918 research outputs found
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CHERIvoke: Characterising pointer revocation using CHERI capabilities for temporal memory safety
A lack of temporal safety in low-level languages has led to an epidemic of use-after-free exploits. These have surpassed in number and severity even the infamous buffer-overflow exploits violating spatial safety. Capability addressing can directly enforce spatial safety for the C language by enforcing bounds on pointers and by rendering pointers unforgeable. Nevertheless, an efficient solution for strong temporal memory safety remains elusive.
CHERI is an architectural extension to provide hardware capability addressing that is seeing significant commercial and open- source interest. We show that CHERI capabilities can be used as a foundation to enable low-cost heap temporal safety by facilitating out-of-date pointer revocation, as capabilities enable precise and efficient identification and invalidation of pointers, even when using unsafe languages such as C. We develop CHERIvoke, a technique for deterministic and fast sweeping revocation to enforce temporal safety on CHERI systems. CHERIvoke quarantines freed data before periodically using a small shadow map to revoke all dangling pointers in a single sweep of memory, and provides a tunable trade-off between performance and heap growth. We evaluate the performance of such a system using high-performance x86 processors, and further analytically examine its primary overheads. When configured with a heap-size overhead of 25%, we find that CHERIvoke achieves an average execution-time overhead of under 5%, far below the overheads associated with traditional garbage collection, revocation, or page-table systems.EP/K026399/1, EP/P020011/1, EP/K008528/
Clinical characteristics of pertussis-associated cough in adults and children: a diagnostic systematic review and meta-analysis
Background: Pertussis (whooping cough) is a highly infective cause of cough that causes significant morbidity and mortality. Existing case definitions include paroxysmal cough, whooping and post-tussive vomiting but diagnosis can be difficult. We determined the diagnostic accuracy of clinical characteristics of pertussis-associated cough. Methods: We systematically searched CINAHL, Embase, Medline and SCI-EXPANDED/CPCI-S up to June 2016. Eligible studies compared clinical characteristics in those positive and negative for Bordetella pertussis infection, confirmed by laboratory investigations. Two authors independently completed screening, data extraction and quality and bias assessments. For each characteristic RevMan was used to produce descriptive forest plots. We used the bivariate meta-analysis method to generate pooled estimates of sensitivity and specificity. Results: Of 1969 identified papers, 53 were included. Forty-one clinical characteristics were assessed for diagnostic accuracy. In adult patients, paroxysmal cough and absence of fever had a high sensitivity (93.2%, CI 83.2-97.4 and 81.8%, CI 72.2-88.7 respectively) and low specificity (20.6%, CI 14.7-28.1 and 18.8%, CI 8.1-37.9 respectively), whereas post-tussive vomiting and whooping had low sensitivity (32.5%, CI 24.5-41.6 and 29.8%, CI 8.0-45.2 respectively) and high specificity (77.7%, CI 73.1-81.7 and 79.5%, CI 69.4-86.9 respectively). Post-tussive vomiting in children is moderately sensitive (60.0%, CI 40.3-77.0) and specific 66.0%, CI 52.5-77.3). Conclusions: In adult patients the presence of whooping or post-tussive vomiting should rule in a possible diagnosis of pertussis, whereas the lack of a paroxysmal cough or the presence of fever should rule it out. In children, post-tussive vomiting is much less helpful as a clinical diagnostic test
Temporal dynamics of aquatic communities and implications for pond conservation
Conservation through the protection of particular habitats is predicated on the assumption that the conservation value of those habitats is stable. We test this assumption for ponds by investigating temporal variation in macroinvertebrate and macrophyte communities over a 10-year period in northwest England. We surveyed 51 ponds in northern England in 1995/6 and again in 2006, identifying all macrophytes (167 species) and all macroinvertebrates (221 species, excluding Diptera) to species. The alpha-diversity, beta-diversity and conservation value of these ponds were compared between surveys. We find that invertebrate species richness increased from an average of 29. 5 species to 39. 8 species between surveys. Invertebrate gamma-diversity also increased between the two surveys from 181 species to 201 species. However, this increase in diversity was accompanied by a decrease in beta-diversity. Plant alpha-, beta and gamma-diversity remained approximately constant between the two periods. However, increased proportions of grass species and a complete loss of charophytes suggests that the communities are undergoing succession. Conservation value was not correlated between sampling periods in either plants or invertebrates. This was confirmed by comparing ponds that had been disturbed with those that had no history of disturbance to demonstrate that levels of correlation between surveys were approximately equal in each group of ponds. This study has three important conservation implications: (i) a pond with high diversity or high conservation value may not remain that way and so it is unwise to base pond conservation measures upon protecting currently-speciose habitats; (ii) maximising pond gamma-diversity requires a combination of late and early succession ponds, especially for invertebrates; and (iii) invertebrate and plant communities in ponds may require different management strategies if succession occurs at varying rates in the two groups
Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS
Congenital melanocytic nevi (CMN) can be associated with neurological abnormalities and an increased risk of melanoma. Mutations in NRAS, BRAF, and Tp53 have been described in individual CMN samples; however, their role in the pathogenesis of multiple CMN within the same subject and development of associated features has not been clear. We hypothesized that a single postzygotic mutation in NRAS could be responsible for multiple CMN in the same individual, as well as for melanocytic and nonmelanocytic central nervous system (CNS) lesions. From 15 patients, 55 samples with multiple CMN were sequenced after site-directed mutagenesis and enzymatic digestion of the wild-type allele. Oncogenic missense mutations in codon 61 of NRAS were found in affected neurological and cutaneous tissues of 12 out of 15 patients, but were absent from unaffected tissues and blood, consistent with NRAS mutation mosaicism. In 10 patients, the mutation was consistently c.181C>A, p.Q61K, and in 2 patients c.182A>G, p.Q61R. All 11 non-melanocytic and melanocytic CNS samples from 5 patients were mutation positive, despite NRAS rarely being reported as mutated in CNS tumors. Loss of heterozygosity was associated with the onset of melanoma in two cases, implying a multistep progression to malignancy. These results suggest that single postzygotic NRAS mutations are responsible for multiple CMN and associated neurological lesions in the majority of cases
<i>Trypanosoma brucei rhodesiense</i> transmitted by a single tsetse fly bite in vervet monkeys as a model of human African trypanosomiasis
Sleeping sickness is caused by a species of trypanosome blood parasite that is transmitted by tsetse flies. To understand better how infection with this parasite leads to disease, we provide here the most detailed description yet of the course of infection and disease onset in vervet monkeys. One infected tsetse fly was allowed to feed on each host individual, and in all cases infections were successful. The characteristics of infection and disease were similar in all hosts, but the rate of progression varied considerably. Parasites were first detected in the blood 4-10 days after infection, showing that migration of parasites from the site of fly bite was very rapid. Anaemia was a key feature of disease, with a reduction in the numbers and average size of red blood cells and associated decline in numbers of platelets and white blood cells. One to six weeks after infection, parasites were observed in the cerebrospinal fluid (CSF), indicating that they had moved from the blood into the brain; this was associated with a white cell infiltration. This study shows that fly-transmitted infection in vervets accurately mimics human disease and provides a robust model to understand better how sleeping sickness develops
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CheriABI: Enforcing Valid Pointer Provenance and Minimizing Pointer Privilege in the POSIX C Run-time Environment
The CHERI architecture allows pointers to be implemented as capabilities (rather than integer virtual addresses) in a manner that is compatible with, and strengthens, the semantics of the C language. In addition to the spatial protections offered by conventional fat pointers, CHERI capabilities offer strong integrity, enforced provenance validity, and access monotonicity. The stronger guarantees of these architectural capabilities must be reconciled with the real-world behavior of operating systems, run-time environments, and applications. When the process model, user-kernel interactions, dynamic linking, and memory management are all considered, we observe that simple derivation of architectural capabilities is insufficient to describe appropriate access to memory. We bridge this conceptual gap with a notional \emph{abstract capability} that describes the accesses that should be allowed at a given point in execution, whether in the kernel or userspace. To investigate this notion at scale, we describe the first adaptation of a full C-language operating system (FreeBSD) with an enterprise database (PostgreSQL) for complete spatial and referential memory safety. We show that awareness of abstract capabilities, coupled with CHERI architectural capabilities, can provide more complete protection, strong compatibility, and acceptable performance overhead compared with the pre-CHERI baseline and software-only approaches. Our observations also have potentially significant implications for other mitigation techniques.This work was supported by the Defense Advanced Research Projects Agency (DARPA) and the Air Force Research Laboratory (AFRL), under contracts FA8750-10-C-0237 (``CTSRD'') and HR0011-18-C-0016 (``ECATS''). The views, opinions, and/or findings contained in this report are those of the authors and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government. We also acknowledge the EPSRC REMS Programme Grant (EP/K008528/1), the ERC ELVER Advanced Grant (789108), Arm Limited, HP Enterprise, and Google, Inc. Approved for Public Release, Distribution Unlimited
Integrating personality research and animal contest theory: aggressiveness in the green swordtail <i>Xiphophorus helleri</i>
