Compiler fuzzing: how much does it matter?

Despite much recent interest in randomised testing (fuzzing) of compilers, the practical impact of fuzzer-found compiler bugs on real-world applications has barely been assessed. We present the first quantitative and qualitative study of the tangible impact of miscompilation bugs in a mature compiler. We follow a rigorous methodology where the bug impact over the compiled application is evaluated based on (1) whether the bug appears to trigger during compilation; (2) the extent to which generated assembly code changes syntactically due to triggering of the bug; and (3) whether such changes cause regression test suite failures, or whether we can manually find application inputs that trigger execution divergence due to such changes. The study is conducted with respect to the compilation of more than 10 million lines of C/C++ code from 309 Debian packages, using 12% of the historical and now fixed miscompilation bugs found by four state-of-the-art fuzzers in the Clang/LLVM compiler, as well as 18 bugs found by human users compiling real code or as a by-product of formal verification efforts. The results show that almost half of the fuzzer-found bugs propagate to the generated binaries for at least one package, in which case only a very small part of the binary is typically affected, yet causing two failures when running the test suites of all the impacted packages. User-reported and formal verification bugs do not exhibit a higher impact, with a lower rate of triggered bugs and one test failure. The manual analysis of a selection of the syntactic changes caused by some of our bugs (fuzzer-found and non fuzzer-found) in package assembly code, shows that either these changes have no semantic impact or that they would require very specific runtime circumstances to trigger execution divergence

Interplay between gut lymphatic vessels and microbiota

Lymphatic vessels play a distinctive role in draining fluid, molecules and even cells from interstitial and serosal spaces back to the blood circulation. Lymph vessels of the gut, and especially those located in the villi (called lacteals), not only serve this primary function, but are also responsible for the transport of lipid moieties absorbed by the intestinal mucosa and serve as a second line of defence against possible bacterial infections. Here, we briefly review the current knowledge of the general mechanisms allowing lymph drainage and propulsion and will focus on the most recent findings on the mutual relationship between lacteals and intestinal microbiota

Cyclin B1-Cdk1 facilitates MAD1 release from the nuclear pore to ensure a robust spindle checkpoint.

How the cell rapidly and completely reorganizes its architecture when it divides is a problem that has fascinated researchers for almost 150 yr. We now know that the core regulatory machinery is highly conserved in eukaryotes, but how these multiple protein kinases, protein phosphatases, and ubiquitin ligases are coordinated in space and time to remodel the cell in a matter of minutes remains a major question. Cyclin B1-Cdk is the primary kinase that drives mitotic remodeling; here we show that it is targeted to the nuclear pore complex (NPC) by binding an acidic face of the kinetochore checkpoint protein, MAD1, where it coordinates NPC disassembly with kinetochore assembly. Localized cyclin B1-Cdk1 is needed for the proper release of MAD1 from the embrace of TPR at the nuclear pore so that it can be recruited to kinetochores before nuclear envelope breakdown to maintain genomic stability

Characterization and control of oocyte large-scale chromatin configuration in different cattle breeds.

