TWAM: A Certifying Abstract Machine for Logic Programs

Type-preserving (or typed) compilation uses typing derivations to certify correctness properties of compilation. We have designed and implemented a type-preserving compiler for a simply-typed dialect of Prolog we call T-Prolog. The crux of our approach is a new certifying abstract machine which we call the Typed Warren Abstract Machine (TWAM). The TWAM has a dependent type system strong enough to specify the semantics of a logic program in the logical framework LF. We present a soundness metatheorem which constitutes a partial correctness guarantee: well-typed programs implement the logic program specified by their type. This metatheorem justifies our design and implementation of a certifying compiler from T-Prolog to TWAM.Comment: 41 pages, under submission to ACM Transactions on Computational Logi

Population assessment of future trajectories in coronary heart disease mortality.

Background: Coronary heart disease (CHD) mortality rates have been decreasing in Iceland since the 1980s, largely reflecting improvements in cardiovascular risk factors. The purpose of this study was to predict future CHD mortality in Iceland based on potential risk factor trends. Methods and findings: The previously validated IMPACT model was used to predict changes in CHD mortality between 2010 and 2040 among the projected population of Iceland aged 25–74. Calculations were based on combining: i) data on population numbers and projections (Statistics Iceland), ii) population risk factor levels and projections (Refine Reykjavik study), and iii) effectiveness of specific risk factor reductions (published meta-analyses). Projections for three contrasting scenarios were compared: 1) If the historical risk factor trends of past 30 years were to continue, the declining death rates of past decades would level off, reflecting population ageing. 2) If recent trends in risk factors (past 5 years) continue, this would result in a death rate increasing from 49 to 70 per 100,000. This would reflect a recent plateau in previously falling cholesterol levels and recent rapid increases in obesity and diabetes prevalence. 3) Assuming that in 2040 the entire population enjoys optimal risk factor levels observed in low risk cohorts, this would prevent almost all premature CHD deaths before 2040. Conclusions: The potential increase in CHD deaths with recent trends in risk factor levels is alarming both for Iceland and probably for comparable Western populations. However, our results show considerable room for reducing CHD mortality. Achieving the best case scenario could eradicate premature CHD deaths by 2040. Public health policy interventions based on these predictions may provide a cost effective means of reducing CHD mortality in the future

Shifts in biogenic carbon flow from particulate to dissolved forms under high carbon dioxide and warm ocean conditions

Photosynthesis by phytoplankton in sunlit surface waters transforms inorganic carbon and nutrients into organic matter, a portion of which is subsequently transported vertically through the water column by the process known as the biological carbon pump (BCP). The BCP sustains the steep vertical gradient in total dissolved carbon, thereby contributing to net carbon sequestration. Any changes in the vertical transportation of the organic matter as a result of future climate variations will directly affect surface ocean carbon dioxide (CO 2) concentrations, and subsequently influence oceanic uptake of atmospheric CO 2 and climate. Here we present results of experiments designed to investigate the potential effects of ocean acidification and warming on the BCP. These perturbation experiments were carried out in enclosures (3,000 L volume) in a controlled mesocosm facility that mimicked future pCO 2 (∼900 ppmv) and temperature (3°C higher than ambient) conditions. The elevated CO 2 and temperature treatments disproportionately enhanced the ratio of dissolved organic carbon (DOC) production to particulate organic carbon (POC) production, whereas the total organic carbon (TOC) production remained relatively constant under all conditions tested. A greater partitioning of organic carbon into the DOC pool indicated a shift in the organic carbon flow from the particulate to dissolved forms, which may affect the major pathways involved in organic carbon export and sequestration under future ocean conditions

Heute des Morgens um 6 Uhr reiseten Se. Königl. Hoheit, unser gnadister Landesherr, von hier ab, nachdem Sie vorher den hieselbst anwesenden Adel folgendergestalt angeredet : [Rede des Herzogs Karl an den anwesenden Adel bei seiner Abreise von Mitau den 26. April 176- und Beantwortung derselben durch den Landhofmeister von der Howen], Mietau, den 26. April

