CRISPR/Cas9‐mediated genome editing: from basic research to translational medicine

The recent development of the CRISPR/Cas9 system as an efficient and accessible programmable genome-editing tool has revolutionized basic science research. CRISPR/Cas9 system-based technologies have armed researchers with new powerful tools to unveil the impact of genetics on disease development by enabling the creation of precise cellular and animal models of human diseases. The therapeutic potential of these technologies is tremendous, particularly in gene therapy, in which a patient-specific mutation is genetically corrected in order to treat human diseases that are untreatable with conventional therapies. However, the translation of CRISPR/Cas9 into the clinics will be challenging, since we still need to improve the efficiency, specificity and delivery of this technology. In this review, we focus on several in vitro, in vivo and ex vivo applications of the CRISPR/Cas9 system in human disease-focused research, explore the potential of this technology in translational medicine and discuss some of the major challenges for its future use in patients.Portuguese Foundation for Science and Technology: UID/BIM/04773/2013 1334 Spanish Ministry of Science, Innovation and Universities RTI2018-094629-B-I00 Portuguese Foundation for Science and Technology SFRH/BPD/100434/2014 European Union (EU) 748585 LPCC-NRS/Terry Fox grantsinfo:eu-repo/semantics/publishedVersio

Inefficient lobbying, populism and oligarchy

This paper analyses the efficiency consequences of lobbying in a production economy with imperfect commitment. We first show that the Pareto efficiency result found for truthful equilibria of common agency games in static exchange economies no longer holds under these more general conditions. We construct a model of pressure groups where the set of e.cient truthful common-agency equilibria has measure zero. Equilibria are generally inefficient as a direct result of the existence of groups with conflicting interests, which allocate real resources to lobbying. If lobbies representing "the poor " and "the rich " have identical organizational capacities, we show that these equilibria are biased towards the poor, who have a comparative advantage in politics, rather than in production. If the pressure groups di.er in their organizational capacity, both pro-rich (oligarchic) and pro-poor (populist) equilibria may arise, all of which are inefficient with respect to the constrained optimum.

Associations of physical activity with driving-related cognitive abilities in older drivers: an exploratory study

The purpose of this study was to examine the associations between physical activity and driving-related cognitive abilities of older drivers. Thirty-eight female and male drivers ages 61 to 81 years (M = 70.2, SD = 5.0) responded to the International Physical Activity Questionnaire and were assessed on a battery of neuropsychological tests, which included measures of visual attention, executive functioning, mental status, visuospatial ability, and memory. A higher amount of reported physical activity was significantly correlated with better scores on tests of visual processing speed and divided visual attention. Higher amounts of physical activity was significantly associated with a better composite score for visual attention, but its correlation with the composite score for executive functioning was not significant. These findings support the hypothesis that physical activity is associated with preservation of specific driving-related cognitive abilities of older adults

Optimization of Neoadjuvant Radiotherapy for zebrafish-avatars – towards personalized medicine

Recently, Fior and colleagues developed zebrafish Patient-derived Xenografts (zPDX) for personalized medicine to quickly screen the recommended Adjuvant Chemotherapies for colorectal cancer (CRC). Now the Lab goal is to test if zPDX can also be used to screen patients for Neoadjuvant Radiotherapy (RT). In rectal cancer the Neoadjuvant RT comprises a short Fractionated RT regimen of 5x5Gy (FRT), used to shrink tumor before surgery. Preliminary results from the Lab showed to be possible to distinguish radiosensitive from radioresistant CRC zebrafish xenografts, using an adapted RT protocol Single-High Dose RT (SHD-RT, 1x25Gy). However this SHD-RT protocol was different from the one given in the clinic (FRT, 5x5Gy), raising the question whether this adaptation is a good proxy of tumor response. Thus, the main goal of this thesis was to compare both RT protocols and test if SHD-RT is suitable to determine tumor radiosensitivity/radioresistance. To address this aim, radiosensitive CRC zebrafish xenografts were generated and distributed into the different experimental conditions: Control (non-irradiated); FRT; and SHD-RT. Our results revealed that SHD-RT induces similar tumor responses to FRT, in 6 days, i.e. both protocols lead to a significant induction of apoptosis and reduction of tumor size, suggesting that SHD-RT is enough for a quick and feasible assay. However, we also investigated further the cumulative effect of radiation and whether “time matters” for the radiobiology of the tumors in this short assay. Indeed, our results showed that cumulative damage and time are crucial factors to reduce the overall tumor size. However, given the similar results in the 6dpi assay, the adapted SHD-RT protocol seemed a practical option for the zPDX assay. Nevertheless this study needs further confirmation with a radioresistant tumor. Moreover, CRC zebrafish avatars were tested for RT and its combination with Chemotherapy, suggesting an increase of apoptotic cells upon the treatment combination

