ABSTRACT
Predicting long-term student achievement is a critical task for teachers and for educational data mining. However, most of the models do not consider two typical situations in real-life classrooms. The first is that teachers develop their own questions for online formative assessment. Therefore, there are a huge number of possible questions, each of which is answered by only a few students. Second, online formative assessment often involves open-ended questions that students answer in writing. These types of questions in online formative assessment are highly valuable. However, analyzing the responses automatically can be a complex process. In this paper, we address these two challenges. We analyzed 621,575 answers to closed-ended questions and 16,618 answers to open-ended questions by 464 fourth-graders from 24 low socioeconomic status (SES) schools. Using regressors obtained from linguistic features of the answers and an automatic incoherent response classifier, we built a linear model that predicts the score on an end-of-year national standardized test. We found that despite answering 36.4 times fewer open-ended questions than closed questions, including features of the students' open responses in our model improved our prediction of their end-of-year test scores. To the best of our knowledge, this is the first time that a predictor of end-of-year test scores has been improved by using automatically detected features of answers to open-ended questions on online formative assessments.
ABSTRACT
COVID-19 has been extremely difficult to control. The lack of understanding of key aspects of pandemics has affected virus transmission. On the other hand, there is a demand to incorporate computational thinking (CT) in the curricula with applications in STEM. However, there are still no exemplars in the curriculum that apply CT to real-world problems such as controlling a pandemic or other similar global crises. In this paper, we fill this gap by proposing exemplars of CT for modeling the pandemic. We designed exemplars following the three pillars of the framework for CT from the Inclusive Mathematics for Sustainability in a Digital Economy (InMside) project by Asia-Pacific Economic Cooperation (APEC): algorithmic thinking, computational modeling, and machine learning. For each pillar, we designed a progressive sequence of activities that covers from elementary to high school. In an experimental study with elementary and middle school students from 2 schools of high vulnerability, we found that the computational modeling exemplar can be implemented by teachers and correctly understood by students. We conclude that it is feasible to introduce the exemplars at all grade levels and that this is a powerful example of Science Technology, Engineering, and Mathematics (STEM) integration that helps reflect and tackle real-world and challenging public health problems of great impact for students and their families.
Subject(s)
COVID-19 , Pandemics , Curriculum , Humans , Pandemics/prevention & control , SARS-CoV-2 , Schools , TeachingABSTRACT
Detecting the direction of the gaze and orientation of the body of both teacher and students is essential to estimate who is paying attention to whom. It also provides vital clues for understanding their unconscious, non-verbal behavior. These are called "honest signals" since they are unconscious subtle patterns in our interaction with other people that help reveal the focus of our attention. Inside the classroom, they provide important clues about teaching practices and students' responses to different conscious and unconscious teaching strategies. Scanning this non-verbal behavior in the classroom can provide important feedback to the teacher in order for them to improve their teaching practices. This type of analysis usually requires sophisticated eye-tracking equipment, motion sensors, or multiple cameras. However, for this to be a useful tool in the teacher's daily practice, an alternative must be found using only a smartphone. A smartphone is the only instrument that a teacher always has at their disposal and is nowadays considered truly ubiquitous. Our study looks at data from a group of first-grade classrooms. We show how video recordings on a teacher's smartphone can be used in order to estimate the direction of the teacher and students' gaze, as well as their body orientation. Using the output from the OpenPose software, we run Machine Learning (ML) algorithms to train an estimator to recognize the direction of the students' gaze and body orientation. We found that the level of accuracy achieved is comparable to that of human observers watching frames from the videos. The mean square errors (RMSE) of the predicted pitch and yaw angles for head and body directions are on average 11% lower than the RMSE between human annotators. However, our solution is much faster, avoids the tedium of doing it manually, and makes it possible to design solutions that give the teacher feedback as soon as they finish the class.
