A Boolean Extension of KLM-Style Conditional Reasoning

Propositional KLM-style defeasible reasoning involves extending propositional logic with a new logical connective that can express defeasible (or conditional) implications, with semantics given by ordered structures known as ranked interpretations. KLM-style defeasi- ble entailment is referred to as rational whenever the defeasible entail- ment relation under consideration generates a set of defeasible implica- tions all satisfying a set of rationality postulates known as the KLM postulates. In a recent paper Booth et al. proposed PTL, a logic that is more expressive than the core KLM logic. They proved an impossibility result, showing that defeasible entailment for PTL fails to satisfy a set of rationality postulates similar in spirit to the KLM postulates. Their interpretation of the impossibility result is that defeasible entailment for PTL need not be unique. In this paper we continue the line of research in which the expressivity of the core KLM logic is extended. We present the logic Boolean KLM (BKLM) in which we allow for disjunctions, conjunctions, and negations, but not nesting, of defeasible implications. Our contribution is twofold. Firstly, we show (perhaps surprisingly) that BKLM is more expressive than PTL. Our proof is based on the fact that BKLM can characterise all single ranked interpretations, whereas PTL cannot. Secondly, given that the PTL impossibility result also applies to BKLM, we adapt the different forms of PTL entailment proposed by Booth et al. to apply to BKLM

Improved homology-driven computational validation of protein-protein interactions motivated by the evolutionary gene duplication and divergence hypothesis

<p>Abstract</p> <p>Background</p> <p>Protein-protein interaction (PPI) data sets generated by high-throughput experiments are contaminated by large numbers of erroneous PPIs. Therefore, computational methods for PPI validation are necessary to improve the quality of such data sets. Against the background of the theory that most extant PPIs arose as a consequence of gene duplication, the sensitive search for homologous PPIs, i.e. for PPIs descending from a common ancestral PPI, should be a successful strategy for PPI validation.</p> <p>Results</p> <p>To validate an experimentally observed PPI, we combine FASTA and PSI-BLAST to perform a sensitive sequence-based search for pairs of interacting homologous proteins within a large, integrated PPI database. A novel scoring scheme that incorporates both quality and quantity of all observed matches allows us (1) to consider also tentative paralogs and orthologs in this analysis and (2) to combine search results from more than one homology detection method. ROC curves illustrate the high efficacy of this approach and its improvement over other homology-based validation methods.</p> <p>Conclusion</p> <p>New PPIs are primarily derived from preexisting PPIs and not invented <it>de novo</it>. Thus, the hallmark of true PPIs is the existence of homologous PPIs. The sensitive search for homologous PPIs within a large body of known PPIs is an efficient strategy to separate biologically relevant PPIs from the many spurious PPIs reported by high-throughput experiments.</p

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Do Political Attitudes Matter for Epistemic Decisions of Scientists?

The epistemic attitudes of scientists, such as epistemic tolerance and authoritarianism, play important roles in the discourse about rivaling theories. Epistemic tolerance stands for the mental attitude of an epistemic agent, e.g., a scientist, who is open to opposing views, while epistemic authoritarianism represents the tendency to uncritically accept views of authorities. Another relevant epistemic factor when it comes to the epistemic decisions of scientists is the skepticism towards the scientific method. However, the question is whether these epistemic attitudes are influenced by their sociopolitical counterparts, such as the researcher's degree of conservatism. To empirically investigate the interplay between epistemic and sociopolitical attitudes of scientists, we conducted a survey with researchers (N = 655) across different disciplines. We propose scales for measuring epistemic tolerance and epistemic authoritarianism, as well as a scale for detecting the participants' readiness to question the scientific method. Furthermore, we investigate the relationship between epistemic tolerance and epistemic authoritarianism on the one hand, and career stage and sociopolitical views on the other hand. Interestingly, our study found only small correlations between the participants' degree of conservatism and their epistemic attitudes. This suggests that political views, against common argumentation, actually do not play an important role in one's scientific decisions. Moreover, social scientists scored higher on the epistemic tolerance and lower on the epistemic authoritarianism scale than natural scientists. Finally, the results indicate that natural scientists question the scientific method less than social scientists