Combination of single walled carbon nanotubes/graphene oxide with paclitaxel: a reactive oxygen species mediated synergism for treatment of lung cancer

Heterogeneity in tumors has led to the development of combination therapies that enable enhanced cell death. Previously explored combination therapies mostly involved the use of bioactive molecules. In this work, we explored a non-conventional strategy of using carbon nanostructures (CNs) single walled carbon nanotube (SWNT) and graphene oxide (GO)] for potentiating the efficacy of a bioactive molecule paclitaxel (Tx)] for the treatment of lung cancer. The results demonstrated enhanced cell death following combination treatment of SWNT/GO and Tx indicating a synergistic effect. In addition, synergism was abrogated in the presence of an anti-oxidant, N-acetyl cysteine (NAC), and was therefore shown to be reactive oxygen species (ROS) dependent. It was further demonstrated using bromodeoxyuridine (BrdU) incorporation assay that treatment with CNs was associated with enhanced mitogen associated protein kinase (MAPK) activation that was ROS mediated. Hence, these results for the first time demonstrated the potential of SWNT/GO as co-therapeutic agents with Tx for the treatment of lung cancer.

ATM- and ATR-mediated phosphorylation of XRCC3 regulates DNA double-strand break-induced checkpoint activation and repair

The RAD51 paralogs XRCC3 and RAD51C have been implicated in homologous recombination (HR) and DNA damage responses. However, the molecular mechanism(s) by which these paralogs regulate HR and DNA damage signaling remains obscure. Here, we show that an SQ motif serine 225 in XRCC3 is phosphorylated by ATR kinase in an ATM signaling pathway. We find that RAD51C but not XRCC2 is essential for XRCC3 phosphorylation, and this modification follows end resection and is specific to S and G(2) phases. XRCC3 phosphorylation is required for chromatin loading of RAD51 and HR-mediated repair of double-strand breaks (DSBs). Notably, in response to DSBs, XRCC3 participates in the intra-S-phase checkpoint following its phosphorylation and in the G(2)/M checkpoint independently of its phosphorylation. Strikingly, we find that XRCC3 distinctly regulates recovery of stalled and collapsed replication forks such that phosphorylation is required for the HR-mediated recovery of collapsed replication forks but is dispensable for the restart of stalled replication forks. Together, these findings suggest that XRCC3 is a new player in the ATM/ATR-induced DNA damage responses to control checkpoint and HR-mediated repair.

Pressure induced structural phase transformation in TiN: a first-principles study

Titanium nitride (TiN), which is widely used for hard coatings, reportedly undergoes a pressure-induced structural phase transformation, from a NaCl to a CsCl structure, at similar to 7 GPa. In this paper, we use first-principles calculations based on density functional theory with a generalized gradient approximation of the exchange correlation energy to determine the structural stability of this transformation. Our results show that the stress required for this structural transformation is substantially lower (by more than an order of magnitude) when it is deviatoric in nature vis-a-vis that under hydrostatic pressure. Local stability of the structure is assessed with phonon dispersion determined at different pressures, and we find that CsCl structure of TiN is expected to distort after the transformation. From the electronic structure calculations, we estimate the electrical conductivity of TiN in the CsCl structure to be about 5 times of that in NaCl structure, which should be observable experimentally. (C) 2013 American Institute of Physics. http://dx.doi.org/10.1063/1.4798591]

Power-law transformation for enhanced recognition of born-digital word images

In this paper, we discuss the issues related to word recognition in born-digital word images. We introduce a novel method of power-law transformation on the word image for binarization. We show the improvement in image binarization and the consequent increase in the recognition performance of OCR engine on the word image. The optimal value of gamma for a word image is automatically chosen by our algorithm with fixed stroke width threshold. We have exhaustively experimented our algorithm by varying the gamma and stroke width threshold value. By varying the gamma value, we found that our algorithm performed better than the results reported in the literature. On the ICDAR Robust Reading Systems Challenge-1: Word Recognition Task on born digital dataset, as compared to the recognition rate of 61.5% achieved by TH-OCR after suitable pre-processing by Yang et. al. and 63.4% by ABBYY Fine Reader (used as baseline by the competition organizers without any preprocessing), we achieved 82.9% using Omnipage OCR applied on the images after being processed by our algorithm.

Heat mediated synthesis of silver nanoparticles using citrus limon (lemon) extract

In the present study, silver nanoparticles were rapidly synthesized by treating silver ions with Citrus limon (lemon) extract at higher temperature. The effect of process parameters like reductant concentration, mixing ratio of the reactants, concentration of silver nitrate and heating time period were studied. The formation of silver nanoparticles was confirmed by surface plasmon resonance as determined by UV-visible spectra in the range of 400-500 nm. X-ray diffraction analysis revealed the distinctive facets (111, 200, 220, 222 and 311 planes) of silver nanoparticles. Nanoparticles below 50 nm with spherical and spheroidal shape were observed from microscopic studies. The study offers a rapid method to synthesize silver nanoparticles within ten minutes of interaction with the bio-reductant.

