High Performance, Point-to-Point, Transmission Line Signaling

Inter-chip signaling latency and bandwidth can be key factors limiting the performance of large VLSI systems. We present a high performance, transmission line signaling scheme for point-to-point communications between VLSI components. In particular, we detail circuitry which allows a pad driver to sense the voltage level on the attached pad during signaling and adjust the drive impedance to match the external transmission line impedance. This allows clean, reflection-free signaling despite the wide range of variations common in IC device processing and interconnect fabrication. Further, we show how similar techniques can be used to adjust the arrival time of signals to allow high signaling bandwidth despite variations in interconnect delays. This scheme employed for high performance signaling is a specific embodiment of a more general technique. Conventional electronic systems must accommodate a range of system characteristics (e.g. delay, voltage, impedance). As a result, circuit designers traditionally build large operating margins into their circuits to guarantee proper operation across all possible ranges of these characteristics. These margins are generally added at the expense of performance. The alternative scheme exemplified here is to sample these system characteristics in the device\u27s final operating environment and use this feedback to tune system operation around the observed characteristics. This tuning operation reduces the range of characteristics the system must accommodate, allowing increased performance. We briefly contrast this sampled, system-level feedback with the more conventional, fine-grained feedback employed on ICs (e.g. PLLs)

GraphStep: A System Architecture for Sparse-Graph Algorithms

Many important applications are organized around long-lived, irregular sparse graphs (e.g., data and knowledge bases, CAD optimization, numerical problems, simulations). The graph structures are large, and the applications need regular access to a large, data-dependent portion of the graph for each operation (e.g., the algorithm may need to walk the graph, visiting all nodes, or propagate changes through many nodes in the graph). On conventional microprocessors, the graph structures exceed on-chip cache capacities, making main-memory bandwidth and latency the key performance limiters. To avoid this “memory wall,” we introduce a concurrent system architecture for sparse graph algorithms that places graph nodes in small distributed memories paired with specialized graph processing nodes interconnected by a lightweight network. This gives us a scalable way to map these applications so that they can exploit the high-bandwidth and low-latency capabilities of embedded memories (e.g., FPGA Block RAMs). On typical spreading activation queries on the ConceptNet Knowledge Base, a sample application, this translates into an order of magnitude speedup per FPGA compared to a state-of-the-art Pentium processor

Amorphous Computing

Amorphous computing is the development of organizational principles and programming languages for obtaining coherent behaviors from the cooperation of myriads of unreliable parts that are interconnected in unknown, irregular, and time-varying ways. The impetus for amorphous computing comes from developments in microfabrication and fundamental biology, each of which is the basis of a kernel technology that makes it possible to build or grow huge numbers of almost-identical information-processing units at almost no cost. This paper sets out a research agenda for realizing the potential of amorphous computing and surveys some initial progress, both in programming and in fabrication. We describe some approaches to programming amorphous systems, which are inspired by metaphors from biology and physics. We also present the basic ideas of cellular computing, an approach to constructing digital-logic circuits within living cells by representing logic levels by concentrations DNA-binding proteins

Preliminary Design of the SAFE Platform

Safe is a clean-slate design for a secure host architecture. It integrates advances in programming languages, operating systems, and hardware and incorporates formal methods at every step. Though the project is still at an early stage, we have assembled a set of basic architectural choices that we believe will yield a high-assurance system. We sketch the current state of the design and discuss several of these choices

Preliminary Design of the SAFE Platform

SAFE is a clean-slate design for a secure host architecture. It integrates advances in programming languages, operating systems, and hardware and incorporates formal methods at every step. Though the project is still at an early stage, we have assembled a set of basic architectural choices that we believe will yield a high-assurance system. We sketch the current state of the design and discuss several of these choices.Engineering and Applied Science

Evolution of electronic and ionic structure of Mg-clusters with the growth cluster size

The optimized structure and electronic properties of neutral and singly charged magnesium clusters have been investigated using ab initio theoretical methods based on density-functional theory and systematic post-Hartree-Fock many-body perturbation theory accounting for all electrons in the system. We have systematically calculated the optimized geometries of neutral and singly charged magnesium clusters consisting of up to 21 atoms, electronic shell closures, binding energies per atom, ionization potentials and the gap between the highest occupied and the lowest unoccupied molecular orbitals. We have investigated the transition to the hcp structure and metallic evolution of the magnesium clusters, as well as the stability of linear chains and rings of magnesium atoms. The results obtained are compared with the available experimental data and the results of other theoretical works.Comment: 30 pages, 10 figures, 3 table

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Molecular imaging of rheumatoid arthritis by radiolabelled monoclonal antibodies: new imaging strategies to guide molecular therapies

The closing of the last century opened a wide variety of approaches for inflammation imaging and treatment of patients with rheumatoid arthritis (RA). The introduction of biological therapies for the management of RA started a revolution in the therapeutic armamentarium with the development of several novel monoclonal antibodies (mAbs), which can be murine, chimeric, humanised and fully human antibodies. Monoclonal antibodies specifically bind to their target, which could be adhesion molecules, activation markers, antigens or receptors, to interfere with specific inflammation pathways at the molecular level, leading to immune-modulation of the underlying pathogenic process. These new generation of mAbs can also be radiolabelled by using direct or indirect method, with a variety of nuclides, depending upon the specific diagnostic application. For studying rheumatoid arthritis patients, several monoclonal antibodies and their fragments, including anti-TNF-α, anti-CD20, anti-CD3, anti-CD4 and anti-E-selectin antibody, have been radiolabelled mainly with 99mTc or 111In. Scintigraphy with these radiolabelled antibodies may offer an exciting possibility for the study of RA patients and holds two types of information: (1) it allows better staging of the disease and diagnosis of the state of activity by early detection of inflamed joints that might be difficult to assess; (2) it might provide a possibility to perform ‘evidence-based biological therapy’ of arthritis with a view to assessing whether an antibody will localise in an inflamed joint before using the same unlabelled antibody therapeutically. This might prove particularly important for the selection of patients to be treated since biological therapies can be associated with severe side-effects and are considerably expensive. This article reviews the use of radiolabelled mAbs in the study of RA with particular emphasis on the use of different radiolabelled monoclonal antibodies for therapy decision-making and follow-up

Msh2 Blocks an Alternative Mechanism for Non-Homologous Tail Removal during Single-Strand Annealing in Saccharomyces cerevisiae

Chromosomal translocations are frequently observed in cells exposed to agents that cause DNA double-strand breaks (DSBs), such as ionizing radiation and chemotherapeutic drugs, and are often associated with tumors in mammals. Recently, translocation formation in the budding yeast, Saccharomyces cerevisiae, has been found to occur at high frequencies following the creation of multiple DSBs adjacent to repetitive sequences on non-homologous chromosomes. The genetic control of translocation formation and the chromosome complements of the clones that contain translocations suggest that translocation formation occurs by single-strand annealing (SSA). Among the factors important for translocation formation by SSA is the central mismatch repair (MMR) and homologous recombination (HR) factor, Msh2. Here we describe the effects of several msh2 missense mutations on translocation formation that suggest that Msh2 has separable functions in stabilizing annealed single strands, and removing non-homologous sequences from their ends. Additionally, interactions between the msh2 alleles and a null allele of RAD1, which encodes a subunit of a nuclease critical for the removal of non-homologous tails suggest that Msh2 blocks an alternative mechanism for removing these sequences. These results suggest that Msh2 plays multiple roles in the formation of chromosomal translocations following acute levels of DNA damage

A Preliminary Analysis of the Immunoglobulin Genes in the African Elephant (Loxodonta africana)

The genomic organization of the IgH (Immunoglobulin heavy chain), Igκ (Immunoglobulin kappa chain), and Igλ (Immunoglobulin lambda chain) loci in the African elephant (Loxodonta africana) was annotated using available genome data. The elephant IgH locus on scaffold 57 spans over 2,974 kb, and consists of at least 112 VH gene segments, 87 DH gene segments (the largest number in mammals examined so far), six JH gene segments, a single μ, a δ remnant, and eight γ genes (α and ε genes are missing, most likely due to sequence gaps). The Igκ locus, found on three scaffolds (202, 50 and 86), contains a total of 153 Vκ gene segments, three Jκ segments, and a single Cκ gene. Two different transcriptional orientations were determined for these Vκ gene segments. In contrast, the Igλ locus on scaffold 68 includes 15 Vλ gene segments, all with the same transcriptional polarity as the downstream Jλ-Cλ cluster. These data suggest that the elephant immunoglobulin gene repertoire is highly diverse and complex. Our results provide insights into the immunoglobulin genes in a placental mammal that is evolutionarily distant from humans, mice, and domestic animals