Leveraging Formal Specifications to Generate Fuzzing Suites

International audienceWhen testing a library, developers typically first have to capture the semantics they want to check. They then write the code implementing these tests and find relevant test cases that expose possible misbehaviours. In this work, we present a tool that automatically takes care of these last two steps by automatically generating fuzz testing suites from OCaml interfaces annotated with formal behavioural specifications. We also show some ongoing experiments on the capabilities and limitations of fuzzing applied to real-world libraries

Identification of post-transcriptionally regulated Xenopus tropicalis maternal mRNAs by microarray

Cytoplasmic control of the adenylation state of mRNAs is a critical post-transcriptional process involved in the regulation of mRNAs stability and translational efficiency. The early development of Xenopus laevis has been a major model for the study of such regulations. We describe here a microarray analysis to identify mRNAs that are regulated by changes in their adenylation state during oogenesis and early development of the diploid frog Xenopus tropicalis. The microarray data were validated using qRT–PCR and direct analysis of the adenylation state of endogenous maternal mRNAs during the period studied. We identified more than 500 mRNAs regulated at the post-transcriptional level among the 3000 mRNAs potentially detected by the microarray. The mRNAs were classified into nine different adenylation behavior categories. The various adenylation profiles observed during oocyte maturation and early development and the analyses of 3′-untranslated region sequences suggest that previously uncharacterized sequence elements control the adenylation behavior of the newly identified mRNAs. These data should prove useful in identifying mRNAs with important functions during oocyte maturation and early development

Single-Molecule LATE-PCR Analysis of Human Mitochondrial Genomic Sequence Variations

It is thought that changes in mitochondrial DNA are associated with many degenerative diseases, including Alzheimer's and diabetes. Much of the evidence, however, depends on correlating disease states with changing levels of heteroplasmy within populations of mitochondrial genomes, rather than individual mitochondrial genomes. Thus these measurements are likely to either overestimate the extent of heteroplasmy due to technical artifacts, or underestimate the actual level of heteroplasmy because only the most abundant changes are observable. In contrast, Single Molecule (SM) LATE-PCR analysis achieves efficient amplification of single-stranded amplicons from single target molecules. The product molecules, in turn, can be accurately sequenced using a convenient Dilute-‘N’-Go protocol, as shown here. Using these novel technologies we have rigorously analyzed levels of mitochondrial genome heteroplasmy found in single hair shafts of healthy adult individuals. Two of the single molecule sequences (7% of the samples) were found to contain mutations. Most of the mtDNA sequence changes, however, were due to the presence of laboratory contaminants. Amplification and sequencing errors did not result in mis-identification of mutations. We conclude that SM-LATE-PCR in combination with Dilute-‘N’-Go Sequencing are convenient technologies for detecting infrequent mutations in mitochondrial genomes, provided great care is taken to control and document contamination. We plan to use these technologies in the future to look for age, drug, and disease related mitochondrial genome changes in model systems and clinical samples

Rural‐Urban Differences in In‐Hospital Mortality Among Admissions for End‐Stage Liver Disease in the United States

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151328/1/lt25587_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151328/2/lt25587.pd

Molecular Dating, Evolutionary Rates, and the Age of the Grasses

Many questions in evolutionary biology require an estimate of divergence times but, for groups with a sparse fossil record, such estimates rely heavily on molecular dating methods. The accuracy of these methods depends on both an adequate underlying model and the appropriate implementation of fossil evidence as calibration points. We explore the effect of these in Poaceae (grasses), a diverse plant lineage with a very limited fossil record, focusing particularly on dating the early divergences in the group. We show that molecular dating based on a data set of plastid markers is strongly dependent on the model assumptions. In particular, an acceleration of evolutionary rates at the base of Poaceae followed by a deceleration in the descendants strongly biases methods that assume an autocorrelation of rates. This problem can be circumvented by using markers that have lower rate variation, and we show that phylogenetic markers extracted from complete nuclear genomes can be a useful complement to the more commonly used plastid markers. However, estimates of divergence times remain strongly affected by different implementations of fossil calibration points. Analyses calibrated with only macrofossils lead to estimates for the age of core Poaceae ∼51-55 Ma, but the inclusion of microfossil evidence pushes this age to 74-82 Ma and leads to lower estimated evolutionary rates in grasses. These results emphasize the importance of considering markers from multiple genomes and alternative fossil placements when addressing evolutionary issues that depend on ages estimated for important group

Single-state Transcarotid Artery Revascularization Experience: Outcomes and Impact on Carotid Procedural and Operative Volumes

Objectives: Transcarotid artery revascularization (TCAR) is an emerging novel approach to carotid intervention, adopted and well-suited for high-risk patients. Our objective was to assess the outcomes of TCAR and determine its impact on the volume of carotid endarterectomy (CEA) and non-TCAR carotid artery stenting (CAS) in a single-state experience. Methods: A large statewide quality consortium registry was queried. The indications and outcomes of TCAR compared with CEA and non-TCAR CAS from January 2018 to October 2019 were reviewed. Non-TCAR CAS included transfemoral, transbrachial stenting and transcarotid stenting without the flow reversal technique. We also assessed the impact of TCAR on the trend of CEA and non-TCAR CAS performed, analyzing data from 2012 to 2019. Outcome comparisons were performed using the χ 2 and Mann-Whitney U tests, depending on the distribution of the outcomes. Results: A total of 438 TCARs were performed by 39 physicians in 16 hospitals; 60% of the patients were asymptomatic and 40% symptomatic. The TCAR indication was physiologic high risk for 369 patients (84%) and restenosis for 69 patients (16%), with most occurring after prior CEA (94%). Of the non-TCAR CAS cases, 94% were performed via transfemoral access. The patients undergoing non-TCAR CAS had the highest 30-day mortality ( P \u3c .001) and the highest incidence of 30-day new neurologic deficits ( P = .008) compared with the patients undergoing CEA and TCAR. CEA had the lowest myocardial infarction rate ( P = .015; Table). The number of TCAR procedures performed and the number of physicians and hospitals performing them increased during the 2-year period. Since the introduction of TCAR, no significant frequency decrease has occurred in the number of non-TCAR CAS or CEA cases by hospitals or physicians (Fig). However, a significant negative trend was found in the number of CEAs performed by physicians since 2012 ( P \u3c .001; Fig). Conclusions: TCAR is a safe method of carotid revascularization and is becoming an increasingly used method. TCAR has not affected the CEA hospital or physician volume since its introduction. CEA volumes and physician usage are declining, which could have future credentialing implications. In the present single-state experience, TCAR compared favorably with CEA and non-TCAR CAS might be less appealing because of its higher neurologic event rate

Post-transcriptional regulation in Xenopus embryos: role and targets of EDEN-BP.

International audienceEDEN (embryo deadenylation element)-dependent deadenylation is a regulatory process that was initially identified in Xenopus laevis early embryos and was subsequently shown to exist in Drosophila oocytes. Recent data showed that this regulatory process is required for somitic segmentation in Xenopus. Inactivation of EDEN-BP (EDEN-binding protein) causes severe segmentation defects, and the expression of segmentation markers in the Notch signalling pathway is disrupted. We showed that the mRNA encoding XSu(H) (Xenopus suppressor of hairless), a protein central to the Notch pathway, is regulated by EDEN-BP. Our data also indicate that other segmentation RNAs are targets for EDEN-BP. To identify new EDEN-BP targets, a microarray analysis has been undertaken

Identification of CUG-BP1/EDEN-BP target mRNAs in Xenopus tropicalis

The early development of many animals relies on the posttranscriptional regulations of maternally stored mRNAs. In particular, the translation of maternal mRNAs is tightly controlled during oocyte maturation and early mitotic cycles in Xenopus. The Embryonic Deadenylation ElemeNt (EDEN) and its associated protein EDEN-BP are known to trigger deadenylation and translational silencing to several mRNAs bearing an EDEN. This Xenopus RNA-binding protein is an ortholog of the human protein CUG-BP1/CELF1. Five mRNAs, encoding cell cycle regulators and a protein involved in the notch pathway, have been identified as being deadenylated by EDEN/EDEN-BP. To identify new EDEN-BP targets, we immunoprecipitated EDEN-BP/mRNA complexes from Xenopus tropicalis egg extracts. We identified 153 mRNAs as new binding targets for EDEN-BP using microarrays. Sequence analyses of the 3′ untranslated regions of the newly identified EDEN-BP targets reveal an enrichment in putative EDEN sequences. EDEN-BP binding to a subset of the targets was confirmed both in vitro and in vivo. Among the newly identified targets, Cdk1, a key player of oocyte maturation and cell cycle progression, is specifically targeted by its 3′ UTR for an EDEN-BP-dependent deadenylation after fertilization

Composition of eggplant cultivars of the Occidental type and implications for the improvement of nutritional and functional quality

We have investigated the diversity for composition in seven eggplant (Solanum melongena) cultivars of the Occidental type. The results show that, with the exception of moisture content and pH, there is a wide diversity for all the analysed traits. Protein content was variable, but generally low. The content in available carbohydrates ranged between 2.99 and 4.19mg100g(-1), and the main soluble sugars were glucose and fructose. The fibre content was the most variable trait. In all cases, the dehydroascorbic acid content was higher than the ascorbic acid content. Total phenolics content was on average thirty-nine-fold higher than vitamin C content. Multivariate analysis showed that accessions from the black and striped groups presented a similar composition profile, while the white and pickling fruits were very distinct. The pickling eggplant H11 is identified as the best source for improving the nutritional and functional properties of Occidental eggplants.This work was partially financed by the Ministerio de Ciencia y Tecnologia (AGL2009-07257 and AGL2012-34213).San José, R.; Sánchez Mata, MDC.; Cámara, MM.; Prohens Tomás, J. (2013). Composition of eggplant cultivars of the Occidental type and implications for the improvement of nutritional and functional quality. International Journal of Food Science and Technology. 48(12):2490-2499. doi:10.1111/ijfs.12240S249024994812Akanitapichat, P., Phraibung, K., Nuchklang, K., & Prompitakkul, S. (2010). Antioxidant and hepatoprotective activities of five eggplant varieties. Food and Chemical Toxicology, 48(10), 3017-3021. doi:10.1016/j.fct.2010.07.045Atkinson, C. J., Nestby, R., Ford, Y. Y., & Dodds, P. A. A. (2005). Enhancing beneficial antioxidants in fruits: A plant physiological perspective. 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Journal of Food Composition and Analysis, 19(6-7), 594-600. doi:10.1016/j.jfca.2006.03.001Hernández-Hernández, O., Ruiz-Aceituno, L., Sanz, M. L., & Martínez-Castro, I. (2011). Determination of Free Inositols and Other Low Molecular Weight Carbohydrates in Vegetables. Journal of Agricultural and Food Chemistry, 59(6), 2451-2455. doi:10.1021/jf1045552Hurtado, M., Vilanova, S., Plazas, M., Gramazio, P., Fonseka, H. H., Fonseka, R., & Prohens, J. (2012). Diversity and Relationships of Eggplants from Three Geographically Distant Secondary Centers of Diversity. PLoS ONE, 7(7), e41748. doi:10.1371/journal.pone.0041748Jenkins, D. J. A. (2003). Effects of a Dietary Portfolio of Cholesterol-Lowering Foods vs Lovastatin on Serum Lipids and C-Reactive Protein. JAMA, 290(4), 502. doi:10.1001/jama.290.4.502Kim, D.-O., Lee, K. W., Lee, H. J., & Lee, C. Y. (2002). Vitamin C Equivalent Antioxidant Capacity (VCEAC) of Phenolic Phytochemicals. 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Increases the Antioxidant Content and the Inhibitory Effect on Human Neutrophil Burst. Journal of Agricultural and Food Chemistry, 58(6), 3371-3379. doi:10.1021/jf903881sLuengwilai, K., Tananuwong, K., Shoemaker, C. F., & Beckles, D. M. (2010). Starch Molecular Structure Shows Little Association with Fruit Physiology and Starch Metabolism in Tomato. Journal of Agricultural and Food Chemistry, 58(2), 1275-1282. doi:10.1021/jf9032393Luthria, D. L. (2012). A simplified UV spectral scan method for the estimation of phenolic acids and antioxidant capacity in eggplant pulp extracts. Journal of Functional Foods, 4(1), 238-242. doi:10.1016/j.jff.2011.11.002Mennella, G., Rotino, G. L., Fibiani, M., D’Alessandro, A., Francese, G., Toppino, L., … Lo Scalzo, R. (2010). Characterization of Health-Related Compounds in Eggplant (Solanum melongenaL.) Lines Derived from Introgression of Allied Species. Journal of Agricultural and Food Chemistry, 58(13), 7597-7603. doi:10.1021/jf101004zMeyer, R. S., Karol, K. G., Little, D. P., Nee, M. H., & Litt, A. (2012). Phylogeographic relationships among Asian eggplants and new perspectives on eggplant domestication. Molecular Phylogenetics and Evolution, 63(3), 685-701. doi:10.1016/j.ympev.2012.02.006Muñoz-Falcón, J. E., Prohens, J., Vilanova, S., & Nuez, F. (2008). Characterization, diversity, and relationships of the Spanish striped (Listada) eggplants: a model for the enhancement and protection of local heirlooms. Euphytica, 164(2), 405-419. doi:10.1007/s10681-008-9688-3Muñoz-Falcón, J. E., Prohens, J., Vilanova, S., & Nuez, F. (2009). Diversity in commercial varieties and landraces of black eggplants and implications for broadening the breeders’ gene pool. Annals of Applied Biology, 154(3), 453-465. doi:10.1111/j.1744-7348.2009.00314.xNicolas, J. J., Richard‐Forget, F. C., Goupy, P. M., Amiot, M., & Aubert, S. Y. (1994). Enzymatic browning reactions in apple and apple products. Critical Reviews in Food Science and Nutrition, 34(2), 109-157. doi:10.1080/10408399409527653Nookaraju, A., Upadhyaya, C. P., Pandey, S. K., Young, K. E., Hong, S. J., Park, S. K., & Park, S. W. (2010). Molecular approaches for enhancing sweetness in fruits and vegetables. Scientia Horticulturae, 127(1), 1-15. doi:10.1016/j.scienta.2010.09.014Perez, P. M. P., & Germani, R. (2007). Elaboração de biscoitos tipo salgado, com alto teor de fibra alimentar, utilizando farinha de berinjela (Solanum melongena, L.). Ciência e Tecnologia de Alimentos, 27(1), 186-192. doi:10.1590/s0101-20612007000100033Picha, D. (2006). HORTICULTURAL CROP QUALITY CHARACTERISTICS IMPORTANT IN INTERNATIONAL TRADE. Acta Horticulturae, (712), 423-426. doi:10.17660/actahortic.2006.712.49Prohens, J., Rodríguez-Burruezo, A., Raigón, M. D., & Nuez, F. (2007). Total Phenolic Concentration and Browning Susceptibility in a Collection of Different Varietal Types and Hybrids of Eggplant: Implications for Breeding for Higher Nutritional Quality and Reduced Browning. Journal of the American Society for Horticultural Science, 132(5), 638-646. doi:10.21273/jashs.132.5.638Prohens, J., Muñoz-Falcón, J. E., Rodríguez-Burruezo, A., Ribas, F., Castro, Á., & Nuez, F. (2009). ‘H15’, an Almagro-type Pickling Eggplant with High Yield and Reduced Prickliness. HortScience, 44(7), 2017-2019. doi:10.21273/hortsci.44.7.2017Raigón, M. D., Prohens, J., Muñoz-Falcón, J. E., & Nuez, F. (2008). Comparison of eggplant landraces and commercial varieties for fruit content of phenolics, minerals, dry matter and protein. Journal of Food Composition and Analysis, 21(5), 370-376. doi:10.1016/j.jfca.2008.03.006Raigón, M. D., Rodríguez-Burruezo, A., & Prohens, J. (2010). Effects of Organic and Conventional Cultivation Methods on Composition of Eggplant Fruits. Journal of Agricultural and Food Chemistry, 58(11), 6833-6840. doi:10.1021/jf904438nRawson, A., Patras, A., Tiwari, B. K., Noci, F., Koutchma, T., & Brunton, N. (2011). Effect of thermal and non thermal processing technologies on the bioactive content of exotic fruits and their products: Review of recent advances. Food Research International, 44(7), 1875-1887. doi:10.1016/j.foodres.2011.02.053Sánchez-Mata, M. C., Cámara-Hurtado, M., Díez-Marqués, C., & Torija-Isasa, M. E. (2000). Comparison of high-performance liquid chromatography and spectrofluorimetry for vitamin C analysis of green beans (Phaseolus vulgaris L.). European Food Research and Technology, 210(3), 220-225. doi:10.1007/pl00005516Sánchez-Mata, M. C., Cabrera Loera, R. D., Morales, P., Fernández-Ruiz, V., Cámara, M., Díez Marqués, C., … Tardío, J. (2011). Wild vegetables of the Mediterranean area as valuable sources of bioactive compounds. 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Predicting the severity of the grass pollen season and the effect of climate change in Northwest Europe

Allergic rhinitis is an inflammation in the nose caused by overreaction of the immune system to allergens in the air. Managing allergic rhinitis symptoms is challenging and requires timely intervention. The following are major questions often posed by those with allergic rhinitis: How should I prepare for the forthcoming season? How will the season's severity develop over the years? No country yet provides clear guidance addressing these questions. We propose two previously unexplored approaches for forecasting the severity of the grass pollen season on the basis of statistical and mechanistic models. The results suggest annual severity is largely governed by preseasonal meteorological conditions. The mechanistic model suggests climate change will increase the season severity by up to 60%, in line with experimental chamber studies. These models can be used as forecasting tools for advising individuals with hay fever and health care professionals how to prepare for the grass pollen season