Short SULF1/SULF2 splice variants predominate in mammary tumours with a potential to facilitate receptor tyrosine kinase-mediated cell signalling

The relative roles of SULF1 and SULF2 enzymes in tumour growth are controversial, but short SULF1/SULF2 splice variants predominate in human mammary tumours despite their non-detectable levels in normal mammary tissue. Compared with the normal, the level of receptor tyrosine kinase (RTK) activity was markedly increased in triple-positive mammary tumours during later stages of tumour progression showing increased p-EGFR, p-FGFR1 and p-cMet activity in triple-positive but not in triple-negative tumours. The abundance of catalytically inactive short SULF1/SULF2 variants permits high levels of HS sulphation and thus growth driving RTK cell signalling in primary mammary tumours. Also observed in this study, however, was increased N-sulphation detected by antibody 10E4 indicating that not only 6-O sulphation but also N-sulphation may contribute to increased RTK cell signalling in mammary tumours. The levels of such increases in not only SULF1/SULF2 but also in pEGFR, pFGFR1, p-cMet and Smad1/5/8 signalling were further enhanced following lymph node metastasis. The over-expression of Sulf1 and Sulf2 variants in mammary tumour-derived MDA-MB231 and MCF7 cell lines by transfection further confirms Sulf1-/Sulf2-mediated differential modulation of growth. The short variants of both Sulf1 and Sulf2 promoted FGF2-induced MDA-MB231 and MCF7 in vitro growth while full-length Sulf1 inhibited growth supporting in vivo mammary tumour cell signalling patterns of growth. Since a number of mammary tumours become drug resistant to hormonal therapy, Sulf1/Sulf2 inhibition could be an alternative therapeutic approach to target such tumours by down-regulating RTK-mediated cell signalling

Study on determining stability domains for nonlinear dynamical systems, II Quarterly progress report, 1 Aug. - 31 Oct. 1966

Stability domain determination for nonlinear dynamical syste

‘So people know I'm a Sikh’: Narratives of Sikh masculinities in contemporary Britain

This article examines British-born Sikh men's identification to Sikhism. In particular, it focuses on the appropriation and use of Sikh symbols amongst men who define themselves as Sikh. This article suggests that whilst there are multiple ways of ‘being’ a Sikh man in contemporary post-colonial Britain, and marking belonging to the Sikh faith, there is also a collectively understood idea of what an ‘ideal’ Sikh man should be. Drawing upon Connell and Messerschmidt's discussion of locally specific hegemonic masculinities (2005. “Hegemonic Masculinity: Rethinking the Concept.” Gender and Society 19 (6): 829–859), it is suggested that an ideal Sikh masculine identity is partly informed by a Khalsa discourse, which informs a particular performance of Sikh male identity, whilst also encouraging the surveillance of young men's activities both by themselves and by others. These Sikh masculinities are complex and multiple, rotating to reaffirm, challenge and redefine contextualised notions of hegemonic masculinity within the Sikh diaspora in post-colonial Britain. Such localised Sikh masculinities may both assert male privilege and reap patriarchal dividends (Connell, W. 1995. Masculinities. Cambridge: Polity Press), resulting in particular British Sikh hegemonic masculinities which seek to shape the performance of masculinity, yet in another context these very same performances of masculinity may also signify a more marginalised masculinity vis-à-vis other dominant hegemonic forms

Signatures of Strong Momentum Localization via Translational-Internal Entanglement

We show that atoms or molecules subject to fields that couple their internal and translational (momentum) states may undergo a crossover from randomization (diffusion) to strong localization (sharpening) of their momentum distribution. The predicted crossover should be manifest by a drastic change of the interference pattern as a function of the coupling fields.Comment: 4 pages, 3 figure

Ion-Acoustic Solitons in Bi-Ion Dusty Plasma

The propagation of ion-acoustic solitons in a warm dusty plasma containing two ion species is investigated theoretically. Using an approach based on the Korteveg-de-Vries equation, it is shown that the critical value of the negative ion density that separates the domains of existence of compressi- on and rarefaction solitons depends continuously on the dust density. A modified Korteveg-de Vries equation for the critical density is derived in the higher order of the expansion in the small parameter. It is found that the nonlinear coefficient of this equation is positive for any values of the dust density and the masses of positive and negative ions. For the case where the negative ion density is close to its critical value, a soliton solution is found that takes into account both the quadratic and cubic nonlinearities. The propagation of a solitary wave of arbitrary amplitude is investigated by the quasi-potential method. It is shown that the range of the dust densities around the critical value within which solitary waves with positive and negative potentials can exist simultaneously is relatively wide.Comment: 17 pages, 5 figure

Contributions of spontaneous phase slippage to linear and non-linear conduction near the Peierls transition in thin samples of o-TaS_3

In the Peierls state very thin samples of TaS_3 (cross-section area \sim 10^{-3} mkm^2) are found to demonstrate smearing of the I-V curves near the threshold field. With approaching the Peierls transition temperature, T_P, the smearing evolves into smooth growth of conductance from zero voltage interpreted by us as the contribution of fluctuations to the non--linear conductance. We identify independently the fluctuation contribution to the linear conductance near T_P. Both linear and non-linear contributions depend on temperature with close activation energies \sim (2 - 4) x 10^3 K and apparently reveal the same process. We reject creep of the {\it continuous} charge-density waves (CDWs) as the origin of this effect and show that it is spontaneous phase slippage that results in creep of the CDW. A model is proposed accounting for both the linear and non-linear parts of the fluctuation conduction up to T_P.Comment: 6 pages, 5 Postscript figure, RevTeX, accepted for publication in PR

A New Option for a Search for Alpha Variation: Narrow Transitions with Enhanced Sensitivity

We consider several transitions between narrow lines that have an enhanced sensitivity to a possible variation of the fine structure constant, alpha. This enhancement may allow a search to be performed with an effective suppression of the systematic sources of uncertainty that are unavoidable in conventional high-resolution spectroscopic measurements. In the future this may provide the strongest laboratory constraints on alpha variation

Hamiltonian formalism and the Garrett-Munk spectrum of internal waves in the ocean

Wave turbulence formalism for long internal waves in a stratified fluid is developed, based on a natural Hamiltonian description. A kinetic equation appropriate for the description of spectral energy transfer is derived, and its self-similar stationary solution corresponding to a direct cascade of energy toward the short scales is found. This solution is very close to the high wavenumber limit of the Garrett-Munk spectrum of long internal waves in the ocean. In fact, a small modification of the Garrett-Munk formalism includes a spectrum consistent with the one predicted by wave turbulence.Comment: 4 pages latex fil