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Cellular phosphatases facilitate combinatorial processing of receptor-activated signals
Dhiraj Kumar, Raina Dua, Ravichandran Srikanth, Shilpi Jayaswal, Zaved Siddiqui, Kanury VS Rao
BMC Research Notes , 2008, DOI: 10.1186/1756-0500-1-81
Abstract: To address the above question we, in the present study, examined the dynamics of signaling from the B cell antigen receptor (BCR) under conditions where individual cellular phosphatases were selectively depleted by siRNA. Results from such experiments revealed a highly enmeshed structure for the signaling network where each signaling node was linked to multiple phosphatases on the one hand, and each phosphatase to several nodes on the other. This resulted in a configuration where individual signaling intermediates could be influenced by a spectrum of regulatory phosphatases, but with the composition of the spectrum differing from one intermediate to another. Consequently, each node differentially experienced perturbations in phosphatase activity, yielding a unique fingerprint of nodal signals characteristic to that perturbation. This heterogeneity in nodal experiences, to a given perturbation, led to combinatorial manipulation of the corresponding signaling axes for the downstream transcription factors.Our cumulative results reveal that it is the tight integration of phosphatases into the signaling network that provides the plasticity by which perturbation-specific information can be transmitted in the form of a multivariate output to the downstream transcription factor network. This output in turn specifies a context-defined response, when translated into the resulting gene expression profile.Reciprocal regulation of protein phosphorylation by kinases and phosphatases represents a key aspect of signal transduction [1-6]. Although information on the role of phosphatases in regulating individual signaling modules continues to accumulate, a larger perspective on how these various interactions integrate to contribute towards signal processing is lacking [7-9]. To explore this we examined the dynamics of signaling from the B cell antigen receptor (BCR) under conditions where individual cellular phosphatases were selectively depleted by siRNA. We found that each phosphat
Defining the antigen receptor-dependent regulatory network that induces arrest of cycling immature B-lymphocytes
Mohammad Jamal, Srikanth Ravichandran, Noor Jailkhani, Samrat Chatterjee, Raina Dua, Kanury VS Rao
BMC Systems Biology , 2010, DOI: 10.1186/1752-0509-4-169
Abstract: Here we employed a systems biology approach that combined extensive experimentation with in silico methodologies to chart the network of receptor-activated pathways that mediated the arrest of immature B cells in the G1 phase of the cell cycle. Interestingly, we found that only a sparse network of signaling intermediates was recruited upon engagement of the antigen receptor. This then led to the activation of a restricted subset of transcription factors, with the consequent induction of genes primarily involved in the cell death pathway. Subsequent experiments revealed that the weak initiation of intracellular signaling pathways derived from desensitization of the receptor-proximal protein tyrosine kinase Lyn, to receptor-dependent activation. Intriguingly, the desensitization was a result of the constitutive activation of this kinase in unstimulated cells, which was likely maintained through a regulatory feedback loop involving the p38 MAP kinase. The high basal activity then attenuated the ability of the antigen receptor to recruit Lyn, and thereby also the downstream signaling intermediates. Finally, integration of these results into a mathematical model provided further substantiation to the novel finding that the ground state of the intracellular signaling machinery constitutes an important determinant of the outcome of receptor-induced cellular responses.Our results identify the global events leading to the G1 arrest and subsequent apoptosis in immature B cells upon receptor activation.Cellular responses to environmental cues are mediated through activation of the signal transduction machinery. This machinery is best represented as a complex network that, in turn, governs the decision-making capabilities of the cell [1,2]. Engagement of a cell surface receptor induces activation of signal transduction cascades that involve a series of phosphorylation/dephosphorylation events. These phosphorylation-dependent signaling events eventually transduce signal to trans
Studies on Dissolution Behaviour of Nanoparticulate Curcumin Formulation  [PDF]
R. Ravichandran
Advances in Nanoparticles (ANP) , 2013, DOI: 10.4236/anp.2013.21010

Curcumin is the main biologically active phytochemical compound of turmeric that has been widely used by ancient cultures throughout Asia. However the dissolution rate limited absorption and pre-absorption degradation limits its use as a potential therapeutic. In this study an attempt has been made to overcome the above limitations by curcumin delivery through nanotechnology. Nanocurcumin solid dosage formulations were prepared and studied for its dissolution behaviour. Considerable improvement in the dissolution behavior was observed in the drug nanocrystal-loaded solid dosage forms. This is expected to enhance the bioavailability of poorly soluble medicinal herbs such as turmeric in the body.

