The 18 September 2011, North Sikkim earthquake

The 18 September 2011, magnitude Mw 6.9 earthquake close to the Nepal-Sikkim border caused significant damage due to ground shaking and caused several landslides. Observations from the post-earthquake surveys in the affected areas within Sikkim suggest that the poorly engineered, multistoried structures were relatively more impacted. Those located on alluvial terraces were also affected. The morphology of the region is prone to landslides and the possibility for their increased intensity during the forthcoming monsoon need to be considered seriously. From the seismotectonic perspective, the mid-crustal focal depth of the North Sikkim earthquake reflects the ongoing deformation of the subducting Indian plate.

IN-VITRO CYTOTOXICITY AND CELL CYCLE ANALYSIS OF TWO NOVEL BIS-1, 2, 4-TRIAZOLE DERIVATIVES: 1,4-BIS[5-(5-MERCAPTO-1,3,4-OXADIAZOL-2-yl-METHYL)-THIO-4-(p-TOLYL)-1, 2,4-TRIAZOL-3-yl]-BUTANE (MNP-14) AND 1,4-BIS[5-(CARBETHOXY-METHYL)-THIO-4-(p-ETHOXY PHENYL)-1,2,4-TRIAZOL-3-yl]-BUTANE (MNP-16)

In the present study, we have tested the cytotoxic and DNA damage activity of two novel bis-1,2,4 triazole derivatives, namely 1,4-bis[5-(5-mercapto-1,3,4-oxadiazol-2-yl-methyl)-thio4-(p-tolyl)-1,2 ,4-triazol-3-yl]-butane (MNP-14) and 1,4-bis[5-(carbethoxy-methyl)-thio-4-(p-ethoxy phenyl) -1,2,4-triazol-3-yl]-butane (MNP-16). The effect of these molecules on cellular apoptosis was also determined. The in-vitro cytotoxicity was evaluated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay as well as Trypan blue dye exclusion methods against human acute lymphoblastic leukemia (MOLT4) and lung cancer cells (A549). Our results showed that MNP-16 induced significant cytotoxicity (IC50 of 3-5 mu M) compared with MNP-14. The cytotoxicity induced by MNP-16 was time and concentration dependent. The cell cycle analysis by flow cytometry (fluorescence-activated cell sorting [FACS]) revealed that though there was a significant increase in the apoptotic population (sub-G1 phase) with an increased concentration of MNP-14 and 16, there was no cell cycle arrest. Further, the comet assay results indicated considerable DNA

Mechanism of Fragility at BCL2 Gene Minor Breakpoint Cluster Region during t(14;18) Chromosomal Translocation

The t(14;18) translocation in follicular lymphoma is one of the most common chromosomal translocations. Breaks in chromosome 18 are localized at the 3'-UTR of BCL2 gene or downstream and are mainly clustered in either the major breakpoint region or the minor breakpoint cluster region (mcr). The recombination activating gene (RAG) complex induces breaks at IgH locus of chromosome 14, whereas the mechanism of fragility at BCL2 mcr remains unclear. Here, for the first time, we show that RAGs can nick mcr; however, the mechanism is unique. Three independent nicks of equal efficiency are generated, when both Mg2+ and Mn2+ are present, unlike a single nick during V(D)J recombination. Further, we demonstrate that RAG binding and nicking at the mcr are independent of nonamer, whereas a CCACCTCT motif plays a critical role in its fragility, as shown by sequential mutagenesis. More importantly, we recapitulate the BCL2 mcr translocation and find that mcr can undergo synapsis with a standard recombination signal sequence within the cells, in a RAG-dependent manner. Further, mutation to the CCACCTCT motif abolishes recombination within the cells, indicating its vital role. Hence, our data suggest a novel, physiologically relevant, nonamer-independent mechanism of RAG nicking at mcr, which may be important for generation of chromosomal translocations in humans.

NMR Analysis of Cross Strand Aromatic Interactions in an 8 Residue Hairpin and a 14 Residue Three Stranded beta-Sheet Peptide

Cross strand aromatic interactions between a facing pair of phenylalanine residues in antiparallel beta-sheet structures have been probed using two structurally defined model peptides. The octapeptide Boc-(LFVPPLFV)-P-D-P-L-OMe (peptide 1) favors the beta-hairpin conformation nucleated by the type II' beta-turn formed by the (D)Pro-(L)Pro segment, placing Phe2 and Phe7 side chains in proximity. Two centrally positioned (D)Pro-(L)Pro segments facilitate the three stranded beta-sheet formation in the 14 residue peptide Boc-LFV(D)P(L)PLFVA(D)P(L)PLFV-OMe (peptide 2) in which the Phe2/Phe7 orientations are similar to that in the octapeptide. The anticipated folded conformations of peptides 1 and 2 are established by the delineation of intramolecularly hydrogen bonded NH groups and by the observation of specific cross strand NOEs. The observation of ring current shifted aromatic protons is a diagnostic of close approach of the Phe2 and Phe7 side chains. Specific assignment of aromatic proton resonances using HSQC and HSQC-TOCSY methods allow an analysis of interproton NOEs between the spatially proximate aromatic rings. This approach facilitates specific assignments in systems containing multiple aromatic rings in spectra at natural abundance. Evidence is presented for a dynamic process which invokes a correlated conformational change about the C-alpha-C-beta(chi(1)) bond for the pair of interacting Phe residues. NMR results suggest that aromatic ring orientations observed in crystals are maintained in solution. Anomalous temperature dependence of ring current induced proton chemical shifts suggests that solvophobic effects may facilitate aromatic ring clustering in apolar solvents.

