Synthesis and in vitro cytotoxic evaluation of novel diazaspiro bicyclo hydantoin derivatives in human leukemia cells: A SAR study

To study the structure activity relationship (SAR) on the cytotoxic activity and probe the structural requirement for the potent antitumor activity, a series of novel diazaspiro bicyclo hydantoin derivatives were designed and synthesized. Their structures were confirmed by H-1 NMR, LCMS and IR analyses. The antiproliferative effect of these compounds were determined against human leukemia, K562 (chronic myelogenous leukemia) and CEM (T-cell leukemia) cells using trypan blue and MTT assay, and the SAR associated with the position of N-terminal substituents in diazaspiro bicyclo hydantoin have also been discussed. It has been observed that these compounds displayed strong, moderate and weak cytotoxic activities. Interestingly, compounds having electron withdrawing groups at third and fourth position of the phenyl ring displayed selectively cytotoxic activities to both the cell lines tested with IC50 value lower than 50 mu M. In addition, the cytotoxic activities of the compounds 7(a-o) bearing the substituents at N-3 position of diazaspiro bicyclo hydantoin increases in the order alkene > ester > ether and plays an important role in determining their antitumor activities. The position and number of substituents in benzyl group attached to N-8 of diazaspiro bicyclo hydantoin nucleus interacted selectively with specific targets leading to the difference of biochemical and pharmacological effects.

A Generalized Approach to Multiresolution Complex SAR Signal Processing

Multiresolution synthetic aperture radar (SAR) image formation has been proven to be beneficial in a variety of applications such as improved imaging and target detection as well as speckle reduction. SAR signal processing traditionally carried out in the Fourier domain has inherent limitations in the context of image formation at hierarchical scales. We present a generalized approach to the formation of multiresolution SAR images using biorthogonal shift-invariant discrete wavelet transform (SIDWT) in both range and azimuth directions. Particularly in azimuth, the inherent subband decomposition property of wavelet packet transform is introduced to produce multiscale complex matched filtering without involving any approximations. This generalized approach also includes the formulation of multilook processing within the discrete wavelet transform (DWT) paradigm. The efficiency of the algorithm in parallel form of execution to generate hierarchical scale SAR images is shown. Analytical results and sample imagery of diffuse backscatter are presented to validate the method.

NMR and X-ray crystallographic studies on cyclic tetrapeptide, cyclo (D-Phe-Pro-Sar-Gly)

The conformation of the synthetic cyclic tetrapeptide cyclo(D-Phe-Pro-Sar-Gly) has been determined in solution using the nuclear magnetic resonance technique and in the crystal state by X-ray crystallography. Results showed that the peptide exhibited two different conformations in solution, conformer 1 having cis-trans-cis-trans peptide bonds and conformer 2 having trans-cis-trans-cis peptide bonds. No intramolecular hydrogen bonds were observed in the structures. The X-ray diffraction studies showed the crystals to be orthorhombic with space group P2(1)2(1)2(1) with unit-cell dimensions, a = 5.790, b = 10.344, c = 31.446 A, Z = 4, R = 0.104 for 2301 observed reflections. The crystal structure showed only one type of conformer having cis-trans-cis-trans peptide bonds similar to the conformer 1 in solution.

A discrete wavelet transform approach to multiresolution complex SAR image generation

We present a signal processing approach using discrete wavelet transform (DWT) for the generation of complex synthetic aperture radar (SAR) images at an arbitrary number of dyadic scales of resolution. The method is computationally efficient and is free from significant system-imposed limitations present in traditional subaperture-based multiresolution image formation. Problems due to aliasing associated with biorthogonal decomposition of the complex signals are addressed. The lifting scheme of DWT is adapted to handle complex signal approximations and employed to further enhance the computational efficiency. Multiresolution SAR images formed by the proposed method are presented.

Energy efficient asymmetric binary search switching technique for SAR ADC

An asymmetric binary search switching technique for a successive approximation register (SAR) ADC is presented, and trade-off between switching energy and conversion cycles is discussed. Without using any additional switches, the proposed technique consumes 46% less switching energy, for a small input swing (0.5 V-ref (P-P)), as compared to the last reported efficient switching technique in literature for an 8-bit SAR ADC. For a full input swing (2 V-ref (P-P)), the proposed technique consumes 16.5% less switching energy.

Preferential condensation of SAR-DNA by histone H1 and its SPKK containing octapeptide repeat motif

Linker histone H1 binds preferentially the scaffold associated region (SAR) DNA elements that contain characteristic oligo dA . dT tracts. In the present study, we have compared the condensation brought about by histone H1 of a SAR DNA fragment in the histone spacer region of Drosophila melanogaster with that of a random DNA (pBR322 EcoRI-SalI) fragment by circular dichroism spectroscopy. The condensation of the SAR DNA fragment by histone H1 is 3-4-fold higher than that of the random DNA fragment. A 16-mer peptide, ATPKKSTKKTPKKAKK, the sequence that is present in the C-terminus of histone H1d, which has recently been shown to possess DIVA and chromatin condensing properties, also condenses the SAR DNA fragment preferentially in a highly cooperative manner. We have proposed a model for the dynamics of chromatin structure involving histone H1-SAR DNA interaction through SPKK containing peptide motifs and its competition by AT-hook peptides present in the nonhistone chromosomal proteins like HMG-I and HMG-Y.

