University of Fribourg

About: University of Fribourg is a education organization based out in Fribourg, Freiburg, Switzerland. It is known for research contribution in the topics: Population & Context (language use). The organization has 6040 authors who have published 14975 publications receiving 542500 citations. The organization is also known as: UNIFR & Universität Freiburg.

Poly(ADP-ribose) polymerase inhibition: past, present and future

Abstract: The process of poly(ADP-ribosyl)ation and the major enzyme that catalyses this reaction, poly(ADP-ribose) polymerase 1 (PARP1), were discovered more than 50 years ago. Since then, advances in our understanding of the roles of PARP1 in cellular processes such as DNA repair, gene transcription and cell death have allowed the investigation of therapeutic PARP inhibition for a variety of diseases — particularly cancers in which defects in DNA repair pathways make tumour cells highly sensitive to the inhibition of PARP activity. Efforts to identify and evaluate potent PARP inhibitors have so far led to the regulatory approval of four PARP inhibitors for the treatment of several types of cancer, and PARP inhibitors have also shown therapeutic potential in treating non-oncological diseases. This Review provides a timeline of PARP biology and medicinal chemistry, summarizes the pathophysiological processes in which PARP plays a role and highlights key opportunities and challenges in the field, such as counteracting PARP inhibitor resistance during cancer therapy and repurposing PARP inhibitors for the treatment of non-oncological diseases. Several poly(ADP-ribose) polymerase (PARP) inhibitors have now been approved as treatments for various types of cancer. In this Review, Curtin and Szabo discuss the history of the development of PARP inhibitors and progress in their use for cancer therapy, as well as the potential for repurposing PARP inhibitors for the treatment of non-oncological diseases such as stroke.

Revisiting User Mobility and Social Relationships in LBSNs: A Hypergraph Embedding Approach

Abstract: Location Based Social Networks (LBSNs) have been widely used as a primary data source to study the impact of mobility and social relationships on each other. Traditional approaches manually define features to characterize users' mobility homophily and social proximity, and show that mobility and social features can help friendship and location prediction tasks, respectively. However, these hand-crafted features not only require tedious human efforts, but also are difficult to generalize. In this paper, by revisiting user mobility and social relationships based on a large-scale LBSN dataset collected over a long-term period, we propose LBSN2Vec, a hypergraph embedding approach designed specifically for LBSN data for automatic feature learning. Specifically, LBSN data intrinsically forms a hypergraph including both user-user edges (friendships) and user-time-POI-semantic hyperedges (check-ins). Based on this hypergraph, we first propose a random-walk-with-stay scheme to jointly sample user check-ins and social relationships, and then learn node embeddings from the sampled (hyper)edges by preserving n-wise node proximity (n = 2 or 4). Our evaluation results show that LBSN2Vec both consistently and significantly outperforms the state-of-the-art graph embedding methods on both friendship and location prediction tasks, with an average improvement of 32.95% and 25.32%, respectively. Moreover, using LBSN2Vec, we discover the asymmetric impact of mobility and social relationships on predicting each other, which can serve as guidelines for future research on friendship and location prediction in LBSNs.

Pre-Mesozoic Alpine basements - Their place in the European Paleozoic framework

Abstract: Prior to their Alpine overprinting, most of the pre-Mesozoic basement areas in Alpine orogenic structures shared a complex evolution, starting with Neoproterozoic sediments that are thought to have received detrital input from both West and East Gondwanan cratonic sources. A subsequent Neoproterozoic–Cambrian active margin setting at the Gondwana margin was followed by a Cambrian–Ordovician rifting period, including an Ordovician cordillera-like active margin setting. During the Late Ordovician and Silurian periods, the future Alpine domains recorded crustal extension along the Gondwana margin, announcing the future opening of the Paleotethys oceanic domain. Most areas then underwent Variscan orogenic events, including continental subduction and collisions with Avalonian-type basement areas along Laurussia and the juxtaposition and the duplication of terrane assemblages during strike slip, accompanied by contemporaneous crustal shortening and the subduction of Paleotethys under Laurussia. Thereafter, the final Pangea assemblage underwent Triassic and Jurassic extension, followed by Tertiary shortening, and leading to the buildup of the Alpine mountain chain. Recent plate-tectonic reconstructions place the Alpine domains in their supposed initial Cambrian–Ordovician positions in the eastern part of the Gondwana margin, where a stronger interference with the Chinese blocks is proposed, at least from the Ordovician onward. For the Visean time of the Variscan continental collision, the distinction of the former tectonic lower-plate situation is traceable but becomes blurred through the subsequent oblique subduction of Paleotethys under Laurussia accompanied by large-scale strike slip. Since the Pennsylvanian, this global collisional scenario has been replaced by subsequent and ongoing shortening and strike slip under rising geothermal conditions, and all of this occurred before all these puzzle elements underwent the complex Alpine reorganization.

Identifying influential spreaders by weighted LeaderRank

Abstract: Identifying influential spreaders is crucial for understanding and controlling spreading processes on social networks. Via assigning degree-dependent weights onto links associated with the ground node, we proposed a variant to a recent ranking algorithm named LeaderRank (Lu et al., 2011). According to the simulations on the standard SIR model, the weighted LeaderRank performs better than LeaderRank in three aspects: (i) the ability to find out more influential spreaders; (ii) the higher tolerance to noisy data; and (iii) the higher robustness to intentional attacks.

Present and future contribution of glacier storage change to runoff from macroscale drainage basins in Europe

Abstract: [1] The contribution of glaciers to runoff from large-scale drainage basins in Europe is analyzed for the major streams originating in the Alps: Rhine, Rhone, Po, and Danube. Detailed information on glacier storage change is available from monthly mass balance data of 50 Swiss glaciers for the period 1908–2008. Storage changes are extrapolated to all glaciers in the European Alps. By comparing monthly runoff yields from glacierized surfaces in the summer months with measured runoff at gauges along the entire length of the streams, the relative portion of water from glacier storage change for each month is calculated. Macroscale drainage basins with a size of 100,000 km2 (1% ice-covered) can show a 25% contribution of glaciers to August runoff over the last century. In the lower Danube (0.06% glacierization) glacier meltwater accounts for 9% of observed runoff in September of the extreme year 2003. The relative importance of glacier contribution to runoff does not scale linearly with the percentage of glacierization, as high glacier runoff in summer dominates lowland areas with little precipitation and high evapotranspiration. Thus, glacial meltwaters are relevant to the hydrological regime of macroscale watersheds and do not only have a regional impact. By transiently modeling future glacier retreat until 2100 using climate scenarios, a reduction of glacierized areas in the Alps to 12% of the current value is found. In consequence, summer runoff contribution from currently glacierized basins will be strongly reduced, intensifying issues with water shortage in summer also in poorly glacierized catchments.