Lymphatic endothelium stimulates melanoma metastasis and invasion via MMP14-dependent Notch3 and b1-integrin activation

Lymphatic invasion and lymph node metastasis correlate with poor clinical outcome in melanoma. However, the mechanisms of lymphatic dissemination in distant metastasis remain incompletely understood. We show here that exposure of expansively growing human WM852 melanoma cells, but not singly invasive Bowes cells, to lymphatic endothelial cells (LEC) in 3D co-culture facilitates melanoma distant organ metastasis in mice. To dissect the underlying molecular mechanisms, we established LEC co-cultures with different melanoma cells originating from primary tumors or metastases. Notably, the expansively growing metastatic melanoma cells adopted an invasively sprouting phenotype in 3D matrix that was dependent on MMP14, Notch3 and β1-integrin. Unexpectedly, MMP14 was necessary for LEC-induced Notch3 induction and coincident β1-integrin activation. Moreover, MMP14 and Notch3 were required for LEC-mediated metastasis of zebrafish xenografts. This study uncovers a unique mechanism whereby LEC contact promotes melanoma metastasis by inducing a reversible switch from 3D growth to invasively sprouting cell phenotype

Decreased carbon accumulation feedback driven by climate-induced drying of two southern boreal bogs over recent centuries

Northern boreal peatlands are important ecosystems in modulating global biogeochemical cycles, yet their biological communities and related carbon dynamics are highly sensitive to changes in climate. Despite this, the strength and recent direction of these feedbacks are still unclear. The response of boreal peatlands to climate warming has received relatively little attention compared with other northern peatland types, despite forming a large northern hemisphere-wide ecosystem. Here, we studied the response of two ombrotrophic boreal peatlands to climate variability over the last c. 200 years for which local meteorological data are available. We used remains from plants and testate amoebae to study historical changes in peatland biological communities. These data were supplemented by peat property (bulk density, carbon and nitrogen content), C-14, Pb-210 and Cs-137 analyses and were used to infer changes in peatland hydrology and carbon dynamics. In total, six peat cores, three per study site, were studied that represent different microhabitats: low hummock (LH), high lawn and low lawn. The data show a consistent drying trend over recent centuries, represented mainly as a change from wet habitat Sphagnum spp. to dry habitat S. fuscum. Summer temperature and precipitation appeared to be important drivers shaping peatland community and surface moisture conditions. Data from the driest microhabitat studied, LH, revealed a clear and strong negative linear correlation (R-2 = .5031; p <.001) between carbon accumulation rate and peat surface moisture conditions: under dry conditions, less carbon was accumulated. This suggests that at the dry end of the moisture gradient, availability of water regulates carbon accumulation. It can be further linked to the decreased abundance of mixotrophic testate amoebae under drier conditions (R-2 = .4207; p <.001). Our study implies that if effective precipitation decreases in the future, the carbon uptake capacity of boreal bogs may be threatened.Peer reviewe

Categorical Dimensions of Human Odor Descriptor Space Revealed by Non-Negative Matrix Factorization

In contrast to most other sensory modalities, the basic perceptual dimensions of olfaction remain unclear. Here, we use non-negative matrix factorization (NMF) – a dimensionality reduction technique – to uncover structure in a panel of odor profiles, with each odor defined as a point in multi-dimensional descriptor space. The properties of NMF are favorable for the analysis of such lexical and perceptual data, and lead to a high-dimensional account of odor space. We further provide evidence that odor dimensions apply categorically. That is, odor space is not occupied homogenously, but rather in a discrete and intrinsically clustered manner. We discuss the potential implications of these results for the neural coding of odors, as well as for developing classifiers on larger datasets that may be useful for predicting perceptual qualities from chemical structures

Receptor modeling of near-roadway aerosol mass spectrometer data in Las Vegas, Nevada, with EPA PMF

