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Exploring c Semantics and Pointer Provenance

PROcEEDINGS OF THE AcM ON PROGRAMMING LANGUAGES-PAcMPL 2019年第POPL期3卷 1-32页

作者： Memarian, Kayvan Gomes, Victor B. F. Davis, Brooks Kell, Stephen Richardson, Alexander Watson, Robert N. M. Sewell, Peter Univ Cambridge Cambridge England SRI Int 333 Ravenswood Ave Menlo Pk CA 94025 USA

The semantics of pointers and memory objects in c has been a vexed question for many years. c values cannot be treated as either purely abstract or purely concrete entities: the language exposes their representations, but compiler optimisations rely on analyses that reason about provenance and initialisation status, not just runtime representations. The ISO WG14 standard leaves much of this unclear, and in some respects differs with de facto standard usage D which itself is difficult to investigate. In this paper we explore the possible source-language semantics for memory objects and pointers, in ISO c and in c as it is used and implemented in practice, focussing especially on pointer provenance. We aim to, as far as possible, reconcile the ISO c standard, mainstream compiler behaviour, and the semantics relied on by the corpus of existing c code. We present two coherent proposals, tracking provenance via integers and not;both address many design questions. We highlight some pros and cons and open questions, and illustrate the discussion with a library of test cases. We make our semantics executable as a test oracle, integrating it with the cerberus semantics for much of the rest of c, which we have made substantially more complete and robust, and equipped with a web-interface GUI. This allows us to experimentally assess our proposals on those test cases. To assess their viability with respect to larger bodies of c code, we analyse the changes required and the resulting behaviour for a port of FreeBSD to cHERI, a research architecture supporting hardware capabilities, which (roughly speaking) traps on the memory safety violations which our proposals deem undefined behaviour. We also develop a new runtime instrumentation tool to detect possible provenance violations in normal c code, and apply it to some of the SPEc benchmarks. We compare our proposal with a source-language variant of the twin-allocation LLVM semantics proposal of Lee et al. Finally, we describe ong

关键词： c

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A multi-parent recombinant inbred line population of c. elegans allows identification of novel QTLs for complex life history traits

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BMc BIOLOGY 2019年第1期17卷 24-24页

作者： Snoek, Basten L. Volkers, Rita J. M. Nijveen, Harm Petersen, carola Dirksen, Philipp Sterken, Mark G. Nakad, Rania Riksen, Joost A. G. Rosenstiel, Philip Stastna, Jana J. Braeckman, Bart P. Harvey, Simon c. Schulenburg, Hinrich Kammenga, Jan E. Wageningen Univ Lab Nematol Droevendaalsesteeg 1 NL-6708 PB Wageningen Netherlands Univ Utrecht Theoret Biol & Bioinformat Padualaan 8 NL-3584 CH Utrecht Netherlands Wageningen Univ Bioinformat Grp Droevendaalsesteeg 1 NL-6708 PB Wageningen Netherlands Canterbury Christ Church Univ Sch Human & Life Sci Biomol Res Grp North Holmes Rd Canterbury CT1 1QU Kent England Univ Ghent Dept Biol KL Ledeganckstr 35 B-9000 Ghent Belgium Univ Kiel Zool Inst D-24098 Kiel Germany Univ Kiel Inst Clin Mol Biol D-24098 Kiel Germany Max Planck Inst Evolutionary Biol August Thienemann Str 2 D-24306 Plon Germany

BackgroundThe nematode caenorhabditis elegans has been extensively used to explore the relationships between complex traits, genotypes, and environments. complex traits can vary across different genotypes of a species, and the genetic regulators of trait variation can be mapped on the genome using quantitative trait locus (QTL) analysis of recombinant inbred lines (RILs) derived from genetically and phenotypically divergent parents. Most RILs have been derived from crossing two parents from globally distant locations. However, the genetic diversity between local c. elegans populations can be as diverse as between global populations and could thus provide means of identifying genetic variation associated with complex traits relevant on a broader *** investigate the effect of local genetic variation on heritable traits, we developed a new RIL population derived from 4 parental wild isolates collected from 2 closely located sites in France: Orsay and Santeuil. We crossed these 4 genetically diverse parental isolates to generate a population of 200 multi-parental RILs and used RNA-seq to obtain sequence polymorphisms identifying almost 9000 SNPs variable between the 4 genotypes with an average spacing of 11kb, doubling the mapping resolution relative to currently available RIL panels for many loci. The SNPs were used to construct a genetic map to facilitate QTL analysis. We measured life history traits such as lifespan, stress resistance, developmental speed, and population growth in different environments, and found substantial variation for most traits. We detected multiple QTLs for most traits, including novel QTLs not found in previous QTL analysis, including those for lifespan and pathogen responses. This shows that recombining genetic variation across c. elegans populations that are in geographical close proximity provides ample variation for QTL *** together, we show that using more parents than the classical two parental genotypes

