Cyclin B1/Cdk1 phosphorylation of mitochondrial p53 induces anti-apoptotic response.

The pro-apoptotic function of p53 has been well defined in preventing genomic instability and cell transformation. However, the intriguing fact that p53 contributes to a pro-survival advantage of tumor cells under DNA damage conditions raises a critical question in radiation therapy for the 50% human cancers with intact p53 function. Herein, we reveal an anti-apoptotic role of mitochondrial p53 regulated by the cell cycle complex cyclin B1/Cdk1 in irradiated human colon cancer HCT116 cells with p53(+/+) status. Steady-state levels of p53 and cyclin B1/Cdk1 were identified in the mitochondria of many human and mouse cells, and their mitochondrial influx was significantly enhanced by radiation. The mitochondrial kinase activity of cyclin B1/Cdk1 was found to specifically phosphorylate p53 at Ser-315 residue, leading to enhanced mitochondrial ATP production and reduced mitochondrial apoptosis. The improved mitochondrial function can be blocked by transfection of mutant p53 Ser-315-Ala, or by siRNA knockdown of cyclin B1 and Cdk1 genes. Enforced translocation of cyclin B1 and Cdk1 into mitochondria with a mitochondrial-targeting-peptide increased levels of Ser-315 phosphorylation on mitochondrial p53, improved ATP production and decreased apoptosis by sequestering p53 from binding to Bcl-2 and Bcl-xL. Furthermore, reconstitution of wild-type p53 in p53-deficient HCT116 p53(-/-) cells resulted in an increased mitochondrial ATP production and suppression of apoptosis. Such phenomena were absent in the p53-deficient HCT116 p53(-/-) cells reconstituted with the mutant p53. These results demonstrate a unique anti-apoptotic function of mitochondrial p53 regulated by cyclin B1/Cdk1-mediated Ser-315 phosphorylation in p53-wild-type tumor cells, which may provide insights for improving the efficacy of anti-cancer therapy, especially for tumors that retain p53

EPR and preparative studies of 5-endo cyclizations of radicals derived from alkenyl NHC-boranes bearing tert-butyl ester substituents

J.C.W. thanks EaStCHEM for financial support, and D.P.C. thanks the US National Science Foundation. Computational support was provided through the EaStCHEM Research Computing Facility.Radical H atom abstraction from a set of N-heterocyclic carbene (NHC) complexes of alkenylboranes bearing two tert-butyl ester substituents was studied by EPR spectroscopy. The initial boraallyl radical intermediates rapidly ring closed onto the O atoms of their distal ester groups in 5-endo mode to yield 1,2-oxaborole radicals. Unexpectedly, two structural varieties of these radicals were identified from their EPR spectra. These proved to be two stable rotamers, in which the carbonyl group of the tert-butyl ester was oriented toward and away from the NHC ring. These rotamers were akin to the s-trans and s-cis rotamers of α,β-unsaturated carbonyl compounds. Their stability was attributed to the quasi-allylic interaction of their unpaired electrons with the carbonyl units of their adjacent ester groups. EPR spectroscopic evidence for two rotamers of the analogous methyl ester containing NHC-oxaborole radicals was also obtained. An improved synthetic procedure for preparing rare NHC-boralactones was developed involving treatment of the alkenyl NHC-boranes with AIBN and tert-dodecanethiol.PostprintPeer reviewe

EPR studies on the addition of ligated boryl radicals to carbonyl compounds

J.C.W. thanks EaStCHEM for financial support and D.P.C. thanks the US National Science Foundation. Computational support was provided through the EaStCHEM Research Computing Facility.The boron-centered radicals derived from alkenyl N-heterocyclic carbene (NHC)-boranes bearing ester substituents were recently found to ring close in 5-endo mode by addition to the oxygen atoms of the ester substituents. The inference from this was that NHC-boryl radicals might add intermolecularly to carbonyl-containing substrates. Several different NHC-boryl radicals were generated by H-atom abstraction from NHC-ligated trihydroborates. Electron paramagnetic resonance (EPR) spectroscopy proved that these did indeed add to the oxygen atoms of diaryl ketones with production of the corresponding bora-ketyl radicals. The same unusual regioselectivity of addition was observed with monoaryl ketones, but no bora-ketyls were observed with dialkyl ketones. Similarly, no bora-ketyl adduct radicals were observed with esters, even esters of benzoic acid. EPR spectroscopic evidence suggested that NHC-boryl radicals were also added to the O-atoms of aromatic aldehydes. Amine-boryl and phosphine-boryl radicals were also observed to add to the O-atom of benzophenone with production of the corresponding ketyl radicals.PostprintPeer reviewe

