Differential Action of Glycoprotein Hormones: Significance in Cancer Progression

Growth of multicellular organisms depends on maintenance of proper balance between proliferation and differentiation. Any disturbance in this balance in animal cells can lead to cancer. Experimental evidence is provided to conclude with special reference to the action of follicle-stimulating hormone (FSH) on Sertoli cells, and luteinizing hormone (LH) on Leydig cells that these hormones exert a differential action on their target cells, i.e., stimulate proliferation when the cells are in an undifferentiated state which is the situation with cancer cells and promote only functional parameters when the cell are fully differentiated. Hormones and growth factors play a key role in cell proliferation, differentiation, and apoptosis. There is a growing body of evidence that various tumors express some hormones at high levels as well as their cognate receptors indicating the possibility of a role in progression of cancer. Hormones such as LH, FSH, and thyroid-stimulating hormone have been reported to stimulate cell proliferation and act as tumor promoter in a variety of hormone-dependent cancers including gonads, lung, thyroid, uterus, breast, prostate, etc. This review summarizes evidence to conclude that these hormones are produced by some cancer tissues to promote their own growth. Also an attempt is made to explain the significance of the differential action of hormones in progression of cancer with special reference to prostate cancer.

Identification and characterization of novel indole based small molecules as anticancer agents through SIRT1 inhibition

In our pursuit to develop new potential anticancer leads, we designed a combination of structural units of indole and substituted triazole; and a library of 1-{1-methyl-2-4-phenyl-5-(propan-2-ylsulfanyl)-4H-1,2,4-triazol-3-yl ]-1H-indol-3-yl}methanamine derivatives was synthesized and characterized. Cytotoxic evaluations of these molecules over a panel of three human cancer cell lines were carried out. Few molecules exhibited potent growth inhibitory action against the treated cancer cell lines at lower micro molar concentration. An in vitro assay investigation of these active compounds using recombinant human SIRT1 enzyme showed that one of the compounds (IT-14) inhibited the deacetylation activity of the enzyme. The in vivo study of IT-14 exemplified its promising action by reducing the prostate weight to the body weight ratio in prostate hyperplasia animal models. A remarkable decrease in the disruption of histoarchitecture of the prostate tissues isolated from IT-14 treated animal compared to that of the positive control was observed. The molecular interactions with SIRT1 enzyme were also supported by molecular docking simulations. Hence this compound can act as a lead molecule to treat prostatic hyperplasia. (C) 2013 Elsevier Masson SAS. All rights reserved.

Polymer Template Assisted Synthesis of Porous Li1.2Mn0.53Ni0.13Co0.13O2 as a High Capacity and High Rate Capability Positive Electrode Material

A porous layered composite of Li2MnO3 and LiMn1/3Co1/3Ni1/3O2 (composition: Li1.2Mn0.53Ni0.13Co0.13O2) is prepared by reverse microemulsion method employing a soft polymer template and studied as a positive electrode material. The precursor is heated at several temperatures between 500 and 900 degrees C. The product samples possess mesoporosity with broadly distributed pores of about 30 nm diameters. There is a decrease in pore volume as well as in surface area by increasing the temperature of preparation. Nevertheless, the electrochemical activity of the composite increases with an increase in temperature. The discharge capacity values of the samples prepared at 800 and 900 degrees C are about 250 mAh g(-1) at a specific current of 40 mA g(-1) with an excellent cycling stability. A value of 225 mAh g(-1) is obtained at the end of 30 charge-discharge cycles. Both these composite samples possess high rate capability, but the 800 degrees C sample is marginally superior to the 900 degrees C sample. A discharge capacity of 100 mAh g(-1) is obtained at a specific current of 1000 mA g(-1). The high rate capability is attributed to porous nature of the composite samples. (C) 2013 The Electrochemical Society. All rights reserved.

