Speeding Up Algorithmic Debugging Using Balanced Execution Trees

Algorithmic debugging is a debugging technique that uses a data structure representing all computations performed during the execution of a program. This data structure is the so-called Execution Tree and it strongly influences the performance of the technique. In this work we present a transformation that automatically improves the structure of the execution trees by collapsing and projecting some strategic nodes. This improvement in the structure implies a better behavior and performance of the standard algorithms that traverse it. We prove that the transformation is sound in the sense that all the bugs found after the transformation are real bugs; and if at least one bug is detectable before the transformation, then at least one bug will also be detectable after the transformation. We have implemented the technique and performed several experiments with real applications. The experimental results confirm the usefulness of the technique.This work has been partially supported by the Spanish Ministerio de Ciencia e Innovación under grants TIN2008-06622-C03-02 and TIN2012-39391-004-04, by the Generalitat Valenciana under grant ACOMP/2009/017, and by the Comunidad de Madrid under grant S2009/TIC-1465. David Insa has been partially supported by the Spanish Ministerio de Educación under grant AP2010-4415.Silva, J.; Insa Cabrera, D.; Riesco, A. (2013). Speeding Up Algorithmic Debugging Using Balanced Execution Trees. En Tests and Proofs. Springer. 133-151. https://doi.org/10.1007/978-3-642-38916-0_8S133151Binks, D.: Declarative Debugging in Gödel. PhD thesis, University of Bristol (1995)Caballero, R.: A Declarative Debugger of Incorrect Answers for Constraint Functional-Logic Programs. In: Proc. of the 2005 ACM SIGPLAN Workshop on Curry and Functional Logic Programming, WCFLP 2005, pp. 8–13. ACM Press (2005)Caballero, R., Hermanns, C., Kuchen, H.: Algorithmic debugging of Java programs. In: López-Fraguas, F.J. (ed.) Proc. of the 15th Workshop on Functional and (Constraint) Logic Programming, WFLP 2006, Madrid, Spain. ENTCS, vol. 177, pp. 75–89. Elsevier (2007)Calejo, M.: A Framework for Declarative Prolog Debugging. PhD thesis, New University of Lisbon (1992)Davie, T., Chitil, O.: Hat-delta: One Right Does Make a Wrong. In: Seventh Symposium on Trends in Functional Programming, TFP 2006 (April 2006)Hirunkitti, V., Hogger, C.J.: A Generalised Query Minimisation for Program Debugging. In: Fritzson, P.A. (ed.) AADEBUG 1993. LNCS, vol. 749, pp. 153–170. Springer, Heidelberg (1993)Insa, D., Silva, J.: Scaling up algorithmic debugging with virtual execution trees. In: Alpuente, M. (ed.) LOPSTR 2010. LNCS, vol. 6564, pp. 149–163. Springer, Heidelberg (2011)Insa, D., Silva, J., Riesco, A.: Speeding up algorithmic debugging using balanced execution trees—detailed results. Technical Report 04/13, Departamento de Sistemas Informáticos y Computación (April 2013)Kokai, G., Nilson, J., Niss, C.: GIDTS: A Graphical Programming Environment for Prolog. In: Workshop on Program Analysis For Software Tools and Engineering, PASTE 1999, pp. 95–104. ACM Press (1999)MacLarty, I.: Practical Declarative Debugging of Mercury Programs. PhD thesis, Department of Computer Science and Software Engineering, University of Melbourne (2005)Maeji, M., Kanamori, T.: Top-Down Zooming Diagnosis of Logic Programs. Technical Report TR-290, Japan (1987)Nilsson, H.: Declarative Debugging for Lazy Functional Languages. PhD thesis, Linköping, Sweden (May 1998)Nilsson, H., Fritzson, P.: Algorithmic Debugging for Lazy Functional Languages. Journal of Functional Programming 4(3), 337–370 (1994)Shapiro, E.Y.: Algorithmic Program Debugging. MIT Press (1982)Silva, J.: A Survey on Algorithmic Debugging Strategies. Advances in Engineering Software 42(11), 976–991 (2011

L’exercice comme approche alternative dans la gestion des algies vasculaires de la face: étude de cas

Introduction : Plusieurs traitements pharmacologi- ques sont utilisés pour soulager la douleur et réduire la durée et la fréquence des crises d’algie vasculaire de la face (CH), mais ces traitements demeurent partiellement efficaces pour plusieurs patients. L’exercice aérobie est actuellement pro- posé pour réduire la prévalence et la gravité des symptômes associés à d’autres types de céphalées, mais son efficacité concernant la gestion des CH n’a pas encore été documentée. Représentation du cas : Cet article décrit le cas d’un homme de 24 ans chez qui on a diagnostiqué des CH épisodiques (1/jour ; > 1 heure). Treize jours après le premier épisode, des exercices aérobies d’intensité modérée étaient effectués (10 à 30 minutes) au début des crises. L’exercice aérobie a réduit à la fois la sévérité et la durée des crises de CH. Conclusion : Cette étude de cas suggère que la réalisation d’exercices aérobies d’intensité modérée au début d’une crise de CH pourrait être une intervention non pharmacolo- gique complémentaire intéressante pour diminuer les symp- tômes douloureux liés à cette condition.Abstract : Background: Various pharmacological treatments have been used to relieve pain and reduce the duration and occurrence of cluster headache (CH) attacks, but these treatments remain partially effective for many patients. Aerobic exercises have been proposed to decrease the prevalence and severity of symptoms associated with other types of headaches, but the effectiveness of aerobic exercise for CH management has not yet been investigated. Case presentation: This report describes the case of a 24 year-old male patient diagnosed with episodic CH (1/day; > 1h). Thirteen days after the first episode, moderate-intensity continuous aerobic exercise was performed (10-30 minutes) at the onset of CH attack. Aerobic exercise reduced both severity and duration of CH attacks. Conclusions: This case report suggests that performing moderate-intensity aerobic exercise at the onset of a CH attack may be an interesting non-pharmacologic intervention that can be used to ease pain symptoms

Non-coding RNA regulation in reproduction: their potential use as biomarkers

[EN] Non-coding RNAs (ncRNAs) are crucial regulatory elements in most biological processes and reproduction is also controlled by them. The different types of ncRNAs, as well as the high complexity of these regulatory pathways, present a complex scenario; however, recent studies have shed some light on these questions, discovering the regulatory function of specific ncRNAs on concrete reproductive biology processes. This mini review will focus on the role of ncRNAs in spermatogenesis and oogenesis, and their potential use as biomarkers for reproductive diseases or for reproduction successSIThe authors would like to acknowledge project AGL2015-68330-C2-1-R (MINECO/FEDER) PTA2016-11987-I contract (MINECO/FEDER) and AQUA-CIBUS international net 318RT0549 funded by CYTE

New adipokines vaspin and omentin, circulating levels, gene expression in adipose tissue and relationship of circulating levels with nonalcoholic fatty liver disease

L'obesitat és una situació d'excés de massa de greix corporal que pot conduir a la síndrome metabòlica (SM). Omentin es produeix i és secretada pel TAV i pot tenir un paper antiinflamatori important en estats pro-inflamatoris. La disminució dels nivells circulants i de l'expressió génica de vaspina s'associa a empitjorament de la diabetis i la pèrdua de pes corporal. Simultàniament a l'augment de la incidència de l'obesitat i la diabetis, augmenta la prevalença de l'hepatopatia grassa no alcohòlica (HGNA). La prova gold standard per al diagnòstic histològic és la biòpsia hepàtica. Atès que és una tècnica invasiva, hi ha un interès en el desenvolupament de biomarcadors no invasius per a la identificació d'esteatohepatitis. Els objectius van ser analitzar els nivells circulants d’omentin i vaspina, la seva expressió gènica en teixit adipós en dones amb obesitat mórbida (OM) enfront de dones amb normopès. Es va examinar la seva associació amb les diferents variables bioquímiques, així com l'ús clínic dels nivells circulants d’omentin i vaspina com a potencials biomarcadors de la presència de HGNA. Primer, es van analitzar els nivells circulants i expressió génica de vaspina i omentina en individus amb pes normal i OM. Després, es van analitzar 40 mostres de fetge de les dones amb OM. Els resultats mostraren disminució dels nivells circulants d’omentin a l'OM, presentant correlació inversa amb els paràmetres glucèmics i amb el SM. L'expressió d’Omentin estava disminuïda en OM. En contrast, els nivells de vaspina en els OM no van ser diferents dels controls, amb una correlació inversa amb els nivells de lipocalina-2 i IL6. L'expressió de vaspina va ser significativament més gran en els OM. Quant a l’HGNA, els resultats van objectivar augment dels nivells circulants d’omentin en els pacients amb EHNA respecte l’esteatosi simple. D'altra banda, el rendiment dels nivells d’omentin per al diagnòstic d’EHNA va mostrar una excel•lent AUROC. Les principals conclusions són que omentin sembla exercir un efecte protector front l'obesitat, mentre que els seus nivells circulants augmenten paradoxalment en els pacients amb EHNA.La obesidad es una situación de exceso de masa grasa corporal que puede conducir al síndrome metabólico (SM). Omentin se produce y es secretada por el TAV y puede tener un papel antiinflamatorio importante en estados pro-inflamatorios. La disminución de los niveles circulantes y de la expresión génica de vaspina se asocia a empeoramiento de la diabetes y la pérdida de peso corporal. Simultaneamente al aumento de la incidencia de la obesidad y la diabetes, aumenta la prevalencia de la hepatopatía grasa no alcohólica (HGNA). Dado que la biopsia hepática es una técnica invasiva, existe un interés en el desarrollo de biomarcadores no invasivos para la identificación de esteatohepatitis. Los objetivos fueron analizar los niveles circulantes de omentin y vaspina, su expresión génica en el tejido adiposo en mujeres con obesidad mórbida frente a mujeres con peso normal. Se examinó su asociación con las variables bioquímicas así como el uso clínico de los niveles circulantes de omentin y vaspina como potenciales biomarcadores de la presencia de la HGNA. Primero, se analizaron los niveles circulantes y la expresión génica de vaspina y omentin en sujetos con normopeso y obesidad mórbida (OM). Después, se analizaron 40 muestras de hígado de las mujeres con OM. Los resultados mostraron disminución de los niveles de omentin en la OM, presentando correlación inversa con los parámetros glucémicos y el SM. La expresión de Omentin estaba disminuida en la OM. En contraste, los niveles séricos de vaspina en los OM no fueron diferentes de los controles, con una correlación inversa con los niveles de lipocalina-2 e IL6. La expresión de vaspina fue mayor en los OM. En cuanto a la HGNA, demostramos un aumento de los niveles circulantes de omentin en los pacientes con EHNA respecto a aquellos con ES. El rendimiento de los niveles de omentin para el diagnóstico de EHNA mostró una excelente AUROC. Las conclusiones son que omentin parece ejercer un efecto protector frente la obesidad, mientras que sus niveles circulantes aumentan paradójicamente en los pacientes con EHNA.Obesity is a situacion with excess of body fat mass that can lead to metabolic syndrome. Omentin is produced and secreted by VAT and may have an important anti-inflammatory role in pro-inflammatory states. Decreases in vaspin expression and plasma levels accompany worsening of diabetes and body weight loss. In parallel with increased incidence of obesity and type 2 diabetes, the prevalence of non-alcoholic fatty liver disease (NAFLD) is growing worldwide. Because liver biopsy is an invasive procedure there is strong interest in developing non-invasive biomarkers for identifying steatohepatitis in NAFLD. The main objectives of this doctoral thesis were to analyze omentin and vaspin gene expression in VAT and SAT as well as circulating levels in a group of morbidly obese women versus normal-weight control women and its associations with the clinical-biochemical variables as well as the clinical use of circulating omentin and vaspin levels as biomarkers for the presence of NAFLD. First, we analyzed the circulating levels and gene expression of vaspin and omentin in normal-weight and morbidly obese (MO) subjects. Then, we analyzed 40 liver samples from MO women. We showed lower circulating omentin levels in the MO, correlating inversely with glucidic metabolism parameters and also with MetS. Omentin mRNA expression in VAT was reduced in MO. In contrast, serum vaspin levels in the MO were not significantly different from those in the controls, correlating inversely with lipocalin-2 and interleukin-6 levels. Vaspin mRNA expression was significantly higher in the MO. Regarding NAFLD, we revealed increased circulating omentin levels in NASH patients in comparison with SS. The performance of omentin in diagnosing NASH showed an excellent AUROC. In conclusion, the main findings of this doctoral thesis are that omentin appears to exert a protective effect against obesity, whereas circulating omentin levels are paradoxically increased in patients with NASH

Probiotics reduce anxiety-related behavior in zebrafish

[EN] There is increasing evidence that gut microbiome could have effects on neurological processes and on behavior. In this study we used the novel tank test (NTT) to analyze zebrafish exploring behavior after four months’ supplementation with probiotics with probed antioxidant and anti-inflammatory properties. Results showed that prolonged ingestion of Lactobacillus rhamnosus CECT8361 and Bifidobacterium longum CECT7347 significantly alters the swimming pattern and mean swimming speed in the zebrafish model. After treatment, zebrafish strongly reduced their bottom-dwelling geotactic behavior when placed in a new tank, which could be correlated to a lower state of anxiety.S

Effect of low sperm quality on progeny: a study on zebrafish as model species

[EN] Nowadays a decrease tendency in human sperm quality has been reported mainly in developed countries. Reproductive technologies have been very valuable in achieving successful pregnancies with low quality sperm samples. However, considering that spermatozoa molecular contribution is increasingly important in recent studies, it is crucial to study whether fertilization with low sperm quality could leave a molecular mark on progeny. This study explores the consequences that fertilization with low sperm quality may have on progeny, using zebrafish as a model. Good and bad breeders were established attending to sperm quality analyses and were individually tracked. Significant differences in fertilization and malformation rates were obtained in progenies between high and low quality sperm samples. Moreover an altered miR profile was found in the progenies of bad zebrafish breeders (upregulation of miR-141 and miR -122 in 24 hpf embryos) and as a consequence, some of their targets involved in male sex development such as dmrt1, suffered downregulation. Our results indicate that fertilizing with high sperm quality samples becomes relevant from a new perspective: to avoid molecular alterations in the progeny that could remain masked and therefore produce unexpected consequences in it.SIThis work was supported by AGL2015 68330-C2-1-R project (MINECO/FEDER), PTA2016-11987-I contract (MINECO/FEDER) and AQUA-CIBUS international net 318RT0549 funded by CYTED (Programa Iberoamericano de Ciencia y Tecnologia para el Desarrollo

Diet Supplemented with Antioxidant and Anti-Inflammatory Probiotics Improves Sperm Quality after Only One Spermatogenic Cycle in Zebrafish Model

[EN] Infertility is a medical concern worldwide and could also have economic consequences in farmed animals. Developing an efficient diet supplement with immediate effects on sperm quality is a promising tool for human reproduction and for domesticated animal species. This study aims at elucidating the effect of a short-time probiotic supplementation consisting of a mixture of two probiotic bacteria with proven antioxidant and anti-inflammatory activities on zebrafish sperm quality and male behavior. For this purpose, three homogeneous groups of males in terms of motility (<60%) were established. The control group was fed with a normal standard diet. The other received supplements: One group (vehicle control) was fed with maltodextrin and the other received a probiotic preparation based on a mixture (1:1) of Lactobacillus rhamnosus CECT8361 and Bifidobacterium longum CECT7347. The feeding regime was 21 days corresponding with a single spermatogenesis in zebrafish. The preparation did not modify animal weight, positively affected the number of fluent males, increased sperm concentration, total motility, progressive motility, and fast spermatozoa subpopulations. Moreover, the animals fed with the supplement showed different behavior patterns compared to control groups. Our results suggest a diet-related modulation on the exploration activity indicating a lower stress-like conduct. The studied formulation described here should be considered as advantageous in male reproductive biotechnologySIThis work was supported by project AGL2015 68330-C2-1-R (MINECO/FEDER)The authors acknowledge contract PTA2016-11987-I (MINECO/FEDER), Biopolis S.L. (Valencia, Spain), AQUA-CIBUS International Net 318RT0549 (CYTED), and the staff from Planta de Cultivos El Bocal (IEO

