Supporting Mastery Learning Through a Multiple-Submission Policy for Assignments in a Purely Online Programming Class

The Learning Edge Momentum (LEM) theory suggests that once students fall behind, it gets more difficult to catch up with the course material. It then becomes increasingly more difficult to connect new, higher-level concepts to those solid edges of knowledge with mastery of basic concepts. Learning for Mastery (LFM) acknowledges that students learn at different paces by allowing students unable to master tests the first time to catch up eventually. This paper describes how an online introductory Python programming course offered to business students followed a multiple-submission policy for assignments to support LFM. The multiple submission policy contributed to the students’ mastery by encouraging individual practice and experimentation while also increasing the students’ comfort level and confidence. The research attempts to find relationships between taking advantage of the multiple-submit policy and results of summative assessments. Qualitative data on students’ self-reported progress per week is cross-referenced with quantitative data from the results of a regression analysis performed on LMS logs related to students’ engagement with course material. Performance on summative assessments is used as the regression’s dependent variable, and engagement with formative assessments in terms of the number of attempts and performance per attempt is used as the explanatory variable

Overcoming transactional distance when conducting online classes on programming for business students: a COVID-19 experience

Studies have shown that transactional distance negatively impacts student learning. In the context of learning, distance pertains to the geographic, pedagogical, and psychological gap between instructors and students. This perception of distance is magnified in online learning because instructors and students do not meet face to face. The gaps involve not only the geographic aspect. Another gap is pedagogical, which depends on the online course\u27s design and structure flexibility and how these align with the students\u27 level of autonomy. Still, another gap is psychological, which relates to how students perceive how much the teacher is accessible or disengaged (level of dialogue) and with students\u27 academic self-efficacy assessments. This paper describes how we could reduce the transactional distance between instructor and students by deliberately designing and conducting mostly asynchronous classes on programming for business students but with the right blend of non-lecture synchronous activities during tight lockdown due to COVID-19. We explain what used to work well before the pandemic where classes were onsite and face-to-face and what mechanisms we used to overcome the lockdown-related gaps. The course was held during Intersession and only had less than six weeks. Based on students\u27 grades and general sentiments, the results were in line with expected learning outcomes, and miscellaneous feedback and comments from students were positive

Designing a Multiple Submission Policy Supporting Mastery Learning for a Design Thinking Class in a Purely Online Learning Environment

Mastery learning is defined as an approach where students are equipped with complex skills required in the VUCA world instead of simple skills that only apply to traditional classrooms. One way to encourage mastery learning in the classroom is through repeated assessment, specifically formative ones. In this paper, we describe our experience in designing a multiple submission policy to support mastery learning for a design thinking class taught purely online amidst lockdowns due to COVID. The transition to online learning and today’s context presented an opportunity to target mastery learning instead of traditional learning outcomes, which we achieved in two ways. First, we elevated the assessments’ level on Bloom’s taxonomy and encouraged iteration by providing feedback to guide metacognition. Second, we built creative confidence providing a safety net for graded assessments, which helped address fears of judgment and lack of control. In the process, we also overcame transactional distance to help promote self-efficacy, especially those with initially low grades. The policy was implemented with the aid of technology, which served as the medium for learning and dialogue. The use of technology in this study allowed for practices that were otherwise not implemented or even considered in previous trials of the class. The study resulted in positive feedback and improved quality of submissions from participants

A novel FRET-based screen in high-throughput format to identify inhibitors of malarial and human glucose transporters

The glucose transporter PfHT is essential to the survival of the malaria parasite Plasmodium falciparum and has been shown to be a druggable target with high potential for pharmacological intervention. Identification of compounds against novel drug targets is crucial to combating resistance against current therapeutics. Here, we describe the development of a cell-based assay system readily adaptable to high-throughput screening that directly measures compound effects on PfHT-mediated glucose transport. Intracellular glucose concentrations are detected using a genetically encoded fluorescence resonance energy transfer (FRET)-based glucose sensor. This allows assessment of the ability of small molecules to inhibit glucose uptake with high accuracy (Z′ factor of >0.8), thereby eliminating the need for radiolabeled substrates. Furthermore, we have adapted this assay to counterscreen PfHT hits against the human orthologues GLUT1, -2, -3, and -4. We report the identification of several hits after screening the Medicines for Malaria Venture (MMV) Malaria Box, a library of 400 compounds known to inhibit erythrocytic development of P. falciparum. Hit compounds were characterized by determining the half-maximal inhibitory concentration (IC(50)) for the uptake of radiolabeled glucose into isolated P. falciparum parasites. One of our hits, compound MMV009085, shows high potency and orthologue selectivity, thereby successfully validating our assay for antimalarial screening

Integrating RTI case management within LGU Health Centers: An intervention study

In 1994, the Philippines’ Department of Health began assessing the feasibility of syndromic management—utilizing flowcharts and algorithms—for reproductive tract infections (RTIs) in the country’s public health facilities. This intervention, in seven primary health care clinics, trained service providers on RTI case management, improved clinical facilities and laboratories, provided supportive supervision and TA, along with developing training materials. Clinical case management was observed for a six month period. The project also included a cost analysis

Identification of druggable small molecule antagonists of the Plasmodium falciparum hexose transporter PfHT and assessment of ligand access to the glucose permeation pathway via FLAG-mediated protein engineering

