Optimal Global Instruction Scheduling for the Itanium® Processor Architecture

On the Itanium 2 processor, effective global instruction scheduling is crucial to high performance. At the same time, it poses a challenge to the compiler: This code generation subtask involves strongly interdependent decisions and complex trade-offs that are difficult to cope with for heuristics. We tackle this NP-complete problem with integer linear programming (ILP), a search-based method that yields provably optimal results. This promises faster code as well as insights into the potential of the architecture. Our ILP model comprises global code motion with compensation copies, predication, and Itanium-specific features like control/data speculation. In integer linear programming, well-structured models are the key to acceptable solution times. The feasible solutions of an ILP are represented by integer points inside a polytope. If all vertices of this polytope are integral, then the ILP can be solved in polynomial time. We define two subproblems of global scheduling in which some constraint classes are omitted and show that the corresponding two subpolytopes of our ILP model are integral and polynomial sized. This substantiates that the found model is of high efficiency, which is also confirmed by the reasonable solution times. The ILP formulation is extended by further transformations like cyclic code motion, which moves instructions upwards out of a loop, circularly in the opposite direction of the loop backedges. Since the architecture requires instructions to be encoded in fixed-sized bundles of three, a bundler is developed that computes bundle sequences of minimal size by means of precomputed results and dynamic programming. Experiments have been conducted with a postpass tool that implements the ILP scheduler. It parses assembly procedures generated by Intel�s Itanium compiler and reschedules them as a whole. Using this tool, we optimize a selection of hot functions from the SPECint 2000 benchmark. The results show a significant speedup over the original code.Globale Instruktionsanordnung hat beim Itanium-2-Prozessor großen Einfluß auf die Leistung und stellt dabei gleichzeitig eine Herausforderung für den Compiler dar: Sie ist mit zahlreichen komplexen, wechselseitig voneinander abhängigen Entscheidungen verbunden, die für Heuristiken nur schwer zu beherrschen sind.Wir lösen diesesNP-vollständige Problem mit ganzzahliger linearer Programmierung (ILP), einer suchbasierten Methode mit beweisbar optimalen Ergebnissen. Das ermöglicht neben schnellerem Code auch Einblicke in das Potential der Itanium- Prozessorarchitektur. Unser ILP-Modell umfaßt globale Codeverschiebungen mit Kompensationscode, Prädikation und Itanium-spezifische Techniken wie Kontroll- und Datenspekulation. Bei ganzzahliger linearer Programmierung sind wohlstrukturierte Modelle der Schlüssel zu akzeptablen Lösungszeiten. Die zulässigen Lösungen eines ILPs werden durch ganzzahlige Punkte innerhalb eines Polytops repräsentiert. Sind die Eckpunkte dieses Polytops ganzzahlig, kann das ILP in Polynomialzeit gelöst werden. Wir definieren zwei Teilprobleme globaler Instruktionsanordnung durch Auslassung bestimmter Klassen von Nebenbedingungen und beweisen, daß die korrespondierenden Teilpolytope unseres ILP-Modells ganzzahlig und von polynomieller Größe sind. Dies untermauert die hohe Effizienz des gefundenen Modells, die auch durch moderate Lösungszeiten bestätigt wird. Das ILP-Modell wird um weitere Transformationen wie zyklische Codeverschiebung erweitert; letztere bezeichnet das Verschieben von Befehlen aufwärts aus einer Schleife heraus, in Gegenrichtung ihrer Rückwärtskanten. Da die Architektur eine Kodierung der Befehle in Dreierbündeln fester Größe vorschreibt, wird ein Bundler entwickelt, der Bündelsequenzen minimaler Länge mit Hilfe vorberechneter Teilergebnisse und dynamischer Programmierung erzeugt. Für die Experimente wurde ein Postpassoptimierer erstellt. Er liest von Intels Itanium-Compiler erzeugte Assemblerroutinen ein und ordnet die enthaltenen Instruktionen mit Hilfe der ILP-Methode neu an. Angewandt auf eine Auswahl von Funktionen aus dem Benchmark SPECint 2000 erreicht der Optimierer eine signifikante Beschleunigung gegenüber dem Originalcode

