Alternative Splicing in Oncogenic Kinases: From Physiological Functions to Cancer

Among the 518 protein kinases encoded by the human kinome, several of them act as oncoproteins in human cancers. Like other eukaryotic genes, oncogenes encoding protein kinases are frequently subjected to alternative splicing in coding as well as noncoding sequences. In the present paper, we will illustrate how alternative splicing can significantly impact on the physiological functions of oncogenic protein kinases, as demonstrated by mouse genetic model studies. This includes examples of membrane-bound tyrosine kinases receptors (FGFR2, Ret, TrkB, ErbB4, and VEGFR) as well as cytosolic protein kinases (B-Raf). We will further discuss how regular alternative splicing events of these kinases are in some instances implicated in oncogenic processes during tumor progression (FGFR, TrkB, ErbB2, Abl, and AuroraA). Finally, we will present typical examples of aberrant splicing responsible for the deregulation of oncogenic kinases activity in cancers (AuroraB, Jak2, Kit, Met, and Ron)

Bandit algorithms for searching large spaces

Bandit games consist of single-state environments in which an agent must sequentially choose actions to take, for which rewards are given. The objective being to maximise the cumulated reward, the agent naturally seeks to build a model of the relationship between actions and rewards. The agent must both choose uncertain actions in order to improve its model (exploration), and actions that are believed to yield high rewards according to the model (exploitation). The choice of an action to take is called a play of an arm of the bandit, and the total number of plays may or may not be known in advance. Algorithms designed to handle the exploration-exploitation dilemma were initially motivated by problems with rather small numbers of actions. But the ideas they were based on have been extended to cases where the number of actions to choose from is much larger than the maximum possible number of plays. Several problems fall into this setting, such as information retrieval with relevance feedback, where the system must learn what a user is looking for while serving relevant documents often enough, but also global optimisation, where the search for an optimum is done by selecting where to acquire potentially expensive samples of a target function. All have in common the search of large spaces. In this thesis, we focus on an algorithm based on the Gaussian Processes probabilistic model, often used in Bayesian optimisation, and the Upper Confidence Bound action-selection heuristic that is popular in bandit algorithms. In addition to demonstrating the advantages of the GP-UCB algorithm on an image retrieval problem, we show how it can be adapted in order to search tree-structured spaces. We provide an efficient implementation, theoretical guarantees on the algorithm's performance, and empirical evidence that it handles large branching factors better than previous bandit-based algorithms, on synthetic trees

Bandit algorithms in recommender systems

Peer reviewe

Training Symbol-Based Equalization for Quadrature Duobinary PDM-FTN Systems

A training symbol-based equalization algorithm is proposed for polarization de-multiplexing in quadrature duobinary (QDB) modulated polarization division multiplexedfaster-than-Nyquist (FTN) coherent optical systems. The proposed algorithm is based on the least mean square algorithm, and multiple location candidates of a symbol are considered in order to make use of the training symbols with QDB modulation.Results show that an excellent convergence performance is obtained using the proposed algorithm under different polarization alignment scenarios. The optical signal-to-noise ratio required to attain a bit error rate of 2*10-2 is reduced by 1.7 and 1.8 dB using the proposed algorithm, compared to systems using the constant modulus algorithm with differential coding for 4-ary quadrature amplitude modulation(4-QAM) and 16-QAM systems with symbol-by-symbol detection, respectively.Furthermore, comparisons with the Tomlinson-Harashima precoding-based FTN systems illustrate that QDB is preferable when 4-QAM is utilized

Protocols and Structures for Inference: A RESTful API for Machine Learning

Abstract Diversity in machine learning APIs (in both software toolkits and web services), works against realising machine learning's full potential, making it difficult to draw on individual algorithms from different products or to compose multiple algorithms to solve complex tasks. This paper introduces the Protocols and Structures for Inference (PSI) service architecture and specification, which presents inferential entities-relations, attributes, learners and predictors-as RESTful web resources that are accessible via a common but flexible and extensible interface. Resources describe the data they ingest or emit using a variant of the JSON schema language, and the API has mechanisms to support non-JSON data and future extension of service features

Experimental investigation of the effect of ionization on the 51V(p,n)51Cr reaction

The investigation of the effects of average atomic ionization on nuclear reactions is of prime importance for nuclear astrophysics. No direct experimental measurement using a plasma target has been done yet. In this regard, we measured for the first time the neutron production of a (p,n) reaction in different states of ionization. The studied nuclear reaction was 51V(p,n)51Cr. We measured a significantly lower neutron production than expected when the target was ionized, even when taking into account existing electron screening theory or the effect of the stopping power in the target on the injected proton beam. This experiment is a first step in the process to characterize the influence of ionization at astrophysically relevant energies.Comment: 20 pages, 10 figures, submitted to EP

Video games in adolescence and emotional functioning: Emotion regulation, emotion intensity, emotion expression, and alexithymia

International audienceVideo-game users represent 40% of the French population and adolescents are the primary users. Yet excessive playing of video games has become a problem in modern society and is manifesting itself in treatment centers for adolescents. Before attempting to gain insight into this problematic use, we must understand video gaming itself and its implications for the gamer. The aim of this research is to propose an understanding of video-game playing based on some dimensions of emotional functioning such as emotion regulation, emotion intensity, emotion expression, and alexithymia. A total of 159 adolescents took part in the study. Regular gamers regulated their emotions more than irregular gamers did. They also felt their emotions more intensely. But regular gamers expressed their emotions less than irregular gamers did. Finally, the regular gamers' alexithymia level was higher than the irregular gamers' level. Especially, they had more difficulty being emotionally reactive. The avatar's evolution in the virtual environment may help mediate adolescents' problematic emotional experiences to give them meaning and enable their appropriation. As such, video games may act as a medium for projecting and experiencing one's emotional life by staging the emotional self, thereby explaining the engagement of adolescents in video gaming

Profiles of Parental Burnout Around the Globe: Similarities and Differences Across 36 Countries

Parental burnout (PB) is a pervasive phenomenon. Parenting is embedded in cultural values, and previous research has shown the role of individualism in PB. In this paper, we reanalyze previously collected data to identify profiles based on the four dimensions of PB, and explore whether these profiles vary across countries’ levels of collectivistic-individualistic (COL-IND) values. Our sample comprised 16,885 individuals from 36 countries (73% women; 27% men), and we used a latent profile approach to uncover PB profiles. The findings showed five profiles: Fulfilled, Not in PB, Low risk of PB, High risk of PB and Burned out. The profiles pointed to climbing levels of PB in the total sample and in each of the three country groups (High COL/Low IND, Medium COL-IND, Low COL/High IND). Exploratory analyses revealed that distinct dimensions of PB had the most prominent roles in the climbing pattern, depending on the countries’ levels of COL/IND. In particular, we found contrast to be a hallmark dimension and an indicator of severe burnout for individualistic countries. Contrary to our predictions, emotional distance and saturation did not allow a clear differentiation across collectivistic countries. Our findings support several research avenues regarding PB measurement and intervention

Profiles of Parental Burnout Around the Globe: Similarities and Differences Across 36 Countries

Parental burnout (PB) is a pervasive phenomenon. Parenting is embedded in cultural values, and previous research has shown the role of individualism in PB. In this paper, we reanalyze previously collected data to identify profiles based on the four dimensions of PB, and explore whether these profiles vary across countries' levels of collectivistic-individualistic (COL-IND) values. Our sample comprised 16,885 individuals from 36 countries (73% women; 27% men), and we used a latent profile approach to uncover PB profiles. The findings showed five profiles: Fulfilled, Not in PB, Low risk of PB, High risk of PB and Burned out. The profiles pointed to climbing levels of PB in the total sample and in each of the three country groups (High COL/Low IND, Medium COL-IND, Low COL/High IND). Exploratory analyses revealed that distinct dimensions of PB had the most prominent roles in the climbing pattern, depending on the countries' levels of COL/IND. In particular, we found contrast to be a hallmark dimension and an indicator of severe burnout for individualistic countries. Contrary to our predictions, emotional distance and saturation did not allow a clear differentiation across collectivistic countries. Our findings support several research avenues regarding PB measurement and intervention