Predicting fatigue in football matches

Football coaches must inevitably prepare their strategies not only for the upcoming match but also be prepared to restructure their strategies during the match itself. But there's more than that. The coach's duties extend beyond the four lines on weekends. The coach and his staff must plan a full week of training while considering everyone's current physical capabilities to avoid excessive fatigue or an injury that could prevent the player from being eligible to play for weeks. It is unquestionably in a coach's best interest to keep his players from being hurt or over-exhausted to the point where they are no longer suitable for the upcoming game. Fatigue or injuries are occurrences that can have a negative impact on every club stakeholder. Following investigations conducted by notable researchers like Bangsbo et al. (2006), Krustrup et al. (2010), Mohr et al. (2003), Rampini et al. (2009), Novak et al. (2021), and others, it was possible to achieve highly encouraging results that could actually be useful for coaches by providing them with knowledge of their players' degrees of fatigue in anticipation by developing a predictive model for three different time periods of anticipation (5-minutes; 10-minutes and 20-minutes) based on accurate monitoring of the players' GPS positions. Academically, it is believed that this work will open the door for more research initiatives of this kind as it was among the first, if not the first, to integrate real data to develop a realistic prediction model that could be used to evaluate fatigue.Os treinadores de futebol devem inevitavelmente preparar as suas estratégias não apenas para o próximo jogo, mas também estar preparados para redesenhar as mesmas durante a própria partida. Mas há mais do que isso. As funções do treinador vão para além das quatro linhas ao fim-de-semana. O treinador e o seu staff devem planear uma semana inteira de treinos, considerando as capacidades físicas, atuais, dos jogadores, com o objetivo de evitar fadiga excessiva ou lesões que possam impedir os jogadores de ser opção para jogar durante semanas. É inquestionavelmente do interesse de um treinador evitar que os seus jogadores se lesionem ou fiquem fatigados ao ponto de não serem opções válidas para o próximo jogo. Fadiga ou lesões são ocorrências que podem ter impacto negativo em todos os stakeholders do clube. Suportado em investigações conduzidas por investigadores notáveis como Bangsbo et al. (2006), Krustrup et al. (2010), Mohr et al. (2003), Rampini et al. (2009), Novak et al. (2021), e outros, foi possível obter resultados altamente encorajadores que podem ser realmente úteis para os treinadores, possibilitando fornecer informação relativamente ao grau de fadiga dos jogadores antecipadamente, através de um modelo preditivo desenvolvido para três diferentes períodos (5-minutos; 10-minutos e 20-minutos) com base na monitorização nas coordenadas GPS. Academicamente, acredita-se que este trabalho poderá abrir portas para mais iniciativas de pesquisa no âmbito, dado que foi uma das primeiras, se não a primeira, a integrar dados reais para desenvolver um modelo preditivo realista que pode ser usado para classificar fadiga

Pervasive business intelligence platform to improve the quality of decision process in primary and secondary education – A Portuguese case study

Business Intelligence (BI) can be seen as a method that gathers information and data from information systems in order to help companies to be more accurate in their decision-making process. Traditionally BI systems were associated with the use of Data Warehouses (DW). The prime purpose of DW is to serve as a repository that stores all the relevant information required for making the correct decision. The necessity to integrate streaming data became crucial with the need to improve the efficiency and effectiveness of the decision process. In primary and secondary education, there is a lack of BI solutions. Due to the schools reality the main purpose of this study is to provide a Pervasive BI solution able to monitoring the schools and student data anywhere and anytime in real-time as well as disseminating the information through ubiquitous devices. The first task consisted in gathering data regarding the different choices made by the student since his enrolment in a certain school year until the end of it. Thereafter a dimensional model was developed in order to be possible building a BI platform. This paper presents the dimensional model, a set of pre-defined indicators, the Pervasive Business Intelligence characteristics and the prototype designed. The main contribution of this study was to offer to the schools a tool that could help them to make accurate decisions in real-time. Data dissemination was achieved through a localized application that can be accessed anywhere and anytime.This work has been supported by FCT - Fundação para a Ciência e Tecnologia within the Project Scope UID/CEC/00319/2013

Intra-industry trade and labor costs: The smooth adjustment hypothesis

We study a situation in which, owing to the exhaustion of non-renewable energy sources, conventional motor vehicles will turn out of use. We consider two scenarios: recycling or dismantling these motor vehicles. M|G|∞ queue system is used to study the process. Through it, we conclude that if the rate of dismantling and recycling of motor vehicles is greater than the rate at which they become idle, the system will tend to get balanced. The model allows also performing a brief study about the recycling or dismantling economic interest.

Controlo robusto de manobras em aviónica

Com este trabalho pretende-se estudar a dinâmica e o controlo robusto de manobras em aviónica. Para isso são estudados diferentes modelos lineares que aproximam o modelo global da aeronave durante manobras como a descolagem, aterragem e o voo planeado. O objectivo inicial é resolver o problema da estabilização (estabilizar o avião ao longo da trajectória de voo usando controlo robusto linear por realimentação de estado) tendo consideração restrições operacionais nas varáveis de estado e accionamentos. Numa segunda fase combinar os resultados obtidos em cada uma das manobras para projectar um piloto automático capaz de garantir bom desempenho em voo planeado para diferentes sequências de manobras (ex. aproximação à pista mais manobra de aterragem) usando o conceito de estabilização simultânea, ou seja por outras palavras pretende-se aplicar apenas um controlador a várias manobras e para isso deve ser realizada uma maquete seguindo todos os passos para se obter um menor erro e uma melhor estabilização por parte do avião quer nas condições de voo estáveis, quer nas variadas deflecções aplicadas em todos os níveis do avião. Aplicam-se as técnicas estudadas a modelos de caças como o F-14 e principalmente o F-16