Made available in DSpace on 2020-12-11T01:57:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Differences in reproductive physiology between cattle breeds may help to explain distinct responses to assisted reproductive techniques and to define breed-specific protocols with improved efficiency. Germinal vesicle (GV) stage oocytes are characterized by increasing levels of chromatin compaction enclosed within the nucleus (graded from GV0 to GV3), associated with different developmental competence. The first objective of this study was to characterize chromatin configuration of GV stage oocytes recovered by OPU at random days of the estrous cycle from Nelore (Bos indices) and Holstein (Bos taurus) cows. In Nelore 90% of the oocytes presented advanced stages of chromatin compaction associated with higher developmental competence (GV2 and GV3), while in Holstein, only 65% of the oocytes were at these stages. Then, aiming to obtain a more homogeneous population of oocytes in Holstein, we tested two synchronization protocols combining aspiration of all visible follicles at a random day (day 0), two IM injections of FSH 12 h apart on day 2, and OPU on day 4 (OPU/D4) or 5 (OPU/D5). The protocol OPU/D4 provided around 45% of the oocytes with low chromatin compaction (GV1), while the protocol OPU/D5 provided 70% of the oocytes at GV2 and 20% at GV3. Finally, we assessed the effects of a culture system known to prevent meiotic resumption on chromatin configuration of the GV2 enriched oocyte population obtained with the protocol OPU/D5. After 9 h of culture most oocytes transited from GV2 to GV3, with 90% of the oocytes at GV3 stage. This study demonstrates differences between Nelore and Holstein cows regarding patterns of chromatin configuration that may account for their different performance in IVM/IVF. In addition, it provides novel references for the design of protocols aiming to regulate oocyte quality before IVM for the optimization of IVF outcomes. (C) 2019 Elsevier Inc. All rights reserved. Sao Paulo State Univ, Inst Biosci, Dept Physiol, Ovarian Mol Physiol Lab, Sao Paulo, Brazil Univ Sao Paulo, Dept Anim Reprod, Sao Paulo, Brazil Univ Milan, Dept Hlth Anim Sci & Food Safety, Reprod & Dev Biol Lab, Milan, Italy Sao Paulo State Univ, Inst Biosci, Dept Physiol, Ovarian Mol Physiol Lab, Sao Paulo, Brazil CAPES: 001 FAPESP: 2017/07588-4 FAPESP: 2016/21671-

Analysis of Secreted Proteins from Prepubertal Ovarian Tissues Exposed In Vitro to Cisplatin and LH

It is well known that secreted and exosomal proteins are associated with a broad range of physiological processes involving tissue homeostasis and differentiation. In the present paper, our purpose was to characterize the proteome of the culture medium in which the oocytes within the primordial/primary follicles underwent apoptosis induced by cisplatin (CIS) or were, for the most part, protected by LH against the drug. To this aim, prepubertal ovarian tissues were cultured under control and in the presence of CIS, LH, and CIS + LH. The culture media were harvested after 2, 12, and 24 h from chemotherapeutic drug treatment and analyzed by liquid chromatography–mass spectrometry (LC-MS). We found that apoptotic conditions generated by CIS in the cultured ovarian tissues and/or oocytes are reflected in distinct changes in the extracellular microenvironment in which they were cultured. These changes became evident mainly from 12 h onwards and were characterized by the inhibition or decreased release of a variety of compounds, such as the proteases Htra1 and Prss23, the antioxidants Prdx2 and Hbat1, the metabolic regulators Ldha and Pkm, and regulators of apoptotic pathways such as Tmsb4x. Altogether, these results confirm the biological relevance of the LH action on prepuberal ovaries and provide novel information about the proteins released by the ovarian tissues exposed to CIS and LH in the surrounding microenvironment. These data might represent a valuable resource for future studies aimed to clarify the effects and identify biomarkers of these compounds’ action on the developing ovary

VST: the telescope progress toward stars

The VST telescope is in an advanced stage of integration in Chile, after a period of work spent mainly on the active optics system, started in mid-2007. We present the results of the recent work on the primary and secondary mirror support systems and on the mirror cell auxiliary units

Comprehensive longitudinal non-invasive quantification of healthspan and frailty in a large cohort (n = 546) of geriatric C57BL/6 J mice

