Composability and Predictability for Independent Application Development, Verification and Execution

System-on-chip (SOC) design gets increasingly complex, as a growing number of applications are integrated in modern systems. Some of these applications have real-time requirements, such as a minimum throughput or a maximum latency. To reduce cost, system resources are shared between applications, making their timing behavior inter-dependent. Real-time requirements must hence be verified for all possible combinations of concurrently executing applications, which is not feasible with commonly used simulation-based techniques. This chapter addresses this problem using two complexity-reducing concepts: composability and predictability. Applications in a composable system are completely isolated and cannot affect each other’s behaviors, enabling them to be independently verified. Predictable systems, on the other hand, provide lower bounds on performance, allowing applications to be verified using formal performance analysis. Five techniques to achieve composability and/or predictability in SOC resources are presented and we explain their implementation for processors, interconnect, and memories in our platform

A composable, energy-managed, real-time MPSOC platform.

Multi-processors systems on chip (MPSOC) platforms emerged in embedded systems as hardware solutions to support the continuously increasing functionality and performance demands in this domain. Such a platform has to execute a mix of applications with diverse performance and timing constraints, i.e., real-time or non-real-time, thus different application schedulers should co-exist on an MPSOC. Moreover, applications share many MPSOC resources, thus their timing depends on the arbitration at these resources. Arbitration may create inter-application dependencies, e.g., the timing of a low priority application depends on the timing of all higher priority ones. Application inter-dependencies make the functional and timing verification and the integration process harder. This is especially problematic for real-time applications, for which fulfilling the time-related constraints should be guaranteed by construction. Moreover, energy and power management, commonly employed in embedded systems, make this verification even more difficult. Typically, energy and power management involves scaling the resources operating point, which has a direct impact on the resource performance, thus influences the application time behaviour. Finally, a small change in one application leads to the need to re-verify all other applications, incurring a large effort. Composability is a property meant to ease the verification and integration process. A system is composable if the functionality and the timing behaviour of each application is independent of other applications mapped on the same platform. Composability is achieved by utilising arbiters that ensure applications independence. In this paper we present the concepts behind a composable, scalable, energy-managed MPSOC platform, able to support different real-time and nonreal time schedulers concurrently, and discuss its advantages and limitations

Regional Conformational Flexibility Couples Substrate Specificity and Scissile Phosphate Diester Selectivity in Human Flap Endonuclease 1

Human flap endonuclease-1 (hFEN1) catalyzes the divalent metal ion-dependent removal of single-stranded DNA protrusions known as flaps during DNA replication and repair. Substrate selectivity involves passage of the 5′-terminus/flap through the arch and recognition of a single nucleotide 3′-flap by the α2–α3 loop. Using NMR spectroscopy, we show that the solution conformation of free and DNA-bound hFEN1 are consistent with crystal structures; however, parts of the arch region and α2–α3 loop are disordered without substrate. Disorder within the arch explains how 5′-flaps can pass under it. NMR and single-molecule FRET data show a shift in the conformational ensemble in the arch and loop region upon addition of DNA. Furthermore, the addition of divalent metal ions to the active site of the hFEN1–DNA substrate complex demonstrates that active site changes are propagated via DNA-mediated allostery to regions key to substrate differentiation. The hFEN1–DNA complex also shows evidence of millisecond timescale motions in the arch region that may be required for DNA to enter the active site. Thus, hFEN1 regional conformational flexibility spanning a range of dynamic timescales is crucial to reach the catalytically relevant ensemble

A composable, energy-managed, real-time MPSOC platform

Multi-processors systems on chip (MPSOC) platforms emerged in embedded systems as hardware solutions to support the continuously increasing functionality and performance demands in this domain. Such a platform has to execute a mix of applications with diverse performance and timing constraints, i.e., real-time or non-real-time, thus different application schedulers should co-exist on an MPSOC. Moreover, applications share many MPSOC resources, thus their timing depends on the arbitration at these resources. Arbitration may create inter-application dependencies, e.g., the timing of a low priority application depends on the timing of all higher priority ones. Application inter-dependencies make the functional and timing verification and the integration process harder. This is especially problematic for real-time applications, for which fulfilling the time-related constraints should be guaranteed by construction. Moreover, energy and power management, commonly employed in embedded systems, make this verification even more difficult. Typically, energy and power management involves scaling the resources operating point, which has a direct impact on the resource performance, thus influences the application time behaviour. Finally, a small change in one application leads to the need to re-verify all other applications, incurring a large effort. Composability is a property meant to ease the verification and integration process. A system is composable if the functionality and the timing behaviour of each application is independent of other applications mapped on the same platform. Composability is achieved by utilising arbiters that ensure applications independence. In this paper we present the concepts behind a composable, scalable, energy-managed MPSOC platform, able to support different real-time and nonreal time schedulers concurrently, and discuss its advantages and limitations