<p>Aggression occurs when individuals compete over limiting resources. While theoretical studies have long placed a strong emphasis on context-specificity of aggression, there is increasing recognition that consistent behavioural differences exist among individuals, and that aggressiveness may be an important component of individual personality. Though empirical studies tend to focus on one aspect or the other, we suggest there is merit in modelling both within-and among-individual variation in agonistic behaviour simultaneously. Here, we demonstrate how this can be achieved using multivariate linear mixed effect models. Using data from repeated mirror trials and dyadic interactions of male green swordtails, <i>Xiphophorus helleri</i>, we show repeatable components of (co)variation in a suite of agonistic behaviour that is broadly consistent with a major axis of variation in aggressiveness. We also show that observed focal behaviour is dependent on opponent effects, which can themselves be repeatable but were more generally found to be context specific. In particular, our models show that within-individual variation in agonistic behaviour is explained, at least in part, by the relative size of a live opponent as predicted by contest theory. Finally, we suggest several additional applications of the multivariate models demonstrated here. These include testing the recently queried functional equivalence of alternative experimental approaches, (e. g., mirror trials, dyadic interaction tests) for assaying individual aggressiveness.</p>
Nitrogen transfer from forage legumes to nine neighbouring plants in a multi-species grassland
Legumes play a crucial role in nitrogen supply to grass-legume mixtures for ruminant fodder. To quantify N transfer from legumes to neighbouring plants in multi-species grasslands we established a grass-legume-herb mixture on a loamy-sandy site in Denmark. White clover (Trifolium repens L.), red clover (Trifolium pratense L.) and lucerne (Medicago sativa L.) were leaf-labelled with 15N enriched urea during one growing season. N transfer to grasses
(Lolium perenne L. and xfestulolium), white clover, red clover, lucerne, birdsfoot trefoil (Lotus corniculatus
L.), chicory (Cichorium intybus L.), plantain (Plantago
lanceolata L.), salad burnet (Sanguisorba minor L.)and caraway (Carum carvi L.) was assessed. Neighbouring plants contained greater amounts of N derived from white clover (4.8 gm-2) compared with red clover (2.2 gm-2) and lucerne (1.1 gm-2). Grasses having fibrous roots received greater amounts of N from legumes than dicotyledonous plants which generally have taproots. Slurry application mainly increased N transfer from legumes to grasses. During the growing season the three legumes transferred approximately 40 kg N ha-1 to neighbouring plants. Below-ground N transfer from legumes to neighbouring plants differed among nitrogen donors and nitrogen receivers and may depend on root characteristics and regrowth strategies of plant species in the multi-species grassland
Abdominal angina due to recurrence of cancer of the papilla of Vater: a case report
Abdominal angina is usually caused by atherosclerotic disease, and other causes are considered uncommon. This is the first report of a case of abdominal angina secondary to neoplastic vascular stenosis caused by local recurrence of an adenocarcinoma of the papilla of Vater. CASE PRESENTATION: An 80-year-old woman of Caucasian origin presented with abdominal pain and diarrhea. She had undergone a pancreaticoduodenectomy for adenocarcinoma of the papilla of Vater four years earlier. Computed tomography revealed a mass surrounding her celiac trunk and superior mesenteric artery. Her abdominal pain responded poorly to analgesic drugs, but disappeared when oral feedings were withheld. A duplex ultrasonography of the patient's splanchnic vessels was consistent with vascular stenosis. Parenteral nutrition was started and the patient remained pain free until her death. CONCLUSION: Pain relief is an important therapeutic target in patients with cancer. In this case, abdominal pain was successfully managed only after the ischemic cause had been identified. The conventional analgesic therapy algorithm based on nonsteroidal anti-inflammatory drugs and opioids had been costly and pointless, whereas the simple withdrawal of oral feeding spared the patient of the discomfort of additional invasive procedures and allowed her to spend her remaining days in a completely pain-free state
TLR9-induced interferon β is associated with protection from gammaherpesvirus-induced exacerbation of lung fibrosis
Abstract
Background
We have shown previously that murine gammaherpesvirus 68 (γHV68) infection exacerbates established pulmonary fibrosis. Because Toll-like receptor (TLR)-9 may be important in controlling the immune response to γHV68 infection, we examined how TLR-9 signaling effects exacerbation of fibrosis in response to viral infection, using models of bleomycin- and fluorescein isothiocyanate-induced pulmonary fibrosis in wild-type (Balb/c) and TLR-9-/- mice.
Results
We found that in the absence of TLR-9 signaling, there was a significant increase in collagen deposition following viral exacerbation of fibrosis. This was not associated with increased viral load in TLR-9-/- mice or with major alterations in T helper (Th)1 and Th2 cytokines. We examined alveolar epithelial-cell apoptosis in both strains, but this could not explain the altered fibrotic outcomes. As expected, TLR-9-/- mice had a defect in the production of interferon (IFN)-β after viral infection. Balb/c fibroblasts infected with γHV68 in vitro produced more IFN-β than did infected TLR-9-/- fibroblasts. Accordingly, in vitro infection of Balb/c fibroblasts resulted in reduced proliferation rates whereas infection of TLR-9-/- fibroblasts did not. Finally, therapeutic administration of CpG oligodeoxynucleotides ameliorated bleomycin-induced fibrosis in wild-type mice.
Conclusions
These results show a protective role for TLR-9 signaling in murine models of lung fibrosis, and highlight differences in the biology of TLR-9 between mice and humans.http://deepblue.lib.umich.edu/bitstream/2027.42/112877/1/13069_2011_Article_57.pd
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