Strategies to Promote Meaningful Student Engagement in Online Settings

Distance learning or online education has increased significantly over the past decade to coincide with easy access to technology and the availability of multifaceted learning management system software that can be used to develop asynchronous educational experiences (Ginder et al., 2018). The increased demand for online education, as well as unprecedented circumstances (Covid-19 Pandemic) that require quick changes to instructional delivery alternatives, have resulted in many traditional face-to-face programs transitioning into online and hybrid (e.g., part online and part face-to-face) programs across curriculum content areas to attract and retain full and part-time learners (DuPont et al., 2018). Effective online instruction must be engaging and meaningful/relevant. Course authors and instructors in higher education must incorporate strategies to maximize student engagement to develop high-quality learning experiences in online environments (Fallahi, 2019; Weidlich & Bastiaens, 2018). This article discusses the application of varied strategies and instructional practices to help instructors in post-secondary educational settings enhance the quality of teaching and social presence in the online learning environment. The strategies addressed are connected to the teachers’ ability to integrate multifaceted learning goals into instructional planning and delivery in order to create effective online learning environments that may improve outcomes for students across settings and content areas (Dixson, 2015; Henrie et al., 2015; Moore & Shemberger, 2019)

Heat-kernel Coefficients and Spectra of the Vector Laplacians on Spherical Domains with Conical Singularities

The spherical domains $S^d_\beta$ with conical singularities are a convenient arena for studying the properties of tensor Laplacians on arbitrary manifolds with such a kind of singular points. In this paper the vector Laplacian on $S^d_\beta$ is considered and its spectrum is calculated exactly for any dimension $d$. This enables one to find the Schwinger-DeWitt coefficients of this operator by using the residues of the $\zeta$-function. In particular, the second coefficient, defining the conformal anomaly, is explicitly calculated on $S^d_\beta$ and its generalization to arbitrary manifolds is found. As an application of this result, the standard renormalization of the one-loop effective action of gauge fields is demonstrated to be sufficient to remove the ultraviolet divergences up to the first order in the conical deficit angle.Comment: plain LaTeX, 23 pp., revised version, a misprint in expressions (1.8) and (4.38) of the second heat coefficient for the vector Laplacian is corrected. No other change

MINERvA neutrino detector response measured with test beam data

The MINERvA collaboration operated a scaled-down replica of the solid scintillator tracking and sampling calorimeter regions of the MINERvA detector in a hadron test beam at the Fermilab Test Beam Facility. This article reports measurements with samples of protons, pions, and electrons from 0.35 to 2.0 GeV/c momentum. The calorimetric response to protons, pions, and electrons are obtained from these data. A measurement of the parameter in Birks' law and an estimate of the tracking efficiency are extracted from the proton sample. Overall the data are well described by a Geant4-based Monte Carlo simulation of the detector and particle interactions with agreements better than 4%, though some features of the data are not precisely modeled. These measurements are used to tune the MINERvA detector simulation and evaluate systematic uncertainties in support of the MINERvA neutrino cross section measurement program.Comment: as accepted by NIM

Epistatic Relationships between sarA and agr in Staphylococcus aureus Biofilm Formation

Background: The accessory gene regulator (agr) and staphylococcal accessory regulator (sarA) play opposing roles in Staphylococcus aureus biofilm formation. There is mounting evidence to suggest that these opposing roles are therapeutically relevant in that mutation of agr results in increased biofilm formation and decreased antibiotic susceptibility while mutation of sarA has the opposite effect. To the extent that induction of agr or inhibition of sarA could potentially be used to limit biofilm formation, this makes it important to understand the epistatic relationships between these two loci. Methodology/Principal Findings: We generated isogenic sarA and agr mutants in clinical isolates of S. aureus and assessed the relative impact on biofilm formation. Mutation of agr resulted in an increased capacity to forma biofilmin the 8325-4 laboratory strain RN6390 but had little impact in clinical isolates S. aureus. In contrast, mutation of sarA resulted in a reduced capacity to form a biofilm in all clinical isolates irrespective of the functional status of agr. This suggests that the regulatory role of sarA in biofilm formation is independent of the interaction between sarA and agr and that sarA is epistatic to agr in this context. This was confirmed by demonstrating that restoration of sarA function restored the ability to form a biofilm even in the corresponding agr mutants. Mutation of sarA in clinical isolates also resulted in increased production of extracellular proteases and extracellular nucleases, both of which contributed to the biofilm-deficient phenotype of sarA mutants. However, studies comparing different strains with and without proteases inhibitors and/or mutation of the nuclease genes demonstrated that the agr-independent, sarA-mediated repression of extracellular proteases plays a primary role in this regard. Conclusions and Significance: The results we report suggest that inhibitors of sarA-mediated regulation could be used to limit biofilm formation in S. aureus and that the efficacy of such inhibitors would not be limited by spontaneous mutation of agr in the human host

The genome of the green anole lizard and a comparative analysis with birds and mammals

The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments. Among amniotes, genome sequences are available for mammals and birds, but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes. Also, A. carolinensis mobile elements are very young and diverse—more so than in any other sequenced amniote genome. The GC content of this lizard genome is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds. We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations.National Science Foundation (U.S.) (NSF grant DEB-0920892)National Science Foundation (U.S.) (NSF grant DEB-0844624)National Human Genome Research Institute (U.S.