Optimal Global Instruction Scheduling for the Itanium® Processor Architecture

On the Itanium 2 processor, effective global instruction scheduling is crucial to high performance. At the same time, it poses a challenge to the compiler: This code generation subtask involves strongly interdependent decisions and complex trade-offs that are difficult to cope with for heuristics. We tackle this NP-complete problem with integer linear programming (ILP), a search-based method that yields provably optimal results. This promises faster code as well as insights into the potential of the architecture. Our ILP model comprises global code motion with compensation copies, predication, and Itanium-specific features like control/data speculation. In integer linear programming, well-structured models are the key to acceptable solution times. The feasible solutions of an ILP are represented by integer points inside a polytope. If all vertices of this polytope are integral, then the ILP can be solved in polynomial time. We define two subproblems of global scheduling in which some constraint classes are omitted and show that the corresponding two subpolytopes of our ILP model are integral and polynomial sized. This substantiates that the found model is of high efficiency, which is also confirmed by the reasonable solution times. The ILP formulation is extended by further transformations like cyclic code motion, which moves instructions upwards out of a loop, circularly in the opposite direction of the loop backedges. Since the architecture requires instructions to be encoded in fixed-sized bundles of three, a bundler is developed that computes bundle sequences of minimal size by means of precomputed results and dynamic programming. Experiments have been conducted with a postpass tool that implements the ILP scheduler. It parses assembly procedures generated by Intel�s Itanium compiler and reschedules them as a whole. Using this tool, we optimize a selection of hot functions from the SPECint 2000 benchmark. The results show a significant speedup over the original code.Globale Instruktionsanordnung hat beim Itanium-2-Prozessor großen Einfluß auf die Leistung und stellt dabei gleichzeitig eine Herausforderung für den Compiler dar: Sie ist mit zahlreichen komplexen, wechselseitig voneinander abhängigen Entscheidungen verbunden, die für Heuristiken nur schwer zu beherrschen sind.Wir lösen diesesNP-vollständige Problem mit ganzzahliger linearer Programmierung (ILP), einer suchbasierten Methode mit beweisbar optimalen Ergebnissen. Das ermöglicht neben schnellerem Code auch Einblicke in das Potential der Itanium- Prozessorarchitektur. Unser ILP-Modell umfaßt globale Codeverschiebungen mit Kompensationscode, Prädikation und Itanium-spezifische Techniken wie Kontroll- und Datenspekulation. Bei ganzzahliger linearer Programmierung sind wohlstrukturierte Modelle der Schlüssel zu akzeptablen Lösungszeiten. Die zulässigen Lösungen eines ILPs werden durch ganzzahlige Punkte innerhalb eines Polytops repräsentiert. Sind die Eckpunkte dieses Polytops ganzzahlig, kann das ILP in Polynomialzeit gelöst werden. Wir definieren zwei Teilprobleme globaler Instruktionsanordnung durch Auslassung bestimmter Klassen von Nebenbedingungen und beweisen, daß die korrespondierenden Teilpolytope unseres ILP-Modells ganzzahlig und von polynomieller Größe sind. Dies untermauert die hohe Effizienz des gefundenen Modells, die auch durch moderate Lösungszeiten bestätigt wird. Das ILP-Modell wird um weitere Transformationen wie zyklische Codeverschiebung erweitert; letztere bezeichnet das Verschieben von Befehlen aufwärts aus einer Schleife heraus, in Gegenrichtung ihrer Rückwärtskanten. Da die Architektur eine Kodierung der Befehle in Dreierbündeln fester Größe vorschreibt, wird ein Bundler entwickelt, der Bündelsequenzen minimaler Länge mit Hilfe vorberechneter Teilergebnisse und dynamischer Programmierung erzeugt. Für die Experimente wurde ein Postpassoptimierer erstellt. Er liest von Intels Itanium-Compiler erzeugte Assemblerroutinen ein und ordnet die enthaltenen Instruktionen mit Hilfe der ILP-Methode neu an. Angewandt auf eine Auswahl von Funktionen aus dem Benchmark SPECint 2000 erreicht der Optimierer eine signifikante Beschleunigung gegenüber dem Originalcode

Chronic Activation of Hepatic Nrf2 Has No Major Effect on Fatty Acid and Glucose Metabolism in Adult Mice

