In situ tropical peatland fire emission factors and their variability, as determined by field measurements in Peninsula Malaysia.

Fires in tropical peatlands account for >25% of estimated total greenhouse gas emissions from deforestation and degradation. Despite significant global and regional impacts, our understanding of specific gaseous fire emission factors (EFs) from tropical peat burning is limited to a handful of studies. Furthermore, there is substantial variability in EFs between sampled fires and/or studies. For example, methane EFs vary by 91% between studies. Here we present new fire EFs for the tropical peatland ecosystem; the first EFs measured for Malaysian peatlands, and only the second comprehensive study of EFs in this crucial environment. During August 2015 (under El Niño conditions) and July 2016, we embarked on field campaigns to measure gaseous emissions at multiple peatland fires burning on deforested land in Southeast Pahang (2015) and oil palm plantations in North Selangor (2016), Peninsula Malaysia. Gaseous emissions were measured using open-path Fourier transform infrared spectroscopy. The IR spectra were used to retrieve mole fractions of twelve different gases present within the smoke (including carbon dioxide and methane), and these measurements used to calculate EFs. Peat samples were taken at each burn site for physicochemical analysis and to explore possible relationships between specific physicochemical properties and fire EFs. Here we present the first evidence to indicate that substrate bulk density affects methane fire EFs reported here. This novel explanation of inter-plume, within-biome variability should be considered by those undertaking greenhouse gas accounting and haze forecasting in this region, and is of importance to peatland management, particularly with respect to artificial compaction

The Detection of Magnetic Fields Toward M17 through the HI Zeeman Effect

We have carried out VLA Zeeman observations of HI absorption lines toward the HII region in the M17 giant molecular cloud complex. The HI absorption lines toward M17 show between 5 and 8 distinct velocity components which vary spatially in a complex manner across the source. We explore possible physical connections between these components and the M17 region based on calculations of HI column densities, line of sight magnetic field strengths, as well as comparisons with a wide array of previous optical, infrared, and radio observations. In particular, an HI component at the same velocity as the southwestern molecular cloud (M17 SW) ~20 km/s seems to originate from the edge-on interface between the HII region and M17 SW, in un-shocked PDR gas. We have detected a steep enhancement in the 20 km/s HI column density and line of sight magnetic field strengths (Blos) toward this boundary. A lower limit for the peak 20 km/s HI column density is N_{HI}/T_s > 5.6 x 10^{19} cm^{-2}/K while the peak Blos is ~ -450 muG. In addition, blended components at velocities of 11-17 km/s appear to originate from shocked gas in the PDR between the HII region and an extension of M17 SW, which partially obscures the southern bar of the HII region. The peak N_{HI}/T_s and Blos for this component are > 4.4 x 10^{19} cm^{-2}/K and +550 muG, respectively. Comparison of the peak magnetic fields detected toward M17 with virial equilibrium calculations suggest that ~1/3 of M17 SW's total support comes from its static magnetic field and the other 2/3 from its turbulent kinetic energy which includes support from Alfven waves.Comment: Contains 29 pages, 14 figures (Latex). Text and figures can be downloaded separately at http://www.pa.uky.edu/~brogan, submitted to Ap

Ozone-CO Correlations Determined by the TES Satellite Instrument in Continental Outflow Regions

Collocated measurements of tropospheric ozone (O3) and carbon monoxide (CO) from the Tropospheric Emission Spectrometer (TES) aboard the EOS Aura satellite provide information on O3-CO correlations to test our understanding of global anthropogenic influence on O3. We examine the global distribution of TES O3-CO correlations in the middle troposphere (618 hPa) for July 2005 and compare to correlations generated with the GEOS-Chem chemical transport model and with ICARTT aircraft observations over the eastern United States (July 2004). The TES data show significant O3-CO correlations downwind of polluted continents, with dO3/dCO enhancement ratios in the range 0.4–1.0 mol mol−1 and consistent with ICARTT data. The GEOS-Chem model reproduces the O3-CO enhancement ratios observed in continental outflow, but model correlations are stronger and more extensive. We show that the discrepancy can be explained by spectral measurement errors in the TES data. These errors will decrease in future data releases, which should enable TES to provide better information on O3-CO correlations.Earth and Planetary SciencesEngineering and Applied Science

Vinflunine: a new active drug for second-line treatment of advanced breast cancer. Results of a phase II and pharmacokinetic study in patients progressing after first-line anthracycline/taxane-based chemotherapy

To evaluate the single agent activity, pharmacokinetics and tolerability of the novel tubulin targeted agent vinflunine (VFL) (320 mg m−2 q 21 days) as second-line chemotherapy in patients with metastatic breast carcinoma (MBC). All patients had disease progression after anthracycline/taxane (A/T) therapy. They could have received a nonanthracycline adjuvant treatment and subsequently received a first-line A/T combination for advanced/metastatic disease; or relapsed >6 months after completion of adjuvant A/T therapy and were subsequently treated with the alternative agent; or relapsed within 6 months from an adjuvant A/T combination. Objective response was documented in 18 of 60 patients enrolled (RR: 30% (95% confidence interval (CI): 18.9–43.2%)). Among the responders, seven patients had relapsed during a period of <3 months from taxane-based regimen yielding a RR of 33.3%. The median duration of response was 4.8 months (95% CI: 4.2–7.2), median progression-free survival was 3.7 months (95% CI: 2.8–4.2) and median overall survival was 14.3 months (95% CI: 9.2–19.6). The most frequent adverse event was neutropenia (grade 3 in 28.3% and grade 4 in 36.7% of patients). No febrile neutropenia was observed. Fatigue (grade 3 in 16.7% of patients) and constipation (grade 3 in 11.7% of patients) were also common; these were non-cumulative and manageable permitting achievement of a good relative dose intensity of 93.5%. Vinflunine is an active agent with acceptable tolerance in the management of MBC patients previously treated with (A/T)-based regimens. These encouraging phase II results warrant further investigation of this novel agent in combination with other active agents in this setting or in earlier stages of disease

