335 research outputs found

    An Elementary Affine λ-Calculus with Multithreading and Side Effects

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    International audienceLinear logic provides a framework to control the complexity of higher-order functional programs. We present an extension of this framework to programs with multithreading and side effects focusing on the case of elementary time. Our main contributions are as follows. First, we introduce a modal call-by-value λ-calculus with multithreading and side effects. Second, we provide a combinatorial proof of termination in elementary time for the language. Third, we introduce an elementary affine type system that guarantees the standard subject reduction and progress properties. Finally, we illustrate the programming of iterative functions with side effects in the presented formalism

    Molecular bases of thermophily in hyperthermophiles

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    I reflect on some of our studies on the hyperthermophilic archaeon, Thermococcus kodakarensis KOD1 and its enzymes. The strain can grow at temperatures up to 100 ℃, and also represents one of the simplest forms of life. As expected, all enzymes, DNA, RNA, cytoplasmic membrane, and cytoplasmic solute displayed remarkable thermostability, and we have determined some of the basic principles that govern this feature. To our delight, many of the enzymes exhibited unique biochemical properties and novel structures not found in mesophilic proteins. Here, I will focus on some enzymes whose three-dimensional structures are characteristic of thermostable enzymes. I will also add some examples on the stabilization of DNA, RNA, cytoplasmic membrane, and cytoplasmic solute

    An artificial impact on the asteroid (162173) Ryugu formed a crater in the gravity-dominated regime

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    The Hayabusa2 spacecraft investigated the small asteroid Ryugu, which has a rubble-pile structure. We describe an impact experiment on Ryugu using Hayabusa2’s Small Carry-on Impactor. The impact produced an artificial crater with a diameter >10 meters, which has a semicircular shape, an elevated rim, and a central pit. Images of the impact and resulting ejecta were recorded by the Deployable CAMera 3 for >8 minutes, showing the growth of an ejecta curtain (the outer edge of the ejecta) and deposition of ejecta onto the surface. The ejecta curtain was asymmetric and heterogeneous and it never fully detached from the surface. The crater formed in the gravity-dominated regime; in other words, crater growth was limited by gravity not surface strength. We discuss implications for Ryugu’s surface age

    The Antigen ASB4 on Cancer Stem Cells Serves as a Target for CTL Immunotherapy of Colorectal Cancer

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    網羅的なHLAリガンドーム解析により,がん幹細胞(cancer stem cell,CSC)に特異的なASB4由来のペプチドIV9を同定し,CSCを特異的に傷害可能なCTL免疫療法となることを示した.更にCSCを標的としたCTL免疫療法が再発予防として有用であることを明らかにした

    Untyping Typed Algebras and Colouring Cyclic Linear Logic

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    We prove "untyping" theorems: in some typed theories (semirings, Kleene algebras, residuated lattices, involutive residuated lattices), typed equations can be derived from the underlying untyped equations. As a consequence, the corresponding untyped decision procedures can be extended for free to the typed settings. Some of these theorems are obtained via a detour through fragments of cyclic linear logic, and give rise to a substantial optimisation of standard proof search algorithms.Comment: 21

    SUMOylation of the Forkhead Transcription Factor FOXL2 Promotes Its Stabilization/Activation through Transient Recruitment to PML Bodies

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    International audienceBACKGROUND: FOXL2 is a transcription factor essential for ovarian development and maintenance. It is mutated in the genetic condition called Blepharophimosis Ptosis Epicantus inversus Syndrome (BPES) and in cases of isolated premature ovarian failure. We and others have previously shown that FOXL2 undergoes several post-translational modifications. METHODS AND PRINCIPAL FINDINGS: Here, using cells in culture, we show that interference with FOXL2 SUMOylation leads to a robust inhibition of its transactivation ability, which correlates with a decreased stability. Interestingly, FOXL2 SUMOylation promotes its transient recruitment to subnuclear structures that we demonstrate to be PML (Promyelocytic Leukemia) Nuclear Bodies. Since PML bodies are known to be sites where post-translational modifications of nuclear factors take place, we used tandem mass spectrometry to identify new post-translational modifications of FOXL2. Specifically, we detected four phosphorylated, one sulfated and three acetylated sites. CONCLUSIONS: By analogy with other transcription factors, we propose that PML Nuclear Bodies might transiently recruit FOXL2 to the vicinity of locally concentrated enzymes that could be involved in the post-translational maturation of FOXL2. FOXL2 acetylation, sulfation, phosphorylation as well as other modifications yet to be discovered might alter the transactivation capacity of FOXL2 and/or its stability, thus modulating its global intracellular activity

    Polyamines Are Required for Virulence in Salmonella enterica Serovar Typhimurium

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    Sensing and responding to environmental cues is a fundamental characteristic of bacterial physiology and virulence. Here we identify polyamines as novel environmental signals essential for virulence of Salmonella enterica serovar Typhimurium, a major intracellular pathogen and a model organism for studying typhoid fever. Central to its virulence are two major virulence loci Salmonella Pathogenicity Island 1 and 2 (SPI1 and SPI2). SPI1 promotes invasion of epithelial cells, whereas SPI2 enables S. Typhimurium to survive and proliferate within specialized compartments inside host cells. In this study, we show that an S. Typhimurium polyamine mutant is defective for invasion, intracellular survival, killing of the nematode Caenorhabditis elegans and systemic infection of the mouse model of typhoid fever. Virulence of the mutant could be restored by genetic complementation, and invasion and intracellular survival could, as well, be complemented by the addition of exogenous putrescine and spermidine to the bacterial cultures prior to infection. Interestingly, intracellular survival of the polyamine mutant was significantly enhanced above the wild type level by the addition of exogenous putrescine and spermidine to the bacterial cultures prior to infection, indicating that these polyamines function as an environmental signal that primes S. Typhimurium for intracellular survival. Accordingly, experiments addressed at elucidating the roles of these polyamines in infection revealed that expression of genes from both of the major virulence loci SPI1 and SPI2 responded to exogenous polyamines and was reduced in the polyamine mutant. Together our data demonstrate that putrescine and spermidine play a critical role in controlling virulence in S. Typhimurium most likely through stimulation of expression of essential virulence loci. Moreover, our data implicate these polyamines as key signals in S. Typhimurium virulence
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