ABSTRACT
Dopamine receptors are integral membrane proteins whose endogenous ligand is dopamine. They play a fundamental role in the central nervous system and dysfunction of dopaminergic neurotransmission is responsible for the generation of a variety of neuropsychiatric disorders. From an evolutionary standpoint, phylogenetic relationships among the DRD1 class of dopamine receptors are still a matter of debate as in the literature different tree topologies have been proposed. In contrast, phylogenetic relationships among the DRD 2 group of receptors are well understood. Understanding the time of origin of the different dopamine receptors is also an issue that needs further study, especially for the genes that have restricted phyletic distributions (e.g., DRD2l and DRD4rs). Thus, the goal of this study was to investigate the evolution of dopamine receptors, with emphasis on shedding light on the phylogenetic relationships among the D1 class of dopamine receptors and the time of origin of the DRD2l and DRD4rs gene lineages. Our results recovered the monophyly of the two groups of dopamine receptors. Within the DRD1 group the monophyly of each paralog was recovered with strong support, and phylogenetic relationships among them were well resolved. Within the DRD1 class of dopamine receptors we recovered the sister group relationship between the DRD1C and DRD1E, and this clade was recovered sister to a cyclostome sequence. The DRD1 clade was recovered sister to the aforementioned clade, and the group containing DRD5 receptors was sister to all other DRD1 paralogs. In agreement with the literature, among the DRD2 class of receptors, DRD2 was recovered sister to DRD3, whereas DRD4 was sister to the DRD2/DRD3 clade. According to our phylogenetic tree, the DRD2l and DRD4rs gene lineages would have originated in the ancestor of gnathostomes between 615 and 473 mya. Conservation of sequences required for dopaminergic neurotransmission and small changes in regulatory regions suggest a functional refinement of the dopaminergic pathways along evolution.
ABSTRACT
Dendritic cells (DCs) in culture express at least connexin43, a protein subunit of gap junctions, and form gap junction channels, which could be important for T-cells activation. Here, we evaluated whether DCs express connexins in vivo and also to identify components of their microenvironment that regulate the functional expression of gap junctions. In vivo studies were performed in lymph nodes of mice under control conditions or after skeletal muscle damage. In double immunolabeling studies, connexin45 was frequently detected in DEC205(+) DCs in lymph nodes of control animals, whereas connexin43 was rarely found in DCs. However, connexin43 was upregulated in DCs after skeletal muscle damage. Upregulation of connexin43 gene expression by tissue damage was also confirmed in mice carrying a beta-galactosidase reporter gene in a connexin43 allele. The effect of several cytokines on the expression of functional gap junctions between cultured DCs was also tested. Under control conditions, cultured DCs did not communicate via gap junctions. However, after treatment with keratinocyte-conditioned medium or cytokine mixtures containing at least TNF-alpha and IL-1beta, they became transiently coupled through a pathway sensitive to octanol, a gap junction blocker. Cellular coupling induced by effective cytokine mixtures was prevented by IL-6. Single cytokines (TNF-alpha, IL-1beta, IFN-gamma, or IL-6) or other mixtures than the described above did not induce coupling via gap junctions. Increased levels of connexin43 and connexin45 protein and mRNA accompanied the appearance of cellular coupling. These studies provide demonstration of connexin expression and regulation by specific danger signals in DCs.
Subject(s)
Connexin 43/genetics , Connexins/genetics , Cytokines/pharmacology , Dendritic Cells/physiology , Muscle, Skeletal/immunology , Muscle, Skeletal/injuries , Animals , Cell Communication/drug effects , Cell Communication/immunology , Cell Line , Culture Media, Conditioned/pharmacology , Dendritic Cells/cytology , Gap Junctions/physiology , Interferon-gamma/pharmacology , Interleukin-1beta/pharmacology , Interleukin-6/pharmacology , Keratinocytes/cytology , Lymph Nodes/cytology , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Mutant Strains , RNA, Messenger/metabolism , Signal Transduction/drug effects , Signal Transduction/immunology , Tumor Necrosis Factor-alpha/pharmacology , Up-Regulation/physiologyABSTRACT
The molecular mechanisms regulating skeletal muscle regeneration and differentiation are not well understood. We analyzed the expression of connexins (Cxs) 40, 43 and 45 in normal and regenerating tibialis anterior muscle and in primary cultures of differentiating myoblasts in adult and newborn mice, respectively. Cxs 45 and 43, but not 40, were strongly expressed in normal muscle and their expression was upregulated during regeneration. Furthermore, the functional role of Cx43 during differentiation and regeneration was examined after induced deletion of Cx43 in transgenic mice. In vivo, the inducible deletion of Cx43 delayed the formation of myofibers and prolonged the expression of myogenin during regeneration. In primary cultures of satellite cell-derived myoblasts, induced deletion of Cx43 led to decreased expression of myogenin and MyoD, dye coupling, creatine kinase activity and myoblast fusion. Thus, the expression of Cx45 and Cx43 is upregulated during skeletal muscle regeneration and Cx43 is required for normal myogenesis in vitro and adult muscle regeneration in vivo.
