QuizMap: Open social student modeling and adaptive navigation support with TreeMaps

In this paper, we present a novel approach to integrate social adaptive navigation support for self-assessment questions with an open student model using QuizMap, a TreeMap-based interface. By exposing student model in contrast to student peers and the whole class, QuizMap attempts to provide social guidance and increase student performance. The paper explains the nature of the QuizMap approach and its implementation in the context of self-assessment questions for Java programming. It also presents the design of a semester-long classroom study that we ran to evaluate QuizMap and reports the evaluation results. © 2011 Springer-Verlag Berlin Heidelberg

Phosphorylation-dependent translocation of sphingosine kinase to the plasma membrane drives its oncogenic signalling

Sphingosine kinase (SK) 1 catalyzes the formation of the bioactive lipid sphingosine 1-phosphate, and has been implicated in several biological processes in mammalian cells, including enhanced proliferation, inhibition of apoptosis, and oncogenesis. Human SK (hSK) 1 possesses high instrinsic catalytic activity which can be further increased by a diverse array of cellular agonists. We have shown previously that this activation occurs as a direct consequence of extracellular signal–regulated kinase 1/2–mediated phosphorylation at Ser225, which not only increases catalytic activity, but is also necessary for agonist-induced translocation of hSK1 to the plasma membrane. In this study, we report that the oncogenic effects of overexpressed hSK1 are blocked by mutation of the phosphorylation site despite the phosphorylation-deficient form of the enzyme retaining full instrinsic catalytic activity. This indicates that oncogenic signaling by hSK1 relies on a phosphorylation-dependent function beyond increasing enzyme activity. We demonstrate, through constitutive localization of the phosphorylation-deficient form of hSK1 to the plasma membrane, that hSK1 translocation is the key effect of phosphorylation in oncogenic signaling by this enzyme. Thus, phosphorylation of hSK1 is essential for oncogenic signaling, and is brought about through phosphorylation-induced translocation of hSK1 to the plasma membrane, rather than from enhanced catalytic activity of this enzyme

Heavy-tailed kernels reveal a finer cluster structure in t-SNE visualisations

T-distributed stochastic neighbour embedding (t-SNE) is a widely used data visualisation technique. It differs from its predecessor SNE by the low-dimensional similarity kernel: the Gaussian kernel was replaced by the heavy-tailed Cauchy kernel, solving the "crowding problem" of SNE. Here, we develop an efficient implementation of t-SNE for a $t$-distribution kernel with an arbitrary degree of freedom $\nu$, with $\nu\to\infty$ corresponding to SNE and $\nu=1$ corresponding to the standard t-SNE. Using theoretical analysis and toy examples, we show that $\nu<1$ can further reduce the crowding problem and reveal finer cluster structure that is invisible in standard t-SNE. We further demonstrate the striking effect of heavier-tailed kernels on large real-life data sets such as MNIST, single-cell RNA-sequencing data, and the HathiTrust library. We use domain knowledge to confirm that the revealed clusters are meaningful. Overall, we argue that modifying the tail heaviness of the t-SNE kernel can yield additional insight into the cluster structure of the data

Voting 'against all' in postcommunist Russia

Since the early 1990s voters in Russia (and most of the other post-Soviet republics) have been offered the opportunity to vote ‘against all’ parties and candidates. Increasing numbers have done so. The evidence of two post-election surveys indicates that ‘against all’ voters are younger than other voters, more urban and more highly educated. They do not reject liberal democracy, but are critical of the contemporary practice of Russian politics and find no parties that adequately reflect their views. With the ending of the ‘against all’ facility in 2006 and other changes in the Russian electoral system under the Putin presidency, levels of turnout are likely to fall further and the protest vote will seek other outlets within or outside the parliamentary system

