The choice of alternative 5' splice sites in influenza virus M1 mRNA is regulated by the viral polymerase complex.

The influenza virus M1 mRNA has two alternative 5' splice sites: a distal 5' splice site producing mRNA3 that has the coding potential for 9 amino acids and a proximal 5' splice site producing M2 mRNA encoding the essential M2 ion-channel protein. Only mRNA3 was made in uninfected cells transfected with DNA expressing M1 mRNA. Similarly, using nuclear extracts from uninfected cells, in vitro splicing of M1 mRNA yielded only mRNA3. Only when the mRNA3 5' splice site was inactivated by mutation was M2 mRNA made in uninfected cells and in uninfected cell extracts. In influenza virus-infected cells, M2 mRNA was made, but only after a delay, suggesting that newly synthesized viral gene product(s) were needed to activate the M2 5' splice site. We present strong evidence that these gene products are the complex of the three polymerase proteins, the same complex that functions in the transcription and replication of the viral genome. Gel shift experiments showed that the viral polymerase complex bound to the 5' end of the viral M1 mRNA in a sequence-specific and cap-dependent manner. During in vitro splicing catalyzed by uninfected cell extracts, the binding of the viral polymerase complex blocked the mRNA3 5' splice site, resulting in the switch to the M2 mRNA 5' splice site and the production of M2 mRNA.

Modulation of 5' splice site choice in pre-messenger RNA by two distinct steps.

Ser/Arg-rich proteins (SR proteins) are essential splicing factors that commit pre-messenger RNAs to splicing and also modulate 5' splice site choice in the presence or absence of functional U1 small nuclear ribonucleoproteins (snRNPs). Here, we perturbed the U1 snRNP in HeLa cell nuclear extract by detaching the U1-specific A protein using a 2'-O-methyl oligonucleotide (L2) complementary to its binding site in U1 RNA. In this extract, the standard adenovirus substrate is spliced normally, but excess amounts of SR proteins do not exclusively switch splicing from the normal 5' splice site to a proximal site (site 125 within the adenovirus intron), suggesting that modulation of 5' splice site choice exerted by SR proteins requires integrity of the U1 snRNP. The observation that splicing does not necessarily follow U1 binding indicates that interactions between the U1 snRNP and components assembled on the 3' splice site via SR proteins may also be critical for 5' splice site selection. Accordingly, we found that SR proteins promote the binding of the U2 snRNP to the branch site and stabilize the complex formed on a 3'-half substrate in the presence or absence of functional U1 snRNPs. A novel U2/U6/3'-half substrate crosslink was also detected and promoted by SR proteins. Our results suggest that SR proteins in collaboration with the U1 snRNP function in two distinct steps to modulate 5' splice site selection.

Stochastic choice analysis of tourism destinations

The analysis of tourist destination choice, defined by intra-country administrative units and by product types “coastal/inland and village/city”, permits the characterisation of tourist flow behaviour, which is fundamental for public planning and business management. In this study, we analyse the determinant factors of tourist destination choice, proposing various research hypotheses relative to the impact of destination attributes and the personal characteristics of tourists. The methodology applied estimates Nested and Random Coefficients Multinomial Logit Models, which allow control over possible correlations among different destinations. The empirical application is realised in Spain on a sample of 3,781 individuals and allows us to conclude that prices, distance to the destination and personal motivations are determinants in destination choice.

Affirmative action and school choice

This paper studies a way of introducing affirmative action in the school choice problem to implement integration policies. The paper proposes the use of a natural two-step mechanism. The (equitable) first step is introduced as an adaptation of the deferred-acceptance algorithm designed by Gale and Shapley, when students are divided into two groups. The (efficient) second step captures the idea of exchanging places inherent to Gale's top trading cycle.

Early considerations proposed to Corporation relative to choice of Professor, [1804]

Small leaf containing handwritten notes outlining the guidelines that should guide the selection of a new Professor. Title transcribed from verso.

Strengthening the strategic choice offered to the EU’s southern Mediterranean neighbours. CEPS Commentary, 1 February 2013

Finding that the European Neighbourhood Policy (ENP) currently lacks a strategic vision that would offer states in the southern Mediterranean substantial returns in exchange for making tough reforms, this CEPS Commentary suggests that this weakness can be overcome through a concrete prospect of regional integration pro-actively driven forward by the European Union. Taking inspiration from current projects such as the Energy Community Treaty, the authors urge the EU to explicitly incorporate “legally binding sectoral multilateralism” into the ENP. This would provide the Union’s partners with a tangible prospect of reaping real long-term benefits from EU cooperation and reinvigorate the ENP for the next decade.

l bilanciamento tra le libertà economiche e i diritti sociali collettivi operato dalla Corte di Giustizia è un contemperamento tra diritti equiordinati?* = The balance between economic freedoms and collective social rights and actions; Court of Justice is a choice between rights equiordinati? Actions by the Court of Justice. WP C.S.D.L.E. “Massimo D’Antona”.INT – 98/2012

In the Viking and Laval judgments and more recently in the Comm. v. Germany ruling, the Court of Justice applied the proportionality test to collective rights, setting a series of restrictions to the exercise of the right to strike and the right to collective bargaining. The way the ECJ balances the economic freedoms and the social rights is indeed very different from that of the Italian Constitutional Court. Unlike the European Union Treaties, the Italian Constitution recognizes an important role to the right to take collective action which has to be connected with article 3, paragraph 2, consequently the right of strike is more protected than the exercise of economic freedoms.

