Recommender Systems

The ongoing rapid expansion of the Internet greatly increases the necessity of effective recommender systems for filtering the abundant information. Extensive research for recommender systems is conducted by a broad range of communities including social and computer scientists, physicists, and interdisciplinary researchers. Despite substantial theoretical and practical achievements, unification and comparison of different approaches are lacking, which impedes further advances. In this article, we review recent developments in recommender systems and discuss the major challenges. We compare and evaluate available algorithms and examine their roles in the future developments. In addition to algorithms, physical aspects are described to illustrate macroscopic behavior of recommender systems. Potential impacts and future directions are discussed. We emphasize that recommendation has a great scientific depth and combines diverse research fields which makes it of interests for physicists as well as interdisciplinary researchers.Comment: 97 pages, 20 figures (To appear in Physics Reports

Measuring Global Credibility with Application to Local Sequence Alignment

Computational biology is replete with high-dimensional (high-D) discrete prediction and inference problems, including sequence alignment, RNA structure prediction, phylogenetic inference, motif finding, prediction of pathways, and model selection problems in statistical genetics. Even though prediction and inference in these settings are uncertain, little attention has been focused on the development of global measures of uncertainty. Regardless of the procedure employed to produce a prediction, when a procedure delivers a single answer, that answer is a point estimate selected from the solution ensemble, the set of all possible solutions. For high-D discrete space, these ensembles are immense, and thus there is considerable uncertainty. We recommend the use of Bayesian credibility limits to describe this uncertainty, where a (1−α)%, 0≤α≤1, credibility limit is the minimum Hamming distance radius of a hyper-sphere containing (1−α)% of the posterior distribution. Because sequence alignment is arguably the most extensively used procedure in computational biology, we employ it here to make these general concepts more concrete. The maximum similarity estimator (i.e., the alignment that maximizes the likelihood) and the centroid estimator (i.e., the alignment that minimizes the mean Hamming distance from the posterior weighted ensemble of alignments) are used to demonstrate the application of Bayesian credibility limits to alignment estimators. Application of Bayesian credibility limits to the alignment of 20 human/rodent orthologous sequence pairs and 125 orthologous sequence pairs from six Shewanella species shows that credibility limits of the alignments of promoter sequences of these species vary widely, and that centroid alignments dependably have tighter credibility limits than traditional maximum similarity alignments

The diversity of myeloid immune cells shaping wound repair and fibrosis in the lung

In healthy circumstances the immune system coordinates tissue repair responses in a tight balance that entails efficient inflammation for removal of potential threats, proper wound closure, and regeneration to regain tissue function. Pathological conditions, continuous exposure to noxious agents, and even ageing can dysregulate immune responses after injury. This dysregulation can lead to a chronic repair mechanism known as fibrosis. Alterations in wound healing can occur in many organs, but our focus lies with the lung as it requires highly regulated immune and repair responses with its continuous exposure to airborne threats. Dysregulated repair responses can lead to pulmonary fibrosis but the exact reason for its development is often not known. Here, we review the diversity of innate immune cells of myeloid origin that are involved in tissue repair and we illustrate how these cell types can contribute to the development of pulmonary fibrosis. Moreover, we briefly discuss the effect of age on innate immune responses and therefore on wound healing and we conclude with the implications of current knowledge on the avenues for future research

Human-correlated genetic HCC models identify combination therapy for precision medicine [Pre-print]

Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is a leading cause of cancer related mortality worldwide. HCC occurs typically from a background of chronic liver disease, caused by a spectrum of predisposing conditions. Tumour development is driven by the expansion of clones that accumulated progressive driver mutations, with hepatocytes the most likely cell of origin. However, the landscape of driver mutations in HCC is independent of the underlying aetiologies. Despite an increasing range of systemic treatment options for advanced HCC outcomes remain heterogeneous and typically poor. Emerging data suggest that drug efficacies depend on disease aetiology and genetic alterations. Exploring subtypes in preclinical models with human relevance will therefore be essential to advance precision medicine in HCC. We generated over twenty-five new genetically-driven in vivo and in vitro HCC models. Our models represent multiple features of human HCC, including clonal origin, histopathological appearance, and metastasis to distant organs. We integrated transcriptomic data from the mouse models with human HCC data and identified four common human-mouse subtype clusters. The subtype clusters had distinct transcriptomic characteristics that aligned with histopathology. In a proof-of-principle analysis, we verified response to standard of care treatment and used a linked in vitro-in vivo pipeline to identify a promising therapeutic candidate, cladribine, that has not been linked to HCC treatment before. Cladribine acts in a highly effective subtype-specific manner in combination with standard of care therapy

Influence of ractopamine hydrochloride supplementation on pancreatic digestive enzyme activity in finishing steers

Sixty-nine finishing steers were randomly assigned to one of two treatment groups: supplementation to provide 0 (CON) or 267 mg d-1 of ractopamine hydrochloride (RAC) for 42 d. Twelve steers were slaughtered for tissue and blood collection. Final body weight (BW) tended to be greater with RAC supplementation. Ractopamine hydrochloride supplementation decreased liver mass as a percentage of BW. Pancreatic protein concentration, digestive enzyme activities, serum glucose and insulin concentrations were not influenced by RAC supplementation. Ractopamine hydrochloride supplementation decreased the pancreatic: α-amylase:trypsin and serum urea-N concentrations. These data suggest that RAC may influence pancreatic exocrine function in cattle.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

CCDC66 frameshift variant associated with a new form of early-onset progressive retinal atrophy in Portuguese Water Dogs.

Aberrant photoreceptor function or morphogenesis leads to blinding retinal degenerative diseases, the majority of which have a genetic aetiology. A variant in PRCD previously identified in Portuguese Water Dogs (PWDs) underlies prcd (progressive rod-cone degeneration), an autosomal recessive progressive retinal atrophy (PRA) with a late onset at 3-6 years of age or older. Herein, we have identified a new form of early-onset PRA (EOPRA) in the same breed. Pedigree analysis suggested an autosomal recessive inheritance. Four PWD full-siblings affected with EOPRA diagnosed at 2-3 years of age were genotyped (173,661 SNPs) along with 2 unaffected siblings, 2 unaffected parents, and 15 unrelated control PWDs. GWAS, linkage analysis and homozygosity mapping defined a 26-Mb candidate region in canine chromosome 20. Whole-genome sequencing in one affected dog and its obligatory carrier parents identified a 1 bp insertion (CFA20:g.33,717,704_33,717,705insT (CanFam3.1); c.2262_c.2263insA) in CCDC66 predicted to cause a frameshift and truncation (p.Val747SerfsTer8). Screening of an extended PWD population confirmed perfect co-segregation of this genetic variant with the disease. Western blot analysis of COS-1 cells transfected with recombinant mutant CCDC66 expression constructs showed the mutant transcript translated into a truncated protein. Furthermore, in vitro studies suggest that the mutant CCDC66 is mislocalized to the nucleus relative to wild type CCDC66. CCDC66 variants have been associated with inherited retinal degenerations (RDs) including canine and murine ciliopathies. As genetic variants affecting the primary cilium can cause ciliopathies in which RD may be either the sole clinical manifestation or part of a syndrome, our findings further support a role for CCDC66 in retinal function and viability, potentially through its ciliary function