Time variant reliability model updating in instrumented dynamical systems based on Girsanov's transformation

The problem of updating the reliability of instrumented structures based on measured response under random dynamic loading is considered. A solution strategy within the framework of Monte Carlo simulation based dynamic state estimation method and Girsanov's transformation for variance reduction is developed. For linear Gaussian state space models, the solution is developed based on continuous version of the Kalman filter, while, for non-linear and (or) non-Gaussian state space models, bootstrap particle filters are adopted. The controls to implement the Girsanov transformation are developed by solving a constrained non-linear optimization problem. Numerical illustrations include studies on a multi degree of freedom linear system and non-linear systems with geometric and (or) hereditary non-linearities and non-stationary random excitations.

Cytochrome P450-mediated metabolism in brain: functional roles and their implications

Introduction: Cytochromes P450 (P450) and associated monooxygenases are a family of heme proteins involved in metabolism of endogenous compounds (arachidonic acid, eicosanoids and prostaglandins) as also xenobiotics including drugs and environmental chemicals. Liver is the major organ involved in P450-mediated metabolism and hepatic enzymes have been characterized. Extrahepatic organs, such as lung, kidney and brain have the capability for biotransformation through P450 enzymes. Brain, including human brain, expresses P450 enzymes that metabolize xenobiotics and endogenous compounds. Areas covered: An overview of P450-mediated metabolism in brain is presented focusing on distinct differences seen in expression of P450 enzymes, generation of unique P450 enzymes in brain through alternate splicing and their consequences in terms of metabolism of psychoactive drugs and inflammatory prompts, such as leukotrienes, thus modulating inflammatory response. Expert opinion: The brain possesses unique P450s that metabolize drugs and endogenous compounds through pathways that are markedly different from that seen in liver indicating that extrapolation directly from liver to brain is not appropriate. It is therefore necessary to characterize the unique brain P450s and their ability to metabolize xenobiotics and endogenous compounds to better understand the functions of this important class of enzymes in brain, especially human brain.

IGF-1 stimulated upregulation of cyclin D1 is mediated via STAT5 signaling pathway in neuronal cells

Signal Transducer and Activator of Transcription (STATs) regulate various target genes such as cyclin D1, MYC, and BCL2 in nonneuronal cells which contribute towards progression as well as prevention of apoptosis and are involved in differentiation and cell survival. However, in neuronal cells, the role of STATs in the activation and regulation of these target genes and their signaling pathways are still not well established. In this study, a robust cyclin D1 expression was observed following IGF-1 stimulation in SY5Y cells as well as neurospheres. JAK/STAT pathway was shown to be involved in this upregulation. A detailed promoter analysis revealed that the specific STAT involved was STAT5, which acted as a positive regulatory element for cyclin D1 expression. Overexpression studies confirmed increase in cyclin D1 expression in response to STAT5a and STAT5b constructs when compared to dominant-negative STAT5. siRNA targeting STAT5, diminished the cyclin D1 expression, further confirming that STAT5 specifically regulated cyclin D1 in neuronal cells. Together, these findings shed new light on the mechanism of IGF-1 mediated upregulation of cyclin D1 expression in neural cell lines as well as in neural stem cells via the JAK/STAT5 signaling cascade.

Diaminotriazine substituted diphenyl ether: reversible structural transformation and solvent dependent solid state fluorescence

The effect of molecular shape and position of hydrogen bonding functionality in the solid state structural self-assembly was investigated using diaminotriazine substituted diphenyl ether based positional isomers (1-5). The molecular shape was modulated by changing diaminotriazine position that produced channel supramolecular structures in 1, 3 and 5. There exists a direct correlation between the molecular shape and three dimensional structures; more linear molecules resulted in close-packing whereas molecules with a labyrinthine topology formed a channel structure. Supramolecular aspects pertaining to the influence of solvent of crystallization in structure formation and reversible structural transformation in solid state were also explored. 1-5 exhibited tunable solid state fluorescence (lambda(max) = 437-496 nm) depending on the diaminotriazine substitutional position and 3 showed solvent-dependent solid state fluorescence. The present study describes the generation of a supramolecular channel structure with functional properties such as tunable fluorescence by varying the position of hydrogen bond functionality and solvent of crystallization.