Chern-Simons terms in Noncommutative Geometry and its application to Bilayer Quantum Hall Systems

Considering bilayer systems as extensions of the planar ones by an internal space of two discrete points, we use the ideas of Noncommutative Geometry to construct the gauge theories for these systems. After integrating over the discrete space we find an effective $2+1$ action involving an extra complex scalar field, which can be interpreted as arising from the tunneling between the layers. The gauge fields are found in different phases corresponding to the different correlations due to the Coulomb interaction between the layers. In a particular phase, when the radial part of the complex scalar field is a constant, we recover the Wen-Zee model of Bilayer Quantum Hall systems. There are some circumstances, where this radial part may become dynamical and cause dissipation in the oscillating supercurrent between the layers.Comment: 17 pages, more explanations have been added to make our points clearer compared with the previous densed versio

Hydrogenation of Magnesium Nickel Boride for Reversible Hydrogen Storage

We report that a ternary magnesium nickel boride (MgNi_(2.5)B_2) mixed with LiH and MgH_2 can be hydrogenated reversibly forming LiBH_4 and Mg_2NiH_4 at temperatures below 300 °C. The ternary boride was prepared by sintering a mechanically milled mixture of MgB_2 and Ni precursors at 975 °C under inert atmosphere. Hydrogenation of the ternary, milled with LiH and MgH_2, was performed under 100 to 160 bar H_2 at temperatures up to 350 °C. Analysis using X-ray diffraction, Fourier transform infrared, and ^(11)B magic angle spinning NMR confirmed that the ternary boride was hydrogenated forming borohydride anions. The reaction was reversible with hydrogenation kinetics that improved over three cycles. This work suggests that there may be other ternary or higher order boride phases useful for reversible hydrogen storage

Flexural Behaviour of Reinforced Concrete Beams Strengthened with a Composite Reinforcement Layer: BFRP Grid and ECC

In this paper, a new strengthening technique for reinforced concrete (RC) beams is proposed by combining Basalt fiber Reinforced Polymer (BFRP) grid and Engineered Cementitious Composites (ECC) as a composite reinforcement layer (CRL). Five RC beams externally bonded with the CRL at the soffit and one control RC beam were tested to investigate their flexural behaviour. The thickness of BFRP grids (i.e. 1 mm, 3 mm and 5 mm) and the bonded length of CRL (i.e. 400 mm, 450 mm and 500 mm) were selected as two main parameters in the test program, while the width and thickness of CRL were fixed approximately at 200 mm and 30 mm, respectively. The test results showed that there is no clear CRL debonding in the strengthened beams. The two final failure modes were concrete crushing or rupture of the BFRP grids, indicating that the proposed technique is effective in suppressing the debonding of externally bonded materials and fully utilizing the material strengths. An analytical model is also presented to predict the load-deflection responses of the strengthened beams, which was validated through comparisons with the test results

Gaseous, PM2.5 Mass, and Speciated Emission Factors from Laboratory Chamber Peat Combustion

