Modular Acquisition and Stimulation System for Timestamp-Driven Neuroscience Experiments

Dedicated systems are fundamental for neuroscience experimental protocols that require timing determinism and synchronous stimuli generation. We developed a data acquisition and stimuli generator system for neuroscience research, optimized for recording timestamps from up to 6 spiking neurons and entirely specified in a high-level Hardware Description Language (HDL). Despite the logic complexity penalty of synthesizing from such a language, it was possible to implement our design in a low-cost small reconfigurable device. Under a modular framework, we explored two different memory arbitration schemes for our system, evaluating both their logic element usage and resilience to input activity bursts. One of them was designed with a decoupled and latency insensitive approach, allowing for easier code reuse, while the other adopted a centralized scheme, constructed specifically for our application. The usage of a high-level HDL allowed straightforward and stepwise code modifications to transform one architecture into the other. The achieved modularity is very useful for rapidly prototyping novel electronic instrumentation systems tailored to scientific research.Comment: Preprint submitted to ARC 2015. Extended: 16 pages, 10 figures. The final publication is available at link.springer.co

Gas phase conformational basicity of carvedilol fragment B, 2(S)-1-(ethylamonium)propane-2-ol: An ab initio study on a protonophoretic of oxidative phosphorylation uncoupling

Carvedilol is cardiovascular drug of proven efficacy. It is believed that carvedilol exerts cardio-protective effects by acting as a mild uncoupler of mitochondrial oxidative phosphorylation, thereby protecting mitochondria from oxidative stress and preserving proper bioenergetics and cardiac function. This uncoupling occurs via a proton-shuttling mechanism involving the amino group of carvedilol's side-chain. However, the molecular details of carvedilol's proton affinity have not yet been completely worked out, especially with regards to the attributes of molecular conformation. In the present study, the full conformational basicity of a fragment of carvedilol, 2(S)-1-(ethylamonium)propane-2-ol (Fragment B), is presented to illustrate the protonophoretic character of carvedilol. Full gas phase geometry optimizations were performed at the ab initio, RHF/3-21G, level of theory for the entire potential energy hypersurface (PEHS) of Fragment B. Subsequently, since deprotonation can occur via two different protons, a two-prong methodology was applied to calculate vertical and adiabatic energies of deprotonation. A total of 18 out of a possible 81 minima converged and the dominant characteristic in all protonated and deprotonated conformers was a gauche plus effect in the rotation about the C-OH bond at the Fragment B stereocentre. Optimized energies of deprotonation ranged from 245 to 262 kcal mol-1 while protons involved in internal hydrogen bonding required an extra 6-8 kcal mol-1 for deprotonation compared to protons that were oriented away from the backbone structure. The overall trend indicates that conformers devoid of significant stabilization interactions possessed lower energies of deprotonation; in other words, as the relative conformer energy increased, vertical and adiabatic energies of deprotonation tended to decrease. Thus, extrapolating to carvedilol and the proton transfer mechanism involved in oxidative phosphorylation uncoupling, events of deprotonation will favour molecular conformations with minimal intramolecular stabilization and with higher relative energies

Dual Space of a Lattice as the Completion of a Pervin Space

16th International Conference, RAMiCS 2017, Lyon, France, May 15-18, 2017, ProceedingsInternational audienceThis survey paper presents well-known results from a new angle. A Pervin space is a set X equipped with a set of subsets,called the blocks of the Pervin space. Blocks are closed under finite intersections and finite unions and hence form a lattice of subsets of X. Pervin spaces are thus easier to define than topological spaces or (quasi)-uniform spaces. As a consequence, most of the standard topological notions, like convergence and cluster points, specialisation order, filtersand Cauchy filters, complete spaces and completion are much easier to define for Pervin spaces. In particular, the completion of a Pervin space turns out to be the dual space (in the sense of Stone) of the original lattice.We show that any lattice of subsets can be described by a set of inequations of the form u ≤ v, where u and v are elements of its dual space. Applications to formal languages and complexity classes are given.Cet article de synthèse présente des résultats bien connus sous un nouvel angle. Un espace de Pervin est unensemble X équipé d'un ensemble de parties, appelé les blocs de l'espace de Pervin. Les blocs sont fermés par intersection finie et union finie et forment ainsi un treillis de parties de X. Les espaces de Pervin sont doncplus faciles à définir que les espaces topologiques ou les espaces (quasi-)uniformes. Par conséquent, la plupart des notions topologiques, comme la convergence et les points d'adhérence, l'ordre de spécialisation, les filtres de Cauchy, les espaces complets et la complétion sont beaucoup plus faciles à définir pour les espaces Pervin. En particulier, la complétion d'un espace Pervin s'avère être l'espace dual (au sens de Stone) du treillis de départ.Nous montrons que tout treillis de parties peut être décrit par un ensemble d'inéquations de la forme u ≤ v, où u et v sont des éléments de son espace dual. On donne des applications aux langages formels et aux classes de complexité

Communication in Clinical Practice, the Perspective of Patients with Cancer: Translation of the PACE (Patient Assessment of Cancer Communication Experiences) Questionnaire to European Portuguese