An 8-to-1 bit 1-MS/s SAR ADC With VGA and Integrated Data Compression for Neural Recording

Low power consumption per channel and data rate minimization are two key challenges which need to be addressed in future generations of neural recording systems (NRS). Power consumption can be reduced by avoiding unnecessary processing whereas data rate is greatly decreased by sending spike time-stamps along with spike features as opposed to raw digitized data. Dynamic range in NRS can vary with time due to change in electrode-neuron distance or background noise, which demands adaptability. An analog-to-digital converter (ADC) is one of the most important blocks in a NRS. This paper presents an 8-bit SAR ADC in 0.13-mu m CMOS technology along with input and reference buffer. A novel energy efficient digital-to-analog converter switching scheme is proposed, which consumes 37% less energy than the present state-of-the-art. The use of a ping-pong input sampling scheme is emphasized for multichannel input to alleviate the bandwidth requirement of the input buffer. To reduce the data rate, the A/D process is only enabled through the in-built background noise rejection logic to ensure that the noise is not processed. The ADC resolution can be adjusted from 8 to 1 bit in 1-bit step based on the input dynamic range. The ADC consumes 8.8 mu W from 1 V supply at 1 MS/s speed. It achieves effective number of bits of 7.7 bits and FoM of 42.3 fJ/conversion-step.

Retrieval and Multi-scale Validation of Soil Moisture from Multi-temporal SAR Data in a Semi-Arid Tropical Region

The current study presents an algorithm to retrieve surface Soil Moisture (SM) from multi-temporal Synthetic Aperture Radar (SAR) data. The developed algorithm is based on the Cumulative Density Function (CDF) transformation of multi-temporal RADARSAT-2 backscatter coefficient (BC) to obtain relative SM values, and then converts relative SM values into absolute SM values using soil information. The algorithm is tested in a semi-arid tropical region in South India using 30 satellite images of RADARSAT-2, SMOS L2 SM products, and 1262 SM field measurements in 50 plots spanning over 4 years. The validation with the field data showed the ability of the developed algorithm to retrieve SM with RMSE ranging from 0.02 to 0.06 m(3)/m(3) for the majority of plots. Comparison with the SMOS SM showed a good temporal behaviour with RMSE of approximately 0.05 m(3)/m(3) and a correlation coefficient of approximately 0.9. The developed model is compared and found to be better than the change detection and delta index model. The approach does not require calibration of any parameter to obtain relative SM and hence can easily be extended to any region having time series of SAR data available.

Melting and superheating of nanowires-a nanotube approach

We have investigated the size-dependent melting of nanotubes based on a thermodynamic approach and shown that the melting temperature of nanotubes depends on the outer radius and on the inner radius through the thickness of the nanotubes. Size-dependent melting of nanowires and thin films has been derived from that of nanotubes. We validate the size-dependent melting of nanotubes, nanowires and thin films by comparing the results with available molecular dynamic simulations and experimental results. It has also been inferred that superheating occurs when the melting starts from the inner surface and proceeds towards the outer surface, while melting point depression occurs when the melting starts from the outer surface and proceeds towards the inner surface.

Synthesis and Identification of a new class of antileukemic agents containing 2-(arylcarboxamide)-(S)-6-amino-4,5,6,7-tetrahydrobenzod]thiazole

Recently we have reported the effect of (S)-6-aryl urea/thiourea substituted-2-amino-4,5,6,7-tetrahydrobenzod]thiazole derivatives as potent anti-leukemic agents. To elucidate further the Structure Activity Relationship (SAR) studies on the anti-leukemic activity of (S)-2,6-diamino-4,5,6,7 tetrahydrobenzod]thiazole moiety, a series of 2-arlycarboxamide substituted-(S)-6-amino-4,5,6,7-tetrahydrobenzod]thiazole were designed, synthesized and evaluated for their anti-leukemic activity by trypan blue exclusion, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) assays and cell cycle analysis. Results suggest that the position, number and bulkiness of the substituent on the phenyl ring of aryl carboxamide moiety at 2nd position of 6-amino-4,5,6,7-tetrhydrobenzod]thiazole play a key role in inhibiting the proliferation of leukemia cells. Compounds with ortho substitution showed poor activity and with meta and para substitution showed good activity. (C) 2010 Elsevier Masson SAS. All rights reserved.

