Synthesis of oligodeoxyribonucleotides containing a tricyclic thio analogue of O6-methylguanine and their recognition by MGMT and Atl1

Promutagenic O6-alkylguanine adducts in DNA are repaired in humans by O6-methylguanine-DNA-methyltransferase (MGMT) in an irreversible reaction. Here we describe the synthesis of a phosphoramidite that allows the preparation of oligodeoxyribonucleotides (ODNs) containing a novel tricyclic thio analogue of O6-methylguanine in which the third ring bridges the 6-thio group and C7 of a 7-deazapurine. These ODNs are very poor substrates for MGMT and poorly recognised by the alkyltransferase-like protein, Atl1. Examination of the active sites of both MGMT and Atl1 suggest large steric clashes hindering binding of the analogue. Such analogues, if mutagenic, are likely to be highly toxic

Experimental characterization of a graded-index ring-core fiber supporting 7 LP mode groups

We design and characterize a graded-index-ring-core fiber supporting 7 LP modegroups (13 spatial modes) for mode multiplexed transmission with low MIMO processing complexity. Spatial and temporal modal properties are analyzed using an SLM-based mode multiplexer/demultiplexer

Radiative corrections to low energy neutrino reactions

We show that the radiative corrections to charged current (CC) nuclear reactions with an electron(positron) in the final state are described by a universal function. The consistency of our treatment of the radiative corrections with the procedure used to extract the value of the axial coupling constant $g_A$ is discussed. To illustrate we apply our results to (anti)neutrino deuterium disintegration and to $pp$ fusion in the sun. The limit of vanishing electron mass is considered, and a simple formula valid for E_{obs}\gsim 1 MeV is obtained. The size of the nuclear structure-dependent effects is also discussed. Finally, we consider CC transitions with an electron(positron) in the initial state and discuss some applications to electron capture reactions.Comment: 23 pages, 5 figure

Basic principles of stable isotope analysis in humanitarian forensic science.

While the identity of a victim of a localized disaster – such as a train or bus crash – may be established quickly through personal effects, fingerprints, dental records, and a comparison of decedent DNA to family reference specimen DNA, a different scenario presents itself in mass disasters, such as the Asian Tsunami of 2004. In the aftermath of the tsunami, visual appearance was initially used to assign “foreign” or “indigenous” classifications to the remains of thousands of victims. However, this visual identification approach was undermined by the speed with which bodies deteriorated under the hot and humid conditions. Time was spent populating ante-mortem DNA databases for different nationalities, which led to problems when creating a post-mortem DNA database because recovery of viable DNA was compromised due to rapid decomposition. As a consequence, only 1.3% of victims were identified by DNA; in contrast, 61% were identified based on dental examination, although this process took several months and a significant number of deceased from the 2004 Asian Tsunami still remain to be identified

UHECR as Decay Products of Heavy Relics? The Lifetime Problem

The essential features underlying the top-down scenarii for UHECR are discussed, namely, the stability (or lifetime) imposed to the heavy objects (particles) whatever they be: topological and non-topological solitons, X-particles, cosmic defects, microscopic black-holes, fundamental strings. We provide an unified formula for the quantum decay rate of all these objects as well as the particle decays in the standard model. The key point in the top-down scenarii is the necessity to adjust the lifetime of the heavy object to the age of the universe. This ad-hoc requirement needs a very high dimensional operator to govern its decay and/or an extremely small coupling constant. The natural lifetimes of such heavy objects are, however, microscopic times associated to the GUT energy scale (sim 10^{-28} sec. or shorter). It is at this energy scale (by the end of inflation) where they could have been abundantly formed in the early universe and it seems natural that they decayed shortly after being formed.Comment: 11 pages, LaTex, no figures, updated versio