Subject(s)
Cell Differentiation , Connexin 43/metabolism , Connexins/metabolism , Muscle, Skeletal/physiology , Regeneration , Animals , Animals, Newborn , Blotting, Western , Cell Fusion , Cells, Cultured , Connexin 43/genetics , Connexins/genetics , Creatine Kinase/metabolism , Desmin/metabolism , Female , Fluorescent Antibody Technique, Indirect , Gene Expression Regulation , Male , Mice , Mice, Transgenic , Myoblasts/cytology , Satellite Cells, Skeletal Muscle/cytology , Up-RegulationABSTRACT
Skeletal muscle differentiation follows an organized sequence of events including commitment, cell cycle withdrawal, and cell fusion to form multinucleated myotubes. The role of adenosine 5'-triphosphate (ATP)-mediated signaling in differentiation of skeletal muscle myoblasts was evaluated in C(2)C(12) cells, a myoblast cell line. Cell differentiation was inhibited by P2X receptor blockers or by degradation of endogenous ATP with apyrase. However, pertussis toxin, known to block only a group of P2Y receptors, did not alter the differentiation process. Cells were heterogeneous in their expression of functional P2X receptors, evaluated by the uptake of fluorescent permeability tracers (Lucifer yellow and ethidium bromide), and by immunofluorescence of P2X(7) receptors. Moreover, xestospongin C, a selective and membrane-permeable inhibitor of IP(3) receptors, inhibited both myotube formation and myogenin expression. Based on these results, we suggest that the known increase in intracellular Ca(2+) concentration required for differentiation is due at least in part to Ca(2+) influx through P2X receptors and Ca(2+) release from intracellular stores. The possible involvement of P2X receptors and other pathways that might set the intracellular Ca(2+) at the level required for myoblast differentiation as well as the possible involvement of gap junction channels in the intercellular transfer of second messengers involved in coordinating myogenesis is proposed.
Subject(s)
Adenosine Triphosphate/metabolism , Muscle Fibers, Skeletal/metabolism , Muscle, Skeletal/growth & development , Receptors, Purinergic P2/metabolism , Sarcolemma/metabolism , Animals , Calcium/metabolism , Calcium Channels/metabolism , Calcium Signaling/drug effects , Calcium Signaling/physiology , Cell Differentiation/drug effects , Cell Differentiation/physiology , Cell Line , Extracellular Fluid/metabolism , Fluorescent Dyes/metabolism , Gap Junctions/metabolism , Inositol 1,4,5-Trisphosphate Receptors , Intracellular Fluid/drug effects , Intracellular Fluid/metabolism , Mice , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Myogenin/biosynthesis , Myogenin/drug effects , Purinergic P2 Receptor Antagonists , Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors , Receptors, Cytoplasmic and Nuclear/metabolism , Receptors, Purinergic P2X , Receptors, Purinergic P2X7ABSTRACT
BACKGROUND: Invasive candidiasis is an increasing problem in neonatal intensive care units worldwide and is an important cause of morbidity, mortality and prolongation of hospital stay. Despite administration of amphotericin B, invasive candidiasis in neonates is sometimes complicated by persistent fungemia and refractory invasive candidiasis. The problem has been augmented by the increasing prevalence of non-albicans species that often are resistant to fluconazole and to amphotericin B. POPULATION AND METHODS: The population consisted of 1 term and 9 premature neonates with invasive candidiasis caused by Candida albicans (n = 4), Candida parapsilosis (n = 3), Candida tropicalis (n = 2) and Candida glabrata (n = 1). Despite initial therapy with deoxycholate amphotericin B, blood cultures remained positive in all patients for 13-49 days. Invasive candidiasis progressed to meningitis and enlarging renal Candida bezoars in the kidney of one patient and an enlarging atrial vegetation in another. Another patient developed severe hypokalemia refractory to potassium supplementation. Two of the C. albicans and all of the non-albicans Candida isolates were resistant to fluconazole; the C. glabrata isolate was resistant to amphotericin B. Amphotericin B was discontinued and caspofungin initiated in all patients in a dosage of 1 mg/kg/d for 2 days followed by 2 mg/kg/d. RESULTS: All positive blood cultures cleared between 3 and 7 days after initiation of caspofungin, the atrial vegetation resolved and the renal Candida bezoars disappeared. Renal and hepatic function tests did not show any values above normal throughout caspofungin therapy. There were no attributable clinical adverse events during the administration of caspofungin in any of the patients. CONCLUSIONS: Caspofungin was effective, safe and well-tolerated as an alternative therapy for persistent and progressive candidiasis in those neonates who were unresponsive to or intolerant of deoxycholate amphotericin B.
