Sensitive and Scalable Online Evaluation with Theoretical Guarantees

Multileaved comparison methods generalize interleaved comparison methods to provide a scalable approach for comparing ranking systems based on regular user interactions. Such methods enable the increasingly rapid research and development of search engines. However, existing multileaved comparison methods that provide reliable outcomes do so by degrading the user experience during evaluation. Conversely, current multileaved comparison methods that maintain the user experience cannot guarantee correctness. Our contribution is two-fold. First, we propose a theoretical framework for systematically comparing multileaved comparison methods using the notions of considerateness, which concerns maintaining the user experience, and fidelity, which concerns reliable correct outcomes. Second, we introduce a novel multileaved comparison method, Pairwise Preference Multileaving (PPM), that performs comparisons based on document-pair preferences, and prove that it is considerate and has fidelity. We show empirically that, compared to previous multileaved comparison methods, PPM is more sensitive to user preferences and scalable with the number of rankers being compared.Comment: CIKM 2017, Proceedings of the 2017 ACM on Conference on Information and Knowledge Managemen

(Total) Vector Domination for Graphs with Bounded Branchwidth

Given a graph $G=(V,E)$ of order $n$ and an $n$-dimensional non-negative vector $d=(d(1),d(2),\ldots,d(n))$, called demand vector, the vector domination (resp., total vector domination) is the problem of finding a minimum $S\subseteq V$ such that every vertex $v$ in $V\setminus S$ (resp., in $V$) has at least $d(v)$ neighbors in $S$. The (total) vector domination is a generalization of many dominating set type problems, e.g., the dominating set problem, the $k$-tuple dominating set problem (this $k$ is different from the solution size), and so on, and its approximability and inapproximability have been studied under this general framework. In this paper, we show that a (total) vector domination of graphs with bounded branchwidth can be solved in polynomial time. This implies that the problem is polynomially solvable also for graphs with bounded treewidth. Consequently, the (total) vector domination problem for a planar graph is subexponential fixed-parameter tractable with respectto $k$, where $k$ is the size of solution.Comment: 16 page

A CT-based revised description and phylogenetic analysis of the skull of the basal maniraptoran Ornitholestes hermanni Osborn 1903

Ornitholestes hermanni was one of the first small-bodiedtheropods named in the 1900s. It is known from a singlespecimen discovered during the American MuseumExpedition of 1900, at the Jurassic Morrison Formationsite known as Bone Cabin Quarry, in Wyoming. It haslong been a critical taxon in understanding the evolutionof the Coelurosauria, the clade that includestyrannosauroids, living birds, and their commonancestors. The holotype specimen comprises a nearlycomplete skull and most of a postcranial skeleton. Despitethis abundant material, its precise phylogeneticrelationships have been difficult to determine. This is inpart due to the intense mediolateral crushing of the skulland the relatively generalized postcranial anatomy. Herewe present the results of a micro- computed tomographybasedinvestigation of the cranial anatomy and subsequentincorporation of these data into a phylogenetic data matrixdesigned to test coelurosaurian interrelationships. We findrobust evidence across different optimality criteria thatOrnitholestes is the earliest-branching oviraptorosaurianspecies. Using parsimony as an optimality criterion, thisphylogenetic position is supported by 14 unambiguoussynapomorphies, including: a short frontal process of thepostorbital; short, deep, and pendant paroccipitalprocesses; a large mandibular foramen; an anterodorsallyoriented dentary symphysis; a surangular that is longerthan the dentary; short maxillary and dentary tooth rows;and procumbent dentary and premaxillary teeth. UsingBayesian fossilized birth-death models, we find highposterior probabilities (>.99) that Ornitholestes is theearliest-branching oviraptorosaurian species. Weadditionally find strong support in both analyses that thesuperficially bat-like and possibly arborealscansoriopterygids are an early branching lineage withinOviraptorosauria. This new phylogenetic position fills in apersistent ghost lineage in Oviraptorosauria and confirmsthat scansoriopterygids are basally branchingoviraptorosaurians that represent an independent origin ofaerial habits, separate from those of dromaeosaurs andavialans.Fil: Chapelle, Kimberley E.. American Museum of Natural History; Estados UnidosFil: Norell, Mark. American Museum of Natural History; Estados UnidosFil: Ford, David P.. University of the Witwatersrand; SudáfricaFil: Hendrickx, Christophe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Radermacher, Viktor J.. University of Minnesota; Estados UnidosFil: Balanoff, Amy. University Johns Hopkins; Estados UnidosFil: Zanno, Lindsay E.. North Carolina Museum of Natural Sciences; Estados UnidosFil: Choiniere, Jonah N.. University of the Witwatersrand; Sudáfrica81st Annual Meeting of the Society of Vertebrate PaleontologyMc LeanEstados UnidosSociety of Vertebrate Paleontolog

Recent advances in clinical practice: Colorectal cancer chemoprevention in the average-risk population

Colorectal cancer (CRC) is one of the most common and lethal malignancies in Western countries. Its development is a multistep process that spans more than 15 years, thereby providing an opportunity for prevention and early detection. The high incidence and mortality rates emphasise the need for prevention and screening. Many countries have therefore introduced CRC screening programmes. It is expected, and preliminary evidence in some countries suggests, that this screening effort will decrease CRCrelated mortality rates. CRC prevention involves a healthy lifestyle and chemoprevention—more specific

Features of mammalian microRNA promoters emerge from polymerase II chromatin immunoprecipitation data

