2-(4-Bromo­phen­yl)-2-oxoethyl anthracene-9-carboxyl­ate

In the title compound, C23H15BrO3, the anthracene ring system is essentially planar [maximum deviation = 0.29 (2) Å] and makes a dihedral angle of 5.74 (8)° with the mean plane of the bromo-substituted benzene ring. An intra­molecular C—H⋯O hydrogen bond generates an S(9) ring motif. In the crystal, mol­ecules are linked by C—H⋯O inter­actions, forming a two-dimensional network parallel to the ac plane. π–π stacking inter­actions are observed between benzene rings [centroid–centroid distances = 3.5949 (14) and 3.5960 (13) Å]

4-(Morpholin-4-yl)-3-(trifluoro­meth­yl)­benzonitrile

In the title benzonitrile compound, C12H11F3N2O, an intra­molecular C—H⋯F hydrogen bond generates an S(7) ring motif. The trifluoro­methyl group is disordered over two orientations with a refined occupancy ratio of 0.549 (16):0.451 (16). The morpholine ring adopts a chair conformation. The benzene ring and mean plane of the morpholine ring make a dihedral angle of 58.04 (10)° with each other. In the crystal, mol­ecules are connected by inter­molecular C—H⋯F and C—H⋯O inter­actions to form R 2 2(8) ring motifs. These inter­actions also link the mol­ecules into chains parallel to the [10] direction

A Novel Genome-Wide Association Study Approach Using Genotyping by Exome Sequencing Leads to the Identification of a Primary Open Angle Glaucoma Associated Inversion Disrupting ADAMTS17

Closed breeding populations in the dog in conjunction with advances in gene mapping and sequencing techniques facilitate mapping of autosomal recessive diseases and identification of novel disease-causing variants, often using unorthodox experimental designs. In our investigation we demonstrate successful mapping of the locus for primary open angle glaucoma in the Petit Basset Griffon Vendéen dog breed with 12 cases and 12 controls, using a novel genotyping by exome sequencing approach. The resulting genome-wide association signal was followed up by genome sequencing of an individual case, leading to the identification of an inversion with a breakpoint disrupting the ADAMTS17 gene. Genotyping of additional controls and expression analysis provide strong evidence that the inversion is disease causing. Evidence of cryptic splicing resulting in novel exon transcription as a consequence of the inversion in ADAMTS17 is identified through RNAseq experiments. This investigation demonstrates how a novel genotyping by exome sequencing approach can be used to map an autosomal recessive disorder in the dog, with the use of genome sequencing to facilitate identification of a disease-associated variant

2-(4-Chloro­phen­yl)-2-oxoethyl 2-meth­oxy­benzoate

In the title compound, C16H13ClO4, the two benzene rings make a dihedral angle of 86.38 (8)°. In the crystal, inter­molecular C—H⋯O hydrogen bonds link the mol­ecules to form columns along the a axis. The mol­ecules are also stabilized by a π–π stacking inter­action, with a centroid–centroid distance of 3.7793 (10) Å between the inversion-related benzene rings

Node-weighted Steiner tree and group Steiner tree in planar graphs

We improve the approximation ratios for two optimization problems in planar graphs. For node-weighted Steiner tree, a classical network-optimization problem, the best achievable approximation ratio in general graphs is Θ [theta] (logn), and nothing better was previously known for planar graphs. We give a constant-factor approximation for planar graphs. Our algorithm generalizes to allow as input any nontrivial minor-closed graph family, and also generalizes to address other optimization problems such as Steiner forest, prize-collecting Steiner tree, and network-formation games. The second problem we address is group Steiner tree: given a graph with edge weights and a collection of groups (subsets of nodes), find a minimum-weight connected subgraph that includes at least one node from each group. The best approximation ratio known in general graphs is O(log3 [superscript 3] n), or O(log2 [superscript 2] n) when the host graph is a tree. We obtain an O(log n polyloglog n) approximation algorithm for the special case where the graph is planar embedded and each group is the set of nodes on a face. We obtain the same approximation ratio for the minimum-weight tour that must visit each group

Genome-Wide Association Studies in Dogs and Humans Identify ADAMTS20 as a Risk Variant for Cleft Lip and Palate

