S100A4 downregulates filopodia formation through increased dynamic instability

Cell migration requires the initial formation of cell protrusions, lamellipodia and/or filopodia, the attachment of the leading lamella to extracellular cues and the formation and efficient recycling of focal contacts at the leading edge. The small calcium binding EF-hand protein S100A4 has been shown to promote cell motility but the direct molecular mechanisms responsible remain to be elucidated. In this work, we provide new evidences indicating that elevated levels of S100A4 affect the stability of filopodia and prevent the maturation of focal complexes. Increasing the levels of S100A4 in a rat mammary benign tumor derived cell line results in acquired cellular migration on the wound healing scratch assay. At the cellular levels, we found that high levels of S100A4 induce the formation of many nascent filopodia, but that only a very small and limited number of those can stably adhere and mature, as opposed to control cells, which generate fewer protrusions but are able to maintain these into more mature projections. This observation was paralleled by the fact that S100A4 overexpressing cells were unable to establish stable focal adhesions. Using different truncated forms of the S100A4 proteins that are unable to bind to myosin IIA, our data suggests that this newly identified functions of S100A4 is myosin-dependent, providing new understanding on the regulatory functions of S100A4 on cellular migration

A simple approach to counterterms in N=8 supergravity

We present a simple systematic method to study candidate counterterms in N=8 supergravity. Complicated details of the counterterm operators are avoided because we work with the on-shell matrix elements they produce. All n-point matrix elements of an independent SUSY invariant operator of the form D^{2k} R^n +... must be local and satisfy SUSY Ward identities. These are strong constraints, and we test directly whether or not matrix elements with these properties can be constructed. If not, then the operator does not have a supersymmetrization, and it is excluded as a potential counterterm. For n>4, we find that R^n, D^2 R^n, D^4 R^n, and D^6 R^n are excluded as counterterms of MHV amplitudes, while only R^n and D^2 R^n are excluded at the NMHV level. As a consequence, for loop order L<7, there are no independent D^{2k}R^n counterterms with n>4. If an operator is not ruled out, our method constructs an explicit superamplitude for its matrix elements. This is done for the 7-loop D^4 R^6 operator at the NMHV level and in other cases. We also initiate the study of counterterms without leading pure-graviton matrix elements, which can occur beyond the MHV level. The landscape of excluded/allowed candidate counterterms is summarized in a colorful chart.Comment: 25 pages, 1 figure, published versio

Anomaly Equations and Intersection Theory

Six-dimensional supergravity theories with N=(1,0) supersymmetry must satisfy anomaly equations. These equations come from demanding the cancellation of gravitational, gauge and mixed anomalies. The anomaly equations have implications for the geometrical data of Calabi-Yau threefolds, since F-theory compactified on an elliptically fibered Calabi-Yau threefold with a section generates a consistent six-dimensional N=(1,0) supergravity theory. In this paper, we show that the anomaly equations can be summarized by three intersection theory identities. In the process we also identify the geometric counterpart of the anomaly coefficients---in particular, those of the abelian gauge groups---that govern the low-energy dynamics of the theory. We discuss the results in the context of investigating string universality in six dimensions.Comment: 29 pages + appendices, 8 figures; v2: minor corrections, references added; v3: minor corrections, reference adde

F-theory on Genus-One Fibrations

We argue that M-theory compactified on an arbitrary genus-one fibration, that is, an elliptic fibration which need not have a section, always has an F-theory limit when the area of the genus-one fiber approaches zero. Such genus-one fibrations can be easily constructed as toric hypersurfaces, and various $SU(5)\times U(1)^n$ and $E_6$ models are presented as examples. To each genus-one fibration one can associate a $\tau$-function on the base as well as an $SL(2,\mathbb{Z})$ representation which together define the IIB axio-dilaton and 7-brane content of the theory. The set of genus-one fibrations with the same $\tau$-function and $SL(2,\mathbb{Z})$ representation, known as the Tate-Shafarevich group, supplies an important degree of freedom in the corresponding F-theory model which has not been studied carefully until now. Six-dimensional anomaly cancellation as well as Witten's zero-mode count on wrapped branes both imply corrections to the usual F-theory dictionary for some of these models. In particular, neutral hypermultiplets which are localized at codimension-two fibers can arise. (All previous known examples of localized hypermultiplets were charged under the gauge group of the theory.) Finally, in the absence of a section some novel monodromies of Kodaira fibers are allowed which lead to new breaking patterns of non-Abelian gauge groups.Comment: 53 pages, 9 figures, 6 tables. v2: references adde

R^4 counterterm and E7(7) symmetry in maximal supergravity

The coefficient of a potential R^4 counterterm in N=8 supergravity has been shown previously to vanish in an explicit three-loop calculation. The R^4 term respects N=8 supersymmetry; hence this result poses the question of whether another symmetry could be responsible for the cancellation of the three-loop divergence. In this article we investigate possible restrictions from the coset symmetry E7(7)/SU(8), exploring the limits as a single scalar becomes soft, as well as a double-soft scalar limit relation derived recently by Arkani-Hamed et al. We implement these relations for the matrix elements of the R^4 term that occurs in the low-energy expansion of closed-string tree-level amplitudes. We find that the matrix elements of R^4 that we investigated all obey the double-soft scalar limit relation, including certain non-maximally-helicity-violating six-point amplitudes. However, the single-soft limit does not vanish for this latter set of amplitudes, which suggests that the E7(7) symmetry is broken by the R^4 term.Comment: 33 pages, typos corrected, published versio

