IntroductionThe pathology of acquired immunodeficiency syndrome (AIDS) should be considered as the sum of effects generated by human immunodeficiency virus (HIV) replication, with direct T-cell destruction, and by a deep alteration in the pattern of soluble factors. The latter largely depends on the extent of viral replication, because it is hindered by effective antiretroviral therapy. HIV/ simian immunodeficiency virus (SIV) Nef, a multifunctional 27-to 34-kd protein expressed early in viral replication, was demonstrated to be a strong candidate for many of the pathogenic effects of HIV/SIV. This was first highlighted by the evidence that monkeys failed to develop the disease on infection with nef-deleted SIV, 1 and later confirmed by the observation that nef transgenic mice developed a syndrome strictly related to AIDS. 2 Furthermore, Nef perturbs the pattern of secreted factors in different cell types. As an example, the engagement of Nef with the chain of T-cell receptor leads to release of Fas-ligand from T cells in an antigenindependent manner. 3 In addition, the expression of Nef in monocytes/macrophages leads to a massive release of macrophage inflammatory protein 1␣/␤ (MIP-1␣/␤) chemokines and of still unknown factor-activating lymphocytes. 4 These soluble factors possibly promote recruitment and activation of T lymphocytes, which become susceptible to HIV replication. Nef is also able to alter some cellular functions, that is, CD4 internalization/ recycling, 5-7 major histocompatibility complex class I surface expression, 8 and src tyrosine kinases signaling (reviewed in Herna Remkema 9 ) through intracellular mechanisms.We were interested in investigating whether the expression of Nef influences the activation of signal tranducers and activators of transcription (STAT) molecules (reviewed in Schindler and Darnell, 10 Leaman et al, 11 Darnell,12 Stark et al, 13 and Bromberg and Darnell 14 ). STAT-governed pathways were first described by Darnell and colleagues by studying the interferon (IFN)-induced intracellular signal transduction. 15 Seven different STATs have been characterized so far. Activation of STATs is involved in the response of a wide number of cytokines, growth factors, and hormones. Typically, binding of cytokines with specific receptors lacking intrinsic kinase activity in its cytoplasmic tail induces receptor aggregation and recruitment of members of Janus kinases. These become activated by phosphorylating themselves and tyrosine residues of the receptor cytoplasmic tails. The receptor phosphotyrosines serve as docking sites for the binding of inactive STAT through the Src-homology 2 (SH2) domains. STAT monomers become phosphorylated at a constant tyrosine residue and dimerize. The activated dimers translocate to the nucleus thereby binding to specific DNA response elements, ultimately influencing gene expression programs. Hence, alterations in the STAT pathways could substantially influence cellular homeostasis. Few reports regarding the effects of HIV-1 infection on STAT activation/...

The Public-Private Partnership is also used, at international level, to carry out interventions in urban variant on areas or buildings that, by enhancing the value of (private) real estate properties, guarantee an economic return for the local community through an extraordinary contribution of urbanization (ECU) paid to the Administration by the private entity. The Italian Regions and Municipalities that have regulated the ECU calculation adopt a procedure of transformation value that does not specify either the duration or the risk-related rate of return of the real estate operation, which are essential factors for its balanced quantification. The paper defines a procedure that integrates methodologies, diffused in practice and literature, with official datasets to determine objectively the ECU, also evaluating its sensitivity to the critical variables of the transformative process. The proposed procedure is easy to apply and adaptable to a wide range of interventions and to different phases of the public-private (re)negotiation. It is in line with the Italian case and it is consistent with the international evaluation standards (IVS), having a general validity in the estimation field.

The insufficiency of public resources in Europe, which increased due to the debt crisis of 2010, has raised the need for combined financing forms to activate urban settlement transformation processes. Among these is the partial recapture of surplus value generated by interventions that derogate from urban planning tools as a regulation form of the differential rent phenomenon. This form of financing recalls the concept of land value recapture; it consists of an extraordinary charge of urbanisation (ECU) paid to policymakers. In Italy, the national law (2014) assigns responsibility for ECU determination to local decision-makers. Their plurality of operational guidelines are generally inspired by the transformation value criterion, and are sometimes methodologically incoherent and dispersive in their modus operandi. To support policymakers in the programming of public works within the limits of their available financial resources, the aim of the present work is to test a coherent, rational and applicable procedure in the field of estimation in order to analytically determine the “surplus value” generated by the intervention ante and post urban variant. The proposed procedural model is based on the structural characterisation of multiple methodologies used in practice and in the literature. The procedure was tested on a case study in the Italian context of Rome City. The results deduced from its implementation clarify that the ECU evaluation must also appropriately weigh the mutual benefits according to the “timing” and “riskiness” of the investment.

No abstract

We develop a methodology which replicates in great accuracy the FTSE Russell indexes reconstitutions, including the quarterly rebalancings due to new initial public offerings (IPOs). While using only data available in the CRSP US Stock database for our index reconstruction, we demonstrate the accuracy of this methodology by comparing it to the original Russell US indexes for the time period between 1989 to 2019. A python package that generates the replicated indexes is also provided [31].As an application, we use our index reconstruction protocol to compute the permanent and temporary price impact on the Russell 3000 annual additions and deletions, and on the quarterly additions of new IPOs . We find that the index portfolios following the Russell 3000 index and rebalanced on an annual basis are overall more crowded than those following the index on a quarterly basis. This phenomenon implies that transaction costs of indexing strategies could be significantly reduced by buying new IPOs additions in proximity to quarterly rebalance dates.