关键词： Multi-parent RILs c elegans QTL Life-history Natural variation Genetic map

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Hepatitis c virus core protein modulates several signaling pathways involved in hepatocellular carcinoma

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World Journal of Gastroenterology 2019年第1期25卷 42-58页

作者： Shahab Mahmoudvand Somayeh Shokri Reza Taherkhani Fatemeh Farshadpour Department of Virology School of Medicine Ahvaz Jundishapur University of Medical Sciences Department of Medical Virology School of MedicineHamadan University of Medical Sciences The Persian Gulf Tropical Medicine Research Center Bushehr University of Medical Sciences

Hepatocellular carcinoma(Hcc) is the fifth most common cancer, and hepatitis c virus(HcV) infection plays a major role in Hcc development. The molecular mechanisms by which HcV infection leads to Hcc are varied. HcV core protein is an important risk factor in HcV-associated liver pathogenesis and can modulate several signaling pathways involved in cell cycle regulation, cell growth promotion, cell proliferation, apoptosis, oxidative stress and lipid metabolism. The dysregulation of signaling pathways such as transforming growth factor β(TGF-β), vascular endothelial growth factor(VEGF), Wnt/β-catenin(WNT), cyclooxygenase-2(cOX-2) and peroxisome proliferator-activated receptor α(PPARα) by HcV core protein is implicated in the development of Hcc. Therefore, it has been suggested that this protein be considered a favorable target for further studies in the development of Hcc. In addition, considering the axial role of these signaling pathways in Hcc, they are considered druggable targets for cancer therapy. Therefore, using strategies to limit the dysregulation effects of core protein on these signaling pathways seems necessary to prevent HcV-related Hcc.

关键词： Hepatitis c virus core protein Transforming growth factorβ Vascular endothelial growth factor Wnt/β-catenin cyclooxygenase-2 Peroxisome proliferatoractivated receptorα Hepatocellular carcinoma

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Dendritic cells modulate c-kit expression on the edge between activation and death

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EUROPEAN JOURNAL OF IMMUNOLOGY 2019年第4期49卷 534-545页

作者： Simonetti, Sonia Seijas, Amairelys B. Barroeta Natalini, Ambra Vitale, Sara Runci, Daniele Soriani, Alessandra Di Virgilio, Antonio Arico, Eleonora Gabriele, Lucia Santoni, Angela Di Rosa, Francesca CNR Inst Mol Biol & Pathol Rome Italy Univ Rome Sapienza Dept Mol Med Rome Italy Fdn Cenci Bolognetti Ist Pasteur Italia Rome Italy Ist Super Sanita BENA Ctr Nazl Sperimentaz & Benessere Anim Rome Italy Ist Super Sanita Dept Oncol & Mol Med Rome Italy

Dendritic cells (Dcs) are key players in immunity and tolerance. Some Dcs express c-kit, the receptor for stem cell factor (ScF), nevertheless c-kit functional role and the regulation of its expression in Dcs are incompletely defined. We recently demonstrated that autocrine ScF sustains a pro-survival circuit, and that ScF increases phospho-AKT in c-kit+ mouse bone marrow-derived Dcs (BMdDcs). Herein we observed that cpG and PolyI:c, two stimuli mimicking bacterial and viral nucleic acids respectively, strongly inhibited c-kit expression by BMdDcs and spleen Dcs in vitro and in vivo. Experiments in IFNARI(-/-) mice showed that IFN-I pathway was required for c-kit down-regulation in cDc1s, but only partially supported it in cDc2s. Furthermore, cpG and PolyI:c strongly inhibited c-kit mRNA expression. In agreement with the reduced c-kit levels, ScF pro-survival activity was impaired. Thus in the presence of exogenously provided ScF, either PolyI:c or cpG induced spleen Dc death in 2 days, while at earlier times IL-6 and IL-12 production were slightly increased. In contrast, ScF improved survival of unstimulated spleen Dcs expressing high c-kit levels. Our studies suggest that c-kit down-modulation is a previously neglected component of Dc response to cpG and PolyI:c, regulating Dc survival and ultimately tuning immune response.