Willingness to participate in future HIV prevention studies among gay and bisexual men in Scotland, UK: a challenge for intervention trials

This article examines willingness to participate in future HIV prevention research among gay and bisexual men in Scotland, UK. Anonymous, self-complete questionnaires and Orasure Gäó oral fluid samples were collected in commercial gay venues. 1,320 men were eligible for inclusion. 78.2% reported willingness to participate in future HIV prevention research; 64.6% for an HIV vaccine, 57.4% for a behaviour change study, and 53.0% for a rectal microbicide. In multivariate analysis, for HIV vaccine research, greater age, minority ethnicity, and not providing an oral fluid sample were associated with lower willingness; heterosexual orientation and not providing an oral fluid sample were for microbicides; higher education and greater HIV treatment optimism were for behaviour change. STI testing remained associated with being more willing to participate in microbicide research and frequent gay scene use remained associated with being more willing to participate in behaviour change research. Having an STI in the past 12 months remained significantly associated with being willing to participate in all three study types. There were no associations between sexual risk behaviour and willingness. Although most men expressed willingness to participate in future research, recruitment of high-risk men, who have the potential to benefit most, is likely to be more challenging

Super Weyl invariance: BPS equations from heterotic worldsheets

It is well-known that the beta functions on a string worldsheet correspond to the target space equations of motion, e.g. the Einstein equations. We show that the BPS equations, i.e. the conditions of vanishing supersymmetry variations of the space-time fermions, can be directly derived from the worldsheet. To this end we consider the RNS-formulation of the heterotic string with (2,0) supersymmetry, which describes a complex torsion target space that supports a holomorphic vector bundle. After a detailed account of its quantization and renormalization, we establish that the cancellation of the Weyl anomaly combined with (2,0) finiteness implies the heterotic BPS conditions: At the one loop level the geometry is required to be conformally balanced and the gauge background has to satisfy the Hermitean Yang-Mills equations.Comment: 1+31 pages LaTeX, 5 figures; final version, discussion relation Weyl invariance and (2,0) finiteness extended, typos correcte

Evanescent light-matter Interactions in Atomic Cladding Wave Guides

Alkali vapors, and in particular rubidium, are being used extensively in several important fields of research such as slow and stored light non-linear optics3 and quantum computation. Additionally, the technology of alkali vapors plays a major role in realizing myriad industrial applications including for example atomic clocks magentometers8 and optical frequency stabilization. Lately, there is a growing effort towards miniaturizing traditional centimeter-size alkali vapor cells. Owing to the significant reduction in device dimensions, light matter interactions are greatly enhanced, enabling new functionalities due to the low power threshold needed for non-linear interactions. Here, taking advantage of the mature Complimentary Metal-Oxide-Semiconductor (CMOS) compatible platform of silicon photonics, we construct an efficient and flexible platform for tailored light vapor interactions on a chip. Specifically, we demonstrate light matter interactions in an atomic cladding wave guide (ACWG), consisting of CMOS compatible silicon nitride nano wave-guide core with a Rubidium (Rb) vapor cladding. We observe the highly efficient interaction of the electromagnetic guided mode with the thermal Rb cladding. The nature of such interactions is explained by a model which predicts the transmission spectrum of the system taking into account Doppler and transit time broadening. We show, that due to the high confinement of the optical mode (with a mode area of 0.3{\lambda}2), the Rb absorption saturates at powers in the nW regime.Comment: 10 Pages 4 Figures. 1 Supplementar

From correlation functions to Wilson loops

We start with an n-point correlation function in a conformal gauge theory. We show that a special limit produces a polygonal Wilson loop with $n$ sides. The limit takes the $n$ points towards the vertices of a null polygonal Wilson loop such that successive distances $x^2_{i,i+1} \to 0$. This produces a fast moving particle that generates a "frame" for the Wilson loop. We explain in detail how the limit is approached, including some subtle effects from the propagation of a fast moving particle in the full interacting theory. We perform perturbative checks by doing explicit computations in N=4 super-Yang-Mills.Comment: 37 pages, 10 figures; typos corrected, references adde

Dose reduction to normal tissues as compared to the gross tumor by using intensity modulated radiotherapy in thoracic malignancies

BACKGROUND AND PURPOSE: Intensity modulated radiotherapy (IMRT) is a powerful tool, which might go a long way in reducing radiation doses to critical structures and thereby reduce long term morbidities. The purpose of this paper is to evaluate the impact of IMRT in reducing the dose to the critical normal tissues while maintaining the desired dose to the volume of interest for thoracic malignancies. MATERIALS AND METHODS: During the period January 2002 to March 2004, 12 patients of various sites of malignancies in the thoracic region were treated using physical intensity modulator based IMRT. Plans of these patients treated with IMRT were analyzed using dose volume histograms. RESULTS: An average dose reduction of the mean values by 73% to the heart, 69% to the right lung and 74% to the left lung, with respect to the GTV could be achieved with IMRT. The 2 year disease free survival was 59% and 2 year overall survival was 59%. The average number of IMRT fields used was 6. CONCLUSION: IMRT with inverse planning enabled us to achieve desired dose distribution, due to its ability to provide sharp dose gradients at the junction of tumor and the adjacent critical organs