The transcription factor NF-E2-related factor 2 (Nrf2) induces cytoprotective genes, but has also been linked to the regulation of hepatic energy metabolism. In order to assess the pharmacological potential of hepatic Nrf2 activation in metabolic disease, Nrf2 was activated over 7 weeks in mice on Western diet using two different siRNAs against kelch-like ECH-associated protein 1 (Keap1), the inhibitory protein of Nrf2. Whole genome expression analysis followed by pathway analysis demonstrated successful knock-down of Keap1 expression and induction of Nrf2-dependent genes involved in anti- oxidative stress defense and biotransformation, proving the activation of Nrf2 by the siRNAs against Keap1. Neither the expression of fatty acid- nor carbohydrate-handling proteins was regulated by Keap1 knock-down. Metabolic profiling of the animals did also not show effects on plasma and hepatic lipids, energy expenditure or glucose tolerance. The data indicate that hepatic Keap1/Nrf2 is not a major regulator of glucose or lipid metabolism in mice

The nitrogen stock of the ice-rich yedoma domain

Recent studies on permafrost organic matter (OM) suggest that a portion of previously frozen carbon will enter the active carbon cycle as high latitudes warm. Less is known about the fate of other OM components, including nutrients such as nitrogen (N). The abundance and availability of N following permafrost thaw will regulate the ability of plants to offset carbon losses. Additionally, lateral N losses could alter aquatic food webs. There is growing evidence that some N is lost vertically as N2O, a greenhouse gas 300 times stronger than CO2 over 100 years. Despite broad recognition of its role regulating both carbon and non-carbon aspects of the permafrost climate feedback, estimates of permafrost N remain uncertain. To address this knowledge gap, we quantified N content for different stratigraphic units, including yedoma, Holocene cover deposits, refrozen thermokarst deposits, taberal sediments, and active layer soils. The resulting N estimates from this one permafrost region were similar in magnitude to previous estimates for the entire permafrost zone. We conclude that the permafrost N pool is much larger than currently appreciated and a substantial pool of permafrost N could be mobilized after thaw, with continental-scale consequences for biogeochemical budgets and global-scale consequences

The Nitrogen Inventory of the Yedoma Permafrost Domain

Fossil organic matter (OM) stored in permafrost is an important subject in climate research. Such OM represents a huge reservoir of carbon (C). Multiple studies suggest its source potential for C release into the active C cycle through permafrost thaw and subsequent microbial turnover in a warming Arctic. However, net ecosystem OM balance in the permafrost region depends on more than just carbon. The abundance and availability of nitrogen (N) following permafrost thaw will influence plant growth, nutrient delivery to aquatic and estuarine ecosystems, and N oxide (N2O) emissions. Despite its central importance to predicting permafrost impacts and feedbacks to climate change, relatively little is known about permafrost N stocks and composition. In this study, we present the most extensive dataset to date of permafrost N in the Siberian and Alaskan Yedoma domain. The Yedoma domain comprises decameter thick ice-rich silts intersected by syngenetic ice wedges, which formed in late Pleistocene tundra-steppe environments, as well as other deposits resulting from permafrost degradation during the Holocene. Together, the deposits in this region constitute a large C inventory storing several hundred Gt C, but are also known to be nutrient-rich due to rapid burial and freezing of plant remains. Hitherto, the total organic C pool of the Yedoma region was quantified, while the total N inventory is lacking so far. Based on the most comprehensive data set of N content in permafrost to date, our study aims to estimate the present pool of N stored in the different stratigraphic units of the Yedoma domain: 1) late Pleistocene Yedoma deposits, 2) in-situ thawed and diagenetically altered Yedoma deposits (taberite), 3) Holocene thermokarst deposits, 4) Holocene cover deposits on top of Yedoma, and 5) the modern active layer of soils. To quantify measurement uncertainty, we estimated nitrogen stocks with bootstrapping techniques. We show that the deposits of the Yedoma region store a substantial pool of N that is expected to get mobilized after thaw and, at least partially, affecting biogeochemical budgets of thawing warming permafrost ecosystems

