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201. Closing the Gap – The Formally Verified Optimizing Compiler CompCert

Author

Kästner, Daniel, Leroy, Xavier, Blazy, Sandrine, Schommer, Bernhard, Schmidt, Michael, Ferdinand, Christian, AbsInt GmbH (Angewandte Informatik), AbsInt, Programming languages, types, compilation and proofs (GALLIUM), Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Software certification with semantic analysis (CELTIQUE), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-LANGAGE ET GÉNIE LOGICIEL (IRISA-D4), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), ITEA 3 project ASSUME, Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1)

Subjects
[INFO.INFO-PL]Computer Science [cs]/Programming Languages [cs.PL], TheoryofComputation_LOGICSANDMEANINGSOFPROGRAMS
Abstract

International audience; CompCert is the first commercially available optimizing compiler that is formally verified, using machine-assisted mathematical proofs, to be free from miscompilation. The executable code it produces is proved to behave exactly as specified by the semantics of the source C program. CompCert's intended use is the compilation of safety-critical and mission-critical software meeting high levels of assurance. This article gives an overview of the design of CompCert and its proof concept, summarizes the resulting confidence argument, and gives an overview of relevant tool qualification strategies. We briefly summarize practical experience and give an overview of recent CompCert developments.

Published
2017

203. Integrated Multi-omic Analysis of Esthesioneuroblastomas Identifies Two Subgroups Linked to Cell Ontogeny

Author

Classe, Marion, primary, Yao, Hui, additional, Mouawad, Roger, additional, Creighton, Chad J., additional, Burgess, Alice, additional, Allanic, Frederick, additional, Wassef, Michel, additional, Leroy, Xavier, additional, Verillaud, Benjamin, additional, Mortuaire, Geoffrey, additional, Bielle, Franck, additional, Le Tourneau, Christophe, additional, Kurtz, Jean-Emmanuel, additional, Khayat, David, additional, Su, Xiaoping, additional, and Malouf, Gabriel G., additional

Published
2018
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205. Abstract LB-114: a-TIGIT antagonist antibody EOS884448 shows dual mechanism of action by restoration of T cell effector functions and preferential depletion of Treg

Author

LEROY, XAVIER, primary, Hoofd, Catherine, additional, Cuende, Julia, additional, Denies, Sofie, additional, Rabolli, Virginie, additional, Preillon, Julie, additional, Lambolez, Florence, additional, Prasad, Shruthi, additional, Mercier, Marjorie, additional, Nyawouame, Florence, additional, Bodo, Véronique, additional, Wald, Noémie, additional, Driessens, Grégory, additional, and Detheux, Michel, additional

Published
2018
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206. Abstract LB-291: EOS100850, an insurmountable and non-brain penetrant A2A receptor antagonist, inhibits adenosine-mediated T cell suppression, demonstrates anti-tumor activity and exhibits best-in class characteristics

Author

Houthuys, Erica, primary, Marillier, Reece, additional, Deregnaucourt, Théo, additional, Brouwer, margreet, additional, Basilico, Paola, additional, Pirson, Romain, additional, Marchante, Joao, additional, Prasad, Shruthi, additional, Hermant, Annelise, additional, Nyawouame, Florence, additional, Preillon, Julie, additional, Frederix, Kim, additional, Michaux, Anne Catherine, additional, Lambolez, Florence, additional, Swiercz, Jakub, additional, Driessens, Gregory, additional, Wald, Noemie, additional, Martinoli, Chiara, additional, Bodo, Veronique, additional, Detheux, Michel, additional, Leroy, Xavier, additional, and Crosignani, Stefano, additional

Published
2018
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210. Biphasic papillary renal cell carcinoma is a rare morphological variant with frequent multifocality: a study of 28 cases

Author

Trpkov, Kiril, primary, Athanazio, Daniel, additional, Magi-Galluzzi, Cristina, additional, Yilmaz, Helene, additional, Clouston, David, additional, Agaimy, Abbas, additional, Williamson, Sean R, additional, Brimo, Fadi, additional, Lopez, Jose I, additional, Ulamec, Monika, additional, Rioux-Leclercq, Nathalie, additional, Kassem, Maysoun, additional, Gupta, Nilesh, additional, Hartmann, Arndt, additional, Leroy, Xavier, additional, Bashir, Samir Al, additional, Yilmaz, Asli, additional, and Hes, Ondřej, additional

