Both RalA and RalB interact with the ubiquitous calcium sensor, calmodulin (CaM). New structural and biophysical characterisation of these interactions strongly suggests that, in the native membrane‐associated state, only RalA can be extracted from the membrane by CaM and this non‐canonical interaction could underpin the divergent signalling roles of these closely related GTPases. The isoform specificity for RalA exhibited by CaM is hypothesised to contribute to the disparate signalling roles of RalA and RalB in mitochondrial dynamics. This would lead to (...) CaM shuttling RalA to the mitochondrial membrane but leaving RalB localisation unperturbed, and in doing so triggering mitochondrial fission pathways rather than mitophagy. (shrink)

New Zealand is a multilingual and multicultural society, where English, Maori, and the New Zealand sign language are designated as its official languages. However, some heritage languages are also taught either within or outside the national education system. During the past decade, an increasing number of students have chosen Mandarin Chinese as an additional language because of its fast-growing importance. To date, studies regarding CAL are mainly based on the mainstream Chinese programs or online platforms, with less attention paid to (...) other types of teaching contexts where there also exist many potential challenges awaiting teachers. To fill in this gap, this study, based on a teaching program consisting of two families in New Zealand, explored the trajectories of a CAL teacher’s emotional labor for 47 weeks to understand how she managed her emotions when she taught the language as well as balanced the relationship among the three parties: the institution, the two families, and herself. Narrative inquiry was used as a methodological approach. The data involved written and spoken narratives. Using inductive and deductive thematic analysis, findings revealed her different understandings of the emotional labor in the two families, respectively, during the program. Further analysis of the data revealed some factors that impacted her emotional labor and how they impacted her teaching in a family-based context. We concluded our study with a discussion of the implications of these findings for teaching CAL in similar contexts. (shrink)

Many clinical and psychological constructs are conceptualized to have multivariate higher-order constructs that give rise to multidimensional lower-order traits. Although recent measurement models and computing algorithms can accommodate item response data with a higher-order structure, there are few measurement models and computing techniques that can be employed in the context of complex research synthesis, such as meta-analysis of individual participant data or integrative data analysis. The current study was aimed at modeling complex item responses that can arise when underlying domain-specific, (...) lower-order traits are hierarchically related to multiple higher-order traits for individual participant data from multiple studies. We formulated a multi-group, multivariate higher-order item response theory (HO-IRT) model from a Bayesian perspective and developed a new Markov chain Monte Carlo (MCMC) algorithm to simultaneously estimate the (a) structural parameters of the first- and second-order latent traits across multiple groups and (b) item parameters of the model. Results from a simulation study support the feasibility of the MCMC algorithm. From the analysis of real data, we found that a bivariate HO-IRT model with different correlation/covariance structures for different studies fit the data best, compared to a univariate HO-IRT model or other alternate models with unreasonable assumptions (i.e., the same means and covariances across studies). Although more work is needed to further develop the method and to disseminate it, the multi-group multivariate HO-IRT model holds promise to derive a common metric for individual participant data from multiple studies in research synthesis studies for robust inference and for new discoveries. (shrink)

The life-long correspondence of David K. Lewis, one of the most influential philosophers of the twentieth century, reveals the development, breadth, and depth of his philosophy in its historical context. The second of this two volume collection focuses on his contributions to philosophical questions of language, mind, and epistemology.

David K. Lewis (1941-2001) was unquestionably one of the most important analytic philosophers of the twentieth century, writing papers and books, largely but not exclusively in metaphysics, that set the intellectual agenda across a huge variety of topics in the last three decades. Some twenty years after his death, this collection of essays reflects the historical importance of Lewis's work by bringing together a range of scholarly reflections on his work. The essays consider a range of topics including the nature (...) of metaphysics, the epistemology of necessary truths, possibility, naturalness, supervenience, time travel, causation, semantics, and ethics. Several of them draw on an exciting new body of material in the Lewisian corpus, his extensive correspondence, recently published in two volumes (OUP, 2020). The wide-ranging topics of these essays illustrate the impressive extent of Lewis's thought and his reach across most areas of analytic philosophy. The chapters collected in this volume adds to the increasing literature on the philosophy of David K. Lewis and will be an important book for those examining his role in the history of analytic philosophy. (shrink)

