• Canada
• Publicationsclose
• Research dataclose
• 2017-2021close
• IL close
• AT close

Collaborative Mixed Reality (MR) systems are at a critical point in time as they are soon to become more commonplace. However, MR technology has only recently matured to the point where researchers can focus deeply on the nuances of supporting collaboration, rather than needing to focus on creating the enabling technology. In parallel, but largely independently, the field of Computer Supported Cooperative Work (CSCW) has focused on the fundamental concerns that underlie human communication and collaboration over the past 30-plus years. Since MR research is now on the brink of moving into the real world, we reflect on three decades of collaborative MR research and try to reconcile it with existing theory from CSCW, to help position MR researchers to pursue fruitful directions for their work. To do this, we review the history of collaborative MR systems, investigating how the common taxonomies and frameworks in CSCW and MR research can be applied to existing work on collaborative MR systems, exploring where they have fallen behind, and look for new ways to describe current trends. Through identifying emergent trends, we suggest future directions for MR, and also find where CSCW researchers can explore new theory that more fully represents the future of working, playing and being with others Refereed/Peer-reviewed

We argue that the abstractions between the layers of the computing stack and the components of computing systems, especially the HW/SW interface, have to be rethought to cope with the ever-growing complexity of problem domains and their manifestations in the underlying computing systems. The divide and conquer approach to hardware/software with a minimal interface is unable to cope with complexity. Rethinking the abstractions and interfaces between the application, system, and architecture can lead to significant benefits in improving performance, efficiency, resilience, security, and programmability, at the same time.

Brain myelin and iron content are important parameters in neurodegenerative diseases such as multiple sclerosis (MS). Both myelin and iron content influence the brain's R2 * relaxation rate. However, their quantification based on R2 * maps requires a realistic tissue model that can be fitted to the measured data. In structures with low myelin content, such as deep gray matter, R2 * shows a linear increase with increasing iron content. In white matter, R2 * is not only affected by iron and myelin but also by the orientation of the myelinated axons with respect to the external magnetic field. Here, we propose a numerical model which incorporates iron and myelin, as well as fibre orientation, to simulate R2 * decay in white matter. Applying our model to fibre orientation-dependent in vivo R2 * data, we are able to determine a unique solution of myelin and iron content in global white matter. We determine an averaged myelin volume fraction of 16.02 ± 2.07% in non-lesional white matter of patients with MS, 17.32 ± 2.20% in matched healthy controls, and 18.19 ± 2.98% in healthy siblings of patients with MS. Averaged iron content was 35.6 ± 8.9 mg/kg tissue in patients, 43.1 ± 8.3 mg/kg in controls, and 47.8 ± 8.2 mg/kg in siblings. All differences in iron content between groups were significant, while the difference in myelin content between MS patients and the siblings of MS patients was significant. In conclusion, we demonstrate that a model that combines myelin-induced orientation-dependent and iron-induced orientation-independent components is able to fit in vivo R2 * data.

As we saw in the previous chapters, various educational interventions have been designed and implemented to prepare health care professionals to practice in the information and Information and Communication Technology (ICT)-rich environment of the twenty-first century. However, for interventions to be effective there is a need for more evidence: we need to know what interventions work best, for what, for whom, and under which conditions. Evaluation is critical for providing this evidence. In this chapter, we will discuss the evaluation of educational interventions in general and of interventions related to challenges of the digital era in particular. We start by defining evaluation and discussing the relationship between evaluation and research, Then, we will describe the three intervention types (simple, complicated, and complex), and the different implications of each. Next, the five attributes of evaluation (reliability, validity, feasibility, acceptability, and educational impact) will be introduced, and the various levels of evaluation discussed with an emphasis on the need to consider cost-effectiveness and the process that learners go through. Subsequently, we will highlight the challenges involved in evaluating educational interventions in general and the specific issues pertaining to informatics-related interventions. Finally, we will use case studies from our own and other's research to illustrate these issues.