Published
2018
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211. Benchmarking implementations of functional languages with ‘Pseudoknot', a float-intensive benchmark

Author

Hartel, Pieter H., Feeley, Marc, Alt, Martin, Augustsson, Lennart, Baumann, Peter, Beemster, Marcel, Chailloux, Emmanuel, Flood, Christine H., Grieskamp, Wolfgang, Van Groningen, John H. G., Hammond, Kevin, Hausman, Bogumil, Ivory, Melody Y., Jones, Richard E., Kamperman, Jasper, Lee, Peter, Leroy, Xavier, Lins, Rafael D., Loosemore, Sandra, Röjemo, Niklas, Serrano, Manuel, Talpin, Jean-Pierre, Thackray, Jon, Thomas, Stephen, Walters, Pum, Weis, Pierre, Wentworth, Peter, Hartel, Pieter H., Feeley, Marc, Alt, Martin, Augustsson, Lennart, Baumann, Peter, Beemster, Marcel, Chailloux, Emmanuel, Flood, Christine H., Grieskamp, Wolfgang, Van Groningen, John H. G., Hammond, Kevin, Hausman, Bogumil, Ivory, Melody Y., Jones, Richard E., Kamperman, Jasper, Lee, Peter, Leroy, Xavier, Lins, Rafael D., Loosemore, Sandra, Röjemo, Niklas, Serrano, Manuel, Talpin, Jean-Pierre, Thackray, Jon, Thomas, Stephen, Walters, Pum, Weis, Pierre, and Wentworth, Peter

Abstract

Over 25 implementations of different functional languages are benchmarked using the same program, a floating-point intensive application taken from molecular biology. The principal aspects studied are compile time and execution time for the various implementations that were benchmarked. An important consideration is how the program can be modified and tuned to obtain maximal performance on each language implementation. With few exceptions, the compilers take a significant amount of time to compile this program, though most compilers were faster than the then current GNU C compiler (GCC version 2.5.8). Compilers that generate C or Lisp are often slower than those that generate native code directly: the cost of compiling the intermediate form is normally a large fraction of the total compilation time. There is no clear distinction between the runtime performance of eager and lazy implementations when appropriate annotations are used: lazy implementations have clearly come of age when it comes to implementing largely strict applications, such as the Pseudoknot program. The speed of C can be approached by some implementations, but to achieve this performance, special measures such as strictness annotations are required by non-strict implementations. The benchmark results have to be interpreted with care. Firstly, a benchmark based on a single program cannot cover a wide spectrum of ‘typical' applications. Secondly, the compilers vary in the kind and level of optimisations offered, so the effort required to obtain an optimal version of the program is similarly varied

Published
2017

212. TMPRSS2-ERG fusion promotes prostate cancer metastases in bone.

Author

Deplus, Rachel, Delliaux, Carine, Marchand, Nathalie, Flourens, Anne, Vanpouille, Nathalie, Leroy, Xavier, De Launoit, Yvan, Duterque-Coquillaud, Martine, Deplus, Rachel, Delliaux, Carine, Marchand, Nathalie, Flourens, Anne, Vanpouille, Nathalie, Leroy, Xavier, De Launoit, Yvan, and Duterque-Coquillaud, Martine

Abstract

Bone metastasis is the major deleterious event in prostate cancer (PCa). TMPRSS2-ERG fusion is one of the most common chromosomic rearrangements in PCa. However, its implication in bone metastasis development is still unclear. Since bone metastasis starts with the tropism of cancer cells to bone through specific migratory and invasive processes involving osteomimetic capabilities, it is crucial to better our understanding of the influence of TMPRSS2-ERG expression in the mechanisms underlying the bone tropism properties of PCa cells. We developed bioluminescent cell lines expressing the TMPRSS2-ERG fusion in order to assess its role in tumor growth and bone metastasis appearance in a mouse model. First, we showed that the TMPRSS2-ERG fusion increases cell migration and subcutaneous tumor size. Second, using intracardiac injection experiments in mice, we showed that the expression of TMPRSS2-ERG fusion increases the number of metastases in bone. Moreover, TMPRSS2-ERG affects the pattern of metastatic spread by increasing the incidence of tumors in hind limbs and spine, which are two of the most frequent sites of human PCa metastases. Finally, transcriptome analysis highlighted a series of genes regulated by the fusion and involved in the metastatic process. Altogether, our work indicates that TMPRSS2-ERG increases bone tropism of PCa cells and metastasis development., info:eu-repo/semantics/published

