A natural compound, methyl angolensate, induces mitochondrial pathway of apoptosis in Daudi cells

Natural products discovered from medicinal plants have played an important role in the treatment of cancer. In an effort to identify novel small molecules which can affect the proliferation of lymphoma cells, we tested methyl angolensate (MA), a plant derived tetranortriterpenoid, purified from the crude extract of the root callus of Soymida febrifuga commonly known as Indian red wood tree. We have tested MA for its cytotoxic properties on Burkitt's lymphoma cell lines, using various cellular assays. We observed that MA induces cytotoxicity in Daudi cells in a dose-dependent manner using trypan blue, MTT and LDH assays. We find that the treatment with MA led to activation of DNA double-strand break repair proteins including KU70 and KU80, suggesting the activation of nonhomologous DNA end joining pathway in surviving cells. Further, we find that methyl angolensate could induce apoptosis by cell cycle analysis, annexin V-FITC staining, DNA fragmentation and PARP cleavage. Besides, MA treatment led to reactive oxygen species generation and loss of mitochondrial transmembrane potential. These results suggest the activation of mitochondrial pathway of apoptosis. Hence, we identify MA as a potential chemotherapeutic agent against Daudi cells.

Synthesis and biological evaluation of novel 2-aralkyl-5-substituted-6-(4 `-fluorophenyl)-imidazo2,1-b]1,3,4]thiadiazole derivatives as potent anticancer agents

Levamisole, the imidazo2,1-b]thiazole derivative has been reported as a potential antitumor agent. In the present study, we synthesized, characterized and evaluated biological activity of its novel analogues with substitution in the aralkyl group and on imidazothiadiazole molecules with same chemical backbone but different side chains namely 2-aralkyl-6-(4'-fluorophenyl)-imidazo2,1-b]1,3,4]thiadiazoles (SCR1), 2-aralkyl-5-bromo-6-(4'-fluorophenyl)-imidazo2,1-b]1,3,4]-thiadiaz oles (SCR2), 2-aralkyl-5-formyl-6-(4'-fluorophenyl)-imidazo2,1-b]1,3,4]-thiadia zoles (SCR3) and 2-aralkyl-5-thiocyanato-6-(4'-fluorophenyl)-imidazo2,1-b]1,3,4]-th iadiazoles (SCR4) on leukemia cells. The cytotoxic studies showed that 3a, 4a, and 4c exhibited strong cytotoxicity while others had moderate cytotoxicity. Among these we chose 4a (IC50, 8 mu M) for understanding its mechanism of cytotoxicity. FACS analysis in conjunction with mitochondrial membrane potential and DNA fragmentation studies indicated that 4a induced apoptosis without cell cycle arrest suggesting that it could be used as a potential chemotherapeutic agent. (C) 2011 Elsevier Masson SAS. All rights reserved.

Simulation and modelling of orbital debris environment by equivalent breakups

It is well known that the increasing space activities pose a serious threat to future missions. This is mainly due to the presence of spent stages, rockets spacecraft and fragments which can lead to collisions. The calculation of the collision probability of future space vehicles with the orbital debris is necessary for estimating the risk. There is lack of adequately catalogued and openly available detailed information on the explosion characteristics of trackable and untrackable debris data. Such a situation compels one to develop suitable mathematical modelling of the explosion and the resultant debris environment. Based on a study of the available information regarding the fragmentation, subsequent evolution and observation, it turns out to be possible to develop such a mathematical model connecting the dynamical features of the fragmentation with the geometrical/orbital characteristics of the debris and representing the environment through the idea of equivalent breakup. (C) 1997 COSPAR.

The effect of SiC particles on the size and morphology of eutectic silicon in cast A356/SiCp composites

Properties of cast aluminium matrix composites are greatly influenced by the nature of distribution of reinforcing phase in the matrix and matrix microstructural length scales, such as grain size, dendrite arm spacing, size and morphology of secondary matrix phases, etc. Earlier workers have shown that SIC reinforcements can act as heterogeneous nucleation sites for Si during solidification of Al-Si-SiC composites. The present study aims at a quantitative understanding of the effect of SiC reinforcements on secondary matrix phases, namely eutectic Si, during solidification of A356 Al-SiC composites. Effect of volume fraction of SiC particulate on size and shape of eutectic Si has been studied at different cooling rates. Results indicate that an increase in SiC volume fraction leads to a reduction in the size of eutectic Si and also changes its morphology from needle-like to equiaxed. This is attributed to the heterogeneous nucleation of eutectic Si on SiC particles. However, SiC particles are found to have negligible influence on DAS. Under all the solidification conditions studied in the present investigation, SiC particles are found to be rejected by the growing dendrites. (C) 1999 Elsevier Science Ltd. All rights reserved.

