IDH1 Mutations in Diffusely Infiltrating Astrocytomas Grade Specificity, Association With Protein Expression, and Clinical Relevance

IDH1 mutations are frequent genetic alterations in low-grade diffuse gliomas and secondary glioblastoma (GBM). To validate mutation frequency, IDH1 gene at codon 132 was sequenced in 74 diffusely infiltrating astrocytomas: diffuse astrocytoma (DA; World Health Organization WHO] grade II), anaplastic astrocytoma (AA; WHO grade III), and GBM (WHO grade IV). All cases were immunostained with IDH1-R132H monoclonal antibody. Mutational status was correlated with mutant protein expression, patient age, duration of symptoms, and prognosis of patients with GBM. We detected 31 (41.9%) heterozygous IDH1 mutations resulting in arginine-to-histidine substitution (R132H;CGT-CAT). All 12 DAs (100%), 13 of 14 AAs (92.9%), and 6 of 48 GBMs (12.5%) (5/6 83.3%] secondary, and 1/42 2.4%] primary) harbored IDH1 mutations. The correlation between mutational status and protein expression was significant (P < .001). IDH1 mutation status, though not associated with prognosis of patients with GBM, showed significant association with younger age and longer duration of symptoms in the whole cohort (P < .001). Our study validates IDH1 mutant protein expression across various grades of astrocytoma, and demonstrates a high incidence of IDH1 mutations in DA, AA, and secondary GBM.

Effect of selenium addition on the GeTe phase change memory alloys

Compositional dependent investigations of the bulk GeTe chalcogenides alloys added with different selenium concentrations are carried out by X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), electron probe micro-analyzer (EPMA) and differential scanning calorimetry (DSC). The measurements reveal that GeTe crystals are predominant in alloys up to 0.20 at.% of Se content indicating interstitial occupancy of Se in the Ge vacancies. Raman modes in the GeTe alloys changes to GeSe modes with the addition of Se. Amorphousness in the alloy increases with increase of Se and 0.50 at.% Se alloy forms a homogeneous amorphous phase with a mixture of Ge-Se and Te-Se bonds. Structural changes are explained with the help of bond theory of solids. Crystallization temperature is found to be increasing with increase of Se, which will enable the amorphous stability. For the optimum 0.50 at.% Se alloy, the melting temperature has reduced which will reduce the RESET current requirement for the phase change memory applications. (C) 2012 Elsevier B.V. All rights reserved.

Ca2+ Binding to the ExDxD Motif Regulates the DNA Cleavage Specificity of a Promiscuous Endonuclease

Most of the restriction endonucleases (REases) are dependent on Mg2+ for DNA cleavage, and in general, Ca2+ inhibits their activity. RKpnI, an HNH active site containing beta beta alpha-Me finger nuclease, is an exception. In presence of Ca2+, the enzyme exhibits high-fidelity DNA cleavage and complete suppression of Mg2+-induced promiscuous activity. To elucidate the mechanism of unusual Ca2+-mediated activity, we generated alanine variants in the putative Ca-2+ binding motif, E(132)xD(134)xD(136), of the enzyme. Mutants showed decreased levels of DNA cleavage in the presence of Ca2+. We demonstrate that ExDxD residues are involved in Ca2+ coordination; however, the invariant His of the catalytic HNH motif acts as a general base for nucleophile activation, and the other two active site residues, D148 and Q175, also participate in Ca2+-mediated cleavage. Insertion of a 10-amino acid linker to disrupt the spatial organization of the ExDxD and HNH motifs impairs Ca2+ binding and affects DNA cleavage by the enzyme. Although ExDxD mutant enzymes retained efficient cleavage at the canonical sites in the presence of Mg2+, the promiscuous activity was greatly reduced, indicating that the carboxyl residues of the acidic triad play an important role in sequence recognition by the enzyme. Thus, the distinct Ca2+ binding motif that confers site specific cleavage upon Ca2+ binding is also critical for the promiscuous activity of the Mg2+-bound enzyme, revealing its role in metal ion-mediated modulation of DNA cleavage.

