Actors that Unify Threads and Events

There is an impedance mismatch between message-passing concurrency and virtual machines, such as the JVM. VMs usually map their threads to heavyweight OS processes. Without a lightweight process abstraction, users are often forced to write parts of concurrent applications in an event-driven style which obscures control flow, and increases the burden on the programmer. In this paper we show how thread-based and event-based programming can be unified under a single actor abstraction. Using advanced abstraction mechanisms of the Scala programming language, we implemented our approach on unmodified JVMs. Our programming model integrates well with the threading model of the underlying VM

Systemic inflammatory responses following welding inhalation challenge test

Peer reviewe

Euclid: Fast two-point correlation function covariance through linear construction

We present a method for fast evaluation of the covariance matrix for a two-point galaxy correlation function (2PCF) measured with the Landy-Szalay estimator. The standard way of evaluating the covariance matrix consists in running the estimator on a large number of mock catalogs, and evaluating their sample covariance. With large random catalog sizes (random-to-data objects' ratio M >> 1) the computational cost of the standard method is dominated by that of counting the data-random and random-random pairs, while the uncertainty of the estimate is dominated by that of data-data pairs. We present a method called Linear Construction (LC), where the covariance is estimated for small random catalogs with a size of M = 1 and M = 2, and the covariance for arbitrary M is constructed as a linear combination of the two. We show that the LC covariance estimate is unbiased. We validated the method with PINOCCHIO simulations in the range r = 20-200 h(-1) Mpc. With M = 50 and with 2h(-1) Mpc bins, the theoretical speedup of the method is a factor of 14. We discuss the impact on the precision matrix and parameter estimation, and present a formula for the covariance of covariance.Peer reviewe

Endoplasmic reticulum stress inhibition protects against excitotoxic neuronal injury in the rat brain.

Elevated brain glutamate with activation of neuronal glutamate receptors accompanies neurological disorders, such as epilepsy and brain trauma. However, the mechanisms by which excitotoxicity triggers neuronal injury are not fully understood. We have studied the glutamate receptor agonist kainic acid (KA) inducing seizures and excitotoxic cell death. KA caused the disintegration of the endoplasmic reticulum (ER) membrane in hippocampal neurons and ER stress with the activation of the ER proteins Bip, Chop, and caspase-12. Salubrinal, inhibiting eIF2alpha (eukaryotic translation initiation factor 2 subunit alpha) dephosphorylation, significantly reduced KA-induced ER stress and neuronal death in vivo and in vitro. KA-induced rise in intracellular calcium was not affected by Salubrinal. The results show that ER responses are essential parts of excitotoxicity mediated by glutamate receptor activation and that Salubrinal decreases neuronal death in vivo. Inhibition of ER stress by small molecular compounds may be beneficial for treatment of various neuronal injuries and brain disorders

Euclid preparation : XVI. Exploring the ultra-low surface brightness Universe with Euclid/VIS

Context. While Euclid is an ESA mission specifically designed to investigate the nature of dark energy and dark matter, the planned unprecedented combination of survey area (similar to 15000 deg(2)), spatial resolution, low sky-background, and depth also make Euclid an excellent space observatory for the study of the low surface brightness Universe. Scientific exploitation of the extended low surface brightness structures requires dedicated calibration procedures that are yet to be tested. Aims. We investigate the capabilities of Euclid to detect extended low surface brightness structure by identifying and quantifying sky-background sources and stray-light contamination. We test the feasibility of generating sky flat-fields to reduce large-scale residual gradients in order to reveal the extended emission of galaxies observed in the Euclid survey. Methods. We simulated a realistic set of Euclid/VIS observations, taking into account both instrumental and astronomical sources of contamination, including cosmic rays, stray-light, zodiacal light, interstellar medium, and the cosmic infrared background, while simulating the effects of background sources in the field of view. Results. We demonstrate that a combination of calibration lamps, sky flats, and self-calibration would enable recovery of emission at a limiting surface brightness magnitude of mu(lim) = 29.5(-0.27)(+0.08) mag arcsec(-2) (3 sigma, 10 x 10 arcsec(2)) in theWide Survey, and it would reach regions deeper by 2 mag in the Deep Surveys. Conclusions. Euclid/VIS has the potential to be an excellent low surface brightness observatory. Covering the gap between pixel-to-pixel calibration lamp flats and self-calibration observations for large scales, the application of sky flat-fielding will enhance the sensitivity of the VIS detector at scales larger than 1 '', up to the size of the field of view, enabling Euclid to detect extended surface brightness structures below mu(lim) = 31 mag arcsec(-2) and beyond.Peer reviewe

