2015 Elsevier B.V. All rights reserved.

Copper oxide nanoparticles: an antidermatophytic agent for Trichophyton spp.

Copper oxide (CuO) is one of the most important transition metal oxides due to its unique properties. It is used in various technological applications such as high critical temperature, superconductors, gas sensors, in photoconductive applications and so on. Recently, it has been used as an antimicrobial agent against various pathogenic bacteria. In the present investigation, we studied the structural and antidermatophytic properties of CuO nanoparticles (NPs) synthesized by a precipitation technique. Copper sulfate was used as a precursor and sodium hydroxide as a reducing agent. Scanning electron microscopy (SEM) showed flower-shaped CuO NPs and X-ray diffraction (XRD) pattern showed the crystalline nature of CuO NPs. These NPs were evaluated against two prevalent species of dermatophytes, i.e. Trichophyton rubrum and T. mentagrophytes by using the broth microdilution technique. Further, the NPs activity was also compared with synthetic sertaconazole. Although better antidermatophytic activity was exhibited with sertaconazole as compared to NPs, being synthetic, sertaconazole may not be preferred, as it shows different adverse effects. Trichophyton mentagrophytes is more susceptible to NPs than T. rubrum. A phylogenetic approach was applied for predicting differences in susceptibility of pathogens.

MnFe2O4-Fe3O4 core-shell nanoparticles as a potential contrast agent for magnetic resonance imaging

In recent years, magnetic core-shell nanoparticles have received widespread attention due to their unique properties that can be used for various applications. We introduce here a magnetic core-shell nanoparticle system for potential application as a contrast agent in magnetic resonance imaging (MRI). MnFe2O4-Fe3O4 core-shell nanoparticles were synthesized by the wet-chemical synthesis method. Detailed structural and compositional charaterization confirmed the formation of a core-shell microstructure for the nanoparticles. Magnetic charaterization revealed the superparamagnetic nature of the as-synthesized core-shell nanoparticles. Average size and saturation magnetization values obtained for the as-synthesized core-shell nanoparticle were 12.5 nm and 69.34 emu g(-1) respectively. The transverse relaxivity value of the water protons obtained in the presence of the core-shell nanoparticles was 184.1 mM(-1) s(-1). To investigate the effect of the core-shell geometry towards enhancing the relaxivity value, transverse relaxivity values were also obtained in the presence of separately synthesized single phase Fe3O4 and MnFe2O4 nanoparticles. Average size and saturation magnetization values for the as-synthesized Fe3O4 nanoparticles were 12 nm and 65.8 emu g(-1) respectively. Average size and saturation magnetization values for the MnFe2O4 nanoparticles were 9 nm and 61.5 emu g(-1) respectively. The transverse relaxivity value obtained in the presence of single phase Fe3O4 and MnFe2O4 nanoparticles was 96.6 and 83.2 mM(-1) s(-1) respectively. All the nanoparticles (core-shell and single phase) were coated with chitosan by a surfactant exchange reaction before determining the relaxivity values. For similar nanoparticle sizes and saturation magnetization values, the highest value of the transverse relaxivity in the case of core-shell nanoparticles clearly illustrated that the difference in the magnetic nature of the core and shell phases in the core-shell nanoparticles creates greater magnetic inhomogeneity in the surrounding medium yielding a high value for proton relaxivity. The MnFe2O4-Fe3O4 core-shell nanoparticles exhibited extremely low toxicity towards the MCF-7 cell line. Taken together, this opens up new avenues for the use of core-shell nanoparticles in MRI.

Performance evaluation of mobile agent based resource management protocol for MANETs

The nodes with dynamicity, and management without administrator are key features of mobile ad hoc networks (1VIANETs). Increasing resource requirements of nodes running different applications, scarcity of resources, and node mobility in MANETs are the important issues to be considered in allocation of resources. Moreover, management of limited resources for optimal allocation is a crucial task. In our proposed work we discuss a design of resource allocation protocol and its performance evaluation. The proposed protocol uses both static and mobile agents. The protocol does the distribution and parallelization of message propagation (mobile agent with information) in an efficient way to achieve scalability and speed up message delivery to the nodes in the sectors of the zones of a MANET. The protocol functionality has been simulated using Java Agent Development Environment (JADE) Framework for agent generation, migration and communication. A mobile agent migrates from central resource rich node with message and navigate autonomously in the zone of network until the boundary node. With the performance evaluation, it has been concluded that the proposed protocol consumes much less time to allocate the required resources to the nodes under requirement, utilize less network resources and increase the network scalability. (C) 2015 Elsevier B.V. All rights reserved.