Over the past several decades, nurses have been increasingly theorizing about the relationships between culture, health, and nursing practice. This culture theorizing has changed over time and has recently been subject to much critical examination. The purpose of this paper is to identify the challenges impeding nurses' ability to build theory about the relationships between culture and health. Through a historical overview, I argue that continued support for the essentialist view of culture can maintain a limited view of complex race (...) relations. I also argue that attempts to apply culture theory, without knowledge of important historical, political, and economic factors, has often resulted in oversimplified versions of what was originally intended. Furthermore, I argue that individual-level interventions alone will be insufficient to address health inequities related to culture. Despite new critical conceptualizations of culture and the uptake of cultural safety, nursing scholars must better address the broader organizational, population, and political interventions needed to address inequities in health. I conclude with suggestions for how nurses might proceed with culture theorizing given these challenges. (shrink)

BackgroundSarcomas are a diverse group of neoplasms that vary greatly in clinical presentation and responsiveness to treatment. Given the differences in the sites of involvement, rarity, and treatment modality, a multidisciplinary approach is required. Previous literature suggests patients with sarcoma suffer from poorer quality of life especially physical and functional wellbeing. Adolescent and young adult patients are an underrepresented population in cancer research and have differing factors influencing QoL.MethodsRetrospective analysis of Young Adult patients enrolled in the Sarcoma Tissue Repository at (...) University of Iowa. QoL was assessed using the self-report FACT-G questionnaire at enrollment and 12 months post-diagnosis; overall scores and the 4 wellbeing subscales were calculated. Linear mixed effects models were used to measure the association between the rate of change in FACT-G subscale scores and baseline clinical, comorbidity, and treatment characteristics.Results49 patients were identified. 57.1% of patients had a malignancy involving an extremity. Mean FACT-G scores of overall wellbeing improved from baseline to 12 months. Social and emotional wellbeing did not differ significantly between baseline and 12 months. Physical wellbeing and functional wellbeing scores improved from baseline to 12 months. No difference was seen for FACT-G overall scores for age, sex, laterality, marital status, performance status, having children, clinical stage, limb surgery, chemotherapy, or tumor size. A difference was demonstrated in physical wellbeing scores for patients with baseline limitation compared to those with no baseline limitation. A difference was demonstrated in social wellbeing based on anatomical site.ConclusionYoung adults with sarcoma treated at a tertiary center had improvements in overall reported QoL at 12 months from diagnosis. Overall baseline QoL scores on FACT-G were lower than the general adult population for YA patients with sarcoma but at 12 months became in line with general population norms. The improvements seen merit further investigation to evaluate how these change over the continuum of care. Quality of life changes may be useful outcomes of interest in sarcoma trials. (shrink)

How We Fight: Ethics in War contains ten groundbreaking essays by some of the leading philosophers of war. The essays offer new perspectives on key debates including pacifism, punitive justifications for war, the distribution of risk between combatants and non-combatants, the structure of 'just war theory', and bases of individual liability in war.

The life-long correspondence of David K. Lewis, one of the most influential philosophers of the twentieth century, reveals the development, breadth, and depth of his philosophy in its historical context. The first of this two volume collection of letters focuses on his contributions to metaphysics, arguably where he made his greatest impact.

Herrera-Ferrá et al.’s (2023) attention to the cultural context of the neurorights movement contributes to the growing conversation on establishing neurorights in response to advancements in neuros...

