Hypoxic cancer cells are resistant to treatment, leading to the selection of cells with a more malignant phenotype. The expression of interleukin-8 (IL-8) plays an important role in the tumorigenesis ...and metastasis of solid tumors including prostate cancer. Recently, we detected elevated expression of IL-8 and IL-8 receptors in human prostate cancer tissue. The objective of the current study was to determine whether hypoxia increases IL-8 and IL-8 receptor expression in prostate cancer cells and whether this contributes to a survival advantage in hypoxic cells. IL-8, CXCR1 and CXCR2 messenger RNA (mRNA) expression in PC3 cells was upregulated in response to hypoxia in a time-dependent manner. Elevated IL-8 secretion following hypoxia was detected by enzyme-linked immunosorbent assay, while immunoblotting confirmed elevated receptor expression. Attenuation of hypoxia-inducible factor (HIF-1) and nuclear factor-κB (NF-κB) transcriptional activity using small interfering RNA (siRNA), a HIF-1 dominant-negative and pharmacological inhibitors, abrogated hypoxia-induced transcription of CXCR1 and CXCR2 in PC3 cells. Furthermore, chromatin-IP analysis demonstrated binding of HIF-1 and NF-κB to CXCR1. Finally, inhibition of IL-8 signaling potentiated etoposide-induced cell death in hypoxic PC3 cells. These results suggest that IL-8 signaling confers a survival advantage to hypoxic prostate cancer cells, and therefore, strategies to inhibit IL-8 signaling may sensitize hypoxic tumor cells to conventional treatments.
Understanding the structure of the wavefunction is essential for depicting the surface states of a topological insulator. Owing to the inherent strong spin-orbit coupling, the conventional ...hand-waving picture of the Dirac surface state with a single chiral spin texture is incomplete, as this ignores the orbital components of the Dirac wavefunction and their coupling to the spin textures. Here, by combining orbital-selective angle-resolved photoemission experiments and first-principles calculations, we deconvolve the in-plane and out-of-plane p-orbital components of the Dirac wavefunction. The in-plane orbital wavefunction is asymmetric relative to the Dirac point. It is predominantly tangential (radial) to the k-space constant energy surfaces above (below) the Dirac point. This orbital texture switch occurs exactly at the Dirac point, and therefore should be intrinsic to the topological physics. Our results imply that the Dirac wavefunction has a spin-orbital texture--a superposition of orbital wavefunctions coupled with the corresponding spin textures. PUBLICATION ABSTRACT
We present measurements of a long-range smoke transport event recorded on 20-21 July 2011 over Halifax, Nova Scotia, Canada, during the Quantifying the impact of BOReal forest fires on Tropospheric ...oxidants over the Atlantic using Aircraft and Satellites (BORTAS-B) campaign. Ground-based Fourier transform spectrometers and photometers detected air masses associated with large wildland fires burning in eastern Manitoba and western Ontario. We investigate a plume with high trace gas amounts but low amounts of particles that preceded and overlapped at the Halifax site with a second plume with high trace gas loadings and significant amounts of particulate material. We show that the first plume experienced a meteorological scavenging event, but the second plume had not been similarly scavenged. This points to the necessity to account carefully for the plume history when considering long-range transport since simultaneous or near-simultaneous times of arrival are not necessarily indicative of either similar trajectories or meteorological history. We investigate the origin of the scavenged plume, and the possibility of an aerosol wet deposition event occurring in the plume ~ 24 h prior to the measurements over Halifax. The region of lofting and scavenging is only monitored on an intermittent basis by the present observing network, and thus we must consider many different pieces of evidence in an effort to understand the early dynamics of the plume. Through this discussion we also demonstrate the value of having many simultaneous remote-sensing measurements in order to understand the physical and chemical behaviour of biomass burning plumes.
Lightning increases the atmosphere's ability to cleanse itself by producing nitric oxide (NO), leading to atmospheric chemistry that forms ozone (O
) and the atmosphere's primary oxidant, the ...hydroxyl radical (OH). Our analysis of a 2012 airborne study of deep convection and chemistry demonstrates that lightning also directly generates the oxidants OH and the hydroperoxyl radical (HO
). Extreme amounts of OH and HO
were discovered and linked to visible flashes occurring in front of the aircraft and to subvisible discharges in electrified anvil regions. This enhanced OH and HO
is orders of magnitude greater than any previous atmospheric observation. Lightning-generated OH in all storms happening at the same time globally can be responsible for a highly uncertain, but substantial, 2 to 16% of global atmospheric OH oxidation.
