The Statistical Relationship between Imports of Investment Goods and Gross Domestic Product in Developing Countries

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Acute inhibition of MEK suppresses congenital melanocytic nevus syndrome in a murine model driven by activated NRAS and Wnt signaling

Congenital melanocytic nevus (CMN) syndrome is the association of pigmented melanocytic nevi with extra-cutaneous features, classically melanotic cells within the central nervous system, most frequently caused by a mutation of NRAS codon 61. This condition is currently untreatable and carries a significant risk of melanoma within the skin, brain, or leptomeninges. We have previously proposed a key role for Wnt signaling in the formation of melanocytic nevi, suggesting that activated Wnt signaling may be synergistic with activated NRAS in the pathogenesis of CMN syndrome. Some familial pre-disposition suggests a germ-line contribution to CMN syndrome, as does variability of neurological phenotypes in individuals with similar cutaneous phenotypes. Accordingly, we performed exome sequencing of germ-line DNA from patients with CMN to reveal rare or undescribed Wnt-signaling alterations. A murine model harboring activated NRASQ61K and Wnt signaling in melanocytes exhibited striking features of CMN syndrome, in particular neurological involvement. In the first model of treatment for this condition, these congenital, and previously assumed permanent, features were profoundly suppressed by acute post-natal treatment with a MEK inhibitor. These data suggest that activated NRAS and aberrant Wnt signaling conspire to drive CMN syndrome. Post-natal MEK inhibition is a potential candidate therapy for patients with this debilitating condition

Time resolved particle dynamics in granular convection

We present an experimental study of the movement of individual particles in a layer of vertically shaken granular material. High-speed imaging allows us to investigate the motion of beads within one vibration period. This motion consists mainly of vertical jumps, and a global ordered drift. The analysis of the system movement as a whole reveals that the observed bifurcation in the flight time is not adequately described by the Inelastic Bouncing Ball Model. Near the bifurcation point, friction plays and important role, and the branches of the bifurcation do not diverge as the control parameter is increased. We quantify the friction of the beads against the walls, showing that this interaction is the underlying mechanism responsible for the dynamics of the flow observed near the lateral wall

Drag Reduction by Polymers in Turbulent Channel Flows: Energy Redistribution Between Invariant Empirical Modes

We address the phenomenon of drag reduction by dilute polymeric additive to turbulent flows, using Direct Numerical Simulations (DNS) of the FENE-P model of viscoelastic flows. It had been amply demonstrated that these model equations reproduce the phenomenon, but the results of DNS were not analyzed so far with the goal of interpreting the phenomenon. In order to construct a useful framework for the understanding of drag reduction we initiate in this paper an investigation of the most important modes that are sustained in the viscoelastic and Newtonian turbulent flows respectively. The modes are obtained empirically using the Karhunen-Loeve decomposition, allowing us to compare the most energetic modes in the viscoelastic and Newtonian flows. The main finding of the present study is that the spatial profile of the most energetic modes is hardly changed between the two flows. What changes is the energy associated with these modes, and their relative ordering in the decreasing order from the most energetic to the least. Modes that are highly excited in one flow can be strongly suppressed in the other, and vice versa. This dramatic energy redistribution is an important clue to the mechanism of drag reduction as is proposed in this paper. In particular there is an enhancement of the energy containing modes in the viscoelastic flow compared to the Newtonian one; drag reduction is seen in the energy containing modes rather than the dissipative modes as proposed in some previous theories.Comment: 11 pages, 13 figures, included, PRE, submitted, REVTeX

Cell surface marker mediated purification of iPS cell intermediates from a reprogrammable mouse model

Mature cells can be reprogrammed to a pluripotent state. These so called induced pluripotent stem (iPS) cells are able to give rise to all cell types of the body and consequently have vast potential for regenerative medicine applications. Traditionally iPS cells are generated by viral introduction of transcription factors Oct-4, Klf-4, Sox-2, and c-Myc (OKSM) into fibroblasts. However, reprogramming is an inefficient process with only 0.1-1% of cells reverting towards a pluripotent state, making it difficult to study the reprogramming mechanism. A proven methodology that has allowed the study of the reprogramming process is to separate the rare intermediates of the reaction from the refractory bulk population. In the case of mouse embryonic fibroblasts (MEFs), we and others have previously shown that reprogramming cells undergo a distinct series of changes in the expression profile of cell surface markers which can be used for the separation of these cells. During the early stages of OKSM expression successfully reprogramming cells lose fibroblast identity marker Thy-1.2 and up-regulate pluripotency associated marker Ssea-1. The final transition of a subset of Ssea-1 positive cells towards the pluripotent state is marked by the expression of Epcam during the late stages of reprogramming. Here we provide a detailed description of the methodology used to isolate reprogramming intermediates from cultures of reprogramming MEFs. In order to increase experimental reproducibility we use a reprogrammable mouse strain that has been engineered to express a transcriptional transactivator (m2rtTA) under control of the Rosa26 locus and OKSM under control of a doxycycline responsive promoter. Cells isolated from these mice are isogenic and express OKSM homogenously upon addition of doxycycline. We describe in detail the establishment of the reprogrammable mice, the derivation of MEFs, and the subsequent isolation of intermediates during reprogramming into iPS cells via fluorescent activated cells sorting (FACS).Christian M. Nefzger, Sara Alaei, Anja S. Knaupp, Melissa L. Holmes, Jose M. Pol

Multi-omic phenotyping reveals host-microbe responses to bariatric surgery, glycaemic control and obesity

Background Resolution of type 2 diabetes (T2D) is common following bariatric surgery, particularly Roux-en-Y gastric bypass. However, the underlying mechanisms have not been fully elucidated. Methods To address this we compare the integrated serum, urine and faecal metabolic profiles of participants with obesity ± T2D (n = 80, T2D = 42) with participants who underwent Roux-en-Y gastric bypass or sleeve gastrectomy (pre and 3-months post-surgery; n = 27), taking diet into account. We co-model these data with shotgun metagenomic profiles of the gut microbiota to provide a comprehensive atlas of host-gut microbe responses to bariatric surgery, weight-loss and glycaemic control at the systems level. Results Here we show that bariatric surgery reverses several disrupted pathways characteristic of T2D. The differential metabolite set representative of bariatric surgery overlaps with both diabetes (19.3% commonality) and body mass index (18.6% commonality). However, the percentage overlap between diabetes and body mass index is minimal (4.0% commonality), consistent with weight-independent mechanisms of T2D resolution. The gut microbiota is more strongly correlated to body mass index than T2D, although we identify some pathways such as amino acid metabolism that correlate with changes to the gut microbiota and which influence glycaemic control. Conclusion We identify multi-omic signatures associated with responses to surgery, body mass index, and glycaemic control. Improved understanding of gut microbiota - host co-metabolism may lead to novel therapies for weight-loss or diabetes. However, further experiments are required to provide mechanistic insight into the role of the gut microbiota in host metabolism and establish proof of causality

Chat mining for gender prediction

The aim of this paper is to investigate the feasibility of predicting the gender of a text document's author using linguistic evidence. For this purpose, term- and style-based classification techniques are evaluated over a large collection of chat messages. Prediction accuracies up to 84.2% are achieved, illustrating the applicability of these techniques to gender prediction. Moreover, the reverse problem is exploited, and the effect of gender on the writing style is discussed. © Springer-Verlag Berlin Heidelberg 2006

Quantitative comparison of single- and two-particle properties in the cuprates

We explore the strong variations of the electronic properties of copper-oxygen compounds across the doping phase diagram in a quantitative way. To this end we calculate the electronic Raman response on the basis of results from angle-resolved photoemission spectroscopy (ARPES). In the limits of our approximations we find agreement on the overdoped side and pronounced discrepancies at lower doping. In contrast to the successful approach for the transport properties at low energies, the Raman and the ARPES data cannot be reconciled by adding angle-dependent momentum scattering. We discuss possible routes towards an explanation of the suppression of spectral weight close to the $(\pi,0)$ points which sets in abruptly close to 21% doping.Comment: 7 pages, 4 figure

Opto-mechanical measurement of micro-trap via nonlinear cavity enhanced Raman scattering spectrum

High-gain resonant nonlinear Raman scattering on trapped cold atoms within a high-fineness ring optical cavity is simply explained under a nonlinear opto-mechanical mechanism, and a proposal using it to detect frequency of micro-trap on atom chip is presented. The enhancement of scattering spectrum is due to a coherent Raman conversion between two different cavity modes mediated by collective vibrations of atoms through nonlinear opto-mechanical couplings. The physical conditions of this technique are roughly estimated on Rubidium atoms, and a simple quantum analysis as well as a multi-body semiclassical simulation on this nonlinear Raman process is conducted.Comment: 7 pages, 2 figure