Efficient runtime systems for speculative parallelization

Manuelle Parallelisierung ist zeitaufwändig und fehleranfällig. Automatische Parallelisierung andererseits findet häufig nur einen Bruchteil der verfügbaren Parallelität. Mithilfe von Spekulation kann jedoch auch für komplexere Programme ein Großteil der Parallelität ausgenutzt werden. Spekulativ parallelisierte Programme benötigen zur Ausführung immer ein Laufzeitsystem, um die spekulativen Annahmen abzusichern und für den Fall des Nichtzutreffens die korrekte Ausführungssemantik sicherzustellen. Solche Laufzeitsysteme sollen die Ausführungszeit des parallelen Programms so wenig wie möglich beeinflussen. In dieser Arbeit untersuchen wir, inwiefern aktuelle Systeme, die Speicherzugriffe explizit und in Software beobachten, diese Anforderung erfüllen, und stellen Änderungen vor, die die Laufzeit massiv verbessern. Außerdem entwerfen wir zwei neue Systeme, die mithilfe von virtueller Speicherverwaltung das Programm indirekt beobachten und dadurch eine deutlich geringere Auswirkung auf die Laufzeit haben. Eines der vorgestellten Systeme ist mittels eines Moduls direkt in den Linux-Betriebssystemkern integriert und bietet so die bestmögliche Effizienz. Darüber hinaus bietet es weitreichendere Sicherheitsgarantien als alle bisherigen Techniken, indem sogar Systemaufrufe zum Beispiel zur Datei Ein- und Ausgabe in der spekulativen Isolation mit eingeschlossen sind. Wir zeigen an einer Reihe von Benchmarks die Überlegenheit unserer Spekulationssyteme über den derzeitigen Stand der Technik. Sämtliche unserer Erweiterungen und Neuentwicklungen stehen als open source zur freien Verfügung. Diese Arbeit ist in englischer Sprache verfasst.Manual parallelization is time consuming and error-prone. Automatic parallelization on the other hand is often unable to extract substantial parallelism. Using speculation, however, most of the parallelism can be exploited even of complex programs. Speculatively parallelized programs always need a runtime system during execution in order to ensure the validity of the speculative assumptions, and to ensure the correct semantics even in the case of misspeculation. These runtime systems should influence the execution time of the parallel program as little as possible. In this thesis, we investigate to which extend state-of-the-art systems which track memory accesses explicitly in software fulfill this requirement. We describe and implement changes which improve their performance substantially. We also design two new systems utilizing virtual memory abstraction to track memory changed implicitly, thus causing less overhead during execution. One of the new systems is integrated into the Linux kernel as a kernel module, providing the best possible performance. Furthermore it provides stronger soundness guarantees than any state-of-the-art system by also capturing system calls, hence including for example file I/O into speculative isolation. In a number of benchmarks we show the performance improvements of our virtual memory based systems over the state of the art. All our extensions and newly developed speculation systems are made available as open source

Sambamba: A runtime system for online adaptive parallelization

Abstract. How can we exploit a microprocessor as efficiently as possible? The "classic" approach is static optimization at compile-time, optimizing a program for all possible uses. Further optimization can only be achieved by anticipating the actual usage profile: If we know, for instance, that two computations will be independent, we can run them in parallel. In the Sambamba project, we replace anticipation by adaptation. Our runtime system provides the infrastructure for implementing runtime adaptive and speculative transformations. We demonstrate our framework in the context of adaptive parallelization. We show the fully automatic parallelization of a small irregular C program in combination with our adaptive runtime system. The result is a parallel execution which adapts to the availability of idle system resources. In our example, this enables a 1.92 fold speedup on two cores while still preventing oversubscription of the system

Natural selection supports escape from concerted evolution of a recently duplicated CEACAM1 paralog in the ruminant CEA gene family

