Understanding the Internet: Model, Metaphor, and Analogy

published or submitted for publicatio

Introduction to Library Trends 50 (1) Summer 2001: Computer-Based Instruction in Libraries and Library Education

published or submitted for publicatio

Introduction to Library Trends 44 (2) Fall 1995: The Library and Undergraduate Education

published or submitted for publicatio

Identification of trans protein QTL for secreted airway mucins in mice and a causal role for Bpifb1

Mucus hyper-secretion is a hallmark feature of asthma and other muco-obstructive airway diseases. The mucin proteins MUC5AC and MUC5B are the major glycoprotein components of mucus and have critical roles in airway defense. Despite the biomedical importance of these two proteins, the loci that regulate them in the context of natural genetic variation have not been studied. To identify genes that underlie variation in airway mucin levels, we performed genetic analyses in founder strains and incipient lines of the Collaborative Cross (CC) in a house dust mite mouse model of asthma. CC founder strains exhibited significant differences in MUC5AC and MUC5B, providing evidence of heritability. Analysis of gene and protein expression of Muc5ac and Muc5b in incipient CC lines (n = 154) suggested that post-transcriptional events were important regulators of mucin protein content in the airways. Quantitative trait locus (QTL) mapping identified distinct, trans protein QTL for MUC5AC (chromosome 13) and MUC5B (chromosome 2). These two QTL explained 18 and 20% of phenotypic variance, respectively. Examination of the MUC5B QTL allele effects and subsequent phylogenetic analysis allowed us to narrow the MUC5B QTL and identify Bpifb1 as a candidate gene. Bpifb1 mRNA and protein expression were upregulated in parallel to MUC5B after allergen challenge, and Bpifb1 knockout mice exhibited higher MUC5B expression. Thus, BPIFB1 is a novel regulator of MUC5B

Restricted access to the NHS during the COVID-19 pandemic : is it time to move away from the rationed clinical response?

Recently a Lancet Commission examined the future prospects of the NHS in the wake of COVID-19. The report cites poor healthcare capacity and chronic staff shortages as key contributing factors to the UK’s inadequate pandemic response. Notable strengths included universal access, the goodwill of staff, and the ability to generate innovative solutions - qualities that are likely to have averted an even deeper national crisis [1]. The prosperity of the NHS is intrinsically connected to the prosperity of the nation. Access to healthcare influences morbidity, mortality, economic activity, and whether or not social restrictions are necessary [2,3]. Public health measures such as timely implementation of social distancing are also important to limit mortality, but going forward it is the capacity to respond in a clinically effective and decisive manner that is vital to diminish the threat associated with the virus [4]. The importance of examining the national clinical response to SARS-CoV-2 cannot be overstated. Arguably the greatest mistake of this pandemic would be failing to prepare for the next. There are also the looming unknowns of SARS-CoV-2 variants [5], the higher rates of Long COVID following more severe disease [6], and the increased healthcare demands associated with delayed presentation of COVID-19 pneumonia [7-11]. Improving the tolerance of society to background levels of SARS-CoV-2 will require an improved clinical response. With this in mind, we examine one aspect of the UK’s clinical response that remains in place today: restricted access to healthcare

Quantum physics meets biology

Quantum physics and biology have long been regarded as unrelated disciplines, describing nature at the inanimate microlevel on the one hand and living species on the other hand. Over the last decades the life sciences have succeeded in providing ever more and refined explanations of macroscopic phenomena that were based on an improved understanding of molecular structures and mechanisms. Simultaneously, quantum physics, originally rooted in a world view of quantum coherences, entanglement and other non-classical effects, has been heading towards systems of increasing complexity. The present perspective article shall serve as a pedestrian guide to the growing interconnections between the two fields. We recapitulate the generic and sometimes unintuitive characteristics of quantum physics and point to a number of applications in the life sciences. We discuss our criteria for a future quantum biology, its current status, recent experimental progress and also the restrictions that nature imposes on bold extrapolations of quantum theory to macroscopic phenomena.Comment: 26 pages, 4 figures, Perspective article for the HFSP Journa

Towards Constraining Glacial Isostatic Adjustment in Greenland Using ICESat and GPS Observations

