On the Expressivity and Applicability of Model Representation Formalisms

A number of first-order calculi employ an explicit model representation formalism for automated reasoning and for detecting satisfiability. Many of these formalisms can represent infinite Herbrand models. The first-order fragment of monadic, shallow, linear, Horn (MSLH) clauses, is such a formalism used in the approximation refinement calculus. Our first result is a finite model property for MSLH clause sets. Therefore, MSLH clause sets cannot represent models of clause sets with inherently infinite models. Through a translation to tree automata, we further show that this limitation also applies to the linear fragments of implicit generalizations, which is the formalism used in the model-evolution calculus, to atoms with disequality constraints, the formalisms used in the non-redundant clause learning calculus (NRCL), and to atoms with membership constraints, a formalism used for example in decision procedures for algebraic data types. Although these formalisms cannot represent models of clause sets with inherently infinite models, through an additional approximation step they can. This is our second main result. For clause sets including the definition of an equivalence relation with the help of an additional, novel approximation, called reflexive relation splitting, the approximation refinement calculus can automatically show satisfiability through the MSLH clause set formalism.Comment: 15 page

Tilt order parameters, polarity and inversion phenomena in smectic liquid crystals

The order parameters for the phenomenological description of the smectic-{\it A} to smectic-{\it C} phase transition are formulated on the basis of molecular symmetry and structure. It is shown that, unless the long molecular axis is an axis of two-fold or higher rotational symmetry, the ordering of the molecules in the smectic-{\it C} phase gives rise to more than one tilt order parameter and to one or more polar order parameters. The latter describe the indigenous polarity of the smectic-{\it C} phase, which is not related to molecular chirality but underlies the appearance of spontaneous polarisation in chiral smectics. A phenomenological theory of the phase transition is formulated by means of a Landau expansion in two tilt order parameters (primary and secondary) and an indigenous polarity order parameter. The coupling among these order parameters determines the possibility of sign inversions in the temperature dependence of the spontaneous polarisation and of the helical pitch observed experimentally for some chiral smectic-{\it $C^{\ast}$} materials. The molecular interpretation of the inversion phenomena is examined in the light of the new formulation.Comment: 12 pages, 5 figures, RevTe

Positive and negative affect, related mental health traits, and cognitive performance: shared genetic architecture and potential causality

Altered affect and cognitive dysfunction are transdiagnostic, burdensome, and pervasive features of many psychiatric conditions which remain poorly understood and have few efficacious treatments. Research on the genetic architecture of these phenotypes and causal relationships between them may provide insight into their aetiology and comorbidity. Using data from the Lifelines Cohort Study, we conducted genome-wide association studies (GWAS) on positive and negative affect and four cognitive domains (working memory, reaction time, visual learning and memory, executive function). Using publicly available large GWAS on related - albeit distinct- phenotypes (depression, anxiety, wellbeing, general cognitive ability [GCA]) we conducted genetic correlation and Mendelian randomization (MR) analyses to examine genetic overlap and causal relationships. We identified one genome-wide hit (p<5x10-8) for reaction time, and many loci with suggestive associations (p<5x10-6; N range= 11-20 independent hits) for other phenotypes. For most phenotypes, gene mapping and tissue expression analysis of suggestive hits from the GWAS showed increased gene expression in brain tissue compared to other tissues. As predicted, negative affect is genetically correlated with mental health phenotypes (depression rg=0.51; anxiety rg=0.70; wellbeing rg=-0.71) and cognitive domains are genetically correlated with GCA and brain volume (rg≤0.66). Genetic correlations between negative and positive affect suggest that they are dissociable constructs (rg=-0.18) with negative affect having higher genetic overlap with GCA than positive affect (rg=-0.19 vs -0.06). This could indicate that negative affect has a higher shared neural basis with GCA than positive affect and/or GCA and negative affect may exhibit causal relationships. MR analyses suggest potential causal effects of higher GCA on reduced negative affect, reduced risk of depression and anxiety, and higher wellbeing, but little impact on positive affect. We also report evidence for potential causal effects of depression and lower wellbeing on reduced GCA. Taken together, these results suggests that GCA may be a valid target for negative affect (but not positive affect) and depression and wellbeing may be valid targets for GCA

Perfectionism and self-conscious emotions in British and Japanese students: Predicting pride and embarrassment after success and failure

