Proof-Pattern Recognition and Lemma Discovery in ACL2

We present a novel technique for combining statistical machine learning for proof-pattern recognition with symbolic methods for lemma discovery. The resulting tool, ACL2(ml), gathers proof statistics and uses statistical pattern-recognition to pre-processes data from libraries, and then suggests auxiliary lemmas in new proofs by analogy with already seen examples. This paper presents the implementation of ACL2(ml) alongside theoretical descriptions of the proof-pattern recognition and lemma discovery methods involved in it

An Agent-Based Simulation for Investigating the Impact of Stereotypes on Task-Oriented Group Formation

In this paper, we introduce an agent-based simulation for investigating the impact of social factors on the formation and evolution of task-oriented groups. Task-oriented groups are created explicitly to perform a task, and all members derive benefits from task completion. However, even in cases when all group members act in a way that is locally optimal for task completion, social forces that have mild effects on choice of associates can have a measurable impact on task completion performance. In this paper, we show how our simulation can be used to model the impact of stereotypes on group formation. In our simulation, stereotypes are based on observable features, learned from prior experience, and only affect an agent\u27s link formation preferences. Even without assuming stereotypes affect the agents\u27 willingness or ability to complete tasks, the long-term modifications that stereotypes have on the agents\u27 social network impair the agents\u27 ability to form groups with sufficient diversity of skills, as compared to agents who form links randomly. An interesting finding is that this effect holds even in cases where stereotype preference and skill existence are completely uncorrelated. © 2011 Springer-Verlag Berlin Heidelberg

Environmental correlates of geographic divergence in a phenotypic trait: A case study using bat echolocation

Divergence in phenotypic traits may arise from the interaction of different evolutionary forces, including different kinds of selection (e.g., ecological), genetic drift, and phenotypic plasticity. Sensory systems play an important role in survival and reproduction, and divergent selection on such systems may result in lineage diversification. Such diversification could be largely influenced by selection in different environments as a result of isolation by environment (IbE). We investigated this process using geographic variation in the resting echolocation frequency of the horseshoe bat species, Rhinolophus damarensis, as a test case. Bats were sampled along a latitudinal gradient ranging from 16°S to 32°S in the arid western half of southern Africa. We measured body size and peak resting frequencies (RF) from handheld individual bats. Three hypotheses for the divergence in RF were tested: (1) James’ Rule, (2) IbE, and (3) genetic drift through isolation by distance (IbD) to isolate the effects of body size, local climatic conditions, and geographic distance, respectively, on the resting frequency of R. damarensis. Our results did not support genetic drift because there was no correlation between RF variation and geographic distance. Our results also did not support James’ Rule because there was no significant relationship between (1) geographic distances and RF, (2) body size and RF, or (3) body size and climatic variables. Instead, we found support for IbE in the form of a correlation between RF and both region and annual mean temperature, suggesting that RF variation may be the result of environmental discontinuities. The environmental discontinuities coincided with previously reported genetic divergence. Climatic gradients in conjunction with environmental discontinuities could lead to local adaptation in sensory signals and directed dispersal such that gene flow is restricted, allowing lineages to diverge. However, our study cannot exclude the role of processes like phenotypic plasticity in phenotypic variation

The application of adjuvant autologous antravesical macrophage cell therapy vs. BCG in non-muscle invasive bladder cancer: a multicenter, randomized trial

<p>Abstract</p> <p>Introduction</p> <p>While adjuvant immunotherapy with Bacille Calmette Guérin (BCG) is effective in non-muscle-invasive bladder cancer (BC), adverse events (AEs) are considerable. Monocyte-derived activated killer cells (MAK) are discussed as essential in antitumoural immunoresponse, but their application may imply risks. The present trial compared autologous intravesical macrophage cell therapy (BEXIDEM^®) to BCG in patients after transurethral resection (TURB) of BC.</p> <p>Materials and methods</p> <p>This open-label trial included 137 eligible patients with TaG1-3, T1G1-2 plurifocal or unifocal tumours and ≥ 2 occurrences within 24 months and was conducted from June 2004 to March 2007. Median follow-up for patients without recurrence was 12 months. Patients were randomized to BCG or mononuclear cells collected by apheresis after ex vivo cell processing and activation (BEXIDEM). Either arm treatment consisted of 6 weekly instillations and 2 cycles of 3 weekly instillations at months 3 and 6. Toxicity profile (primary endpoint) and prophylactic effects (secondary endpoint) were assessed.</p> <p>Results</p> <p>Patient characteristics were evenly distributed. Of 73 treated with BCG and 64 with BEXIDEM, 85% vs. 45% experienced AEs and 26% vs. 14% serious AEs (SAE), respectively (p < 0.001). Recurrence occurred significantly less frequent with BCG than with BEXIDEM (12% vs. 38%; p < 0.001).</p> <p>Discussion</p> <p>This initial report of autologous intravesical macrophage cell therapy in BC demonstrates BEXIDEM treatment to be safe. Recurrence rates were significantly lower with BCG however. As the efficacy of BEXIDEM remains uncertain, further data, e.g. marker lesions studies, are warranted.</p> <p>Trial registration</p> <p>The trial has been registered in the ISRCTN registry <url>http://isrctn.org</url> under the registration number ISRCTN35881130.</p

Cloning, annotation and developmental expression of the chicken intestinal MUC2 gene

Intestinal mucin 2 (MUC2) encodes a heavily glycosylated, gel-forming mucin, which creates an important protective mucosal layer along the gastrointestinal tract in humans and other species. This first line of defense guards against attacks from microorganisms and is integral to the innate immune system. As a first step towards characterizing the innate immune response of MUC2 in different species, we report the cloning of a full-length, 11,359 bp chicken MUC2cDNA, and describe the genomic organization and functional annotation of this complex, 74.5 kb locus. MUC2 contains 64 exons and demonstrates distinct spatiotemporal expression profiles throughout development in the gastrointestinal tract; expression increases with gestational age and from anterior to posterior along the gut. The chicken protein has a similar domain organization as the human orthologue, with a signal peptide and several von Willebrand domains in the N-terminus and the characteristic cystine knot at the C-terminus. The PTS domain of the chicken MUC2 protein spans ~1600 amino acids and is interspersed with four CysD motifs. However, the PTS domain in the chicken diverges significantly from the human orthologue; although the chicken domain is shorter, the repetitive unit is 69 amino acids in length, which is three times longer than the human. The amino acid composition shows very little similarity to the human motif, which potentially contributes to differences in the innate immune response between species, as glycosylation across this rapidly evolving domain provides much of the musical barrier. Future studies of the function of MUC2 in the innate immune response system in chicken could provide an important model organism to increase our understanding of the biological significance of MUC2 in host defense and highlight the potential of the chicken for creating new immune-based therapies