Findings from a survey applied on a Portuguese General Hospital

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Spatiotemporal control of mitotic exit during anaphase by an aurora B-Cdk1 crosstalk

According to the prevailing ‘clock’ model, chromosome decondensation and nuclear envelope reformation when cells exit mitosis are byproducts of Cdk1 inactivation at the metaphase-anaphase transition, controlled by the spindle assembly checkpoint. However, mitotic exit was recently shown to be a function of chromosome separation during anaphase, assisted by a midzone Aurora B phosphorylation gradient-the ‘ruler’ model. Here we found that Cdk1 remains active during anaphase due to ongoing APC/CCdc20- and APC/CCdh1-mediated degradation of B-type Cyclins in Drosophila and human cells. Failure to degrade B-type Cyclins during anaphase prevented mitotic exit in a Cdk1-dependent manner. Cyclin B1-Cdk1 localized at the spindle midzone in an Aurora B-dependent manner, with incompletely separated chromosomes showing the highest Cdk1 activity. Slowing down anaphase chromosome motion delayed Cyclin B1 degradation and mitotic exit in an Aurora B-dependent manner. Thus, a crosstalk between molecular ‘rulers’ and ‘clocks’ licenses mitotic exit only after proper chromosome separation.We thank Eric Griffis, Jean-René Huynh, Claudio Sunkel, Jonathon Pines, Melina Schuh and Christian Lehner for the kind gift of reagents, and Marco Gonzalez-Gaitán for supporting OA during the final stages of this work. LPC is the recipient of a Marie Skłodowska-Curie Action fellowship (grant agreement 746515). EMS holds an FCT Investigator position and his work is supported by Fundac¸ ão para a Ciência e a Tecnologia (PTDC/BEX-BCM/0432/2014). This work was supported by R01GM107026 grant to TJM and a Commonwealth Honors College grant to CMC Confocal and FLIM microscopy data collection was performed in the Light Microscopy Facility and Nikon Center of Excellence at the Institute for Applied Life Sciences, University of Massachusetts Amherst with support from the Massachusetts Life Science Center. Work in the HM lab is supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 681443) and FLAD Life Science 2020

Towards general cooperative game playing

Attempts to develop generic approaches to game playing have been around for several years in the field of Artificial Intelligence. However, games that involve explicit cooperation among otherwise competitive players cooperative negotiation games have not been addressed by current approaches. Yet, such games provide a much richer set of features, related with social aspects of interactions, which make them appealing for envisioning real-world applications. This work proposes a generic agent architecture Alpha to tackle cooperative negotiation games, combining elements such as search strategies, negotiation, opponent modeling and trust management. The architecture is then validated in the context of two different games that fall in this category Diplomacy and Werewolves. Alpha agents are tested in several scenarios, against other state-of-the-art agents. Besides highlighting the promising performance of the agents, the role of each architectural component in each game is assessed. (c) Springer International Publishing AG, part of Springer Nature 2018

Study of the combination of self-activating photodynamic therapy and chemotherapy for cancer treatment