Strategy-proof choice of acts : a preliminary study

We model social choices as acts mapping states of the world to (social) outcomes. A (social choice) rule assigns an act to every profile of subjective expected utility preferences over acts. A rule is strategy-proof if no agent ever has an incentive to misrepresent her beliefs about the world or her valuation of the outcomes; it is ex-post efficient if the act selected at any given preference profile picks a Pareto-efficient outcome in every state of the world. We show that every two-agent ex-post efficient and strategy-proof rule is a top selection: the chosen act picks the most preferred outcome of some (possibly different) agent in every state of the world. The states in which an agent’s top outcome is selected cannot vary with the reported valuations of the outcomes but may change with the reported beliefs. We give a complete characterization of the ex-post efficient and strategy-proof rules in the two-agent, two-state case, and we identify a rich class of such rules in the two-agent case.

The Border Management Programme in Central Asia: Explaining the European Union's Choice of Implementing Partners. Bruges Regional Integration & Global Governance Papers 3/2014

Between 2003 and 2014 the European Union’s (EU) Border Management Programme in Central Asia was implemented by the United Nations Development Programme (UNDP). However, the latter’s implementing responsibilities have just come to an end, with the next phase of the programme to be implemented by an EU member state consortium. This paper seeks to explain why the EU chose the UNDP to implement the programme in the first place; why the programme was redelegated to the UNDP over successive phases; and why, in the end, the EU has opted for a member state consortium to implement the next phase of the programme. The paper will draw on two alternative accounts of delegation: the principal-agent approach and normative institutionalism. Ultimately, it will be argued that both the EU’s decision(s) to delegate (and redelegate) implementing responsibilities to the UNDP, and its subsequent decision to drop the organisation in favour of an EU member state consortium, were driven for the most part by a rationalist ‘logic of consequentiality’. At the same time, a potential secondary role of a normative institutionalist ‘logic of appropriateness’ – as a supplementary approach – will not be discounted.

No other choice but co-operation. The background of Lithuania's and Latvia's relations with Belarus. OSW Commentary No. 99, 2013-01-04

For years now Belarus has been a key economic partner for Lithuania and Latvia. These two Baltic states have well-developed port infrastructure and thus provide what are the geographically closest and also the cheapest exit to international outlets for Belarusia’s petrochemical and chemical industries, both of which are export-oriented. As a result, the transit of Belarusian goods is one of the major sources of income for the state budgets of the two countries. This economic interdependence has affected the stance Riga and Vilnius take on Minsk at the EU forum. When in February and March 2012 the Council of the European Union was resolving the issue of imposing economic sanction on selected Belarusian companies which backed Alyaksandr Lukashenka’s regime, this triggered a discussion on what the point of such measures is and on possible economic losses in Lithuania and Latvia. As a result of firm resistance from Latvia (which was backed by Slovenia), the Council removed those companies which were most strongly engaged in co-operation with Latvian partners from the list of those to be covered with economic sanctions. Lithuania, which is more critical of the political situation in Belarus, did not express its official opposition to the sanctions. Despite some differences in the policies adopted by Riga and Vilnius, it turned out that Minsk could count on strong support from local business groups in both of these countries, as these groups fear impediments in this highly profitable co-operation and also retaliation from the Belarusian government. The existing economic bonds mean that neither Vilnius nor Riga have any other choice but to co-operate with Belarus. They must therefore adopt a carefully balanced policy towards Minsk. At the same time, being EU member states, they do not officially deny that a problem exists with the violation of human rights by Alyaksandr Lukashenka’s regime. It is for this reason that the governments of Latvia and Lithuania will be interested in maintaining the status quo in relations with Minsk. On the other hand, Belarus in a way also has no other choice but to use the ports in Lithuania and Latvia, and this will prevent it from excessively escalating tension in relations with these two countries.

Is Vietnam the Right Choice for Foreign Investment?: The Case of the European Union’s Slipping Opportunity. ACES Working Papers, 2012

This analysis is broken into three interdependent sections: First, an analysis of the restrictions placed on foreign direct investment in Vietnam captures the current freedoms and inhibitors of investment in Vietnam. Foreign direct investment is defined by the UN as an investment made to acquire a lasting interest in or effective control over an enterprise operating outside of the economy of the investor. Second, a cursory look at the macroeconomic risks, to which investment dollars are susceptible, will paint a realistic portrait of return of foreign investment. Finally, this paper will examine the current, and historical, trade relationship between Vietnam and the European Union, in order to convey that the opportunity for investment in Vietnam remains to be an opportunity for Europe’s developed economies.