Set-theoretical and Combinatorial Instruments for Problem Space Analysis in Adaptive Serious Games.

The Computerized Adaptive Practice (CAP) system describes a set of algorithms for assessing player’s expertise and difficulties of in-game problems and for adapting the latter to the former. However, an effective use of CAP requires that in-game problems are designed carefully and refined over time to avoid possible barriers to learning. This study proposes a methodology and three different instruments for analyzing the problem set in CAP-enabled games. The instruments include the Guttman scale, a ranked order, and a Hasse diagram that offer analysis at different levels of granularity and complexity. The methodology proposes to use quantified difficulty measures to infer topology of the problem set. It is well-suited for serious games that emphasize practice and repetitive play. The emphasis is put on the simplicity of use and visualization of the problem space to maximally support teachers and game developers in designing and refining CAP-enabled games. Two case studies demonstrate practical applications of the proposed instruments on empirical data. Future research directions are proposed to address potential drawbacks.This study is part of the RAGE project. The RAGE project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 644187. This publication reflects only the author's view. The European Commission is not responsible for any use that may be made of the information it contains

On the Structure of Infrared Singularities of Gauge-Theory Amplitudes

A closed formula is obtained for the infrared singularities of dimensionally regularized, massless gauge-theory scattering amplitudes with an arbitrary number of legs and loops. It follows from an all-order conjecture for the anomalous-dimension matrix of n-jet operators in soft-collinear effective theory. We show that the form of this anomalous dimension is severely constrained by soft-collinear factorization, non-abelian exponentiation, and the behavior of amplitudes in collinear limits. Using a diagrammatic analysis, we demonstrate that these constraints imply that to three-loop order the anomalous dimension involves only two-parton correlations, with the possible exception of a single color structure multiplying a function of conformal cross ratios depending on the momenta of four external partons, which would have to vanish in all two-particle collinear limits. We argue that such a function does not appear at three-loop order, and that the same is true in higher orders. Our formula predicts Casimir scaling of the cusp anomalous dimension to all orders in perturbation theory, and we explicitly check that the constraints exclude the appearance of higher Casimir invariants at four loops. Using known results for the quark and gluon form factors, we derive the three-loop coefficients of the 1/epsilon^n pole terms (with n=1,...,6) for an arbitrary n-parton scattering amplitude in massless QCD. This generalizes Catani's two-loop formula proposed in 1998.Comment: 46 pages, 9 figures; v2: improved treatment of collinear limits, references added; v3: improved discussion of non-abelian exponentiation, references updated; v4: typo in eq. (17) fixed, references updated; v5: additional term in (17

Current correlators to all orders in the quark masses

The contributions to the coefficient functions of the quark and the mixed quark-gluon condensate to mesonic correlators are calculated for the first time to all orders in the quark masses, and to lowest order in the strong coupling constant. Existing results on the coefficient functions of the unit operator and the gluon condensate are reviewed. The proper factorization of short- and long-distance contributions in the operator product expansion is discussed in detail. It is found that to accomplish this task rigorously the operator product expansion has to be performed in terms of non-normal-ordered condensates. The resulting coefficient functions are improved with the help of the renormalization group. The scale invariant combination of dimension 5 operators, including mixing with the mass operator, which is needed for the renormalization group improvement, is calculated in the leading order.Comment: 24 pages, LateX file, TUM-T31-21/92, 1 postscript file include

Review of AdS/CFT Integrability: An Overview

This is the introductory chapter of a review collection on integrability in the context of the AdS/CFT correspondence. In the collection we present an overview of the achievements and the status of this subject as of the year 2010.Comment: 31 pages, v2: reference added, references to other chapters updated, v3: footnote 1 on location of references added, v4: minor changes, references added, accepted for publication in Lett. Math. Phys, v5: minor corrections, links to chapters updated, attached IntAdS.pdf with all chapters in one file, see http://arxiv.org/src/1012.3982/anc/IntAdS.pdf or http://www.phys.ethz.ch/~nbeisert/IntAdS.pd

Long-term acquired everolimus resistance in pancreatic neuroendocrine tumours can be overcome with novel PI3K-AKT-mTOR inhibitors