RAPID HUMAN ACTION RECOGNITION IN H.264/AVC COMPRESSED DOMAIN FOR VIDEO SURVEILLANCE

This paper discusses a novel high-speed approach for human action recognition in H. 264/AVC compressed domain. The proposed algorithm utilizes cues from quantization parameters and motion vectors extracted from the compressed video sequence for feature extraction and further classification using Support Vector Machines (SVM). The ultimate goal of our work is to portray a much faster algorithm than pixel domain counterparts, with comparable accuracy, utilizing only the sparse information from compressed video. Partial decoding rules out the complexity of full decoding, and minimizes computational load and memory usage, which can effect in reduced hardware utilization and fast recognition results. The proposed approach can handle illumination changes, scale, and appearance variations, and is robust in outdoor as well as indoor testing scenarios. We have tested our method on two benchmark action datasets and achieved more than 85% accuracy. The proposed algorithm classifies actions with speed (>2000 fps) approximately 100 times more than existing state-of-the-art pixel-domain algorithms.

Consequences of Converting Graded to Action Potentials upon Neural Information Coding and Energy Efficiency

Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na+ and K+ channels, with generator potential and graded potential models lacking voltage-gated Na+ channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na+ channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a `footprint' in the generator potential that obscures incoming signals. These three processes reduce information rates by similar to 50% in generator potentials, to similar to 3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation.

Depression biased non-Hebbian spike-timing-dependent synaptic plasticity in the rat subiculum

The subiculum is a structure that forms a bridge between the hippocampus and the entorhinal cortex (EC), and plays a major role in the memory consolidation process. Here, we demonstrate spike-timing-dependent plasticity (STDP) at the proximal excitatory inputs on the subicular pyramidal neurons of juvenile rat. Causal (positive) pairing of a single EPSP with a single back-propagating action potential (bAP) after a time interval of 10 ms (+10 ms) failed to induce plasticity. However, increasing the number of bAPs in a burst to three, at two different frequencies of 50 Hz (bAP burst) and 150 Hz, induced long-term depression (LTD) after a time interval of +10 ms in both the regular-firing (RF), and the weak burst firing (WBF) neurons. The LTD amplitude decreased with increasing time interval between the EPSP and the bAP burst. Reversing the order of the pairing of the EPSP and the bAP burst induced LTP at a time interval of -10 ms. This finding is in contrast with reports at other synapses, wherein prebefore postsynaptic (causal) pairing induced LTP and vice versa. Our results reaffirm the earlier observations that the relative timing of the pre- and postsynaptic activities can lead to multiple types of plasticity profiles. The induction of timing-dependent LTD (t-LTD) was dependent on postsynaptic calcium change via NMDA receptors in the WBF neurons, while it was independent of postsynaptic calcium change, but required active L-type calcium channels in the RF neurons. Thus the mechanism of synaptic plasticity may vary within a hippocampal subfield depending on the postsynaptic neuron involved. This study also reports a novel mechanism of LTD induction, where L-type calcium channels are involved in a presynaptically induced synaptic plasticity. The findings may have strong implications in the memory consolidation process owing to the central role of the subiculum and LTD in this process.

Design and Synthesis of New Benzimidazole-Carbazole Conjugates for the Stabilization of Human Telomeric DNA, Telomerase Inhibition, and Their Selective Action on Cancer Cells

Cell-permeable small molecules that enhance the stability of the G-quadruplex (G4) DNA structures are currently among the most intensively pursued ligands for inhibition of the telomerase activity. Herein we report the design and syntheses of four novel benzimidazole carbazole conjugates and demonstrate their high binding affinity to G4 DNA. Si nuclease assay confirmed the ligand mediated G-quadruplex DNA protection. Additional evidence from Telomeric Repeat Amplification Protocol (TRAP-LIG) assay demonstrated efficient telomerase inhibition activity by the ligands. Two of the ligands showed IC50 values in the sub-micromolar range in the TRAP-LIG assay, which are the best among the benzimidazole derivatives reported so far. The ligands also exhibited cancer cell selective nuclear internalization, nuclear condensation, fragmentation, and eventually antiproliferative activity in long-term cell viability assays. Annexin V-FITC/PI staining assays confirm that the cell death induced by the ligands follows an apoptotic pathway. An insight into the mode of ligand binding was obtained from the molecular dynamics simulations.

