CHERI Concentrate: Practical Compressed Capabilities

We present CHERI Concentrate, a new fat-pointer compression scheme applied to CHERI, the most developed capability-pointer system at present. Capability fat-pointers are a primary candidate for enforcing fine-grained and non-bypassable security properties in future computer systems, although increased pointer size can severely affect performance. Thus, several proposals for capability compression have been suggested but these did not support legacy instruction sets, ignored features critical to the existing software base, and also introduced design inefficiencies to RISC-style processor pipelines. CHERI Concentrate improves on the state-of-the-art region-encoding efficiency, solves important pipeline problems, and eases semantic restrictions of compressed encoding, allowing it to protect a full legacy software stack. We analyze and extend logic from the open-source CHERI prototype processor design on FPGA to demonstrate encoding efficiency, minimize delay of pointer arithmetic, and eliminate additional load-to-use delay. To verify correctness of our proposed high-performance logic, we present a HOL4 machine-checked proof of the decode and pointer-modify operations. Finally, we measure a 50%-75% reduction in L2 misses for many compiled C-language benchmarks running under a commodity operating system using compressed 128-bit and 64-bit formats, demonstrating both compatibility with and increased performance over the uncompressed, 256-bit format

CHERI JNI: Sinking the Java Security Model into the C

Java provides security and robustness by building a high- level security model atop the foundation of memory protection. Unfortunately, any native code linked into a Java program – including the million lines used to implement the standard library – is able to bypass both the memory protection and the higher-level policies. We present a hardware-assisted implementation of the Java native code interface, which extends the guarantees required for Java’s security model to native code. Our design supports safe direct access to buffers owned by the JVM, including hardware-enforced read-only access where appropriate. We also present Java language syntax to declaratively describe isolated compartments for native code. We show that it is possible to preserve the memory safety and isolation requirements of the Java security model in C code, allowing native code to run in the same process as Java code with the same impact on security as running equivalent Java code. Our approach has a negligible impact on performance, compared with the existing unsafe native code interface. We demonstrate a prototype implementation running on the CHERI microprocessor synthesized in FPGA.Defense Advanced Research Projects Agency Google, Inc. Isaac Newton Trust Thales E-Securit

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Marketing Research

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Solid-supported boronic acid conjugates for sugar and glycopeptide recognition

The Fmoc synthetic strategy was employed to synthesise two identical combinatorial peptide libraries on a hydrophilic PEG-PS resin. One library was appended with boronic acid moieties at two positionally-fixed locations. Successful inclusion of the boronic acid units was confirmed using a novel UV fluorescent colorimetric assay employing carminic acid as the dye compound. A study of the effect had by the resin-bound peptides bearing boronic acid groups on the binding characteristics of vancomycin, a medically relevant antibiotic glycoprotein, was conducted. In all, 132 library compounds were tested for their binding affinity with vancomycin, via immobilisation of the glycopeptide onto the solid support through hydrogen bonding or complexation with the boronic acid moieties. Subsequent cleavage via acidolysis afforded vancomycin containing solutions which were quantified by growth inhibition of methicillin susceptible Staphylococcus aureus. Comparison of the diameters of the resultant zones of inhibition and those produced by vancomycin of known concentrations afforded a means of calculating the vancomycin concentration of the cleavage solutions, and thereby determining the binding affinity of vancomycin to each peptide sequence. Five peptide sequences and twenty one of the peptidyl-boronic acid sequences showed zones of inhibition, demonstrating their reversible affinity for vancomycin. Three peptide sequences showed zones of inhibition in both libraries. The presence of boronic acid was therefore shown to impart, enhance, detract and remove the affinity of vancomycin to a range of resin-bound peptide sequences.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Solid-supported boronic acid conjugates for sugar and glycopeptide recognition

The Fmoc synthetic strategy was employed to synthesise two identical combinatorial peptide libraries on a hydrophilic PEG-PS resin. One library was appended with boronic acid moieties at two positionally-fixed locations. Successful inclusion of the boronic acid units was confirmed using a novel UV fluorescent colorimetric assay employing carminic acid as the dye compound. A study of the effect had by the resin-bound peptides bearing boronic acid groups on the binding characteristics of vancomycin, a medically relevant antibiotic glycoprotein, was conducted. In all, 132 library compounds were tested for their binding affinity with vancomycin, via immobilisation of the glycopeptide onto the solid support through hydrogen bonding or complexation with the boronic acid moieties. Subsequent cleavage via acidolysis afforded vancomycin containing solutions which were quantified by growth inhibition of methicillin susceptible Staphylococcus aureus. Comparison of the diameters of the resultant zones of inhibition and those produced by vancomycin of known concentrations afforded a means of calculating the vancomycin concentration of the cleavage solutions, and thereby determining the binding affinity of vancomycin to each peptide sequence. Five peptide sequences and twenty one of the peptidyl-boronic acid sequences showed zones of inhibition, demonstrating their reversible affinity for vancomycin. Three peptide sequences showed zones of inhibition in both libraries. The presence of boronic acid was therefore shown to impart, enhance, detract and remove the affinity of vancomycin to a range of resin-bound peptide sequences

The emerging world of small ORFs

Small open reading frames (sORFs) are an often overlooked feature of plant genomes. Initially found in plant viral RNAs and considered an interesting curiosity, an increasing number of these sORFs have been shown to encode functional peptides or play a regulatory role. The recent discovery that many of these sORFs initiate with start codons other than AUG, together with the identification of functional small peptides encoded in supposedly noncoding primary miRNA transcripts (pri-miRs), has drastically increased the number of potentially functional sORFs within the genome. Here we review how advances in technology, notably ribosome profiling (RP) assays, are complementing bioinformatics and proteogenomic methods to provide powerful ways to identify these elusive features of plant genomes, and highlight the regulatory roles sORFs can play