Terminal regions confer plasticity to the tetrameric assembly of human HspB2 and HspB3

Heterogeneity in small heat shock proteins (sHsps) spans multiple spatiotemporal regimes – from fast fluctuations of part of the protein, to conformational variability of tertiary structure, plasticity of the interfaces, and polydispersity of the inter-converting, and co-assembling oligomers. This heterogeneity and dynamic nature of sHsps has significantly hindered their structural characterisation. Atomic-coordinates are particularly lacking for vertebrate sHsps, where most available structures are of extensively truncated homomers. sHsps play important roles in maintaining protein levels in the cell and therefore in organismal health and disease. HspB2 and HspB3 are vertebrate sHsps that are found co-assembled in neuromuscular cells, and variants thereof are associated with disease. Here, we present the structure of human HspB2/B3, which crystallised as a hetero-tetramer in a 3:1 ratio. In the HspB2/B3 tetramer, the four a-crystallin domains (ACDs) assemble into a flattened tetrahedron which is pierced by two non-intersecting approximate dyads. Assembly is mediated by flexible “nuts and bolts” involving IXI/V motifs from terminal regions filling ACD pockets. Parts of the N-terminal region bind in an unfolded conformation into the anti-parallel shared ACD dimer grooves. Tracts of the terminal regions are not resolved, most likely due to their disorder in the crystal lattice. This first structure of a full-length human sHsp heteromer reveals the heterogeneous interactions of the terminal regions and suggests a plasticity that is important for the cytoprotective functions of sHsps

Optical nanofibers and spectroscopy

We review our recent progress in the production and characterization of tapered optical fibers with a sub-wavelength diameter waist. Such fibers exhibit a pronounced evanescent field and are therefore a useful tool for highly sensitive evanescent wave spectroscopy of adsorbates on the fiber waist or of the medium surrounding. We use a carefully designed flame pulling process that allows us to realize preset fiber diameter profiles. In order to determine the waist diameter and to verify the fiber profile, we employ scanning electron microscope measurements and a novel accurate in situ optical method based on harmonic generation. We use our fibers for linear and non-linear absorption and fluorescence spectroscopy of surface-adsorbed organic molecules and investigate their agglomeration dynamics. Furthermore, we apply our spectroscopic method to quantum dots on the surface of the fiber waist and to caesium vapor surrounding the fiber. Finally, towards dispersive measurements, we present our first results on building and testing a single-fiber bi-modal interferometer.Comment: 13 pages, 18 figures. Accepted for publication in Applied Physics B. Changes according to referee suggestions: changed title, clarification of some points in the text, added references, replacement of Figure 13

Possible origins of macroscopic left-right asymmetry in organisms

I consider the microscopic mechanisms by which a particular left-right (L/R) asymmetry is generated at the organism level from the microscopic handedness of cytoskeletal molecules. In light of a fundamental symmetry principle, the typical pattern-formation mechanisms of diffusion plus regulation cannot implement the "right-hand rule"; at the microscopic level, the cell's cytoskeleton of chiral filaments seems always to be involved, usually in collective states driven by polymerization forces or molecular motors. It seems particularly easy for handedness to emerge in a shear or rotation in the background of an effectively two-dimensional system, such as the cell membrane or a layer of cells, as this requires no pre-existing axis apart from the layer normal. I detail a scenario involving actin/myosin layers in snails and in C. elegans, and also one about the microtubule layer in plant cells. I also survey the other examples that I am aware of, such as the emergence of handedness such as the emergence of handedness in neurons, in eukaryote cell motility, and in non-flagellated bacteria.Comment: 42 pages, 6 figures, resubmitted to J. Stat. Phys. special issue. Major rewrite, rearranged sections/subsections, new Fig 3 + 6, new physics in Sec 2.4 and 3.4.1, added Sec 5 and subsections of Sec