Tamás Róbert Mezei

Oral administration of pyrophosphate inhibits connective tissue calcification

Various disorders including pseudoxanthoma elasticum (PXE) and generalized arterial calcification of infancy (GACI), which are caused by inactivating mutations in ABCC6 and ENPP1, respectively, present with extensive tissue calcification due to reduced plasma pyrophosphate (PPi). However, it has always been assumed that the bioavailability of orally administered PPi is negligible. Here, we demonstrate increased PPi concentration in the circulation of humans after oral PPi administration. Furthermore, in mouse models of PXE and GACI, oral PPi provided via drinking water attenuated their ectopic calcification phenotype. Noticeably, provision of drinking water with 0.3 mM PPi to mice heterozygous for inactivating mutations in Enpp1 during pregnancy robustly inhibited ectopic calcification in their Enpp1−/− offspring. Our work shows that orally administered PPi is readily absorbed in humans and mice and inhibits connective tissue calcification in mouse models of PXE and GACI. PPi, which is recognized as safe by the FDA, therefore not only has great potential as an effective and extremely low‐cost treatment for these currently intractable genetic disorders, but also in other conditions involving connective tissue calcification.

Mobile versus Point Guards

We study the problem of guarding orthogonal art galleries with horizontal mobile guards (alternatively, vertical) and point guards, using “rectangular vision”. We prove a sharp bound on the minimum number of point guards required to cover the gallery in terms of the minimum number of vertical mobile guards and the minimum number of horizontal mobile guards required to cover the gallery. Furthermore, we show that the latter two numbers can be computed in linear time.

Terminal-pairability in complete bipartite graphs

Abstract We investigate the terminal-pairability problem in the case when the base graph is a complete bipartite graph, and the demand graph is also bipartite with the same color classes. We improve the lower bound on maximum value of Δ ( D ) which still guarantees that the demand graph D is terminal-pairable in this setting. We also prove a sharp theorem on the maximum number of edges such a demand graph can have.