Synthesis, structural characterization, thermal studies and chain dynamics of poly(methacrylonitrile peroxide) by NMR spectroscopy

Poly(methacrylonitrile peroxide) (PMNP) has been synthesized from methacrylonitrile by free radical initiated oxidative polymerization and characterized by different spectroscopic methods. NMR spectroscopy confirmed the alternating copolymer structure with labile peroxy bonds in the main chain. The extreme instability of PMNP was noted from FTIR spectroscopy. Thermal degradation studies by using differential scanning calorimetry and thermogravimetry have revealed that PMNP degrades highly exothermically and the heat of degradation, 42.5 kcal mol−1, is of the same order as that reported for other vinyl polyperoxides. Mass spectral fragmentation pattern under electron impact (EI) condition has also been investigated. The mechanism of the primary exothermic degradation has been substantiated by thermochemical calculations. The chain dynamics of the polyperoxide chain has been studied by means of 13C spin–lattice relaxation times (T1) of the main chain as well as the side chain carbons. The temperature dependence of the spin–lattice relaxation times shows that the PMNP is more flexible compared to the analogous poly(styrene peroxide).

Synthesis and Microstructure of Laser Surface Alloyed Al–Sn–Si Layer on Commercial Aluminum Substrate

A new type of bearing alloy containing ultrafine sized tin and silicon dispersions in aluminum was designed using laser surface alloying and laser remelting techniques. The microstructures of these non-equilibrium processed alloys were studied in detail using scanning and transmission electron microscopy. The microstructures revealed three distinct morphologies of tin particles namely elongated particles co-existing with silicon, globular particles, and very fine particles. Our detailed analyses using cellular growth theories showed that the formation of these globular tin particles was due to the pinching off of the tin rich liquid in the inter-cellular space by the growth of aluminum secondary dendrite arms. Evidence of fine recrystallized aluminum grains at the top layer due to constrained solidification was shown. Thermal analyses suggested that melting of the spherical shaped tin particles was controlled by the binary aluminum-tin eutectic reaction, whereas non-spherical tin particles melted via the tin-silicon eutectic reaction.

Texture evolution in an Al-Cu alloy during equal channel angular pressing: the effect of starting microstructure

In this article, the effect of initial microstructure on the texture evolution in 2014 Al alloy during equal channel angular pressing (ECAP) through route A has been reported. Three heat treatment conditions were chosen to generate the initial microstructures, namely (i) the recrystallization anneal (as-received), (ii) solution treatment at 768 K for 1 h, and (iii) solution treatment (768 K for 1 h) plus aging at 468 K for 5 h. Texture analyses were performed using orientation distribution function (ODF) method. The texture strength after ECAP processing was different for the three samples in the order, solutionised > solutionised plus aged condition > as-received. The prominent texture components were A (E) /(A) over bar (E) and B(E)/(B) over bar (E) in addition to several weaker components for the three materials. The strong texture evolution in solutionised condition has been attributed to higher strain hardening of the matrix due to higher amount of solute. In case of the as-received as well as solutionised plus aged alloy, the weaker texture could be due to the strain scattering from extensive precipitate fragmentation and dissolution during ECAP.

Intercalative pyrimido[4',5':4,5]thieno(2,3-b)quinolines induce apoptosis in leukemic cells: a comparative study of methoxy and morpholino substitution

DNA intercalating molecules are promising anticancer agents. Polycyclic aromatic molecules such as ellipticine intercalate into double-stranded DNA and affect major physiological functions. In the present study, we have characterized two molecules with the same chemical backbone but different side chains, namely 8-methoxy pyrimido[4',5':4,5]thieno (2,3-b)quinoline-4(3H)-one (MPTQ) and 4-morpholino pyrimido[4',5':4,5]thieno(2,3-b)quinoline (morpho-PTQ) at the 8th and 4th position, respectively. Although both MPTQ and morpho-PTQ show similar biophysical properties with high DNA affinity, here we show that they differ in their biological activities. We find that MPTQ is many fold more potent than morpho-PTQ and is cytotoxic against different leukemic cell lines. IC(50) value of methoxy PTQ was estimated between 2-15 A mu M among the leukemic cells studied, while it was more than 200 A mu M when morpho-PTQ was used. Cell cycle analysis shows an increase in sub-G1 phase, without any particular cell cycle arrest. Annexin V staining in conjunction with comet assay and DNA fragmentation suggest that MPTQ induces cytotoxicity by activating apoptosis. Thus the observed low IC(50) value of MPTQ makes it a promising cancer chemotherapeutic agent.

