363 research outputs found
The impact of the Troika’s austerity measures on the Portuguese labour law system: a general assessment of the scope of social sovereignty in the light of the Constitutional Tribunal Case Law
No full textI Centri di Assistenza Fiscale (CAF) e l’ordinamento comunitario del mercato e della concorrenza
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ANALYSIS OF THE IN VIVO FUNCTION OF HASPIN KINASE USING ZEBRAFISH AS A MODEL SYSTEM: KNOCKDOWN AND KNOCKOUT APPROACHES
No full textThe Haspin gene encodes an atypical serine/threonine mitotic kinase first discovered in mouse spermatocytes and preferentially expressed in tissues with a high rate of proliferating cells. Haspin acts at metaphase by phosphorylating threonine 3 of histone H3 (H3Thr3PH) and this modification allows the recruitment of the chromosomal passenger complex, a key factor required to orchestrate different steps of mitosis. In human cells, HASPIN depletion causes a decrease in H3Thr3 levels, resulting in premature loss of sister chromatid cohesion and in defects in chromosome alignment at metaphase. Haspin has been found in all eukaryotic organisms; however, up to know, its role during animal embryonic development has never been investigated. We decided to investigate its function and expression during zebrafish embryonic development and, to this aim, we took advantage of a morpholino (MO)-mediated knockdown approach and of the CRISPR-Cas9 knockout strategy.
We identified and cloned the zebrafish haspin ortholog, together with a previously unknown splicing isoform, and we clarified its expression pattern during embryogenesis and in some adult tissues. We demonstrated a relevant maternal contribution for the haspin transcript and important levels of zygotic expression in tissues with a high rate of proliferating cells, such as the developing brain and hematopoietic tissues. We also detected haspin transcript in the adult gonads and found that its expression is significantly switched on after injury during adult fin tissue regeneration.
Interestingly, after Haspin functional inactivation using two different MOs, a translation blocking (ATG MO) and a splicing one, we demonstrated that Haspin is involved in H3Thr3PH also in zebrafish. Moreover, microinjection of the haspin ATG MO results in high embryo mortality and severe defects during epiboly stages, indicating important alterations in cellular rearrangements and movements.
A haspin stable mutant line was generated by using the CRISPR-Cas9 technology: we isolated three different mutant haspin alleles, all causing the formation of premature stop codons. Although they do not show evident phenotypic alterations during embryogenesis, embryos carrying a homozygous genotype for these mutations are not able to reach the adulthood stage, showing a high rate of mortality in the first three weeks of larval development, indicating that Haspin is fundamental for larval survival and growth.
To conclude, we clarified various aspects of haspin expression pattern during zebrafish development and in adult organs. Even though we were not able yet to unambiguously define the phenotypic effect of Haspin functional inactivation by using a MO-mediated approach, we paved the way for the analysis of the effect of a complete haspin gene knockout during zebrafish development by generating a haspin stable KO line and by showing that this null mutant allele significantly affects larval survival and growth
Improving Drilling Operations Management Using Combined Simulation
No full textThis paper presents an integrated logistic study to estimate the fitness for purpose of a Supply Base
during the development and exploitation of the XY gas field. The logistic study includes a dynamic
modelling of the overall system (incoming logistic flow, base occupation and outgoing logistic flow) in order
to properly evaluate possible necessary actions to be implemented in order to ensure the reliability and
availability of the base services and to define the costs related to the activities to be carried out along the
project schedule
The Portuguese Constitutional Court case law on austerity measures: a reappraisal
No full textIn different cases in these last years, the Portuguese Constitutional Tribunal (PCT) has reviewed the legality on some of the austerity measures agreed with (but effectively imposed by) the Trojka – the European Commission (Commission), the European Central Bank (ECB) and the International Monetary Fund (IMF) – as conditions for the release of the loan package granted to Portugal in May 2011. As it is well-known, some of those austerity measures have been declared unconstitutional. This paper tries to shed some light on a number of questions, both theoretical and practical, to which those judgments give rise.
The jurisprudence of the PCT raises crucial issues which the constitutional courts of EU Member States will certainly need to address in the future: what is the boundary between judicial activism and the judicial recognition of fundamental social rights as a remedy to the legislature’s minimalism in ensuring the protection of those rights? When can legislative action, insofar as resulting from the democratic process, no longer be regarded as the best way to secure that the rights of citizens are safeguarded? To what extent can judges require the legislature to take social rights ‘seriously’?
In this regard, we believe that, even though judges obviously do not create the law, they should be active – rather than activist or creative – agents of change whenever constitutional rights are put at risk by national legislation – whether or not the latter is the result of an international obligation or constraint – in order to behave as guardians of last resort for citizens’ fundamental rights.In different cases in these last years, the Portuguese Constitutional Tribunal (PCT) has reviewed the legality on some of the austerity measures agreed with (but effectively imposed by) the Trojka – the European Commission (Commission), the European Central Bank (ECB) and the International Monetary Fund (IMF) – as conditions for the release of the loan package granted to Portugal in May 2011. As it is well-known, some of those austerity measures have been declared unconstitutional. This paper tries to shed some light on a number of questions, both theoretical and practical, to which those judgments give rise.
The jurisprudence of the PCT raises crucial issues which the constitutional courts of EU Member States will certainly need to address in the future: what is the boundary between judicial activism and the judicial recognition of fundamental social rights as a remedy to the legislature’s minimalism in ensuring the protection of those rights? When can legislative action, insofar as resulting from the democratic process, no longer be regarded as the best way to secure that the rights of citizens are safeguarded? To what extent can judges require the legislature to take social rights ‘seriously’?
In this regard, we believe that, even though judges obviously do not create the law, they should be active – rather than activist or creative – agents of change whenever constitutional rights are put at risk by national legislation – whether or not the latter is the result of an international obligation or constraint – in order to behave as guardians of last resort for citizens’ fundamental rights.Refereed Working Papers / of international relevanc
The multi-path Traveling Salesman Problem with stochastic travel costs
No full textGiven a set of nodes, where each pair of nodes is connected by several paths and each path shows a stochastic travel cost with unknown distribution, the multipath Traveling Salesman Problem with stochastic travel costs aims at finding an
expected minimum Hamiltonian tour connecting all nodes. Under a mild assumption on the unknown probability distribution a deterministic approximation of the
stochastic problem is given. The comparison of such approximation with a Montecarlo simulation shows both the accuracy and the eciency of the deterministic approximation, with a mean percentage gap around 2% and a reduction of the computational times of two orders of magnitude
A comparison of production policies in remanufacturing systems
No full textIn remanufacturing systems material management and production planning, unlike what happens in traditional production settings, are made difficult by a wider uncertainty affecting the quantity, the quality and the timing of recovered products/components. This instability makes the problem of defining an optimal inventory control policy more complicated as well as not unique within the product life cycle. In this article, after having reviewed the existing literature on inventory management in remanufacturing systems, a particular policy for material management and production planning in a hybrid remanufacturing system has been proposed. The considered model a multi stage inventory model. The comparison of the proposed policy with some others already present in literature, in different scenarios related to the product life cycle and with the change of several cost parameters, is carried out using the discrete event simulation approach. This allows us to identify in what circumstances such a policy is preferable to the others
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