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Abstract Medulloblastoma (MB) is the most prevalent brain cancer in children. Four subgroups of MB have been identified; of these, Group 3 is the most metastatic. Its genetics and biology remain less clear than the other groups, and it has a poor prognosis and few effective treatments available. Tumor hypoxia and the resulting metabolism are known to be important in the growth and survival of tumors but, to date, have been only minimally explored in MB. Here we show that Group 3 MB tumors do not depend on the canonical transcription factor hypoxia-inducible factor-1α (HIF-1α) to mount an adaptive response to hypoxia. We discovered that HIF-1α is rendered inactive either through post-translational methylation, preventing its nuclear localization specifically in Group 3 MB, or by a low expression that prevents modulation of HIF-target genes. Strikingly, we found that HIF-2 takes over the role of HIF-1 in the nucleus and promotes the activation of hypoxia-dependent anabolic pathways. The exclusion of HIF-1 from the nucleus in Group 3 MB cells enhances the reliance on HIF-2’s transcriptional role, making it a viable target for potential anticancer strategies. By combining pharmacological inhibition of HIF-2α with the use of metformin, a mitochondrial complex I inhibitor to block respiration, we effectively induced Group 3 MB cell death, surpassing the effectiveness observed in Non-Group 3 MB cells. Overall, the unique dependence of MB cells, but not normal cells, on HIF-2-mediated anabolic metabolism presents an appealing therapeutic opportunity for treating Group 3 MB patients with minimal toxicity.

Abstract Medulloblastoma is a cancerous brain tumor that affects mostly children. Among the four groups defined by molecular characteristics, Group 3, the least well characterized, is also the least favorable, with a survival rate of 50%. Current treatments, based on surgery, radiotherapy, and chemotherapy, are not adequate and the lack of understanding of the different molecular features of Group 3 tumor cells makes the development of effective therapies challenging. In this study, the problem of medulloblastoma is approached from a metabolic standpoint in a low oxygen microenvironment. We establish that Group 3 cells use both the mitochondrial glycerol-3 phosphate (G3PS) and malate-aspartate shuttles (MAS) to produce NADH. Small molecules that target G3PS and MAS show a greater ability to decrease cell proliferation and induce apoptosis specifically of Group 3 cells. In addition, as Group 3 cells show improved respiration in hypoxia, the use of Phenformin, a mitochondrial complex 1 inhibitor, alone or in combination, induced significant cell death. Furthermore, inhibition of the cytosolic NAD+ recycling enzyme lactate dehydrogenase A (LDHA), enhanced the effects of the NADH shuttle inhibitors. In a 3D model using Group 3 human cerebellar organoids, tumor cells also underwent apoptosis upon treatment with NADH shuttle inhibitors. Our study demonstrates metabolic heterogeneity depending on oxygen concentrations and provides potential therapeutic solutions for patients in Group 3 whose tumors are the most aggressive.

RESUMEN El objetivo de este trabajo consistió en analizar el impacto de un modelo de evaluación recíproca en el aprendizaje de los alumnos en deportes de equipo en contexto escolar. La muestra estuvo compuesta por 48 alumnos divididos en un grupo experimental (24 sujetos) y un grupo control (24 sujetos) pertenecientes a dos cursos de 2º de la Enseñanza Secundaria Obligatoria (ESO). La variable dependiente es aprendizaje alcanzado por los alumnos en los deportes de Baloncesto, Balonmano y Fútbol-sala en su conocimiento declarativo, la toma de decisión y la ejecución motriz de las habilidades técnico-tácticas. Para ello se utilizaron dos instrumentos adaptados del Games Performance Assessment Instrument (GPAI): un cuestionario para medir el conocimiento declarativo y un formato de campo para analizar a través de la observación la toma de decisiones y la ejecución de las habilidades en situaciones de juego. En la comparación entre el grupo experimental y el grupo control en el desarrollo de tres unidades didácticas de Baloncesto, Balonmano y Fútbol-sala, el grupo experimental (aquel que realizó la evaluación recíproca) mejoró significativamente más que el grupo control en todos los indicadores evaluados. La evaluación recíproca de los alumnos permitió mejorar el aprendizaje en los deportes de equipo y parece constituirse como un instrumento de aprendizaje muy útil en la enseñanza de la educación física Palabras Clave: Evaluación recíproca, deportes de equipo, toma de decisión, ejecución de habilidades, educación física. ABSTRACT Evaluating students´ performance in team sports at school is a problem many investigators have faced. Our study has aimed to build, to apply and to verify the effectiveness, in students´ learning, an adaptation of the Assessment Process of Performance in team sports (GPAI), created by Oslin, Mitchell and Griffin (1998) to be used in the Physical Education subject at school. The sample consisted of 48 pupils divides into an experimental group (24 pupils) and a control group (24 pupils) belonging to the second year of the Enseñanza Secundaria Obligatoria (ESO). The dependent variable was the performance obtained by pupils in their declarative knowledge, general game performance decision making and skill execution. As assessment instruments were used the written questionnaire, to evaluate pupils´ declarative knowledge and the observation of pupils´ performance in a game situation by a team of three experts to check the levels of qualify in decision making and the skill execution. Analysing the information differences were found in the results of an experimental group and a control group. The experimental group of pupils has been submitted to an observation program of their peer´ performance in game. We can verify statistically significant differences in the results of both groups in the following aspects: declarative knowledge, general game performance decision making and skill execution. These results achieved in the final evaluation were better in the experimental group. Key Words: Assessment, Physical Education, peer´ assessment, decision making, skill execution, team sports.