TÜR-i eksemplari R Est.A-4675(II) (konvoluut) 7. alligaathttp://tartu.ester.ee/record=b1433027~S1*es

Insights into GABA receptor signalling in TM3 Leydig cells

gamma-Aminobutyric acid (GABA) is an emerging signalling molecule in endocrine organs, since it is produced by endocrine cells and acts via GABA(A) receptors in a paracrine/autocrine fashion. Testicular Leydig cells are producers and targets for GABA. These cells express GABA(A) receptor subunits and in the murine Leydig cell line TM3 pharmacological activation leads to increased proliferation. The signalling pathway of GABA in these cells is not known in this study. We therefore attempted to elucidate details of GABA(A) signalling in TM3 and adult mouse Leydig cells using several experimental approaches. TM3 cells not only express GABA(A) receptor subunits, but also bind the GABA agonist {[}H-3] muscimol with a binding affinity in the range reported for other endocrine cells (K-d = 2.740 +/- 0.721 nM). However, they exhibit a low B-max value of 28.08 fmol/mg protein. Typical GABA(A) receptor-associated events, including Cl- currents, changes in resting membrane potential, intracellular Ca2+ or cAMP, were not measurable with the methods employed in TM3 cells, or, as studied in part, in primary mouse Leydig cells. GABA or GABA(A) agonist isoguvacine treatment resulted in increased or decreased levels of several mRNAs, including transcription factors (c-fos, hsf-1, egr-1) and cell cycle-associated genes (Cdk2, cyclin D1). In an attempt to verify the cDNA array results and because egr-1 was recently implied in Leydig cell development, we further studied this factor. RT-PCR and Western blotting confirmed a time-dependent regulation of egr-1 in TM3. In the postnatal testis egr-1 was seen in cytoplasmic and nuclear locations of developing Leydig cells, which bear GABA(A) receptors and correspond well to TM3 cells. Thus, GABA acts via an untypical novel signalling pathway in TM3 cells. Further details of this pathway remain to be elucidated. Copyright (c) 2005 S. Karger AG, Base

Airfoil data sensitivity analysis for actuator disc simulations used in wind turbine applications

To analyse the sensitivity of blade geometry and airfoil characteristics on the prediction of performance characteristics of wind farms, large-eddy simulations using an actuator disc (ACD) method are performed for three different blade/airfoil configurations. The aim of the study is to determine how the mean characteristics of wake flow, mean power production and thrust depend on the choice of airfoil data and blade geometry. In order to simulate realistic conditions, pre-generated turbulence and wind shear are imposed in the computational domain. Using three different turbulence intensities and varying the spacing between the turbines, the flow around 4-8 aligned turbines is simulated. The analysis is based on normalized mean streamwise velocity, turbulence intensity, relative mean power production and thrust. From the computations it can be concluded that the actual airfoil characteristics and blade geometry only are of importance at very low inflow turbulence. At realistic turbulence conditions for an atmospheric boundary layer the specific blade characteristics play an minor role on power performance and the resulting wake characteristics. The results therefore give a hint that the choice of airfoil data in ACD simulations is not crucial if the intention of the simulations is to compute mean wake characteristics using a turbulent inflow

Studies on the clinical significance of nonesterified and total cholesterol in urine

