The epigenetic control of E-box and Myc-dependent chromatin modifications regulate the licensing of lamin B2 origin during cell cycle

Recent genome-wide mapping of the mammalian replication origins has suggested the role of transcriptional regulatory elements in origin activation. However, the nature of chromatin modifications associated with such trans-factors or epigenetic marks imprinted on cis-elements during the spatio-temporal regulation of replication initiation remains enigmatic. To unveil the molecular underpinnings, we studied the human lamin B2 origin that spatially overlaps with TIMM 13 promoter. We observed an early G1-specific occupancy of c-Myc that facilitated the loading of mini chromosome maintenance protein (MCM) complex during subsequent mid-G1 phase rather stimulating TIMM 13 gene expression. Investigations on the Myc-induced downstream events suggested a direct interaction between c-Myc and histone methyltransferase mixed-lineage leukemia 1 that imparted histone H3K4me3 mark essential for both recruitment of acetylase complex HBO1 and hyperacetylation of histone H4. Contemporaneously, the nucleosome remodeling promoted the loading of MCM proteins at the origin. These chromatin modifications were under the tight control of active demethylation of E-box as evident from methylation profiling. The active demethylation was mediated by the Ten-eleven translocation (TET)-thymine DNA glycosylase-base excision repair (BER) pathway, which facilitated spatio-temporal occupancy of Myc. Intriguingly, the genome-wide 43% occurrence of E-box among the human origins could support our hypothesis that epigenetic control of E-box could be a molecular switch for the licensing of early replicating origins

Non-Destructive Evaluation—A Pivotal Technology for Qualification of Composite Aircraft Structures

Tremendous advances in composite materials and a deeper understanding of their behavior have been responsible for the increased use of composites in the development of advanced, new generation civil and military aircraft. Composites play an important role in any aircraft development programme and are strong contenders to their metal counterparts due to their significant contributions towards improving strength, stiffness, fatigue properties & weight reduction. As materials, structural design & processing have evolved, strong emphasis is placed on effective & reliable damage detection, durability and damage tolerance. As a consequence, Non-destructive Evaluation (NDE) has also undergone significant advances towards meeting the growing demands of quality assurance. Advanced Composites Division (ACD) of National Aerospace Laboratories (NAL), has been involved in the development of composite structures for both civil and military aircraft for over a decade and a half. Innovative composite processing methods like co-curing/co-bonding have been successfully employed to realize airworthy structures. The role of NDE in the development of these structures has been critical and not limited to damage detection alone. On several occasions, NDE has provided valuable inputs towards improving design and process parameters. In-spite of the complexity of the structures, stringent quality requirements and tight delivery schedules, NDE has been successful in certifying these composite structures for airworthiness. This paper discusses the implementation of key NDE techniques like ultrasonics, radiography, acoustic emission and thermography for reliable flaw detection, characterization and quality assurance of composite aircraft structures

Geometric phase for a dimerized disordered continuum: Topological shot noise

Geometric phase shift associated with an electron propagating through a dimerized-disordered continuum is shown to be 0, or $\pm \pi$ (modulo 2$\pi$), according as the associated circuit traversed in the two-dimensional parameter space excludes, or encircles a certain singularity. This phase-shift is a topological invariant. Its discontinuous dependence on the electron energy and disorder implies a statistical spectral and conductance fluctuation in a corresponding mesoscopic system. Inasmuch as the fluctuation derives from the discreteness of the phase shift, it may aptly be called a topological shot-noise.Comment: 10 pages(LATEX) + 1 figure, (revised version). Will appear in Europhys. Let