Subject(s)
Antifungal Agents/therapeutic use , Candidiasis/drug therapy , Peptides, Cyclic/therapeutic use , Candida/drug effects , Candida/isolation & purification , Candidiasis/microbiology , Caspofungin , Drug Resistance, Fungal , Echinocandins , Humans , Infant, Newborn , Infant, Premature , Lipopeptides , Microbial Sensitivity Tests , Peptides, Cyclic/adverse effectsABSTRACT
We analyzed the expression of connexin(Cx)43 in proliferating and differentiating C(2)C(12) cells and in myoblasts obtained from newborn mice. Cx43 was present in both cell types and under both conditions. The functional role of gap junctional communication (GJC) during terminal differentiation was evaluated in C(2)C(12) myoblasts in the presence or absence of the gap junction blocker 18beta-glycyrrhetinic acid (beta-GA). Differentiation was temporally analyzed through myogenin expression, activity of creatine kinase (CK), and yield of multinucleated cells. In cells treated with beta-GA, the CK activity and myotube formation were reversibly blocked. While in control cultures positive myogenin expression was seen in cell clusters, in beta-GA treated cultures the myogenin immunoreactivity was detected in few, preferentially sparse cells. The role of Cx43 during terminal differentiation was evaluated in cultures of myoblasts obtained from Cx43(Cre-ER(T)/fl) transgenic mice. Inducible deletion of Cx43 was obtained upon activation of Cre-ER(T) via 4-OH-tamoxifen applications. Cx43 deletion led to a drastic decrease in myogenin expression at 24 h of differentiation as compared to myoblasts from control mice. Our results indicate that Cx43-containing gap junctions are required for normal skeletal muscle terminal differentiation. These channels might provide a pathway for the intercellular transfer of signals involved in myogenesis.
Subject(s)
Cell Communication/physiology , Cell Differentiation/physiology , Connexin 43/metabolism , Gap Junctions/metabolism , Muscle Development/physiology , Animals , Cell Communication/drug effects , Cell Differentiation/drug effects , Cell Division/drug effects , Cell Division/physiology , Cells, Cultured , Connexin 43/genetics , Creatine Kinase/metabolism , Glycyrrhetinic Acid/pharmacology , Mice , Mice, Transgenic , Muscle Development/drug effects , Muscle Development/genetics , Muscle, Skeletal , Myogenin/metabolismABSTRACT
The dihydropyridine receptor (DHPR), normally a voltage-dependent calcium channel, functions in skeletal muscle essentially as a voltage sensor, triggering intracellular calcium release for excitation-contraction coupling. In addition to this fast calcium release, via ryanodine receptor (RYR) channels, depolarization of skeletal myotubes evokes slow calcium waves, unrelated to contraction, that involve the cell nucleus (Jaimovich, E., R. Reyes, J.L. Liberona, and J.A. Powell. 2000. Am. J. Physiol. Cell Physiol. 278:C998-C1010). We tested the hypothesis that DHPR may also be the voltage sensor for these slow calcium signals. In cultures of primary rat myotubes, 10 micro M nifedipine (a DHPR inhibitor) completely blocked the slow calcium (fluo-3-fluorescence) transient after 47 mM K(+) depolarization and only partially reduced the fast Ca(2+) signal. Dysgenic myotubes from the GLT cell line, which do not express the alpha(1) subunit of the DHPR, did not show either type of calcium transient following depolarization. After transfection of the alpha(1) DNA into the GLT cells, K(+) depolarization induced slow calcium transients that were similar to those present in normal C(2)C(12) and normal NLT cell lines. Slow calcium transients in transfected cells were blocked by nifedipine as well as by the G protein inhibitor, pertussis toxin, but not by ryanodine, the RYR inhibitor. Since slow Ca(2+) transients appear to be mediated by IP(3), we measured the increase of IP(3) mass after K(+) depolarization. The IP(3) transient seen in control cells was inhibited by nifedipine and was absent in nontransfected dysgenic cells, but alpha(1)-transfected cells recovered the depolarization-induced IP(3) transient. In normal myotubes, 10 micro M nifedipine, but not ryanodine, inhibited c-jun and c-fos mRNA increase after K(+) depolarization. These results suggest a role for DHPR-mediated calcium signals in regulation of early gene expression. A model of excitation-transcription coupling is presented in which both G proteins and IP(3) appear as important downstream mediators after sensing of depolarization by DHPR.