CoCREATE: Collaborative Curriculum Reimagining and Enhancement Aiming to Transform Education

The establishment of TU Dublin in January 2019 provided a unique opportunity to create a bespoke curriculum framework for students, staff and stakeholders of TU Dublin, produced by the students, staff and stakeholders of TU Dublin. A curriculum framework is a set of guiding values that inform the design of teaching and learning activities within TU Dublin. A Teaching Fellowship Team, comprising eighteen teaching academics from across the three TU Dublin campuses and supported extensively by the Learning Teaching and Technology Centre (LTTC), was formed to collaboratively craft, in partnership with all stakeholders, a curriculum framework for TU Dublin. Working collaboratively under the project name CoCREATE (Collaborative Curriculum Reimagining and Enhancement Aiming to Transform Education) the Teaching Fellowship Team developed TU Dublin’s CoCREATED Curriculum Framework over eighteen months. The design and development of the CoCREATED Curriculum Framework was informed by consultation with all key stakeholders across all campuses, examination and synthesis of local, national and international best practice and policy, as well as relevant scholarly literature. The framework is underpinned by the core values and mission of TU Dublin, as well as local and national strategic plans. It provides a distinctive but tangible learning philosophy for all at TU Dublin. The framework is both considered, flexible and progressive so as to adapt to the diversity within TU Dublin, including accredited programmes, and is inclusive of all learners across the university. The four curriculum values of the TU Dublin CoCREATED Curriculum Framework are: Step forward and try new things Use all of our talents; everyone has something to learn and something to teach Make our learning experience active, useful and related to the world Create the space and time to do work that matters This new, dynamic and evolving TU Dublin CoCREATED Curriculum Framework characterises an innovative, responsive and caring learning environment for the diversity of our university’s student population across all programme levels. Simultaneously, it developed a synergy between staff, students, professional bodies, industry and community partners through a collaborative design process. It is as inspiring, distinctive and pioneering as Ireland’s first Technological University. The CoCREATED Curriculum Framework will support staff and students to develop a unique approach to teaching and learning, which will characterise a TU Dublin teaching and learning experience, and ultimately a TU Dublin graduate, in a competitive national and international higher education space. Going forward, the TU Dublin CoCREATED Curriculum Framework will empower the judicious creation of rich and diverse curricula across all disciplines and levels within TU Dublin, from apprenticeship, through undergraduate, to structured PhD

Long-Term ERK Inhibition in

Induction of compensatory mechanisms and ERK reactivation has limited the effectiveness of Raf and MEK inhibitors in -mutant cancers. We determined that direct pharmacologic inhibition of ERK suppressed the growth of a subset of -mutant pancreatic cancer cell lines and that concurrent phosphatidylinositol 3-kinase (PI3K) inhibition caused synergistic cell death. Additional combinations that enhanced ERK inhibitor action were also identified. Unexpectedly, long-term treatment of sensitive cell lines caused senescence, mediated in part by MYC degradation and p16 reactivation. Enhanced basal PI3K-AKT-mTOR signaling was associated with de novo resistance to ERK inhibitor, as were other protein kinases identified by kinome-wide siRNA screening and a genetic gain-of-function screen. Our findings reveal distinct consequences of inhibiting this kinase cascade at the level of ERK

An agenda for creative practice in the new mobilities paradigm

Creative practices have made a standing contribution to mobilities research. We write this article as a collective of 25 scholars and practitioners to make a provocation: to further position creative mobilities research as a fundamental contribution and component in this field. The article explores how creative forms of research—whether in the form of artworks, exhibitions, performances, collaborations, and more—has been a foundational part of shaping the new mobilities paradigm, and continues to influence its methodological, epistemological, and ontological concerns. We tour through the interwoven history of art and mobilities research, outlining five central contributions that creativity brings. Through short vignettes of each author’s creative practice, we discuss how creativity has been key to the evolution and emergence of how mobilities research has expanded to global audiences of scholars, practitioners, and communities. The article concludes by highlighting the potency of the arts for lively and transdisciplinary pathways for future mobilities research in the uncertainties that lay ahead

HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype.

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.0 × 10-8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification

Early In-Hospital Mortality following Trainee Doctors' First Day at Work

BACKGROUND:There is a commonly held assumption that early August is an unsafe period to be admitted to hospital in England, as newly qualified doctors start work in NHS hospitals on the first Wednesday of August. We investigate whether in-hospital mortality is higher in the week following the first Wednesday in August than in the previous week. METHODOLOGY:A retrospective study in England using administrative hospital admissions data. Two retrospective cohorts of all emergency patients admitted on the last Wednesday in July and the first Wednesday in August for 2000 to 2008, each followed up for one week. PRINCIPAL FINDINGS:The odds of death for patients admitted on the first Wednesday in August was 6% higher (OR 1.06, 95% CI 1.00 to 1.15, p=0.05) after controlling for year, gender, age, socio-economic deprivation and co-morbidity. When subdivided into medical, surgical and neoplasm admissions, medical admissions admitted on the first Wednesday in August had an 8% (OR 1.08, 95% CI 1.01 to 1.16, p=0.03) higher odds of death. In 2007 and 2008, when the system for junior doctors' job applications changed, patients admitted on Wednesday August 1(st) had 8% higher adjusted odds of death than those admitted the previous Wednesday, but this was not statistically significant (OR 1.08, 95% CI 0.95 to 1.23, p=0.24). CONCLUSIONS:We found evidence that patients admitted on the first Wednesday in August have a higher early death rate in English hospitals compared with patients admitted on the previous Wednesday. This was higher for patients admitted with a medical primary diagnosis

Diversification in the inositol tris/tetrakisphosphate kinase (ITPK) family: crystal structure and enzymology of the outlier AtITPK4

Myo-inositol tris/tetrakisphosphate kinases (ITPKs) catalyze diverse phosphotransfer reactions with myo-inositol phosphate and myo-inositol pyrophosphate substrates. However, the lack of structures of nucleotide-coordinated plant ITPKs thwarts a rational understanding of phosphotransfer reactions of the family. Arabidopsis possesses a family of four ITPKs of which two isoforms, ITPK1 and ITPK4, control inositol hexakisphosphate and inositol pyrophosphate levels directly or by provision of precursors. Here, we describe the specificity of Arabidopsis ITPK4 to pairs of enantiomers of diverse inositol polyphosphates and show how substrate specificity differs from Arabidopsis ITPK1. Moreover, we provide a description of the crystal structure of ATP-coordinated AtITPK4 at 2.11 Å resolution that, along with a description of the enantiospecificity of the enzyme, affords a molecular explanation for the diverse phosphotransferase activity of this enzyme. That Arabidopsis ITPK4 has a KM for ATP in the tens of micromolar range, potentially explains how, despite the large-scale abolition of InsP6, InsP7 and InsP8 synthesis in Atitpk4 mutants, Atitpk4 lacks the phosphate starvation responses of Atitpk1 mutants. We further demonstrate that Arabidopsis ITPK4 and its homologues in other plants possess an N-terminal haloacid dehalogenase-like fold not previously described. The structural and enzymological information revealed will guide elucidation of ITPK4 function in diverse physiological contexts, including InsP8-dependent aspects of plant biology

2018: Art & Mobilities Network Inaugural Symposium Instant Journal (Peter Scott Gallery)

"Mobilities has been gaining momentum through networks, conferences, books, special issues, exhibitions and in the practices of artists, writers and curators. In recognition of this activity we are forming an Art & Mobilities network through which to consolidate, celebrate and develop this work.Inspired by the recent foregrounding of Mobility and the Humanities (Pearce & Merriman, 2018) and drawing on last November's successful Mobile Utopia Exhibition amongst others, the Centre for Mobilities Research (CEMORE) at Lancaster University are pleased to hold a UK Art & Mobilities Network Inaugural Symposium 2018 on the 3rd of July 2018. The aim of the symposium is to bring together people in the UK who are active in the field of mobilities and art in order to discuss the distinctive contribution that art makes to mobilities research and vice versa. We would be delighted if you can join us for this one-day event to help shape the network, particularly in the context of a fast-changing world, not just socio-politically but in terms of the place of art in the academy and vice versa. There are nearly 30 key international artists and researchers gathered on this day both locally and via Skype. We invite all participants in the symposium to bring with them an artwork, artefact, written statement or quote that can be displayed as a ‘pop up’ exhibition. These artefacts will be used during the day to focus discussion around different facets of mobilities and art." (Jen Southern, Kai Syng Tan, Emma Rose, Linda O'Keeffe Editors

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

High-resolution profiling of homing endonuclease binding and catalytic specificity using yeast surface display

Experimental analysis and manipulation of protein–DNA interactions pose unique biophysical challenges arising from the structural and chemical homogeneity of DNA polymers. We report the use of yeast surface display for analytical and selection-based applications for the interaction between a LAGLIDADG homing endonuclease and its DNA target. Quantitative flow cytometry using oligonucleotide substrates facilitated a complete profiling of specificity, both for DNA-binding and catalysis, with single base pair resolution. These analyses revealed a comprehensive segregation of binding specificity and affinity to one half of the pseudo-dimeric interaction, while the entire interface contributed specificity at the level of catalysis. A single round of targeted mutagenesis with tandem affinity and catalytic selection steps provided mechanistic insights to the origins of binding and catalytic specificity. These methods represent a dynamic new approach for interrogating specificity in protein–DNA interactions

Setting our sights on infectious diseases

In May 2019, the Wellcome Centre for Anti-Infectives Research (WCAIR) at the University of Dundee, UK, held an international conference with the aim of discussing some key questions around discovering new medicines for infectious diseases and a particular focus on diseases affecting Low and Middle Income Countries. There is an urgent need for new drugs to treat most infectious diseases. We were keen to see if there were lessons that we could learn across different disease areas and between the preclinical and clinical phases with the aim of exploring how we can improve and speed up the drug discovery, translational, and clinical development processes. We started with an introductory session on the current situation and then worked backward from clinical development to combination therapy, pharmacokinetic/pharmacodynamic (PK/PD) studies, drug discovery pathways, and new starting points and targets. This Viewpoint aims to capture some of the learnings