Pharmacokinetic Study of Nanoparticulate Curcumin: Oral Formulation for Enhanced Bioavailability  [PDF]
R. Ravichandran
Journal of Biomaterials and Nanobiotechnology (JBNB) , 2013, DOI: 10.4236/jbnb.2013.43037

Curcumin, a bioactive component of turmeric, which is a commonly used spice and nutritional supplement, is isolated from the rhizomes of Curcuma longa Linn. (Zingiberaceae). In recent years, the potential pharmacological actions of Curcumin in inflammatory disorders, cardiovascular disease, cancer, Alzheimer’s disease and neurological disorders have been shown. However, the clinical application of Curcumin is severely limited by its main drawbacks such as instability, low solubility, poor bioavailability and rapid metabolism. Multifarious nanotechnology-based drug delivery systems for Curcumin including liposomes, polymeric nanoparticles, solid lipid nanoparticles, micelles, nanogels, nanoemulsions, complexes and dendrimer/dimer, have been attempted to enhance the oral bioavailability, biological activity or tissue-targeting ability of Curcumin. We attempted the nanosuspensions based delivery of curcumin. Nanonisation renders curcumin completely dispersible in aqueous media. To enhance the curcumin absorption by oral administration, nanoparticulate solid oral formulation of curcumin was prepared by us and the resulting capsule was then examined for its efficiency on bioavailability in Male Wistar rats at a dose of 100 mg curcumin/kg body weight and the pharmacokinetic parameters were compared to those of normal curcumin powder and a commercial curcumin capsule CUR-500. The bio-distribution of curcumin in organs of rat was also studied. Nanoparticulation significantly raised the curcumin concentration in selective organs in the body. The results obtained provide promising results for nanoparticulate Curcumin to improve its biological activities. Enhanced bioavailability of curcumin in the form of nanoparticle is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease. The available information also strongly suggests that nano-formulation of ingredients such as curcumin may be used as a novel nutrient delivery system too.

A Statistical Model for the Relative Hydraulic Conductivity of Water Phase in Unsaturated Soils  [PDF]
Nadarajah Ravichandran, Shada Krishnapillai
International Journal of Geosciences (IJG) , 2011, DOI: 10.4236/ijg.2011.24051
Abstract: Permeability coefficients of fluids occupying the pore space of a porous medium have significant influence on the flow of these fluids through the porous medium. In the case of unsaturated soils, in addition to other parameters such as void ratio, void distribution, particle size distribution and initial density the degree of saturation also affects the permeability coefficient of water. The degree of saturation, in unsaturated soil, is directly related to the matric suction of the soil through soil water characteristic curve. Matric suction is one of the two stress state variables widely used to characterize the deformation behavior of unsaturated soils. Therefore, it can be stated that both flow and deformation behaviors of unsaturated soil are affected by the permeability coefficient of water. Numerical modeling of coupled deformation-flow behavior of unsaturated soil requires a mathematical equation that relates the permeability coefficient to the degree of saturation. Since the parameters that affect the permeability coefficient of water in unsaturated soil have similar direct or indirect effects on the soil water characteristic curve, permeability can be effectively predicted using the soil water characteristic curve as done in statistical models. In this paper, a statistical model is proposed for the permeability of water in unsaturated soil using soil water characteristic curve of the soil. The calibrated parameters of the soil water characteristic curve are directly used in the prediction of permeability with- out additional calibration using measured permeability data. The predictive capability of the new equation is verified by matching the measured data of eight different soils found in the literature.
Enhanced Adaptive Approach of Video Coding at Very Low Bit Rate Using MSPIHT Algorithm  [PDF]
C. Ravichandran, N. Malmurugan
Circuits and Systems (CS) , 2016, DOI: 10.4236/cs.2016.78107
Abstract: Nowadays video coding approach is a major key in many applications for easy transmission and storage consumption. The process of transformation is based on the empirical wavelet transform (EWT). The encoding process of video data provides secure and less consumption of storage and the reconstruction process consists of the reverse process with the extraction. In this paper, the coding of video is carried out at a very low bit rate with the enhancement of performance by proposing an approach of modified Set Partitioning in Hierarchical Tree (MSPIHT). This method encodes the high frequency frames with the scheduling of wavelet transform for efficient performances of encoding and improves the ability of both the frequency and time. By applying empirical wavelet transform on each video frame, the component of video frequency is extracted and the?low frequency frame is encoded by the H.264/AVC standard. The low coefficient values are ignored in applying the threshold and in the reconstruction process, HBLPCE method is used for?imaging?enhancement. The simulation of the proposed approach analysis shows better performance in reliable process and efficiency when compared to existing.
