Implications of substrate geometry and coating thickness on the cracking resistance of polymer-based protective coatings

Welded steel T-sections of different weld fillet geometries coated with water ballast tank protective coatings were subjected to thermal cycling with a temperature range from 60°C to -10°C. Cracks developed in the coatings at the weld line, propagating longitudinally along it. The number of cycles required to create 1 mm cracks was strongly dependent on the weld geometry and the coating Dry Film Thickness (DFT). Finite Element Modelling (FEM) was employed to calculate thermally induced strain fields in the coatings subjected to the same temperature range. FEM predicted that the greatest strain concentrations are present at the coating surface within the weld fillet region. Increased DFT and decreased fillet radius leads to increased maximum principal strains. Numerical analysis predicts that greatest strain ranges promoting the earliest cracking/failure are found in thicker coatings applied to smaller weld radii. Experimental observations confirm this

Association between aspirin use and biliary tract cancer survival

Peer reviewedPublisher PD

Public Health and the Built Environment: Historical, Empirical, and Theoretical Foundations for an Expanded Role

In 2000, the Center for Disease Control and Prevention\u27s National Center for Environmental Health issued a report that explored some of the ways in which sprawl impacts public health. The report has generated great interest, and state health officials are beginning to discuss the relationship between land use and public health. The CDC report has also produced a backlash. For example, the Southern California Building Industry Association labeled the report a ludicrous sham and argued that the CDC should stick to fighting physical diseases, not defending political ones. In this environment, it is understandable if the CDC looks to such critiques as simply the latest partisan recruit to a political debate. But critics of the CDC\u27s efforts in this area may substantially overstate their case in the other direction. There is now and has long been a demonstrated connection between health, including physical disease, and the built environment. Moreover, government has intervened in the past in response to this connection and it continues to do so. While neither past practice nor current evidence make government intervention inevitable, this paper argues that such intervention is appropriate and supported by theory as well as history and empirical evidence

Dietary nitrate and diet quality: An examination of changing dietary intakes within a representative sample of Australian women

Dietary nitrate is increasingly linked to a variety of beneficial health outcomes. Our purpose was to estimate dietary nitrate consumption and identify key dietary changes which have occurred over time within a representative sample of Australian women. Women from the 1946–1951 cohort of the Australian Longitudinal Study on Women’s Health with complete food frequency questionnaire data for both 2001 and 2013 were included for analysis. Dietary nitrate intakes were calculated using key published nitrate databases. Diet quality scores including the Australian Recommended Food Score, the Mediterranean Diet Score and the Nutrient Rich Foods Index were calculated along with food group serves as per the Australian Dietary Guidelines. Wilcoxon matched pairs tests were used to test for change in dietary intakes and Spearman’s correlations were used to examine associations. In our sample of 8161 Australian women, dietary nitrate intakes were on average 65–70 mg/day, and we detected a significant increase in dietary nitrate consumption over time (+6.57 mg/day). Vegetables were the primary source of dietary nitrate (81–83%), in particular lettuce (26%), spinach (14–20%), beetroot (10–11%), and celery (7–8%) contributed primarily to vegetable nitrate intakes. Further, increased dietary nitrate intakes were associated with improved diet quality scores (r = 0.3, p \u3c 0.0001). Although there is emerging evidence indicating that higher habitual dietary nitrate intakes are associated with reduced morbidity and mortality, future work in this area should consider how dietary nitrate within the context of overall diet quality can facilitate health to ensure consistent public health messages are conveyed

Multifocal multi-organ ischaemia and infarction in a preterm baby due to maternal intravenous cocaine use: a case report

<p>Abstract</p> <p>Introduction</p> <p>Although the adverse effects of cocaine use in pregnancy are well recognised, we believe this case highlights the importance of considering the route of administration, and suggests the possibility of multifocal damage relating to intravenous use.</p> <p>Case presentation</p> <p>A Caucasian female baby of 29-weeks' gestation was spontaneously delivered and subsequently developed multi-organ failure considered unrelated to simple prematurity. Intensive care was re-orientated following the development of massive intraventricular haemorrhage.</p> <p>Conclusion</p> <p>This case illustrates the need for regular cranial ultrasound in babies of pregnancies at risk due to intravenous cocaine use and also the necessity of counselling women who misuse cocaine in the antenatal period. As such, this article will be of most interest to paediatric and obstetric staff.</p

Bioengineered small extracellular vesicles deliver multiple SARS‐CoV‐2 antigenic fragments and drive a broad immunological response

