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Increasing availability of immersive virtual reality (IVR) systems, such as the Cave Automatic Virtual Environment (CAVE) and head-mounted displays, for use in education contexts is providing new opportunities and challenges for instructional designers. By highlighting the affordances of IVR specific to the CAVE, the authors emphasize the importance of establishing new instructional strategy guidelines to mitigate the risk of designing lessons with CAVEs and other IVRs that simply overload learners with unnecessary information and impede overall learning. This information is then applied to create a framework of best practices for designing IVR lessons and instructional materials to effectively incorporate the technology and create opportunities for positive learning. This framework focuses on areas of content, differentiated instruction, interactivity of instruction, presentation of learning materials, virtual and physical spaces, and technical knowledge.

This paper describes the findings of a pilot study that used robotics and game design to develop middle school students' computational thinking strategies. One hundred and twenty-four students engaged in LEGO® EV3 robotics and created games using Scalable Game Design software. The results of the study revealed students' prepost self-efficacy scores on the construct of computer use declined significantly, while the constructs of videogaming and computer gaming remained unchanged. When these constructs were analyzed by type of learning environment, self-efficacy on videogaming increased significantly in the combined robotics/gaming environment compared with the gaming-only context. Student attitudes toward STEM, however, did not change significantly as a result of the study. Finally, children's computational thinking (CT) strategies varied by method of instruction as students who participated in holistic game development (i.e., Project First) had higher CT ratings. This study contributes to the STEM education literature on the use of robotics and game design to influence self-efficacy in technology and CT, while informing the research team about the adaptations needed to ensure project fidelity during the remaining years of the study.

This article explains a professional development experience of fifth to twelfth grade teachers in using geographic information systems (GIS) and global positioning systems (GPS) technologies to enhance classroom teaching and learning environments. A key challenge faced by the developers was whether teachers would value the technology tools enough to warrant the time necessary to develop the skills for productive use of the technology. Based on five years' experience, researchers identified seven key components and elaborated on them with examples and related processes.

This dissertation describes studies exploring the coordination chemistry and reactivity of molybdenum complexes bearing a flexible and redox non-innocent para-terphenyl diphosphine ligand. Within this context, transformations relevant to energy storage and conversion, fundamental structure function studies, and unusual group transfer reactivity are presented.Chapter 2 accounts the ability of Mo para-terphenyl diphosphine complexes to catalyze extensive ammonia borane dehydrogenation, releasing greater than two equiv. of hydrogen (H2). Initially believed to be a frontrunner as a high energy density H2 storage medium, AB is a Lewis acid/base adduct that features both hydridic B–H bond and protic N–H bonds. As a highly reactive molecule, the controlled dehydrogenation of AB, accessing ≥2 of the 3 stored equiv. of H2, is uncommon. We disclose a catalytic system, utilizing an earth-abundant metal, that is capable of such reactivity. The mechanism by which the catalysis proceeds is dependent on the oxidation state of the precatalyst, with MoII proceeding through a II/IV cycle and Mo0 proceeding through a 0/II cycle. Several Mo hydride complexes were characterized in conjunction with this work. Importantly, the ability of the para-terphenyl diphosphine ancillary ligand to support a range of Mo oxidation states and coordination numbers was established, a feature that provides a foundation for the work presented in subsequent chapters.In Chapter 3, new features of the para-terphenyl diphosphine ligand were discovered, namely facilitation of electron loading that subsuequently leads to small molecule functionalization and cleavage. From the Mo dicarbonyl complex described in Chapter 2, stepwise reduction affords Mo0 , Mo-II, and Mo-III compounds, all of which were characterized both structurally and by a variety of spectroscopies. The latter two complexes were demonstrated to react with silyl electrophiles, instigating deoxygenative reductive coupling of the bound CO ligands to a metal-free C2O1 fragment. This remarkable four-electron process was studied in detail, characterizing twelve different reaction intermediates, including rare examples of bis(siloxy)carbyne, terminal carbide , and mixed dicarbyne motifs. The cleavage of a bound carbon monoxide (CO), subsequent coupling, and spontaneous product release was an unprecendented sequence of chemical transformations, the detailed mechanistic study of which provides valuable precedent for catalyses for the conversion of C1oxygenates to multicarbon products.Chapter 4 discusses continuations of this work in an attempt to model Fischer-Tropsch catalysis with higher fidelity. To this end, the silyl electrophiles used in the fundamental studies in Chapter 3 needed to be replaced with protons. Addition of protons to the super-reduced Mo complexes resulted in formal arene hydrogenation; no evidence for C– O functionalization was obtained. These diene-linked complexes; however, provided an opportunity to explore how the nature of the basal π-system effects CO catenation chemistry and ultimately led to the preparation of a Mo-bound C3O3unit derived entirely from CO. Reactivity with protons was likewise explored for downstream intermediates. Carbide protonation yields a stable methylidyne carbonyl complex, that, upon treatment with hydride, forms a methylidene. Comparison to a silyl-bearing model system suggests that subsequent carbene carbonylation affords enthenone.