Data Intelligent Low Power High Performance TCAM for IP-Address Lookup Table  [PDF]
K. Mathan, T. Ravichandran
Circuits and Systems (CS) , 2016, DOI: 10.4236/cs.2016.711313
Abstract: This paper represents current research in low-power Very Large Scale Integration (VLSI) domain. Nowadays low power has become more sought research topic in electronic industry. Power dissipation is the most important area while designing the VLSI chip. Today almost all of the high speed switching devices include the Ternary Content Addressable Memory (TCAM) as one of the most important features. When a device consumes less power that becomes reliable and it would work with more efficiency. Complementary Metal Oxide Semiconductor (CMOS) technology is best known for low power consumption devices. This paper aims at designing a router application device which consumes less power and works more efficiently. Various strategies, methodologies and power management techniques for low power circuits and systems are discussed in this research. From this research the challenges could be developed that might be met while designing low power high performance circuit. This work aims at developing Data Aware AND-type match line architecture for TCAM. A TCAM macro of 256 × 128 was designed using Cadence Advanced Development Environment (ADE) with 90 nm technology file from Taiwan Semiconductor Manufacturing Company (TSMC). The
Effects of Invasion of Water with and without Surfactant on the Oil Production and Flowback through an Oil Wet Matrix—A Microfluidic Chip Based Study  [PDF]
Srikanth Tangirala, James Sheng
Open Journal of Yangtze Oil and Gas (OJOGas) , 2018, DOI: 10.4236/ojogas.2018.34024
Abstract: The invasion of hydraulic fracturing fluids into the matrix through a relatively conductive fracture network causes capillary entrapment of the fluids that lead to the reduction of relative permeability of oil during production. Such a formation damage could be alleviated by the use of surfactants, however, their use does not always guarantee an efficient oil recovery. Through a microfluidic-chip based experimental study, the present work highlights the factors that control the later oil productivity and flowback especially through an oil-wetting matrix. The results from this study indicate that for an oil-wet formation, at shallow invasions, a water-based fracture fluid gives higher later oil production rates than a moderate IFT-reducing surfactant, and at deep invasions, the latter fluid gives better later oil production rates than the former. These results are very useful to the oil industry in making well informed decisions for selecting appropriate fracture fluids to stimulate oil-wet formations.
A Flexible Model for Moisture-Suction Relationship for Unsaturated Soils and Its Application  [PDF]
Nadarajah Ravichandran, Shada H. Krishnapillai
International Journal of Geosciences (IJG) , 2011, DOI: 10.4236/ijg.2011.23022
Abstract: The mathematical equation for the moisture-suction relationship also known as soil water characteristic curve (SWCC) is one of the constitutive relations necessary for the computational modeling of deformation and flow problems of unsaturated soil using the finite element method. In this paper, a new empirical equa-tion for the SWCC is developed that incorporates the actual airentry suction and the maximum possible suction of the soil as input parameters. The capability of the new model is investigated by fitting the experimental data for twelve different soils that includes sands, silts, and clays. The model fits the experimental data well including in high suction range which is one of the difficulties observed in other commonly used models such as the Brooks and Corey, van Genuchten, and Fredlund and Xing models. The numerical stability and the performance of the new model at low and high degrees of saturations in finite element simulation are investigated by simulating the dynamic response of a compacted embankment and the results are compared with similar predictions made using widely used SWCC models.
Improving the Predictive Capability of Popular SWCCs by Incorporating Maximum Possible Suction  [PDF]
Shada H. Krishnapillai, Nadarajah Ravichandran
International Journal of Geosciences (IJG) , 2011, DOI: 10.4236/ijg.2011.24049
Abstract: Soil-water characteristic curve (SWCC) that represents the relationship between the soil moisture and matric suction is one of the important constitutive models required for numerical modeling of unsaturated soils. An effective SWCC model should be capable of calculating the moisture-suction variation for the entire range of degree of saturation. Applicability of popular SWCC models such as Brooks and Corey, van Genuchten, and Fredlund and Xing is limited, especially in low (< 20%) degree of saturation range. In this study, all these models are modified by incorporating maximum suction as one of the model parameters, so that these models can be effectively used over the entire range of degree of saturation. The Fredlund et al (1994) permeability function is also modified based on the modification to the Fredlund and Xing SWCC model. The applicability of the improved models is investigated by calibrating the SWCC of various types of soil and presented in this paper. Based on this study it can be concluded that the modified models are flexible enough to fit the experimental data for the entire range of degree of saturation.
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