Analysing Astronomy Algorithms for GPUs and Beyond

Astronomy depends on ever increasing computing power. Processor clock-rates have plateaued, and increased performance is now appearing in the form of additional processor cores on a single chip. This poses significant challenges to the astronomy software community. Graphics Processing Units (GPUs), now capable of general-purpose computation, exemplify both the difficult learning-curve and the significant speedups exhibited by massively-parallel hardware architectures. We present a generalised approach to tackling this paradigm shift, based on the analysis of algorithms. We describe a small collection of foundation algorithms relevant to astronomy and explain how they may be used to ease the transition to massively-parallel computing architectures. We demonstrate the effectiveness of our approach by applying it to four well-known astronomy problems: Hogbom CLEAN, inverse ray-shooting for gravitational lensing, pulsar dedispersion and volume rendering. Algorithms with well-defined memory access patterns and high arithmetic intensity stand to receive the greatest performance boost from massively-parallel architectures, while those that involve a significant amount of decision-making may struggle to take advantage of the available processing power.Comment: 10 pages, 3 figures, accepted for publication in MNRA

The lid method for exhaustive exploration of metastable states of complex systems

The `lid' algorithm performs an exhaustive exploration of neighborhoods of local energy minima of energy landscapes. This paper describes an implementation of the algorithm, including issues of parallel performance and scalability. To illustrate the versatility of the approach and to stress the common features present in landscapes of quite different systems, we present selected results for 1) a spin glass, 2) a ferromagnet, 3) a covalent network model for glassy systems, and 4) a polymer. The exponential nature of the local density of states found in these systems and its relation to the ordering transition is briefly commented upon.Comment: RevTeX, 11 pages, 1 figur

Non-smooth optimization methods for computation of the conditional value-at-risk and portfolio optimization

We examine numerical performance of various methods of calculation of the Conditional Value-at-risk (CVaR), and portfolio optimization with respect to this risk measure. We concentrate on the method proposed by Rockafellar and Uryasev in (Rockafellar, R.T. and Uryasev, S., 2000, Optimization of conditional value-at-risk. Journal of Risk, 2, 21-41), which converts this problem to that of convex optimization. We compare the use of linear programming techniques against a non-smooth optimization method of the discrete gradient, and establish the supremacy of the latter. We show that non-smooth optimization can be used efficiently for large portfolio optimization, and also examine parallel execution of this method on computer clusters.<br /

Staphylococcal protein Ecb impairs complement receptor-1 mediated recognition of opsonized bacteria

Staphyloccus aureus is a major human pathogen leading frequently to sepsis and soft tissue infections with abscesses. Multiple virulence factors including several immune modulating molecules contribute to its survival in the host. When S. aureus invades the human body, one of the first line defenses is the complement system, which opsonizes the bacteria with C3b and attract neutrophils by release of chemotactic peptides. Neutrophils express Complement receptor-1 [CR1, CD35) that interacts with the C3b-opsonized particles and thereby plays an important role in pathogen recognition by phagocytic cells. In this study we observed that a fraction of S. aureus culture supernatant prevented binding of C3b to neutrophils. This fraction consisted of S. aureus leukocidins and Efb. The C-terminus of Efb is known to bind C3b and shares significant sequence homology to the extracellular complement binding protein [Ecb). Here we show that S. aureus Ecb displays various mechanisms to block bacterial recognition by neutrophils. The presence of Ecb blocked direct interaction between soluble CR1 and C3b and reduced the cofactor activity of CR1 in proteolytic inactivation of C3b. Furthermore, Ecb could dose-dependently prevent recognition of C3b by cell-bound CR1 that lead to impaired phagocytosis of NHS-opsonized S. aureus. Phagocytosis was furthermore reduced in the presence of soluble CR1 [sCR1). These data indicate that the staphylococcal protein Ecb prevents recognition of C3b opsonized bacteria by neutrophil CR1 leading to impaired killing by phagocytosis and thereby contribute to immune evasion of S. aureus.Peer reviewe

