Continuous Hands-off Control by CLOT Norm Minimization

In this paper, we consider hands-off control via minimization of the C LOT (Combined L -One and Two) norm. The maximum hands-off control is the L 0 -optimal (or the sparsest) control among all feasible controls that are bounded b y a specified value and transfer the state from a given initial state to the origin within a fixed time dura tion. In general, the maximum hands-off control is a bang-off-bang control taking value s of ± 1 and 0. For many real applications, such discontinuity in the control is not desirable. To ob tain a continuous but still relatively sparse control, we propose to use the CLOT norm, a conv ex combination of L 1 and L 2 norms. We show by numerical simulation that the CLOT control is con tinuous and much sparser (i.e. has longer time duration on which the control takes 0) than the conventional EN (elastic net) control, which is a convex combination of L 1 and squared L 2 norms

Detecting Drowsy Learners at the Wheel of e-Learning Platforms with Multimodal Learning Analytics

Learners are expected to stay wakeful and focused while interacting with e-learning platforms. Although wakefulness of learners strongly relates to educational outcomes, detecting drowsy learning behaviors only from log data is not an easy task. In this study, we describe the results of our research to model learners’ wakefulness based on multimodal data generated from heart rate, seat pressure, and face recognition. We collected multimodal data from learners in a blended course of informatics and conducted two types of analysis on them. First, we clustered features based on learners’ wakefulness labels as generated by human raters and ran a statistical analysis. This analysis helped us generate insights from multimodal data that can be used to inform learner and teacher feedback in multimodal learning analytics. Second, we trained machine learning models with multiclass-Support Vector Machine (SVM), Random Forest (RF) and CatBoost Classifier (CatBoost) algorithms to recognize learners’ wakefulness states automatically. We achieved an average macro-F1 score of 0.82 in automated user-dependent models with CatBoost. We also showed that compared to unimodal data from each sensor, the multimodal sensor data can improve the accuracy of models predicting the wakefulness states of learners while they are interacting with e-learning platforms

The protective role of the 3-mercaptopyruvate sulfurtransferase (3-MST)-hydrogen sulfide (H₂S) pathway against experimental osteoarthritis.

Osteoarthritis (OA) is characterized by the formation and deposition of calcium-containing crystals in joint tissues, but the underlying mechanisms are poorly understood. The gasotransmitter hydrogen sulfide (H <sub>2</sub> S) has been implicated in mineralization but has never been studied in OA. Here, we investigated the role of the H <sub>2</sub> S-producing enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) in cartilage calcification and OA development. 3-MST expression was analyzed in cartilage from patients with different OA degrees, and in cartilage stimulated with hydroxyapatite (HA) crystals. The modulation of 3-MST expression in vivo was studied in the meniscectomy (MNX) model of murine OA, by comparing sham-operated to MNX knee cartilage. The role of 3-MST was investigated by quantifying joint calcification and cartilage degradation in WT and 3-MST <sup>-/-</sup> meniscectomized knees. Chondrocyte mineralization in vitro was measured in WT and 3-MST <sup>-/-</sup> cells. Finally, the effect of oxidative stress on 3-MST expression and chondrocyte mineralization was investigated. 3-MST expression in human cartilage negatively correlated with calcification and OA severity, and diminished upon HA stimulation. In accordance, cartilage from menisectomized OA knees revealed decreased 3-MST if compared to sham-operated healthy knees. Moreover, 3-MST <sup>-/-</sup> mice showed exacerbated joint calcification and OA severity if compared to WT mice. In vitro, genetic or pharmacologic inhibition of 3-MST in chondrocytes resulted in enhanced mineralization and IL-6 secretion. Finally, oxidative stress decreased 3-MST expression and increased chondrocyte mineralization, maybe via induction of pro-mineralizing genes. 3-MST-generated H <sub>2</sub> S protects against joint calcification and experimental OA. Enhancing H <sub>2</sub> S production in chondrocytes may represent a potential disease modifier to treat OA

The human epidermal growth factor receptor (EGFR) gene in European patients with advanced colorectal cancer harbors infrequent mutations in its tyrosine kinase domain

ABSTRACT: BACKGROUND: The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptors, is a transmembrane tyrosine kinase (TK) activated by the binding of extracellular ligands of the EGF-family and involved in triggering the MAPK signaling pathway, which leads to cell proliferation. Mutations in the EGFR tyrosine kinase domain are frequent in non-small-cell lung cancer (NSCLC). However, to date, only very few, mainly non-European, studies have reported rare EGFR mutations in colorectal cancer (CRC). METHODS: We screened 236 clinical tumor samples from European patients with advanced CRC by direct DNA sequencing to detect potential, as yet unknown mutations, in the EGFR gene exons 18 to 21, mainly covering the EGFR TK catalytic domain. RESULTS: EGFR sequences showed somatic missense mutations in exons 18 and 20 at a frequency of 2.1% and 0.4% respectively. Somatic SNPs were also found in exons 20 and 21 at a frequency of about 3.1% and 0.4% respectively. Of these mutations, four have not yet been described elsewhere. CONCLUSIONS: These mutation frequencies are higher than in a similarly sized population characterized by Barber and colleagues, but still too low to account for a major role played by the EGFR gene in CRC.Peer reviewe

Novel iodinated tracers, MIBG and BMIPP, for nuclear cardiology

With the rapid growth of molecular biology, in vivo imaging of such molecular process (i.e., molecular imaging) has been well developed. The molecular imaging has been focused on justifying advanced treatments and for assessing the treatment effects. Most of molecular imaging has been developed using PET camera and suitable PET radiopharmaceuticals. However, this technique cannot be widely available and we need alternative approach. 123I-labeled compounds have been also suitable for molecular imaging using single-photon computed tomography (SPECT) 123I-labeled meta-iodobenzylguanidine (MIBG) has been used for assessing severity of heart failure and prognosis. In addition, it has a potential role to predict fatal arrhythmia, particularly for those who had and are planned to receive implantable cardioverter-defibrillator treatment. 123I-beta-methyl-iodophenylpentadecanoic acid (BMIPP) plays an important role for identifying ischemia at rest, based on the unique capability to represent persistent metabolic alteration after recovery of ischemia, so called ischemic memory. Since BMIPP abnormalities may represent severe ischemia or jeopardized myocardium, it may permit risk analysis in CAD patients, particularly for those with chronic kidney disease and/or hemodialysis patients. This review will discuss about recent development of these important iodinated compounds