The COVID‐19 pandemic highlighted the clear risk that zoonotic viruses pose to global health and economies. The scientific community responded by developing several efficacious vaccines which were expedited by the global need for vaccines. The emergence of SARS‐CoV‐2 breakthrough infections highlights the need for additional vaccine modalities to provide stronger, long‐lived protective immunity. Here we report the design and preclinical testing of small extracellular vesicles (sEVs) as a multi‐subunit vaccine. Cell lines were engineered to produce sEVs containing either the SARS‐CoV‐2 Spike receptor‐binding domain, or an antigenic region from SARS‐CoV‐2 Nucleocapsid, or both in combination, and we tested their ability to evoke immune responses in vitro and in vivo. B cells incubated with bioengineered sEVs were potent activators of antigen‐specific T cell clones. Mice immunised with sEVs containing both sRBD and Nucleocapsid antigens generated sRBD‐specific IgGs, nucleocapsid‐specific IgGs, which neutralised SARS‐CoV‐2 infection. sEV‐based vaccines allow multiple antigens to be delivered simultaneously resulting in potent, broad immunity, and provide a quick, cheap, and reliable method to test vaccine candidates

Manipulating transcription factors in human induced pluripotent cell-derived cells to enhance the production and the maturation of red blood cells

The most widely transfused blood component is red blood cells (RBCs), and voluntary donation is the main resource for RBC transfusion. In the UK, 7,000 units of RBCs are transfused daily but this life-saving cell therapy is completely dependent on donors and there are persistent problems associated with transfusion transmitted infections and in blood group compatibility. Furthermore, the quality, safety and efficiency of donated RBCs gradually decrease with storage time. A number of novel sources of RBCs are being explored including the production of RBCs from adult haematopoietic progenitor cells, erythroid progenitor cell lines and induced pluripotent stem cells (iPSCs). The iPSC source could essentially provide a limitless supply and a route to producing cells that are matched to the recipient. A number of protocols have been described to produce mature RBCs from human pluripotent stem cells but they are relatively inefficient and would be difficult to scale up to the levels required for clinical translation. We tested and evaluated a defined feeder- and serum-free differentiation protocol for deriving erythroid cells from hiPSCs. RBC production was not efficient, the cells that were produced did not enucleate efficiently and they expressed embryonic rather than adult globin. We hypothesised that the production of RBCs from iPSCs could be enhanced by enforced expression of erythroid-specific transcription factors (TFs). Previous studies had demonstrated that Krüppel-like factor 1 (KLF1) plays an important role in RBC development and maturation so we generated iPSC lines expressing a tamoxifen-inducible KLF1-ERT2 fusion protein. Using zinc finger nuclease technology, we targeted the expression cassette to the AAVS1 locus to ensure consistent expression levels and to avoid integration site specific effects and/or silencing. These iKLF1 iPSCs were applied to our defined RBC differentiation protocol and the activity of KLF1 was induced by adding tamoxifen. Activation of KLF1 from day 10 accelerated erythroid differentiation and maturation with an increase in the proportion of erythroblasts, a higher level of expression of erythroid genes associated with maturation and an apparently more robust morphology. However, KLF1 activation had an anti-proliferation effect resulting in significantly less cell generated overall and HPLC analysis demonstrated that KLF1-activated cells expressed higher levels of embryonic globin compared to control iPSCs-derived cells. Many of the effects that were observed when KLF1 was activated from day 10 were not observed when activated from day 18. We therefore concluded that activation of exogenous KLF1 is able to promote erythroid cell production and maturation in progenitors (day 10) but not at the later stage of erythropoiesis (day 18). We hypothesised that KLF1 might require a co-factor to regulate RBC maturation and adult globin expression at the later stage of erythropoiesis. The TF, B-cell lymphoma/leukaemia 11a (BCL11A), plays a key role in the suppression of foetal globin expression, thereby completing globin switching to adult globin. Preliminary data showed that iPSC-derived erythroid cells were able to express adult globin when transduced with a BCL11A-expressing lentiviral-vector. Based on that finding we then generated an iPSC line expressing tamoxifen-inducible BCL11AERT2 and KLF1-ERT2 fusion proteins, applied this iBK iPSC line to our differentiation protocol. Activation of both TFs from day 18 slightly increased the expression of genes associated with RBC maturation and the inclusion of BCL11A appeared to eliminate the anti-proliferation effect of KLF1. Most importantly, activation of both BCL11A and KLF1 from day 18 of the differentiation protocol increased the production of α- globin (foetal / adult globin) indicating that some definitive-like erythroid cells might be generated by activation of both TFs at the later stage of erythroid differentiation. Collectively, these findings demonstrate that enforced expression of erythroid TFs could be a useful strategy to enhance RBC maturation from iPSCs

