A methodology pruning the search space of six compiler transformations by addressing them together as one problem and by exploiting the hardware architecture details

Today’s compilers have a plethora of optimizations-transformations to choose from, and the correct choice, order as well parameters of transformations have a significant/large impact on performance; choosing the correct order and parameters of optimizations has been a long standing problem in compilation research, which until now remains unsolved; the separate sub-problems optimization gives a different schedule/binary for each sub-problem and these schedules cannot coexist, as by refining one degrades the other. Researchers try to solve this problem by using iterative compilation techniques but the search space is so big that it cannot be searched even by using modern supercomputers. Moreover, compiler transformations do not take into account the hardware architecture details and data reuse in an efficient way. In this paper, a new iterative compilation methodology is presented which reduces the search space of six compiler transformations by addressing the above problems; the search space is reduced by many orders of magnitude and thus an efficient solution is now capable to be found. The transformations are the following: loop tiling (including the number of the levels of tiling), loop unroll, register allocation, scalar replacement, loop interchange and data array layouts. The search space is reduced (a) by addressing the aforementioned transformations together as one problem and not separately, (b) by taking into account the custom hardware architecture details (e.g., cache size and associativity) and algorithm characteristics (e.g., data reuse). The proposed methodology has been evaluated over iterative compilation and gcc/icc compilers, on both embedded and general purpose processors; it achieves significant performance gains at many orders of magnitude lower compilation time

A high-performance matrix-matrix multiplication methodology for CPU and GPU architectures

Current compilers cannot generate code that can compete with hand-tuned code in efficiency, even for a simple kernel like matrix–matrix multiplication (MMM). A key step in program optimization is the estimation of optimal values for parameters such as tile sizes and number of levels of tiling. The scheduling parameter values selection is a very difficult and time-consuming task, since parameter values depend on each other; this is why they are found by using searching methods and empirical techniques. To overcome this problem, the scheduling sub-problems must be optimized together, as one problem and not separately. In this paper, an MMM methodology is presented where the optimum scheduling parameters are found by decreasing the search space theoretically, while the major scheduling sub-problems are addressed together as one problem and not separately according to the hardware architecture parameters and input size; for different hardware architecture parameters and/or input sizes, a different implementation is produced. This is achieved by fully exploiting the software characteristics (e.g., data reuse) and hardware architecture parameters (e.g., data caches sizes and associativities), giving high-quality solutions and a smaller search space. This methodology refers to a wide range of CPU and GPU architectures

Multiple populations in globular clusters. Lessons learned from the Milky Way globular clusters

Recent progress in studies of globular clusters has shown that they are not simple stellar populations, being rather made of multiple generations. Evidence stems both from photometry and spectroscopy. A new paradigm is then arising for the formation of massive star clusters, which includes several episodes of star formation. While this provides an explanation for several features of globular clusters, including the second parameter problem, it also opens new perspectives about the relation between globular clusters and the halo of our Galaxy, and by extension of all populations with a high specific frequency of globular clusters, such as, e.g., giant elliptical galaxies. We review progress in this area, focusing on the most recent studies. Several points remain to be properly understood, in particular those concerning the nature of the polluters producing the abundance pattern in the clusters and the typical timescale, the range of cluster masses where this phenomenon is active, and the relation between globular clusters and other satellites of our Galaxy.Comment: In press (The Astronomy and Astrophysics Review

High resolution 3-Dimensional imaging of the human cardiac conduction system from microanatomy to mathematical modeling

Cardiac arrhythmias and conduction disturbances are accompanied by structural remodelling of the specialised cardiomyocytes known collectively as the cardiac conduction system. Here, using contrast enhanced micro-computed tomography, we present, in attitudinally appropriate fashion, the first 3-dimensional representations of the cardiac conduction system within the intact human heart. We show that cardiomyocyte orientation can be extracted from these datasets at spatial resolutions approaching the single cell. These data show that commonly accepted anatomical representations are oversimplified. We have incorporated the high-resolution anatomical data into mathematical simulations of cardiac electrical depolarisation. The data presented should have multidisciplinary impact. Since the rate of depolarisation is dictated by cardiac microstructure, and the precise orientation of the cardiomyocytes, our data should improve the fidelity of mathematical models. By showing the precise 3-dimensional relationships between the cardiac conduction system and surrounding structures, we provide new insights relevant to valvar replacement surgery and ablation therapies. We also offer a practical method for investigation of remodelling in disease, and thus, virtual pathology and archiving. Such data presented as 3D images or 3D printed models, will inform discussions between medical teams and their patients, and aid the education of medical and surgical trainees