A globally relevant stock of soil nitrogen in the Yedoma permafrost domain

Nitrogen regulates multiple aspects of the permafrost climate feedback, including plant growth, organic matter decomposition, and the production of the potent greenhouse gas nitrous oxide. Despite its importance, current estimates of permafrost nitrogen are highly uncertain. Here, we compiled a dataset of >2000 samples to quantify nitrogen stocks in the Yedoma domain, a region with organic-rich permafrost that contains ~25% of all permafrost carbon. We estimate that the Yedoma domain contains 41.2 gigatons of nitrogen down to ~20 metre for the deepest unit, which increases the previous estimate for the entire permafrost zone by ~46%. Approximately 90% of this nitrogen (37 gigatons) is stored in permafrost and therefore currently immobile and frozen. Here, we show that of this amount, ¾ is stored >3 metre depth, but if partially mobilised by thaw, this large nitrogen pool could have continental-scale consequences for soil and aquatic biogeochemistry and global-scale consequences for the permafrost feedback

Modulation of the substrate specificity of the kinase PDK1 by distinct conformations of the full-length protein

The activation of at least 23 different mammalian kinases requires the phosphorylation of their hydrophobic motifs by the kinase PDK1. A linker connects the phosphoinositide-binding PH domain to the catalytic domain, which contains a docking site for substrates called the PIF pocket. Here, we used a chemical biology approach to show that PDK1 existed in equilibrium between at least three distinct conformations with differing substrate specificities. The inositol polyphosphate derivative HYG8 bound to the PH domain and disrupted PDK1 dimerization by stabilizing a monomeric conformation in which the PH domain associated with the catalytic domain and the PIF pocket was accessible. In the absence of lipids, HYG8 potently inhibited the phosphorylation of Akt (also termed PKB) but did not affect the intrinsic activity of PDK1 or the phosphorylation of SGK, which requires docking to the PIF pocket. In contrast, the small molecule valsartan bound to the PIF pocket and stabilized a second distinct monomeric conformation. Our study reveals dynamic conformations of full-length PDK1 in which the location of the linker and the PH domain relative to the catalytic domain determines the selective phosphorylation of PDK1 substrates. The study further suggests new approaches for the design of drugs to selectively modulate signaling downstream of PDK1

Kinematic analysis of the super-extended HI disk of the nearby spiral galaxy M 83

Funding: CE, FB, AB, IB, JdB and JP acknowledge funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No.726384/Empire). TGW acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 694343). JMDK gratefully acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme via the ERC Starting Grant MUSTANG (grant agreement number 714907). SCOG acknowledges funding from the European Research Council via the ERC Synergy Grant “ECOGAL – Understanding our Galactic ecosystem: From the disk of the Milky Way to the formation sites of stars and planets” (project ID 855130). WJGdB received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 882793 ‘MeerGas’).We present new HI observations of the nearby massive spiral galaxy M83, taken with the VLA at 21″ angular resolution (≈500 pc) of an extended (1.5 deg2) 10-point mosaic combined with GBT single dish data. We study the super-extended HI disk of M83 (∼50 kpc in radius), in particular disc kinematics, rotation and the turbulent nature of the atomic interstellar medium. We define distinct regions in the outer disk (rgal > central optical disk), including ring, southern area, and southern and northern arm. We examine HI gas surface density, velocity dispersion and non-circular motions in the outskirts, which we compare to the inner optical disk. We find an increase of velocity dispersion (σv) towards the pronounced HI ring, indicative of more turbulent HI gas. Additionally, we report over a large galactocentric radius range (until rgal ∼ 50 kpc) that σv is slightly larger than thermal (i.e. > 8 km s-1). We find that a higher star formation rate (as traced by FUV emission) is not always necessarily associated with a higher HI velocity dispersion, suggesting that radial transport could be a dominant driver for the enhanced velocity dispersion. We further find a possible branch that connects the extended HI disk to the dwarf irregular galaxy UGCA365, that deviates from the general direction of the northern arm. Lastly, we compare mass flow rate profiles (based on 2D and 3D tilted ring models) and find evidence for outflowing gas at rgal ∼ 2 kpc, inflowing gas at rgal ~ 5.5 kpc and outflowing gas at rgal ~ 14 kpc. We caution that mass flow rates are highly sensitive to the assumed kinematic disk parameters, in particular, to the inclination.Publisher PDFPeer reviewe