Influence of land use changes in river basins on diversity and distribution of amphibians

Land-use changes influence local biodiversity directly, and also cumulatively, contribute to regional and global changes in natural systems and quality of life. Consequent to these, direct impacts on the natural resources that support the health and integrity of living beings are evident in recent times. The Western Ghats being one of the global biodiversity hotspots, is reeling under a tremendous pressure from human induced changes in terms of developmental projects like hydel or thermal power plants, big dams, mining activities, unplanned agricultural practices,monoculture plantations, illegal timber logging, etc. This has led to the once contiguous forest habitats to be fragmented in patches, which in turn has led to the shrinkage of original habitat for the wildlife, change in the hydrological regime of the catchment, decreased inflow in streams,human-animal conflicts, etc. Under such circumstances, a proper management practice is called for requiring suitable biological indicators to show the impact of these changes, set priority regions and in developing models for conservation planning. Amphibians are regarded as one of the best biological indicators due to their sensitivity to even the slightest changes in the environment and hence they could be used as surrogates in conservation and management practices. They are the predominating vertebrates with a high degree of endemism (78%) in Western Ghats. The present study is an attempt to bring in the impacts of various land-uses on anuran distribution in three river basins. Sampling was carried out for amphibians during all seasons of 2003-2006 in basins of Sharavathi, Aghanashini and Bedthi. There are as many as 46 species in the region, one of which is new to science and nearly 59% of them are endemic to the Western Ghats. They belong to nine families, Dicroglossidae being represented by 14 species,followed by Rhacophoridae (9 species) and Ranidae (5 species). Species richness is high in Sharavathi river basin, with 36 species, followed by Bedthi 33 and Aghanashini 27. The impact of land-use changes, was investigated in the upper catchment of Sharavathi river basin. Species diversity indices, relative abundance values, percentage endemics gave clear indication of differences in each sub-catchment. Karl Pearson’s correlation coefficient (r) was calculated between species richness, endemics, environmental descriptors, land-use classes and fragmentation metrics. Principal component analysis was performed to depict the influence of these variables. Results show that sub-catchments with lesser percentage of forest, low canopy cover, higher amount of agricultural area, low rainfall have low species richness, less endemic species and abundant non-endemic species, whereas endemism, species richness and abundance of endemic species are more in the sub-catchments with high tree density, endemic trees, canopy cover, rainfall and lower amount of agriculture fields. This analysis aided in prioritising regions in the Sharavathi river basin for further conservation measures.

Climate change and Indian forests

An assessment of the impact of projected climate change on forest ecosystems in India based on climate projections of the Regional Climate Model of the Hadley Centre (HadRM3) and the global dynamic vegetation model IBIS for A1B scenario is conducted for short-term (2021-2050) and long-term (2071-2100) periods. Based on the dynamic global vegetation modelling, vulnerable forested regions of India have been identified to assist in planning adaptation interventions. The assessment of climate impacts showed that at the national level, about 45% of the forested grids is projected to undergo change. Vulnerability assessment showed that such vulnerable forested grids are spread across India. However, their concentration is higher in the upper Himalayan stretches, parts of Central India, northern Western Ghats and the Eastern Ghats. In contrast, the northeastern forests, southern Western Ghats and the forested regions of eastern India are estimated to be the least vulnerable. Low tree density, low biodiversity status as well as higher levels of fragmentation, in addition to climate change, contribute to the vulnerability of these forests. The mountainous forests (sub-alpine and alpine forest, the Himalayan dry temperate forest and the Himalayan moist temperate forest) are susceptible to the adverse effects of climate change. This is because climate change is predicted to be larger for regions that have greater elevations.

Synthesis and Antileukemic Activity of Novel 4-(3-(Piperidin-4-yl) Propyl)Piperidine Derivatives

To explore the anticancer effect associated with the piperidine framework, several (substituted phenyl) {4-[3-(piperidin-4-yl)propyl]piperidin-1-yl} methanone derivatives 3(a-i) were synthesized. Variation in the functional group at N-terminal of the piperidine led to a set of compounds bearing amide moiety. Their chemical structures were confirmed by (1)H NMR, IR and mass spectra analysis. Among these, compounds 3a, 3d and 3e were endowed with antiproliferative activity. The most active compound among this series was 3a with nitro and fluoro substitution on the phenyl ring of aryl carboxamide moiety, which inhibited the growth of human leukemia cells (K562 and Reh) at low concentration. Comparison with other derivative (3h) results shown by LDH assay, cell cycle analysis and DNA fragmentation suggested that 3a is more potent to induce apoptosis.