Cobalt(II), Nickel(II) and Copper(II) complexes of a tetradentate Schiff base as photosensitizers: Quantum yield of O-1(2) generation and its promising role in anti-tumor activity

In the present investigation, a Schiff base N'(1),N'(3)-bis(E)-(5-bromo-2-hydroxyphenyl)methylidene]benzene-1,3-d icarbohydrazide and its metal complexes have been synthesized and characterized. The DNA-binding studies were performed using absorption spectroscopy, emission spectra, viscosity measurements and thermal denatuaration studies. The experimental evidence indicated that, the Co(II), Ni(II) and Cu(II) complexes interact with calf thymus DNA through intercalation with an intrinsic binding constant K-b of 2.6 x 10(4) M-1, 5.7 x 10(4) M-1 and 4.5 x 10(4) M-1, respectively and they exhibited potent photo-damage abilities on pUC19 DNA, through singlet oxygen generation with quantum yields of 0.32, 0.27 and 0.30 respectively. The cytotoxic activity of the complexes resulted that they act as a potent photosensitizers for photochemical reactions. (C) 2012 Elsevier B.V. All rights reserved.

Exploiting the Structure of the Constraint Graph for Efficient Points-to Analysis

Points-to analysis is a key compiler analysis. Several memory related optimizations use points-to information to improve their effectiveness. Points-to analysis is performed by building a constraint graph of pointer variables and dynamically updating it to propagate more and more points-to information across its subset edges. So far, the structure of the constraint graph has been only trivially exploited for efficient propagation of information, e.g., in identifying cyclic components or to propagate information in topological order. We perform a careful study of its structure and propose a new inclusion-based flow-insensitive context-sensitive points-to analysis algorithm based on the notion of dominant pointers. We also propose a new kind of pointer-equivalence based on dominant pointers which provides significantly more opportunities for reducing the number of pointers tracked during the analysis. Based on this hitherto unexplored form of pointer-equivalence, we develop a new context-sensitive flow-insensitive points-to analysis algorithm which uses incremental dominator update to efficiently compute points-to information. Using a large suite of programs consisting of SPEC 2000 benchmarks and five large open source programs we show that our points-to analysis is 88% faster than BDD-based Lazy Cycle Detection and 2x faster than Deep Propagation. We argue that our approach of detecting dominator-based pointer-equivalence is a key to improve points-to analysis efficiency.

Nanostructured Pd modified Ni/CeO2 catalyst for water gas shift and catalytic hydrogen combustion reaction

Nanostructured Pd-modified Ni/CeO2 catalyst was synthesized in a single step by solution combustion method and characterized by XRD, TEM, XPS, TPR and BET surface analyzer techniques. The catalytic performance of this compound was investigated by performing the water gas shift (WGS) and catalytic hydrogen combustion (CHC) reaction. The present compound is highly active and selective (100%) toward H-2 production for the WGS reaction. A lack of CO methanation activity is an important finding of present study and this is attributed to the ionic substitution of Pd and Ni species in CeO2. The creation of oxide vacancies due to ionic substitution of aliovalent ions induces dissociation of H2O that is responsible for the improved catalytic activity for WGS reaction. The combined H-2-TPR and XPS results show a synergism exists among Pd, Ni and ceria support. The redox reaction mechanism was used to correlate experimental data for the WGS reaction and a mechanism involving the interaction of adsorbed H-2 and O-2 through the hydroxyl species was proposed for CHC reaction. The parity plot shows a good correspondence between the experimental and predicted reaction rates. (c) 2012 Elsevier B.V. All rights reserved.

