Mathematical modeling of the metastatic process

Mathematical modeling in cancer has been growing in popularity and impact since its inception in 1932. The first theoretical mathematical modeling in cancer research was focused on understanding tumor growth laws and has grown to include the competition between healthy and normal tissue, carcinogenesis, therapy and metastasis. It is the latter topic, metastasis, on which we will focus this short review, specifically discussing various computational and mathematical models of different portions of the metastatic process, including: the emergence of the metastatic phenotype, the timing and size distribution of metastases, the factors that influence the dormancy of micrometastases and patterns of spread from a given primary tumor.Comment: 24 pages, 6 figures, Revie

Upper- and mid-mantle interaction between the Samoan plume and the Tonga-Kermadec slabs

Mantle plumes are thought to play a key role in transferring heat from the core\u2013mantle boundary to the lithosphere, where it can significantly influence plate tectonics. On impinging on the lithosphere at spreading ridges or in intra-plate settings, mantle plumes may generate hotspots, large igneous provinces and hence considerable dynamic topography. However, the active role of mantle plumes on subducting slabs remains poorly understood. Here we show that the stagnation at 660 km and fastest trench retreat of the Tonga slab in Southwestern Pacific are consistent with an interaction with the Samoan plume and the Hikurangi plateau. Our findings are based on comparisons between 3D anisotropic tomography images and 3D petrological-thermo-mechanical models, which self-consistently explain several unique features of the Fiji\u2013Tonga region. We identify four possible slip systems of bridgmanite in the lower mantle that reconcile the observed seismic anisotropy beneath the Tonga slab (VSH4VSV) with thermo-mechanical calculations

Increased Mobility of Metal Oxide Nanoparticles Due to Photo and Thermal Induced Disagglomeration

Significant advances have been made on our understanding of the fate and transport of engineered nanomaterials. One unexplored aspect of nanoparticle aggregation is how environmental stimuli such as light exposure and temperature variations affect the mobility of engineered nanoparticles. In this study, TiO2, ZnO, and CeO2 were chosen as model materials for investigating the mobility of nanoparticles under three external stimuli: heat, light and sonication. Sunlight and high power sonication were able to partially disagglomerate metal oxide clusters, but primary particles bonded by solid state necks were left intact. A cycle of temperature increase from 25°C to 65°C and then decrease back was found to disagglomerate the compact clusters in the heating phase and reagglomerate them as more open fractal structures during the cooling phase. A fractal model summing the pair-wise DLVO interactions between primary particles within two fractal agglomerates predicts weak attractions on the order of a few kT. Our study shows that common environmental stimuli such as light exposure or temperature variation can disagglomerate nanoparticle clusters and enhance their mobility in open waters. This phenomenon warrants attention since it is likely that metal oxide nanoparticles will experience these natural stimuli during their transport in the environment

Estimates of CO2 from fires in the United States: implications for carbon management

<p>Abstract</p> <p>Background</p> <p>Fires emit significant amounts of CO₂to the atmosphere. These emissions, however, are highly variable in both space and time. Additionally, CO₂emissions estimates from fires are very uncertain. The combination of high spatial and temporal variability and substantial uncertainty associated with fire CO₂emissions can be problematic to efforts to develop remote sensing, monitoring, and inverse modeling techniques to quantify carbon fluxes at the continental scale. Policy and carbon management decisions based on atmospheric sampling/modeling techniques must account for the impact of fire CO₂emissions; a task that may prove very difficult for the foreseeable future. This paper addresses the variability of CO₂emissions from fires across the US, how these emissions compare to anthropogenic emissions of CO₂and Net Primary Productivity, and the potential implications for monitoring programs and policy development.</p> <p>Results</p> <p>Average annual CO₂emissions from fires in the lower 48 (LOWER48) states from 2002–2006 are estimated to be 213 (± 50 std. dev.) Tg CO₂yr^-1and 80 (± 89 std. dev.) Tg CO₂yr^-1in Alaska. These estimates have significant interannual and spatial variability. Needleleaf forests in the Southeastern US and the Western US are the dominant source regions for US fire CO₂emissions. Very high emission years typically coincide with droughts, and climatic variability is a major driver of the high interannual and spatial variation in fire emissions. The amount of CO₂emitted from fires in the US is equivalent to 4–6% of anthropogenic emissions at the continental scale and, at the state-level, fire emissions of CO₂can, in some cases, exceed annual emissions of CO₂from fossil fuel usage.</p> <p>Conclusion</p> <p>The CO₂released from fires, overall, is a small fraction of the estimated average annual Net Primary Productivity and, unlike fossil fuel CO₂emissions, the pulsed emissions of CO₂during fires are partially counterbalanced by uptake of CO₂by regrowing vegetation in the decades following fire. Changes in fire severity and frequency can, however, lead to net changes in atmospheric CO₂and the short-term impacts of fire emissions on monitoring, modeling, and carbon management policy are substantial.</p

