Cell mixing induced by myc is required for competitive tissue invasion and destruction

Cell-cell intercalation is used in several developmental processes to shape the normal body plan. There is no clear evidence that intercalation is involved in pathologies. Here we use the proto-oncogene myc to study a process analogous to early phase of tumour expansion: myc-induced cell competition. Cell competition is a conserved mechanism driving the elimination of slow-proliferating cells (so-called 'losers') by faster-proliferating neighbours (so-called 'winners') through apoptosis and is important in preventing developmental malformations and maintain tissue fitness. Here we show, using long-term live imaging of myc-driven competition in the Drosophila pupal notum and in the wing imaginal disc, that the probability of elimination of loser cells correlates with the surface of contact shared with winners. As such, modifying loser-winner interface morphology can modulate the strength of competition. We further show that elimination of loser clones requires winner-loser cell mixing through cell-cell intercalation. Cell mixing is driven by differential growth and the high tension at winner-winner interfaces relative to winner-loser and loser-loser interfaces, which leads to a preferential stabilization of winner-loser contacts and reduction of clone compactness over time. Differences in tension are generated by a relative difference in F-actin levels between loser and winner junctions, induced by differential levels of the membrane lipid phosphatidylinositol (3,4,5)-trisphosphate. Our results establish the first link between cell-cell intercalation induced by a proto-oncogene and how it promotes invasiveness and destruction of healthy tissues.

Uso de DES y RANS no estacionario para la simulación del flujo alrededor de una carena Wigley - Use of Unsteady RANS and DES to simulate flows around a Wigley Hull)

Computer Fluid Dynamics tools have already become a valuable instrument for Naval Architects during the ship design process, thanks to their accuracy and the available computer power. Unfortunately, the development of RANSE codes, generally used when viscous effects play a major role in the flow, has not reached a mature stage, being the accuracy of the turbulence models and the free surface representation the most important sources of uncertainty. Another level of uncertainty is added when the simulations are carried out for unsteady flows, as those generally studied in seakeeping and maneuvering analysis and URANS equations solvers are used. Present work shows the applicability and the benefits derived from the use of new approaches for the turbulence modeling (Detached Eddy Simulation) and the free surface representation (Level Set) on the URANS equations solver CFDSHIP-Iowa. Compared to URANS, DES is expected to predict much broader frequency contents and behave better in flows where boundary layer separation plays a major role. Level Set methods are able to capture very complex free surface geometries, including breaking and overturning waves. The performance of these improvements is tested in set of fairly complex flows, generated by a Wigley hull at pure drift motion, with drift angle ranging from 10 to 60 degrees and at several Froude numbers to study the impact of its variation. Quantitative verification and validation are performed with the obtained results to guarantee their accuracy. The results show the capability of the CFDSHIP-Iowa code to carry out time-accurate simulations of complex flows of extreme unsteady ship maneuvers. The Level Set method is able to capture very complex geometries of the free surface and the use of DES in unsteady simulations highly improves the results obtained. Vortical structures and instabilities as a function of the drift angle and Fr are qualitatively identified. Overall analysis of the flow pattern shows a strong correlation between the vortical structures and free surface wave pattern. Karman-like vortex shedding is identified and the scaled St agrees well with the universal St value. Tip vortices are identified and the associated helical instabilities are analyzed. St using the hull length decreases with the increase of the distance along the vortex core (x), which is similar to results from other simulations. However, St scaled using distance along the vortex cores shows strong oscillations compared to almost constants for those previous simulations. The difference may be caused by the effect of the free-surface, grid resolution, and interaction between the tip vortex and other vortical structures, which needs further investigations. This study is exploratory in the sense that finer grids are desirable and experimental data is lacking for large α, especially for the local flow. More recently, high performance computational capability of CFDSHIP-Iowa V4 has been improved such that large scale computations are possible. DES for DTMB 5415 with bilge keels at α = 20º were conducted using three grids with 10M, 48M and 250M points. DES analysis for flows around KVLCC2 at α = 30º is analyzed using a 13M grid and compared with the results of DES on the 1.6M grid by. Both studies are consistent with what was concluded on grid resolution herein since dominant frequencies for shear-layer, Karman-like, horse-shoe and helical instabilities only show marginal variation on grid refinement. The penalties of using coarse grids are smaller frequency amplitude and less resolved TKE. Therefore finer grids should be used to improve V&V for resolving most of the active turbulent scales for all different Fr and α, which hopefully can be compared with additional EFD data for large α when it becomes available.