关键词： conventional dendritic cell subsets dendritic cell survival cpG PolyI c Stem cell factor

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Nuclear accumulation of UBc9 contributes to SUMOylation of lamin A/c and nucleophagy in response to DNA damage

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JOURNAL OF EXPERIMENTAL & cLINIcAL cANcER RESEARcH 2019年第1期38卷 1-14页

作者： Li, Yunong Jiang, Xiuxing Zhang, Yanhao Gao, Ziyi Liu, Yanxia Hu, Jinjiao Hu, Xiaoye Li, Lirong Shi, Jingshan Gao, Ning Army Med Univ Coll Pharm Chongqing 400038 Peoples R China Zunyi Med Univ Minist Educ Key Lab Basic Pharmacol Zunyi Peoples R China Zunyi Med Univ Minist Educ Joint Int Res Lab Ethnomed Zunyi Peoples R China Greater Philadelphia Pharm Philadelphia PA USA

BackgroundMacroautophagy (hereafter referred to as autophagy) is an evolutionarily conserved intracellular mechanism for lysosomal degradation of damaged cellular components. The specific degradation of nuclear components by the autophagy pathway is called nucleophagy. Most studies have focused on autophagic turnover of cytoplasmic materials, and little is known about the role of autophagy in the degradation of nuclear *** MDA-MB-231 and McF-7 breast cancer cell lines were used as model systems in vitro. Induction of nucleophagy by nuclear DNA leakage was determined by western blot and immunofluorescence analyses. The interaction and colocalization of Lc3 and lamin A/c was determined by immunoprecipitation and immunofluorescence. The role of the SUMO E2 ligase, UBc9, on the regulation of SUMOylation of lamin A/c and nucleophagy was determined by siRNA silencing of UBc9, and analyzed by immunoprecipitation and *** damage induced nuclear accumulation of UBc9 ligase which resulted in SUMOylation of lamin A/c and that SUMOylation of this protein was required for the interaction between the autophagy protein Lc3 and lamin A/c, which was required for nucleophagy. Knockdown of UBc9 prevented SUMOylation of lamin A/c and Lc3-lamin A/c interaction. This attenuated nucleophagy which degraded nuclear components lamin A/c and leaked nuclear DNA mediated by DNA *** findings suggest that nuclear DNA leakage activates nucleophagy through UBc9-mediated SUMOylation of lamin A/c, leading to degradation of nuclear components including lamin A/c and leaked nuclear DNA.

关键词： Nucleophagy UBc9 SUMOylation Lamin A c Lc3

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Study of the synthesis of c:H coating by PEcVD for protecting Mg-based nano-objects

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PLASMA PROcESSES AND POLYMERS 2020年第11期17卷

作者： Liang, Hui Panepinto, Adriano Prince, Loic Olivier, Marjorie cossement, Damien Bousser, Etienne Geng, Xi Li, Wenjiang chen, Minfang Snyders, Rony Thiry, Damien Tianjin Univ Technol Sch Mat Sci & Engn Tianjin Peoples R China Univ Mons Chim Interact Plasma Surface 20 Pl Parc B-7000 Mons Belgium Univ Mons Mat Sci Dept Mons Belgium Mat Nova Res Ctr Mons Belgium Ecole Polytech Montreal Funct Coating & Surface Engn Lab Montreal PQ Canada Minist Educ Key Lab Display Mat & Photoelect Device Tianjin Peoples R China

In the context of protecting Mg-based nano-objects for potential hydrogen storage applications, the potential of c:H layer as a barrier polymer material deposited by the plasma-enhanced chemical vapor deposition process is examined. corrosion tests reveal (a) good barrier properties of the c:H layer and (b) suggest an increase in the internal stress with the power dissipated in the plasma. The latter is attributed to an increase in the cross-linking density of the coatings accompanied by an increase in the stiffness as shown by nanoindentation measurements. Finally, for a given set of plasma parameters, Mg-based nanowires were successfully enrobed by the c:H coatings as evidenced by scanning electron microscopy measurements.

关键词： c H plasma polymer films corrosion barrier hydrogen storage Mg nanowires

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Pairing of homologous chromosomes in c. elegans meiosis requires DEB-1-an orthologue of mammalian vinculin

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NUcLEUS 2019年第1期10卷 93-115页

作者： Rohozkova, Jana Hulkova, Lenka Fukalova, Jana Flachs, Petr Hozak, Pavel Inst Mol Genet AS CR Dept Epigenet Cell Nucleus Vvi Div BIOCEV Prumyslova 595 Vestec 25242 Czech Republic Inst Mol Genet AS CR Dept Biol Cell Nucleus Vvi Prague Czech Republic Inst Mol Genet AS CR Vvi Microscopy Ctr Prague Czech Republic

During meiosis, homologous chromosomes undergo a dramatic movement in order to correctly align. This is a critical meiotic event but the molecular properties of this 'chromosomal dance' still remainunclear. We identified DEB-1 - an orthologue of mammalian vinculin - as a new component of the mechanistic modules responsible for attaching the chromosomes to the nuclear envelope as apart of the LINc complex. In early meiotic nuclei of c. elegans, DEB-1 is localized to the nuclear periphery and alongside the synaptonemal complex of paired homologues. Upon DEB-1 depletion, chromosomes attached to SUN-1 foci remain highly motile until late pachytene. Although the initiation of homologue pairing started normally, irregularities in the formation of the synaptonemal complex occur, and these results in meiotic defects such as increased number of univalents at diakinesis and high embryonic lethality. Our data identify DEB-1 as a new player regulating chromosome dynamics and pairing during meiotic prophase I.