Although the Plasmodium falciparum hexose transporter PfHT has emerged as a promising target for anti-malarial therapy, previously identified small-molecule inhibitors have lacked promising drug-like structural features necessary for development as clinical therapeutics. Taking advantage of emerging insight into structure/function relationships in homologous facilitative hexose transporters and our novel high throughput screening platform, we investigated the ability of compounds satisfying Lipinksi rules for drug likeness to directly interact and inhibit PfHT. The Maybridge HitFinder chemical library was interrogated by searching for compounds that reduce intracellular glucose by >40% at 10 μM. Testing of initial hits via measurement of 2-deoxyglucose (2-DG) uptake in PfHT over-expressing cell lines identified 6 structurally unique glucose transport inhibitors. WU-1 (3-(2,6-dichlorophenyl)-5-methyl-N-[2-(4-methylbenzenesulfonyl)ethyl]-1,2-oxazole-4-carboxamide) blocked 2-DG uptake (IC50 = 5.8 ± 0.6 μM) with minimal effect on the human orthologue class I (GLUTs 1–4), class II (GLUT8) and class III (GLUT5) facilitative glucose transporters. WU-1 showed comparable potency in blocking 2-DG uptake in freed parasites and inhibiting parasite growth, with an IC50 of 6.1 ± 0.8 μM and EC50 of 5.5 ± 0.6 μM, respectively. WU-1 also directly competed for N-[2-[2-[2-[(N-biotinylcaproylamino)ethoxy)ethoxyl]-4-[2-(trifluoromethyl)-3H-diazirin-3-yl]benzoyl]-1,3-bis(mannopyranosyl-4-yloxy)-2-propylamine (ATB-BMPA) binding and inhibited the transport of D-glucose with an IC50 of 5.9 ± 0.8 μM in liposomes containing purified PfHT. Kinetic analysis revealed that WU-1 acts as a non-competitive inhibitor of zero-trans D-fructose uptake. Decreased potency for WU-1 and the known endofacial ligand cytochalasin B was observed when PfHT was engineered to contain an N-terminal FLAG tag. This modification resulted in a concomitant increase in affinity for 4,6-O-ethylidene-α-D-glucose, an exofacially directed transport antagonist, but did not alter the Km for 2-DG. Taken together, these data are consistent with a model in which WU-1 binds preferentially to the transporter in an inward open conformation and support the feasibility of developing potent and selective PfHT antagonists as a novel class of anti-malarial drugs.</div

The Extracellular Domain of Notch2 Increases Its Cell-Surface Abundance and Ligand Responsiveness during Kidney Development

SummaryNotch2, but not Notch1, plays indispensable roles in kidney organogenesis, and Notch2 haploinsufficiency is associated with Alagille syndrome. We proposed that proximal nephron fates are regulated by a threshold that requires nearly all available free Notch intracellular domains (NICDs) but could not identify the mechanism that explains why Notch2 (N2) is more important than Notch1 (N1). By generating mice that swap their ICDs, we establish that the overall protein concentration, expression domain, or ICD amino acid composition does not account for the differential requirement of these receptors. Instead, we find that the N2 extracellular domain (NECD) increases Notch protein localization to the cell surface during kidney development and is cleaved more efficiently upon ligand binding. This context-specific asymmetry in NICD release efficiency is further enhanced by Fringe. Our results indicate that an elevated N1 surface level could compensate for the loss of N2 signal in specific cell contexts

Structure-guided evolution of cyan fluorescent proteins towards a quantum yield of 93%

Cyan variants of green fluorescent protein are widely used as donors in Förster resonance energy transfer experiments. The popular, but modestly bright, Enhanced Cyan Fluorescent Protein (ECFP) was sequentially improved into the brighter variants Super Cyan Fluorescent Protein 3A (SCFP3A) and mTurquoise, the latter exhibiting a high-fluorescence quantum yield and a long mono-exponential fluorescence lifetime. Here we combine X-ray crystallography and excited-state calculations to rationalize these stepwise improvements. The enhancement originates from stabilization of the seventh β-strand and the strengthening of the sole chromophore-stabilizing hydrogen bond. The structural analysis highlighted one suboptimal internal residue, which was subjected to saturation mutagenesis combined with fluorescence lifetime-based screening. This resulted in mTurquoise2, a brighter variant with faster maturation, high photostability, longer mono-exponential lifetime and the highest quantum yield measured for a monomeric fluorescent protein. Together, these properties make mTurquoise2 the preferable cyan variant of green fluorescent protein for long-term imaging and as donor for Förster resonance energy transfer to a yellow fluorescent protein

Cochlin Induced TREK-1 Co-Expression and Annexin A2 Secretion: Role in Trabecular Meshwork Cell Elongation and Motility

Fluid flow through large interstitial spaces is sensed at the cellular level, and mechanistic responses to flow changes enables expansion or contraction of the cells modulating the surrounding area and brings about changes in fluid flow. In the anterior eye chamber, aqueous humor, a clear fluid, flows through trabecular meshwork (TM), a filter like region. Cochlin, a secreted protein in the extracellular matrix, was identified in the TM of glaucomatous patients but not controls by mass spectrometry. Cochlin undergoes shear induced multimerization and plays a role in mechanosensing of fluid shear. Cytoskeletal changes in response to mechanosensing in the ECM by cochlin will necessitate transduction of mechanosensing. TREK-1, a stretch activated outward rectifying potassium channel protein known to act as mechanotransducer was found to be expressed in TM. Cochlin expression results in co-expression of TREK-1 and filopodia formation. Prolonged cochlin expression results in expression and subsequent secretion of annexin A2, a protein known to play a role in cytoskeletal remodeling. Cochlin interacts with TREK-1 and annexin A2. Cochlin-TREK-1 interaction has functional consequences and results in changes in cell shape and motility. Annexin A2 expression and secretion follows cochlin-TREK-1 syn-expression and correlates with cell elongation. Thus cytoskeleton changes in response to fluid shear sensed by cochlin are further mediated by TREK-1 and annexin A2