Antipsychotics and Torsadogenic Risk: Signals Emerging from the US FDA Adverse Event Reporting System Database

Background: Drug-induced torsades de pointes (TdP) and related clinical entities represent a current regulatory and clinical burden. Objective: As part of the FP7 ARITMO (Arrhythmogenic Potential of Drugs) project, we explored the publicly available US FDA Adverse Event Reporting System (FAERS) database to detect signals of torsadogenicity for antipsychotics (APs). Methods: Four groups of events in decreasing order of drug-attributable risk were identified: (1) TdP, (2) QT-interval abnormalities, (3) ventricular fibrillation/tachycardia, and (4) sudden cardiac death. The reporting odds ratio (ROR) with 95 % confidence interval (CI) was calculated through a cumulative analysis from group 1 to 4. For groups 1+2, ROR was adjusted for age, gender, and concomitant drugs (e.g., antiarrhythmics) and stratified for AZCERT drugs, lists I and II (http://www.azcert.org, as of June 2011). A potential signal of torsadogenicity was defined if a drug met all the following criteria: (a) four or more cases in group 1+2; (b) significant ROR in group 1+2 that persists through the cumulative approach; (c) significant adjusted ROR for group 1+2 in the stratum without AZCERT drugs; (d) not included in AZCERT lists (as of June 2011). Results: Over the 7-year period, 37 APs were reported in 4,794 cases of arrhythmia: 140 (group 1), 883 (group 2), 1,651 (group 3), and 2,120 (group 4). Based on our criteria, the following potential signals of torsadogenicity were found: amisulpride (25 cases; adjusted ROR in the stratum without AZCERT drugs = 43.94, 95 % CI 22.82-84.60), cyamemazine (11; 15.48, 6.87-34.91), and olanzapine (189; 7.74, 6.45-9.30). Conclusions: This pharmacovigilance analysis on the FAERS found 3 potential signals of torsadogenicity for drugs previously unknown for this risk

Regulatory Constructivism: Application of Q Methodology in Italy and China

Conventional view holds that beliefs play an important role in the development of regulations but there is little evidence to support this claim. We use Comparative Q Methodology to systematically map out and compare the beliefs of public officers in China and Italy, two countries with contrasting sets of institutions but have both adopted similar ideas about integrated water resource management. We find some similarities and differences in the beliefs of public officers in both countries. In particular, we find that in both countries beliefs on the regulation of water utilities are diverse and fragmented on issues such as ownership structure of water utilities, how water infrastructure development should be funded, and how tariffs should be regulated. Our findings have two implications for theory, methods and practice. First, the Q methodology is a useful tool for systematically mapping out the beliefs of regulators and managers. Second, systematically mapping out beliefs will help facilitate the development of an alternative regime of regulation such as negotiated rule making. This alternative regime can provide substantial benefits such as more efficient rule making, more cost effective enforcement and compliance, and more equitable in terms of balancing the interests of stakeholders

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Emerging New Crop Pests: Ecological Modelling and Analysis of the South American Potato Psyllid Russelliana solanicola (Hemiptera: Psylloidea) and Its Wild Relatives

© 2017 Syfert et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Substrate specificities of inteins investigated by QuickDrop-cassette mutagenesis

Inteins catalyze self-excision from host precursor proteins while concomitantly ligating the flanking substrates (exteins) with a peptide bond. Noncatalytic extein residues near the splice junctions, such as the residues at the -1 and +2 positions, often strongly influence the protein-splicing efficiency. The substrate specificities of inteins have not been studied for many inteins. We developed a convenient mutagenesis platform termed "QuickDrop"-cassette mutagenesis for investigating the influences of 20 amino acid types at the -1 and +2 positions of different inteins. We elucidated 17 different profiles of the 20 amino acid dependencies across different inteins. The substrate specificities will accelerate our understanding of the structure-function relationship at the splicing junctions for broader applications of inteins in biotechnology and molecular biosciences.Peer reviewe