Field template-based design and biological evaluation of new sphingosine kinase 1 inhibitors

Purpose: Sphingosine kinase 1 (SK1) is a protooncogenic enzyme expressed in many human tumours and is associated with chemoresistance and poor prognosis. It is a potent therapy target and its inhibition chemosensitises solid tumours. Despite recent advances in SK1 inhibitors synthesis and validation, their clinical safety and chemosensitising options are not well described. In this study, we have designed, synthesised and tested a new specific SK1 inhibitor with a low toxicity profile. Methods: Field template molecular modelling was used for compound design. Lead compounds were tested in cell and mouse cancer models. Results: Field template analysis of three known SK1 inhibitors, SKI-178, 12aa and SK1-I, was performed and compound screening identified six potential new SK1 inhibitors. SK1 activity assays in both cell-free and in vitro settings showed that two compounds were effective SK1 inhibitors. Compound SK-F has potently decreased cancer cell viability in vitro and sensitised mouse breast tumours to docetaxel (DTX) in vivo, without significant whole-body toxicity. Conclusion: Through field template screening, we have identified a new SK1 inhibitor, SK-F, which demonstrated antitumour activity in vitro and in vivo without overt toxicity when combined with DTX

Motor activity improves temporal expectancy

Certain brain areas involved in interval timing are also important in motor activity. This raises the possibility that motor activity might influence interval timing. To test this hypothesis, we assessed interval timing in healthy adults following different types of training. The pre- and post-training tasks consisted of a button press in response to the presentation of a rhythmic visual stimulus. Alterations in temporal expectancy were evaluated by measuring response times. Training consisted of responding to the visual presentation of regularly appearing stimuli by either: (1) pointing with a whole-body movement, (2) pointing only with the arm, (3) imagining pointing with a whole-body movement, (4) simply watching the stimulus presentation, (5) pointing with a whole-body movement in response to a target that appeared at irregular intervals (6) reading a newspaper. Participants performing a motor activity in response to the regular target showed significant improvements in judgment times compared to individuals with no associated motor activity. Individuals who only imagined pointing with a whole-body movement also showed significant improvements. No improvements were observed in the group that trained with a motor response to an irregular stimulus, hence eliminating the explanation that the improved temporal expectations of the other motor training groups was purely due to an improved motor capacity to press the response button. All groups performed a secondary task equally well, hence indicating that our results could not simply be attributed to differences in attention between the groups. Our results show that motor activity, even when it does not play a causal or corrective role, can lead to improved interval timing judgments

