314 research outputs found

    Categories of First-Order Quantifiers

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    One well known problem regarding quantifiers, in particular the 1storder quantifiers, is connected with their syntactic categories and denotations. The unsatisfactory efforts to establish the syntactic and ontological categories of quantifiers in formalized first-order languages can be solved by means of the so called principle of categorial compatibility formulated by Roman Suszko, referring to some innovative ideas of Gottlob Frege and visible in syntactic and semantic compatibility of language expressions. In the paper the principle is introduced for categorial languages generated by the Ajdukiewicz’s classical categorial grammar. The 1st-order quantifiers are typically ambiguous. Every 1st-order quantifier of the type k \u3e 0 is treated as a two-argument functorfunction defined on the variable standing at this quantifier and its scope (the sentential function with exactly k free variables, including the variable bound by this quantifier); a binary function defined on denotations of its two arguments is its denotation. Denotations of sentential functions, and hence also quantifiers, are defined separately in Fregean and in situational semantics. They belong to the ontological categories that correspond to the syntactic categories of these sentential functions and the considered quantifiers. The main result of the paper is a solution of the problem of categories of the 1st-order quantifiers based on the principle of categorial compatibility

    Localization from sigma-model geodesics

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    We use a novel method based on the semi-classical analysis of sigma-models to describe the phenomenon of strong localization in quasi one-dimensional conductors, obtaining the full distribution of transmission eigenvalues. For several symmetry classes, describing random superconducting and chiral Hamiltonians, the target space of the appropriate sigma-model is a (super)group manifold. In these cases our approach turns out to be exact. The results offer a novel perspective on localization.Comment: Published versio

    X-linked hypomyelination with spondylometaphyseal dysplasia (H-SMD) associated with mutations in AIFM1

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    An X-linked condition characterized by the combination of hypomyelinating leukodystrophy and spondylometaphyseal dysplasia (H-SMD) has been observed in only four families, with linkage to Xq25-27, and recent genetic characterization in two families with a common AIFM1 mutation. In our study, 12 patients (6 families) with H-SMD were identified and underwent comprehensive assessment accompanied by whole-exome sequencing (WES). Pedigree analysis in all families was consistent with X-linked recessive inheritance. Presentation typically occurred between 12 and 36 months. In addition to the two disease-defining features of spondylometaphyseal dysplasia and hypomyelination on MRI, common clinical signs and symptoms included motor deterioration, spasticity, tremor, ataxia, dysarthria, cognitive defects, pulmonary hypertension, nystagmus, and vision loss due to retinopathy. The course of the disease was slowly progressive. All patients had maternally inherited or de novo mutations in or near exon 7 of AIFM1, within a region of 70 bp, including synonymous and intronic changes. AIFM1 mutations have previously been associated with neurologic presentations as varied as intellectual disability, hearing loss, neuropathy, and striatal necrosis, while AIFM1 mutations in this small region present with a distinct phenotype implicating bone. Analysis of cell lines derived from four patients identified significant reductions in AIFM1 mRNA and protein levels in osteoblasts. We hypothesize that AIFM1 functions in bone metabolism and myelination and is responsible for the unique phenotype in this condition.</p

    Polygenic risk score for schizophrenia was not associated with glycemic level (HbA1c) in patients with non-affective psychosis: Genetic Risk and Outcome of Psychosis (GROUP) cohort study

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    Introduction: Type 2 diabetes (T2D) is a common comorbidity in patients with schizophrenia (SCZ). The underlying pathophysiologic mechanisms are yet to be fully elucidated, although it can be argued that shared genes, environmental factors or their interaction effect are involved. This study investigated the association between polygenic risk score of SCZ (PRSSCZ) and glycated haemoglobin (HbA1c) while adjusting for polygenic risk score of T2D (PRST2D), and clinical and demographic covariables. Methods: Genotype, clinical and demographic data of 1129 patients with non-affective psychosis were extracted from Genetic Risk and Outcome of Psychosis (GROUP) cohort study. The glycated haemoglobin (HbA1c) was the outcome. PRS was calculated using standard methods. Univariable and multivariable linear regression analyses were applied to estimate associations. Additionally, sensitivity analysis based on multiple imputation was done. After correction for multiple testing, a two-sided p-value ≤.003 was considered to discover evidence for an association. Results: Of 1129 patients, 75.8% were male with median age of 29 years. The mean (standard deviation) HbA1c level was 35.1 (5.9) mmol/mol. There was no evidence for an association between high HbA1c level and increased PRSSCZ (adjusted regression coefficient (aβ) = 0.69, standard error (SE) = 0.77, p-value =.37). On the other hand, there was evidence for an association between high HbA1c level and increased PRST2D (aβ = 0.93, SE = 0.32, p-value =.004), body mass index (aβ = 0.20, SE = 0.08, p-value =.01), diastolic blood pressure (aβ = 0.08, SE = 0.04, p-value =.03), late age of first psychosis onset (aβ = 0.19, SE = 0.05, p-value =.0004) and male gender (aβ = 1.58, SE = 0.81, p-value =.05). After multiple testing correction, there was evidence for an association between high HbA1c level and late age of first psychosis onset. Evidence for interaction effect between PRSscz and antipsychotics was not observed. The multiple imputation-based sensitivity analysis provided consistent results with complete case analysis. Conclusions: Glycemic dysregulation in patients with SCZ was not associated with PRSSCZ. This suggests that the mechanisms of hyperglycemia or diabetes are at least partly independent from genetic predisposition to SCZ. Our findings show that the change in HbA1c level can be caused by at least in part due to PRST2D, late age of illness onset, male gender, and increased body mass index and diastolic blood pressure

    Bayesian Inference for Identifying Interaction Rules in Moving Animal Groups

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    The emergence of similar collective patterns from different self-propelled particle models of animal groups points to a restricted set of “universal” classes for these patterns. While universality is interesting, it is often the fine details of animal interactions that are of biological importance. Universality thus presents a challenge to inferring such interactions from macroscopic group dynamics since these can be consistent with many underlying interaction models. We present a Bayesian framework for learning animal interaction rules from fine scale recordings of animal movements in swarms. We apply these techniques to the inverse problem of inferring interaction rules from simulation models, showing that parameters can often be inferred from a small number of observations. Our methodology allows us to quantify our confidence in parameter fitting. For example, we show that attraction and alignment terms can be reliably estimated when animals are milling in a torus shape, while interaction radius cannot be reliably measured in such a situation. We assess the importance of rate of data collection and show how to test different models, such as topological and metric neighbourhood models. Taken together our results both inform the design of experiments on animal interactions and suggest how these data should be best analysed

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
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