Downregulation of 26S proteasome catalytic activity promotes epithelial-mesenchymal transition.

The epithelial-mesenchymal transition (EMT) endows carcinoma cells with phenotypic plasticity that can facilitate the formation of cancer stem cells (CSCs) and contribute to the metastatic cascade. While there is substantial support for the role of EMT in driving cancer cell dissemination, less is known about the intracellular molecular mechanisms that govern formation of CSCs via EMT. Here we show that β2 and β5 proteasome subunit activity is downregulated during EMT in immortalized human mammary epithelial cells. Moreover, selective proteasome inhibition enabled mammary epithelial cells to acquire certain morphologic and functional characteristics reminiscent of cancer stem cells, including CD44 expression, self-renewal, and tumor formation. Transcriptomic analyses suggested that proteasome-inhibited cells share gene expression signatures with cells that have undergone EMT, in part, through modulation of the TGF-β signaling pathway. These findings suggest that selective downregulation of proteasome activity in mammary epithelial cells can initiate the EMT program and acquisition of a cancer stem cell-like phenotype. As proteasome inhibitors become increasingly used in cancer treatment, our findings highlight a potential risk of these therapeutic strategies and suggest a possible mechanism by which carcinoma cells may escape from proteasome inhibitor-based therapy

A new interpretation of total column BrO during Arctic spring

Emission of bromine from sea-salt aerosol, frost flowers, ice leads, and snow results in the nearly complete removal of surface ozone during Arctic spring. Regions of enhanced total column BrO observed by satellites have traditionally been associated with these emissions. However, airborne measurements of BrO and O3 within the convective boundary layer (CBL) during the ARCTAS and ARCPAC field campaigns at times bear little relation to enhanced column BrO. We show that the locations of numerous satellite BrO “hotspots” during Arctic spring are consistent with observations of total column ozone and tropopause height, suggesting a stratospheric origin to these regions of elevated BrO. Tropospheric enhancements of BrO large enough to affect the column abundance are also observed, with important contributions originating from above the CBL. Closure of the budget for total column BrO, albeit with significant uncertainty, is achieved by summing observed tropospheric partial columns with calculated stratospheric partial columns provided that natural, short-lived biogenic bromocarbons supply between 5 and 10 ppt of bromine to the Arctic lowermost stratosphere. Proper understanding of bromine and its effects on atmospheric composition requires accurate treatment of geographic variations in column BrO originating from both the stratosphere and troposphere

A new interpretation of total column BrO during Arctic spring

Emission of bromine from sea-salt aerosol, frost flowers, ice leads, and snow results in the nearly complete removal of surface ozone during Arctic spring. Regions of enhanced total column BrO observed by satellites have traditionally been associated with these emissions. However, airborne measurements of BrO and O3 within the convective boundary layer (CBL) during the ARCTAS and ARCPAC field campaigns at times bear little relation to enhanced column BrO. We show that the locations of numerous satellite BrO "hotspots" during Arctic spring are consistent with observations of total column ozone and tropopause height, suggesting a stratospheric origin to these regions of elevated BrO. Tropospheric enhancements of BrO large enough to affect the column abundance are also observed, with important contributions originating from above the CBL. Closure of the budget for total column BrO, albeit with significant uncertainty, is achieved by summing observed tropospheric partial columns with calculated stratospheric partial columns provided that natural, short-lived biogenic bromocarbons supply between 5 and 10 ppt of bromine to the Arctic lowermost stratosphere. Proper understanding of bromine and its effects on atmospheric composition requires accurate treatment of geographic variations in column BrO originating from both the stratosphere and troposphere. Copyright 2010 by the American Geophysical Union

Regional prediction of landslide hazard using probability analysis of intense rainfall in the Hoa Binh province, Vietnam.

The main objective of this study is to assess regional landslide hazards in the Hoa Binh province of Vietnam. A landslide inventory map was constructed from various sources with data mainly for a period of 21 years from 1990 to 2010. The historic inventory of these failures shows that rainfall is the main triggering factor in this region. The probability of the occurrence of episodes of rainfall and the rainfall threshold were deduced from records of rainfall for the aforementioned period. The rainfall threshold model was generated based on daily and cumulative values of antecedent rainfall of the landslide events. The result shows that 15-day antecedent rainfall gives the best fit for the existing landslides in the inventory. The rainfall threshold model was validated using the rainfall and landslide events that occurred in 2010 that were not considered in building the threshold model. The result was used for estimating temporal probability of a landslide to occur using a Poisson probability model. Prior to this work, five landslide susceptibility maps were constructed for the study area using support vector machines, logistic regression, evidential belief functions, Bayesian-regularized neural networks, and neuro-fuzzy models. These susceptibility maps provide information on the spatial prediction probability of landslide occurrence in the area. Finally, landslide hazard maps were generated by integrating the spatial and the temporal probability of landslide. A total of 15 specific landslide hazard maps were generated considering three time periods of 1, 3, and 5 years