The aim of our study was to assess the importance of the CXC chemokine and interleukin (IL)-8 in promoting the transition of prostate cancer (CaP) to the androgen-independent state. Stimulation of ...the androgen-dependent cell lines, LNCaP and 22Rv1, with exogenous recombinant human interleukin-8 (rh-IL-8) increased androgen receptor (AR) gene expression at the messenger RNA (mRNA) and protein level, assessed by quantitative polymerase chain reaction and immunoblotting, respectively. Using an androgen response element-luciferase construct, we demonstrated that rh-IL-8 treatment also resulted in increased AR transcriptional activity in both these cell lines, and a subsequent upregulation of prostate-specific antigen and cyclin-dependent kinase 2 mRNA transcript levels in LNCaP cells. Blockade of CXC chemokine receptor-2 signaling using a small molecule antagonist (AZ10397767) attenuated the IL-8-induced increases in AR expression and transcriptional activity. Furthermore, in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, coadministration of AZ10397767 reduced the viability of LNCaP and 22Rv1 cells exposed to bicalutamide. Our data show that IL-8 signaling increases AR expression and promotes ligand-independent activation of this receptor in two androgen-dependent cell lines, describing two mechanisms by which this chemokine may assist in promoting the transition of CaP to the androgen-independent state. In addition, our data show that IL-8-promoted regulation of the AR attenuates the effectiveness of the AR antagonist bicalutamide in reducing CaP cell viability.
Using angle resolved photoemission spectroscopy measurements of Bi
Sr
CaCu
O
over a wide range of doping levels, we present a universal form for the non-Fermi liquid electronic interactions in the ...nodal direction in the exotic normal state phase. It is described by a continuously varying power law exponent versus energy and temperature (hence named a Power Law Liquid or PLL), which with doping varies smoothly from a quadratic Fermi Liquid in the overdoped regime, to a linear Marginal Fermi Liquid at optimal doping, to a non-quasiparticle non-Fermi Liquid in the underdoped regime. The coupling strength is essentially constant across all regimes and is consistent with Planckian dissipation. Using the extracted PLL parameters we reproduce the experimental optics and resistivity over a wide range of doping and normal-state temperature values, including the T* pseudogap temperature scale observed in the resistivity curves. This breaks the direct link to the pseudogapping of antinodal spectral weight observed at similar temperature scales and gives an alternative direction for searches of the microscopic mechanism.
Radiotherapy is an effective treatment of intermediate/high-risk locally advanced prostate cancer, however, >30% of patients relapse within 5 years. Clinicopathological parameters currently fail to ...identify patients prone to systemic relapse and those whom treatment intensification may be beneficial. The purpose of this study was to independently validate the performance of a 70-gene Metastatic Assay in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy.
A bridging cohort of prostate cancer diagnostic biopsy specimens was profiled to enable optimization of the Metastatic Assay threshold before further independent clinical validation in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy. Multivariable Cox proportional hazard regression analysis was used to assess assay performance in predicting biochemical failure-free survival (BFFS) and metastasis-free survival (MFS).
Gene expression analysis was carried out in 248 patients from the independent validation cohort and the Metastatic Assay applied. Ten-year MFS was 72% for Metastatic Assay positive patients and 94% for Metastatic Assay negative patients HR = 3.21 (1.35–7.67); P=0.003. On multivariable analysis the Metastatic Assay remained predictive for development of distant metastases HR = 2.71 (1.11–6.63); P=0.030. The assay retained independent prognostic performance for MFS when assessed with the Cancer of the Prostate Assessment Score (CAPRA) HR = 3.23 (1.22–8.59); P=0.019 whilst CAPRA itself was not significant HR = 1.88, (0.52–6.77); P=0.332. A high concordance 100% (61.5–100) for the assay result was noted between two separate foci taken from 11 tumours, whilst Gleason score had low concordance.
The Metastatic Assay demonstrated significant prognostic performance in patients treated with radical radiotherapy both alone and independent of standard clinical and pathological variables. The Metastatic Assay could have clinical utility when deciding upon treatment intensification in high-risk patients. Genomic and clinical data are available as a public resource.
