Reconciling float-based and tracer-based estimates of lateral diffusivities

Lateral diffusivities are computed from synthetic particles and tracers advected by a velocity field derived from sea-surface height measurements from the South Pacific, in a region west of Drake Passage. Three different estimates are compared: (1) the tracer-based “effective diffusivity” of Nakamura (1996), (2) the growth of the second moment of a cloud of tracer and (3) the single- and two-particle Lagrangian diffusivities. The effective diffusivity measures the cross-stream component of eddy mixing, so this article focuses on the meridional diffusivities for the others, as the mean flow (the ACC) is zonally oriented in the region. After an initial transient of a few weeks, the effective diffusivity agrees well with the meridional diffusivity estimated both from the tracer cloud and from the particles. This proves that particle- and tracer-based estimates of eddy diffusivities are equivalent, despite recent claims to the contrary. Convergence among the three estimates requires that the Lagrangian diffusivities be estimated using their asymptotic values, not their maximum values. The former are generally much lower than the latter in the presence of a mean flow. Sampling the long-time asymptotic behavior of Lagrangian diffusivities requires very large numbers of floats in field campaigns. For example, it is shown that hundreds of floats would be necessary to estimate the vertical and horizontal variations in eddy diffusivity in a sector of the Pacific Southern Ocean

Southern Ocean biogenic blooms freezing-in Oligocene colder climates

AbstractCrossing a key atmospheric CO2 threshold triggered a fundamental global climate reorganisation ~34 million years ago (Ma) establishing permanent Antarctic ice sheets. Curiously, a more dramatic CO2 decline (~800–400 ppm by the Early Oligocene(~27 Ma)), postdates initial ice sheet expansion but the mechanisms driving this later, rapid drop in atmospheric carbon during the early Oligocene remains elusive and controversial. Here we use marine seismic reflection and borehole data to reveal an unprecedented accumulation of early Oligocene strata (up to 2.2 km thick over 1500 × 500 km) with a major biogenic component in the Australian Southern Ocean. High-resolution ocean simulations demonstrate that a tectonically-driven, one-off reorganisation of ocean currents, caused a unique period where current instability coincided with high nutrient input from the Antarctic continent. This unrepeated and short-lived environment favoured extreme bioproductivity and enhanced sediment burial. The size and rapid accumulation of this sediment package potentially holds ~1.067 × 1015 kg of the ‘missing carbon’ sequestered during the decline from an Eocene high CO2-world to a mid-Oligocene medium CO2-world, highlighting the exceptional role of the Southern Ocean in modulating long-term climate.</jats:p

Androgen receptor protein is down-regulated by basic fibroblast growth factor in prostate cancer cells

Interactions between polypeptide growth factors and the androgen receptor (AR) are important for regulation of cellular events in carcinoma of the prostate. Basic fibroblast growth factor (bFGF), the prototype of heparin-binding growth factors, and the AR are commonly expressed in prostate cancer. bFGF diminished prostate-specific antigen protein in the supernatants of androgen-stimulated human prostate cancer cells LNCaP by 80%. In the present study, we asked whether the bFGF effect on prostate-specific antigen is preceded by action on AR expression. LNCaP cells were treated with bFGF and AR protein expression was determined by immunoblotting and ligand binding assay. bFGF down-regulated AR protein in a dose-dependent manner showing a maximal effect at 50 ng ml−1both in the presence or absence of dihydrotestosterone. Down-regulation of AR protein expression occurred already after 8 h of bFGF treatment and a maximal inhibition was observed 24 h after addition of bFGF to culture media. As AR expression can be reduced by an increase in intracellular calcium levels, we investigated whether the bFGF effect on AR protein is mediated by this mechanism. Calcium release from intracellular stores and store-operated calcium influx after treatment with either bFGF or calcium ionophore A 23187 were measured by single cell fluorescence technique. The ionophore A 23187 was able to induce calcium influx and an increase in cytoplasmic calcium concentration in LNCaP cells. In contrast, bFGF was incapable of eliciting a similar effect. In contrast to AR protein, AR mRNA levels were not affected by bFGF as shown by semiquantitative reverse transcription polymerase chain reaction. In summary, these studies show that bFGF is a potent negative regulator of AR protein expression in the human prostate cancer cell line LNCaP. © 2000 Cancer Research Campaig

All Doors Lead to the Kitchen – Sustainability and Wellbeing Challenges in a Shared Centrepiece of Living

