Human phosphodiesterase 4D7 (PDE4D7) expression is increased in TMPRSS2-ERG positive primary prostate cancer and independently adds to a reduced risk of post-surgical disease progression

background: There is an acute need to uncover biomarkers that reflect the molecular pathologies, underpinning prostate cancer progression and poor patient outcome. We have previously demonstrated that in prostate cancer cell lines PDE4D7 is downregulated in advanced cases of the disease. To investigate further the prognostic power of PDE4D7 expression during prostate cancer progression and assess how downregulation of this PDE isoform may affect disease outcome, we have examined PDE4D7 expression in physiologically relevant primary human samples. methods: About 1405 patient samples across 8 publically available qPCR, Affymetrix Exon 1.0 ST arrays and RNA sequencing data sets were screened for PDE4D7 expression. The TMPRSS2-ERG gene rearrangement status of patient samples was determined by transformation of the exon array and RNA seq expression data to robust z-scores followed by the application of a threshold >3 to define a positive TMPRSS2-ERG gene fusion event in a tumour sample. results: We demonstrate that PDE4D7 expression positively correlates with primary tumour development. We also show a positive association with the highly prostate cancer-specific gene rearrangement between TMPRSS2 and the ETS transcription factor family member ERG. In addition, we find that in primary TMPRSS2-ERG-positive tumours PDE4D7 expression is significantly positively correlated with low-grade disease and a reduced likelihood of progression after primary treatment. Conversely, PDE4D7 transcript levels become significantly decreased in castration resistant prostate cancer (CRPC). conclusions: We further characterise and add physiological relevance to PDE4D7 as a novel marker that is associated with the development and progression of prostate tumours. We propose that the assessment of PDE4D7 levels may provide a novel, independent predictor of post-surgical disease progression

An investigation into the fertilizer potential of slaughterhouse cattle paunch

In Australia, the red meat processing industry actively seeks approaches to improve the management of solid waste from processing operations and enhance the environmental performance. Recycling of paunch waste to farmland could be a cost-effective and practicable environmental option. However, little is known about the agronomic value of fresh and composted paunch, and the associated requirements for land application. Therefore, a short-term experimental work was undertaken to assess potential risks due to weed seed contamination and determine the agronomic response of ryegrass (Lolium perenne L.) to soil incorporation of paunch. The risk of weed contamination from soil application of paunch appeared to be low; however, methods that account for viability of seeds may be required to fully discard such a risk. Soil application of paunch at field equivalent rates of 150-300 kg ha-1 of N increased dry matter yield by ≈30% on average compared with untreated grass, but was approximately 35% lower than a mineral fertilizer treatment applied at the same rates. Dry matter yield of paunch-treated grass was between 2000 and 3000 kg per ha over four consecutive cuts at 25-day intervals. Nitrogen use-efficiency of paunch was approximately 10% (range: 3% to 20%, depending on paunch type), and total N in harvested plant material showed values, which were between 2% and 3%. Overall, there appears to be potential for paunch-derived products to be used as a source of carbon and nutrients in crop production. Areas that merit a research priority within this space are also outlined in this paper. Such work is required to inform soil-, climate- and crop-specific land application rates, optimize agronomic performance, and minimize environmental concerns. There is also a requirement for the value proposition to industry to be determined, including reduced cost of disposal of material via gate fees and fertilizer replacement value

On the Stability of the Mean-Field Glass Broken Phase under Non-Hamiltonian Perturbations

We study the dynamics of the SK model modified by a small non-hamiltonian perturbation. We study aging, and we find that on the time scales investigated by our numerical simulations it survives a small perturbation (and is destroyed by a large one). If we assume we are observing a transient behavior the scaling of correlation times versus the asymmetry strength is not compatible with the one expected for the spherical model. We discuss the slow power law decay of observable quantities to equilibrium, and we show that for small perturbations power like decay is preserved. We also discuss the asymptotically large time region on small lattices.Comment: 34 page

Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1

Brief periods of sleep loss have long-lasting consequences such as impaired memory consolidation. Structural changes in synaptic connectivity have been proposed as a substrate of memory storage. Here, we examine the impact of brief periods of sleep deprivation on dendritic structure. In mice, we find that five hours of sleep deprivation decreases dendritic spine numbers selectively in hippocampal area CA1 and increased activity of the filamentous actin severing protein cofilin. Recovery sleep normalizes these structural alterations. Suppression of cofilin function prevents spine loss, deficits in hippocampal synaptic plasticity, and impairments in long-term memory caused by sleep deprivation. The elevated cofilin activity is caused by cAMP-degrading phosphodiesterase-4A5 (PDE4A5), which hampers cAMP-PKA-LIMK signaling. Attenuating PDE4A5 function prevents changes in cAMP-PKA-LIMK-cofilin signaling and cognitive deficits associated with sleep deprivation. Our work demonstrates the necessity of an intact cAMP-PDE4-PKA-LIMK-cofilin activation-signaling pathway for sleep deprivation-induced memory disruption and reduction in hippocampal spine density

Dynamic Critical Behavior of the Swendsen-Wang Algorithm: The Two-Dimensional 3-State Potts Model Revisited

We have performed a high-precision Monte Carlo study of the dynamic critical behavior of the Swendsen-Wang algorithm for the two-dimensional 3-state Potts model. We find that the Li-Sokal bound ($\tau_{int,E} \geq const \times C_H$) is almost but not quite sharp. The ratio $\tau_{int,E} / C_H$ seems to diverge either as a small power ($\approx 0.08$) or as a logarithm.Comment: 35 pages including 3 figures. Self-unpacking file containing the LaTeX file, the needed macros (epsf.sty, indent.sty, subeqnarray.sty, and eqsection.sty) and the 3 Postscript figures. Revised version fixes a normalization error in \xi (with many thanks to Wolfhard Janke for finding the error!). To be published in J. Stat. Phys. 87, no. 1/2 (April 1997

Quenched Random Graphs

Spin models on quenched random graphs are related to many important optimization problems. We give a new derivation of their mean-field equations that elucidates the role of the natural order parameter in these models.Comment: 9 pages, report CPTH-A264.109

Computing the Roughening Transition of Ising and Solid-On-Solid Models by BCSOS Model Matching

We study the roughening transition of the dual of the 2D XY model, of the Discrete Gaussian model, of the Absolute Value Solid-On-Solid model and of the interface in an Ising model on a 3D simple cubic lattice. The investigation relies on a renormalization group finite size scaling method that was proposed and successfully tested a few years ago. The basic idea is to match the renormalization group flow of the interface observables with that of the exactly solvable BCSOS model. Our estimates for the critical couplings are $\beta_R^{XY}=1.1199(1)$, $K_R^{DG}=0.6653(2)$ and $K_R^{ASOS}=0.80608(2)$ for the XY-model, the Discrete Gaussian model and the Absolute Value Solid-On-Solid model, respectively. For the inverse roughening temperature of the Ising interface we find $K_R^{Ising}= 0.40758(1)$. To the best of our knowledge, these are the most precise estimates for these parameters published so far.Comment: 25 pages, LaTeX file, no figure

Dynamic Critical Behavior of a Swendsen-Wang-Type Algorithm for the Ashkin-Teller Model

We study the dynamic critical behavior of a Swendsen-Wang-type algorithm for the Ashkin--Teller model. We find that the Li--Sokal bound on the autocorrelation time ($\tau_{{\rm int},{\cal E}} \ge {\rm const} \times C_H$) holds along the self-dual curve of the symmetric Ashkin--Teller model, and is almost but not quite sharp. The ratio $\tau_{{\rm int},{\cal E}} / C_H$ appears to tend to infinity either as a logarithm or as a small power ($0.05 \leq p \leq 0.12$). In an appendix we discuss the problem of extracting estimates of the exponential autocorrelation time.Comment: 59 pages including 3 figures, uuencoded g-compressed ps file. Postscript size = 799740 byte