Concerted evolution is often observed in multigene families such as the CEA gene family. As a result, sequence similarity of paralogous genes is significantly higher than expected from their evolutionary distance. Gene conversion, a "copy paste" DNA repair mechanism that transfers sequences from one gene to another and homologous recombination are drivers of concerted evolution. Nevertheless, some gene family members escape concerted evolution and acquire sufficient sequence differences that orthologous genes can be assigned in descendant species. Reasons why some gene family members can escape while others are captured by concerted evolution are poorly understood. By analyzing the entire CEA gene family in cattle (Bos taurus) we identified a member (CEACAM32) that was created by gene duplication and cooption of a unique transmembrane domain exon in the most recent ancestor of ruminants. CEACAM32 shows a unique, testis-specific expression pattern. Phylogenetic analysis indicated that CEACAM32 is not involved in concerted evolution of CEACAM1 paralogs in ruminants. However, analysis of gene conversion events revealed that CEACAM32 is subject to gene conversion but remarkably, these events are found in the leader exon and intron sequences but not in exons coding for the Ig-like domains. These findings suggest that natural selection hinders gene conversion affecting protein sequences of the mature protein and thereby support escape of CEACAM32 from concerted evolution

High Irritation and Removal Rates After Plate or Nail Fixation in Patients With Displaced Midshaft Clavicle Fractures

Background: Studies comparing plate with intramedullary nail fixation of displaced midshaft clavicle fractures show faster recovery in the plate group and implant-related complications in both groups after short-term followup (6 or 12 months). Knowledge of disability, complications, and removal rates beyond the first postoperative year will help surgeons in making a decision regarding optimal implant choice. However, comparative studies with followup beyond the first year or two are scarce. Questions/purposes: We asked: (1) Does plate fixation or intramedullary nail fixation for displaced midshaft clavicle fractures result in less disability? (2) Which type of fixation, plate or intramedullary, is more frequently associated with implant-related irritation and implant removal? (3) Is plate or intramedullary fixation associated with postoperative complications beyond the first postoperative year? Methods: Between January 2011 and August 2012, patients with displaced midshaft clavicle fractures were enrolled and randomized to plate or intramedullary nail fixation. A total of 58 patients with plate and 62 patients with intramedullary nails initially were enrolled. Minimum followup was 30 months (mean, 39 months; range, 30–51 months). Two patients (3%) with plate fixation and two patients (3%) with intramedullary nails were lost to followup. The Qui

Operative treatment of dislocated midshaft clavicular fractures: Plate or intramedullary nail fixation?: A randomized controlled trial

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A randomized controlled trial of nonoperative treatment versus open reduction and internal fixation for stable, displaced, partial articular fractures of the radial head: The RAMBO trial

Background: The choice between operative or nonoperative treatment is questioned for partial articular fractures of the radial head that have at least 2 millimeters of articular step-off on at least one radiograph (defined as displaced), but less than 2 millimeter of gap between the fragments (defined as stable) and that are not associated with an elbow dislocation, interosseous ligament injury, or other fractures. These kinds of fractures are often classified as Mason type-2 fractures. Retrospective comparative studies suggest that operative treatment might be better than nonoperative treatment, but the long-term results of nonoperative treatment are very good. Most experts agree that problems like reduced range of motion, painful crepitation, nonunion or bony ankylosis are infrequent with both nonoperative and operative treatment of an isolated displaced partial articular fracture of the radial head, but determining which patients will have problems is difficult. A prospective, randomized comparison would help minimize bias and determine the balance between operative and nonoperative risks and benefits. Methods/Design. The RAMBO trial (Radial Head - Amsterdam - Amphia - Boston - Others) is an international prospective, randomized, multicenter trial. The primary objective of this study is to compare patient related outcome defined by the \u27Disabilities of Arm, Shoulder and Hand (DASH) score\u27 twelve months after injury between operative and nonoperative treated patients. Adult patients with partial articular fractures of the radial head that comprise at least 1/3rd of the articular surface, have ≥ 2 millimeters of articular step-off but less than 2 millimeter of gap between the fragments will be enrolled. Secondary outcome measures will be the Mayo Elbow Performance Index (MEPI), the Oxford Elbow Score (OES), pain intensity through the \u27Numeric Rating Scale\u27, range of motion (flexion arc and rotational arc), radiographic appearance of the fracture (heterotopic ossification, radiocapitellar and ulnohumeral arthrosis, fracture healing, and signs of implant loosening or breakage) and adverse events (infection, nerve injury, secondary interventions) after one year. Discussion. The successful completion of this trial will provide evidence on the best treatment for stable, displaced, partial articular fractures of the radial head. Trial registration. The trial is registered at the Dutch Trial Register: NTR3413. © 2014Bruinsma et al.; licensee BioMed Central Ltd