2-(4-Chlorobenzyl)-6-arylimidazo2,1-b]1,3,4]thiadiazoles: Synthesis, cytotoxic activity and mechanism of action

The cytotoxic activity of a new series of 2-(4'-chlorobenzyl)-5,6-disubstituted imidazo2,1-b]1,3,4]wthiadiazoles against different human and murine cancer cell lines is reported. Among the tested compounds, two derivatives namely 2-(4-chlorobenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo2,1-1)]1,3,4]th iadiazole-5-carbaldehyde 4i and 2-(4-chlorobenzyl)-6-(2-oxo-2H-chromen-3-ypimidazo2,1-1)]1,3,4]thi adiazol-5-yl thiocyanate 5i emerged as the most potent against all the cell lines. To investigate the mechanism of action, we selected compounds 4i for cell cycle study, analysis of mitochondrial membrane potential and Annexin V-FITC flow cytometric analysis and DNA fragmentation assay. Results showed that 4i induced cytotoxicity by inducing apoptosis without arresting the cell cycle. (C) 2014 Elsevier Masson SAS. All rights reserved.

Porous lithium rich Li1.2Mn0.54Ni0.22Fe0.04O2 prepared by microemulsion route as a high capacity and high rate capability positive electrode material

A porous layered composite of Li2MnO3 and LiMn0.35Ni0.55Fe0.1O2 (composition:Li1.2Mn0.54Ni0.22Fe0.04O2) is prepared by inverse microemulsion method and studied as a positive electrode material. The precursor is heated at several temperatures between 500 and 900 degrees C. The X-ray diffraction, scanning electron microscopy, and transmission electron microscopy studies suggested that well crystalline submicronsized particles are obtained. The product samples possess mesoporosity with broadly distributed pores around 10 similar to 50 nm diameter. Pore volume and surface area decrease by increasing the temperature of preparation. However, the electrochemical activity of the composite samples increases with an increase in temperature. The discharge capacity values of the samples prepared at 900 degrees C are about 186 mAh g(-1) at a specific current of 25 mA g(-1) with an excellent cycling stability. The composite sample also possesses high rate capability. The high rate capability is attributed to the porous nature of the material. (C) 2014 Elsevier Ltd. All rights reserved.

Performance comparison for 12 V lead-carbon hybrid ultracapacitors with substrate-integrated and conventional pasted positive plates

Lead-carbon hybrid ultracapacitors comprise positive lead dioxide plates of the lead-acid battery and negative plates of carbon-based electrical double-layer capacitors (EDLCs). Accordingly, a lead-carbon hybrid ultracapacitor has the features of both the battery and that of an EDLC. In this study, the development and performance comparison between the two types of lead-carbon hybrid ultracapacitors, namely those with substrate-integrated and conventional pasted positive plates, is presented as such a study is lacking in the literature. The study suggests that the faradaic efficiencies for both types of lead-carbon hybrid ultracapacitors are comparable. However, their capacitance values as well as energy and power densities differ significantly. For substrate-integrated positive plate hybrid ultracapacitor, capacitance and energy density values are lower, but power density values are higher than pasted positive plate lead-carbon hybrid ultracapacitors due to their shorter response time. Accordingly, internal resistance values are also lower for substrate-integrated lead-carbon hybrid ultracapacitors. Both types of lead-carbon hybrid ultracapacitors exhibit good cycle life of 100,000 pulse charge-discharge cycles with only a nominal loss in their capacitance values.

NUMERICAL STUDIES OF DYNAMO ACTION IN A TURBULENT SHEAR FLOW. I.

