Abstract Games of Argumentation Strategy and Game-Theoretical Argument Strength

We define a generic notion of abstract games of argumentation strategy for (attack-only and bipolar) argumentation frameworks, which are zero-sum games whereby two players put forward sets of arguments and get a reward for their combined choices. The value of these games, in the classical game-theoretic sense, can be used to define measures of (quantitative) game-theoretic strength of arguments, which are different depending on whether either or both players have an “agenda” (i.e. an argument they want to be accepted). We show that this general scheme captures as a special instance a previous proposal in the literature (single agenda, attack-only frameworks), and seamlessly supports the definition of a spectrum of novel measures of game-theoretic strength where both players have an agenda and/or bipolar frameworks are considered. We then discuss the applicability of these instances of game-theoretic strength in different contexts and analyse their basic properties

Visual art inspired by the collective feeding behavior of sand-bubbler crabs

Sand--bubblers are crabs of the genera Dotilla and Scopimera which are known to produce remarkable patterns and structures at tropical beaches. From these pattern-making abilities, we may draw inspiration for digital visual art. A simple mathematical model is proposed and an algorithm is designed that may create such sand-bubbler patterns artificially. In addition, design parameters to modify the patterns are identified and analyzed by computational aesthetic measures. Finally, an extension of the algorithm is discussed that may enable controlling and guiding generative evolution of the art-making process

The effect of time constraint on anticipation, decision making, and option generation in complex and dynamic environments

Researchers interested in performance in complex and dynamic situations have focused on how individuals predict their opponent(s) potential courses of action (i.e., during assessment) and generate potential options about how to respond (i.e., during intervention). When generating predictive options, previous research supports the use of cognitive mechanisms that are consistent with long-term working memory (LTWM) theory (Ericsson and Kintsch in Phychol Rev 102(2):211–245, 1995; Ward et al. in J Cogn Eng Decis Mak 7:231–254, 2013). However, when generating options about how to respond, the extant research supports the use of the take-the-first (TTF) heuristic (Johnson and Raab in Organ Behav Hum Decis Process 91:215–229, 2003). While these models provide possible explanations about how options are generated in situ, often under time pressure, few researchers have tested the claims of these models experimentally by explicitly manipulating time pressure. The current research investigates the effect of time constraint on option-generation behavior during the assessment and intervention phases of decision making by employing a modified version of an established option-generation task in soccer. The results provide additional support for the use of LTWM mechanisms during assessment across both time conditions. During the intervention phase, option-generation behavior appeared consistent with TTF, but only in the non-time-constrained condition. Counter to our expectations, the implementation of time constraint resulted in a shift toward the use of LTWM-type mechanisms during the intervention phase. Modifications to the cognitive-process level descriptions of decision making during intervention are proposed, and implications for training during both phases of decision making are discussed

Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis

The finding of TDP-43 as a major component of ubiquitinated protein inclusions in amyotrophic lateral sclerosis (ALS) has led to the identification of 30 mutations in the transactive response-DNA binding protein (TARDBP) gene, encoding TDP-43. All but one are in exon 6, which encodes the glycine-rich domain. The aim of this study was to determine the frequency of TARDBP mutations in a large cohort of motor neurone disease patients from Northern England (42 non-superoxide dismutase 1 (SOD1) familial ALS (FALS), nine ALS-frontotemporal dementia, 474 sporadic ALS (SALS), 45 progressive muscular atrophy cases). We identified four mutations, two of which were novel, in two familial (FALS) and two sporadic (SALS) cases, giving a frequency of TARDBP mutations in non-SOD1 FALS of 5% and SALS of 0.4%. Analysis of clinical data identified that patients had typical ALS, with limb or bulbar onset, and showed considerable variation in age of onset and rapidity of disease course. However, all cases had an absence of clinically overt cognitive dysfunction

The alpha 7 nicotinic receptor agonist PHA-543613 hydrochloride inhibits <i>Porphyromonas gingivalis</i>-induced expression of interleukin-8 by oral keratinocytes

Objective: The alpha 7 nicotinic receptor (α7nAChR) is expressed by oral keratinocytes. α7nAChR activation mediates anti-inflammatory responses. The objective of this study was to determine if α7nAChR activation inhibited pathogen-induced interleukin-8 (IL-8) expression by oral keratinocytes.&lt;p&gt;&lt;/p&gt; Materials and methods: Periodontal tissue expression of α7nAChR was determined by real-time PCR. OKF6/TERT-2 oral keratinocytes were exposed to &lt;i&gt;Porphyromonas gingivalis&lt;/i&gt; in the presence and absence of a α7nAChR agonist (PHA-543613 hydrochloride) alone or after pre-exposure to a specific α7nAChR antagonist (α-bungarotoxin). Interleukin-8 (IL-8) expression was measured by ELISA and real-time PCR. Phosphorylation of the NF-κB p65 subunit was determined using an NF-κB p65 profiler assay and STAT-3 activation by STAT-3 in-cell ELISA. The release of ACh from oral keratinocytes in response to &lt;i&gt;P. gingivalis&lt;/i&gt; lipopolysaccharide was determined using a GeneBLAzer M3 CHO-K1-blacell reporter assay.&lt;p&gt;&lt;/p&gt; Results: Expression of α7nAChR mRNA was elevated in diseased periodontal tissue. PHA-543613 hydrochloride inhibited &lt;i&gt;P. Gingivalis&lt;/i&gt;-induced expression of IL-8 at the transcriptional level. This effect was abolished when cells were pre-exposed to a specific α7nAChR antagonist, α-bungarotoxin. PHA-543613 hydrochloride downregulated NF-κB signalling through reduced phosphorylation of the NF-κB p65-subunit. In addition, PHA-543613 hydrochloride promoted STAT-3 signalling by maintenance of phosphorylation. Furthermore, oral keratinocytes upregulated ACh release in response to &lt;i&gt;P. Gingivalis&lt;/i&gt; lipopolysaccharide.&lt;p&gt;&lt;/p&gt; Conclusion: These data suggest that α7nAChR plays a role in regulating the innate immune responses of oral keratinocytes.&lt;p&gt;&lt;/p&gt