En este artículo se estudian los efectos del rendimiento y el azar en la posición que ocupan los equipos en la clasificación de la Liga Española de Fútbol en la temporada 2003-2004. Para ello, se utiliza una metodología basada en la regresión lineal y la comparación de medias. Los resultados empíricos sugieren que el azar puede tener relevancia para explicar el resultado de los equipos en un único partido, pero que a partir de cierta cantidad de encuentros el rendimiento es el factor determinante para dar cuenta de los puntos que alcanzan los conjuntos. PALABRAS CLAVE: azar, fútbol, rendimiento, resultadoIn this paper, the effects of performance and random in the position of each team in the Spanish Soccer League in the season 2003-2004 are analysed. The research is based on linear regression analysis and mean comparison tests. My findings lead me to conclude that hazard is a relevant variable for explaining the result of the teams in one only match. However, the higher the number of matches taken into account, the more important performance and the less random. KEY WORDS: random, performance, result, soccer

RESUMEN Los objetivos de este trabajo son dos. En primer lugar estudiar los efectos que tiene disputar un partido de la Liga de Campeones sobre el resultado alcanzado por los equipos en la Liga Española en esa misma semana. En segundo lugar, verificar si la probabilidad de ganar frente a perder en la Liga Española es mayor o no para los equipos con experiencia en la Liga de Campeones frente a aquellos otros conjuntos que disputan por primera vez esta competición. La muestra consiste en 184 partidos de la Liga Española de Fútbol jugados por los equipos que se encontraban simultáneamente disputando la primera fase de la Liga de Campeones en las temporadas 2003-2004, 2004-2005 y 2005-2006. Los datos utilizados en la investigación han sido tomados de la página oficial de la Liga de Campeones, de la Liga Española y suministrados por GECA SPORT. De acuerdo con los resultados de la estimación de un modelo logit multinomial, disputar un partido de la Liga de Campeones durante la semana de competición no reduce la probabilidad de los equipos de ganar frente a perder en el partido de la Liga Nacional. Incluso tiene un efecto positivo para los equipos debutantes en la competición europea: cuando juegan durante la semana tienen más probabilidades de ganar en la Liga Nacional (p Palabras clave: resultado, fútbol, Liga de Campeones. logit multinomial, Liga Española ABSTRACT This paper has two goals. First, studying the impact of playing in the Champions League on the results in the Spanish League. Second, analyzing whether being a beginner team in the Champions League is a relevant variable in explaining the impact of playing in the Champions League on the results in the Spanish League. The empirical analysis is based on data from 184 matches in the Spanish Soccer League for those teams playing at the same time both competitions. Data used in the research were given by GECA SPORT and taken from the official site of the Champions League and the Spanish League. According to the estimation of a mutinomial logit model, playing in the Champions League has no a statistically significant impact on the probability of winning a given match in the Spanish League. On the contrary, it has a positive effect for beginner teams in the Champions League: their probability of winning a given match is higher in those weeks when they play in the Champions League (p Key words: result, soccer, Champions League, logit multinomial, Spanish Soccer League