We perform numerical experiments to study the shear dynamo problem where we look for the growth of a large-scale magnetic field due to non-helical stirring at small scales in a background linear shear flow in previously unexplored parameter regimes. We demonstrate the large-scale dynamo action in the limit where the fluid Reynolds number (Re) is below unity while the magnetic Reynolds number (Rm) is above unity; the exponential growth rate scales linearly with shear, which is consistent with earlier numerical works. The limit of low Re is particularly interesting, as seeing the dynamo action in this limit would provide enough motivation for further theoretical investigations, which may focus attention on this analytically more tractable limit of Re < 1 compared to the more formidable limit of Re > 1. We also perform simulations in the regimes where (i) both (Re, Rm) < 1, and (ii) Re > 1 and Rm < 1, and compute all of the components of the turbulent transport coefficients (alpha(ij) and alpha(ij)) using the test-field method. A reasonably good agreement is observed between our results and the results of earlier analytical works in similar parameter regimes.

Human Action Recognition in Compressed Domain using PBL-McRBFN Approach

Large variations in human actions lead to major challenges in computer vision research. Several algorithms are designed to solve the challenges. Algorithms that stand apart, help in solving the challenge in addition to performing faster and efficient manner. In this paper, we propose a human cognition inspired projection based learning for person-independent human action recognition in the H.264/AVC compressed domain and demonstrate a PBL-McRBEN based approach to help take the machine learning algorithms to the next level. Here, we use gradient image based feature extraction process where the motion vectors and quantization parameters are extracted and these are studied temporally to form several Group of Pictures (GoP). The GoP is then considered individually for two different bench mark data sets and the results are classified using person independent human action recognition. The functional relationship is studied using Projection Based Learning algorithm of the Meta-cognitive Radial Basis Function Network (PBL-McRBFN) which has a cognitive and meta-cognitive component. The cognitive component is a radial basis function network while the Meta-Cognitive Component(MCC) employs self regulation. The McC emulates human cognition like learning to achieve better performance. Performance of the proposed approach can handle sparse information in compressed video domain and provides more accuracy than other pixel domain counterparts. Performance of the feature extraction process achieved more than 90% accuracy using the PTIL-McRBFN which catalyzes the speed of the proposed high speed action recognition algorithm. We have conducted twenty random trials to find the performance in GoP. The results are also compared with other well known classifiers in machine learning literature.

An Optical How Feature and McFIS Based Approach for 3-Dimensional Human Action Recognition

We propose to develop a 3-D optical flow features based human action recognition system. Optical flow based features are employed here since they can capture the apparent movement in object, by design. Moreover, they can represent information hierarchically from local pixel level to global object level. In this work, 3-D optical flow based features a re extracted by combining the 2-1) optical flow based features with the depth flow features obtained from depth camera. In order to develop an action recognition system, we employ a Meta-Cognitive Neuro-Fuzzy Inference System (McFIS). The m of McFIS is to find the decision boundary separating different classes based on their respective optical flow based features. McFIS consists of a neuro-fuzzy inference system (cognitive component) and a self-regulatory learning mechanism (meta-cognitive component). During the supervised learning, self-regulatory learning mechanism monitors the knowledge of the current sample with respect to the existing knowledge in the network and controls the learning by deciding on sample deletion, sample learning or sample reserve strategies. The performance of the proposed action recognition system was evaluated on a proprietary data set consisting of eight subjects. The performance evaluation with standard support vector machine classifier and extreme learning machine indicates improved performance of McFIS is recognizing actions based of 3-D optical flow based features.

Action Recognition from Motion Capture Data using Meta-cognitive RBF Network Classifier

Action recognition plays an important role in various applications, including smart homes and personal assistive robotics. In this paper, we propose an algorithm for recognizing human actions using motion capture action data. Motion capture data provides accurate three dimensional positions of joints which constitute the human skeleton. We model the movement of the skeletal joints temporally in order to classify the action. The skeleton in each frame of an action sequence is represented as a 129 dimensional vector, of which each component is a 31) angle made by each joint with a fixed point on the skeleton. Finally, the video is represented as a histogram over a codebook obtained from all action sequences. Along with this, the temporal variance of the skeletal joints is used as additional feature. The actions are classified using Meta-Cognitive Radial Basis Function Network (McRBFN) and its Projection Based Learning (PBL) algorithm. We achieve over 97% recognition accuracy on the widely used Berkeley Multimodal Human Action Database (MHAD).