A New LC-MS/MS Method for the Quantification of Endogenous and Vinyl Chloride-Induced 7-(2-Oxoethyl)Guanine in Sprague–Dawley Rats

Vinyl chloride (VC) is an industrial chemical that is known to be carcinogenic to animals and humans. VC primarily induces hepatic angiosarcomas following high exposures (≥50 ppm). VC is also found in Superfund sites at ppb concentrations as a result of microbial metabolism of trichloroethylene and perchloroethylene. Here, we report a new sensitive LC-MS/MS method to analyze the major DNA adduct formed by VC, 7-(2-oxoethylguanine) (7-OEG). We used this method to analyze tissue DNA from both adult and weanling rats exposed to 1100 ppm [13C2]-VC for 5 days. After neutral thermal hydrolysis, 7-OEG was derivatized with O-t-butyl hydroxylamine to an oxime adduct, followed by LC-MS/MS analysis. The limit of detection was 1 fmol and the limit of quantitation was 1.5 fmol on the column. The use of stable isotope VC allowed us to demonstrate for the first time that endogenous 7-OEG was present in tissue DNA. We hypothesized that endogenous 7-OEG was formed from lipid peroxidation and demonstrated the formation of [13C2]-7-OEG from the reaction of calf thymus DNA with [13C18]-ethyl linoleate (EtLa) under peroxidizing conditions. The concentrations of endogenous 7-OEG in liver, lung, kidney, spleen, testis and brain DNA from adult and weanling rats typically ranged from 1.0-10.0 adducts per 106 guanine. The exogenous 7-OEG in liver DNA from adult rats exposed to 1100 ppm [13C2]-VC for 5 days was 104.0 ± 23.0 adducts per 106 guanine (n=4), while concentrations in other tissues ranged from 1.0-39.0 adducts per 106 guanine (n=4). Although endogenous concentrations of 7-OEG in tissues in weanling rats were similar to those of adult rats, exogenous [13C2]-7-OEG concentrations were higher in weanlings, averaging 300 adducts per 106 guanine in liver. Studies on the persistence of [13C2]-7-OEG in adult rats sacrificed 2, 4, and 8 wks post exposure to [13C2]-VC demonstrated a half-life of 7-OEG of 4 days in both liver and lung

Microphase separation of highly amphiphilic, low N polymers by photoinduced copper-mediated polymerization, achieving sub-2 nm domains at half-pitch

The lower limit of domain size resolution using microphase separation of short poly(acrylic acid) homopolymers equipped with a short fluorinated tail, posing as an antagonist 'A block' in pseudo AB block copolymers has been investigated. An alkyl halide initiator with a fluorocarbon chain was utilized as a first 'A block' in the synthesis of low molecular weight polymers (1400-4300 g mol -1) using photoinduced Cu(ii)-mediated polymerization allowing for very narrow dispersity. Poly(tert-butyl acrylate) was synthesized and subsequently deprotected to give very low degrees of polymerization (N), amphiphilic polymers with low dispersity (D = 1.06-1.13). By exploiting the high driving force for demixing and the well-defined 'block' sizes, we are able to control the nanostructure in terms of domain size (down to 3.4 nm full-pitch) and morphology. This work demonstrates the simple and highly controlled synthesis of polymers to push the boundaries of the smallest achievable domain sizes obtained from polymer self-assembly

Efficient Network Reconstruction from Dynamical Cascades Identifies Small-World Topology of Neuronal Avalanches

Cascading activity is commonly found in complex systems with directed interactions such as metabolic networks, neuronal networks, or disease spreading in social networks. Substantial insight into a system's organization can be obtained by reconstructing the underlying functional network architecture from the observed activity cascades. Here we focus on Bayesian approaches and reduce their computational demands by introducing the Iterative Bayesian (IB) and Posterior Weighted Averaging (PWA) methods. We introduce a special case of PWA, cast in nonparametric form, which we call the normalized count (NC) algorithm. NC efficiently reconstructs random and small-world functional network topologies and architectures from subcritical, critical, and supercritical cascading dynamics and yields significant improvements over commonly used correlation methods. With experimental data, NC identified a functional and structural small-world topology and its corresponding traffic in cortical networks with neuronal avalanche dynamics

Metabolic Networks of Sodalis glossinidius: A Systems Biology Approach to Reductive Evolution

