Learning from the children : exploring preschool children's encounters with ICT at home

This paper is an account of our attempts to understand preschool children's experiences with information and communication technologies (ICT) at home. Using case study data, we focus on what we can learn from talking directly to the children that might otherwise have been overlooked and on describing and evaluating the methods we adopted to ensure that we maximised the children's contributions to the research. By paying attention to the children's perspectives we have learned that they are discriminating users of ICT who evaluate their own performances, know what gives them pleasure and who differentiate between operational competence and the substantive activities made possible by ICT

From research to design: Perspectives on early years and digital technologies

The three papers explore how we can use existing research traditions to create challenging new directions for design and development of technologies for the early years. The papers focus on literacy, numeracy and reflections on the design process

Mixed Mood State Behaviors and Circadian Dysfunction following Homocysteic Acid Treatment: Potential Animal Model for Bipolar Disorder

Bipolar disorder is a neuropsychiatric disease characterized by cyclical fluctuations of mood states between mania and depression. Circadian rhythm abnormalities and inconsistent sleep patterns are two common symptoms of bipolar disorder (Millar, Epsie, & Scott, 2004). Elevated levels of homocysteine, in the blood or cerebrospinal fluid, commonly occurs in patients with neuropsychiatric illnesses, including bipolar disorder (Bell et al., 1992; Boushey, Beresford, Omenn, & Motulsky, 1995). Homocysteic acid (HCA), an endogenous metabolite of homocysteine, has been implicated as a harmful neurotoxin and agonist of NMDA receptors. We have previously shown that postnatal administration of HCA (from postnatal day 3-21) in Sprague Dawley rats results in both mania-like and depressive-like behaviors, suggesting that this may serve as a novel animal model for bipolar disorder. The purpose of the present study was to characterize any circadian abnormalities that may be present in HCA-treated rats, as sleep and circadian dysfunction are common symptoms of bipolar disorder. In addition, we also characterized the developmental onset of the mania-like and depressive-like behaviors in this model. Prior to puberty, we found that HCA-treated rats exhibited no manic-like behaviors and only a trend toward depressive-like behaviors. After puberty, however, HCA-treated rats presented a mixed mood-state of both manic-like and depressive-like behaviors, along with significant dysfunction in the circadian clock. Specifically, both the free-running period and the amplitude of the rhythm were significantly reduced following HCA treatment. We are currently using microarray analyses to determine differences in circadian gene expression levels between HCA treated animals and controls. Additionally, we are examining the therapeutic role of lithium for reversing the circadian disruptions exhibited by the HCA-treated animals. Altogether, the findings of the present study provide strong evidence in support of the HCA model’s face validity for bipolar disorder, allowing us to better understand the mechanisms underlying the development of this disease

Cholesterol-sensitive Cdc42 activation regulates actin polymerization for endocytosis via the GEEC pathway

Glycosyl-phosphatidylinositol (GPI)-anchored proteins (GPI-APs) are present at the surface of living cells in cholesterol dependent nanoscale clusters. These clusters appear to act as sorting signals for the selective endocytosis of GPI-APs via a Cdc42-regulated, dynamin and clathrin-independent pinocytic pathway called the GPI-AP-enriched early endosomal compartments (GEECs) pathway. Here we show that endocytosis via the GEECs pathway is inhibited by mild depletion of cholesterol, perturbation of actin polymerization or overexpression of the Cdc42/Rac-interactive-binding (CRIB) motif of neural Wiskott-Aldrich syndrome protein (N-WASP). Consistent with the involvement of Cdc42-based actin nanomachinery, nascent endocytic vesicles containing cargo for the GEEC pathway co-localize with fluorescent protein-tagged isoforms of Cdc42, CRIB domain, N-WASP and actin; high-resolution electron microscopy on plasma membrane sheets reveals Cdc42-labelled regions rich in green fluorescent protein-GPI. Using total internal reflection fluorescence microscopy at the single-molecule scale, we find that mild cholesterol depletion alters the dynamics of actin polymerization at the cell surface by inhibiting Cdc42 activation and consequently its stabilization at the cell surface. These results suggest that endocytosis into GEECs occurs through a cholesterol-sensitive, Cdc42-based recruitment of the actin polymerization machinery

H-Ras Nanocluster Stability Regulates the Magnitude of MAPK Signal Output

H-Ras is a binary switch that is activated by multiple co-factors and triggers several key cellular pathways one of which is MAPK. The specificity and magnitude of downstream activation is achieved by the spatio-temporal organization of the active H-Ras in the plasma membrane. Upon activation, the GTP bound H-Ras binds to Galectin-1 (Gal-1) and becomes transiently immobilized in short-lived nanoclusters on the plasma membrane from which the signal is propagated to Raf. In the current study we show that stabilizing the H-Ras-Gal-1 interaction, using bimolecular fluorescence complementation (BiFC), leads to prolonged immobilization of H-Ras.GTP in the plasma membrane which was measured by fluorescence recovery after photobleaching (FRAP), and increased signal out-put to the MAPK module. EM measurements of Raf recruitment to the H-Ras.GTP nanoclusters demonstrated that the enhanced signaling observed in the BiFC stabilized H-Ras.GTP nanocluster was attributed to increased H-Ras immobilization rather than to an increase in Raf recruitment. Taken together these data demonstrate that the magnitude of the signal output from a GTP-bound H-Ras nanocluster is proportional to its stability