© Ginn et al. 2016.The indexing methods currently used for serial femtosecond crystallography were originally developed for experiments in which crystals are rotated in the X-ray beam, providing significant three-dimensional information. On the other hand, shots from both X-ray free-electron lasers and serial synchrotron crystallography experiments are still images, in which the few three-dimensional data available arise only from the curvature of the Ewald sphere. Traditional synchrotron crystallography methods are thus less well suited to still image data processing. Here, a (...) new indexing method is presented with the aim of maximizing information use from a still image given the known unit-cell dimensions and space group. Efficacy for cubic, hexagonal and orthorhombic space groups is shown, and for those showing some evidence of diffraction the indexing rate ranged from 90% to 151%. Here, the indexing rate refers to the number of lattices indexed per image. (shrink)

Decentralized autonomous organizations (DAOs) are a new, rapidly-growing class of organizations governed by smart contracts. Here we describe how researchers can contribute to the emerging science of DAOs and other digitally-constituted organizations. From granular privacy primitives to mechanism designs to model laws, we identify high-impact problems in the DAO ecosystem where existing gaps might be tackled through a new data set or by applying tools and ideas from existing research fields such as political science, computer science, economics, law, and organizational (...) science. Our recommendations encompass exciting research questions as well as promising business opportunities. We call on the wider research community to join the global effort to invent the next generation of organizations. (shrink)

In this paper, we explore best practices for asynchronous discussions in graduate online bioethics education. We explain that online approaches have advantages and challenges in contrast to in-person discussions. Online challenges are lack of visual or auditory cues and technical access. Advantages include extended opportunities for specific focus, thoughtful reflection, and critical review. We found no significant review of related best practices in bioethics. Our more general literature review of graduate education and online approaches, plus experience in our own bioethics (...) graduate program, suggest provisional best practices that we detail. We reason that online graduate discussion provisionally should aim for a “community of inquiry” framework that incorporates cognitive, social, and teaching “presences,” as well as a learning presence. However, we also note unresolved concerns about whether the framework sufficiently addresses learning, is complete, and captures communicative functions. Drawing further on the literature, we also suggest best practices for instructor feedback to students about their discussion performance, including that remarks should be timely and specific. Summaries from two courses in our graduate bioethics program illustrate how we implement discussion strategies. Finally, we review assessment strategies and suggest that embedded formative assessments in discussion support and demonstrate deeper learning. Limitations in generalizability include that our review targets asynchronous and text-based online discussion, our program assessments do not necessarily detail best practices, student expectations and approaches could be rather particular to our program, and specific bioethics content in principle could alter best practices. (shrink)

Distinguished contributors take up eminent scholar Daniel R. Schwarz’s reading of modern fiction and poetry as mediating between human desire and human action. The essayists follow Schwarz’s advice, “always the text, always historicize,” thus making this book relevant to current debates about the relationships between literature, ethics, aesthetics, and historical contexts.

Substantial research efforts have been devoted to developing a cure for autism, but some advocates of people with autism claim that these efforts are misguided and even harmful. They claim that there is nothing wrong with people with autism, so there is nothing to cure. Others argue that autism is a serious and debilitating disorder and that a cure for autism would be a wonderful medical breakthrough. Our goal in this essay is to evaluate what assumptions underlie each of these (...) positions. We evaluate the arguments made on each side, reject those that are implausible and then highlight the key assumptions of those that remain. (shrink)

How might artificial neural networks (ANNs) inform cognitive science? Often cognitive scientists use ANNs but do not examine their internal structures. In this paper, we use ANNs to explore how cognition might represent musical properties. We train ANNs to classify musical chords, and we interpret network structure to determine what representations ANNs discover and use. We find connection weights between input units and hidden units can be described using Fourier phase spaces, a representation studied in musical set theory. We find (...) the total signal coming through these weighted connection weights is a measure of the similarity between two Fourier structures: the structure of the hidden unit's weights and the structure of the stimulus. This is surprising because neither of these Fourier structures is computed by the hidden unit. We then show how output units use such similarity measures to classify chords. However, we also find different types of units—units that use different activation functions—use this similarity measure very differently. This result, combined with other findings, indicates that while our networks are related to the Fourier analysis of musical sets, they do not perform Fourier analyses of the kind usually described in musical set theory. Our results show Fourier representations of music are not limited to musical set theory. Our results also suggest how cognitive psychologists might explore Fourier representations in musical cognition. Critically, such theoretical and empirical implications require researchers to understand how network structure converts stimuli into responses. (shrink)