Background:The mTOR-inhibitor everolimus improves progression-free survival in advanced pancreatic neuroendocrine tumours (PNETs). However, adaptive resistance to mTOR inhibition is described.Methods:QGP-1 and BON-1, two human PNET cell lines, were cultured with increasing concentrations of everolimus up to 22 weeks to reach a dose of 1 μM everolimus, respectively, 1000-fold and 250-fold initial IC 50. Using total DNA content as a measure of cell number, growth inhibitory dose-response curves of everolimus were determined at the end of resistance induction and over time after everolimus withdrawal. Response to ATP-competitive mTOR inhibitors OSI-027 and AZD2014, and PI3K-mTOR inhibitor NVP-BEZ235 was studied. Gene expression of 10 PI3K-Akt-mTOR pathway-related genes was evaluated using quantitative real-time PCR (RT-qPCR).Results:Long-term everolimus-treated BON-1/R and QGP-1/R showed a significant reduction in everolimus sensitivity. During a drug holiday, gradual return of everolimus sensitivity in BON-1/R and QGP-1/R led to complete reversal of resistance after 10-12 weeks. Treatment with AZD2014, OSI-027 and NVP-BEZ235 had an inhibitory effect on cell proliferation in both sensitive and resistant cell lines. Gene expression in BON-1/R revealed downregulation of MTOR, RICTOR, RAPTOR, AKT and HIF1A, whereas 4EBP1 was upregulated. In QGP-1/R, a downregulation of HIF1A and an upregulation of ERK2 were observed.Conclusions:Long-term everolimus resistance was induced in two human PNET cell lines. Novel PI3K-AKT-mTOR pathway-targeting drugs can overcome everolimus resistance. Differential gene expression profiles suggest different mechanisms of everolimus resistance in BON-1 and QGP-1

Effect of elective neck dissection versus sentinel lymph node biopsy on shoulder morbidity and health-related quality of life in patients with oral cavity cancer: A longitudinal comparative cohort study

Objective: To research the difference in shoulder morbidity and health-related quality of life between patients with cT1-2N0 oral cavity squamous cell carcinoma that undergo either elective neck dissection (END) or a sentinel lymph node biopsy (SLNB) based approach of the neck. Materials and methods: A longitudinal study with measurements before surgery, 6 weeks, 6 months, and 12 months after surgery. Shoulder morbidity were determined with measurements of active range of motion of the shoulder and patient-reported outcomes for shoulder morbidity (SDQ, SPADI) and health-related quality of life (HR-QoL) (EQ5D, EORTC-QLQ-HN35). Linear mixed model analyses were used to analyze differences over time between patients that had END, SLNB or SLNB followed by complementing neck dissection. Results: We included 69 patients. Thirty-three patients were treated with END. Twenty-seven patients had SLNB without complementing neck dissection (SLNB), and nine were diagnosed lymph node positive followed by completion neck dissection (SLNB + ND). Ipsilateral shoulder abduction (P = .031) and forward flexion (P = .039) were significantly better for the SLNB group at 6 weeks post-intervention compared to the END and SLNB + ND group. No significant differences for shoulder morbidity, or health-related quality of life were found at 6 weeks, 6 months, and 12 months between the three groups. Conclusion: With oncologic equivalence for the END and SLNB as strategies for the cN0 neck already demonstrated, and the SLNB being more cost-effective, our demonstrated benefit in short-term shoulder function strengthens the choice for the SLNB as a preferred treatment strategy

Obstructions and lines of marginal stability from the world-sheet

The behaviour of supersymmetric D-branes under deformations of the closed string background is studied using world-sheet methods. We explain how lines of marginal stability and obstructions arise from this point of view. We also show why N=2 B-type branes may be obstructed against (cc) perturbations, but why such obstructions do not occur for N=4 superconformal branes at c=6, i.e. for half-supersymmetric D-branes on K3. Our analysis is based on a field theory approach in superspace, as well as on techniques from perturbed conformal field theory.Comment: 32 page

Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion

2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy

Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204-A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49-2.19); P for trend=1.90 × 10 â ̂'9). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities