Hierarchical strategies for efficient fault recovery on the reconfigurable PAnDA device

A novel hierarchical fault-tolerance methodology for reconfigurable devices is presented. A bespoke multi-reconfigurable FPGA architecture, the programmable analogue and digital array (PAnDA), is introduced allowing fine-grained reconfiguration beyond any other FPGA architecture currently in existence. Fault blind circuit repair strategies, which require no specific information of the nature or location of faults, are developed, exploiting architectural features of PAnDA. Two fault recovery techniques, stochastic and deterministic strategies, are proposed and results of each, as well as a comparison of the two, are presented. Both approaches are based on creating algorithms performing fine-grained hierarchical partial reconfiguration on faulty circuits in order to repair them. While the stochastic approach provides insights into feasibility of the method, the deterministic approach aims to generate optimal repair strategies for generic faults induced into a specific circuit. It is shown that both techniques successfully repair the benchmark circuits used after random faults are induced in random circuit locations, and the deterministic strategies are shown to operate efficiently and effectively after optimisation for a specific use case. The methods are shown to be generally applicable to any circuit on PAnDA, and to be straightforwardly customisable for any FPGA fabric providing some regularity and symmetry in its structure

Open-ended evolution to discover analogue circuits for beyond conventional applications

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s10710-012-9163-8. Copyright @ Springer 2012.Analogue circuits synthesised by means of open-ended evolutionary algorithms often have unconventional designs. However, these circuits are typically highly compact, and the general nature of the evolutionary search methodology allows such designs to be used in many applications. Previous work on the evolutionary design of analogue circuits has focused on circuits that lie well within analogue application domain. In contrast, our paper considers the evolution of analogue circuits that are usually synthesised in digital logic. We have developed four computational circuits, two voltage distributor circuits and a time interval metre circuit. The approach, despite its simplicity, succeeds over the design tasks owing to the employment of substructure reuse and incremental evolution. Our findings expand the range of applications that are considered suitable for evolutionary electronics

A Crystal Structure of the Bifunctional Antibiotic Simocyclinone D8, Bound to DNA Gyrase

Simocyclinones are bifunctional antibiotics that inhibit bacterial DNA gyrase by preventing DNA binding to the enzyme. We report the crystal structure of the complex formed between the N-terminal domain of the Escherichia coli gyrase A subunit and simocyclinone D8, revealing two binding pockets that separately accommodate the aminocoumarin and polyketide moieties of the antibiotic. These are close to, but distinct from, the quinolone-binding site, consistent with our observations that several mutations in this region confer resistance to both agents. Biochemical studies show that the individual moieties of simocyclinone D8 are comparatively weak inhibitors of gyrase relative to the parent compound, but their combination generates a more potent inhibitor. Our results should facilitate the design of drug molecules that target these unexploited binding pockets

Four Phosphates at One Blow: Access to Pentaphosphorylated Magic Spot Nucleotides and Their Analysis by Capillary Electrophoresis

The complex phosphorylation pattern of natural and modified pentaphosphorylated magic spot nucleotides is generated in a highly efficient way. A cyclic pyrophosphoryl phosphoramidite (cPyPA) reagent is used to introduce four phosphates on nucleosides regioselectively in a one-flask key transformation. The obtained magic spot nucleotides are used to develop a capillary electrophoresis UV detection method, enabling nucleotide assignment in complex bacterial extracts

A Multi-objective Evolutionary Approach for Efficient Kernel Size and Shape for CNN

While state-of-the-art development in CNN topology, such as VGGNet and ResNet, have become increasingly accurate, these networks are computationally expensive involving billions of arithmetic operations and parameters. To improve the classification accuracy, state-of-the-art CNNs usually involve large and complex convolutional layers. However, for certain applications, e.g. Internet of Things (IoT), where such CNNs are to be implemented on resource-constrained platforms, the CNN architectures have to be small and efficient. To deal with this problem, reducing the resource consumption in convolutional layers has become one of the most significant solutions. In this work, a multi-objective optimisation approach is proposed to trade-off between the amount of computation and network accuracy by using Multi-Objective Evolutionary Algorithms (MOEAs). The number of convolution kernels and the size of these kernels are proportional to computational resource consumption of CNNs. Therefore, this paper considers optimising the computational resource consumption by reducing the size and number of kernels in convolutional layers. Additionally, the use of unconventional kernel shapes has been investigated and results show these clearly outperform the commonly used square convolution kernels. The main contributions of this paper are therefore a methodology to significantly reduce computational cost of CNNs, based on unconventional kernel shapes, and provide different trade-offs for specific use cases. The experimental results further demonstrate that the proposed method achieves large improvements in resource consumption with no significant reduction in network performance. Compared with the benchmark CNN, the best trade-off architecture shows a reduction in multiplications of up to 6X and with slight increase in classification accuracy on CIFAR-10 dataset.Comment: 13 pages paper, plus 17 papers supplementary material

The price of tumor control

Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects

Functional and symptom impact of trametinib versus chemotherapy in BRAF V600E advanced or metastatic melanoma: quality-of-life analyses of the METRIC study

We report the first quality-of-life assessment of a MEK inhibitor in metastatic melanoma from a phase III study. Trametinib prolonged progression-free survival and improved overall survival versus chemotherapy in patients with BRAF V600 mutation-positive melanoma. Less functional impairment, smaller declines in health status, and less exacerbation of symptoms were observed with trametini