Magnetic Energy Powers the Corona: How We Can Understand its 3D Storage & Release

The coronal magnetic field is the prime driver behind many as-yet unsolved mysteries: solar eruptions, coronal heating, and the solar wind, to name a few. It is, however, still poorly observed and understood. We highlight key questions related to magnetic energy storage, release, and transport in the solar corona, and their relationship to these important problems. We advocate for new and multi-point co-optimized measurements, sensitive to magnetic field and other plasma parameters, spanning from optical to $\gamma$-ray wavelengths, to bring closure to these long-standing and fundamental questions. We discuss how our approach can fully describe the 3D magnetic field, embedded plasma, particle energization, and their joint evolution to achieve these objectives.Comment: White paper submitted to the Decadal Survey for Solar and Space Physics (Heliophysics) 2024-2033; 16 pages, 3 figure

COMPLETE: A flagship mission for complete understanding of 3D coronal magnetic energy release

COMPLETE is a flagship mission concept combining broadband spectroscopic imaging and comprehensive magnetography from multiple viewpoints around the Sun to enable tomographic reconstruction of 3D coronal magnetic fields and associated dynamic plasma properties, which provide direct diagnostics of energy release. COMPLETE re-imagines the paradigm for solar remote-sensing observations through purposefully co-optimized detectors distributed on multiple spacecraft that operate as a single observatory, linked by a comprehensive data/model assimilation strategy to unify individual observations into a single physical framework. We describe COMPLETE's science goals, instruments, and mission implementation. With targeted investment by NASA, COMPLETE is feasible for launch in 2032 to observe around the maximum of Solar Cycle 26.Comment: White paper submitted to the Decadal Survey for Solar and Space Physics (Heliophysics) 2024-2033; 10 pages, 6 figures, 1 tabl

Improving Multi-Dimensional Data Formats, Access, and Assimilation Tools for the Twenty-First Century

Heliophysics image data largely relies on a forty-year-old ecosystem built on the venerable Flexible Image Transport System (FITS) data standard. While many in situ measurements use newer standards, they are difficult to integrate with multiple data streams required to develop global understanding. Additionally, most data users still engage with data in much the same way as they did decades ago. However, contemporary missions and models require much more complex support for 3D multi-parameter data, robust data assimilation strategies, and integration of multiple individual data streams required to derive complete physical characterizations of the Sun and Heliospheric plasma environment. In this white paper we highlight some of the 21$^\mathsf{st}$ century challenges for data frameworks in heliophysics, consider an illustrative case study, and make recommendations for important steps the field can take to modernize its data products and data usage models. Our specific recommendations include: (1) Investing in data assimilation capability to drive advanced data-constrained models, (2) Investing in new strategies for integrating data across multiple instruments to realize measurements that cannot be produced from single observations, (3) Rethinking old data use paradigms to improve user access, develop deep understanding, and decrease barrier to entry for new datasets, and (4) Investing in research on data formats better suited for multi-dimensional data and cloud-based computing.Comment: White paper submitted to the Decadal Survey for Solar and Space Physics (Heliophysics) 2024-2033; 9 pages, 3 figure

XLF-Cernunnos promotes DNA ligase IV–XRCC4 re-adenylation following ligation

XLF-Cernunnos (XLF) is a component of the DNA ligase IV–XRCC4 (LX) complex, which functions during DNA non-homologous end joining (NHEJ). Here, we use biochemical and cellular approaches to probe the impact of XLF on LX activities. We show that XLF stimulates adenylation of LX complexes de-adenylated by pyrophosphate or following LX decharging during ligation. XLF enhances LX ligation activity in an ATP-independent and dependent manner. ATP-independent stimulation can be attributed to enhanced end-bridging. Whilst ATP alone fails to stimulate LX ligation activity, addition of XLF and ATP promotes ligation in a manner consistent with XLF-stimulated readenylation linked to ligation. We show that XLF is a weakly bound partner of the tightly associated LX complex and, unlike XRCC4, is dispensable for LX stability. 2BN cells, which have little, if any, residual XLF activity, show a 3-fold decreased ability to repair DNA double strand breaks covering a range of complexity. These findings strongly suggest that XLF is not essential for NHEJ but promotes LX adenylation and hence ligation. We propose a model in which XLF, by in situ recharging DNA ligase IV after the first ligation event, promotes double stranded ligation by a single LX complex