307 research outputs found
Operationalising a Threshold Concept in Economics: A Pilot Study Using Multiple Choice Questions on Opportunity Cost
This paper addresses the emerging educational framework that envisions threshold concepts as mediators of learning outcomes. While the threshold concepts framework is highly appealing on a theoretical level, few researchers have attempted to measure threshold concept acquisition empirically. Achieving this would open a new arena for exploration and debate in the threshold concepts field, and provide potential results to inform teaching practice. We begin the process of operationalising threshold concepts in economics by attempting to measure students' grasp of the threshold concept of opportunity cost in an introductory economics class. We suggest two potential measures and correlate them with an array of ex ante and ex post variables, including students' expectations of success, prior misconceptions about economics and the work of economists, and actual success in the course. Results cast new light onto the factors that influence the acquisition of threshold concepts, the relationship between threshold concept acquisition and final learning outcomes, and the empirical viability of threshold concepts generally.
Targeted redox inhibition of protein phosphatase 1 by Nox4 regulates eIF2a-mediated stress signaling
Source: doi: 10.15252/embj.201592394Phosphorylation of translation initiation factor 2α (eIF2α) attenuates global protein synthesis but enhances translation of activating transcription factor 4 (ATF4) and is a crucial evolutionarily conserved adaptive pathway during cellular stresses. The serine–threonine protein phosphatase 1 (PP1) deactivates this pathway whereas prolonging eIF2α phosphorylation enhances cell survival. Here, we show that the reactive oxygen species‐generating NADPH oxidase‐4 (Nox4) is induced downstream of ATF4, binds to a PP1‐targeting subunit GADD34 at the endoplasmic reticulum, and inhibits PP1 activity to increase eIF2α phosphorylation and ATF4 levels. Other PP1 targets distant from the endoplasmic reticulum are unaffected, indicating a spatially confined inhibition of the phosphatase. PP1 inhibition involves metal center oxidation rather than the thiol oxidation that underlies redox inhibition of protein tyrosine phosphatases. We show that this Nox4‐regulated pathway robustly enhances cell survival and has a physiologic role in heart ischemia–reperfusion and acute kidney injury. This work uncovers a novel redox signaling pathway, involving Nox4–GADD34 interaction and a targeted oxidative inactivation of the PP1 metal center, that sustains eIF2α phosphorylation to protect tissues under stress
Large enhancement of deuteron polarization with frequency modulated microwaves
We report a large enhancement of 1.7 in deuteron polarization up to values of
0.6 due to frequency modulation of the polarizing microwaves in a two liters
polarized target using the method of dynamic nuclear polarization. This target
was used during a deep inelastic polarized muon-deuteron scattering experiment
at CERN. Measurements of the electron paramagnetic resonance absorption spectra
show that frequency modulation gives rise to additional microwave absorption in
the spectral wings. Although these results are not understood theoretically,
they may provide a useful testing ground for the deeper understanding of
dynamic nuclear polarization.Comment: 10 pages, including the figures coming in uuencoded compressed tar
files in poltar.uu, which also brings cernart.sty and crna12.sty files neede
Spin Structure of the Proton from Polarized Inclusive Deep-Inelastic Muon-Proton Scattering
We have measured the spin-dependent structure function in inclusive
deep-inelastic scattering of polarized muons off polarized protons, in the
kinematic range and . A
next-to-leading order QCD analysis is used to evolve the measured
to a fixed . The first moment of at is .