Regarding self-conscious emotions, studies have shown that different forms of perfectionism show different relationships with pride, shame, and embarrassment depending on success and failure. What is unknown is whether these relationships also show cultural variations. Therefore, we conducted a study investigating how self-oriented and socially prescribed perfectionism predicted pride and embarrassment after success and failure comparing 363 British and 352 Japanese students. Students were asked to respond to a set of scenarios where they imagined achieving either perfect (success) or flawed results (failure). In both British and Japanese students, self-oriented perfectionism positively predicted pride after success and embarrassment after failure whereas socially prescribed perfectionism predicted embarrassment after success and failure. Moreover, in Japanese students, socially prescribed perfectionism positively predicted pride after success and self-oriented perfectionism negatively predicted pride after failure. The findings have implications for our understanding of perfectionism indicating that the perfectionism–pride relationship not only varies between perfectionism dimensions, but may also show cultural variations

A prosody-based vector-space model of dialog activity for information retrieval

Search in audio archives is a challenging problem. Using prosodic information to help find relevant content has been proposed as a complement to word-based retrieval, but its utility has been an open question. We propose a new way to use prosodic information in search, based on a vector-space model, where each point in time maps to a point in a vector space whose dimensions are derived from numerous prosodic features of the local context. Point pairs that are close in this vector space are frequently similar, not only in terms of the dialog activities, but also in topic. Using proximity in this space as an indicator of similarity, we built support for a query-by-example function. Searchers were happy to use this function, and it provided value on a large testset. Prosody-based retrieval did not perform as well as word-based retrieval, but the two sources of information were often non-redundant and in combination they sometimes performed better than either separately.We thank Martha Larson, Alejandro Vega, Steve Renals, Khiet Truong, Olac Fuentes, David Novick, Shreyas Karkhedkar, Luis F. Ramirez, Elizabeth E. Shriberg, Catharine Oertel, Louis-Philippe Morency, Tatsuya Kawahara, Mary Harper, and the anonymous reviewers. This work was supported in part by the National Science Foundation under Grants IIS-0914868 and IIS-1241434 and by the Spanish MEC under contract TIN2011-28169-C05-01.Ward, NG.; Werner, SD.; García-Granada, F.; Sanchís Arnal, E. (2015). A prosody-based vector-space model of dialog activity for information retrieval. Speech Communication. 68:85-96. doi:10.1016/j.specom.2015.01.004S85966

Identification and characterization of an inhibitory fibroblast growth factor receptor 2 (FGFR2) molecule, up-regulated in an Apert Syndrome mouse model

AS (Apert syndrome) is a congenital disease composed of skeletal, visceral and neural abnormalities, caused by dominant-acting mutations in FGFR2 [FGF (fibroblast growth factor) receptor 2]. Multiple FGFR2 splice variants are generated through alternative splicing, including PTC (premature termination codon)-containing transcripts that are normally eliminated via the NMD (nonsense-mediated decay) pathway. We have discovered that a soluble truncated FGFR2 molecule encoded by a PTC-containing transcript is up-regulated and persists in tissues of an AS mouse model. We have termed this IIIa–TM as it arises from aberrant splicing of FGFR2 exon 7 (IIIa) into exon 10 [TM (transmembrane domain)]. IIIa–TM is glycosylated and can modulate the binding of FGF1 to FGFR2 molecules in BIAcore-binding assays. We also show that IIIa–TM can negatively regulate FGF signalling in vitro and in vivo. AS phenotypes are thought to result from gain-of-FGFR2 signalling, but our findings suggest that IIIa–TM can contribute to these through a loss-of-FGFR2 function mechanism. Moreover, our findings raise the interesting possibility that FGFR2 signalling may be a regulator of the NMD pathway

Effects of experimentally added salmon subsidies on resident fishes via direct and indirect pathways