A Guide to Localized Frames and Applications to Galerkin-like Representations of Operators

This chapter offers a detailed survey on intrinsically localized frames and the corresponding matrix representation of operators. We re-investigate the properties of localized frames and the associated Banach spaces in full detail. We investigate the representation of operators using localized frames in a Galerkin-type scheme. We show how the boundedness and the invertibility of matrices and operators are linked and give some sufficient and necessary conditions for the boundedness of operators between the associated Banach spaces.Comment: 32 page

Quality or equality? The Norwegian experience with medical monopolies

BACKGROUND: In order to maintain both quality and efficiency of health services in a small country with a scattered population, Norway established a monopoly system for 38 highly specialized medical services. The geographical distributions of these services, which are provided by one or two university hospitals only, were analysed. METHODS: The counties of residence for 2 711 patients admitted for the first time in 2001 to these 31 monopolies and 7 duopolies were identified. RESULTS: The general tendency observed was that with increasing distance from residential home to monopoly hospitals there was a declining coverage of these health services. The same pattern was found even with regard to explicit diagnoses or treatments such as organ transplantations (except renal transplantations). Duopolies seemed to yield a more even geographical distribution of the services. CONCLUSION: Monopolies may serve as a useful means for maintaining quality in highly specialized medical services, but seem to have an inherent tendency to do this at the expense of geographical equality

CDNF Protein Therapy in Parkinson’s Disease

Neurotrophic factors (NTF) are a subgroup of growth factors that promote survival and differentiation of neurons. Due to their neuroprotective and neurorestorative properties, their therapeutic potential has been tested in various neurodegenerative diseases. Bioavailability of NTFs in the target tissue remains a major challenge for NTF-based therapies. Various intracerebral delivery approaches, both protein and gene transfer-based, have been tested with varying outcomes. Three growth factors, glial cell-line derived neurotrophic factor (GDNF), neurturin (NRTN) and platelet-derived growth factor (PDGF-BB) have been tested in clinical trials in Parkinson?s Disease (PD) during the past 20 years. A new protein can now be added to this list, as cerebral dopamine neurotrophic factor (CDNF) has recently entered clinical trials. Despite their misleading names, CDNF, together with its closest relative mesencephalic astrocyte-derived neurotrophic factor (MANF), form a novel family of unconventional NTF that are both structurally and mechanistically distinct from other growth factors. CDNF and MANF are localized mainly to the lumen of endoplasmic reticulum (ER) and their primary function appears to be modulation of the unfolded protein response (UPR) pathway. Prolonged ER stress, via the UPR signaling pathways, contributes to the pathogenesis in a number of chronic degenerative diseases, and is an important target for therapeutic modulation. Intraputamenally administered recombinant human CDNF has shown robust neurorestorative effects in a number of small and large animal models of PD, and had a good safety profile in preclinical toxicology studies. Intermittent monthly bilateral intraputamenal infusions of CDNF are currently being tested in a randomized placebo-controlled phase I?II clinical study in moderately advanced PD patients. Here, we review the history of growth factor-based clinical trials in PD, and discuss how CDNF differs from the previously tested growth factors.Peer reviewe

Exploring cosmic origins with CORE : Mitigation of systematic effects

We present an analysis of the main systematic effects that could impact the measurement of CMB polarization with the proposed CORE space mission. We employ timeline to-map simulations to verify that the CORE instrumental set-up and scanning strategy allow us to measure sky polarization to a level of accuracy adequate to the mission science goals. We also show how the CORE observations can be processed to mitigate the level of contamination by potentially worrying systematics, including intensity-to-polarization leakage due to bandpass mismatch, asymmetric main beams, pointing errors and correlated noise. We use analysis techniques that are well validated on data from current missions such as Planck to demonstrate how the residual contamination of the measurements by these effects can be brought to a level low enough not to hamper the scientific capability of the mission, nor significantly increase the overall error budget. We also present a prototype of the CORE photometric calibration pipeline, based on that used for Planck, and discuss its robustness to systematics, showing how CORE can achieve its calibration requirements. While a fine-grained assessment of the impact of systematics requires a level of knowledge of the system that can only be achieved in a future study phase, the analysis presented here strongly suggests that the main areas of concern for the CORE mission can be addressed using existing knowledge, techniques and algorithms.Peer reviewe