Ambient non-refractory PM&lt;sub&gt;1&lt;/sub&gt; aerosol particles were measured with an Aerodyne High Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-AMS) at an elementary school 18 m from the US 95 freeway soundwall in Las Vegas, Nevada, during January 2008. Additional collocated continuous measurements of black carbon (BC), carbon monoxide (CO), nitrogen oxides (NO&lt;sub&gt;x&lt;/sub&gt;), and meteorological data were collected. The US~Environmental Protection Agency's (EPA) positive matrix factorization (PMF) data analysis tool was used to apportion organic matter (OM) as measured by HR-AMS, and rotational tools in EPA PMF were used to better characterize the solution space and pull resolved factors toward known source profiles. Three- to six-factor solutions were resolved. The four-factor solution was the most interpretable, with the typical AMS PMF factors of hydrocarbon-like organic aerosol (HOA), low-volatility oxygenated organic aerosol (LV-OOA), biomass burning organic aerosol (BBOA), and semi-volatile oxygenated organic aerosol (SV-OOA). When the measurement site was downwind of the freeway, HOA composed about half the OM, with SV-OOA and LV-OOA accounting for the rest. Attempts to pull the PMF factor profiles toward source profiles were successful but did not qualitatively change the results, indicating that these factors are very stable. Oblique edges were present in G-space plots, suggesting that the obtained rotation may not be the most plausible one. Since solutions found by pulling the profiles or using &lt;i&gt;F&lt;/i&gt;&lt;sub&gt;peak&lt;/sub&gt; retained these oblique edges, there appears to be little rotational freedom in the base solution. On average, HOA made up 26% of the OM, while LV-OOA was highest in the afternoon and accounted for 26% of the OM. BBOA occurred in the evening hours, was predominantly from the residential area to the north, and on average constituted 12% of the OM; SV-OOA accounted for the remaining third of the OM. Use of the pulling techniques available in EPA PMF and ME-2 suggested that the four-factor solution was very stable

Matching techniques ride to rescue OLED displays

Combinatorial optimization problems have recently emerged in the design of controllers for OLED displays. The objective is to decompose an image into subframes minimizing the addressing time and thereby also the amplitude of the electrical current through the diodes, which has a direct impact on the lifetime of such a display. To this end, we model this problem as an integer linear program. Subsequently, we refine this formulation by exploiting the combinatorial structure of the problem. We propose a fully combinatorial separation routine for the LP-relaxation based on matching techniques. It can be used as an oracle in various frameworks to derive approximation algorithms or heuristics. We establish NP-hardness and hardness of approximation. Nevertheless, we are able to work around this issue by only focusing on a subsets of the variables and provide experimental evidence that they are sufficient to come up with near optimal solutions in practice. On this basis, one can derive custom-tailored solutions adapting to technical constraints such as memory requirements. By allowing the addressing of distributed doublelines, we improve the addressing time in cases where previous approaches fall short due to their restriction to consecutive doublelines

Degeneracy in Candecomp/Parafac and Indscal Explained For Several Three-Sliced Arrays With A Two-Valued Typical Rank

The Candecomp/Parafac (CP) method decomposes a three-way array into a prespecified number R of rank-1 arrays, by minimizing the sum of squares of the residual array. The practical use of CP is sometimes complicated by the occurrence of so-called degenerate sequences of solutions, in which several rank-1 arrays become highly correlated in all three modes and some elements of the rank-1 arrays become arbitrarily large. We consider the real-valued CP decomposition of all known three-sliced arrays, i.e., of size p×q×3, with a two-valued typical rank. These are the 5×3×3 and 8×4×3 arrays, and the 3×3×4 and 3×3×5 arrays with symmetric 3×3 slices. In the latter two cases, CP is equivalent to the Indscal model. For a typical rank of {m,m+1}, we consider the CP decomposition with R=m of an array of rank m+1. We show that (in most cases) the CP objective function does not have a minimum but an infimum. Moreover, any sequence of feasible CP solutions in which the objective value approaches the infimum will become degenerate. We use the tools developed in Stegeman (2006), who considers p×p×2 arrays, and present a framework of analysis which is of use to the future study of CP degeneracy related to a two-valued typical rank. Moreover, our examples show that CP uniqueness is not necessary for degenerate solutions to occur