Published
2017

214. Formally Verifying a Compiler: What Does It Mean, Exactly? (Invited Talk)

Author

Leroy, Xavier

Subjects
000 Computer science, knowledge, general works, Computer Science
Abstract

Compilers, and especially optimizing compilers, are complicated programs. Bugs in compilers happen, and can lead to miscompilation: the production of wrong executable code from a correct source program. Miscompilation is documented in the literature and a concern for high-assurance software, as it endangers the guarantees obtained by source-level formal verification of programs. Compiler verification is a radical solution to the miscompilation problem: by applying program proof to the compiler itself, we can obtain mathematically strong guarantees that the generated executable code is faithful to the semantics of the source program. The state of the art in this line of research is arguably the CompCert verified compiler. This talk will give an overview of this optimizing C compiler and of its formal verification, conducted with the Coq proof assistant. A formal verification is as good as the specifications it uses. In other words, verification reduces the problem of trusting a large implementation to that of ensuring that its formal specification enforce the intended correctness properties. In the case of CompCert, the correctness statement that is proved is rather complex, as it involves large operational semantics (for the C language and for the assembly languages of the target architectures) and simulations between these semantics that support both choice refinement and behavior refinement. The talk will review and discuss these elements of the specification, along with some of the accompanying proof principles.

Published
2016
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216. Expanding the clinicopathological spectrum of succinate dehydrogenase-deficient renal cell carcinoma with a focus on variant morphologies: a study of 62 new tumors in 59 patients

Author

Fuchs, Talia L., Maclean, Fiona, Turchini, John, Vargas, A. Cristina, Bhattarai, Selina, Agaimy, Abbas, Hartmann, Arndt, Kao, Chia-Sui, Ellis, Carla, Bonert, Michael, Leroy, Xavier, Kunju, Lakshmi P., Schwartz, Lauren, Matsika, Admire, Williamson, Sean R., Rao, Priya, Divatia, Mukul, Guarch, Rosa, Algaba, Ferran, Balancin, Marcelo L., Zhou, Ming, Samaratunga, Hemamali, da Cunha, Isabela Werneck, Brimo, Fadi, Ryan, Andrew, Clouston, David, Aron, Manju, O’Donnell, Marie, Chan, Emily, Hirsch, Michelle S., Moch, Holger, Pang, Chun-Yin, Wah, Cheuk, Yin, Weihua, Perry-Keene, Joanna, Yilmaz, Asli, Chou, Angela, Clarkson, Adele, van der Westhuizen, Gerhard, Morrison, Ella, Zwi, Jonathan, Hes, Ondrej, Trpkov, Kiril, and Gill, Anthony J.

Abstract

Most succinate dehydrogenase (SDH)-deficient renal cell carcinomas (RCCs) demonstrate stereotypical morphology characterized by bland eosinophilic cells with frequent intracytoplasmic inclusions. However, variant morphologic features have been increasingly recognized. We therefore sought to investigate the incidence and characteristics of SDH-deficient RCC with variant morphologies. We studied a multi-institutional cohort of 62 new SDH-deficient RCCs from 59 patients. The median age at presentation was 39 years (range 19–80), with a slight male predominance (M:F = 1.6:1). A relevant family history was reported in 9 patients (15%). Multifocal or bilateral tumors were identified radiologically in 5 patients (8%). Typical morphology was present at least focally in 59 tumors (95%). Variant morphologies were seen in 13 (21%) and included high-grade nuclear features and various combinations of papillary, solid, and tubular architecture. Necrosis was present in 13 tumors, 7 of which showed variant morphology. All 62 tumors demonstrated loss of SDHB expression by immunohistochemistry. None showed loss of SDHA expression. Germline SDHmutations were reported in all 18 patients for whom the results of testing were known. Among patients for whom follow-up data was available, metastatic disease was reported in 9 cases, 8 of whom had necrosis and/or variant morphology in their primary tumor. Three patients died of disease. In conclusion, variant morphologies and high-grade nuclear features occur in a subset of SDH-deficient RCCs and are associated with more aggressive behavior. We therefore recommend grading all SDH-deficient RCCs and emphasize the need for a low threshold for performing SDHB immunohistochemistry in any difficult to classify renal tumor, particularly if occurring at a younger age.