Cancer is a very challenging disease to treat, both in terms of treatment eficiency and side-effects. To overcome these problems, there have been extensive studies regarding the possibility of improving treatment by employing combination therapy, and by exploring therapeutic modalities with reduced side-effects (such as photodynamic therapy (PDT)). Herein, this work has two aims: (i) to develop self-activating photosensitizers for use in light-free photodynamic therapy, which would eliminate light-related restrictions that this therapy currently possesses; (ii) to assess their co-treatment potential when combined with reference chemotherapeutic agents (Tamoxifen and Metformin). We synthesized three new photosensitizers capable of self-activation and singlet oxygen production via a chemiluminescent reaction involving only a cancer marker and without requiring a light source. Cytotoxicity assays demonstrated the cytotoxic activity of all photosensitizers for prostate and breast tumor cell lines. Analysis of co-treatment effects revealed significant improvements for breast cancer, producing better results for all combinations than just for the individual photosensitizers and even Tamoxifen. By its turn, co-treatment for prostate cancer only presented better results for one combination than for just the isolated photosensitizers and Metformin. Nevertheless, it should be noted that the cytotoxicity of the isolated photosensitizers in prostate tumor cells was already very appreciable.This research was co-funded by Fundação para a Ciência e Tecnologia (FCT) and FEDER through COMPETE-POFC, grant number PTDC/QEQ-QFI/0289/2014; funded by FEDER through COMPETE2020, grant POCI-01-0145-FEDER-006980; funded by FEDER through NORTE2020, grant number NORTE-01-0145-FEDER 000028; co-funded by Fundação para a Ciência e Tecnologia (FCT) and FEDER through COMEPETE2020-POCI, grant number POCI-01-0145-FEDER-007274; co-funded by Fundação para a Ciência e Tecnologia (FCT) and FEDER, grant number IF/00092/2014/CP1255/CT0004; funded by Fundação para a Ciência e Tecnologia (FCT), grant number SFRH/BD/140734/2018; funded by Fundação para a Ciência e Tecnologia (FCT), grant number UID/QUI/50006/2013; funded by Fundação para a Ciência e Tecnologia (FCT), grant number PTDC/BIA-MIA/29059/2017; funded by Fundação para a Ciência e Tecnologia (FCT), grant number CEECIND/01425/2017; funded by Fundação para a Ciência e Tecnologia (FCT), grant number SFRH/BD/143211/2019

Lilia, A Showcase for Fast Bootstrap of Conversation-Like Dialogues Based on a Goal-Oriented System

International audienceRecently many works have proposed to cast human-machine interaction in a sentence generation scheme. Neural networks models can learn how to generate a probable sentence based on the user's statement along with a partial view of the dialogue history. While appealing to some extent, these approaches require huge training sets of general-purpose data and lack a principled way to intertwine language generation with information retrieval from back-end resources to fuel the dialogue with actualised and precise knowledge. As a practical alternative, in this paper, we present Lilia, a showcase for fast bootstrap of conversation-like dialogues based on a goal-oriented system. First, a comparison of goal-oriented and conversational system features is led, then a conversion process is described for the fast bootstrap of a new system, finalised with an on-line training of the system's main components. Lilia is dedicated to a chitchat task, where speakers exchange viewpoints on a displayed image while trying collaboratively to derive its author's intention. Evaluations with user trials showed its efficiency in a realistic setup

Shape controlled iron oxide nanoparticles: inducing branching and controlling particle crystallinity

Anisotropic nanoparticles (NPs) have garnered a great deal of attention for their applications in catalysis, magnetism and biomedicine. However, synthetic strategies to grow such NPs are still limited as their growth mechanisms are poorly understood. This work presents the synthesis of iron oxide nanoparticles (IONPs) based on the decomposition of iron(III) acetylacetonate in organic solvents to form anisotropic IONPs that are branched or multiply branched. We fully explore their growth parameters to understand the effect of varying amounts of oleylamine (OAm), as well as a nitrogen purge on particle morphology. We show here the synthetic relationship between a wide range of sizes and shapes of IONPs that are both isotropic and anisotropic. Of all the parameters, the amount of oleylamine in the reaction is the key to tune the particle size while the effect of a nitrogen gas purge during synthesis was shown to be crucial for the formation of the branched and multiply branched NPs. Two multiply branched NP systems with only a small difference in the synthetic conditions were shown to have radically different magnetic properties, such as heating in an alternating magnetic field. This was attributed to the defects found in the structure of one and not in the other. By following their development during growth, crystal defects were observed in both systems during the early stages of the reaction. However, for the multiply branched structure that became single crystalline, the aggregation of the nuclei occurred earlier in the reaction, allowing more time for growth and crystallite rearrangement to occur. These results have wide ranging implications for controlling the properties of anisotropic nanomaterials with similar structures, including their magnetic behavior