Exact Phase Retrieval in Principal Shift-Invariant Spaces

We address the problem of phase retrieval from Fourier transform magnitude spectrum for continuous-time signals that lie in a shift-invariant space spanned by integer shifts of a generator kernel. The phase retrieval problem for such signals is formulated as one of reconstructing the combining coefficients in the shift-invariant basis expansion. We develop sufficient conditions on the coefficients and the bases to guarantee exact phase retrieval, by which we mean reconstruction up to a global phase factor. We present a new class of discrete-domain signals that are not necessarily minimum-phase, but allow for exact phase retrieval from their Fourier magnitude spectra. We also establish Hilbert transform relations between log-magnitude and phase spectra for this class of discrete signals. It turns out that the corresponding continuous-domain counterparts need not satisfy a Hilbert transform relation; notwithstanding, the continuous-domain signals can be reconstructed from their Fourier magnitude spectra. We validate the reconstruction guarantees through simulations for some important classes of signals such as bandlimited signals and piecewise-smooth signals. We also present an application of the proposed phase retrieval technique for artifact-free signal reconstruction in frequency-domain optical-coherence tomography (FDOCT).

The cis-Diammineplatinum(II) Complex of Curcumin: A Dual Action DNA Crosslinking and Photochemotherapeutic Agent

Pt(cur)(NH3)(2)](NO3) (1), a curcumin-bound cis-diammineplatinum(II) complex, nicknamed Platicur, as a novel photoactivated chemotherapeutic agent releases photoactive curcumin and an active platinum(II) species upon irradiation with visible light. The hydrolytic instability of free curcumin reduces upon binding to platinum(II). Interactions of 1 with 5'-GMP and ct-DNA indicated formation of platinum-bound DNA adducts upon exposure to visible light (lambda = 400-700 nm). It showed apoptotic photocytotoxicity in cancer cells (IC50 approximate to 15 mu M), thus forming (OH)-O-center dot, while remaining passive in the darkness (IC50 > 200 mu M). A comet assay and platinum estimation suggest Pt-DNA crosslink formation. The fluorescence microscopic images showed cytosolic localization of curcumin, thus implying possibility of dual action as a chemo-and phototherapeutic agent.

Microhomology-mediated end joining is the principal mediator of double-strand break repair during mitochondrial DNA lesions

Mitochondrial DNA (mtDNA) deletions are associated with various mitochondrial disorders. The deletions identified in humans are flanked by short, directly repeated mitochondrial DNA sequences; however, the mechanism of such DNA rearrangements has yet to be elucidated. In contrast to nuclear DNA (nDNA), mtDNA is more exposed to oxidative damage, which may result in double-strand breaks (DSBs). Although DSB repair in nDNA is well studied, repair mechanisms in mitochondria are not characterized. In the present study, we investigate the mechanisms of DSB repair in mitochondria using in vitro and ex vivo assays. Whereas classical NHEJ (C-NHEJ) is undetectable, microhomology-mediated alternative NHEJ efficiently repairs DSBs in mitochondria. Of interest, robust microhomology-mediated end joining (MMEJ) was observed with DNA substrates bearing 5-, 8-, 10-, 13-, 16-, 19-, and 22-nt microhomology. Furthermore, MMEJ efficiency was enhanced with an increase in the length of homology. Western blotting, immunoprecipitation, and protein inhibition assays suggest the involvement of CtIP, FEN1, MRE11, and PARP1 in mitochondrial MMEJ. Knock-down studies, in conjunction with other experiments, demonstrated that DNA ligase III, but not ligase IV or ligase I, is primarily responsible for the final sealing of DSBs during mitochondrial MMEJ. These observations highlight the central role of MMEJ in maintenance of mammalian mitochondrial genome integrity and is likely relevant for deletions observed in many human mitochondrial disorders.