Euglena sp as a suitable source of lipids for potential use as biofuel and sustainable wastewater treatment

Prolific algal growth in sewage ponds with high organic loads in the tropical regions can provide cost-effective and efficient wastewater treatment and biofuel production. This work examines the ability of Euglena sp. growing in wastewater ponds for biofuel production and treatment of wastewater. The algae were isolated from the sewage treatment plants and were tested for their nutrient removal capability. Compared to other algae, Euglena sp. showed faster growth rates with high biomass density at elevated concentrations of ammonium nitrogen (NH4-N) and organic carbon (C). Profuse growth of these species was observed in untreated wastewaters with a mean specific growth rate (mu) of 0.28 day(-1) and biomass productivities of 132 mg L-1 day(-1). The algae cultured within a short period of 8 days resulted in the 98 % removal of NH4-N, 93 % of total nitrogen 85 % of ortho-phosphate, 66 % of total phosphate and 92 % total organic carbon. Euglenoids achieved a maximum lipid content of 24.6 % (w/w) with a biomass density of 1.24 g L-1 (dry wt.). Fourier transform infrared spectra showed clear transitions in biochemical compositions with increased lipid/protein ratio at the end of the culture. Gas chromatography and mass spectrometry indicated the presence of high contents of palmitic, linolenic and linoleic acids (46, 23 and 22 %, respectively), adding to the biodiesel quality. Good lipid content (comprised quality fatty acids), efficient nutrient uptake and profuse biomass productivity make the Euglena sp. as a viable source for biofuel production in wastewaters.

Cytotoxicity of aluminium oxide nanoparticles towards fresh water algal isolate at low exposure concentrations

The growing commercial applications had brought aluminium oxide nanoparticles under,toxicologists' purview. In the present study, the cytotoxicity of two different sized aluminium oxide nanoparticles (ANP(1), mean hydrodynamic diameter 82.6 +/- 22 nm and ANP(2), mean hydrodynamic diameter 246.9 +/- 39 nm) towards freshwater algal isolate Chlorella ellipsoids at low exposure levels (<= 1 mu g/mL) using sterile lake water as the test medium was assessed. The dissolution of alumina nanoparticles and consequent contribution towards toxicity remained largely unexplored owing to its presumed insoluble nature. Herein, the leached Al3+ ion mediated toxicity has been studied along with direct particulate toxicity to bring out the dynamics of toxicity through colloidal stability, biochemical, spectroscopic and microscopic analyses. The mean hydrodynamic diameter increased with time both for ANP(1) 82.6 +/- 22 nm (0 h) to 246.3 +/- 59 nm (24h), to 1204 +/- 140 nm (72 h)] and ANP(2) 246.9 +/- 39 nm (Oh) to 368.28 +/- 48 nm (24 h), to 1225.96 +/- 186 nm (72 h)] signifying decreased relative abundance of submicron sized particles (<1000 nm). The detailed cytotoxicity assays showed a significant reduction in the viability dependent on dose and exposure. A significant increase in ROS and LDH levels were noted for both ANPs at 1 mu g/mL concentration. The zeta potential and FT-IR analyses suggested surface chemical interaction between nanoparticles and algal cells. The substantial morphological changes and cell wall damage were confirmed through microscopic analyses (SEM, TEM, and CLSM). At 72 h, significant Al3+ ion release in the test medium 0.092 mu g/mL for ANP(1), and 0.19 mu g/mL for ANP(2)] was noted, and the resulting suspension containing leached ions caused significant cytotoxicity, revealing a substantial ionic contribution. This study indicates that both the nano-size and ionic dissolution play a significant role in the cytotoxicity of ANPs towards freshwater algae, and the exposure period largely determines the prevalent mode of nano-toxicity.

Identification of fault location in power distribution system with distributed generation using support vector machines

This paper presents a multi-class support vector machine (SVMs) approach for locating and diagnosing faults in electric power distribution feeders with the penetration of Distributed Generations (DGs). The proposed approach is based on the three phase voltage and current measurements which are available at all the sources i.e. substation and at the connection points of DG. To illustrate the proposed methodology, a practical distribution feeder emanating from 132/11kV-grid substation in India with loads and suitable number of DGs at different locations is considered. To show the effectiveness of the proposed methodology, practical situations in distribution systems (DS) such as all types of faults with a wide range of varying fault locations, source short circuit (SSC) levels and fault impedances are considered for studies. The proposed fault location scheme is capable of accurately identify the fault type, location of faulted feeder section and the fault impedance. The results demonstrate the feasibility of applying the proposed method in practical in smart grid distribution automation (DA) for fault diagnosis.