Morphology and kinematics of Lynds 1642

The high latitude translucent molecular cloud L1642 has been mapped in the J=1-0 and J=2-1 transitions of 12CO, 13CO and C18O using the SEST radio telescope. We have analysed the morphology and velocity structure of the cloud using the Positive Matrix Factorization (PMF) method. The results show that L1642 is composed of a main structure at radial velocity 0.2 km/s while the higher velocity components at ~0.5 and 1.0 km/s form an incomplete ring around it, suggesting an expanding shell structure. Fainter emission extends to the north with a still higher velocity of up to 1.6 km/s. Such a velocity structure suggests an elongated morphology in the line of sight direction. The physical properties of the cloud have been investigated assuming LTE conditions, but non-LTE radiative transfer models are also constructed for the 13CO observations. We confirm that L1642 follows an r^-1 density distribution in its outer parts while the distribution is considerably flatter in the core. The cloud is close to virial equilibrium. In an Appendix the PMF results are compared with the view obtained through the analysis of channel maps and by the use of Principal Component Analysis (PCA). Both PMF and PCA present the observations as a linear combination of basic spectral shapes that are extracted from the data. Comparison of the methods shows that the PMF method in particular is able to produce a presentation of the complex velocity that is both compact and easily interpreted.Comment: Accepted to A&

The Effects of Particulate Matter Sources on Daily Mortality: A Case-Crossover Study of Barcelona, Spain

Background: Dozens of studies link acute exposure to particulate matter (PM) air pollution with premature mortality and morbidity, but questions remain about which species and sources in the vast PM mixture are responsible for the observed health effects. Although a few studies exist on the effects of species and sources in U.S. cities, European cities—which have a higher proportion of diesel engines and denser urban populations—have not been well characterized. Information on the effects of specific sources could aid in targeting pollution control and in articulating the biological mechanisms of PM

Understanding atmospheric organic aerosols via factor analysis of aerosol mass spectrometry: a review

Organic species are an important but poorly characterized constituent of airborne particulate matter. A quantitative understanding of the organic fraction of particles (organic aerosol, OA) is necessary to reduce some of the largest uncertainties that confound the assessment of the radiative forcing of climate and air quality management policies. In recent years, aerosol mass spectrometry has been increasingly relied upon for highly time-resolved characterization of OA chemistry and for elucidation of aerosol sources and lifecycle processes. Aerodyne aerosol mass spectrometers (AMS) are particularly widely used, because of their ability to quantitatively characterize the size-resolved composition of submicron particles (PM1). AMS report the bulk composition and temporal variations of OA in the form of ensemble mass spectra (MS) acquired over short time intervals. Because each MS represents the linear superposition of the spectra of individual components weighed by their concentrations, multivariate factor analysis of the MS matrix has proved effective at retrieving OA factors that offer a quantitative and simplified description of the thousands of individual organic species. The sum of the factors accounts for nearly 100% of the OA mass and each individual factor typically corresponds to a large group of OA constituents with similar chemical composition and temporal behavior that are characteristic of different sources and/or atmospheric processes. The application of this technique in aerosol mass spectrometry has grown rapidly in the last six years. Here we review multivariate factor analysis techniques applied to AMS and other aerosol mass spectrometers, and summarize key findings from field observations. Results that provide valuable information about aerosol sources and, in particular, secondary OA evolution on regional and global scales are highlighted. Advanced methods, for example a-priori constraints on factor mass spectra and the application of factor analysis to combined aerosol and gas phase data are discussed. Integrated analysis of worldwide OA factors is used to present a holistic regional and global description of OA. Finally, different ways in which OA factors can constrain global and regional models are discussed