Artificial additions of nutrients of differing forms such as salmon carcasses and analog pellets (i.e. pasteurized fishmeal) have been proposed as a means of stimulating aquatic productivity and enhancing populations of anadromous and resident fishes. Nutrient mitigation to enhance fish production in stream ecosystems assumes that the central pathway by which effects occur is bottom-up, through aquatic primary and secondary production, with little consideration of reciprocal aquatic-terrestrial pathways. The net outcome (i.e. bottom-up vs. top-down) of adding salmon-derived materials to streams depend on whether or not these subsidies indirectly intensify predation on in situ prey via increases in a shared predator or alleviate such predation pressure. We conducted a 3-year experiment across nine tributaries of the N. Fork Boise River, Idaho, USA, consisting of 500-m stream reaches treated with salmon carcasses (n = 3), salmon carcass analog (n = 3), and untreated control reaches (n = 3). We observed 2–8 fold increases in streambed biofilms in the 2–6 weeks following additions of both salmon subsidy treatments in years 1 and 2 and a 1.5-fold increase in standing crop biomass of aquatic invertebrates to carcass additions in the second year of our experiment. The consumption of benthic invertebrates by stream fishes increased 110–140% and 44–66% in carcass and analog streams in the same time frame, which may have masked invertebrate standing crop responses in years 3 and 4. Resident trout directly consumed 10.0–24.0 g·m-2·yr-1 of salmon carcass and \u3c1–11.0 g·m-2·yr-1 of analog material, which resulted in 1.2–2.9 g·m-2·yr-1 and 0.03–1.4 g·m-2·yr-1 of tissue produced. In addition, a feedback flux of terrestrial maggots to streams contributed 0.0–2.0 g·m-2·yr-1 to trout production. Overall, treatments increased annual trout production by 2–3 fold, though density and biomass were unaffected. Our results indicate the strength of bottom-up and top-down responses to subsidy additions was asymmetrical, with top-down forces masking bottom-up effects that required multiple years to manifest. The findings also highlight the need for nutrient mitigation programs to consider multiple pathways of energy and nutrient flow to account for the complex effects of salmon subsidies in stream-riparian ecosystems

Importance of heterogeneity in Porhyromonas gingivalis lipopolysaccharide lipid A in tissue specific inflammatory signaling

Lipopolysaccharide (LPS) of Porphyromonas gingivalis exists in at least two known forms, O-LPS and A-LPS. A-LPS shows heterogeneity in which two isoforms designated LPS1435/1449 and LPS1690 appear responsible for tissue specific immune signalingpathways activation and increased virulence. The modification of lipid A to tetra-acylated1435/1449 and/or penta-acylated1690 fatty acids indicates poor growth conditions and bioavailability of hemin. Hemin protects P. gingivalis from serum resistance and the lipid A serves as a site for its binding. The LPS1435/1449 and LPS1690 isoforms can produce opposite effects on the human Toll-like receptors (TLR) TLR 2 and TLR 4 activation. This enabless P. gingivalis to select the conditions for its entry, survival and that of its co-habiting species in the host, orchestrating its virulence to control innate immune pathway activation and biofilm dysbiosis. Thismini review describes a number of effects that LPS1435/1449 and LPS1690 can exert on the host tissues such as deregulation of the innate immune system, subversion of host cell autophagy, regulation of outer membrane vesicle production and adverse effects on pregnancy outcome. The ability to change its LPS1435/1449 and/or LPS1690 composition may enables P. gingivalis to paralyze local pro-inflammatory cytokine production, thereby gaining access to its primary location in periodontal tissue

Adaptor Template Oligo-Mediated Sequencing (ATOM-Seq) is a new ultra-sensitive UMI-based NGS library preparation technology for use with cfDNA and cfRNA

Liquid biopsy testing utilising Next Generation Sequencing (NGS) is rapidly moving towards clinical adoption for personalised oncology. However, before NGS can fulfil its potential any novel testing approach must identify ways of reducing errors, allowing separation of true low-frequency mutations from procedural artefacts, and be designed to improve upon current technologies. Popular NGS technologies typically utilise two DNA capture approaches; PCR and ligation, which have known limitations and seem to have reached a development plateau with only small, stepwise improvements being made. To maximise the ultimate utility of liquid biopsy testing we have developed a highly versatile approach to NGS: Adaptor Template Oligo Mediated Sequencing (ATOM-Seq). ATOM-Seq's strengths and versatility avoid the major limitations of both PCR- and ligation-based approaches. This technology is ligation free, simple, efficient, flexible, and streamlined, and it offers novel advantages that make it perfectly suited for use on highly challenging clinical material. Using reference and clinical materials, we demonstrate detection of known SNVs down to allele frequencies of 0.1% using as little as 20–25 ng of cfDNA, as well as the ability to detect fusions from RNA. We illustrate ATOM-Seq’s suitability for clinical testing by showing high concordance rates between paired cfDNA and FFPE clinical samples