Published
2021
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217. Signet-ring cell adenocarcinoma of sinonasal tract: an immunohistochemical study of the mucins profile

Author

Castillo, Christine, Buob, David, Mortuaire, Geoffrey, Chevalier, Dominique, Aubert, Sebastien, Copin, Marie-Christine, and Leroy, Xavier

Subjects
Immunohistochemistry -- Usage, Nose cancer -- Diagnosis, Nose cancer -- Care and treatment, Nose cancer -- Development and progression, Nose cancer -- Genetic aspects, Nose cancer -- Research, Tumor suppressor genes -- Physiological aspects, Tumor suppressor genes -- Research
Abstract

Context.--Adenocarcinomas of the sinonasal tract are classified into 4 categories: salivary-type, intestinal-type, nonintestinal-type, and metastatic. Signet-ring cell carcinoma is the rarest form of intestinal-type adenocarcinoma. Only isolated cases have been reported in the literature. Objective.--To evaluate clinical attributes, morphology, and immunohistochemistry in signet-ring cell carcinoma of the sinonasal tract. Design.--Seventy-three cases of primary sinonasal adenocarcinomas were retrieved from the files. Only 5 signet-ring cell adenocarcinomas (tumors composed of more than 90% signet-ring cells) were identified. In all cases, clinical data and histologic slides were available and were reviewed. Consecutive tissue sections were immunostained with monoclonal antibodies against MUC2, MUC5AC, MUC5B, MUC6, p53 protein, and MIB-1. Results.--Four of our 5 patients were woodworkers. They were treated by surgical excision and radiotherapy. Patient follow-up ranged from 11 to 84 months. Three patients presented an unfavorable evolution and died of metastatic spread. Microscopically, the tumors produced abundant mucin deposits, which accumulated in large extracellular pools. Tumor cells were predominantly signet-ring cells floating in the pools of mucin. The mucins profile was [MUC2.sup.+], [MUC5AC.sup.+], [MUC5B.sup.+], and [MUC6.sup.-]. Eighty percent of cells were immunostained by p53 protein antibody and 60% cells with MIB-1 antibody. Conclusions.--The mucin profile is similar to the profile described in digestive tract adenocarcinoma. It is not useful to differentiate between metastatic adenocarcinoma and primary intestinal-type sinonasal adenocarcinoma. Clinical data and immunochemistry with p53 protein and MIB-1 confirm that sinonasal signet-ring cell carcinoma is a high-grade and aggressive tumor., Adenocarcinomas, with exclusion of salivary gland types, represent about 3.8% of all primary malignant neoplasms of the sinonasal tract. (1) Sinonasal tract adenocarcinomas are classified as salivary-type, intestinal-type, nonintestinal-type, and [...]

Published
2007

218. Renal cell carcinoma with rhabdoid features: an aggressive neoplasm with overexpression of p53

Author

Leroy, Xavier, Zini, Laurent, Buob, David, Ballereau, Charles, Villers, Arnauld, and Aubert, Sebastien

Subjects
Immunohistochemistry -- Observations -- Case studies, Tumor proteins -- Research -- Case studies, Carcinoma, Renal cell -- Case studies -- Research, Health
Abstract

* Context.--Adult renal cell carcinoma (RCC) with rhabdoid features is a recently recognized morphologic variant of kidney carcinoma. To date, only very few studies have been published on this subject [...]