The kitchen figures a central place in the home where a significant share of a household’s resource consumption takes place. Sharing the kitchen between multiple households has potential to bring positive sustainability effects due to more efficient use of both material resources and energy. The concept of shared kitchens has, however, thus far had a limited diffusion. This paper explores the potential of shared kitchens as a future sustainable living environment by studying user experiences from a Living Lab setting. It builds the base for an overarching larger European collaboration on how future shared kitchens should be designed in order to support everyday practices while optimising the conditions for achieving positive impact on both sustainability and wellbeing. Findings are presented from five focus areas concerning different use contexts: (1) accessing, (2) cooking, (3) living and socialising, (4) storing, and (5) cleaning

Deep-Reaching Global Ocean Overturning Circulation Generated by Surface Buoyancy Forcing

In contrast with the atmosphere, which is heated from below by solar radiation, the ocean is both heated and cooled from above. To drive a deep-reaching overturning circulation in this context, it is generally assumed that either intense interior mixing by winds and internal tides, or wind-driven upwelling is required; in their absence, the circulation is thought to collapse to a shallow surface cell. We demonstrate, using a primitive equation model with an idealized domain and no wind forcing, that the surface temperature forcing can in fact drive an interhemispheric overturning provided that there is an open channel unblocked in the zonal direction, such as in the Southern Ocean. With this geometry, rotating horizontal convection, in combination with asymmetric surface cooling between the north and south, drives a deep-reaching two-cell overturning circulation. The resulting vertical mid-depth stratification closely resembles that of the real ocean, suggesting that wind-driven pumping is not necessary to produce a deep-reaching overturning circulation, and that buoyancy forcing plays a more important role than is usually assumed

Targeting the glucocorticoid receptor signature gene Mono Amine Oxidase-A enhances the efficacy of chemo- and anti-androgen therapy in advanced prostate cancer

Despite increasing options for treatment of castration-resistant prostate cancer, development of drug resistance is inevitable. The glucocorticoid receptor (GR) is a prime suspect for acquired therapy resistance, as prostate cancer (PCa) cells are able to increase GR signaling during anti-androgen therapy and thereby circumvent androgen receptor (AR)-blockade and cell death. As standard AR-directed therapies fail to block the GR and GR inhibitors might result in intolerable side effects, the identification of GR signature genes, which are better suited for a targeted approach, is of clinical importance. Therefore, the specific epithelial and stromal GR signature was determined in cancer-associated fibroblasts as well as in abiraterone and enzalutamide-resistant cells after glucocorticoid (GC) treatment. Microarray and ChIP analysis identified MAO-A as a directly up-regulated mutual epithelial and stromal GR target, which is induced after GC treatment and during PCa progression. Elevated MAO-A levels were confirmed in in vitro cell models, in primary tissue cultures after GC treatment, and in patients after neoadjuvant chemotherapy with GCs. MAO-A expression correlates with GR/AR activity as well as with a reduced progression-free survival. Pharmacological MAO-A inhibition combined with 2(nd) generation AR signaling inhibitors or chemotherapeutics results in impaired growth of androgen-dependent, androgen-independent, and long-term anti-androgen-treated cells. In summary, these findings demonstrate that targeting MAO-A represents an innovative therapeutic strategy to synergistically block GR and AR dependent PCa cell growth and thereby overcome therapy resistance.Prostatic carcinom

Prostate-specific antigen testing in Tyrol, Austria: prostate cancer mortality reduction was supported by an update with mortality data up to 2008

Objectives: The objective of this study was to update an in-depth analysis of the time trend for prostate cancer (PCA) mortality in the population of Tyrol by 5 years, namely to 2008. In Tyrol, prostate-specific antigen (PSA) tests were introduced in 1988/89; more than three-quarters of all men in the age group 45–74 had at least one PSA test in the past decade. Methods: We applied the same model as in a previous publication, i.e., an age-period-cohort model using Poisson regression, to the mortality data covering more than three decades from 1970 to 2008. Results: For Tyrol from 2004 to 2008 in the age group 60+ period terms show a significant reduction in prostate cancer mortality with a risk ratio of 0.70 (95% confidence interval 0.57, 0.87) for Tyrol, and for Austria excluding Tyrol a moderate reduction with a risk ratio of 0.92 (95% confidence interval 0.87, 0.97), each compared to the mortality rate in the period 1989–1993. Conclusions: This update strengthens our previously published results, namely that PSA testing offered to a population at no charge can reduce prostate cancer mortality. The extent of mortality reduction is in line with that reported in the other recent publications. However, our data do not permit us to fully assess the harms associated with PCA screening, and no recommendation for PSA screening can be made without a careful evaluation of overdiagnosis and overtreatment