This result is below the prediction of the Ellis-Jaffe sum rule by more than
two standard deviations. The singlet axial charge is found to be . In the Adler-Bardeen factorization scheme, is
required to bring in agreement with the Quark-Parton Model. A
combined analysis of all available proton and deuteron data confirms the
Bjorken sum rule.Comment: 33 pages, 22 figures, uses ReVTex and smc.sty. submitted to Physical
Review
Crohn's disease adherent-invasive Escherichia coli colonize and induce strong gut inflammation in transgenic mice expressing human CEACAM
Abnormal expression of CEACAM6 is observed at the apical surface of the ileal epithelium in Crohn's disease (CD) patients, and CD ileal lesions are colonized by pathogenic adherent-invasive Escherichia coli (AIEC). We investigated the ability of AIEC reference strain LF82 to colonize the intestinal mucosa and to induce inflammation in CEABAC10 transgenic mice expressing human CEACAMs. AIEC LF82 virulent bacteria, but not nonpathogenic E. coli K-12, were able to persist in the gut of CEABAC10 transgenic mice and to induce severe colitis with reduced survival rate, marked weight loss, increased rectal bleeding, presence of erosive lesions, mucosal inflammation, and increased proinflammatory cytokine expression. The colitis depended on type 1 pili expression by AIEC bacteria and on intestinal CEACAM expression because no sign of colitis was observed in transgenic mice infected with type 1 pili–negative LF82-ΔfimH isogenic mutant or in wild-type mice infected with AIEC LF82 bacteria. These findings strongly support the hypothesis that in CD patients having an abnormal intestinal expression of CEACAM6, AIEC bacteria via type 1 pili expression can colonize the intestinal mucosa and induce gut inflammation. Thus, targeting AIEC adhesion to gut mucosa represents a new strategy for clinicians to prevent and/or to treat ileal CD
Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF
The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at
the Fermilab Long-Baseline Neutrino Facility (LBNF) is described
Effect of oral lactulose on clinical and immunohistochemical parameters in patients with inflammatory bowel disease: a pilot study
<p>Abstract</p> <p>Background</p> <p>The prebiotic potential of lactulose is well established and preclinical studies demonstrated a protective effect of lactulose in murine models of colitis. The aim of the present study was to investigate the clinical and histological efficacy of lactulose in patients with inflammatory bowel disease (IBD), for which probiotic therapy yielded promising results.</p> <p>Methods</p> <p>Patients were treated with standard medication alone or combined with 10 g lactulose daily as adjuvant therapy for 4 months. Clinical efficacy of treatment was assessed using clinical activity indices, a quality of life index (IBDQ), endoscopic scores, defecation frequency and monitoring corticosteroid medication. Orsomucoid, alpha1-antitrypsin and other laboratory parameters were determined. In addition, in some participants colonic biopsies were analyzed with haematoxylin-eosin staining or with antibodies against HLA-DR, CD68, IgA and CD3, and evaluated systematically. All measurements were performed both at enrolment and at the end of the trial.</p> <p>Results</p> <p>14 patients presenting ulcerative colitis (UC) and 17 patients presenting Crohn's disease (CD), most of them in a clinically active state, were enrolled in this pilot study. After 4 month no significant improvement of clinical activity index, endoscopic score or immunohistochemical parameters was observed in CD or UC patients receiving lactulose in comparison to the control group. However, significant improvement of quality of life was observed in UC patients receiving lactulose compared to the control group (p = 0.04).</p> <p>Conclusion</p> <p>The findings of the present pilot study indicate that oral lactulose has no beneficial effects in IBD patients in particular with regard to clinical activity, endoscopic score or immunohistochemical parameters. The importance of the beneficial effect of lactulose in UC patients regarding the quality of life needs further evaluation in larger controlled clinical trials.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN92101486</p
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
Predicting Landscape-Genetic Consequences of Habitat Loss, Fragmentation and Mobility for Multiple Species of Woodland Birds
Inference concerning the impact of habitat fragmentation on dispersal and gene flow is a key theme in landscape genetics. Recently, the ability of established approaches to identify reliably the differential effects of landscape structure (e.g. land-cover composition, remnant vegetation configuration and extent) on the mobility of organisms has been questioned. More explicit methods of predicting and testing for such effects must move beyond post hoc explanations for single landscapes and species. Here, we document a process for making a priori predictions, using existing spatial and ecological data and expert opinion, of the effects of landscape structure on genetic structure of multiple species across replicated landscape blocks. We compare the results of two common methods for estimating the influence of landscape structure on effective distance: least-cost path analysis and isolation-by-resistance. We present a series of alternative models of genetic connectivity in the study area, represented by different landscape resistance surfaces for calculating effective distance, and identify appropriate null models. The process is applied to ten species of sympatric woodland-dependant birds. For each species, we rank a priori the expectation of fit of genetic response to the models according to the expected response of birds to loss of structural connectivity and landscape-scale tree-cover. These rankings (our hypotheses) are presented for testing with empirical genetic data in a subsequent contribution. We propose that this replicated landscape, multi-species approach offers a robust method for identifying the likely effects of landscape fragmentation on dispersal
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