Gas-liquid chromatographic determinations of nonesterified and total urinary cholesterol were performed in 137 normals, 264 patients with various internal diseases without evidence of neoplasias or diseases of the kidney or urinary tract, 497 patients with malignancies and 236 patients with diseases of the kidney, urinary tract infections or prostatic adenoma with residual urine. A normal range (mean±2 SD) of 0.2–2.2 mg/24 hours nonesterified cholesterol (NEC) and of 0.3–3.0 mg/24 hours total cholesterol (TC) was calculated. Values of urinary cholesterol excretion were independent of age and sex and did not correlate with cholesterol levels in plasma. Patients with various internal diseases, without evidence of neoplasias nor diseases of the kidney or obstruction of the urinary tract, showed normal urinary cholesterol excretions, as did patients with infections of the urinary tract. However, elevated urinary cholesterol was found in patients with diseases of the kidney or urinary tract obstruction (prostatic adenoma with residual urine), malignant diseases of the urogenital tract and metastasing carcinoma of the breast. In patients with other malignant diseases urinary cholesterol was usually normal. Lesions of the urothelial cell membranes are considered to be the most likely cause of urinary cholesterol hyperexcretion. The clinical value of urinary cholesterol determinations as a possible screening test for urogenital carcinomas in unselected populations is limited by lacking specificity, expensive methodology and low prevalence of the mentioned carcinomas, although elevated urinary cholesterol excretions have been observed in early clinical stages of urogenital cancers

Coupling of alpha(1)-Adrenoceptors to ERK1/2 in the Human Prostate

Introduction: alpha(1)-Adrenoceptors are considered critical for the regulation of prostatic smooth muscle tone. However, previous studies suggested further alpha(1)-adrenoceptor functions besides contraction. Here, we investigated whether alpha(1)-adrenoceptors in the human prostate may activate extracellular signal-regulated kinases (ERK1/2). Methods: Prostate tissues from patients undergoing radical prostatectomy were stimulated in vitro. Activation of ERK1/2 was assessed by Western blot analysis. Expression of ERK1/2 was studied by immunohistochemistry. The effect of ERK1/2 inhibition by U0126 on phenylephrine-induced contraction was studied in organ-bath experiments. Results: Stimulation of human prostate tissue with noradrenaline (30 mu M) or phenylephrine (10 mu M) resulted in ERK activation. This was reflected by increased levels of phosphorylated ERK1/2. Expression of ERK1/2 in the prostate was observed in smooth muscle cells. Incubation of prostate tissue with U0126 (30 mu M) resulted in ERK1/2 inhibition. Dose-dependent phenylephrine-induced contraction of prostate tissue was not modulated by U0126. Conclusions: alpha(1)-Adrenoceptors in the human prostate are coupled to ERK1/2. This may partially explain previous observations suggesting a role of alpha(1)-adrenoceptors in the regulation of prostate growth. Copyright (C) 2011 S. Karger AG, Base

The role of ongoing dendritic oscillations in single-neuron dynamics

The dendritic tree contributes significantly to the elementary computations a neuron performs while converting its synaptic inputs into action potential output. Traditionally, these computations have been characterized as temporally local, near-instantaneous mappings from the current input of the cell to its current output, brought about by somatic summation of dendritic contributions that are generated in spatially localized functional compartments. However, recent evidence about the presence of oscillations in dendrites suggests a qualitatively different mode of operation: the instantaneous phase of such oscillations can depend on a long history of inputs, and under appropriate conditions, even dendritic oscillators that are remote may interact through synchronization. Here, we develop a mathematical framework to analyze the interactions of local dendritic oscillations, and the way these interactions influence single cell computations. Combining weakly coupled oscillator methods with cable theoretic arguments, we derive phase-locking states for multiple oscillating dendritic compartments. We characterize how the phase-locking properties depend on key parameters of the oscillating dendrite: the electrotonic properties of the (active) dendritic segment, and the intrinsic properties of the dendritic oscillators. As a direct consequence, we show how input to the dendrites can modulate phase-locking behavior and hence global dendritic coherence. In turn, dendritic coherence is able to gate the integration and propagation of synaptic signals to the soma, ultimately leading to an effective control of somatic spike generation. Our results suggest that dendritic oscillations enable the dendritic tree to operate on more global temporal and spatial scales than previously thought