Quantifying Risk Factors for Human Brucellosis in Rural Northern Tanzania

Brucellosis is a zoonosis of veterinary, public health and economic significance in most developing countries. Human brucellosis is a severely debilitating disease that requires prolonged treatment with a combination of antibiotics. The disease can result in permanent and disabling sequel, and results in considerable medical expenses in addition to loss of income due to loss of working hours. A study was conducted in Northern Tanzania to determine the risk factors for transmission of brucellosis to humans in Tanzania. This was a matched case-control study. Any patient with a positive result by a competitive ELISA (c-ELISA) test for brucellosis, and presenting to selected hospitals with at least two clinical features suggestive of brucellosis such as headache, recurrent or continuous fever, sweating, joint pain, joint swelling, general body malaise or backache, was defined as a case. For every case in a district, a corresponding control was traced and matched by sex using multistage cluster sampling. Other criteria for inclusion as a control included a negative c-ELISA test result and that the matched individual would present to hospital if falls sick. Multivariable analysis showed that brucellosis was associated with assisted parturition during abortion in cattle, sheep or goat. It was shown that individuals living in close proximity to other households had a higher risk of brucellosis. People who were of Christian religion were found to have a higher risk of brucellosis compared to other religions. The study concludes that assisting an aborting animal, proximity to neighborhoods, and Christianity were associated with brucellosis infection. There was no association between human brucellosis and Human Immunodeficiency Virus (HIV) serostatus. Protecting humans against contact with fluids and tissues during assisted parturition of livestock may be an important means of reducing the risk of transferring brucellosis from livestock to humans. These can be achieved through health education to the communities where brucellosis is common

Massive mortality of invasive bivalves as a potential resource subsidy for the adjacent terrestrial food web

Large-scale mortality of invasive bivalves was observed in the River Danube basin in the autumn of 2011 due to a particularly low water discharge. The aim of this study was to quantify and compare the biomass of invasive and native bivalve die-offs amongst eight different sites and to assess the potential role of invasive bivalve die-offs as a resource subsidy for the adjacent terrestrial food web. Invasive bivalve die-offs dominated half of the study sites and their highest density and biomass were recorded at the warm water effluent. The density and biomass values recorded in this study are amongst the highest values recorded for aquatic ecosystems and show that a habitat affected by heated water can sustain an extremely high biomass of invasive bivalves. These mortalities highlight invasive bivalves as a major resource subsidy, possibly contributing remarkable amounts of nutrients and energy to the adjacent terrestrial ecosystem. Given the widespread occurrence of these invasive bivalves and the predicted increase in the frequency and intensity of extreme climatic events, the ecological impacts generated by their massive mortalities should be taken into account in other geographical areas as well.The authors are grateful to David Strayer for valuable comments on a previous version of the manuscript. Special thanks to the Danube-Ipoly National Park for the help in field work. Ronaldo Sousa was supported by the project "ECOIAS" funded by the Portuguese Foundation for the Science and the Technology and COMPETE funds (contract: PTDC/AAC-AMB/116685/2010)

Subduction controls the distribution and fragmentation of Earth’s tectonic plates

International audienceThe theory of plate tectonics describes how the surface of the Earth is split into an organized jigsaw of seven large plates 1 of similar sizes and a population of smaller plates, whose areas follow a fractal distribution 2,3. The reconstruction of global tectonics during the past 200 My 4 suggests that this layout is probably a long-term feature of our planet, but the forces governing it are unknown. Previous studies 3,5,6 , primarily based on statistical properties of plate distributions, were unable to resolve how the size of plates is determined by lithosphere properties and/or underlying mantle convection. Here, we demonstrate that the plate layout of the Earth is produced by a dynamic feedback between mantle convection and the strength of the lithosphere. Using 3D spherical models of mantle convection with plate-like behaviour that match the plate size-frequency distribution observed for Earth, we show that subduction geometry drives the tectonic fragmentation that generates plates. The spacing between slabs controls the layout of large plates, and the stresses caused by the bending of trenches, break plates into smaller fragments. Our results explain why the fast evolution in small back-arc plates 7,8 reflects the dramatic changes in plate motions during times of major reorganizations. Our study opens the way to use convection simulations with plate-like behaviour to unravel how global tectonics and mantle convection are dynamically connected