Impact of heavy metals on bacterial communities from mangrove soils of the Mahanadi Delta (India)

This study aimed to assess soil nutrient status and heavy metal content and their impact on the predominant soil bacterial communities of mangroves of the Mahanadi Delta. Mangrove soil of the Mahanadi Delta is slightly acidic and the levels of soil nutrients such as carbon, nitrogen, phosphorous and potash vary with season and site. The seasonal average concentrations (g/g) of various heavy metals were in the range: 14810-63370 (Fe), 2.8-32.6 (Cu), 13.4-55.7 (Ni), 1.8-7.9 (Cd), 16.6-54.7 (Pb), 24.4-132.5 (Zn) and 13.3-48.2 (Co). Among the different heavy metals analysed, Co, Cu and Cd were above their permissible limits, as prescribed by Indian Standards (Co=17g/g, Cu=30 g/g, Cd=3-6 g/g), indicating pollution in the mangrove soil. A viable plate count revealed the presence of different groups of bacteria in the mangrove soil, i.e. heterotrophs, free-living N-2 fixers, nitrifyers, denitrifyers, phosphate solubilisers, cellulose degraders and sulfur oxidisers. Principal component analysis performed using multivariate statistical methods showed a positive relationship between soil nutrients and microbial load. Whereas metal content such as Cu, Co and Ni showed a negative impact on some of the studied soil bacteria.

Multifunctional Properties of Multistage Spark Plasma Sintered HA-BaTiO3-Based Piezobiocomposites for Bone Replacement Applications

This work reports the processing-microstructure-property correlation of novel HA-BaTiO3-based piezobiocomposites, which demonstrated the bone-mimicking functional properties. A series of composites of hydroxyapatite (HA) with varying amounts of piezoelectric BaTiO3 (BT) were optimally processed using uniquely designed multistage spark plasma sintering (SPS) route. Transmission electron microscopy imaging during in situ heating provides complementary information on the real-time observation of sintering behavior. Ultrafine grains (0.50m) of HA and BT phases were predominantly retained in the SPSed samples. The experimental results revealed that dielectric constant, AC conductivity, piezoelectric strain coefficient, compressive strength, and modulus values of HA-40wt% BT closely resembles with that of the natural bone. The addition of 40wt% BT enhances the long-crack fracture toughness, compressive strength, and modulus by 132%, 200%, and 165%, respectively, with respect to HA. The above-mentioned exceptional combination of functional properties potentially establishes HA-40wt% BT piezocomposite as a new-generation composite for orthopedic implant applications.

A multi-level multi-scale approach to study essential genes in Mycobacterium tuberculosis

Background: The set of indispensable genes that are required by an organism to grow and sustain life are termed as essential genes. There is a strong interest in identification of the set of essential genes, particularly in pathogens, not only for a better understanding of the pathogen biology, but also for identifying drug targets and the minimal gene set for the organism. Essentiality is inherently a systems property and requires consideration of the system as a whole for their identification. The available experimental approaches capture some aspects but each method comes with its own limitations. Moreover, they do not explain the basis for essentiality in most cases. A powerful prediction method to recognize this gene pool including rationalization of the known essential genes in a given organism would be very useful. Here we describe a multi-level multi-scale approach to identify the essential gene pool in a deadly pathogen, Mycobacterium tuberculosis. Results: The multi-level workflow analyses the bacterial cell by studying (a) genome-wide gene expression profiles to identify the set of genes which show consistent and significant levels of expression in multiple samples of the same condition, (b) indispensability for growth by using gene expression integrated flux balance analysis of a genome-scale metabolic model, (c) importance for maintaining the integrity and flow in a protein-protein interaction network and (d) evolutionary conservation in a set of genomes of the same ecological niche. In the gene pool identified, the functional basis for essentiality has been addressed by studying residue level conservation and the sub-structure at the ligand binding pockets, from which essential amino acid residues in that pocket have also been identified. 283 genes were identified as essential genes with high-confidence. An agreement of about 73.5% is observed with that obtained from the experimental transposon mutagenesis technique. A large proportion of the identified genes belong to the class of intermediary metabolism and respiration. Conclusions: The multi-scale, multi-level approach described can be generally applied to other pathogens as well. The essential gene pool identified form a basis for designing experiments to probe their finer functional roles and also serve as a ready shortlist for identifying drug targets.

