THE ANTICOAGULANT AND ANTILYMPHOMA PROPERTIES OF ARSENIC AZOPROTEINS : I. ANTICOAGULANT EFFECTS OF ARSENIC AZOPROTEINS IN VIVO AND IN VITRO: COMPARISON OF ARSENICALS AS ANTICOAGULANTS AND AS ANTILYMPHOMA AGENTS: MOLECULAR STRUCTURE IN RELATION TO ANTICOAGULANT AND ANTILYMPHOMA PROPERTIES

Experiments given in this paper have shown that 4-arsonophenylazoproteins possess marked anticoagulant activity both in vivo and in vitro. Mice and rabbits given moderate amounts of the arsenic azoprotein, for example, often bled to death from injuries that proved trivial in control animals, and their blood remained liquid during many hours' postmortem even when left in contact with transected tissues, fibrinolysis having no part in the outcome. So, too, the addition of minute amounts of 4-arsonophenylazoprotein to plasma procured from citrated rabbit or human blood greatly prolonged the time required for clotting after recalcification. Other arsenic-containing compounds,—for example, those in which arsenic See PDF for Structure was joined to amino acids or peptides through the azo linkage, or to proteins through couplings other than the azo linkage,—were largely devoid of anticoagulant and antilymphoma effects. The findings as a whole show clearly that the structural requirements for anticoagulant and antilymphoma effects are: (a) possession of negatively charged arsonic or arsinoso groups, (b) large molecular size (protein), and (c) linkage of arsenic-containing groups to protein through the azo bond. Two acidic azoproteins that were devoid of arsenic,—namely 4-carboxyphenylazoprotein and 4-sulfonophenylazoprotein,—were also found to have marked anticoagulant effects in vitro, but they had no inhibitory action against cells of Lymphoma 6C3HED in vivo, even when they were given to mice in maximum tolerated amounts. The essential part played by arsenic in the antilymphoma activity of arsenic azoproteins was further emphasized by the action of dimercaprol (BAL) in preventing the antilymphoma effects of 4-arsonophenylazoprotein on Lymphoma 6C3HED cells in vivo. In an associated paper the anticoagulant and antilymphoma effects of 4-arsonophenylazoproteins are studied further, and consideration is given to the ways in which these effects may be brought about

Genetic recombination is targeted towards gene promoter regions in dogs

The identification of the H3K4 trimethylase, PRDM9, as the gene responsible for recombination hotspot localization has provided considerable insight into the mechanisms by which recombination is initiated in mammals. However, uniquely amongst mammals, canids appear to lack a functional version of PRDM9 and may therefore provide a model for understanding recombination that occurs in the absence of PRDM9, and thus how PRDM9 functions to shape the recombination landscape. We have constructed a fine-scale genetic map from patterns of linkage disequilibrium assessed using high-throughput sequence data from 51 free-ranging dogs, Canis lupus familiaris. While broad-scale properties of recombination appear similar to other mammalian species, our fine-scale estimates indicate that canine highly elevated recombination rates are observed in the vicinity of CpG rich regions including gene promoter regions, but show little association with H3K4 trimethylation marks identified in spermatocytes. By comparison to genomic data from the Andean fox, Lycalopex culpaeus, we show that biased gene conversion is a plausible mechanism by which the high CpG content of the dog genome could have occurred.Comment: Updated version, with significant revision

Ethnicity and the Writing of Medieval Scottish history

Historians have long tended to define medieval Scottish society in terms of interactions between ethnic groups. This approach was developed over the course of the long nineteenth century, a formative period for the study of medieval Scotland. At that time, many scholars based their analysis upon scientific principles, long since debunked, which held that medieval 'peoples' could only be understood in terms of 'full ethnic packages'. This approach was combined with a positivist historical narrative that defined Germanic Anglo-Saxons and Normans as the harbingers of advances of Civilisation. While the prejudices of that era have largely faded away, the modern discipline still relies all too often on a dualistic ethnic framework. This is particularly evident in a structure of periodisation that draws a clear line between the 'Celtic' eleventh century and the 'Norman' twelfth. Furthermore, dualistic oppositions based on ethnicity continue, particularly in discussions of the law, kingship, lordship and religion

Acidogenic Potential of “Sugar-Free” Cough Drops

A patient presented with extensive marginal ditching around restorations recently placed during whole-mouth rehabilitation. The patient was not xerostomic and was otherwise normal except for the self-reported excessive use of “sugar-free” cough drops sweetened with sorbitol and Isomalt® (an equimolar mix of glucosyl-mannitol and glucosylsorbitol). This prompted an in vitro investigation to determine whether Streptococcus sobrinus 6715, a cariogenic streptococcus, could grow and produce acid in growth medium containing an aqueous extract of such “sugar-free” cough drops. The results indicate that S. sobrinus 6715 uses Isomalt® and sorbitol extensively, producing terminal culture pH as low as 4.2 when grown on medium with cough drop extract containing these sugars. This pH is sufficient to demineralize dental enamel. Patients should be cautioned against the chronic overuse of “sugar-free” cough drops and other “sugar-free” confections sweetened with a mixture of Isomalt® and sorbitol