Cleft lip with or without cleft palate (CL/P) is the most commonly occurring craniofacial birth defect. We provide insight into the genetic etiology of this birth defect by performing genome-wide association studies in two species: dogs and humans. In the dog, a genome-wide association study of 7 CL/P cases and 112 controls from the Nova Scotia Duck Tolling Retriever (NSDTR) breed identified a significantly associated region on canine chromosome 27 (unadjusted p=1.1 x 10-13; adjusted p= 2.2 x 10-3). Further analysis in NSDTR families and additional full sibling cases identified a 1.44 Mb homozygous haplotype (chromosome 27: 9.29 – 10.73 Mb) segregating with a more complex phenotype of cleft lip, cleft palate, and syndactyly (CLPS) in 13 cases. Whole-genome sequencing of 3 CLPS cases and 4 controls at 15X coverage led to the discovery of a frameshift mutation within ADAMTS20 (c.1360_1361delAA (p.Lys453Ilefs*3)), which segregated concordant with the phenotype. In a parallel study in humans, a family-based association analysis (DFAM) of 125 CL/P cases, 420 unaffected relatives, and 392 controls from a Guatemalan cohort, identified a suggestive association (rs10785430; p =2.67 x 10-6) with the same gene, ADAMTS20. Sequencing of cases from the Guatemalan cohort was unable to identify a causative mutation within the coding region of ADAMTS20, but four coding variants were found in additional cases of CL/P. In summary, this study provides genetic evidence for a role of ADAMTS20 in CL/P development in dogs and as a candidate gene for CL/P development in humans

Exploiting the Temporal Logic Hierarchy and the Non-Confluence Property for Efficient LTL Synthesis

The classic approaches to synthesize a reactive system from a linear temporal logic (LTL) specification first translate the given LTL formula to an equivalent omega-automaton and then compute a winning strategy for the corresponding omega-regular game. To this end, the obtained omega-automata have to be (pseudo)-determinized where typically a variant of Safra's determinization procedure is used. In this paper, we show that this determinization step can be significantly improved for tool implementations by replacing Safra's determinization by simpler determinization procedures. In particular, we exploit (1) the temporal logic hierarchy that corresponds to the well-known automata hierarchy consisting of safety, liveness, Buechi, and co-Buechi automata as well as their boolean closures, (2) the non-confluence property of omega-automata that result from certain translations of LTL formulas, and (3) symbolic implementations of determinization procedures for the Rabin-Scott and the Miyano-Hayashi breakpoint construction. In particular, we present convincing experimental results that demonstrate the practical applicability of our new synthesis procedure

How brains make decisions

This chapter, dedicated to the memory of Mino Freund, summarizes the Quantum Decision Theory (QDT) that we have developed in a series of publications since 2008. We formulate a general mathematical scheme of how decisions are taken, using the point of view of psychological and cognitive sciences, without touching physiological aspects. The basic principles of how intelligence acts are discussed. The human brain processes involved in decisions are argued to be principally different from straightforward computer operations. The difference lies in the conscious-subconscious duality of the decision making process and the role of emotions that compete with utility optimization. The most general approach for characterizing the process of decision making, taking into account the conscious-subconscious duality, uses the framework of functional analysis in Hilbert spaces, similarly to that used in the quantum theory of measurements. This does not imply that the brain is a quantum system, but just allows for the simplest and most general extension of classical decision theory. The resulting theory of quantum decision making, based on the rules of quantum measurements, solves all paradoxes of classical decision making, allowing for quantitative predictions that are in excellent agreement with experiments. Finally, we provide a novel application by comparing the predictions of QDT with experiments on the prisoner dilemma game. The developed theory can serve as a guide for creating artificial intelligence acting by quantum rules.Comment: Latex file, 20 pages, 3 figure

Mutations in the SLC2A9 Gene Cause Hyperuricosuria and Hyperuricemia in the Dog

Allantoin is the end product of purine catabolism in all mammals except humans, great apes, and one breed of dog, the Dalmatian. Humans and Dalmatian dogs produce uric acid during purine degradation, which leads to elevated levels of uric acid in blood and urine and can result in significant diseases in both species. The defect in Dalmatians results from inefficient transport of uric acid in both the liver and renal proximal tubules. Hyperuricosuria and hyperuricemia (huu) is a simple autosomal recessive trait for which all Dalmatian dogs are homozygous. Therefore, in order to map the locus, an interbreed backcross was used. Linkage mapping localized the huu trait to CFA03, which excluded the obvious urate transporter 1 gene, SLC22A12. Positional cloning placed the locus in a minimal interval of 2.5 Mb with a LOD score of 17.45. A critical interval of 333 kb containing only four genes was homozygous in all Dalmatians. Sequence and expression analyses of the SLC2A9 gene indicated three possible mutations, a missense mutation (G616T;C188F) and two promoter mutations that together appear to reduce the expression levels of one of the isoforms. The missense mutation is associated with hyperuricosuria in the Dalmatian, while the promoter SNPs occur in other unaffected breeds of dog. Verification of the causative nature of these changes was obtained when hyperuricosuric dogs from several other breeds were found to possess the same combination of mutations as found in the Dalmatian. The Dalmatian dog model of hyperuricosuria and hyperuricemia underscores the importance of SLC2A9 for uric acid transport in mammals