OBJECTIVES/GOALS: Time restricted feeding (TRF) in diet induced obesity (DIO) has several health benefits, including improved metabolic rhythms and inflammation. Our lab has shown that TRF in DIO significantly reduces renal and aortic damage. The main goal of our research is to understand how TRF impacts aortic function, organ damage, and T cell activation in DIO. METHODS/STUDY POPULATION: We will use a 20-week DIO model, where mice will be on 20 weeks of normal fat diet (ND) or high fat diet (HFD). During weeks 18-20, mice will go through TRF intervention where food is restricted to the 12-hour active period or continue ad libitum feeding. At the end of the 2-week TRF intervention or continued ad libitum feeding, aortic stiffness will be measured via pulse wave velocity measurements. We will also collect kidney, aorta, and small intestine at the end of the 20-week protocol for flow cytometric analysis of tissue T cell activation as well as histological assessments. This will allow us to determine the relationship with organ damage, organ function, and the T cell response. We will also analyze tissue and circulating levels of inflammatory T cell-derived cytokines such as interleukin-17A (IL-17A) via ELISA. RESULTS/ANTICIPATED RESULTS: DIO mice showed significantly increased aortic stiffness (measured by pulse wave velocity) compared to mice on ND. Interestingly, TRF intervention in DIO mice reduced aortic stiffness compared to DIO ad libitum. Histological assessments also showed that TRF abolished aortic and kidney fibrosis suggesting a role for the timing of feeding in regulating aortic function and organ damage from chronic HFD. We have several ongoing experiments to determine the T cell response with TRF in DIO mice. We predict that TRF in DIO mice will significantly decrease inflammatory T cells and reduce cytokine abundance in target organs. DISCUSSION/SIGNIFICANCE: Our lab has shown that TRF reduces aortic thickness and aortic and kidney fibrosis, but the driving mechanisms are unknown. We propose that TRF reduces T cell activation in DIO mice leading to reduced organ damage. Our work will provide insight on how TRF in DIO regulates the T cell response and may improve inflammation in the kidney and aorta.

Structural transformation is a key indicator of economic development. We present the first time series of male labor sectoral shares for England and Wales before 1800, using a large sample of probate and apprenticeship data to produce national- and county-level estimates. England experienced a rapid decline in the share of workers in agriculture between the early seventeenth and the beginning of the eighteenth centuries, associated with rising agricultural and especially industrial productivity; Wales saw few changes. Our results show that England experienced unusually early structural change and highlight the mid-seventeenth century as a turning point.

On March 18, 2015, an arbitral tribunal (Tribunal) constituted in accordance with Annex VII to the 1982 United Nations Convention on the Law of the Sea (Convention) under the auspices of the Permanent Court of Arbitration handed down its award in a proceeding brought by Mauritius in 2010 challenging the United Kingdom’s establishment of a marine protected area (MPA) around the Chagos Islands in the Indian Ocean, which are claimed by Mauritius. The Tribunal held that it did not have jurisdiction under the Convention to address whether the United Kingdom or Mauritius has the rights of a coastal state regarding the Chagos Islands. Nevertheless, the Tribunal also held that, in creating the MPA by unilateral declaration, the United Kingdom had failed to take into account certain legitimate interests of Mauritius and had thereby breached its obligations under Articles 2(3), 56(2), and 194(4) of the Convention.

On October 12, 1984, a five-member Chamber of the International Court of Justice rendered its decision in the maritime boundary dispute between the United States and Canada in the Gulf of Maine area. The Chamber delimited the continental shelves and 200-nautical-mile fisheries zones by setting one line between the two countries off the East Coast of North America. The Chamber’s Judgment, which under Article 27 of the Statute of the Court is considered as if it were rendered by the full 15-member Court, is likely to attract considerable comment. We will resist the temptation to add our views to that substantive commentary, leaving analysis for the time being to others not so closely associated with the case.

The establishment of maritime boundaries between neighboring states is a matter of increasing interest and concern in international relations. Although states have had to deal with territorial sea and other maritime boundaries in years past, the extension of fisheries jurisdiction and claimed economic zones out to 200 nautical miles and the rapid advance in the technology of hydrocarbon development on the continental shelf have created a problem of totally new dimensions. These developments have given rise to many new boundaries between opposite and adjacent states which require delimitation and have made many potential boundaries more important to the states concerned.