Background: Genome reduction is a common evolutionary process affecting bacterial lineages that establish symbiotic or pathogenic associations with eukaryotic hosts. Such associations yield highly reduced genomes with greatly streamlined metabolic abilities shaped by the type of ecological association with the host. Sodalis glossinidius, the secondary endosymbiont of tsetse flies, represents one of the few complete genomes available of a bacterium at the initial stages of this process. In the present study, genome reduction is studied from a systems biology perspective through the reconstruction and functional analysis of genome-scale metabolic networks of S. glossinidius. Results: The functional profile of ancestral and extant metabolic networks sheds light on the evolutionary events underlying transition to a host-dependent lifestyle. Meanwhile, reductive evolution simulations on the extant metabolic network can predict possible future evolution of S. glossinidius in the context of genome reduction. Finally, knockout simulations in different metabolic systems reveal a gradual decrease in network robustness to different mutational events for bacterial endosymbionts at different stages of the symbiotic association. Conclusions: Stoichiometric analysis reveals few gene inactivation events whose effects on the functionality of S. glossinidius metabolic systems are drastic enough to account for the ecological transition from a free-living to hostdependent lifestyle. The decrease in network robustness across different metabolic systems may be associated with th

Femtosecond laser driven high-flux highly collimated MeV-proton beam

金沢大学先端科学・社会共創推進機構Highlly collimated energetic protons whose energies are up to 4 MeV are generated by an intense femtosecond Titanium Sappheire laser pulse interacting with a 7.5, 12.5, and 25 μm-thick Polyimide tape target and 5 μm-thick copper target. We find no clear difference on the proton spectra from 7.5, 12.5, and 25 μm Polyimide tape target. The highest conversion efficiency from laser energy into protons of ∼3% is observed with a 7.5 μm thick Polyimide target. The quality of the proton beam is good enough to obtain a clear projection image of a mesh having 10 μm line and space structure, installed into the passage of the beam. We obtain clear vertical lines on the proton intensity profiles from the copper target, which are considered to be transferred from the surface of the copper target. From it, we can restrict the size of the proton emitting region to be ∼20μm. © 2008 American Institute of Physics.Embargo Period 12 month

Atomic Layer Deposition of 2D Metal Dichalcogenides for Electronics, Catalysis, Energy Storage, and Beyond

2D transition metal dichalcogenides (TMDCs) are among the most exciting materials of today. Their layered crystal structures result in unique and useful electronic, optical, catalytic, and quantum properties. To realize the technological potential of TMDCs, methods depositing uniform films of controlled thickness at low temperatures in a highly controllable, scalable, and repeatable manner are needed. Atomic layer deposition (ALD) is a chemical gas-phase thin film deposition method capable of meeting these challenges. In this review, the applications evaluated for ALD TMDCs are systematically examined, including electronics and optoelectonics, electrocatalysis and photocatalysis, energy storage, lubrication, plasmonics, solar cells, and photonics. This review focuses on understanding the interplay between ALD precursors and deposition conditions, the resulting film characteristics such as thickness, crystallinity, and morphology, and ultimately device performance. Through rational choice of precursors and conditions, ALD is observed to exhibit potential to meet the varying requirements of widely different applications. Beyond the current state of ALD TMDCs, the future prospects, opportunities, and challenges in different applications are discussed. The authors hope that the review aids in bringing together experts in the fields of ALD, TMDCs, and various applications to eventually realize industrial applications of ALD TMDCs.Peer reviewe

Principles of genetic circuit design

Cells navigate environments, communicate and build complex patterns by initiating gene expression in response to specific signals. Engineers seek to harness this capability to program cells to perform tasks or create chemicals and materials that match the complexity seen in nature. This Review describes new tools that aid the construction of genetic circuits. Circuit dynamics can be influenced by the choice of regulators and changed with expression 'tuning knobs'. We collate the failure modes encountered when assembling circuits, quantify their impact on performance and review mitigation efforts. Finally, we discuss the constraints that arise from circuits having to operate within a living cell. Collectively, better tools, well-characterized parts and a comprehensive understanding of how to compose circuits are leading to a breakthrough in the ability to program living cells for advanced applications, from living therapeutics to the atomic manufacturing of functional materials.National Institute of General Medical Sciences (U.S.) (Grant P50 GM098792)National Institute of General Medical Sciences (U.S.) (Grant R01 GM095765)National Science Foundation (U.S.). Synthetic Biology Engineering Research Center (EEC0540879)Life Technologies, Inc. (A114510)National Science Foundation (U.S.). Graduate Research FellowshipUnited States. Office of Naval Research. Multidisciplinary University Research Initiative (Grant 4500000552