Autobiographies are an effective tool for assessing students' predispositions toward science and mathematics content and identifying any changes in attitude over time. The purpose of this study was to analyze autobiographies of students enrolled in elementary education methods classes to determine the kinds of K‐12 and college content course experiences affecting their perceptions of mathematics or science. Special attention was given to recollections of events that had positive or negative effects on students' interest in and attitudes toward science or mathematics, their confidence in these areas, and transitions in attitude throughout their experiences. Ninety‐eight autobiographies were collected and analyzed, revealing attitudes that were generally more positive than expected, five major emergent themes, and important information about when and why transitions in attitudes occurred.

The purpose of this study was to collect the knowledge and opinion held by a Delphi panel of leaders and researchers of successful exemplary educational telecommunications projects requiring collaboration across multiple sites. A parallel objective was to synthesize and analyze this knowledge and to communicate the results as a resource for people who are interested in creating similar learning environments. The Delphi technique was used to gather information from a panel of seven experts in telecollaborative projects about successful elements of these projects as well as obstacles to success. Thirty-nine items received high ratings from the panelists and had a high consensus level among the panel. These critical items included 25 essential elements, six highly detrimental obstacles, and eight comments regarding successful implementation of telecollaborative projects. The conclusions provide guidelines for teachers, students, project leaders, design and hardware/software issues. Teachers need to be aware of the time and energy requirements before they decide to participate. Students need to be responsible for communicating with distant peers and mentors. Project leaders will need to devote tremendous time, effort and patience into the project. Project activities must be designed to include shared tasks or goals to provide an authentic purpose for communicating. Finally, teachers must have technical support for hardware and software.

The computer maker, which hasn't announced a new name yet, says it will maintain headquarters in both hometowns, Burroughs' Detroit and Sperry's Blue Bell, Pa. But some people in Detroit wonder. Why, they ask, are several top Burroughs executives trying to sell their old homes and looking for new ones near Blue Bell? Why is W. Michael Blumenthal, chairman and chief executive officer, looking for a house, possibly near Princeton, N.J., where associates say he has made it known he might like to retire someday? Why are the planning and mergers-and-acquisitions staffs moving to Blue Bell? A Burroughs spokeswoman says that Mr. Blumenthal will keep his Ann Arbor, Mich., home and that other migrating executives will maintain Detroit apartments and split their time evenly. She says Joseph J. Kroger, former Sperry president and vice chairman of the new company, will eventually have a Michigan home.

Based on preclinical work, we found that combination of poly (ADP-ribose) polymerase (PARP) inhibitors with drugs that inhibit the homologous recombination repair (HRR) pathway (such as PI3K inhibitors) might sensitise HRR-proficient epithelial ovarian cancers to PARP inhibitors. We aimed to assess the safety and identify the recommended phase 2 dose of the PARP inhibitor olaparib in combination with the PI3K inhibitor alpelisib in patients with epithelial ovarian cancer and in patients with breast cancer. In this multicentre, open-label, phase 1b trial following a 3 + 3 dose-escalation design, we recruited patients aged 18 years or older with the following key eligibility criteria: confirmed diagnosis of either recurrent ovarian, fallopian tube, or primary peritoneal cancer of high-grade serous histology; confirmed diagnosis of either recurrent ovarian, fallopian tube, or primary peritoneal cancer of any histology with known germline BRCA mutations; confirmed diagnosis of recurrent breast cancer of triple-negative histology; or confirmed diagnosis of recurrent breast cancer of any histology with known germline BRCA mutations. Additional patients with epithelial ovarian cancer were enrolled in a dose-expansion cohort. Four dose levels were planned: the starting dose level of alpelisib 250 mg once a day plus olaparib 100 mg twice a day (dose level 0); alpelisib 250 mg once a day plus olaparib 200 mg twice a day (dose level 1); alpelisib 300 mg once a day plus olaparib 200 mg twice a day (dose level 2); and alpelisib 200 mg once a day plus olaparib 200 mg twice a day (dose level 3). Both drugs were administered orally, in tablet formulation. The primary objective was to identify the maximum tolerated dose and the recommended phase 2 dose of the combination of alpelisib and olaparib for patients with epithelial ovarian cancer and patients with breast cancer. Analyses included all patients who received at least one dose of the study drugs. The trial is active, but closed to enrolment; follow-up for patients who completed treatment is ongoing. This trial is registered with ClinicalTrials.gov, number NCT01623349. Between Oct 3, 2014, and Dec 21, 2016, we enrolled 34 patients (28 in the dose-escalation cohort and six in the dose-expansion cohort); two in the dose-escalation cohort were ineligible at the day of scheduled study initiation. Maximum tolerated dose and recommended phase 2 dose were identified as alpelisib 200 mg once a day plus olaparib 200 mg twice a day (dose level 3). Considering all dose levels, the most common treatment-related grade 3–4 adverse events were hyperglycaemia (five [16%] of 32 patients), nausea (three [9%]), and increased alanine aminotransferase concentrations (three [9%]). No treatment-related deaths occurred. Dose-limiting toxic effects included hyperglycaemia and fever with decreased neutrophil count. Of the 28 patients with epithelial ovarian cancer, ten (36%) achieved a partial response and 14 (50%) had stable disease according to Response Evaluation Criteria in Solid Tumors 1.1. Combining alpelisib and olaparib is feasible with no unexpected toxic effects. The observed activity provides preliminary clinical evidence of synergism between olaparib and alpelisib, particularly in epithelial ovarian cancer, and warrants further investigation. Ovarian Cancer Dream Team (Stand Up To Cancer, Ovarian Cancer Research Alliance, National Ovarian Cancer Coalition), Breast Cancer Research Foundation, Novartis.