RESUMEN El objetivo de este estudio consistió en examinar el efecto de la localización del partido, el nivel del oponente y el marcador sobre la actividad física de los jugadores en el fútbol de alto nivel. Para ello fueron analizados 27 partidos disputados por un equipo de fútbol profesional en la temporada 2005-2006 de la Liga Española de Fútbol de Primera División utilizando un sistema computerizado de análisis del juego. La variable dependiente consistió en la distancia cubierta por los jugadores a diferentes intensidades. Los datos fueron analizados mediante un análisis de regresión lineal que incorporó cuatro variables independientes: el marcador del partido, la localización del encuentro (casa o fuera), el nivel del oponente y el puesto específico de los jugadores. Los resultados indican que la distancia cubierta por los jugadores a diferentes intensidades estuvo influida por una o más variables contextuales, con la localización del partido y, sobre todo, el marcador como aspectos más relevantes. Los futbolistas recorrieron menos distancia a alta intensidad (>19.1 km/h) cuando tuvieron el marcador a favor que cuando iban perdiendo. Los jugadores que jugaron en casa cubrieron una distancia mayor que los visitantes a baja intensidad (< 14.1 km/h), pero no se apreciaron diferencias a media, submáxima o máxima intensidad .No hubo diferencias entre ningún puesto específico cuando se comparó la distancia cubierta a baja intensidad. Sin embargo, los delanteros y los interiores laterales cubrieron una distancia mayor que los defensas y los mediocentros a submáxima y máxima intensidad.Palabras Clave: análisis del juego, variables contextuales, fútbol. rendimiento físico. ABSTRACT The aim of this study was to evaluate the effect of match location, quality of the opposition and match status on the work-rate of elite soccer player. Twenty-seven Spanish Premier League matches played by a professional soccer team were monitored in the 2005-2006 season using a multiple-camera match analyses system. Dependent variables were the distance covered by players at different intensities. Data were analyzed using a linear regression analysis with four independent variables: the match status, the match location, the quality of the opponent and the positional role of the players. The distance covered by players at different work intensities was influenced by situational variables, particularly by match location and match status. The top-class players performed less high-intensity activity (>19.1 km/h) when winning than when they were losing, but more distance was covered by walking and jogging when winning. The home teams covered a greater distance than away teams at low intensity (< 14.1 km/h), but no differences were found at medium, submaximal or maximal intensities. There were no differences between players of any position when comparing the distance covered at low intensities. However, at submaximal and maximal intensities external midfield players and forwards covered greater distances than defenders and central midfield players.Key Words: time-motion analysis, contextual factors, soccer, physical performance.

The aim of this study is to analyze the influence of performance and chance on the results obtained by teams in football official competitions with different formats of competition. The research is based in data from 190 matches of the 2006/2007 Spanish Football League, 64 matches of the 2006 World Cup Germany and 125 matches of the 2005/20006 European Champions League. Performance is measured as the difference between shots attempted and shots received by a team in each game. Results from linear regression analysis show that in competitions with a league system, (Spanish Football League, first round of the 2006 World Cup Germany and first round of the 2005/20006 European Champions League) performance is a statistically significant variable for explaining the results obtained by teams. In competitions with a Knock-Out system (second round of the 2006 World Cup Germany and second round of the 2005/20006 European Champions League) there is not statistically significant differences in the performance obtained by winners and losers. I find that chance is a relevant variable for explaining the results of teams in competitions with a Knock-Out system. Key words:Schedukle of competition, peformance, chance, football

The aim of this study was to evaluate the effect of match location, quality of the opposition and match status on the work-rate of elite soccer player. Twenty-seven Spanish Premier League matches played by a professional soccer team were monitored in the 2005-2006 season using a multiple-camera match analyses system. Dependent variables were the distance covered by players at different intensities. Data were analyzed using a linear regression analysis with four independent variables: the match status, the match location, the quality of the opponent and the positional role of the players. The distance covered by players at different work intensities was influenced by situational variables, particularly by match location and match status. The top-class players performed less high-intensity activity (>19.1 km/h) when winning than when they were losing, but more distance was covered by walking and jogging when winning. The home teams covered a greater distance than away teams at low intensity (< 14.1 km/h), but no differences were found at medium, submaximal or maximal intensities. There were no differences between players of any position when comparing the distance covered at low intensities. However, at submaximal and maximal intensities external midfield players and forwards covered greater distances than defenders and central midfield players. Key Words: time-motion analysis, contextual factors, soccer, physical performance.