Diffusivity of methyl bromide in water

The oceans are important in the geochemical cycle of methyl bromide, as both a source of natural methyl bromide and a sink for anthropogenic methyl bromide. Air-sea exchange rate calculations are based on measured concentration differences across the air-sea surface, on various gas exchange wind speed relationships, and on the diffusivity of methyl bromide in seawater. In this study, the diffusivity of methyl bromide in pure water has been experimentally determined over the temperature range 5-20°C. The diffusivity varied from 9.85 x 10-6 cm2 s-1 at 5°C to 1.50 x 10-5 cm2 s-1 at 19.4°C. The values obtained in this study are ~ 8-35% higher than those derived from semi-empirical estimates. The diffusivity of methyl bromide in 3.5% NaCl solution was also measured at 13°C and found to be the same as the diffusivity measured in pure water. This is a surprising result given the viscosity differences between these two media. Schmidt numbers (Sc) for seawater have been calculated as a function of temperature from the pure water diffusivities. Schmidt numbers varied from 1585 at 5°C to 700 at 20°C

Characterization of cell death induced by vinflunine, the most recent Vinca alkaloid in clinical development

Vinflunine, the most recent Vinca alkaloid in clinical development, demonstrated superior antitumour activity to other Vincas in preclinical tumour models. This study aimed to define its molecular mechanisms of cell killing in both parental sensitive and vinflunine-resistant P388 leukaemia cells. Vinflunine treatment of these cells resulted in apoptosis characterized by DNA fragmentation and proteolytic cleavage of poly-(ADP-ribose) polymerase. Apoptosis-inducing concentrations of vinflunine caused c-Jun N-terminal kinase 1 stimulation, as well as caspases-3/7 activation. This activation of caspases and the induction of apoptosis could be inhibited by the caspase inhibitor acetyl-Asp-Glu-Val-Asp-aldehyde. Interestingly, the apoptosis signal triggered by vinflunine in these P388 cells was not mediated through Bcl-2 phosphorylation. In addition, when vinflunine resistance was developed in P388 cells, it was associated with resistance to vinflunine-induced apoptosis, as reflected by a loss of capacity to induce DNA fragmentation and PARP degradation, and characterized by increased levels of Bcl-2 and Bfl-1/A1. Therefore, these data indirectly implicate Bcl-2 and Bfl-1/A1 in vinflunine-induced cell death mechanisms

Identifying Compound-Target Associations by Combining Bioactivity Profile Similarity Search and Public Databases Mining

Molecular target identification is of central importance to drug discovery. Here, we developed a computational approach, named bioactivity profile similarity search (BASS), for associating targets to small molecules by using the known target annotations of related compounds from public databases. To evaluate BASS, a bioactivity profile database was constructed using 4296 compounds that were commonly tested in the US National Cancer Institute 60 human tumor cell line anticancer drug screen (NCI-60). Each compound was used as a query to search against the entire bioactivity profile database, and reference compounds with similar bioactivity profiles above a threshold of 0.75 were considered as neighbor compounds of the query. Potential targets were subsequently linked to the identified neighbor compounds by using the known targets o

Degradation of Internalized αvβ5 Integrin Is Controlled by uPAR Bound uPA: Effect on β1 Integrin Activity and α-SMA Stress Fiber Assembly

Myofibroblasts (Mfs) that persist in a healing wound promote extracellular matrix (ECM) accumulation and excessive tissue contraction. Increased levels of integrin αvβ5 promote the Mf phenotype and other fibrotic markers. Previously we reported that maintaining uPA (urokinase plasminogen activator) bound to its cell-surface receptor, uPAR prevented TGFβ-induced Mf differentiation. We now demonstrate that uPA/uPAR controls integrin β5 protein levels and in turn, the Mf phenotype. When cell-surface uPA was increased, integrin β5 levels were reduced (61%). In contrast, when uPA/uPAR was silenced, integrin β5 total and cell-surface levels were increased (2–4 fold). Integrin β5 accumulation resulted from a significant decrease in β5 ubiquitination leading to a decrease in the degradation rate of internalized β5. uPA-silencing also induced α-SMA stress fiber organization in cells that were seeded on collagen, increased cell area (1.7 fold), and increased integrin β1 binding to the collagen matrix, with reduced activation of β1. Elevated cell-surface integrin β5 was necessary for these changes after uPA-silencing since blocking αvβ5 function reversed these effects. Our data support a novel mechanism by which downregulation of uPA/uPAR results in increased integrin αvβ5 cell-surface protein levels that regulate the activity of β1 integrins, promoting characteristics of the persistent Mf