Published
2007

220. Targeting miR-21 decreases expression of multi-drug resistant genes and promotes chemosensitivity of renal carcinoma

Author

Gaudelot, Kelly, primary, Gibier, Jean-Baptiste, additional, Pottier, Nicolas, additional, Hémon, Brigitte, additional, Van Seuningen, Isabelle, additional, Glowacki, François, additional, Leroy, Xavier, additional, Cauffiez, Christelle, additional, Gnemmi, Viviane, additional, Aubert, Sébastien, additional, and Perrais, Michaël, additional

Published
2017
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224. Incidence, clinicopathological features and fusion transcript landscape of translocation renal cell carcinomas

Author

Classe, Marion, primary, Malouf, Gabriel G, additional, Su, Xiaoping, additional, Yao, Hui, additional, Thompson, Erika J, additional, Doss, Denaha J, additional, Grégoire, Valérie, additional, Lenobin, Julien, additional, Fantoni, Jean-Christophe, additional, Sudour-Bonnange, Hélène, additional, Khayat, David, additional, Aubert, Sébastien, additional, Tannir, Nizar M, additional, and Leroy, Xavier, additional

Published
2017
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227. Tuberous sclerosis complex: Hamartin and tuberin expression in renal cysts and its discordant expression in renal neoplasms

Author

Bonsib, Stephen M., primary, Boils, Christie, additional, Gokden, Neriman, additional, Grignon, David, additional, Gu, Xin, additional, Higgins, John P.T., additional, Leroy, Xavier, additional, McKenney, Jesse K., additional, Nasr, Samih H., additional, Phillips, Carrie, additional, Sangoi, Ankur R., additional, Wilson, Jon, additional, and Zhang, Ping L., additional

Published
2016
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228. CPP '15: Proceedings of the 2015 Conference on Certified Programs and Proofs

Author

Leroy, Xavier, Tiu, Alwen, Programming languages, types, compilation and proofs (GALLIUM), Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), School of Computer Engineering [Singapore], and Nanyang Technological University [Singapour]

Subjects
[INFO.INFO-PL]Computer Science [cs]/Programming Languages [cs.PL]
Abstract

International audience; he CPP series of meetings aims to cover those topics in computer science and mathematics in which certification via formal techniques is crucial. Topics of interest range from interactive and automated theorem proving to program proof to the mechanization of mathematics, with the production of independently-checkable certificates as a recurring theme

Published
2015

239. Formally Verifying a Compiler: What Does It Mean, Exactly? (Invited Talk)

Author

Xavier Leroy, Leroy, Xavier, Xavier Leroy, and Leroy, Xavier

Abstract

Compilers, and especially optimizing compilers, are complicated programs. Bugs in compilers happen, and can lead to miscompilation: the production of wrong executable code from a correct source program. Miscompilation is documented in the literature and a concern for high-assurance software, as it endangers the guarantees obtained by source-level formal verification of programs. Compiler verification is a radical solution to the miscompilation problem: by applying program proof to the compiler itself, we can obtain mathematically strong guarantees that the generated executable code is faithful to the semantics of the source program. The state of the art in this line of research is arguably the CompCert verified compiler. This talk will give an overview of this optimizing C compiler and of its formal verification, conducted with the Coq proof assistant. A formal verification is as good as the specifications it uses. In other words, verification reduces the problem of trusting a large implementation to that of ensuring that its formal specification enforce the intended correctness properties. In the case of CompCert, the correctness statement that is proved is rather complex, as it involves large operational semantics (for the C language and for the assembly languages of the target architectures) and simulations between these semantics that support both choice refinement and behavior refinement. The talk will review and discuss these elements of the specification, along with some of the accompanying proof principles.

Published
2016
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240. Bilateral Renal Oncocytosis With Renal Failure

Author

Leroy, Xavier, Lemaitre, Laurent, De La Taille, Alexandre, Hazzan, Marc, Delepaul, Bruno, Couturier, Jerome, and Gosselin, Bernard

Subjects
Chronic kidney failure -- Causes of -- Complications and side effects, Epithelial tumors -- Causes of -- Complications and side effects, Carcinoma, Renal cell -- Complications and side effects, Health
Abstract

* Oncocytosis is a term recently used to describe diffuse renal involvement by numerous oncocytic nodules. We report herein a case of a 53-year-old man with end-stage renal disease requiring hemodialysis. His kidneys were involved by numerous tumors. Histologic examination revealed more than 100 oncocytomas and an associated papillary renal cell carcinoma in the right kidney. (Arch Pathol Lab Med. 2001;125:683-685), Immunohistochemical and Cytogenetic Study of a Case Associated With a Papillary Renal Cell Carcinoma Oncocytoma is a benign epithelial tumor representing approximately 5% to 7% of all primary renal neoplasms. [...]

Published
2001

241. Inflammatory Pseudotumor of the Renal Pelvis

Author

Leroy, Xavier, Copin, Marie-Christine, Graziana, Jean Pierre, Wacrenier, Agnes, and Gosselin, Bernard

Subjects
Kidney diseases -- Research, Pelvic inflammatory disease -- Research
Abstract

* We describe 2 cases of inflammatory pseudotumor of the renal pelvis. Case 1, the male patient, was 37 years old, and case 2, the female patient, was 54 years old. Both patients presented with macroscopic hematuria and flank pain. Computed topographic (CT) scan and ureterocystoscopy revealed in case 1 a mass in the left renal pelvis and the calyces. In case 2, urography showed a lacuna of the renal pelvis, and CT scan showed an irregular thickening of the renal pelvis. In both cases, the preoperative clinical diagnosis was urothelial carcinoma, and both patients underwent nephrectomy. Microscopic examination revealed in case 1 a tumor of the renal pelvis composed of spindle cells with eosinophilic cytoplasm in a myxold and vascular stroma with abundant inflammatory infiltrate. In case 2, the tumor was composed of densely basophilic spindle cells in a fascicular pattern intermingled with lymphocytes and plasma cells and involving the lamina propria of the renal pelvis. The spindle cells reacted strongly with antibody to vimentin and focally with antibodies to smooth muscle actin and muscle-specific actin. In the urogenital tract inflammatory pseudotumor involves preferentially the urinary bladder. Rare cases have been reported in the kidney. The 2 cases presented here are unusual due to the location in the renal pelvis, mimicking urothelial carcinoma. (Arch Pathol Lab Med. 2000;124:1209-1212), A Report of 2 Cases With Clinicopathologic and Immunohistochemical Study Inflammatory pseudotumor (IPT), also termed inflammatory myofibroblastic tumor was first described in the lung. It is a pseudosarcomatous neoplasm now [...]

Published
2000

242. Type-Based Analysis of Uncaught Exceptions

Author

LEROY, XAVIER and PESSAUX, FRANCOIS

Abstract

1. INTRODUCTION Many modern programming languages such as Ada, Modula-3, ML, and Java provide built-in support for exceptions: raising an exception at some program point transfers control to the nearest […], This article presents a program analysis to estimate uncaught exceptions in ML programs. This analysis relies on unification-based type inference in a nonstandard type system, using rows to approximate both the flow of escaping exceptions (a la effect systems) and the flow of result values (a la control-flow analyses). The resulting analysis is efficient and precise; in particular, arguments carried by exceptions are accurately handled. Categories and Subject Descriptors: D.2.5 [Software Engineering]: Testing and Debugging--Error handling and recovery; Symbolic execution; D.3.2 [Programming Languages]: Language Classifications--Applicative (functional) languages; ML; F.3.2 [Logics and Meanings of Programs]: Semantics of Programming Languages--Program analysis; Operational semantics; F.3.3 [Logics and Meanings of Programs]: Studies of Program Constructs--Control primitives; Type structure General Terms: Languages, Reliability, Theory Additional Key Words and Phrases: Caml, exceptions, polymorphism, rows, static debugging, SML, type and effect systems, type inference

Published
2000

243. Formal verification of a static analyzer: abstract interpretation in type theory

Author

Leroy, Xavier, Programming languages, types, compilation and proofs (GALLIUM), Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), and ANR-11-INSE-0003,VERASCO,Vérification formelle d'analyseurs statiques et de compilateurs(2011)

Subjects
[INFO.INFO-PL]Computer Science [cs]/Programming Languages [cs.PL]
Abstract

International audience; This invited talk describes the logical foundations and the status of the ongoing Verasco project, whose aim is to formalize and prove sound a static analyzer for the C programming language based on abstract interpretation, using the Coq proof assistant. (Joint work with David Pichardie, Sandrine Blazy, Jacques-Henri Jourdan, and Vincent Laporte.)

