Reduction of bone cancer pain by CB1 activation and TRPV1 inhibition

ArticleJOURNAL OF ANESTHESIA. 24(2):328-332 (2010)journal articl

Helmholtz: A Verifier for Tezos Smart Contracts Based on Refinement Types

27th International Conference, TACAS 2021, Held as Part of the European Joint Conferences on Theory and Practice of Software, ETAPS 2021, Luxembourg City, Luxembourg, March 27 - April 1, 2021Part of the Lecture Notes in Computer Science book series (LNTCS, volume 12652)A smart contract is a program executed on a blockchain, based on which many cryptocurrencies are implemented, and is being used for automating transactions. Due to the large amount of money that smart contracts deal with, there is a surging demand for a method that can statically and formally verify them. This tool paper describes our type-based static verification tool HELMHOLTZ for Michelson, which is a statically typed stack-based language for writing smart contracts that are executed on the blockchain platform Tezos. HELMHOLTZ is designed on top of our extension of Michelson’s type system with refinement types. HELMHOLTZ takes a Michelson program annotated with a user-defined specification written in the form of a refinement type as input; it then typechecks the program against the specification based on the refinement type system, discharging the generated verification conditions with the SMT solver Z3. We briefly introduce our refinement type system for the core calculus Mini-Michelson of Michelson, which incorporates the characteristic features such as compound datatypes (e.g., lists and pairs), higher-order functions, and invocation of another contract. HELMHOLTZ successfully verifies several practical Michelson programs, including one that transfers money to an account and that checks a digital signature

Helmholtz: A Verifier for Tezos Smart Contracts Based on Refinement Types

A smart contract is a program executed on a blockchain, based on which many cryptocurrencies are implemented, and is being used for automating transactions. Due to the large amount of money that smart contracts deal with, there is a surging demand for a method that can statically and formally verify them. This article describes our type-based static verification tool HELMHOLTZ for Michelson, which is a statically typed stack-based language for writing smart contracts that are executed on the blockchain platform Tezos. HELMHOLTZ is designed on top of our extension of Michelson’s type system with refinement types. HELMHOLTZ takes a Michelson program annotated with a user-defined specification written in the form of a refinement type as input; it then typechecks the program against the specification based on the refinement type system, discharging the generated verification conditions with the SMT solver Z3. We briefly introduce our refinement type system for the core calculus Mini-Michelson of Michelson, which incorporates the characteristic features such as compound datatypes (e.g., lists and pairs), higher-order functions, and invocation of another contract. HELMHOLTZ successfully verifies several practical Michelson programs, including one that transfers money to an account and that checks a digital signature

Bone cancer induces a unique central sensitization through synaptic changes in a wide area of the spinal cord

<p>Abstract</p> <p>Background</p> <p>Chronic bone cancer pain is thought to be partly due to central sensitization. Although murine models of bone cancer pain revealed significant neurochemical changes in the spinal cord, it is not known whether this produces functional alterations in spinal sensory synaptic transmission. In this study, we examined excitatory synaptic responses evoked in substantia gelatinosa (SG, lamina II) neurons in spinal cord slices of adult mice bearing bone cancer, using whole-cell voltage-clamp recording techniques.</p> <p>Results</p> <p>Mice at 14 to 21 days after sarcoma implantation into the femur exhibited hyperalgesia to mechanical stimuli applied to the skin of the ipsilateral hind paw, as well as showing spontaneous and movement evoked pain-related behaviors. SG neurons exhibited spontaneous excitatory postsynaptic currents (EPSCs). The amplitudes of spontaneous EPSCs were significantly larger in cancer-bearing than control mice without any changes in passive membrane properties of SG neurons. In the presence of TTX, the amplitude of miniature EPSCs in SG neurons was increased in cancer-bearing mice and this was observed for cells sampled across a wide range of lumbar segmental levels. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor- and <it>N</it>-methyl-<it>D</it>-aspartate (NMDA) receptor-mediated EPSCs evoked by focal stimulation were also enhanced in cancer-bearing mice. Dorsal root stimulation elicited mono- and/or polysynaptic EPSCs that were caused by the activation of Aδ and/or C afferent fibers in SG neurons from both groups of animals. The number of cells receiving monosynaptic inputs from Aδ and C fibers was not different between the two groups. However, the amplitude of the monosynaptic C fiber-evoked EPSCs and the number of SG neurons receiving polysynaptic inputs from Aδ and C fibers were increased in cancer-bearing mice.</p> <p>Conclusions</p> <p>These results show that spinal synaptic transmission mediated through Aδ and C fibers is enhanced in the SG across a wide area of lumbar levels following sarcoma implantation in the femur. This widespread spinal sensitization may be one of the underlying mechanisms for the development of chronic bone cancer pain.</p

Polymorphisme extensionnel (théorie et applications)

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