Hedgehog pathway mutations drive oncogenic transformation in high-risk T-cell acute lymphoblastic leukemia.

The role of Hedgehog signaling in normal and malignant T-cell development is controversial. Recently, Hedgehog pathway mutations have been described in T-ALL, but whether mutational activation of Hedgehog signaling drives T-cell transformation is unknown, hindering the rationale for therapeutic intervention. Here, we show that Hedgehog pathway mutations predict chemotherapy resistance in human T-ALL, and drive oncogenic transformation in a zebrafish model of the disease. We found Hedgehog pathway mutations in 16% of 109 childhood T-ALL cases, most commonly affecting its negative regulator PTCH1. Hedgehog mutations were associated with resistance to induction chemotherapy (P = 0.009). Transduction of wild-type PTCH1 into PTCH1-mutant T-ALL cells induced apoptosis (P = 0.005), a phenotype that was reversed by downstream Hedgehog pathway activation (P = 0.007). Transduction of most mutant PTCH1, SUFU, and GLI alleles into mammalian cells induced aberrant regulation of Hedgehog signaling, indicating that these mutations are pathogenic. Using a CRISPR/Cas9 system for lineage-restricted gene disruption in transgenic zebrafish, we found that ptch1 mutations accelerated the onset of notch1-induced T-ALL (P = 0.0001), and pharmacologic Hedgehog pathway inhibition had therapeutic activity. Thus, Hedgehog-activating mutations are driver oncogenic alterations in high-risk T-ALL, providing a molecular rationale for targeted therapy in this disease

Lessons for non-VA care delivery systems from the U.S. Department of Veterans Affairs Quality Enhancement Research Initiative: QUERI Series

The U.S. Veterans Health Administration (VHA) may have a very different structure and function from the organizations and practices that provide medical care to most Americans, but those organizations and practices could learn a lot from the VHA's Quality Enhancement Research Initiative (QUERI). There are at least six topics of increasing importance for implementation research where QUERI experience should be of value to other non-VHA organizations, both within and external to the United States: 1) Researcher-clinical leader partnerships for care improvement; 2) Attention to culture, capacity, leadership, and a supportive infrastructure; 3) Practical economic evaluation of quality implementation efforts; 4) Human subject protection problems; 5) Sustainability of improvements; and 6) Scale-up and spread of improvements

Site-specific chromatin immunoprecipitation: a selective method to individually analyze neighboring transcription factor binding sites in vivo

<p>Abstract</p> <p>Background</p> <p>Transcription factors (TFs) and their binding sites (TFBSs) play a central role in the regulation of gene expression. It is therefore vital to know how the allocation pattern of TFBSs affects the functioning of any particular gene in vivo. A widely used method to analyze TFBSs in vivo is the chromatin immunoprecipitation (ChIP). However, this method in its present state does not enable the individual investigation of densely arranged TFBSs due to the underlying unspecific DNA fragmentation technique. This study describes a site-specific ChIP which aggregates the benefits of both EMSA and in vivo footprinting in only one assay, thereby allowing the individual detection and analysis of single binding motifs.</p> <p>Findings</p> <p>The standard ChIP protocol was modified by replacing the conventional DNA fragmentation, i. e. via sonication or undirected enzymatic digestion (by MNase), through a sequence specific enzymatic digestion step. This alteration enables the specific immunoprecipitation and individual examination of occupied sites, even in a complex system of adjacent binding motifs in vivo. Immunoprecipitated chromatin was analyzed by PCR using two primer sets - one for the specific detection of precipitated TFBSs and one for the validation of completeness of the enzyme digestion step. The method was established exemplary for Sp1 TFBSs within the <it>egfr </it>promoter region. Using this site-specific ChIP, we were able to confirm four previously described Sp1 binding sites within <it>egfr </it>promoter region to be occupied by Sp1 in vivo. Despite the dense arrangement of the Sp1 TFBSs the improved ChIP method was able to individually examine the allocation of all adjacent Sp1 TFBS at once. The broad applicability of this site-specific ChIP could be demonstrated by analyzing these SP1 motifs in both osteosarcoma cells and kidney carcinoma tissue.</p> <p>Conclusions</p> <p>The ChIP technology is a powerful tool for investigating transcription factors in vivo, especially in cancer biology. The established site-specific enzyme digestion enables a reliable and individual detection option for densely arranged binding motifs in vivo not provided by e.g. EMSA or in vivo footprinting. Given the important function of transcription factors in neoplastic mechanism, our method enables a broad diversity of application options for clinical studies.</p