Development of a low-seroprevalence, αvβ6 integrin-selective virotherapy based on human adenovirus type 10

Oncolytic virotherapies (OV) hold immense clinical potential. OV based on human adenoviruses (HAdV) derived from HAdV with naturally low rates of pre- existing immunity will be beneficial for future clinical translation. We generated a low- seroprevalence HAdV-D10 serotype vector incorporating an αvβ6 integrin-selective peptide, A20, to target αvβ6-positive tumor cell types. HAdV-D10 has limited natural tropism. Structural and biological studies of HAdV-D10 knob protein highlighted low-affinity engagement with native adenoviral receptors CAR and sialic acid. HAdV-D10 fails to engage blood coagulation factor X, potentially eliminating “off-target” hepatic sequestration in vivo. We engineered an A20 peptide that selectively binds αvβ6 integrin into the DG loop of HAdV-D10 fiber knob. Assays in αvβ6+ cancer cell lines demonstrated significantly increased transduction mediated by αvβ6-targeted variants compared with controls, confirmed microscopically. HAdV-D10.A20 resisted neutralization by neutralizing HAdV-C5 sera. Systemic delivery of HAdV-D10.A20 resulted in significantly increased GFP expression in BT20 tumors. Replication-competent HAdV-D10.A20 demonstrated αvβ6 integrin-selective cell killing in vitro and in vivo. HAdV-D10 possesses characteristics of a promising virotherapy, combining low seroprevalence, weak receptor interactions, and reduced off-target uptake. Incorporation of an αvβ6 integrin-selective peptide resulted in HAdV-D10.A20, with significant potential for clinical translation

Distribution of Income and Taxes in Slovenia and Croatia

The purpose of this article is to estimate the redistributive effects of personal income tax (PIT) in Slovenia and Croatia. The decomposition of the Gini coefficient developed by Aronson, Johnson & Lambert reveals only a limited difference between potential and actual redistribution, with this loss being a consequence of the different tax treatment of taxpayers with equal pre-tax income. The results also suggest that Croatia experiences greater income inequality among taxpayers than Slovenia. Another decomposition of inequality measure indicates that some types of income — especially wages — contribute a constant and high proportion to the overall inequality seen in both countries during the period examined.

Working for 200 Euro? The Unintended Effects of Traineeship Reform on Youth Labor Market Outcomes

This paper evaluates the effects of an active labor market policy (ALMP) reform, the so-called SOR measure (vocational training for work without commencing employment), on youth labor market outcomes in the newest EU member state—Croatia. In 2012, SOR was redesigned to ease the first labor market entry and promote on-the-job training, enabling a young person without relevant work experience to get a one-year contract and a net monthly remuneration of 210 euro, while after 2014, the measure also became a part of the European Youth Guarantee. Pooling Croatian Labor Force Surveys from 2007 to 2016 and using the difference-in-difference strategy, we estimate the causal intent-to-treat effect of the program reform on labor market outcomes. The main results indicate that the reform has had, at best, neutral effects on employment and unemployment, while there is evidence that a portion of young individuals was propelled into inactivity. Though expected, adverse effect on wages—both at the mean and at higher percentiles of the wage distribution—is driven mostly by wages received by women and university graduates