Magnetic and dielectric interactions in nano zinc ferrite powder: Prepared by self-sustainable propellant chemistry technique

The structural, magnetic and dielectric properties of nano zinc ferrite prepared by the propellant chemistry technique are studied. The PXRD measurement at room temperature reveal that the compound is in cubic spinel phase, belong to the space group Fd (3) over barm. The unit cell parameters have been estimated from Rietveld refinement. The calculated force constants from FTIR spectrum corresponding to octahedral and tetrahedral sites at 375 and 542 cm(-1) are 6.61 x 10(2) and 3.77 x 10(2) N m(-1) respectively; these values are slightly higher compared to the other ferrite systems. Magnetic hysteresis and EPR spectra show superparamagnetic property nearly to room temperature due to comparison values between magnetic anisotropy energy and the thermal energy. The calculated values of saturation magnetization, remenant magnetization, coercive field and magnetic moment supports for the existence of multi domain particles in the sample. The temperature dependent magnetic field shows the spin freezing state at 30 K and the blocking temperature at above room temperature. The frequency dependent dielectric interactions show the variation of dielectric constant, dielectric loss and impedance as similar to other ferrite systems. The AC conductivity in the prepared sample is due to the presence of electrons, holes and polarons. The synthesized material is suitable for nano-electronics and biomedical applications. (C) 2014 Elsevier B.V. All rights reserved.

Effective Q Criterion for Disk Stability in an External Potential

The standard Q criterion (with Q > 1) describes the stability against local, axisymmetric perturbations in a disk supported by rotation and random motion. Most astrophysical disks, however, are under the influence of an external gravitational potential, which can significantly affect their stability. A typical example is a galactic disk embedded in a dark matter halo. Here, we do a linear perturbation analysis for a disk in an external potential and obtain a generalized dispersion relation and the effective stability criterion. An external potential, such as that due to the dark matter halo concentric with the disk, contributes to the unperturbed rotational field and significantly increases its stability. We obtain the values for the effective Q parameter for the Milky Way and for a low surface brightness galaxy, UGC 7321. We find that in each case the stellar disk by itself is barely stable and it is the dark matter halo that stabilizes the disk against local, axisymmetric gravitational instabilities. Thus, the dark matter halo is necessary to ensure local disk stability. This result has been largely missed so far because in practice the Q parameter for a galactic disk is obtained using the observed rotational field that already includes the effect of the halo

Iron(III) benzhydroxamates of dipicolylamines for photocytotoxicity in red light and cellular imaging

Benzhydroxamate (BHA) iron(III) complexes Fe(BHA)(L)ClICI (I, 2)], where L is (phenyl)dipicolylamine (phdpa in I) and (pyrenyl)dipicolylamine (pydpa in 2), were prepared and their photocytotoxicity in visible (400-700 nm) and red (600-720 nm) light was studied. Complex 1 was structurally characterized by X-ray crystallography. The complexes have high-spin iron(III) centers. Complex 2, with a pyrenyl fluorophore, was used for cellular imaging, showing both mitochondrial and nuclear localization in the fluorescence microscopic study. The complex exhibited photocytotoxicity in red light in HeLa cancer cells, giving IC50 value of 24.4(+/- 0.4) pM, but remained essentially non-toxic in the dark. The involvement of reactive oxygen species and an apoptotic nature of cell death were observed from the cellular studies. (C) 2014 Elsevier Ltd. All rights reserved.