The effect of minor addition of Ni on the microstructural evolution and mechanical properties of suction cast Al-0.14 at. pct Sc binary alloy

Aluminum scandium binary alloys represent a promising precipitation-hardening alloy system. However, the hardness of the binary alloys decreases with the rapid coarsening of Al3Sc precipitate during high-temperature aging. In the current study, we report a new approach to compensate for the loss of mechanical properties by combining rapid solidification with very small ternary addition of transition metal Ni. This addition yields dispersion, and at a critical concentration improves the mechanical properties. We explore additions of a maximum of 0.06 at. pct of Nickel to a binary Al-0.14 at. pct Sc alloy, which yield nickel-rich dispersions. We report two kinds of biphasic dispersions containing AlNi2Sc/Al9Ni2 and alpha-Al/Al9Ni2 phase combinations. The maximum improvement in mechanical properties occurs with the addition of 0.045 at. pct Ni with a yield strength of 239 +/- A 7 MPa for an aging treatment at 583 K (310 A degrees C) for 15 hours. DOI: 10.1007/s11661-013-1624-z (C) The Minerals, Metals & Materials Society and ASM International 2013

Unprecedented formation of a 14-membered dihydropyran macrocycle via sequential olefin cross metathesis-intramolecular hetero Diels-Alder reaction

Formation of a 2,3-dihydro-4H-pyran containing 14-membered macrocycle by sequential olefin cross metathesis and a highly regiospecific hetero Diels-Alder reaction was observed in the reaction of a hydroxydienone derived from tartaric acid with Grubbs' second generation catalyst. It was found that the free alcohol in the hydroxyenone led to the macrocycle formation, while protection of the hydroxy group formed the ring closing metathesis product. (C) 2013 Elsevier Ltd. All rights reserved.

Polynomial time and parameterized approximation algorithms for boxicity

The boxicity (cubicity) of a graph G, denoted by box(G) (respectively cub(G)), is the minimum integer k such that G can be represented as the intersection graph of axis parallel boxes (cubes) in ℝ k . The problem of computing boxicity (cubicity) is known to be inapproximable in polynomial time even for graph classes like bipartite, co-bipartite and split graphs, within an O(n 0.5 − ε ) factor for any ε > 0, unless NP = ZPP. We prove that if a graph G on n vertices has a clique on n − k vertices, then box(G) can be computed in time n22O(k2logk) . Using this fact, various FPT approximation algorithms for boxicity are derived. The parameter used is the vertex (or edge) edit distance of the input graph from certain graph families of bounded boxicity - like interval graphs and planar graphs. Using the same fact, we also derive an O(nloglogn√logn√) factor approximation algorithm for computing boxicity, which, to our knowledge, is the first o(n) factor approximation algorithm for the problem. We also present an FPT approximation algorithm for computing the cubicity of graphs, with vertex cover number as the parameter.

G-Quadruplex Structures Formed at the HOX11 Breakpoint Region Contribute to Its Fragility during t(10;14) Translocation in T-Cell Leukemia

The t(10;14) translocation involving the HOX11 gene is found in several T-cell leukemia patients. Previous efforts to determine the causes of HOX11 fragility were not successful. The role of non-B DNA structures is increasingly becoming an important cause of genomic instability. In the present study, bioinformatics analysis revealed two G-quadruplex-forming motifs at the HOX11 breakpoint cluster. Gel shift assays showed formation of both intra- and intermolecular G-quadruplexes, the latter being more predominant. The structure formation was dependent on four stretches of guanines, as revealed by mutagenesis. Circular dichroism analysis identified parallel conformations for both quadruplexes. The non-B DNA structure could block polymerization during replication on a plasmid, resulting in consistent K K+-dependent pause sites, which were abolished upon mutation of G-motifs, thereby demonstrating the role of the stretches of guanines even on double-stranded DNA. Extrachromosomal assays showed that the G-quadruplex motifs could block transcription, leading to reduced expression of green fluorescent protein (GFP) within cells. More importantly, sodium bisulfite modification assay showed the single-stranded character at regions I and II of HOX11 in the genome. Thus, our findings suggest the occurrence of G-quadruplex structures at the HOX11 breakpoint region, which could explain its fragility during the t(10;14) translocation.

Unconstrained Homooligomeric gamma-Peptides Show High Propensity for C-14 Helix Formation

Monosubstituted gamma(4)-residues (gamma(4)Leu, gamma(4)Ile, and gamma(4)Val) form helices even in short homooligomeric sequences. C-14 helix formation is established by X-ray diffraction in homooligomeric (gamma)(n) tetra-, hexa- and decapeptide sequences demonstrating the high propensity of gamma residues, with proteinogenic side chains, to adopt locally folded conformations.