Using non-verbal cues to (automatically) assess children’s performance difficulties with arithmetic problems

Intelligent tutoring systems often make use of students’ answers to adapt instruction or feedback on a task. In this paper, we explore the alternative possibility of adapting a system based on the perceived affective and cognitive state of a student. A system can potentially better adapt to the needs of each individual student by using non-verbal behavior. We used a new experimental paradigm inspired by ‘brain training’ software to collect primary school children’s answers to easy and difficult arithmetic problems and made audiovisual recordings of their answers. Adult observers rated these films on perceived difficulty level. Results showed that adults were able to correctly interpret children’s perceived level of difficulty, especially if they saw their face (compared to hearing their voice). They paid attention to features such as ‘looking away’, and ‘frowning’. Then we checked whether we could also automatically predict if the posed problem was either easy or difficult based on the first second of their response. This ‘thin-slice analysis’ could correctly predict the difficulty level in 71% of all cases. When trained on sufficiently many recordings, Adaptive Tutoring Systems should be able to detect children’s state and adapt the difficulty level of their learning materials accordingly.     

How students structure and relate argumentative knowledge when learning together with diagrams

When students learn together by discussing a topic, they sometimes are asked to construct an argumentative diagram. An argumentative diagram consists of boxes with arguments and arrows that relate these boxes. Constructing argumentative diagrams can be especially useful for structuring and relating argumentative knowledge. However, students do not always seem to use a diagram’s structure and relations to their benefit. To focus on structure and relations, 46 secondary school students were asked to either label the boxes in a diagram with argumentative labels such as ‘argument in favor’ and ‘rebuttal’, or to label the arrows with more causal labels such as ‘but’, and ‘because’. The students discussed two topics in dyads using a computer environment with chat and diagram. Then a post-test was given to assess their opinion and arguments. We found no difference between conditions in the extent to which students broadened and deepened their discussion. However, students who labeled the arrows contrasted subtopics more. The students who contrasted subtopics more showed better results on the post-test. Instruction and diagram design can thus influence students’ discussion, although the general results also show us that students need more instruction and reflection to optimally benefit from argumentative diagrams.     

Development of a submerged aquatic vegetation community index of biotic integrity for use in Lake Ontario coastal wetlands

Submerged aquatic vegetation (SAV) supports biodiversity in the Great Lakes basin by providing an important source of food and habitat for breeding marsh birds and fish and it is desirable to have indices enabling reporting on the condition of SAV, to complement already available indices for the condition of fish, aquatic macroinvertebrate, and bird communities and water quality. We developed a SAV index of biotic integrity (SAV IBI) with 6 years of quadrat-based vegetation species composition data (2003, 2005–2009) collected across 46 coastal wetlands on the Canadian side of Lake Ontario. We evaluated the suitability of thirteen potential metrics that described species richness, floristic quality, and cover. Metrics with a significant linear or non-linear response to disturbance (as assessed by a water quality index; WQI) were retained for use in the SAV IBI. Retained metrics included turbidity-intolerant species richness, native species richness, coefficient of conservatism, and total cumulative coverage. Lower SAV IBI scores indicated poorer coastal wetland conditions. Coastal wetlands in poor condition were located in more urbanized watersheds (e.g., Durham Region) relative to wetlands in more natural watersheds. Fish and breeding bird community condition showed strong significant relationships with the SAV IBI, suggesting that SAV was an important component of fish and bird biodiversity. Our SAV assessment index and its relationship to faunal diversity can be used to inform conservation decisions.     

Acute Cycling Exercise Induces Changes in Red Blood Cell Deformability and Membrane Lipid Remodeling

Here we describe the effects of a controlled, 30 min, high-intensity cycling test on blood rheology and the metabolic profiles of red blood cells (RBCs) and plasma from well-trained males. RBCs demonstrated decreased deformability and trended toward increased generation of microparticles after the test. Meanwhile, metabolomics and lipidomics highlighted oxidative stress and activation of membrane lipid remodeling mechanisms in order to cope with altered properties of circulation resulting from physical exertion during the cycling test. Of note, intermediates from coenzyme A (CoA) synthesis for conjugation to fatty acyl chains, in parallel with reversible conversion of carnitine and acylcarnitines, emerged as metabolites that significantly correlate with RBC deformability and the generation of microparticles during exercise. Taken together, we propose that RBC membrane remodeling and repair plays an active role in the physiologic response to exercise by altering RBC properties.     