Groundwater Management in India:Physical, Institutional and Policy Alternatives

Groundwater constitutes a vital natural resource for sustaining India’s agricultural economy and meeting the country’s social, ecological and environmental goals. It is a unique resource, widely available, providing security against droughts and yet it is closely linked to surface-water resources and the hydrological cycle. Its availability depends on geo-hydrological conditions and characteristics of aquifers, from deep to alluvium, sediment crystalline rocks to basalt formations; and agro-climate from humid to subhumid and semi-arid to arid. Its reliable supply, uniform quality and temperature, relative turbidity, pollution-safe, minimal evaporation losses, and low cost of development are attributes making groundwater more attractive compared to other resources. It plays a key role in the provision of safe drinking water to rural populations. For example, already almost 80% of domestic water use in rural areas in India is groundwater-supplied, and much of it is being supplied to farms, villages and small towns. Inadequate control of the use of groundwater, indiscriminate application of agrochemicals and unrestrained pollution of the rural environment by other human activities make groundwater usage unsustainable, necessitating proper management in the face of the twin demand for water of good quality for domestic supply and adequate supply for irrigation, ensuring equity, efficiency and sustainability of the resource. Groundwater irrigation has overtaken surface irrigation in the early 1980s, supported by well energization. It is estimated that there are about 24 million energised wells and tube wells now and it is driven by demand rather than availability, evident through the greater occurrence of wells in districts with high population densities. Apart from aquifer characteristics, land fragmentation and landholding size are the factors that decide the density of wells. The ‘rise and fall’ of local economies dependent on groundwater can be summarized as: the green revolution of 1980s, groundwaterbased agrarian boom, early symptoms of groundwater overdraft, and decline of the groundwater socio-ecology. The social characteristics and policy interventions typical of each stage provide a fascinating insight into the human-resource dynamics. This book is a compilation of nine research papers discussing various aspects of groundwater management. It attempts to integrate knowledge about the physical system, the socio-economic system, the institutional set-up and the policy environment to come out with a more realistic analysis of the situation with regard to the nature, characteristics and intensity of resource use, the size of the economy the use generates, and the negative socioeconomic consequences. Complex variables addressed in this regard focusing on northern Gujarat are the stock of groundwater available in the region, its hydrodynamics, its net outflows against inflows, the economics of its intensive use (particularly irrigation in semi-arid and arid regions), its criticality in the regional hydroecological regime, ethical aspects and social aspects of its use. The first chapter by Dinesh Kumar and Singh, dwells on complex groundwater socio-ecology of India, while emphasizing the need for policy measures to address indiscriminate over-exploitation of dwindling resources. The chapter also explores the nature of groundwater economy and the role of electricity prices on it. The next chapter on groundwater issue in north Gujarat provides a description of groundwater resource characteristics followed by a detailed analysis of the groundwater depletion and quality deterioration problems in the region and their undesirable consequences on the economy, ecosystem health and the society. Considering water-buyers and wellowning farmers individually, a methodology for economic valuation of groundwater in regions where its primary usage is in agriculture, and as assessment of the groundwater economy based on case studies from north Gujarat is presented in the fourth chapter. The next chapter focuses on the extent of dependency of milk production on groundwater, which includes the water embedded in green and dry fodder and animal feed. The study made a realistic estimate of irrigation water productivity in terms of the physics and economics of milk production. The sixth chapter analyses the extent of reduction in water usage, increase in yield and overall increase in physical productivity of alfalfa with the use of the drip irrigation system. The chapter also provides a detailed synthesis of the costs and benefits associated with the use of drip irrigation systems. A linear programmingbased optimization model with the objective to minimize groundwater use taking into account the interaction between two distinct components – farming and dairying under the constraints of food security and income stability for different scenarios, including shift in cropping pattern, introduction of water-efficient crops, water- saving technologies in addition to the ‘business as usual’ scenario is presented in the seventh chapter. The results show that sustaining dairy production in the region with reduced groundwater draft requires crop shifts and adoption of water-saving technologies. The eighth chapter provides evidences to prove that the presence of adequate economic incentive would encourage farmers to adopt water-saving irrigation devices, based on the findings of market research with reference to the level of awareness among farmers of technologies and the factors that decide the adoption of water-saving technologies. However, now the marginal cost of using electricity for agricultural pumping is almost zero. The economic incentives are strong and visible only when the farmers are either water-buyers or have to manage irrigation with limited water from tube-well partnerships. The ninth chapter explores the socio-economic viability of increasing the power tariff and inducing groundwater rationing as a tool for managing energy and groundwater demand, considering the current estimate of the country’s annual economic loss of Rs 320 billion towards electricity subsidy in the farm sector. The tenth chapter suggests private tradable property rights and development of water markets as the institutional tool for achieving equity, efficiency and sustainability of groundwater use. It identifies the externalities for local groundwater management and emphasizes the need for managing groundwater by local user groups, supported by a thorough analysis of groundwater socio-ecology in India. An institutional framework for managing the resource based on participatory approach that is capable of internalizing the externalities, comprising implementation of institutional and technical alternatives for resource management is also presented. Major findings of the analyses and key arguments in each chapter are summarized in the concluding chapter. Case studies of the social and economic benefits of groundwater use, where that use could be described as unsustainable, are interesting. The benefits of groundwater use are outlined and described with examples of social and economic impacts of groundwater and the negative aspects of groundwater development with the compilation of environmental problems based on up-to-date research results. This publication with a well-edited compilation of case studies is informative and constitutes a useful publication for students and professionals.