The key factors underlying the development of allergic diseases-the propensity for a minority of individuals to develop dysfunctional responses to harmless environmental molecules-remain undefined. We report a pathway of immune counter-regulation that suppresses the development of aeroallergy and shrimp-induced anaphylaxis. In mice, signaling through epithelially expressed dectin-1 suppresses the development of type 2 immune responses through inhibition of interleukin-33 (IL-33) secretion and the subsequent recruitment of IL-13-producing innate lymphoid cells. Although this homeostatic pathway is functional in respiratory epithelial cells from healthy humans, it is dramatically impaired in epithelial cells from asthmatic and chronic rhinosinusitis patients, resulting in elevated IL-33 production. Moreover, we identify an association between a single-nucleotide polymorphism (SNP) in the dectin-1 gene loci and reduced pulmonary function in two cohorts of asthmatics. This intronic SNP is a predicted eQTL (expression quantitative trait locus) that is associated with reduced dectin-1 expression in human tissue. We identify invertebrate tropomyosin, a ubiquitous arthropod-derived molecule, as an immunobiologically relevant dectin-1 ligand that normally serves to restrain IL-33 release and dampen type 2 immunity in healthy individuals. However, invertebrate tropomyosin presented in the context of impaired dectin-1 function, as observed in allergic individuals, leads to unrestrained IL-33 secretion and skewing of immune responses toward type 2 immunity. Collectively, we uncover a previously unrecognized mechanism of protection against allergy to a conserved recognition element omnipresent in our environment.

We review the current status of the radioisotopes program at the Soreq Applied Research Accelerator Facility (SARAF), where we utilize an electrostatic-ion-beam trap and a magneto-optical trap for studying the nuclear $\beta$-decay from trapped radioactive atoms and ions. The differential energy spectra of $\beta$'s and recoil ions emerging from the decay is sensitive to beyond standard model interactions and is complementary to high energy searches. The completed facility SARAF-II will be one of the world's most powerful deuteron, proton and fast neutron sources, producing light radioactive isotopes in unprecedented amounts, needed for obtaining enough statistics for a high precision measurement.

Studying the complex mechanisms underlying breast cancer metastasis and therapy response necessitates relevant in vivo models, particularly syngeneic models with an intact immune system. Two syngeneic spontaneously metastatic sublines, D2A1-m1 and D2A1-m2, were generated from the poorly metastasising BALB/c-derived D2A1 cell line by serial in vivo passaging. In vivo and in vitro analyses revealed distinct and shared characteristics of the metastatic D2A1-m1 and D2A1-m2 sublines. In particular, D2A1-m1 cells are more aggressive in experimental metastasis assays, while D2A1-m2 cells are more efficient at disseminating from the primary tumour in spontaneous metastasis assays. Surprisingly, classical metastasis-associated in vitro phenotypes, such as enhanced proliferation, migration and invasion, are reduced in the sublines compared to the parental cell line. Further, evasion of immune control cannot fully explain their enhanced metastatic properties. By contrast, both sublines show increased resistance to apoptosis when cultured in non-adherent conditions and, for the D2A1-m2 subline, increased 3D tumour spheroid growth. Moreover, the enhanced spontaneous metastatic phenotype of the D2A1-m2 subline is associated with an increased ability to recruit an activated tumour stroma. The metastatic D2A1-m1 and D2A1-m2 cell lines provide additional syngeneic models for investigating the different steps of the metastatic cascade and thereby represent valuable tools for breast cancer researchers. Finally, this study highlights that morphology and cell behaviour in 2D cell-based assays cannot be used as a reliable predictor of metastatic behaviour in vivo.