Cellular Chaperone Function of Intrinsically Disordered Dehydrin ERD14

Disordered plant chaperones play key roles in helping plants survive in harsh conditions, and they are indispensable for seeds to remain viable. Aside from well-known and thoroughly characterized globular chaperone proteins, there are a number of intrinsically disordered proteins (IDPs) that can also serve as highly effective protecting agents in the cells. One of the largest groups of disordered chaperones is the group of dehydrins, proteins that are expressed at high levels under different abiotic stress conditions, such as drought, high temperature, or osmotic stress. Dehydrins are characterized by the presence of different conserved sequence motifs that also serve as the basis for their categorization. Despite their accepted importance, the exact role and relevance of the conserved regions have not yet been formally addressed. Here, we explored the involvement of each conserved segment in the protective function of the intrinsically disordered stress protein (IDSP) A. thaliana’s Early Response to Dehydration (ERD14). We show that segments that are directly involved in partner binding, and others that are not, are equally necessary for proper function and that cellular protection emerges from the balanced interplay of different regions of ERD14.     

p130Cas Is Correlated with EREG Expression and a Prognostic Factor Depending on Colorectal Cancer Stage and Localization Reducing FOLFIRI Efficacy

p130 Crk-associated substrate (p130Cas) is associated with poor prognosis and treatment resistance in breast and lung cancers. To elucidate p130Cas functional and clinical role in colorectal cancer (CRC) progression/therapy resistance, we performed cell culture experiments and bioinformatic/statistical analyses of clinical data sets. p130Cas expression was associated with poor survival in the cancer genome atlas (TCGA) data set. Knockdown/reconstitution experiments showed that p130Cas drives migration but, unexpectedly, inhibits proliferation in CRC cells. TCGA data analyses identified the growth factor epiregulin (EREG) as inversely correlated with p130Cas. p130Cas knockdown and simultaneous EREG treatment further enhanced proliferation. RNA interference and EREG treatment experiments suggested that p130Cas/EREG limit each other’s expression/activity. Inverse p130Cas/EREG Spearman correlations were prominent in right-sided and earlier stage CRC. p130Cas was inducible by 5-fluorouracil (5-FU) and FOLFIRI (folinic acid, 5-FU, irinotecan), and p130Cas and EREG were upregulated in distant metastases ({"type":"entrez-geo","attrs":{"text":"GSE121418","term_id":"121418"}}GSE121418). Positive p130Cas/EREG correlations were observed in metastases, preferentially in post-treatment samples (especially pulmonary metastases). p130Cas knockdown sensitized CRC cells to FOLFIRI independent of EREG treatment. RNA sequencing and gene ontology analyses revealed that p130Cas is involved in cytochrome P450 drug metabolism and epithelial-mesenchymal transition. p130Cas expression was associated with poor survival in right-sided, stage I/II, MSS (microsatellite stable), or BRAF-mutated CRC. In summary, p130Cas represents a prognostic factor and potential therapeutic target in CRC.     

Myelin Quantification in White Matter Pathology of Progressive Multiple Sclerosis Post-Mortem Brain Samples: A New Approach for Quantifying Remyelination

Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system (CNS). Repair through remyelination can be extensive, but quantification of remyelination remains challenging. To date, no method for standardized digital quantification of remyelination of MS lesions exists. This methodological study aims to present and validate a novel standardized method for myelin quantification in progressive MS brains to study myelin content more precisely. Fifty-five MS lesions in 32 tissue blocks from 14 progressive MS cases and five tissue blocks from 5 non-neurological controls were sampled. MS lesions were selected by macroscopic investigation of WM by standard histopathological methods. Tissue sections were stained for myelin with luxol fast blue (LFB) and histological assessment of de- or remyelination was performed by light microscopy. The myelin quantity was estimated with a novel myelin quantification method (MQM) in ImageJ. Three independent raters applied the MQM and the inter-rater reliability was calculated. We extended the method to diffusely appearing white matter (DAWM) and encephalitis to test potential wider applicability of the method. Inter-rater agreement was excellent (ICC = 0.96) and there was a high reliability with a lower- and upper limit of agreement up to −5.93% to 18.43% variation in myelin quantity. This study builds on the established concepts of histopathological semi-quantitative assessment of myelin and adds a novel, reliable and accurate quantitative measurement tool for the assessment of myelination in human post-mortem samples.     