Frailty is an age-related condition characterized by a multisystem functional decline, increased vulnerability to stressors, and adverse health outcomes. Quantifying the degree of frailty in humans and animals is a health measure useful for translational geroscience research. Two frailty measurements, namely the frailty phenotype (FP) and the clinical frailty index (CFI), have been validated in mice and are frequently applied in preclinical research. However, these two tools are based on different concepts and do not necessarily identify the same mice as frail. In particular, the FP is based on a dichotomous classification that suffers from high sample size requirements and misclassification problems. Based on the monthly longitudinal non-invasive assessment of frailty in a large cohort of mice, here we develop an alternative scoring method, which we called physical function score (PFS), proposed as a continuous variable that resumes into a unique function, the five criteria included in the FP. This score would not only reduce misclassification of frailty but it also makes the two tools, PFS and CFI, integrable to provide an overall measurement of health, named vitality score (VS) in aging mice. VS displays a higher association with mortality than PFS or CFI and correlates with biomarkers related to the accumulation of senescent cells and the epigenetic clock. This longitudinal non-invasive assessment strategy and the VS may help to overcome the different sensitivity in frailty identification, reduce the sample size in longitudinal experiments, and establish the effectiveness of therapeutic/preventive interventions for frailty or other age-related diseases in geriatric animals

Desmoglein 2 is a substrate of kallikrein 7 in pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>In a previous report we have demonstrated that the chymotryptic-like serine protease kallikrein 7 (<it>KLK7</it>/hK7) is overexpressed in pancreatic cancer. In normal skin, hK7 is thought to participate in skin desquamation by contributing in the degradation of desmosomal components, such as desmogleins. Thus, the ability of hK7 to degrade desmogleins was assessed and the effect of hK7 expression on desmoglein 2 was examined in cultured pancreatic cancer cells.</p> <p>Methods</p> <p>The expression of Dsg1, Dsg2, and Dsg3 in pancreatic tissues was examined by immunohistochemistry and their expression in two pancreatic cancer cell lines, BxPC-3 and Panc-1, was determined by western blot analysis. The ability of hK7 to degrade Dsg1 and Dsg2 was investigated using <it>in vitro </it>degradation assays. BxPC-3 cells stably transfected to overexpress hK7 were used to examine the effect of hK7 on cell-surface resident Dsg2.</p> <p>Results</p> <p>The levels of immunoreactive Dsg1 and Dsg2 were reduced in pancreatic adenocarcinomas compared with both normal pancreatic and chronic pancreatitis tissues. Among the desmosomal proteins examined, Dsg2 exhibited robust expression on the surface of BxPC-3 cells. When hK7 was overexpressed in this cell line, there was a significant increase in the amount of soluble Dsg2 released into the culture medium compared with vector-transfected control cells.</p> <p>Conclusion</p> <p>A reduction in the amount of the cell adhesion components Dsg1 and Dsg2 in pancreatic tumors suggests that loss of these desmosomal proteins may play a role in pancreatic cancer invasion. Using <it>in vitro </it>degradation assays, both Dsg1 and Dsg2 could be readily proteolyzed by hK7, which is overexpressed in pancreatic adenocarcinomas. The enforced expression of hK7 in BxPC-3 cells that express significant amounts of Dsg2 resulted in a marked increase in the shedding of soluble Dsg2, which is consistent with the notion that aberrant expression of hK7 in pancreatic tumors may result in diminished cell-cell adhesion and facilitate tumor cell invasion.</p

Perrault Aux Prises Avec la Fontaine: Imitation, Compétition et Correction Dans Les Fables de Faërne (1699)

Known especially for his fairy tales, Charles Perrault is also the author of the Fables de Faërne (1699). In this French translation of the Neo-Latin volume Fabulae Centum (1564), written by the Italian humanist Gabriel Faerno, Perrault had to position himself against his renowned predecessor Jean de La Fontaine, who had been dominating fable literature for decades. Perrault could either imitate his famous example, or evade it, due to anxiety of influence. To illustrate this inner struggle, we systematically compare both authors’ fables, concentrating our analysis on versification (metre and rhyme), vocabulary and apostrophe. In our comparison, we constantly verify whether any of the resemblances could be attributable to other French, versified fable books read by both Perrault and La Fontaine. Occasionally, this seems to be the case for the anonymous collection L’Esbatement moral des animaux (1578).Vakpublicati