Exotic trees

We discuss the scaling properties of free branched polymers. The scaling behaviour of the model is classified by the Hausdorff dimensions for the internal geometry: d_L and d_H, and for the external one: D_L and D_H. The dimensions d_H and D_H characterize the behaviour for long distances while d_L and D_L for short distances. We show that the internal Hausdorff dimension is d_L=2 for generic and scale-free trees, contrary to d_H which is known be equal two for generic trees and to vary between two and infinity for scale-free trees. We show that the external Hausdorff dimension D_H is directly related to the internal one as D_H = \alpha d_H, where \alpha is the stability index of the embedding weights for the nearest-vertex interactions. The index is \alpha=2 for weights from the gaussian domain of attraction and 0<\alpha <2 for those from the L\'evy domain of attraction. If the dimension D of the target space is larger than D_H one finds D_L=D_H, or otherwise D_L=D. The latter result means that the fractal structure cannot develop in a target space which has too low dimension.Comment: 33 pages, 6 eps figure

Targeting and Function of the Mitochondrial Fission Factor GDAP1 Are Dependent on Its Tail-Anchor

Proteins controlling mitochondrial dynamics are often targeted to and anchored into the mitochondrial outer membrane (MOM) by their carboxyl-terminal tail-anchor domain (TA). However, it is not known whether the TA modulates protein function. GDAP1 is a mitochondrial fission factor with two neighboring hydrophobic domains each flanked by basic amino acids (aa). Here we define GDAP1 as TA MOM protein. GDAP1 carries a single transmembrane domain (TMD) that is, together with the adjacent basic aa, critical for MOM targeting. The flanking N-terminal region containing the other hydrophobic domain is located in the cytoplasm. TMD sequence, length, and high hydrophobicity do not influence GDAP1 fission function if MOM targeting is maintained. The basic aa bordering the TMD in the cytoplasm, however, are required for both targeting of GDAP1 as part of the TA and GDAP1-mediated fission. Thus, this GDAP1 region contains critical overlapping motifs defining intracellular targeting by the TA concomitant with functional aspects

Allele-specific miRNA-binding analysis identifies candidate target genes for breast cancer risk

Most breast cancer (BC) risk-associated single-nucleotide polymorphisms (raSNPs) identified in genome-wide association studies (GWAS) are believed to cis-regulate the expression of genes. We hypothesise that cis-regulatory variants contributing to disease risk may be affecting microRNA (miRNA) genes and/or miRNA binding. To test this, we adapted two miRNA-binding prediction algorithms-TargetScan and miRanda-to perform allele-specific queries, and integrated differential allelic expression (DAE) and expression quantitative trait loci (eQTL) data, to query 150 genome-wide significant ( P≤5×10-8 ) raSNPs, plus proxies. We found that no raSNP mapped to a miRNA gene, suggesting that altered miRNA targeting is an unlikely mechanism involved in BC risk. Also, 11.5% (6 out of 52) raSNPs located in 3'-untranslated regions of putative miRNA target genes were predicted to alter miRNA::mRNA (messenger RNA) pair binding stability in five candidate target genes. Of these, we propose RNF115, at locus 1q21.1, as a strong novel target gene associated with BC risk, and reinforce the role of miRNA-mediated cis-regulation at locus 19p13.11. We believe that integrating allele-specific querying in miRNA-binding prediction, and data supporting cis-regulation of expression, improves the identification of candidate target genes in BC risk, as well as in other common cancers and complex diseases.Funding Agency Portuguese Foundation for Science and Technology CRESC ALGARVE 2020 European Union (EU) 303745 Maratona da Saude Award DL 57/2016/CP1361/CT0042 SFRH/BPD/99502/2014 CBMR-UID/BIM/04773/2013 POCI-01-0145-FEDER-022184info:eu-repo/semantics/publishedVersio

Cajoling or coercing: would electoral engineering resolve the young citizen–state disconnect?

The relationships between citizens and their states are undergoing significant stresses across advanced liberal democracies. In Britain, this disconnect is particularly evident amongst young citizens. This article considers whether different electoral engineering methods - designed either to cajole or compel youth to vote - might arrest the decline in their political engagement. Data collected in 2011 from a national survey of 1,025 British 18 year olds and from focus groups involving 86 young people, reveal that many young people claim that they would be more likely to vote in future elections if such electoral reforms were implemented. However, it is questionable whether or not such increased electoral participation would mean that they would feel truly connected to the democratic process. In particular, forcing young people to vote through the introduction of compulsory voting may actually serve to reinforce deepening resentments, rather than engage them in a positive manner