Performance prediction for complex parallel applications

Today`s massively parallel machines are typically message-passing systems consisting of hundreds or thousands of processors. Implementing parallel applications efficiently in this environment is a challenging task, and poor parallel design decisions can be expensive to correct. Tools and techniques that allow the fast and accurate evaluation of different parallelization strategies would significantly improve the productivity of application developers and increase throughput on parallel architectures. This paper investigates one of the major issues in building tools to compare parallelization strategies: determining what type of performance models of the application code and of the computer system are sufficient for a fast and accurate comparison of different strategies. The paper is built around a case study employing the Performance Prediction Tool (PerPreT) to predict performance of the Parallel Spectral Transform Shallow Water Model code (PSTSWM) on the Intel Paragon. 13 refs., 6 tabs

Modelling parallel database management systems for performance prediction

Abstract unavailable please refer to PD

A versatile nanobody-based toolkit to analyze retrograde transport from the cell surface

Retrograde transport of membranes and proteins from the cell surface is essential to maintain homeostasis and compartment identity. Following internalization via clathrin-dependent or -independent endocytosis, lipid and protein cargoes first populate early endosomes from where they are further redirected either along the endo-lysosomal system, recycled to the plasma membrane, or targeted to the trans-Golgi network (TGN) compartment. A number of distinct sorting machineries have been implicated in retrograde transport from endosomes to the TGN, among them the AP-1/clathrin machinery. Apart from an involvement in retrograde transport, AP-1/clathrin carriers have a well-established function in cargo export from the TGN. Even though the concept of bidirectional traffic at the TGN-to-endosome interface is commonly accepted, there is still uncertainty about the precise contribution of AP-1 to retrograde transport, since the conclusions of most studies were based on altered receptor steady-state distribution or mislocalization analysis upon knockdown or knockout of AP-1. Their readouts may be misleading, because the observed phenotype may be an indirect consequence of long-term AP-1 depletion, the result of upregulation of alternative pathways to compensate for the reduced or missing protein, thereby potentially masking the true AP-1 phenotype. To elucidate the involvement of AP-1 in endosome-to-TGN traffic, we set up a more generic approach allowing us to follow cargo molecules during their retrograde transport from the plasma membrane. To this end, we established a versatile nanobody-based approach conferring recombinant protein cargo to be tracked from the cell surface biochemically, by live cell imaging, and by electron microscopy. We engineered and bacterially expressed functionalized anti-GFP nanobodies fused to a sulfation consensus motif, to fluorophores, or to a peroxidase reporter. These functionalized nanobodies are specifically captured by EGFP-modified receptor proteins at the cell surface and transported piggyback to the receptor’s homing compartments. Using the sulfatable nanobody, we could biochemically determine the kinetics of bonafide sorting receptors, the MPRs, from the cell surface to the TGN. In combination with the knocksideways approach to look at the immediate and direct consequences of AP-1 inactivation, we could also show the role of AP-1/clathrin carriers in retrograde transport of MPRs from endosomes to the TGN. At the same time, however, we also evidenced that an AP-1 knockdown and knockout produced conflicting results when compared to acute inactivation strategies. Collectively, the present study describes a versatile nanobody-based approach to analyze retrograde transport of cargo proteins from the cell surface, and moreover provides insights into the role of the AP-1/clathrin machinery in retrograde transport

A Computational Model for Simulation, Visualization and Evaluation of Mandatory and Optional Building Occupancy Scenarios

Evaluating design decisions is an important factor in a post-positivist design process. Understanding how people move in space is an important part of the evaluation processes. However, making accurate predictions of occupants’ movements is a challenge mainly due to the differences between individual occupants, their unique preferences in relation to environmental qualities, the types of scenarios with which they become engaged, and multiple dimensions of the environmental factors that affect occupants’ decisions. This study suggests a model to simulate and visualize mandatory occupancy scenarios, which are task-based, and optional occupancy scenarios, which are attraction-based. The impact of environmental qualities is largely overlooked in existing simulation models in both of these scenarios. Existing simulation models for mandatory scenarios are often based on finding shortest or fastest paths and for optional scenarios mainly rely on the field of visibility. The original contribution of the simulation models that this study suggests is simultaneous consideration of environmental qualities, path simplicity, and visibility in addition to desires such as travel time or distance minimization. The integration of these models unlocks new potentials that the individual components do not include. The individual techniques that will be used to develop the occupancy simulation models are validated in the exiting literature experimentally. However, this study does not include conducting field studies to validate the integrated model. If the observed walking trails of humans are provided, the suggested models in this study can be validated through a fine-tuning process that reproduces the observed trails. The simulation results can finally be used for evaluation purposes to help designers at the design phase and facility managers in after design phases to make informed decisions. This study provides a software solution that implements the suggested model to support its feasibility. This software uses a Building Information Model (BIM) to represent the built environment, an Agent-Based Model (ABM) to simulate the occupants, a list of research evidence to encode agent’s reactions to the environment, a Discrete Event Simulation (DES) model to represent the tasks in mandatory scenarios, and the field of visibility (isovist) to simulate an occupant’s viewshed. In this software, evaluation is a process of data query from the information collected by the agents during the simulations. The data query logic can be set according to the interests of designers or facility managers

A Framework for the Design and Analysis of High-Performance Applications on FPGAs using Partial Reconfiguration

The field-programmable gate array (FPGA) is a dynamically reconfigurable digital logic chip used to implement custom hardware. The large densities of modern FPGAs and the capability of the on-thely reconfiguration has made the FPGA a viable alternative to fixed logic hardware chips such as the ASIC. In high-performance computing, FPGAs are used as co-processors to speed up computationally intensive processes or as autonomous systems that realize a complete hardware application. However, due to the limited capacity of FPGA logic resources, denser FPGAs must be purchased if more logic resources are required to realize all the functions of a complex application. Alternatively, partial reconfiguration (PR) can be used to swap, on demand, idle components of the application with active components. This research uses PR to swap components to improve the performance of the application given the limited logic resources available with smaller but economical FPGAs. The swap is called ”resource sharing PR”. In a pipelined design of multiple hardware modules (pipeline stages), resource sharing PR is a technique that uses PR to improve the performance of pipeline bottlenecks. This is done by reconfiguring other pipeline stages, typically those that are idle waiting for data from a bottleneck, into an additional parallel bottleneck module. The target pipeline of this research is a two-stage “slow-toast” pipeline where the flow of data traversing the pipeline transitions from a relatively slow, bottleneck stage to a fast stage. A two stage pipeline that combines FPGA-based hardware implementations of well-known Bioinformatics search algorithms, the X! Tandem algorithm and the Smith-Waterman algorithm, is implemented for this research; the implemented pipeline demonstrates that characteristics of these algorithm. The experimental results show that, in a database of unknown peptide spectra, when matching spectra with 388 peaks or greater, performing resource sharing PR to instantiate a parallel X! Tandem module is worth the cost for PR. In addition, from timings gathered during experiments, a general formula was derived for determining the value of performing PR upon a fast module

Physiology, syntrophy and viral interplay in the marine sponge holobiont

Holobionts result from intimate associations of eukaryotic hosts and microbes and are now widely accepted as ubiquitous and important elements of nature. Marine sponge holobionts combine simple morphology and complex microbiology whilst diverging early in the animal kingdom. As filter feeders, sponges feed on planktonic bacteria, but also harbour stable species-specific microbial consortia. This interaction with bacteria renders sponges to exciting systems to study basal determinants of animal-microbe symbioses. While inventories of symbiont taxa and gene functions continue to grow, we still know little about the symbiont physiology, cellular interactions and metabolic currencies within sponges. This limits our mechanistic understanding of holobiont stability and function. Therefore, this PhD thesis set out to study the questions of what individual symbionts actually do and how they interact. The first part of this thesis focuses on the cell physiology of cosmopolitan sponge symbionts. For the first time, I characterised the ultrastructure of dominant sponge symbiont clades within sponge tissue by establishing fluorescence in situ hybridization-correlative light and electron microscopy (FISH-CLEM). In combination with genome-centred metatranscriptomics, this approach revealed structural adaptations of symbionts to process complex holobiont-derived nutrients (i.e., bacterial microcompartments and bipolar storage polymers). Next, we unravelled complementary symbiont physiologies and cell co-localisation indicating vivid symbiont-symbiont metabolic interactions within the holobiont. This suggests strategies of nutritional resource partitioning and syntrophy to dominate over spatial segregation to avoid competitive exclusion- a mechanistic framework to sustain high microbial diversity. By combining stable isotope pulse-chase experiments with metabolic imaging, we demonstrated that symbionts can account for up to 60 % of the heterotrophic carbon and nitrogen assimilation in sponges. Thus, sponge symbiont action determines sponge-driven biochemical cycles in marine ecosystems. Finally, I explored the role of phages in the sponge holobiont focussing on tripartie phage-microbe-host interplay. Sponges appeared as rich reservoirs of novel viral diversity with 491 previously unidentified genus-level viral clades. Further, sponges harboured highly individual, yet species-specific viral communities. Importantly, I discovered that phages, termed “Ankyphages”, abundantly encode ankyrin proteins. Such “Ankyphages” I found to be widespread in host-associated environments, including humans. Using macrophage infection assays I showed that phage ankyrins aid bacteria in eukaryote immune evasion by downregulating eukaryotic antibacterial immunity. Thus, I identified a potentially widespread mechanism of tripartite phage-prokaryote-host interplay where phages foster animal-microbe symbioses. Altogether, I draw three main conclusions: The sponge holobiont is a metabolically intertwined ecosystem, with symbiont action impacting the environment, and tripartite phage-prokaryote-eukaryote interplay fostering symbiosis