As arguably the simplest free-living animals, placozoans may represent a primitive metazoan form, yet their biology is poorly understood. Here we report the sequencing and analysis of the ∼98 million base pair nuclear genome of the placozoan Trichoplax adhaerens . Whole-genome phylogenetic analysis suggests that placozoans belong to a ‘eumetazoan’ clade that includes cnidarians and bilaterians, with sponges as the earliest diverging animals. The compact genome shows conserved gene content, gene structure and synteny in relation to the human and other complex eumetazoan genomes. Despite the apparent cellular and organismal simplicity of Trichoplax , its genome encodes a rich array of transcription factor and signalling pathway genes that are typically associated with diverse cell types and developmental processes in eumetazoans, motivating further searches for cryptic cellular complexity and/or as yet unobserved life history stages. The genes for a simple life Often touted as the 'simplest' free-living animal alive, Trichoplax is central to the debate on early animal origins. It is a disk-shaped placozoan (meaning a 'flat animal') about a millimetre across and was first observed growing on the walls of an aquarium. Now the genome of Trichoplax adhaerens has been sequenced and analysed. The organism retains many features of the last common ancestor with cnidarians and bilaterians, calculated to have existed more than 600 million years ago. But Trichoplax also contains genes for developmental patterns and cell types which have never been seen in this animal, suggesting that there may be stages in its life cycle that have not yet been observed. The genome sequence for Trichoplax adhaerens is analysed, and it is reported that the organism retains many features of the last common ancestor with cnidarians and bilaterians, estimated to be over 600 million years ago. However, T. adhaerens also contains genes for developmental patterns and cell types which have never been seen in this animal, suggesting that we might still not know the full story.

Myosin motors perform many fundamental functions in eukaryotic cells by providing force generation, transport or tethering capacity. Motor activity control within the cell involves on/off switches, however, few examples are known of how myosins regulate speed or processivity and fine-tune their activity to a specific cellular task. Here, we describe a phosphorylation event for myosins of class VI (MYO6) in the motor domain, which accelerates its ATPase activity leading to a 4-fold increase in motor speed determined by actin-gliding assays, single molecule mechanics and stopped flow kinetics. We demonstrate that the serine/threonine kinase DYRK2 phosphorylates MYO6 at S267 in vitro. Single-molecule optical-tweezers studies at low load reveal that S267-phosphorylation results in faster nucleotide-exchange kinetics without change in the working stroke of the motor. The selective increase in stiffness of the acto-MYO6 complex when proceeding load-dependently into the nucleotide-free rigor state demonstrates that S267-phosphorylation turns MYO6 into a stronger motor. Finally, molecular dynamic simulations of the nucleotide-free motor reveal an alternative interaction network within insert-1 upon phosphorylation, suggesting a molecular mechanism, which regulates insert-1 positioning, turning the S267-phosphorylated MYO6 into a faster motor. Myosin motors perform many fundamental functions in eukaryotic cells by providing force generation, transport or tethering capacity. Here, the authors show that a single phosphorylation event can modulate actin-activated ATPase activity and change the mechanical properties of myosin-VI.