Spatial Data Mining and Modeling for visualisation of Rapid Urbanisation

Rapid urbanisation in India has posed serious challenges to the decision makers in regional planning involving plethora of issues including provision of basic amenities (like electricity, water, sanitation, transport, etc.). Urban planning entails an understanding of landscape and urban dynamics with causal factors. Identifying, delineating and mapping landscapes on temporal scale provide an opportunity to monitor the changes, which is important for natural resource management and sustainable planning activities. Multi-source, multi-sensor, multi-temporal, multi-frequency or multi-polarization remote sensing data with efficient classification algorithms and pattern recognition techniques aid in capturing these dynamics. This paper analyses the landscape dynamics of Greater Bangalore by: (i) characterisation of direct impervious surface, (ii) computation of forest fragmentation indices and (iii) modeling to quantify and categorise urban changes. Linear unmixing is used for solving the mixed pixel problem of coarse resolution super spectral MODIS data for impervious surface characterisation. Fragmentation indices were used to classify forests – interior, perforated, edge, transitional, patch and undetermined. Based on this, urban growth model was developed to determine the type of urban growth – Infill, Expansion and Outlying growth. This helped in visualising urban growth poles and consequence of earlier policy decisions that can help in evolving strategies for effective land use policies.

Effect of Electromagnetic Stirring on Macrosegregation during Solidification of a Binary Alloy

The effect of electromagnetic stirring of melt on the final macrosegregation in the continuous casting of an aluminium alloy billet is studied numerically. A continuum mixture model for solidification in presence of electromagnetic stirring is presented. As a case study, simulations are performed for direct chill (DC) casting of an Al-Cu alloy and the effect of electromagnetic stirring on macrosegregation is analysed. The model predicts the temperature, velocity, and species distribution in the mold. As a special case, we have also studied the case in which dendritic particles are fragmented at the interface due to vigorous electromagnetic stirring. For this case, an additional conservation equation for the transport of solid fraction is solved. For modeling the resistance offered by moving solid crystals, a switching function in the momentum equations is used for variation of viscosity. The fragmentation and transport of dendritic particles has a profound effect on the final macrosegregation and microstructure of the solidified billet. It is found that the application of electromagnetic stirring in continuous casting of billets results in better temperature uniformity and macrosegregation pattern.

Modeling of growth and motion of equiaxed dendrites in a convecting melt

A numerical micro-scale model is developed to study the behavior of dendrite growth in presence of melt convection. In this method, an explicit, coupled enthalpy model is used to simulate the growth of an equiaxed dendrite, while a Volume of Fluid (VOF) method is used to track the movement of the dendrite in the convecting melt in a two-dimensional Eulerian framework. Numerical results demonstrate the effectiveness of the enthalpy model in simulating the dendritic growth involving complex shape, and the accuracy of VOF method in conserving mass and preserving the complex dendritic shape during motion. Simulations are performed in presence of uniform melt flow for both fixed and moving dendrites, and the difference in dendrite morphology is shown.