A role for mospd1 in mesenchymal stem cell proliferation and differentiation

Mesenchymal stem cells (MSCs) isolated from many tissues including bone marrow and fat can be expanded in vitro and can differentiate into a range of different cell types such as bone, cartilage, and adipocytes. MSCs can also exhibit immunoregulatory properties when transplanted but, although a number of clinical trials using MSCs are in progress, the molecular mechanisms that control their production, proliferation, and differentiation are poorly understood. We identify MOSPD1 as a new player in this process. We generated MOSPD1‐null embryonic stem cells (ESCs) and demonstrate that they are deficient in their ability to differentiate into a number of cell lineages including osteoblasts, adipocytes, and hematopoietic progenitors. The self‐renewal capacity of MOSPD1‐null ESCs was normal and they exhibited no obvious defects in early germ layer specification nor in epithelial to mesenchymal transition (EMT), indicating that MOSPD1 functions after these key steps in the differentiation process. Mesenchymal stem cell (MSC)‐like cells expressing CD73, CD90, and CD105 were generated from MOSPD1‐null ESCs but their growth rate was significantly impaired implying that MOSPD1 plays a role in MSC proliferation. Phenotypic deficiencies exhibited by MOSPD1‐null ESCs were rescued by exogenous expression of MOSPD1, but not MOSPD3 indicating distinct functional properties of these closely related genes. Our in vitro studies were supported by RNA‐sequencing data that confirmed expression of Mospd1 mRNA in cultured, proliferating perivascular pre‐MSCs isolated from human tissue. This study adds to the growing body of knowledge about the function of this largely uncharacterized protein family and introduces a new player in the control of MSC proliferation and differentiation. Stem Cells 2015;33:3077–308

2005 AAPP Monograph Series

The African American Professors Program (AAPP) at the University of South Carolina is proud to publish the fifth edition of its annual monograph series. The program recognizes the significance of offering its scholars avenue to engage actively in research and publish papers related thereto. Parallel with the publication of their refereed manuscripts is the opportunity to gain visibility among scholars throughout institutions worldwide. Scholars who have contributed manuscripts for this monograph are to be commended for adding this additional responsibility to their academic workload. Writing across disciplines adds to the intellectual diversity of these papers. From neophytes, relatively speaking, to an array of very experienced individuals, the chapters have been researched and comprehensively written. Founded in 1997 through the Department of Educational Leadership and Policies in the College of Education, AAPP was designed to address the underrepresentation of African American professors on college and university campuses. Its mission is to expand the pool of these professors in critical academic and research areas. Sponsored by the University of South Carolina, the W. K. Kellogg Foundation, and the South Carolina General Assembly, the program recruits doctoral students for disciplines in which African Americans currently are underrepresented among faculty in higher education. The continuation of this monograph series is seen as responding to a window of opportunity to be sensitive to an academic expectation of graduates as they pursue career placement and, at the same time, one that allows for the dissemination of AAPP products to a broader community. The importance of this monograph series has been voiced by one of our 2002 AAPP graduates, Dr. Shundele LaTjuan Dogan, a recent Administrative Fellow at Harvard University and now a Program Officer for the Southern Education Foundation, Atlanta, Georgia. Dr. Dogan wrote: One thing in particular that I want to thank you for is having the African American Professors Program scholars publish articles for the monograph. I have to admit that writing the articles seemed like extra work at the time. However, in my recent interview process, organizations have asked me for samples of my writing. Including an article from a published monograph helped to make my portfolio much more impressive. You were \u27right on target\u27 in having us do the monograph series. (MPP 2003 Monograph, p. xi) The African American Professors Program offers this 2005 publication as a contribution to its readership and hopes that you will be inspired by this select group of manuscripts. John McFadden, Ph.D. The Benjamin Elijah Mays Professor Director, African American Professors Program University of South Carolinahttps://scholarcommons.sc.edu/mcfadden_monographs/1007/thumbnail.jp

Landscape science: a Russian geographical tradition

The Russian geographical tradition of landscape science (landshaftovedenie) is analyzed with particular reference to its initiator, Lev Semenovich Berg (1876-1950). The differences between prevailing Russian and Western concepts of landscape in geography are discussed, and their common origins in German geographical thought in the late nineteenth and early twentieth centuries are delineated. It is argued that the principal differences are accounted for by a number of factors, of which Russia's own distinctive tradition in environmental science deriving from the work of V. V. Dokuchaev (1846-1903), the activities of certain key individuals (such as Berg and C. O. Sauer), and the very different social and political circumstances in different parts of the world appear to be the most significant. At the same time it is noted that neither in Russia nor in the West have geographers succeeded in specifying an agreed and unproblematic understanding of landscape, or more broadly in promoting a common geographical conception of human-environment relationships. In light of such uncertainties, the latter part of the article argues for closer international links between the variant landscape traditions in geography as an important contribution to the quest for sustainability