A42F-03: Small-Scale Variability in Tropical Tropopause Layer Humidity

Recent advances in statistical parameterizations of cirrus cloud processes for use in global models are highlighting the need for information about small-scale fluctuations in upper tropospheric humidity and the physical processes that control the humidity variability. To address these issues, we have analyzed high-resolution airborne water vapor measurements obtained in the Airborne Tropical TRopopause EXperiment (ATTREX) over the tropical Pacific between 14 and 20 km. Using accurate and precise 1-Hz water vapor measurements along approximately-level aircraft flight legs, we calculate structure functions spanning horizontal scales ranging from about 0.2 to 50 km, and we compare the water vapor variability in the lower (about 14 km) and upper (16-19 km) Tropical Tropopause Layer (TTL). We also compare the magnitudes and scales of variability inside TTL cirrus versus in clear-sky regions. The measurements show that in the upper TTL, water vapor concentration variance is stronger inside cirrus than in clear-sky regions. Using simulations of TTL cirrus formation, we show that small variability in clear-sky humidity is amplified by the strong sensitivity of ice nucleation rate to supersaturation, which results in highly-structured clouds that subsequently drive variability in the water vapor field. In the lower TTL, humidity variability is correlated with recent detrainment from deep convection. The structure functions indicate approximately power-law scaling with spectral slopes ranging from about minus 5 divided by 3, to minus 2

Stakeholder Expectations of Future Policy Implementation Compared to Formal Policy Trajectories: Scenarios for Agricultural Food Systems in the Mekong Delta

The development of a coherent and coordinated policy for the management of large socio-agricultural systems, such as the Mekong delta in southern Vietnam, is reliant on aligning the development, delivery, and implementation of policy on national to local scales. Effective decision making is linked to a coherent, broadly-shared vision of the strategic management of socio-agricultural systems. However, when policies are ambiguous, and at worst contradictory, long-term management and planning can consequently suffer. These potential adverse impacts may be compounded if stakeholders have divergent visions of the current and future states of socio-agricultural systems. Herein we used a transferable, scenario-based methodology which uses a standard quadrant matrix in order to explore both anticipated and idealized future states. Our case study was the Mekong delta. The scenario matrix was based upon two key strategic choices (axis) for the delta, derived from analysis of policy documents, literature, stakeholder engagement, and land use models. These are: (i) who will run agriculture in the future, agri-business or the established commune system; and (ii) to what degree sustainability will be incorporated into production. During a workshop meeting, stakeholders identified that agri-business will dominate future agricultural production in the delta but showed a clear concern that sustainability might consequently be undermined despite policy claims of the contrary. As such, our study highlights an important gap between national expectations and regional perspectives. Our results suggest that the new development plans for the Mekong delta (which comprise a new Master Plan and a new 5-year socio-economic development plan), which emphasize agro-business development, should adopt approaches that address concerns of sustainability as well as a more streamlined policy formulation and implementation that accounts for stakeholder concerns at both provincial and national levels

Efficacy of a novel online integrated treatment for problem gambling and tobacco smoking: Results of a randomized controlled trial

Background and aimsProblem gambling and tobacco use are highly comorbid among adults. However, there are few treatment frameworks that target both gambling and tobacco use simultaneously (i.e., an integrated approach), while also being accessible and evidence-based. The aim of this two-arm open label RCT was to examine the efficacy of an integrated online treatment for problem gambling and tobacco use.MethodsA sample of 209 participants (M$_{age}$ = 37.66, SD = 13.81; 62.2% female) from North America were randomized into one of two treatment conditions (integrated [n = 91] or gambling only [n = 118]) that lasted for eight weeks and consisted of seven online modules. Participants completed assessments at baseline, after treatment completion, and at 24-week follow-up.ResultsWhile a priori planned generalized linear mixed models showed no condition differences on primary (gambling days, money spent, time spent) and secondary outcomes, both conditions did appear to significantly reduce problem gambling and smoking behaviours over time. Post hoc analyses showed that reductions in smoking and gambling craving were correlated with reductions in days spent gambling, as well as with gambling disorder symptoms. Relatively high (versus low) nicotine replacement therapy use was associated with greater reductions in gambling behaviours in the integrated treatment condition.Discussion and conclusionsWhile our open label RCT does not support a clear benefit of integrated treatment, findings suggest that changes in smoking and gambling were correlated over time, regardless of treatment condition, suggesting that more research on mechanisms of smoking outcomes in the context of gambling treatment may be relevant