Bimetallic core-shell nanocomposites using weak reducing agent and their transformation to alloy nanostructures

An in situ seeding growth methodology towards the preparation of core-shell nanoparticles composed of noble metals has been developed by employing trimethylamine borane (TMAB) as the reducing agent. Being a weak reducing agent, TMAB is able to distinguish the smallest reduction potential window of any two metals which renders selective reduction of metal ions thus affording a core-shell architecture of the nanoparticles. A dramatic effect of solvent was noted during the reduction of Ag+ ions: an immediate reduction took place at room temperature when dry THF was used as solvent however, usage of wet THF (THF used directly from the bottle) brings out the reduction only at reflux conditions. In the case of Au and Pd nanoparticles, preparation was found to be independent of the quality of solvent used. Au nanoparticles are realized at room temperature whereas reflux conditions are required in the case of Pd nanoparticles. This difference in behavior of the monometallic nanoparticles was successfully exploited to construct different noble metal nanoparticles with core-shell architectures such as Au@Ag, Ag@Au, and Ag@Pd. Transformation of these core-shell nanoparticles to their thermodynamically stable alloy counterparts is also demonstrated under very mild conditions reported to date.

Antibody-mediated catalysis: Induction and therapeutic relevance

Abzymes are immunoglobulins endowed with enzymatic activities. The catalytic activity of an abzyme resides in the variable domain of the antibody, which is constituted by the close spatial arrangement of amino acid residues involved in catalysis. The origin of abzymes is conferred by the innate diversity of the immunoglobulin gene repertoire. Under deregulated immune conditions, as in autoimmune diseases, the generation of abzymes to self-antigens could be deleterious. Technical advancement in the ability to generate monoclonal antibodies has been exploited in the generation of abzymes with defined specificities and activities. Therapeutic applications of abzymes are being investigated with the generation of monoclonal abzymes against several pathogenesis-associated antigens. Here, we review the different contexts in which abzymes are generated, and we discuss the relevance of monoclonal abzymes for the treatment of human diseases.

Heat and mass transfer and chemical transformation in a cerium nitrate droplet

This paper deals with the thermo-physical changes that a droplet undergoes when it is radiatively heated in a levitated environment. The heat and mass transport model has been developed along with chemical kinetics within a cerium nitrate droplet. The chemical transformation of cerium nitrate to ceria during the process is predicted using Kramers' reaction mechanism which justifies the formation of ceria at a very low temperature as observed in experiments. The rate equation modeled by Kramers is modified suitably to be applicable within the framework of a droplet, and predicts experimental results well in both bulk form of cerium nitrate and in aqueous cerium nitrate droplet. The dependence of dissociation reaction rate on droplet size is determined and the transient mass concentration of unreacted cerium nitrate is reported. The model is validated with experiments both for liquid phase vaporization and chemical reaction. Vaporization and chemical conversion are simulated for different ambient conditions. The competitive effects of sensible heating rate and the rate of vaporization with diffusion of cerium nitrate is seen to play a key role in determining the mass fraction of ceria formed within the droplet. Spatially resolved modeling of the droplet enables the understanding of the conversion of chemical species in more detail.

Isothermal transformation of beta-phase in Cu-rich Cu-Al-Sn alloys

Microstructural changes resulting from isothermal decomposition of the beta-phase have been studied in Cu-rich binary Cu-Al and ternary Cu-Al-Sn alloys containing up to 3 at.% Sn at temperatures from 873 to 673 K. Results are presented as TTT diagrams. The decomposition occurs in several stages, each of which involves the establishment of metastable equilibrium between beta and one or more of the product phases alpha, beta(1) and gamma(2). Addition of Sn has been shown to increase the stability of the ordered beta(1)-phase in relation to beta. In alloys containing more than 2 at.% Sn, the beta(1) emerges as a stable phase. At low Sn concentrations beta(1) is metastable. An important new finding is the existence of three-phase equilibrium microstructure containing alpha, beta(1) and gamma(2). Increasing addition of Sn alters the morphology of beta(1) from rosettes to dendrites and finally to Widmanstatten needles.

Electron microscopy of microstructural transformation in electrodeposited Ni-rich, Ag-Ni film

Ag-Ni films were electrodeposited over a Cu substrate. Structural characterization revealed a fibrous microstructure with an amorphous structure for the as-deposited film. Isothermal annealing at 400 degrees C of the film inside transmission electron microscope led to amorphous-to-crystalline transition along with the evolution of nano-sized particles in the microstructure. The crystalline phase was Ni-Ag solid solution. The relative volume fraction of the nano-sized particles increased gradually with time. There was however no detectable decomposition of solid solution phase till about 4 h of annealing. Beyond 4 h phase separation initiated and pure Ag and Ni phases formed in the film. This study provides a methodology by which microstructural engineering of as-electrodeposited amorphous Ag-Ni films can be conducted to isolate a particular microstructure in order to tap specific potentially usable functionalities. (C) 2013 Elsevier B.V. All rights reserved.