Published
2014

244. Proof assistants in computer science research

Author

Leroy, Xavier, Programming languages, types, compilation and proofs (GALLIUM), Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institut Henri Poincaré, and ANR-11-INSE-0003,VERASCO,Vérification formelle d'analyseurs statiques et de compilateurs(2011)

Subjects
[INFO.INFO-PL]Computer Science [cs]/Programming Languages [cs.PL], TheoryofComputation_LOGICSANDMEANINGSOFPROGRAMS
Abstract

International audience; This invited talk reflects on how the use of proof assistants is changing the way we do research in various areas of computer science. Three examples are presented: programming languages metatheory (the POPLmark challenge), deductive verification of software (the seL4 project), and formally-verified compilation (the CompCert project).

Published
2014

245. Prognostic value of microRNA expression pattern in upper tract urothelial carcinoma

Author

Izquierdo Reyes, Laura, Ingelmo-Torres, Mercedes, Mallofré i Gómez, Carme, Lozano Salvatella, Juan José, Verhasselt-Crinquette, Marie, LeRoy, Xavier, Colin, Pierre, Comperat, Eva, Roupret, Morgan, Alcaraz Asensio, Antonio, Mengual Brichs, Lourdes, and Universitat de Barcelona

Subjects
Micro RNAs, MicroRNAs, Reacció en cadena de la polimerasa, Càncer, Malalties de l'aparell urinari, Diseases of the urinary organs, Cancer, Polymerase chain reaction
Abstract

OBJECTIVE: To examine the microRNA (miRNA) expression pattern in tumour samples from patients with progressing and non-progressing upper tract urothelial carcinoma (UTUC) in order to identify putative miRNAs that may be used as prognostic markers. PATIENTS AND METHODS: We conducted a multicentre, retrospective study of formalin-fixed paraffin-embedded tissue samples from 150 patients with UTUC who had undergone radical nephroureterectomy. Global miRNA expression patterns were analysed in 18 selected samples from patients with UTUC using TaqMan arrays. The differential expression of five key miRNAs was validated by quantitative polymerase chain reaction in an independent cohort of 132 samples from patients with UTUC. Models to predict tumour progression and cancer-specific survival that included miRNA expression patterns were developed by Cox regression analysis. RESULTS: Twenty-six miRNAs were found to be aberrantly expressed between samples from patients with progressing and non-progressing UTUC and five of these were selected for subsequent studies. The regression analysis identified tumour stage and miR-31 and miR-149 expression as independently associated with tumour progression and tumour stage and miR-149 expression as independently associated with cancer-specific survival. The risk scores derived from these miRNA models were able to discriminate two groups with a highly significantly different probability of tumour progression (hazard ratio [HR] 4.78; P < 0.001) and death (HR 276; P = 0.004). CONCLUSIONS: There is a differential miRNA expression pattern between patients with progressing and non-progressing UTUC. The identification of new miRNAs associated with a high probability of tumour recurrence and cancer-specific survival in patients with UTUC and their combination in a robust, easy-to-use and reliable algorithm may help tailor treatment and surveillance strategies in these patients.

Published
2014

246. The CompCert memory model

Author

Leroy, Xavier, Appel, Andrew W., Blazy, Sandrine, Stewart, Gordon, Programming languages, types, compilation and proofs (GALLIUM), Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Department of Computer Science, Princeton University, Software certification with semantic analysis (CELTIQUE), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-LANGAGE ET GÉNIE LOGICIEL (IRISA-D4), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Appel, Andrew W., ANR-11-INSE-0003,VERASCO,Vérification formelle d'analyseurs statiques et de compilateurs(2011), LANGAGE ET GÉNIE LOGICIEL (IRISA-D4), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria), CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)

Subjects
[INFO.INFO-PL]Computer Science [cs]/Programming Languages [cs.PL], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2014

247. Liste des collaborateurs

Author

Leroy Xavier, Rioux-Leclercq Nathalie, Aubert Sébastien, Compérat Eva, L’Herminé-Coulomb Aurore, and Lejeune Sophie

