Effectiveness and practical implicability of motivational low-threshold support methods on the performance of building factual knowledge of students with learning difficulties in math

This dissertation presents four studies published in peer-reviewed journals focusing on improving the development of mathematical factual knowledge of students with learning difficulties. Mastering fluency building with basic math facts is considered a strong predictor to achieve sufficient or above mathematical competencies. Struggling with this development can already lead to students’ demotivation, frustration and avoiding further engagement. Therefore, all papers were conducted with the aim to provide access to methods that help overcome this hurdle with different motivational support for those struggling students and into a deeper engagement of mathematical competency acquisition. One study focused on the impact of enhancing students’ motivation by implementing a combined multicomponent motivational system (MMS). The second study used a specially designed combination of the previously examined motivational methods that math racetracks enhanced. After this examination, again an extension was made by a combination of the previous examined methods with peer tutoring. All three papers were evaluated regarding their effectivity concerning the development of math fact fluency. The final paper evaluated the effectiveness of a response card intervention on the participation of low-performers during their math class. For the purpose of the research, single-case designs were applied and the studies were conducted in elementary and secondary grades in regular and special schools. This alone led to participants with very heterogeneous conditions and further research will be necessary to underline these studies’ findings. Still, all four papers’ results indicated that all interventions concerning motivation, racetracks and response cards are highly effective and therefore could provide students and teachers alike with an opportunity to enrich the classroom through a significant increase of students’ performance and engagement into mastering mathematical basic facts fluency. Providing teachers with effective, easy-to-implement methods in their classroom independent of special needs or not as well as of grade is an aim any research should try to meet more often, and which, in this case, can be considered successfully achieved

Effects of Explicit Timing on the Reading Fluency of Third Graders with Learning Challenges

In this study, we examined the impact of a simple explicit-timing intervention on low-achieving third-grade students’ ability to read more rapidly and accurately. We implemented an ABAB design with four struggling readers to establish experimental control and to evaluate the effects of the treatment in terms of the target variable. The results indicated that explicit timing was very helpful in increasing the participants’ reading rates. That is, each of the four students demonstrated better mean results in the B phases than in the A phases. The article closes with a discussion of the practical implications and applications of the findings, including limitations to be addressed in future studies

DNA-PKcs-Mediated Transcriptional Regulation Drives Prostate Cancer Progression and Metastasis.

Emerging evidence demonstrates that the DNA repair kinase DNA-PKcs exerts divergent roles in transcriptional regulation of unsolved consequence. Here, in vitro and in vivo interrogation demonstrate that DNA-PKcs functions as a selective modulator of transcriptional networks that induce cell migration, invasion, and metastasis. Accordingly, suppression of DNA-PKcs inhibits tumor metastases. Clinical assessment revealed that DNA-PKcs is significantly elevated in advanced disease and independently predicts for metastases, recurrence, and reduced overall survival. Further investigation demonstrated that DNA-PKcs in advanced tumors is highly activated, independent of DNA damage indicators. Combined, these findings reveal unexpected DNA-PKcs functions, identify DNA-PKcs as a potent driver of tumor progression and metastases, and nominate DNA-PKcs as a therapeutic target for advanced malignancies

TMPRSS2-ERG -specific transcriptional modulation is associated with prostate cancer biomarkers and TGF-β signaling

<p>Abstract</p> <p>Background</p> <p><it>TMPRSS2-ERG </it>gene fusions occur in about 50% of all prostate cancer cases and represent promising markers for molecular subtyping. Although <it>TMPRSS2-ERG </it>fusion seems to be a critical event in prostate cancer, the precise functional role in cancer development and progression is still unclear.</p> <p>Methods</p> <p>We studied large-scale gene expression profiles in 47 prostate tumor tissue samples and in 48 normal prostate tissue samples taken from the non-suspect area of clinical low-risk tumors using Affymetrix GeneChip Exon 1.0 ST microarrays.</p> <p>Results</p> <p>Comparison of gene expression levels among <it>TMPRSS2-ERG </it>fusion-positive and negative tumors as well as benign samples demonstrated a distinct transcriptional program induced by the gene fusion event. Well-known biomarkers for prostate cancer detection like <it>CRISP3 </it>were found to be associated with the gene fusion status. WNT and TGF-β/BMP signaling pathways were significantly associated with genes upregulated in <it>TMPRSS2-ERG </it>fusion-positive tumors.</p> <p>Conclusions</p> <p>The <it>TMPRSS2-ERG </it>gene fusion results in the modulation of transcriptional patterns and cellular pathways with potential consequences for prostate cancer progression. Well-known biomarkers for prostate cancer detection were found to be associated with the gene fusion. Our results suggest that the fusion status should be considered in retrospective and future studies to assess biomarkers for prostate cancer detection, progression and targeted therapy.</p

Dual inhibition of AKT‐mTOR and AR signaling by targeting HDAC3 in PTEN‐ or SPOP‐mutated prostate cancer

Abstract AKT‐mTOR and androgen receptor (AR) signaling pathways are aberrantly activated in prostate cancer due to frequent PTEN deletions or SPOP mutations. A clinical barrier is that targeting one of them often activates the other. Here, we demonstrate that HDAC3 augments AKT phosphorylation in prostate cancer cells and its overexpression correlates with AKT phosphorylation in patient samples. HDAC3 facilitates lysine‐63‐chain polyubiquitination and phosphorylation of AKT, and this effect is mediated by AKT deacetylation at lysine 14 and 20 residues and HDAC3 interaction with the scaffold protein APPL1. Conditional homozygous deletion of Hdac3 suppresses prostate tumorigenesis and progression by concomitant blockade of AKT and AR signaling in the Pten knockout mouse model. Pharmacological inhibition of HDAC3 using a selective HDAC3 inhibitor RGFP966 inhibits growth of both PTEN‐deficient and SPOP‐mutated prostate cancer cells in culture, patient‐derived organoids and xenografts in mice. Our study identifies HDAC3 as a common upstream activator of AKT and AR signaling and reveals that dual inhibition of AKT and AR pathways is achievable by single‐agent targeting of HDAC3 in prostate cancer

The Effects of a Multicomponent Motivational System Intervention Using Peer-Tutoring for Implementation on the Automation of Single-Digit Addition Tasks of Four Struggling Elementary Students

Derived math fact fluency becomes more imperative across all mathematical content areas during a students' mathematics development. However, many of them struggle to automate the most basic math facts sufficiently and therefore are not able to deal with more complex mathematical problems. This leads to the fact that many of them are already left behind in the early years of their school careers whether they have diagnosed learning disabilities or not. In this single-case research project, we evaluated a peer-tutoring approach designed to extend the number of automated single-digit addition tasks for four struggling elementary students through a multicomponent motivational system including immediate correction of errors, graphical feedback on performance, positive reinforcement, direct instruction flashcards, and a racetrack game. A multiple-baseline design (ABE) across subjects was applied to assess the effects of the treatment. The results indicate significant and large effects of the intervention on the number of automated math facts for the participants. This substantiates the assumption that the math-fact recall performance of struggling students can be improved through the method of peer tutoring even with the limited resources available in everyday school life