This paper has two goals. First, studying the impact of playing in the Champions League on the results in the Spanish League. Second, analyzing whether being a beginner team in the Champions League is a relevant variable in explaining the impact of playing in the Champions League on the results in the Spanish League. The empirical analysis is based on data from 184 matches in the Spanish Soccer League for those teams playing at the same time both competitions. Data used in the research were given by GECA SPORT and taken from the official site of the Champions League and the Spanish League. According to the estimation of a mutinomial logit model, playing in the Champions League has no a statistically significant impact on the probability of winning a given match in the Spanish League. On the contrary, it has a positive effect for beginner teams in the Champions League: their probability of winning a given match is higher in those weeks when they play in the Champions League (p

In this paper, the impact of the coach´s change on the results obtained by teams in the Spanish Soccer League is analyzed. The empirical analysis is based on data from the 1997-1998 to the 2006-2007 seasons of the First and Second Spanish Soccer League. According to the estimations based on linear regression analysis and mean comparison test, the first conclusion is that teams with a new coach obtain more points in comparison with the results reached by the dismissed coach. Moreover, it has been verified that the winning effect of the new coach does not have a linear influence throughout the time. The positive effect of the coach's change on the result of teams diminishes progressively up to managing to be annulled. In other words, the higher the number of days the lower the impact of the winning effect of the new coaches. Finally, it has been verified that the effect of the coach´s change on the results of teams is not different when there are compared the First one and the Second Division of the Spanish Soccer League. Key Words:coach´s change, soccer, linear regression analysis, results.

In this paper, the effects of performance and random in the position of each team in the Spanish Soccer League in the season 2003-2004 are analysed. The research is based on linear regression analysis and mean comparison tests. My findings lead me to conclude that hazard is a relevant variable for explaining the result of the teams in one only match. However, the higher the number of matches taken into account, the more important performance and the less random. KEY WORDS: random, performance, result, soccer

Evaluating students´ performance in team sports at school is a problem many investigators have faced. Our study has aimed to build, to apply and to verify the effectiveness, in students´ learning, an adaptation of the Assessment Process of Performance in team sports (GPAI), created by Oslin, Mitchell and Griffin (1998) to be used in the Physical Education subject at school. The sample consisted of 48 pupils divides into an experimental group (24 pupils) and a control group (24 pupils) belonging to the second year of the Enseñanza Secundaria Obligatoria (ESO). The dependent variable was the performance obtained by pupils in their declarative knowledge, general game performance decision making and skill execution. As assessment instruments were used the written questionnaire, to evaluate pupils´ declarative knowledge and the observation of pupils´ performance in a game situation by a team of three experts to check the levels of qualify in decision making and the skill execution. Analysing the information differences were found in the results of an experimental group and a control group. The experimental group of pupils has been submitted to an observation program of their peer´ performance in game. We can verify statistically significant differences in the results of both groups in the following aspects: declarative knowledge, general game performance decision making and skill execution. These results achieved in the final evaluation were better in the experimental group. Key Words: Assessment, Physical Education, peer´ assessment, decision making, skill execution, team sports.

Background: Several techniques have been described to repair giant omphaloceles. Component Separation Technique (CST) is a surgical technique first reported in adults to repair large abdominal wall defects. The purpose of this study is to describe our experience using this technique in repairing large ventral hernias secondary to giant omphaloceles in children. Methods: Nine patients with giant omphalocele were treated. The abdominal wall was reconstructed using CST, based on the enlargement of the abdominal wall by separate mobilization of the muscular layers. Patients were monitored for complications during admission, postoperative complications, and all patients were seen for follow-up. Results: Component separation technique was performed at a median age of 7.2 years. The median diameter of the hernia was 109.8 cm2. There was no mortality. Minor complications were seen (infection, skin necrosis, and hematoma). There were no recurrences after an average follow-up of 3.3 years (2 - 4 years). Conclusions: Component separation technique is a valuable method for repairing large ventral hernias as a consequence of giant omphaloceles in children. Our series supports the use of CST in children, in a wide age range, from newborns for primary closure to adolescence in cases of giant ventral hernias secondary to omphaloceles with multiple previous surgeries. Level of Evidence: II

Ciudad Limpia Valdivia is a Web and Mobile application which attempts to tackle some of the Municipality of Valdivia in Chile’s waste collection issues. It is based on Free and Open Source Software and it is currently in the last stage of prototyping. The tool is expected to improve the communication between the users and the service provider. It also has educational materials about waste management and other related environmental issues to guide the users to minimize the waste production and optimize the way it is handled before it is collected. The main features of the solution are: a dynamic map viewer showing the position of the Municipality’s waste collection trucks and estimated future trajectories, a form to report illegal dumping microsites, notifications from the Municipality about the status of the service, educational content and contact list of other independent initiatives related to waste collection. The potential impact of the tool was evaluated on the city’s test pilot sector by means of a neighbourhood survey. It showed that the solution might have a positive impact in the coordination in terms of the service operation. The estimation of the trucks’ future trajectory will be developed using machine learning or computational intelligence algorithms. The integration of FOSS technologies has been essential to address challenges found during development as well as to adapt the tool to new scenarios. The feedback from the Municipality and the community has proved to be very important to define a concrete solution.

Abstract Background Most of our understanding on the social behavior and genomics of bees and other social insects is centered on the Western honey bee, Apis mellifera. The genus Apis, however, is a highly derived branch comprising less than a dozen species, four of which genomically characterized. In contrast, for the equally highly eusocial, yet taxonomically and biologically more diverse Meliponini, a full genome sequence was so far available for a single Melipona species only. We present here the genome sequence of Frieseomelitta varia, a stingless bee that has, as a peculiarity, a completely sterile worker caste. Results The assembly of 243,974,526 high quality Illumina reads resulted in a predicted assembled genome size of 275 Mb composed of 2173 scaffolds. A BUSCO analysis for the 10,526 predicted genes showed that these represent 96.6% of the expected hymenopteran orthologs. We also predicted 169,371 repetitive genomic components, 2083 putative transposable elements, and 1946 genes for non-coding RNAs, largely long non-coding RNAs. The mitochondrial genome comprises 15,144 bp, encoding 13 proteins, 22 tRNAs and 2 rRNAs. We observed considerable rearrangement in the mitochondrial gene order compared to other bees. For an in-depth analysis of genes related to social biology, we manually checked the annotations for 533 automatically predicted gene models, including 127 genes related to reproductive processes, 104 to development, and 174 immunity-related genes. We also performed specific searches for genes containing transcription factor domains and genes related to neurogenesis and chemosensory communication. Conclusions The total genome size for F. varia is similar to the sequenced genomes of other bees. Using specific prediction methods, we identified a large number of repetitive genome components and long non-coding RNAs, which could provide the molecular basis for gene regulatory plasticity, including worker reproduction. The remarkable reshuffling in gene order in the mitochondrial genome suggests that stingless bees may be a hotspot for mtDNA evolution. Hence, while being just the second stingless bee genome sequenced, we expect that subsequent targeting of a selected set of species from this diverse clade of highly eusocial bees will reveal relevant evolutionary signals and trends related to eusociality in these important pollinators.

ABSTRACT Corn grain yield, nitrogen (N) fertilizer efficiency and distribution to corn alone and three forms of corn and palisadegrass (Urochloa spp.) intercropping implantation was investigated. A field experiment with 15N labeling fertilizer was performed in randomized block design. No form of palisadegrass intercropping implantation affected corn grain yield, total N accumulation and N use efficiency (NUE), which were 8.7 t ha-1, 205 kg ha-1 and 37% respectively. The palisadegrass produced on average 1.9 t of dry mass, absorbing a maximum of 6 kg ha-1 or 5.5% of N fertilizer during corn growing. Furthermore, the palisadegrass did not affect N fertilizer distribution in soil-plant system, in which 28.2% was recovered in the soil and 40.4% in the plants (corn + palisadegrass). The results show that for the three intercropping implantation methods the palisadegrass did not compete with corn for N fertilizer.