Inhibition of Carbonic Anhydrase 2 Overcomes Temozolomide Resistance in Glioblastoma Cells

About 95% of Glioblastoma (GBM) patients experience tumor relapse as a consequence of resistance to the first-line standard chemotherapy using temozolomide (TMZ). Recent studies reported consistently elevated expression levels of carbonic anhydrase CA2 in recurrent glioblastoma and temozolomide-resistant glioblastoma stem-like cells (GSCs). Here we show that CA2 is preferentially expressed in GSCs and upregulated by TMZ treatment. When expressed in GBM cell lines, CA2 exerts significant metabolic changes reflected by enhanced oxygen consumption and increased extracellular acidification causing higher rates of cell invasion. Notably, GBM cells expressing CA2 respond to combined treatment with TMZ and brinzolamide (BRZ), a non-toxic and potent CA2 inhibitor. Interestingly, brinzolamide was more effective than the pan-CA inhibitor Acetazolamide (ACZ) to sensitize naïve GSCs and TMZ-resistant GSCs to TMZ induced cell death. Mechanistically, we demonstrated that the combined treatment of GBM stem cells with TMZ and BRZ caused autophagy of GBM cell lines and GSCs, reflected by enhanced LC3 cleavage (LC3-II) and p62 reduction. Our findings illustrate the potential of CA2 as a chemo-sensitizing drug target in recurrent GBM and propose a combined treatment of TMZ with CA2 inhibitor to tackle GBM chemoresistance and recurrence.     

Supercritical carbon dioxide extraction of onion oleoresin

Supercritical carbon dioxide (SC-CO₂) extraction on a laboratory-scale, was applied to produce oleoresin from dried onion (Allium cepa L). The goal of this work was to determine the optimal conditions of extraction for producing oleoresin with the highest yield and the best quality. A polynomial model was developed on the data. The square of correlation coefficient was R²=0·9022 (at P⩽0·05). The statistical analysis showed that the extraction pressure, temperature, and time have significant influence on the yield of the oleoresin. Increasing these parameters resulted in an increase in the yield. Maximum yield was obtained when the extraction pressure and temperature were above 350 bar and 57°C, respectively. At the lowest pressure (150 bar) applied the highest concentration of sulphur was produced in the oleoresin. The concentration of sulphur increased as a function of temperature when the pressure was maintained at 300 and 400 bar. The composition of volatile compounds of oleoresin differed from that of distilled onion oil. © 1998 SCI.     

Role and Regulation of Mechanotransductive HIF-1α Stabilisation in Periodontal Ligament Fibroblasts

Orthodontic tooth movement (OTM) creates compressive and tensile strain in the periodontal ligament, causing circulation disorders. Hypoxia-inducible factor 1α (HIF-1α) has been shown to be primarily stabilised by compression, but not hypoxia in periodontal ligament fibroblasts (PDLF) during mechanical strain, which are key regulators of OTM. This study aimed to elucidate the role of heparan sulfate integrin interaction and downstream kinase phosphorylation for HIF-1α stabilisation under compressive and tensile strain and to which extent downstream synthesis of VEGF and prostaglandins is HIF-1α-dependent in a model of simulated OTM in PDLF. PDLF were subjected to compressive or tensile strain for 48 h. In various setups HIF-1α was experimentally stabilised (DMOG) or destabilised (YC-1) and mechanotransduction was inhibited by surfen and genistein. We found that HIF-1α was not stabilised by tensile, but rather by compressive strain. HIF-1α stabilisation had an inductive effect on prostaglandin and VEGF synthesis. As expected, HIF-1α destabilisation reduced VEGF expression, whereas prostaglandin synthesis was increased. Inhibition of integrin mechanotransduction via surfen or genistein prevented stabilisation of HIF-1α. A decrease in VEGF expression was observed, but not in prostaglandin synthesis. Stabilisation of HIF-1α via integrin mechanotransduction and downstream phosphorylation of kinases seems to be essential for the induction of VEGF, but not prostaglandin synthesis by PDLF during compressive (but not tensile) orthodontic strain.