The estimation of truncation error by tau-estimation revisited

The aim of this paper was to accurately estimate the local truncation error of partial differential equations, that are numerically solved using a finite difference or finite volume approach on structured and unstructured meshes. In this work, we approximated the local truncation error using the @t-estimation procedure, which aims to compare the residuals on a sequence of grids with different spacing. First, we focused the analysis on one-dimensional scalar linear and non-linear test cases to examine the accuracy of the estimation of the truncation error for both finite difference and finite volume approaches on different grid topologies. Then, we extended the analysis to two-dimensional problems: first on linear and non-linear scalar equations and finally on the Euler equations. We demonstrated that this approach yields a highly accurate estimation of the truncation error if some conditions are fulfilled. These conditions are related to the accuracy of the restriction operators, the choice of the boundary conditions, the distortion of the grids and the magnitude of the iteration error.

Two gonadotropin-releasing hormone receptor subtypes with distinct ligand selectivity and differential distribution in brain and pituitary in the goldfish (Carassius auratus)

In the goldfish (Carassius auratus) the two endogenous forms of gonadotropin-releasing hormone (GnRH), namely chicken GnRH II ([His5,Trp7,Tyr8]GnRH) and salmon GnRH ([Trp7,Leu8]GnRH), stimulate the release of both gonadotropins and growth hormone from the pituitary. This control is thought to occur by means of the stimulation of distinct GnRH receptors. These receptors can be distinguished on the basis of differential gonadotropin and growth hormone releasing activities of naturally occurring GnRHs and GnRHs with variant amino acids in position 8. We have cloned the cDNAs of two GnRH receptors, GfA and GfB, from goldfish brain and pituitary. Although the receptors share 71% identity, there are marked differences in their ligand selectivity. Both receptors are expressed in the pituitary but are differentially expressed in the brain, ovary, and liver. Thus we have found and cloned two full-length cDNAs that appear to correspond to different forms of GnRH receptor, with distinct pharmacological characteristics and tissue distribution, in a single species.

Theory and calculation of the nonlinear energy transfer between sea waves in deep water /

"May 1982."

A course in mathematical analysis.

An unabridged and unaltered republication of the Hedrick-Dunkel translation (v. 1-2); v. 3. newly translated by Howard G. Bergmann.

An elementary treatise on curves, functions, and forces.

Available on demand as hard copy or computer file from Cornell University Library.

Four lectures on mathematics, delivered at Columbia University in 1911,

I. The defintion of solutions of linear partial differnetial equations by boundary conditions.--II. Contemporary researches in differential equations, integral equations, and integro-differential equations.--III. Analysis situs in connection with correspondences and differential equations.--IV. Elementary solutions of partial differential equations and Green's functions.

Estimating the specific heat capacity of starch-water-glycerol systems as a function of temperature and compositions

Increasing interests in the use of starch as biodegradable plastic materials demand, amongst others, accurate information on thermal properties of starch systems particularly in the processing of thermoplastic starch (TPS), where plasticisers (water and glycerol) are added. The specific heat capacity of starch-water-glycerol mixtures was determined within a temperature range of 40-120degreesC. A modulated temperature differential scanning calorimeter (MTDSC) was employed and regression equations were obtained to predict the specific heat capacity as a function of temperature, water and glycerol content for four maize starches of differing amylose content (0 - 85%). Generally, temperature and water content are directly proportional to the specific heat capacity of the systems, but the influence of glycerol content on the thermal property varied according to the starch type.

On the chaotic rotation of a liquid-filled gyrostat via the Melnikov-Holmes-Marsden integral

The non-linear motions of a gyrostat with an axisymmetrical, fluid-filled cavity are investigated. The cavity is considered to be completely filled with an ideal incompressible liquid performing uniform rotational motion. Helmholtz theorem, Euler's angular momentum theorem and Poisson equations are used to develop the disturbed Hamiltonian equations of the motions of the liquid-filled gyrostat subjected to small perturbing moments. The equations are established in terms of a set of canonical variables comprised of Euler angles and the conjugate angular momenta in order to facilitate the application of the Melnikov-Holmes-Marsden (MHM) method to investigate homoclinic/heteroclinic transversal intersections. In such a way, a criterion for the onset of chaotic oscillations is formulated for liquid-filled gyrostats with ellipsoidal and torus-shaped cavities and the results are confirmed via numerical simulations. (c) 2006 Elsevier Ltd. All rights reserved.

Probing three-way interactions in moderated multiple regression:Development and application of a slope difference test

Researchers often use 3-way interactions in moderated multiple regression analysis to test the joint effect of 3 independent variables on a dependent variable. However, further probing of significant interaction terms varies considerably and is sometimes error prone. The authors developed a significance test for slope differences in 3-way interactions and illustrate its importance for testing psychological hypotheses. Monte Carlo simulations revealed that sample size, magnitude of the slope difference, and data reliability affected test power. Application of the test to published data yielded detection of some slope differences that were undetected by alternative probing techniques and led to changes of results and conclusions. The authors conclude by discussing the test's applicability for psychological research. Copyright 2006 by the American Psychological Association.

Premature cardiovascular events and mortality in south Asians with type 2 diabetes in the United Kingdom Asian Diabetes Study - effect of ethnicity on risk

Background/Aim - People of south Asian origin have an excessive risk of morbidity and mortality from cardiovascular disease. We examined the effect of ethnicity on known risk factors and analysed the risk of cardiovascular events and mortality in UK south Asian and white Europeans patients with type 2 diabetes over a 2 year period. Methods - A total of 1486 south Asian (SA) and 492 white European (WE) subjects with type 2 diabetes were recruited from 25 general practices in Coventry and Birmingham, UK. Baseline data included clinical history, anthropometry and measurements of traditional risk factors – blood pressure, total cholesterol, HbA1c. Multiple linear regression models were used to examine ethnicity differences in individual risk factors. Ten-year cardiovascular risk was estimated using the Framingham and UKPDS equations. All subjects were followed up for 2 years. Cardiovascular events (CVD) and mortality between the two groups were compared. Findings - Significant differences were noted in risk profiles between both groups. After adjustment for clustering and confounding a significant ethnicity effect remained only for higher HbA1c (0.50 [0.22 to 0.77]; P?=?0.0004) and lower HDL (-0.09 [-0.17 to -0.01]; P?=?0.0266). Baseline CVD history was predictive of CVD events during follow-up for SA (P?difference of 7.4 years (95% CI 1.0 to 13.7 years), P?=?0.023. The adjusted odds ratio of CVD event or death from CVD was greater but not significantly so in SA than in WE (OR 1.4 [0.9 to 2.2]). Limitations - Fewer events in both groups and short period of follow-up are key limitations. Longer follow-up is required to see if the observed differences between the ethnic groups persist. Conclusion - South Asian patients with type 2 diabetes in the UK have a higher cardiovascular risk and present with cardiovascular events at a significantly younger age than white Europeans. Enhanced and ethnicity specific targets and effective treatments are needed if these inequalities are to be reduced.

On the numerical solution of a Cauchy problem for the Laplace equation via a direct integral equation approach

We investigate the problem of determining the stationary temperature field on an inclusion from given Cauchy data on an accessible exterior boundary. On this accessible part the temperature (or the heat flux) is known, and, additionally, on a portion of this exterior boundary the heat flux (or temperature) is also given. We propose a direct boundary integral approach in combination with Tikhonov regularization for the stable determination of the temperature and flux on the inclusion. To determine these quantities on the inclusion, boundary integral equations are derived using Green’s functions, and properties of these equations are shown in an L2-setting. An effective way of discretizing these boundary integral equations based on the Nystr¨om method and trigonometric approximations, is outlined. Numerical examples are included, both with exact and noisy data, showing that accurate approximations can be obtained with small computational effort, and the accuracy is increasing with the length of the portion of the boundary where the additionally data is given.

Fast reconstruction of harmonic functions from Cauchy data using integral equation techniques

We consider the problem of stable determination of a harmonic function from knowledge of the solution and its normal derivative on a part of the boundary of the (bounded) solution domain. The alternating method is a procedure to generate an approximation to the harmonic function from such Cauchy data and we investigate a numerical implementation of this procedure based on Fredholm integral equations and Nyström discretization schemes, which makes it possible to perform a large number of iterations (millions) with minor computational cost (seconds) and high accuracy. Moreover, the original problem is rewritten as a fixed point equation on the boundary, and various other direct regularization techniques are discussed to solve that equation. We also discuss how knowledge of the smoothness of the data can be used to further improve the accuracy. Numerical examples are presented showing that accurate approximations of both the solution and its normal derivative can be obtained with much less computational time than in previous works.

An alternating boundary integral based method for a Cauchy problem for the Laplace equation in a quadrant

We study the Cauchy problem for the Laplace equation in a quadrant (quarter-plane) containing a bounded inclusion. Given the values of the solution and its derivative on the edges of the quadrant the solution is reconstructed on the boundary of the inclusion. This is achieved using an alternating iterative method where at each iteration step mixed boundary value problems are being solved. A numerical method is also proposed and investigated for the direct mixed problems reducing these to integral equations over the inclusion. Numerical examples verify the efficiency of the proposed scheme.