Introduction: Communication in clinical practice is essential to healthcare quality, especially in Oncology. The Patient Assessment of Communication Experiences questionnaire evaluates the perspective of cancer patients towards communication and identifies areas that can be improved. This study consists in its translation and validation to European Portuguese, to identify these areas. Material and methods: We performed a descriptive, observational, cross-sectional study. The translation was conducted according to the World Health Organization's guidelines. We applied the questionnaires to a convenience sample, in patients under systemic antineoplastic treatment at the Day Hospital of Centro Hospitalar Universitário do Porto, between January and March 2020. We calculated the Cronbach's Alpha for each phase of care, the bivariate and multiple correlations and, for each question, the percentage of "non applicable" and most positive answers. Results: We had 100 participants. The instrument we obtained ha good internal consistency, but the classification of some questions does not correlate sufficiently with the global opinion about the experiences with communication in the respective phase. The diagnosis phase revealed a lower proportion of positive experiences, particularly in terms of receiving the bad news. Conclusion: This study translates and validates part of the communication assessment instrument PACE to the Portuguese language and elicits the necessity to invest in the phase of diagnosis and disclosure of bad news.ste trabalho não recebeu qualquer tipo de suporte financeiro de nenhuma entidade no domínio público ou privado

Fungal iron availability during deep seated candidiasis is defined by a complex interplay involving systemic and local events

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Profiling the circulating miRnome reveals a temporal regulation of the bone injury response

Bone injury healing is an orchestrated process that starts with an inflammatory phase followed by repair and remodelling of the bone defect. The initial inflammation is characterized by local changes in immune cell populations and molecular mediators, including microRNAs (miRNAs). However, the systemic response to bone injury remains largely uncharacterized. Thus, this study aimed to profile the changes in the plasma miRnome after bone injury and determine its biological implications. Methods: A rat model of femoral bone defect was used, and animals were evaluated at days 3 and 14 after injury. Non-operated (NO) and sham operated animals were used as controls. Blood and spleen were collected and peripheral blood mononuclear cells (PBMC) and plasma were separated. Plasma miRnome was determined by RT-qPCR array and bioinformatics Ingenuity pathway analysis (IPA) was performed. Proliferation of bone marrow mesenchymal stem/stromal cells (MSC) was evaluated by Ki67 staining and high-throughput cell imaging. Candidate miRNAs were evaluated in splenocytes by RT-qPCR, and proteins found in the IPA analysis were analysed in splenocytes and PBMC by Western blot. Results: Bone injury resulted in timely controlled changes to the miRNA expression profile in plasma. At day 3 there was a major down-regulation of miRNA levels, which was partially recovered by day 14 post-injury. Interestingly, bone injury led to a significant up-regulation of let-7a, let-7d and miR-21 in plasma and splenocytes at day 14 relative to day 3 after bone injury, but not in sham operated animals. IPA predicted that most miRNAs temporally affected were involved in cellular development, proliferation and movement. MSC proliferation was analysed and found significantly increased in response to plasma of animals days 3 and 14 post-injury, but not from NO animals. Moreover, IPA predicted that miRNA processing proteins Ago2 and Dicer were specifically inhibited at day 3 post-injury, with Ago2 becoming activated at day 14. Protein levels of Ago2 and Dicer in splenocytes were increased at day 14 relative to day 3 post-bone injury and NO animals, while in PBMC, levels were reduced at day 3 (albeit Dicer was not significant) and remained low at day 14. Ephrin receptor B6 followed the same tendency as Ago2 and Dicer, while Smad2/3 was significantly decreased in splenocytes from day 14 relative to NO and day 3 post-bone injury animals. Conclusion: Results show a systemic miRNA response to bone injury that is regulated in time and is related to inflammation resolution and the start of bone repair/regeneration, unravelling candidate miRNAs to be used as biomarkers in the monitoring of healthy bone healing and as therapeutic targets for the development of improved bone regeneration therapies.This work was funded by project NORTE-01-0145-FEDER-000012, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and AO Foundation-Switzerland (project S-15-83S). AMS, MIA, CC and JHT were supported by FCT-Fundação para a Ciência e a Tecnologia, through fellowships SFRH/BD/ 85968/2012, SFRH/BPD/91011/2012, SFRH/BDP/ 87071/2012 and SFRH/BD/112832/2015, respecttively. Work in Dr. Calin's laboratory is supported by National Institutes of Health (NIH/NCATS) grant UH3TR00943-01 through the NIH Common Fund, Office of Strategic Coordination (OSC), the NIH/NCI grant 1R01CA182905-01, a U54 grant-UPR/MDACC Partnership for Excellence in Cancer Research 2016 Pilot Project, a Team DOD (CA160445P1) grant, a Ladies Leukemia League grant, a CLL Moonshot Flagship project, a SINF 2017 grant, and the Estate of C. G. Johnson, J

Promoting academic development through situated critical reflection

Many changes in higher education derived from Europe-wide initiatives such as the Bologna process have given increasing attention to student-centred teaching approaches, allied to growth in teachers’ academic development (Clarke & Reid, 2013; HE Academy, 2011). Our study is one component of a long-standing project focused on ways to promote academic development in the context of higher education. Work since 2001 has provided a strong understanding of the dynamics of student-generated questioning, inquiry-based learning and academic practices (Pedrosa de Jesus, Lopes, Moreira & Watts, 2012)