ABSTRACT In Lao People’s Democratic Republic (Lao PDR), reports on disease frequency are very limited. This study aimed to report frequencies of the main cause of admission among inpatients of a tertiary general hospital (Mittaphab Hospital) in Vientiane. Subjects were inpatients who were admitted from January 3 to February 2 in 2017. The dataset were made as a pilot run to establish hospital statistics. The data on sex, age, address (province), dates of admission and discharge, and main diagnosis were collected from paper-based medical charts. International Classification of Diseases 10 was applied for classifying the main diagnosis. During the 1-month period, 1,201 inpatients (637 males and 564 females) were admitted, including 171 (14.2%) aged <20 years and 254 (21.1%) aged ≥60 years. About 20% patients were from outside of Vientiane. Among them, 67.5% (62.5% in males and 73.8% in females) were admitted within 7 days. The main causes with more than 10% in males were injury and poisoning S00-T98 (49.8%), while those in females were injury and poisoning S00-T98 (25.2%), pregnancy and childbirth O00-O99 (19.0%), and diseases of genitourinary system N00-N99 (13.7%). Injury and poisoning S00-T98 among inpatients aged <20 years was 81.8% in males and 59.0% in females. Among those aged 20–59 years, it was 49.9% and 22.4%, and among those aged ≥60 years it was 22.3% and 16.9%, respectively. This is the first report on the frequencies of main diseases among inpatients in Lao PDR. Injury was the first main cause of admission at the tertiary hospital.

This preregistered study tested three theoretical proposals for how children form productive yet restricted linguistic generalizations, avoiding errors such as *The clown laughed the man, across three age groups (5–6 years, 9–10 years, adults) and five languages (English, Japanese, Hindi, Hebrew and K'iche'). Participants rated, on a five-point scale, correct and ungrammatical sentences describing events of causation (e.g., *Someone laughed the man; Someone made the man laugh; Someone broke the truck; ?Someone made the truck break). The verb-semantics hypothesis predicts that, for all languages, by-verb differences in acceptability ratings will be predicted by the extent to which the causing and caused event (e.g., amusing and laughing) merge conceptually into a single event (as rated by separate groups of adult participants). The entrenchment and preemption hypotheses predict, for all languages, that by-verb differences in acceptability ratings will be predicted by, respectively, the verb's relative overall frequency, and frequency in nearly-synonymous constructions (e.g., X made Y laugh for *Someone laughed the man). Analysis using mixed effects models revealed that entrenchment/preemption effects (which could not be distinguished due to collinearity) were observed for all age groups and all languages except K'iche', which suffered from a thin corpus and showed only preemption sporadically. All languages showed effects of event-merge semantics, except K'iche' which showed only effects of supplementary semantic predictors. We end by presenting a computational model which successfully simulates this pattern of results in a single discriminative-learning mechanism, achieving by-verb correlations of around r = 0.75 with human judgment data.

The protein kinase Akt controls myriad signaling processes in cells, ranging from growth and proliferation to differentiation and metabolism. Akt is activated by a combination of binding to the lipid second messenger PI(3,4,5)P3 and its subsequent phosphorylation by phosphoinositide-dependent kinase 1 and mechanistic target of rapamycin complex 2. The relative contributions of these mechanisms to Akt activity and signaling have hitherto not been understood. Here, we show that phosphorylation and activation by membrane binding are mutually interdependent. Moreover, the converse is also true: Akt is more rapidly dephosphorylated in the absence of PIP3, an autoinhibitory process driven by the interaction of its PH and kinase domains. We present biophysical evidence for the conformational changes in Akt that accompany its activation on membranes, show that Akt is robustly autoinhibited in the absence of PIP3 irrespective of its phosphorylation, and map the autoinhibitory PH−kinase interface. Finally, we present a model for the activation and inactivation of Akt by an ordered series of membrane binding, phosphorylation, dissociation, and dephosphorylation events. Significance Akt is a paradigmatic lipid-activated kinase, which is frequently hyperactivated in human cancer. In the absence of PI(3,4,5)P3 or PI(3,4)P2, Akt is maintained in an inactive conformation by an inhibitory interaction between its membrane-binding PH domain and its kinase domain. Here, we describe the conformational changes associated with its binding to PI(3,4,5)P3, leading to disruption of the inhibitory PH−kinase interface, and its consequent activation by protein kinases. Intriguingly, we find that reversal of those conformational changes promotes its inactivation by protein phosphatases. The activation of Akt is thereby restricted to discrete membrane locations, and it is rapidly inactivated upon dissociation. We propose a model in which activation, substrate phosphorylation, and inactivation of Akt are tightly coupled to the membrane.