An observation on n-permutability

We prove that in a regular category all reflexive and transitive relations are symmetric if and only if every internal category is an internal groupoid. In particular, these conditions hold when the category is n-permutable for some n.Comment: 6 page

Wobbling laser beam welding of copper

The increase of electrical components in automotive industry and the expansion of renewable energy generation lead to a rising need of a reliable and highly productive welding process for copper. Laser beam welding of copper has been a challenge due to the high thermal conductivity of Cu and its low absorptivity of laser radiation. However, recent developments suggest that these problems can be overcome by power spatial modulation of the beam. This research work was developed at Carrs Welding Technologies, UK, aiming to study the feasibility of fiber laser to weld electrolytic copper components to batteries. The main goal was to determine the parameter combination that allows to obtain a welded seam free of porosity and other weld defects with a penetration of 1.5 mm without losing electrical conductivity which was a mandatory requirement. In a first stage, multiple weld beads with different welding parameter combinations were produced in order to determine the influence of each parameter in the process. In the second stage, single-mode and multimode fiber lasers were compared. The outcome of these two stages were examined using metallography and electrical conductivity tests, namely, Eddy Currents. The results have shown that power spatial modulation can supress porosities, weld shape defects and spatter. A penetration of 1.5 mm can be achieved for a multimode beam power above 4 kW, welding speed between 3.5 and 4 m/min with a circular spatial modulation with a beam rotation of 0.6 to 1 mm diameter at 100 Hz frequency. The hardness measured suggest that there is no significant variation of mechanical resistance of the joins compared to the base material. Electrical conductivity measurements showed there is no variation in the welds. Finally, single-mode fiber laser produced narrow and deeper welds than when multimode fibers were tested, as expecte

The born global phenomenon: the Portuguese case

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and EconomicsThe growing significance of companies that conduct international business at or near their funding has been critically challenging previous incremental models of international expansion. This thesis aims to cross-compare, by means of a multiple-case study, eight Portuguese start-ups among themselves and with the theoretical concept of born global firms versus traditional ones. This work project finds that: (1) active entrepreneurs with global vision from inception are essential for the implementation of international strategies; (2) only formal network plays a key role for successful internationalization and (3) inimitable sources of value creation, niche-focused strategies and unique intangible assets are also crucial

The role of GSH signaling in mitophagy induced by reactive oxygen species: potential target for neuroprotection in stroke?

Mitochondria are involved in numerous cellular processes, including energy production and cell death regulation. Simultaneously, these are the main cellular producers of reactive oxygen species (ROS), particularly when dysfunctional. ROS accumulation leads to oxidative stress which is associated with pathologies, such as stroke and neurodegenerative diseases. So, elimination of ROS-producing damaged mitochondria is key for maintaining cell homeostasis. Mitophagy, consists of the selective degradation of excessive or damaged mitochondria. The accumulation of ROS and mitochondrial depolarization stimulates PTEN-induced kinase 1 (PINK1)/PARKIN-mediated mitophagy. Concomitantly, ROS are counteracted by glutathione, a key antioxidant. ROS oxidize glutathione and stimulate protein S-glutathionylation, a post- translation modification capable of modulate protein function. Here, the main goal was to ex- plore the molecular mechanisms underlying mitophagy, in particular the role of ROS and/or glutathione signaling in mitophagy progression, with a special focus on protein S-glutathi- onylation. We hypothesized that mitophagy can be regulated by glutathione signaling, namely that the accumulation of mitochondrial ROS stimulates the production and oxidation of gluta- thione, which enhances/stimulates mitophagy by protein glutathionylation of mitophagy-re- lated proteins. Using human cell lines, SH-SY5Y and SH-SY5Y mitoQC, mitochondrial dysfunc- tion was stimulated with the classical uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP). ROS generation and PINK1/PARKIN-dependent mitophagy were observed after CCCP treatment. Likewise, the catalytic subunit of the rate limiting enzyme for glutathione synthesis, Glutamate-Cysteine Ligase, is upregulated in CCCP-treated cells. Notably, we show for the first time that CCCP treatment induces protein S-glutathionylation of PINK1. Furthermore, we also found fluorescence measure on a microplate reader to be a possible new technique to assess mitophagy. Understating mitophagy mechanisms and how these are regulated is key to stimulate cytoprotection by preventing cell death. Thus, this can eventually contribute to new strategies against diseases characterized by mitochondrial damage, like stroke.As mitocôndrias são essenciais em processos celulares como produção de energia e regulação da morte celular. Simultaneamente, são as principais produtoras de espécies reativas de oxigênio (ROS), particularmente quando disfuncionais. A acumulação de ROS leva a stress oxidativo que está associado a patologias, como acidente vascular cerebral e doenças neuro- degenerativas. Assim, a eliminação de mitocôndrias danificadas produtoras de ROS é funda- mental para a homeostase celular. A mitofagia consiste na degradação seletiva de mitocôn- drias excessivas ou danificadas. Acumulação de ROS e despolarização mitocondrial estimulam mitofagia via quinase 1 induzida por PTEN (PINK1)/PARKIN. Concomitantemente, ROS são neutralizados pela glutationa, um antioxidante chave. As ROS oxidam a glutationa e estimulam s-glutationilização, uma modificação pós-traducional capaz de modular a função proteica. Aqui, o objetivo foi explorar os mecanismos subjacentes à mitofagia, particularmente o papel da sinalização de ROS e/ou glutationa na progressão da mitofagia, com foco especial na s- glutationilização. Colocamos a hipótese que a mitofagia pode ser regulada pela sinalização da glutationa, nomeadamente que a acumulação de ROS mitocondriais estimula a produção e oxidação de glutationa, que estimula a mitofagia por S-glutationilização de proteínas relacio- nadas com mitofagia. Em linhas celulares humanas, SH-SY5Y e SH-SY5Y mitoQC, disfunção mitocondrial foi estimulada com carbonyl cyanide m-chlorophenylhydrazone (CCCP). Geração de ROS e mitofagia dependente de PINK1/PARKIN foram observados após tratamento com CCCP. Igualmente, a subunidade catalítica da enzima limitante da síntese de glutationa, Gluta- mato-Cisteína Ligase, é sobre-expressa em células tratadas com CCCP. Notavelmente, mostra- mos que tratamento com CCCP induz glutationilização de PINK1. Além disso, também desco- brimos que medir fluorescência num leitor de microplacas é uma possível técnica para avaliar mitofagia. Compreender os mecanismos de mitofagia e como são regulados é fundamental para estimular a citoproteção prevenindo a morte celular. E eventualmente contribuir para novas estratégias contra doenças caracterizadas por danos mitocondriais, como o acidente vascular cerebral