Time Evolution of Unstable Particle Decay Seen with Finite Resolution

Time evolution of the decay process of unstable particles is investigated in field theory models. We first formulate how to renormalize the non-decay amplitude beyond perturbation theory and then discuss short-time behavior of very long-lived particles. Two different formalisms, one that does and one that does not, assume existence of the asymptotic field of unstable particles are considered. The non-decay amplitude is then calculated by introducing a finite time resolution of measurement, which makes it possible to discuss both renormalizable and non-renormalizable decay interaction including the nucleon decay. In ordinary circumstances the onset of the exponential decay law starts at times as early as at roughly the resolution time, but with an enhanced amplitude which may be measurable. It is confirmed that the short-time formula $1 - \Gamma t$ of the exponential decay law may be used to set limits on the nucleon decay rate in underground experiments. On the other hand, an exceptional example of S-wave decay of very small Q-value is found, which does not have the exponential period at all.Comment: 26 pages, LATEX file with 8 PS figure

Lung disease phenotypes caused by overexpression of combinations of α-, β-, and γ-subunits of the epithelial sodium channel in mouse airways

The epithelial Na+ channel (ENaC) regulates airway surface hydration. In mouse airways, ENaC is composed of three subunits, α, β, and γ, which are differentially expressed (α > β > γ). Airway-targeted overexpression of the β subunit results in Na+ hyperabsorption, causing airway surface dehydration, hyperconcentrated mucus with delayed clearance, lung inflammation, and perinatal mortality. Notably, mice overexpressing the α- or γ-subunit do not exhibit airway Na+ hyperabsorption or lung pathology. To test whether overexpression of multiple ENaC subunits produced Na+ transport and disease severity exceeding that of βENaC-Tg mice, we generated double (αβ, αγ, βγ) and triple (αβγ) transgenic mice and characterized their lung phenotypes. Double αγENaC-Tg mice were indistinguishable from WT littermates. In contrast, double βγENaC-Tg mice exhibited airway Na+ absorption greater than that of βENaC-Tg mice, which was paralleled by worse survival, decreased mucociliary clearance, and more severe lung pathology. Double αβENaC-Tg mice exhibited Na+ transport rates comparable to those of βENaC-Tg littermates. However, αβENaC-Tg mice had poorer survival and developed severe parenchymal consolidation. In situ hybridization (RNAscope) analysis revealed both alveolar and airway αENaC-Tg overexpression. Triple αβγENaC-Tg mice were born in Mendelian proportions but died within the first day of life, and the small sample size prevented analyses of cause(s) of death. Cumulatively, these results indicate that overexpression of βENaC is rate limiting for generation of pathological airway surface dehydration. Notably, airway co-overexpression of β- and γENaC had additive effects on Na+ transport and disease severity, suggesting dose dependency of these two variables

Can forest management based on natural disturbances maintain ecological resilience?

Given the increasingly global stresses on forests, many ecologists argue that managers must maintain ecological resilience: the capacity of ecosystems to absorb disturbances without undergoing fundamental change. In this review we ask: Can the emerging paradigm of natural-disturbance-based management (NDBM) maintain ecological resilience in managed forests? Applying resilience theory requires careful articulation of the ecosystem state under consideration, the disturbances and stresses that affect the persistence of possible alternative states, and the spatial and temporal scales of management relevance. Implementing NDBM while maintaining resilience means recognizing that (i) biodiversity is important for long-term ecosystem persistence, (ii) natural disturbances play a critical role as a generator of structural and compositional heterogeneity at multiple scales, and (iii) traditional management tends to produce forests more homogeneous than those disturbed naturally and increases the likelihood of unexpected catastrophic change by constraining variation of key environmental processes. NDBM may maintain resilience if silvicultural strategies retain the structures and processes that perpetuate desired states while reducing those that enhance resilience of undesirable states. Such strategies require an understanding of harvesting impacts on slow ecosystem processes, such as seed-bank or nutrient dynamics, which in the long term can lead to ecological surprises by altering the forest's capacity to reorganize after disturbance