Microbes Bind Complement Inhibitor Factor H via a Common Site

To cause infections microbes need to evade host defense systems, one of these being the evolutionarily old and important arm of innate immunity, the alternative pathway of complement. It can attack all kinds of targets and is tightly controlled in plasma and on host cells by plasma complement regulator factor H (FH). FH binds simultaneously to host cell surface structures such as heparin or glycosaminoglycans via domain 20 and to the main complement opsonin C3b via domain 19. Many pathogenic microbes protect themselves from complement by recruiting host FH. We analyzed how and why different microbes bind FH via domains 19–20 (FH19-20). We used a selection of FH19-20 point mutants to reveal the binding sites of several microbial proteins and whole microbes (Haemophilus influenzae, Bordetella pertussis, Pseudomonas aeruginosa, Streptococcus pneumonia, Candida albicans, Borrelia burgdorferi, and Borrelia hermsii). We show that all studied microbes use the same binding region located on one side of domain 20. Binding of FH to the microbial proteins was inhibited with heparin showing that the common microbial binding site overlaps with the heparin site needed for efficient binding of FH to host cells. Surprisingly, the microbial proteins enhanced binding of FH19-20 to C3b and down-regulation of complement activation. We show that this is caused by formation of a tripartite complex between the microbial protein, FH, and C3b. In this study we reveal that seven microbes representing different phyla utilize a common binding site on the domain 20 of FH for complement evasion. Binding via this site not only mimics the glycosaminoglycans of the host cells, but also enhances function of FH on the microbial surfaces via the novel mechanism of tripartite complex formation. This is a unique example of convergent evolution resulting in enhanced immune evasion of important pathogens viautilization of a “superevasion site.

Paricalcitol versus cinacalcet plus low-dose vitamin D for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis: study design and baseline characteristics of the IMPACT SHPT study

Background. Paricalcitol and cinacalcet are common therapies for patients on haemodialysis with secondary hyperparathyroidism (SHPT). We conducted a multi-centre study in 12 countries to compare the safety and efficacy of paricalcitol and cinacalcet for the treatment of SHPT

No evidence of hemoglobin damage by SARS-CoV-2 infection

SARS-CoV-2 disease (COVID-19) has affected over 22 million patients worldwide as of August 2020. As the medical community seeks better understanding of the underlying pathophysiology of COVID-19, several theories have been proposed. One widely shared theory suggests that SARS-CoV-2 proteins directly interact with human hemoglobin (Hb) and facilitate removal of iron from the heme prosthetic group, leading to the loss of functional hemoglobin and accumulation of iron. Herein, we refute this theory. We compared clinical data from 21 critically ill COVID-19 patients to 21 non-COVID-19 ARDS patient controls, generating hemoglobin-oxygen dissociation curves from venous blood gases. This curve generated from the COVID-19 cohort matched the idealized oxygen-hemoglobin dissociation curve well (Pearson correlation, R2 = 0.97, P<0.0001; CV(RMSD) = 7.3%). We further analyzed hemoglobin, total bilirubin, lactate dehydrogenase, iron, ferritin, and haptoglobin levels. For all analyzed parameters, patients with COVID-19 had similar levels compared to patients with ARDS without COVID-19. These results indicate that patients with COVID-19 do not exhibit any hemolytic anemia or a shift in the normal hemoglobin-oxygen dissociation curve. We therefore conclude that COVID-19 does not impact oxygen delivery through a mechanism involving red cell hemolysis and subsequent removal of iron from the heme prosthetic group in hemoglobin

Accelerated large-scale multiple sequence alignment

<p>Abstract</p> <p>Background</p> <p>Multiple sequence alignment (MSA) is a fundamental analysis method used in bioinformatics and many comparative genomic applications. Prior MSA acceleration attempts with reconfigurable computing have only addressed the first stage of progressive alignment and consequently exhibit performance limitations according to Amdahl's Law. This work is the first known to accelerate the third stage of progressive alignment on reconfigurable hardware.</p> <p>Results</p> <p>We reduce subgroups of aligned sequences into discrete profiles before they are pairwise aligned on the accelerator. Using an FPGA accelerator, an overall speedup of up to 150 has been demonstrated on a large data set when compared to a 2.4 GHz Core2 processor.</p> <p>Conclusions</p> <p>Our parallel algorithm and architecture accelerates large-scale MSA with reconfigurable computing and allows researchers to solve the larger problems that confront biologists today. Program source is available from <url>http://dna.cs.byu.edu/msa/</url>.</p