Background: MicroRNAs (miRNAs) are short, non-coding RNA regulators of protein coding genes. miRNAs play a very important role in diverse biological processes and various diseases. Many algorithms are able to predict miRNA genes and their targets, but their transcription regulation is still under investigation. It is generally believed that intragenic miRNAs (located in introns or exons of protein coding genes) are co-transcribed with their host genes and most intergenic miRNAs transcribed from their own RNA polymerase II (Pol II) promoter. However, the length of the primary transcripts and promoter organization is currently unknown. Methodology: We performed Pol II chromatin immunoprecipitation (ChIP)-chip using a custom array surrounding regions of known miRNA genes. To identify the true core transcription start sites of the miRNA genes we developed a new tool (CPPP). We showed that miRNA genes can be transcribed from promoters located several kilobases away and that their promoters share the same general features as those of protein coding genes. Finally, we found evidence that as many as 26% of the intragenic miRNAs may be transcribed from their own unique promoters. Conclusion: miRNA promoters have similar features to those of protein coding genes, but miRNA transcript organization is more complex. © 2009 Corcoran et al

Nonlinear partial differential equations and applications: Gene expression profiling of isogenic cells with different TP53 gene dosage reveals numerous genes that are affected by TP53 dosage and identifies CSPG2 as a direct target of p53

TP53 does not fully comply with the Knudson model [Knudson, A. G., Jr. (1971) Proc. Natl. Acad. Sci. USA 68, 820–823] in that a reduction of constitutional expression of p53 may be sufficient for tumor predisposition . This finding suggests a gene-dosage effect for p53 function. To determine whether TP53 gene dosage affects the transcriptional regulation of target genes, we performed oligonucleotide-array gene expression analysis by using human cells with wild-type p53 (p53 +/+), or with one (p53 +/−), or both (p53 −/−) TP53 alleles disrupted by homologous recombination. We identified 35 genes whose expression is significantly correlated to the dosage of TP53. These genes are involved in a variety of cellular processes including signal transduction, cell adhesion, and transcription regulation. Several of them are involved in neurogenesis and neural crest migration, developmental processes in which p53 is known to play a role. Motif search analysis revealed that of the genes highly expressed in p53 +/+ and +/− cells, several contain a putative p53 consensus binding site (bs), suggesting that they could be directly regulated by p53. Among those genes, we chose CSPG2 (which encodes versican) for further study because it contains a bona fide p53 bs in its first intron and its expression highly correlates with TP53 dosage. By using in vitro and in vivo assays, we showed CSPG2 to be directly transactivated by p53. In conclusion, we developed a strategy to demonstrate that many genes are affected by TP53 gene dosage for their expression. We report several candidate genes as potential downstream targets of p53 in nonstressed cells. Among them, CSPG2 is validated as being directly transactivated by p53. Our method provides a useful tool to elucidate additional mechanisms by which p53 exerts its functions

Profiling allele-specific gene expression in brains from individuals with autism spectrum disorder reveals preferential minor allele usage.

One fundamental but understudied mechanism of gene regulation in disease is allele-specific expression (ASE), the preferential expression of one allele. We leveraged RNA-sequencing data from human brain to assess ASE in autism spectrum disorder (ASD). When ASE is observed in ASD, the allele with lower population frequency (minor allele) is preferentially more highly expressed than the major allele, opposite to the canonical pattern. Importantly, genes showing ASE in ASD are enriched in those downregulated in ASD postmortem brains and in genes harboring de novo mutations in ASD. Two regions, 14q32 and 15q11, containing all known orphan C/D box small nucleolar RNAs (snoRNAs), are particularly enriched in shifts to higher minor allele expression. We demonstrate that this allele shifting enhances snoRNA-targeted splicing changes in ASD-related target genes in idiopathic ASD and 15q11-q13 duplication syndrome. Together, these results implicate allelic imbalance and dysregulation of orphan C/D box snoRNAs in ASD pathogenesis

An activating mutation in the CSF3R gene induces a hereditary chronic neutrophilia

We identify an autosomal mutation in the CSF3R gene in a family with a chronic neutrophilia. This T617N mutation energetically favors dimerization of the granulocyte colony-stimulating factor (G-CSF) receptor transmembrane domain, and thus, strongly promotes constitutive activation of the receptor and hypersensitivity to G-CSF for proliferation and differentiation, which ultimately leads to chronic neutrophilia. Mutant hematopoietic stem cells yield a myeloproliferative-like disorder in xenotransplantation and syngenic mouse bone marrow engraftment assays. The survey of 12 affected individuals during three generations indicates that only one patient had a myelodysplastic syndrome. Our data thus indicate that mutations in the CSF3R gene can be responsible for hereditary neutrophilia mimicking a myeloproliferative disorder

No association between germline allele-specific expression of TGFBR1 and colorectal cancer risk in Caucasian and Ashkenazi populations

Background: germline allele-specific expression (ASE) of the TGFBR1 gene has been reported as a strong risk factor for colorectal cancer (CRC) with an odds ratio close to 9. Considering the potential implications of the finding, we undertook the task of validating the initial results in this study. Methods: allele-specific expression was measured using the highly quantitative and robust technique of pyrosequencing. Individuals from two different populations were studied, one Caucasian-dominated and the other of Ashkenazi Jewish descent, with different sources of non-tumoral genetic material in each. Results: our results showed no statistically significant differences in the degree of ASE between CRC patients and controls, considering ASE as either a quantitative or a binary trait. Using defined cutoff values to categorise ASE, 1.0% of blood lymphocytes from informative Israeli cases (total n=96) were ASE positive (median 1.00; range 0.76-1.31) and 2.2% of informative matched controls (total n=90) were ASE positive (median 1.00; range 0.76-1.87). Likewise, normal mucosae from Spanish patients (median 1.03; range: 0.68-1.43; n=75) did not show significant differences in the degree of ASE when compared with the Israeli patients or controls. Conclusions: taken together, these results suggest that ASE of TGFBR1 does not confer an increased risk of CRC