Published
2014

248. Differential sensitivity of prostate tumor derived endothelial cells to sorafenib and sunitinib

Author

Fiorio Pla, Alessandra, Brossa, Alessia, Bernardini, Michela, Genova, Tullio, Grolez, Guillaume, Villers, Arnaud, Leroy, Xavier, Prevarskaya, Natalia, Gkika, Dimitra, Bussolati, Benedetta, Rôle des canaux ioniques membranaires et du calcium intracellulaire dans la physiopathologie de la prostate, Université de Lille, Sciences et Technologies-Institut National de la Santé et de la Recherche Médicale (INSERM), Dipartimento di Scienze della Vita e Biologia dei Sistemi, Università degli studi di Torino (UNITO), Molecular Biotechnology Center, Service Urologie, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille, Service d'anatomopathologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), This study was supported by Italian Ministry of University and Research(MIUR) Prin08 to BB and by grants from Ministère de l’Education Nationale,Inserm, France to DG. MB is supported by the Vinci program 2012-UniversitéFranco Italienne., Taibi, Nadia, Università degli studi di Torino = University of Turin (UNITO), Département de neurologie [Lille], Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 (PHYCELL), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille

Subjects
Male, Niacinamide, Cancer Research, Indoles, Cell Survival, [SDV]Life Sciences [q-bio], Angiogenesis Inhibitors, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, urologic and male genital diseases, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Movement, Cell Line, Tumor, Sunitinib, Genetics, Humans, Pyrroles, Phosphorylation, Protein Kinase Inhibitors, Cell Proliferation, Neoplasm Staging, Prostate cancer, Phenylurea Compounds, VEGF receptor, Anti-angiogenic therapy, Endothelial Cells, Prostatic Neoplasms, Middle Aged, Sorafenib, Vascular Endothelial Growth Factor Receptor-2, female genital diseases and pregnancy complications, Androgen receptor, Oncology, Drug Resistance, Neoplasm, Drug resistance, Neoplasm Grading, Biomarkers, Research Article
Abstract

Background Prostate cancer is the second leading cause of male cancer death in developed countries. Although the role of angiogenesis in its progression is well established, the efficacy of anti-angiogenic therapy is not clearly proved. Whether this could depend on differential responses between tumor and normal endothelial cells has not been tested. Methods We isolated and characterized three lines of endothelial cells from prostate cancer and we tested the effect of Sunitinib and Sorafenib, and the combined treatment with the anti-androgen Casodex, on their angiogenic functions. Results Endothelial cells isolated from prostate tumors showed angiogenic properties and expression of androgen and vascular endothelial cell growth factor receptors. Sunitinib affected their proliferation, survival and motility while Sorafenib only showed a minor effect. At variance, Sunitinib and Sorafenib showed similar cytotoxic and anti-angiogenic effects on normal endothelial cells. Sorafenib and Sunitinib inhibited vascular endothelial cell growth factor receptor2 phosphorylation of prostate cancer endothelial cells, while they differentially modulated Akt phosphorylation as no inhibitory effect of Sorafenib was observed on Akt activation. The combined treatment of Casodex reverted the observed resistance to Sorafenib both on cell viability and on Akt activation, whereas it did not modify the response to Sunitinib. Conclusions Our study demonstrates a resistant behavior of endothelial cells isolated from prostate cancer to Sorafenib, but not Sunitinib. Moreover, it shows the benefit of a multi-target therapy combining anti-angiogenic and anti-hormonal drugs to overcome resistance. Electronic supplementary material The online version of this article (doi:10.1186/1471-2407-14-939) contains supplementary material, which is available to authorized users.

Published
2013

250. Estrogen related receptor alpha in castration-resistant prostate cancer cells promotes tumor progression in bone

Author

Fradet, Anais, primary, Bouchet, Mathilde, additional, Delliaux, Carine, additional, Gervais, Manon, additional, Kan, Casina, additional, Benetollo, Claire, additional, Pantano, Francesco, additional, Vargas, Geoffrey, additional, Bouazza, Lamia, additional, Croset, Martine, additional, Bala, Yohann, additional, Leroy, Xavier, additional, Rosol, Thomas J, additional, Rieusset, Jennifer, additional, Bellahcène, Akeila, additional, Castronovo, Vincent, additional, Aubin, Jane E, additional, Clézardin, Philippe, additional, Duterque-Coquillaud, Martine, additional, and Bonnelye, Edith, additional

Published
2016
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