In Vitro Generation of Zebrafish PGC-Like Cells

[EN] The possibility of generating primordial germ cells (PGCs) in vitro from noncommitted embryonic cells represents an extremely useful tool in current research. Primordial germ cell in vitro differentiation has been successfully reported in mammals. However, contrary to fish, PGC specification in mammals is an inductive mechanism. This study is the first to date to describe a rapid method for PGC in vitro differentiation in teleosts. Primordial germ cell-like cells were characterized by several lines of evidence, including gene expression, cell complexity, size, and image analysis for the quantification of fluorescence under vasa promoter. Moreover, differentiated cells were able to colonize the genital ridge after transplantation. Differentiation treatments increased the number of PGCs in culture, causing differentiation of cells rather than inducing their proliferation. These results open up the possibility of differentiating genetically modified embryonic cells to PGC-like cells to ensure their transmission to the progeny and could be crucial for an in-depth understanding of germline differentiation in teleostsSISupported by Fundación Ramón Areces and Ministerio de Ciencia e Innovación grant MICINN AGL2009-06994, Ramón y Cajal Program grant RYC-2008-02339, Junta de Castilla y León grants E-24-2009-0036681 and EDU/346/2013, and Fondo Social Europeo. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscrip

Impact of different levels of handling on Solea senegalensis culture: effects on growth and molecular markers of stress

[EN] Aquaculture routine practices may cause stress induction on the fish and compromise their welfare affecting the production. This experiment aimed to evaluate the potential links between handling during culture with stress responses and growth on Senegalese sole (Solea senegalensis). We worked with two fish cohorts in terms of initial body weight and culture stage: Trial 1 included specimens in the fattening stage (226 ± 4.96 g) and Trial 2 animals in the pre-fattening stage (27.20 ± 0.44 g). The tested culture protocol, which lasted 6 and 4 months for Trial 1 and 2, respectively, mainly reduced handling-derived stressors in the experimental tanks via lowering routine samplings to a minimum. This decrease of the handling-derived stress was reflected in both trials with lower concentration of circulating cortisol in blood plasma from the experimental fish when compared to controls. Moreover, the proposed protocol promoted higher growth in the fish cultured in the less disturbing protocol in Trial 2. Higher specific growth rates and mean body weight and length were reported. In order to further explore the potential beneficial effects of our protocol, we studied the musculoskeletal from Trial 2 gene expression of key genes regulating glucocorticoid signaling pathway and apoptosis: glucocorticoid receptors 1 and 2 (gr1, gr2), heat shock protein 90 AA (hsp90aa), and caspase 6 (casp6). In line with the cortisol reduced level in this trial, gr1, hsp90aa, and casp6 genes showed lower expression in the samples coming from the experimental group. The findings of this study provide valuable information to the aquaculture industry for the management of Solea senegalensis stress and welfare.SIPublicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCL

Artificial Neural Network (ANN) as a tool to reduce human-animal interaction improves Senegalese sole production

El artículo pertenece al special issue Big Data Analysis in Biomolecular Research, Bioinformatics, and Systems Biology with Complex Networks and Multi-Label Machine Learning Models[EN] Manipulation is usually required for biomass calculation and food estimation for optimal fish growth in production facilities. However, the advances in computer-based systems have opened a new range of applied possibilities. In this study we used image analysis and a neural network algorithm that allowed us to successfully provide highly accurate biomass data. This developed system allowed us to compare the effects of reduced levels of human-animal interaction on the culture of adult Senegalese sole (Solea senegalensis) in terms of body weight gain. For this purpose, 30 adult fish were split into two homogeneous groups formed by three replicates (n = 5) each: a control group (CTRL), which was standard manipulated and an experimental group (EXP), which was maintained under a lower human-animal interaction culture using our system for biomass calculation. Visible implant elastomer was, for the first time, applied as tagging technology for tracking soles during the experiment (four months). The experimental group achieved a statistically significant weight gain (p < 0.0100) while CTRL animals did not report a statistical before-after weight increase. Individual body weight increment was lower (p < 0.0100) in standard-handled animals. In conclusion, our experimental approach provides evidence that our developed system for biomass calculation, which implies lower human-animal interaction, improves biomass gain in Senegalese sole individuals in a short period of time.S