We perform time- and angle-resolved photoemission spectroscopy (trARPES) on optimally doped Bi2Sr2CaCu2O8+δ (BSCCO-2212) using sufficient energy resolution (9 meV) to resolve the k -dependent ...near-nodal gap structure on time scales where the concept of an electronic pseudotemperature is a useful quantity, i.e., after electronic thermalization has occurred. We study the ultrafast evolution of this gap structure, uncovering a very rich landscape of decay rates as a function of angle, temperature, and energy. We explicitly focus on the quasiparticle states at the gap edge as well as on the spectral weight inside the gap that “fills” the gap—understood as an interaction, or self-energy effect—and we also make high resolution measurements of the nodal states, enabling a direct and accurate measurement of the electronic temperature (or pseudotemperature) of the electrons in the system. Rather than the standard method of interpreting these results using individual quasiparticle scattering rates that vary significantly as a function of angle, temperature, and energy, we show that the entire landscape of relaxations can be understood by modeling the system as following a nonequilibrium, electronic pseudotemperature that controls all electrons in the zone. Furthermore, this model has zero free parameters, as we obtain the crucial information of the SC gap Δ and the gap-filling strength ΓTDoS by connecting to static ARPES measurements. The quantitative and qualitative agreement between data and model suggests that the critical parameters and interactions of the system, including the pairing interactions, follow parametrically from the electronic pseudotemperature. We expect that this concept will be relevant for understanding the ultrafast response of a great variety of electronic materials, even though the electronic pseudotemperature may not be directly measurable.
We have successfully reproduced the Ozone ENSO Index (OEI) in the Goddard Earth Observing System (GEOS) chemistry‐climate model (CCM) forced by observed sea surface temperatures over a 25‐year ...period. The vertical ozone response to ENSO is consistent with changes in the Walker circulation. We derive the sensitivity of simulated ozone to ENSO variations using linear regression analysis. The western Pacific and Indian Ocean region shows similar positive ozone sensitivities from the surface to the upper troposphere, in response to positive anomalies in the Niño 3.4 Index. The eastern and central Pacific region shows negative sensitivities with the largest sensitivity in the upper troposphere. This vertical response compares well with that derived from SHADOZ ozonesondes in each region. The OEI reveals a response of tropospheric ozone to circulation change that is nearly independent of changes in emissions and thus it is potentially useful in chemistry‐climate model evaluation.
Key Points
We have successfully reproduced the Ozone ENSO Index in GEOS CCM
The vertical ozone response is consistent with changes in Walker and Hadley cell
OEI response is independent of changes in emissions and useful in CCM evaluation
The response of stratospheric climate and circulation to increasing amounts of greenhouse gases (GHGs) and ozone recovery in the twenty-first century is analyzed in simulations of 11 ...chemistry–climate models using near-identical forcings and experimental setup. In addition to an overall global cooling of the stratosphere in the simulations (0.59 ± 0.07 K decade−1at 10 hPa), ozone recovery causes a warming of the Southern Hemisphere polar lower stratosphere in summer with enhanced cooling above. The rate of warming correlates with the rate of ozone recovery projected by the models and, on average, changes from 0.8 to 0.48 K decade−1at 100 hPa as the rate of recovery declines from the first to the second half of the century. In the winter northern polar lower stratosphere the increased radiative cooling from the growing abundance of GHGs is, in most models, balanced by adiabatic warming from stronger polar downwelling. In the Antarctic lower stratosphere the models simulate an increase in low temperature extremes required for polar stratospheric cloud (PSC) formation, but the positive trend is decreasing over the twenty-first century in all models. In the Arctic, none of the models simulates a statistically significant increase in Arctic PSCs throughout the twenty-first century. The subtropical jets accelerate in response to climate change and the ozone recovery produces a westward acceleration of the lower-stratospheric wind over the Antarctic during summer, though this response is sensitive to the rate of recovery projected by the models. There is a strengthening of the Brewer–Dobson circulation throughout the depth of the stratosphere, which reduces the mean age of air nearly everywhere at a rate of about 0.05 yr decade−1in those models with this diagnostic. On average, the annual mean tropical upwelling in the lower stratosphere (∼70 hPa) increases by almost 2% decade−1, with 59% of this trend forced by the parameterized orographic gravity wave drag in the models. This is a consequence of the eastward acceleration of the subtropical jets, which increases the upward flux of (parameterized) momentum reaching the lower stratosphere in these latitudes.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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