A real-space study of random extended defects in solids : application to disordered Stone-Wales defects in graphene

We propose here a first-principles, parameter free, real space method for the study of disordered extended defects in solids. We shall illustrate the power of the technique with an application to graphene sheets with randomly placed Stone-Wales defects and shall examine the signature of such random defects on the density of states as a function of their concentration. The technique is general enough to be applied to a whole class of systems with lattice translational symmetry broken not only locally but by extended defects and defect clusters. The real space approach will allow us to distinguish signatures of specific defects and defect clusters.Comment: 11 pages, 24 figure

Structural Adjustment, Global Trade and the New Political Economy of Development

Biplab Dasgupta. Structural Adjustment Global Trade and the New Political Economy of Development. New Delhi. Sage Publications. 1998. Price Indian Rupees 450 (hardback). The author has written a very topical book the relevance of which cannot be understated. At the core of the book the author discusses the concept of the new political economy of development which forms the theoretical underpinnings that lie behind the structural adjustment/ stabilisation programmes of the international financial institutions such as the World Bank and the International Monetary Fund. Biplab Dasgupta has very concisely and succinctly analysed the new political economy of development which has, as its centre-piece, a blind faith in the operation of free-market forces. This can be traced back to the Reagan and Thatcher years, which saw a shift away from interventionist policies to allowing the markets to decide

The making of ferromagnetic Fe doped ZnO nano-clusters

In this letter, the authors present a study of the energetics and magnetic interactions in Fe doped ZnO clusters by ab-initio density functional calculations. The results indicate that defects under suitable conditions can induce ferromagnetic interactions between the dopant Fe atoms whereas antiferromagnetic coupling dominates in a neutral defect-free cluster. The calculations also reveal an unusual ionic state of the dopant Fe atom residing at the surface of the cluster, a feature that is important to render the cluster ferromagnetic.Comment: 3 pages, 3 figure

Purification and biochemical characterization of a protein-palmitoyl acyltransferase from human erythrocytes

Protein palmitoylation involves the post-translational attachment of palmitate in thioester linkage to cysteine residues of proteins. The labile nature of the thioester linkage makes possible the palmitoylation-depalmitoylation cycles that have emerged in recent times as additions to the repertoire of cellular control mechanisms. However, detailed understanding of these cycles has been limited by the lack of knowledge of the transferases and thioesterases likely to be involved. Here, we describe the purification of a protein-palmitoyl acyltransferase (PAT) from human erythrocytes. PAT behaved as a peripheral membrane protein and catalyzed the attachment of palmitate in thioester linkage to the β-subunit of spectrin. On SDS-polyacrylamide gel electrophoresis, PAT appeared as a 70-kDa polypeptide. Antibody against this polypeptide could immunodeplete PAT activity from the crude extract, confirming the assignment of the 70-kDa polypeptide as PAT. PAT-mediated spectrin palmitoylation could be inhibited by nonradioactive palmitoyl-, myristoyl-, or stearoyl-CoA. The apparent Km for palmitoyl-CoA was 16μM

FOXD1-ALDH1A3 signaling is a determinant for the self-renewal and tumorigenicity of mesenchymal glioma stem cells

Glioma stem-like cells (GSC) with tumor-initiating activity orchestrate the cellular hierarchy in glioblastoma and engender therapeutic resistance. Recent work has divided GSC into two subtypes with a mesenchymal (MES) GSC population as the more malignant subtype. In this study, we identify the FOXD1-ALDH1A3 signaling axis as a determinant of the MES GSC phenotype. The transcription factor FOXD1 is expressed predominantly in patient-derived cultures enriched with MES, but not with the proneural GSC subtype. shRNA-mediated attenuation of FOXD1 in MES GSC ablates their clonogenicity in vitro and in vivo. Mechanistically, FOXD1 regulates the transcriptional activity of ALDH1A3, an established functional marker for MES GSC. Indeed, the functional roles of FOXD1 and ALDH1A3 are likely evolutionally conserved, insofar as RNAi-mediated attenuation of their orthologous genes in Drosophila blocks formation of brain tumors engineered in that species. In clinical specimens of high-grade glioma, the levels of expression of both FOXD1 and ALDH1A3 are inversely correlated with patient prognosis. Finally, a novel small-molecule inhibitor of ALDH we developed, termed GA11, displays potent in vivo efficacy when administered systemically in a murine GSC-derived xenograft model of glioblastoma. Collectively, our findings define a FOXD1-ALDH1A3 pathway in controling the clonogenic and tumorigenic potential of MES GSC in glioblastoma tumors

Coordinated targeting of S6K1/2 and AXL disrupts pyrimidine biosynthesis in PTEN-deficient glioblastoma

Intrinsic resistance to targeted therapeutics in PTEN-deficient glioblastoma (GBM) is mediated by redundant signaling networks that sustain critical metabolic functions. Here we demonstrate that coordinated inhibition of the ribosomal protein S6 kinase 1 (S6K1) and the receptor tyrosine kinase AXL using LY-2584702 and BMS-777607 can overcome network redundancy to reduce GBM tumor growth. This combination of S6K1 and AXL inhibition suppressed glucose flux to pyrimidine biosynthesis. Genetic inactivation studies to map the signaling network indicated that both S6K1 and S6K2 transmit growth signals in PTEN-deficient GBM. Kinome-wide ATP binding analysis in inhibitor-treated cells revealed that LY-2584702 directly inhibited S6K1, and substrate phosphorylation studies showed that BMS-777607 inactivation of upstream AXL collaborated to reduce S6K2-mediated signal transduction. Thus, combination targeting of S6K1 and AXL provides a kinase-directed therapeutic approach that circumvents signal transduction redundancy to interrupt metabolic function and reduce growth of PTEN-deficient GBM