The calcium-binding protein S100P in normal and malignant human tissues

<p>Abstract</p> <p>Background</p> <p>S100P is a Ca²⁺binding protein overexpressed in a variety of cancers, and thus, has been considered a potential tumor biomarker. Very little has been studied about its normal expression and functions.</p> <p>Methods</p> <p>We examined S100P expression in normal human tissues by quantitative reverse transcription polymerase chain reaction and immunohistochemistry. S100P protein expression was also studied in a series of tumors, consisting of 74 ovarian, 11 pancreatic, 56 gastric, 57 colorectal, 89 breast and 193 prostate carcinomas using a novel anti-S100P monoclonal antibody.</p> <p>Results</p> <p>Among the normal tissues, the highest S100P mRNA levels were observed in the placenta and esophagus. Moderate signals were also detected in the stomach, duodenum, large intestine, prostate and leukocytes. At the protein level, the highest reactions for S100P were seen in the placenta and stomach. Immunostaining of tumor specimens showed that S100P protein is expressed in all the tumor categories included in the study, being most prevalent in gastric tumors.</p> <p>Conclusion</p> <p>Based on our observations, S100P is widely expressed in both normal and malignant tissues. The high expression in some tumors suggests that it may represent a potential target molecule for future diagnostic and therapeutic applications.</p

A randomized controlled trial of nonoperative treatment versus open reduction and internal fixation for stable, displaced, partial articular fractures of the radial head: The RAMBO trial

Background: The choice between operative or nonoperative treatment is questioned for partial articular fractures of the radial head that have at least 2 millimeters of articular step-off on at least one radiograph (defined as displaced), but less than 2 millimeter of gap between the fragments (defined as stable) and that are not associated with an elbow dislocation, interosseous ligament injury, or other fractures. These kinds of fractures are often classified as Mason type-2 fractures. Retrospective comparative studies suggest that operative treatment might be better than nonoperative treatment, but the long-term results of nonoperative treatment are very good. Most experts agree that problems like reduced range of motion, painful crepitation, nonunion or bony ankylosis are infrequent with both nonoperative and operative treatment of an isolated displaced partial articular fracture of the radial head, but determining which patients will have problems is difficult. A prospective, randomized comparison would help minimize bias and determine the balance between operative and nonoperative risks and benefits. Methods/Design. The RAMBO trial (Radial Head - Amsterdam - Amphia - Boston - Others) is an international prospective, randomized, multicenter trial. The primary objective of this study is to compare patient related outcome defined by the 'Disabilities of Arm, Shoulder and Hand (DASH) score' twelve months after injury between operative and nonoperative treated patients. Adult patients with partial articular fractures of the radial head that comprise at least 1/3rd of the articular surface, have ≥ 2 millimeters of articular step-off but less than 2 millimeter of gap between the fragments will be enrolled. Secondary outcome measures will be the Mayo Elbow Performance Index (MEPI), the Oxford Elbow Score (OES), pain intensity through the 'Numeric Rating Scale', range of motion (flexion arc and rotational arc), radiographic appearance of the fracture (heterotopic ossification, radiocapitellar and ulnohumeral arthrosis, fracture healing, and signs of implant loosening or breakage) and adverse events (infection, nerve injury, secondary interventions) after one year. Discussion. The successful completion of this trial will provide evidence on the best treatment for stable, displaced, partial articular fractures of the radial head. Trial registration. The trial is registered at the Dutch Trial Register: NTR3413