Phosphorylation of androgen receptors at serine 515 is a potential prognostic marker for triple negative breast cancer

1.7 million cases of breast cancer are diagnosed every year with 522,000 deaths. Molecular classifications of breast cancer have resulted in improved treatments. However, treatments for triple negative breast cancer (TNBC) are lacking. Analysis of molecular targets for TNBC is a priority. One potential candidate is androgen receptor (AR) phosphorylation. This study assessed the role of AR phosphorylation at ser81/ser515 and their two upstream effectors, cyclin-dependent kinase 1 (pCDK1) and extracellular-regulated kinase 1/2 (pERK1/2) in 332 ductal breast cancer patients by immunohistochemistry. pERK1/2 combined with AR-515 associated with improved cancer-specific survival (CSS, p = 0.038), decreased size (p = 0.001), invasive grade (p < 0.001), necrosis (p = 0.003), b-lymphocytes (p = 0.020), molecular subtype (p < 0.001) and estrogen receptor (ER)/progesterone receptor (PR)-status (p < 0.001). The cohort was therefore stratified into ER+ve and ER-ve patients. In ER+ve tumours, pERK1/2 combined with AR-515 associated with improved CSS (p = 0.038), smaller size (p = 0.004), invasive grade (p = 0.001), decreased b-lymphocytes (p = 0.013) and increased plasma cells (p = 0.048). In contrast, in TNBC patients, phosphorylation of AR-515 associated with poorer CSS (p = 0.007). pERK1/2 combined with AR-515 associated with decreased inflammation (p = 0.003), increased tumour stroma (p = 0.003) and tumour budding (p = 0.011), with trends towards decrease CSS (p = 0.065) and macrophage levels (p = 0.093). In Conclusions, AR-515 may be an important regulator of inflammation in breast cancer potential via ERK1/2 phosphorylation. AR-515 is a potential prognostic marker and therapeutic target for TNBC

Loss of signal transducer and activator of transcription 1 is associated with prostate cancer recurrence

STAT1 loss has previously been implicated in cell line studies to modify prostate cancer cell growth and survival, however the clinical significance of this has not previously been established. This study investigated if STAT1 loss was associated with patient outcome measures and the phenotypic consequence of STAT1 silencing. STAT1 expression was assessed in two patient cohorts with localised (n = 78) and advanced prostate cancer at initial diagnosis (n = 39) by immunohistochemistry (IHC). Impact of STAT1 silencing on prostate cancer cells lines was assessed using Cell Death detection ELISA, TLDA gene signature apoptosis arrays, WST-1 assay, xCELLigence system, clonogenic assay, and wound healing assay. In the localised patient cohort, low expression of STAT1 was associated with shorter time to disease recurrence (3.8 vs 7.3 years, P = 0.02) and disease specific survival (6.6 vs 9.3 years, P = 0.05). In the advanced patient cohort, low expression was associated with shorter time to disease recurrence (2.0 vs 3.9 years, P = 0.001). When STAT1 was silenced in PC3 cells (AR negative) and LNCaP cells (AR positive) silencing did not influence levels of apoptosis in either cell line and had little effect on cell viability in the LNCaP cells. In contrast, STAT1 silencing in the PC3 cells resulted in a pronounced increase in cell viability (WST-1 assay: mock silenced vs STAT1 silenced, P < 0.001), clonagenicity (clonogenic assay: mock silenced vs STAT1 silenced, P < 0.001), and migration (wound healing: mock silenced vs STAT1 silenced, P < 0.001). In conclusion, loss of STAT1 may promote prostate cancer recurrence in AR negative patients via increasing cell viability

Observations of H3+ in the Diffuse Interstellar Medium

Surprisingly large column densities of H3+ have been detected using infrared absorption spectroscopy in seven diffuse cloud sightlines (Cygnus OB2 12, Cygnus OB2 5, HD 183143, HD 20041, WR 104, WR 118, and WR 121), demonstrating that H3+ is ubiquitous in the diffuse interstellar medium. Using the standard model of diffuse cloud chemistry, our H3+ column densities imply unreasonably long path lengths (~1 kpc) and low densities (~3 cm^-3). Complimentary millimeter-wave, infrared, and visible observations of related species suggest that the chemical model is incorrect and that the number density of H3+ must be increased by one to two orders of magnitude. Possible solutions include a reduced electron fraction, an enhanced rate of H2 ionization, and/or a smaller value of the H3+ dissociative recombination rate constant than implied by laboratory experiments.Comment: To be published in Astrophysical Journal, March 200

Experimental Verification of 3D Plasmonic Cloaking in Free-Space

We report the experimental verification of metamaterial cloaking for a 3D object in free space. We apply the plasmonic cloaking technique, based on scattering cancellation, to suppress microwave scattering from a finite-length dielectric cylinder. We verify that scattering suppression is obtained all around the object in the near- and far-field and for different incidence angles, validating our measurements with analytical results and full-wave simulations. Our near-field and far-field measurements confirm that realistic and robust plasmonic metamaterial cloaks may be realized for elongated 3D objects with moderate transverse cross-section at microwave frequencies.Comment: 12 pages, 8 figures, published in NJ

Massive creation of entangled exciton states in semiconductor quantum dots

An intense laser pulse propagating in a medium of inhomogeneously broadened quantum dots massively creates entangled exciton states. After passage of the pulse all single-exciton states remain unpopulated (self-induced transparency) whereas biexciton coherence (exciton entanglement) is generated through two-photon transitions. We propose several experimental techniques for the observation of such unexpected behavior

A new theoretical paradigm to describe hysteresis, discrete memory and nonlinear elastic wave propagation in rock

International audienceThe velocity of sound in rock is a strong function of pressure, indicating that wave propagation in rocks is very nonlinear. The quasistatic elastic properties of rocks axe hysteretic, possessing discrete memory. In this paper a new theory is developed, placing all of these properties (nonlinearity, hysteresis, and memory) on equal footing. The starting point of the new theory is closer to a microscopic description of a rock than the starting point of the traditional five-constant theory of nonlinear elasticity. However, this starting point (the number density ? of generic mechanical elements in an abstract space) is deliberately independent of a specific microscopic model. No prejudice is imposed as to the mechanism causing nonlinear response in the microscopic mechanical elements. The new theory (1) relates suitable stress-strain measurements to the number density ? and (2) uses the number density ? to find the behaviour of nonlinear elastic waves. Thus the new theory provides for the synthesis of the full spectrum of elastic behaviours of a rock. Early development of the new theory is sketched in this contribution

Whispering Vortices

Experiments indicating the excitation of whispering gallery type electromagnetic modes by a vortex moving in an annular Josephson junction are reported. At relativistic velocities the Josephson vortex interacts with the modes of the superconducting stripline resonator giving rise to novel resonances on the current-voltage characteristic of the junction. The experimental data are in good agreement with analysis and numerical calculations based on the two-dimensional sine--Gordon model.Comment: 5 pages, 5 figures, text shortened to fit 4 pages, correction of typo