Peat fuels representing four biomes of boreal (western Russia and Siberia), temperate (northern Alaska, USA), subtropical (northern and southern Florida, USA), and tropical (Borneo, Malaysia) regions were burned in a laboratory chamber to determine gas and particle emission factors (EFs). Tests with 25 % fuel moisture were conducted with predominant smoldering combustion conditions (average modified combustion efficiency (MCE) =0.82+/-0.08). Average fuel-based EFCO2 (carbon dioxide) are highest (1400 +/- 38 g kg(-1)) and lowest (1073 +/- 63 g kg(-1)) for the Alaskan and Russian peats, respectively. EFCO (carbon monoxide) and EFCH4 (methane) are similar to 12 %15 % and similar to 0.3 %0.9 % of EFCO2, in the range of 157171 and 310 g kg(-1), respectively. EFs for nitrogen species are at the same magnitude as EFCH4, with an average of 5.6 +/- 4.8 and 4.7 +/- 3.1 g kg(-1) for EFNH3 (ammonia) and EFHCN (hydrogen cyanide); 1.9+/-1.1 g kg(-1) for EFNOx (nitrogen oxides); and 2.4+/-1.4 and 2.0 +/- 0.7 g kg(-1) for EFNOy (total reactive nitrogen) and EFN2O (nitrous oxide). An oxidation flow reactor (OFR) was used to simulate atmospheric aging times of similar to 2 and similar to 7 d to compare fresh (upstream) and aged (downstream) emissions. Filter-based EFPM2.5 varied by \u3e 4-fold (1461 g kg(-1)) without appreciable changes between fresh and aged emissions. The majority of EFPM2.5 consists of EFOC (organic carbon), with EFOC / EFPM2.5 ratios in the range of 52 %98 % for fresh emissions and similar to 14 %23 % degradation after aging. Reductions of EFOC (similar to 79 g kg(-1)) after aging are most apparent for boreal peats, with the largest degradation in low-temperature OC1 that evolves at \u3c 140 degrees C, indicating the loss of high-vapor-pressure semivolatile organic compounds upon aging. The highest EFLevoglucosan is found for Russian peat (similar to 16 g kg(-1)), with similar to 35 %50 % degradation after aging. EFs for water-soluble OC (EFWSOC) account for similar to 20 %62 % of fresh EFOC. The majority (\u3e 95 %) of the total emitted carbon is in the gas phase, with 54 %75 % CO2, followed by 8 %30 % CO. Nitrogen in the measured species explains 24 %52 % of the consumed fuel nitrogen, with an average of 35 +/- 11 %, consistent with past studies that report similar to 1/3 to 2/3 of the fuel nitrogen measured in biomass smoke. The majority (\u3e 99 %) of the total emitted nitrogen is in the gas phase, with an average of 16.7 % as NH3 and 9.5 % as HCN center dot N2O and NOy constituted 5.7 % and 2.9 % of consumed fuel nitrogen. EFs from this study can be used to refine current emission inventories

IDENTIFICATION OF THE ORIGINS OF ELEVATED ATMOSPHERIC MERCURY EPISODES USING A LAGRANGIAN MODELLING SYSTEM

We report the application of a receptor-oriented transport model, the Stochastic Time-Inverted Lagrangian Transport (STILT) model, to the interpretation of hourly total gaseous mercury (TGM) concentrations at three monitoring sites in Southern Ontario during four episodes of high TGM. STILT is a Lagrangian modelling system (Lin, J.C. et al. 2003) that simulates the transport of ensembles of air parcels backward in time from an observation point to upstream locations where surface inputs of target species occurred. A complete inventory of anthropogenic and natural mercury sources were used to compute the emissions. The study was initiated by simulating the mercury concentrations in a North American domain using CMAQ-Hg, a regional Eulerian chemical transport model (CTM). The STILT model was applied to several short episodes (usually lasting for 1-4 days) in which the TGM measurements at four air quality measurement stations in Southern Ontario significantly exceeded the predictions of the CTM. The STILT analysis compared the origins of air parcels arriving during the elevated TGM episodes with those of air parcels arriving at proximal times when the measurements and the CTM predictions were both low. The results consist of the STILT–predicted hourly concentrations at the measurement site as well as the surface footprint where the mercury responsible for the episode was emitted. The temporal STILT prediction is in better agreement with the measured time series than that of CMAQ-Hg. We believe this is partly due to the superior ability of STILT to capture near-field influences and partly due to the spatial averaging inherent in Eulerian modelling. Also, the predicted footprint locations were reasonable, coinciding with known locations of large mercury sources during the high episodes and with cleaner areas otherwise