SalmoNet, an integrated network of ten Salmonella enterica strains reveals common and distinct pathways to host adaptation

Salmonella enterica is a prominent bacterial pathogen with implications on human and animal health. Salmonella serovars could be classified as gastro-intestinal or extra-intestinal. Genome-wide comparisons revealed that extra-intestinal strains are closer relatives of gastro-intestinal strains than to each other indicating a parallel evolution of this trait. Given the complexity of the differences, a systems-level comparison could reveal key mechanisms enabling extra-intestinal serovars to cause systemic infections. Accordingly, in this work, we introduce a unique resource, SalmoNet, which combines manual curation, high-throughput data and computational predictions to provide an integrated network for Salmonella at the metabolic, transcriptional regulatory and protein-protein interaction levels. SalmoNet provides the networks separately for five gastro-intestinal and five extra-intestinal strains. As a multi-layered, multi-strain database containing experimental data, SalmoNet is the first dedicated network resource for Salmonella. It comprehensively contains interactions between proteins encoded in Salmonella pathogenicity islands, as well as regulatory mechanisms of metabolic processes with the option to zoom-in and analyze the interactions at specific loci in more detail. Application of SalmoNet is not limited to strain comparisons as it also provides a Salmonella resource for biochemical network modeling, host-pathogen interaction studies, drug discovery, experimental validation of novel interactions, uncovering new pathological mechanisms from emergent properties and epidemiological studies. SalmoNet is available at http://salmonet.org

Models and data analysis tools for the Solar Orbiter mission

Context. The Solar Orbiter spacecraft will be equipped with a wide range of remote-sensing (RS) and in situ (IS) instruments to record novel and unprecedented measurements of the solar atmosphere and the inner heliosphere. To take full advantage of these new datasets, tools and techniques must be developed to ease multi-instrument and multi-spacecraft studies. In particular the currently inaccessible low solar corona below two solar radii can only be observed remotely. Furthermore techniques must be used to retrieve coronal plasma properties in time and in three dimensional (3D) space. Solar Orbiter will run complex observation campaigns that provide interesting opportunities to maximise the likelihood of linking IS data to their source region near the Sun. Several RS instruments can be directed to specific targets situated on the solar disk just days before data acquisition. To compare IS and RS, data we must improve our understanding of how heliospheric probes magnetically connect to the solar disk.Aims. The aim of the present paper is to briefly review how the current modelling of the Sun and its atmosphere can support Solar Orbiter science. We describe the results of a community-led effort by European Space Agency's Modelling and Data Analysis Working Group (MADAWG) to develop different models, tools, and techniques deemed necessary to test different theories for the physical processes that may occur in the solar plasma. The focus here is on the large scales and little is described with regards to kinetic processes. To exploit future IS and RS data fully, many techniques have been adapted to model the evolving 3D solar magneto-plasma from the solar interior to the solar wind. A particular focus in the paper is placed on techniques that can estimate how Solar Orbiter will connect magnetically through the complex coronal magnetic fields to various photospheric and coronal features in support of spacecraft operations and future scientific studies.Methods. Recent missions such as STEREO, provided great opportunities for RS, IS, and multi-spacecraft studies. We summarise the achievements and highlight the challenges faced during these investigations, many of which motivated the Solar Orbiter mission. We present the new tools and techniques developed by the MADAWG to support the science operations and the analysis of the data from the many instruments on Solar Orbiter.Results. This article reviews current modelling and tool developments that ease the comparison of model results with RS and IS data made available by current and upcoming missions. It also describes the modelling strategy to support the science operations and subsequent exploitation of Solar Orbiter data in order to maximise the scientific output of the mission.Conclusions. The on-going community effort presented in this paper has provided new models and tools necessary to support mission operations as well as the science exploitation of the Solar Orbiter data. The tools and techniques will no doubt evolve significantly as we refine our procedure and methodology during the first year of operations of this highly promising mission.Peer reviewe

Development and validation of a targeted gene sequencing panel for application to disparate cancers

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy

Homologous recombination DNA repair defects in PALB2- associated breast cancers

Abstract: Mono-allelic germline pathogenic variants in the Partner And Localizer of BRCA2 (PALB2) gene predispose to a high-risk of breast cancer development, consistent with the role of PALB2 in homologous recombination (HR) DNA repair. Here, we sought to define the repertoire of somatic genetic alterations in PALB2-associated breast cancers (BCs), and whether PALB2-associated BCs display bi-allelic inactivation of PALB2 and/or genomic features of HR-deficiency (HRD). Twenty-four breast cancer patients with pathogenic PALB2 germline mutations were analyzed by whole-exome sequencing (WES, n = 16) or targeted capture massively parallel sequencing (410 cancer genes, n = 8). Somatic genetic alterations, loss of heterozygosity (LOH) of the PALB2 wild-type allele, large-scale state transitions (LSTs) and mutational signatures were defined. PALB2-associated BCs were found to be heterogeneous at the genetic level, with PIK3CA (29%), PALB2 (21%), TP53 (21%), and NOTCH3 (17%) being the genes most frequently affected by somatic mutations. Bi-allelic PALB2 inactivation was found in 16 of the 24 cases (67%), either through LOH (n = 11) or second somatic mutations (n = 5) of the wild-type allele. High LST scores were found in all 12 PALB2-associated BCs with bi-allelic PALB2 inactivation sequenced by WES, of which eight displayed the HRD-related mutational signature 3. In addition, bi-allelic inactivation of PALB2 was significantly associated with high LST scores. Our findings suggest that the identification of bi-allelic PALB2 inactivation in PALB2-associated BCs is required for the personalization of HR-directed therapies, such as platinum salts and/or PARP inhibitors, as the vast majority of PALB2-associated BCs without PALB2 bi-allelic inactivation lack genomic features of HRD