Ultrafine graphene oxide-CoFe2O4 nanoparticle composite as T-1 and T-2 contrast agent for magnetic resonance imaging

Graphene oxide-CoFe2O4 nanoparticle composites were synthesized using a two step synthesis method in which graphene oxide was initially synthesized followed by precipitation of CoFe2O4 nanoparticles in a reaction mixture containing graphene oxide. Samples were extracted from the reaction mixture at different times at 80 degrees C. All the extracted samples contained CoFe2O4 nanoparticles formed over the graphene oxide. It was observed that the increase in the reflux time significantly increased the saturation magnetization value for the superparamagnetic nanoparticles in the composite. It was also noticed that the size of the nanoparticles increased with increase in the reflux time. Transverse relaxivity of the water protons increased monotonically with increase in the reflux time. Whereas, the longitudinal relaxivity value initially increased and then decreased with the reflux time. Graphene oxide-CoFe2O4 nanoparticle composites also exhibit biocompatibility towards the MCF-7 cell line.

Efecto de arreglos topológicos (doble surco) sobre el crecimiento, desarrollo y rendimiento del maiz (Zea mays L.) como cultivo principal, en asocio con leguminosas (Vigna unguiculata L. walp)

El presente estudio se estableció en terrenos del Centro Experimental La Compañía, ubicado en el municipio de Masatepe, departamento de Carazo, durante la época de primera comprendida entre los meses de junio a octubre de 1995. Con el objetivo de estudiar el efecto de los diferentes arreglos de siembra, sobre el Crecimiento, Desarrollo y Rendimiento del maíz (Zea mays L.) como cultivo principal, en asocio con frijol (Viqna unguiculata L. Watp). Los tratamientos en estudio fueron: Tratamiento uno maíz como cultivo puro a 80 cm entre calle. Tratamiento dos maíz a 80 cm, más leguminosa de cobertura un surco de maíz y un surco de leguminosa (1:1). Tratamiento tres, maíz a doble surcos (20 cm entre surco) calle ancha a 140 cm con dos surcos de leguminosas de coberturas entre a 50 cm. Tratamiento cuatro, maíz doble surcos (40 cm entre surcos) calle ancha a 120 con dos surcos de leguminosas entre a 40 cm entre sí. Se utilizó un diseño de Bloque Completo al Azar con cuatro repeticiones. Los resultados obtenidos demuestran que el asocio de maíz-leguminosas, no afectan significativamente el crecimiento, desarrollo y rendimiento del maíz como cultivo principal. Además podemos afirmar que al comparar los rendimientos, del cultivo puro con los asocios, hay una mejor eficiencia en el aprovechamiento del uso potencial de los suelos.

Practical matching of principal stress field geometries in composite components

A simple composite design methodology has been developed from the basic principles of composite component failure. This design approach applies the principles of stress field matching to develop suitable reinforcement patterns around three-dimensional details such as lugs in mechanical components. The resulting patterns are essentially curvilinear orthogonal meshes, adjusted to meet the restrictions imposed by geometric restraints and the intended manufacturing process. Whilst the principles behind the design methodology can be applied to components produced by differing manufacturing processes, the results found from looking at simple generic example problems suggest a realistic and practical generic manufacturing approach. The underlying principles of the design methodology are described and simple analyses are used to help illustrate both the methodology and how such components behave. These analyses suggest it is possible to replace high-strength steel lugs with composite components whose strength-to-weight ratio is some 4-5 times better. © 1998 Elsevier Science Ltd. All rights reserved.

Anaesthetic impairment of immune function is mediated via GABA(A) receptors.

BACKGROUND: GABA(A) receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die. As many anaesthetics act via GABA(A) receptors, the aim of this study was to determine if these receptors are present on immune cells, and could play a role in immunocompromising patients. PRINCIPAL FINDINGS: We demonstrate, using RT-PCR, that monocytes express GABA(A) receptors constructed of α1, α4, β2, γ1 and/or δ subunits. Whole cell patch clamp electrophysiological studies show that GABA can activate these receptors, resulting in the opening of a chloride-selective channel; activation is inhibited by the GABA(A) receptor antagonists bicuculline and picrotoxin, but not enhanced by the positive modulator diazepam. The anaesthetic drugs propofol and thiopental, which can act via GABA(A) receptors, impaired monocyte function in classic immunological chemotaxis and phagocytosis assays, an effect reversed by bicuculline and picrotoxin. SIGNIFICANCE: Our results show that functional GABA(A) receptors are present on monocytes with properties similar to CNS GABA(A) receptors. The functional data provide a possible explanation as to why chronic propofol and thiopental administration can increase the risk of infection in critically ill patients: their action on GABA(A) receptors inhibits normal monocyte behaviour. The data also suggest a potential solution: monocyte GABA(A) receptors are insensitive to diazepam, thus the use of benzodiazepines as an alternative anesthetising agent may be advantageous where infection is a life threatening problem.