Constraining glacial isostatic adjustment (GIA) i.e. the Earth’s viscoelastic response to past ice changes, is an important task, because GIA is a significant correction in gravity-based ice sheet mass balance estimates. Here, we investigate how temporal variations in the observed and modeled crustal displacements due to the Earth’s response to ongoing ice mass changes can contribute to the process of constraining GIA. We use mass change grids of the Greenland ice sheet (GrIS) derived from NASA’s high resolution Ice, Cloud and land Elevation Satellite (ICESat) data in three overlapping time spans covering the period 2004–2009 to estimate temporal variations in the elastic response due to present day ice mass loss. The modeled crustal displacements (elastic + GIA) are compared with GPS time series from five permanent sites (KELY, KULU, QAQ1, THU2, and SCOR). We find, that the modeled pattern of elastic crustal displacements shows pronounced variation during the observation period, where an increase in elastic displacement is found at the northwest coast of Greenland, while a decrease is found at the southeast coast. This pattern of temporal changes is supported by the GPS observations. We find, that the temporal behavior of the ICESat-based modeled elastic response agrees well with the GPS observations at the sites KELY, QAQ1, and SCOR. This suggests, that our elastic models are able to resolve the temporal changes in the observed uplift, which indicates that the elastic uplift models are reliable at these sites. Therefore, we conclude that these sites are useful for constraining GIA

Deweyan tools for inquiry and the epistemological context of critical pedagogy

This article develops the notion of resistance as articulated in the literature of critical pedagogy as being both culturally sponsored and cognitively manifested. To do so, the authors draw upon John Dewey\u27s conception of tools for inquiry. Dewey provides a way to conceptualize student resistance not as a form of willful disputation, but instead as a function of socialization into cultural models of thought that actively truncate inquiry. In other words, resistance can be construed as the cognitive and emotive dimensions of the ongoing failure of institutions to provide ideas that help individuals both recognize social problems and imagine possible solutions. Focusing on Dewey\u27s epistemological framework, specifically tools for inquiry, provides a way to grasp this problem. It also affords some innovative solutions; for instance, it helps conceive of possible links between the regular curriculum and the study of specific social justice issues, a relationship that is often under-examined. The aims of critical pedagogy depend upon students developing dexterity with the conceptual tools they use to make meaning of the evidence they confront; these are background skills that the regular curriculum can be made to serve even outside social justice-focused curricula. Furthermore, the article concludes that because such inquiry involves the exploration and potential revision of students\u27 world-ordering beliefs, developing flexibility in how one thinks may be better achieved within academic subjects and topics that are not so intimately connected to students\u27 current social lives, especially where students may be directly implicated

Impact of a (poly)phenol-rich extract from the brown algae Ascophyllum nodosum on DNA damage and antioxidant activity in an overweight or obese population: a randomized controlled trial

Background Epidemiologic evidence suggests that a diet rich in (poly)phenols has beneficial effects on many chronic diseases. Brown seaweed is a rich source of (poly)phenols. Objective The aim of this study was to investigate the bioavailability and effect of a brown seaweed (Ascophyllum nodosum) (poly)phenol extract on DNA damage, oxidative stress, and inflammation in vivo. Design A randomized, double-blind, placebo-controlled crossover trial was conducted in 80 participants aged 30–65 y with a body mass index (in kg/m2) ≥25. The participants consumed either a 400-mg capsule containing 100 mg seaweed (poly)phenol and 300 mg maltodextrin or a 400-mg maltodextrin placebo control capsule daily for an 8-wk period. Bioactivity was assessed with a panel of blood-based markers including lymphocyte DNA damage, plasma oxidant capacity, C-reactive protein (CRP), and inflammatory cytokines. To explore the bioavailability of seaweed phenolics, an untargeted metabolomics analysis of urine and plasma samples after seaweed consumption was determined by ultra-high-performance liquid chromatography–high-resolution mass spectrometry. Results Consumption of the seaweed (poly)phenols resulted in a modest decrease in DNA damage but only in a subset of the total population who were obese. There were no significant changes in CRP, antioxidant status, or inflammatory cytokines. We identified phlorotannin metabolites that are considered potential biomarkers of seaweed consumption including pyrogallol/phloroglucinol-sulfate, hydroxytrifurahol A-glucuronide, dioxinodehydroeckol-glucuronide, diphlorethol sulfates, C-O-C dimer of phloroglucinol sulfate, and C-O-C dimer of phloroglucinol. Conclusions To the best of our knowledge, this work represents the first comprehensive study investigating the bioactivity and bioavailability of seaweed (poly)phenolics in human participants. We identified several potential biomarkers of seaweed consumption. Intriguingly, the modest improvements in DNA damage were observed only in the obese subset of the total population. The subgroup analysis should be considered exploratory because it was not preplanned; therefore, it was not powered adequately. Elucidation of the biology underpinning this observation will require participant stratification according to weight in future studies. This trial was registered at clinicaltrials.gov as NCT02295878