The Reaction of a Nitro-Capped Cobalt(III) Cage Complex With Base: the Crystal Structure of a Contracted Cage Complex, and the Mechanism of Its Formation

The synthesis, properties and crystal structure of the cage complex (1-hydroxy-8-methyl-3,6,10,13,15,18-hexaazabicyclo[6.6.5]nonadecane)cobalt(III) chloride hydrate ([Co(Me,OH-absar)] C13.H2O) are reported. The mechanism of the formation of this contracted cavity cage from a nitro-capped hexaazabicycloicosane type cage has been investigated. Treatment of (1-methyl-8-nitro-3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane)cobalt(III) chloride ([Co(Me,NO2-sar)] 3+) with excess base in aqueous solution leads initially to rapid (t1/2 < 1 ms) and reversible deprotonation of one coordinated secondary amine. This species undergoes a retro-Mannich type reaction and imine hydrolysis (t1/2 almost-equal-to 90 s). Quenching the reaction with acid gives rise to a pair of isomeric intermediate species which have been isolated and characterized. They have a pendant arm macrocyclic structure, resulting from the loss of a methylene unit from one of the arms of the cap. Heating either isomer in aqueous solution gives the new cage compound with the contracted cap. It is postulated that this occurs through a Nef reaction, resulting in the formation of a ketone which then condenses with the coordinated primary amine. A comparison with the corresponding bicycloicosane analogue indicates a reduced chromophoric cavity size for the contracted cage. The reduction potential of the cobalt(III)/cobalt(II) couple is 170 mV more negative for the smaller cage, and, in the electronic spectrum of the cobalt(III) complex, the d-d transitions are both shifted to higher energy, corresponding to a stronger ligand field.

Synthetic aperture radar: A focus on current problems

Synthetic aperture radar (SAR) is a powerful tool for mapping and remote sensing. The theory and operation of SAR have seen a period of intense activity in recent years. This paper attempts to review some of the more advanced topics studied in connection with modern SAR systems based on digital processing. Following a brief review of the principles involved in the operation of SAR, attention is focussed on special topics such as advanced SAR modelling and focussing techniques, in particular clutterlock and autofocus, Doppler centroid (DC) estimation methods involving seismic migration technique, moving target imaging, bistatic radar imaging, effects of system nonlinearities, etc.

Efficient syntheses of benzothiazepines as antagonists for the mitochondrial sodium-calcium exchanger: Potential therapeutics for type II diabetes

Type II diabetes mellitus is a chronic metabolic disorder that can lead to serious cardiovascular, renal, neurologic, and retinal complications. While several drugs are currently prescribed to treat type II diabetes, their efficacy is limited by mechanism-related side effects (weight gain, hypoglycemia, gastrointestinal distress), inadequate efficacy for use as monotherapy, and the development of tolerance to the agents. Consequently, combination therapies are frequently employed to effectively regulate blood glucose levels. We have focused on the mitochondrial sodium-calcium exchanger (mNCE) as a novel target for diabetes drug discovery. We have proposed that inhibition of the mNCE can be used to regulate calcium flux across the mitochondrial membrane, thereby enhancing mitochondrial oxidative metabolism, which in turn enhances glucose-stimulated insulin secretion (GSIS) in the pancreatic beta-cell. In this paper, we report the facile synthesis of benzothiazepines and derivatives by S-alkylation using 2-aminobenzhydrols. The syntheses of other bicyclic analogues based on benzothiazepine, benzothiazecine, benzodiazecine, and benzodiazepine templates are also described. These compounds have been evaluated for their inhibition of mNCE activity, and the results from the structure-activity relationship (SAR) studies are discussed.

Size-dependent cohesive energy and melting of non-spherical nanoparticles

All most all theoretical models assume spherical nanoparticles. However, thermodynamic properties of non-spherical nanoparticles are the subject of recent interests. In this article, we have discussed the size-dependent cohesive energy and melting of non-spherical nanoparticles based on liquid-drop model. The surface to volume ratio is different for different shapes of nanoparticles and as a consequence, the variation of cohesive energy and melting of non-spherical nanoparticles is different from that of spherical case. By analyzing the reported experimental results, it has been observed that liquid-drop model can be used to understand the size-dependent cohesive energy and melting of non-spherical nanoparticles.

Integration of speckle de-noising and image segmentation using synthetic aperture radar image for flood extent extraction

Flood is one of the detrimental hydro-meteorological threats to mankind. This compels very efficient flood assessment models. In this paper, we propose remote sensing based flood assessment using Synthetic Aperture Radar (SAR) image because of its imperviousness to unfavourable weather conditions. However, they suffer from the speckle noise. Hence, the processing of SAR image is applied in two stages: speckle removal filters and image segmentation methods for flood mapping. The speckle noise has been reduced with the help of Lee, Frost and Gamma MAP filters. A performance comparison of these speckle removal filters is presented. From the results obtained, we deduce that the Gamma MAP is reliable. The selected Gamma MAP filtered image is segmented using Gray Level Co-occurrence Matrix (GLCM) and Mean Shift Segmentation (MSS). The GLCM is a texture analysis method that separates the image pixels into water and non-water groups based on their spectral feature whereas MSS is a gradient ascent method, here segmentation is carried out using spectral and spatial information. As test case, Kosi river flood is considered in our study. From the segmentation result of both these methods are comprehensively analysed and concluded that the MSS is efficient for flood mapping.