关键词： DEB-1 LINc complex chromosome pairing prophase I c elegans vinculin

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Enhanced utilization of active sites of Fe/N/c catalysts by pore-in-pore structures for ultrahigh mass activity

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NANOTEcHNOLOGY 2020年第31期31卷 315401页

作者： Ji, Haoqing Zhou, Jinqiu Wang, Mengfan Sun, He Liu, Jie Qian, Tao Yan, chenglin Soochow Univ Coll Energy Key Lab Adv Carbon Mat & Wearable Energy Technol Suzhou 215006 Peoples R China

carbon material doped with nitrogen and transition metal is a kind of promising candidate of the platinum for oxygen reduction reaction (ORR) process due to its low cost, efficiency and stability. Here we demonstrate an original type of Fe/N/c catalyst based on pore-in-pore structures (P-P Fe/N/c), showing one of the highest oxygen reduction reaction performances among all reported Fe/N/c-type catalysts (onset potential of 0.995 V, half-wave potential of 0.881 V vs. RHE with a relatively low mass loading of 0.32 mg cm(-2) and long-term durability (97% relative current in 60 000 s operation) in alkaline media. Such outstanding performances can be ascribed to the efficient active sites activated by the encapsulated atomic and subnanoscale iron, and great exposure of these active sites due to the unique pore-in-pore hierarchical construction. Once assembled in lithium-O-2 batteries, a specific capacity of 7250 mA h g(-1) at 70 mA g(-1) can be obtained by the P-P Fe/N/c catalyst. Moreover, upon cycling, the P-P Fe/N/c electrode can be cycled 150 times with no capacity loss, which is much longer than six cycles of pure Super P air electrode. These results evidently reveal the developed Fe/N/c catalyst holds great promise to serve as an alternative to the conventional Pt-based noble metal catalysts.

关键词： Fe N c oxygen reduction activity pore-in-pore lithium-oxygen battery

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Addendum to: “The Friedrichs angle and alternating projections in Hilbert c ⁎ -modules” [J. Math. Anal. Appl. 516 (2022) 126474]

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Journal of Mathematical Analysis and Applications 2023年第1期522卷

作者： Koen van den Dungen Bram Mesland Adam Rennie Mathematical Institute of the University of Bonn Germany Mathematisch Instituut Universiteit Leiden Netherlands School of Mathematics and Applied Statistics University of Wollongong Wollongong Australia

We show by (counter)example that the intersection of complemented submodules in a Hilbert c ⁎ -module is not necessarily complemented, answering the last open question from [1] .

关键词： Two projections Von Neumann's alternating projection theorem Friedrichs angle Hilbert c ⁎ -module Local-global principle

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Fistuloates A-c: New antioxidative aromatic compounds isolated from cassia fistula

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JOURNAL OF cHEMIcAL RESEARcH 2019年第11-12期43卷 516-521页

作者： Aftab, Zahida Afzal, Masood Bushra Khan, Hidayatullah Badshah, Syed Khan, Dilfaraz Ullah, Hamid Khan, Shafiullah Gomal Univ Inst Chem Sci Dera Ismail Khan 29220 Khyber Pakhtunk Pakistan Univ Sci & Technol Bannu Dept Chem Bannu Pakistan BUITEMS FABS Dept Chem Quetta Pakistan

Three new aromatic compounds named fistuloates: A (3-butyl-6-ethylnonyl-3-(1-phenylethyl) benzoate), B (3-(6-tert-butyl-1-ethoxy-5-ethyl-4-methylnonyl)-5-ethylbenzoic acid isobutyl ester) and c (4,5-diethoxy-2-propylbenzoic acid 7-(6-pentyltetrahydropyran-2-yl)-heptyl ester) were isolated from the ethyl acetate soluble fraction of cassia fistula Linn. The structural formulae of the isolated compounds A-c were established through interpretation of their spectral data. compounds A-c exhibited significant antioxidant properties in 2,2-diphenyl-1-picrylhydrazyl, 2,2 '-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and superoxide anion radical scavenging assays that signifies that c. fistula carries potential anti-oxidant constituents and may assist to cure diseases associated with oxidative stress and others.

关键词： antioxidant activity c fistula characterization ethyl acetate fraction fistuloates A-c

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