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

A Particle-based Multiscale Solver for Compressible Liquid-Vapor Flow

To describe complex flow systems accurately, it is in many cases important to account for the properties of fluid flows on a microscopic scale. In this work, we focus on the description of liquid-vapor flow with a sharp interface between the phases. The local phase dynamics at the interface can be interpreted as a Riemann problem for which we develop a multiscale solver in the spirit of the heterogeneous multiscale method, using a particle-based microscale model to augment the macroscopic two-phase flow system. The application of a microscale model makes it possible to use the intrinsic properties of the fluid at the microscale, instead of formulating (ad-hoc) constitutive relations

Cyber Space Odyssey: A Competitive, Team-Oriented Serious Game in Computer Networking

Cyber Space Odyssey (CSO) is a novel serious game supporting computer networking education by engaging students in a race to successfully perform various cybersecurity tasks in order to collect clues and solve a puzzle in virtual near-Earth 3D space. Each team interacts with the game server through a dedicated client presenting a multimodal interface, using a game controller for navigation and various desktop computer networking tools of the trade for cybersecurity tasks on the game\u27s physical network. Specifically, teams connect to wireless access points, use packet monitors to intercept network traffic, decrypt and reverse engineer that traffic, craft well-formed and meaningful responses, and transmit those responses. Successful completion of these physical network actions to solve a sequence of increasingly complex problems is necessary to progress through the virtual, story-driven adventure. Use of the networking tools reinforces networking theory and offers hands-on practical training requisite for today\u27s cyberoperators. This paper presents the learning outcomes targeted by a classroom intervention based on CSO, the design and implementation of the game, a pedagogical overview of the overall intervention, and four years of quantitative and qualitative data assessing its effectiveness

Local forage fish abundance influences foraging effort and offspring condition in an endangered marine predator

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.All data will be archived in the Dryad Digital Repository and BirdLife Seabird Tracking Database.1. Understanding the functional relationship between marine predators and their prey is vital to inform ecosystem-based management. However, collecting concurrent data on predator behaviour and their prey at relevant scales is challenging. Moreover, opportunities to study these relationships in the absence of industrial fishing are extremely rare. 2. We took advantage of an experimental fisheries closure to study how local prey abundance influences foraging success and chick condition of Endangered African penguins Spheniscus demersus in the Benguela Ecosystem. 3. We tracked 75 chick-provisioning penguins with GPS-time-depth devices, measured body condition of 569 chicks, quantified the diet of 83 breeding penguins and conducted 12 forage fish hydro-acoustic surveys within a 20 km radius of Robben Island, South Africa, over three years (2011–2013). Commercial fishing for the penguins’ main prey, sardine Sardinops sagax and anchovy Engraulis encrasicolus, was prohibited within this 20 km radius during the study period. 4. Local forage fish abundance explained 60% of the variation in time spent diving for 14 penguins at sea within 2 days of a hydro-acoustic survey. Penguin foraging effort (time spent diving, number of wiggles per trip, number of foraging dives and the maximum distance travelled) increased and offspring body condition decreased as forage fish abundance declined. In addition, quantile regression revealed that variation in foraging effort increased as prey abundance around the colony declined. 5. Policy implications. Our results demonstrate that local forage fish abundance influences seabird foraging and offspring fitness. They also highlight the potential for offspring condition and the mean-variance relationship in foraging behaviour to act as leading indicators of poor prey abundance. By rapidly indicating periods where forage resources are scarce, these metrics could help limit seabird-fisheries competition and aid the implementation of dynamic ocean managemen

Breakdown of the Landauer bound for information erasure in the quantum regime

A known aspect of the Clausius inequality is that an equilibrium system subjected to a squeezing \d S of its entropy must release at least an amount |\dbarrm Q|=T|\d S| of heat. This serves as a basis for the Landauer principle, which puts a lower bound $T\ln 2$ for the heat generated by erasure of one bit of information. Here we show that in the world of quantum entanglement this law is broken. A quantum Brownian particle interacting with its thermal bath can either generate less heat or even {\it adsorb} heat during an analogous squeezing process, due to entanglement with the bath. The effect exists even for weak but fixed coupling with the bath, provided that temperature is low enough. This invalidates the Landauer bound in the quantum regime, and suggests that quantum carriers of information can be much more efficient than assumed so far.Comment: 13 pages, revtex, 2 eps figure

Number partitioning as random energy model

Number partitioning is a classical problem from combinatorial optimisation. In physical terms it corresponds to a long range anti-ferromagnetic Ising spin glass. It has been rigorously proven that the low lying energies of number partitioning behave like uncorrelated random variables. We claim that neighbouring energy levels are uncorrelated almost everywhere on the energy axis, and that energetically adjacent configurations are uncorrelated, too. Apparently there is no relation between geometry (configuration) and energy that could be exploited by an optimization algorithm. This ``local random energy'' picture of number partitioning is corroborated by numerical simulations and heuristic arguments.Comment: 8+2 pages, 9 figures, PDF onl

Adaptive Optics for Astronomy

Adaptive Optics is a prime example of how progress in observational astronomy can be driven by technological developments. At many observatories it is now considered to be part of a standard instrumentation suite, enabling ground-based telescopes to reach the diffraction limit and thus providing spatial resolution superior to that achievable from space with current or planned satellites. In this review we consider adaptive optics from the astrophysical perspective. We show that adaptive optics has led to important advances in our understanding of a multitude of astrophysical processes, and describe how the requirements from science applications are now driving the development of the next generation of novel adaptive optics techniques.Comment: to appear in ARA&A vol 50, 201