2018 GJMPP Monograph Series: Grace Jordan McFadden Professors Program

The Grace Jordan McFadden Professors Program (GJMPP), formerly the African American Professors Program (AAPP)/Carolina Diversity Professors Program (CDPP) at the University of South Carolina, is honored to publish its seventeenth edition of this annual monograph series. GJMPP recognizes the significance of offering its scholars a venue through which they have the opportunity to engage in research and to publish their refereed papers that continually contribute to their respective academic areas. Parallel with the publication of their manuscripts is a venue to gain visibility among colleagues throughout postsecondary institutions at national and international levels. Scholars who have contributed papers for this monograph are acknowledged for embracing the value of including this responsibility within their doctoral milieu. Writing across disciplines adds broadly to the intellectual diversity of these manuscripts. From neophytes to quite experienced individuals, the chapters have been researched and written with vigor. Founded in 1997 through the Department of Educational Leadership and Policies in the College of Education, AAPP was designed originally to address the under-representation 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 historically 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 and others 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, to allow for the dissemination of products of scholarship to a broader community. The importance of this series has been voiced by one of our 2002 AAPP graduates, Dr. Shundelle LaTjuan Dogan, formerly an Administrative Fellow at Harvard University, a Program Officer for the Southern Education Foundation, and a Program Officer for the Arthur M. Blank Foundation in Atlanta, Georgia. She recently completed an appointment as Corporate Citizenship and Corporate Affairs Manager for IBM International Business Machines in Atlanta and is currently a consultant with a focus on philanthropy and social impact. She is currently Assistant Vice President for Social Impact and Innovation at Emory University. Dr. Dogan has written an impressive Foreword for the 2014 monograph. In a personal letter, which is cited in an earlier monograph, Dr. Dogan penned: “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 ‘right on target’ in having us do the monograph series” (AAPP 2003, Monograph, p. xi). The Grace Jordan McFadden Professors Program purports to advance the tradition of spearheading international scholarship in higher education as evidenced through inspiration from this group of interdisciplinary manuscripts. I hope that you will envision these published papers to serve as an invaluable contribution to your own professional and career enhancement. John McFadden, PhD The Benjamin Elijah Mays Distinguished Professor Emeritus Director, Grace Jordan McFadden Professors Program University of South Carolina Columbia, South Carolinahttps://scholarcommons.sc.edu/mcfadden_monographs/1010/thumbnail.jp

[(18)F]FDG-PET/CT metabolic parameters as useful prognostic factors in cervical cancer patients treated with chemo-radiotherapy.

To compare the prognostic value of different anatomical and functional metabolic parameters determined using [(18)F]FDG-PET/CT with other clinical and pathological prognostic parameters in cervical cancer (CC). Thirty-eight patients treated with standard curative doses of chemo-radiotherapy (CRT) underwent pre- and post-therapy [(18)F]FDG-PET/CT. [(18)F]FDG-PET/CT parameters including mean tumor standardized uptake values (SUV), metabolic tumor volume (MTV) and tumor glycolytic volume (TGV) were measured before the start of CRT. The post-treatment tumor metabolic response was evaluated. These parameters were compared to other clinical prognostic factors. Survival curves were estimated by using the Kaplan-Meier method. Cox regression analysis was performed to determine the independent contribution of each prognostic factor. After 37 months of median follow-up (range, 12-106), overall survival (OS) was 71 % [95 % confidence interval (CI), 54-88], disease-free survival (DFS) 61 % [95 % CI, 44-78] and loco-regional control (LRC) 76 % [95 % CI, 62-90]. In univariate analyses the [(18)F]FDG-PET/CT parameters unfavorably influencing OS, DFS and LRC were pre-treatment TGV-cutoff ≥562 (37 vs. 76 %, p = 0.01; 33 vs. 70 %, p = 0.002; and 55 vs. 83 %, p = 0.005, respectively), mean pre-treatment tumor SUV cutoff ≥5 (57 vs. 86 %, p = 0.03; 36 vs. 88 %, p = 0.004; 65 vs. 88 %, p = 0.04, respectively) and a partial tumor metabolic response after treatment (9 vs. 29 %, p = 0.0008; 0 vs. 83 %, p < 0.0001; 22 vs. 96 %, p < 0.0001, respectively). After multivariate analyses a partial tumor metabolic response after treatment remained as an independent prognostic factor unfavorably influencing DFS and LRC (RR 1:7.7, p < 0.0001, and RR 1:22.6, p = 0.0003, respectively) while the pre-treatment TGV-cutoff ≥562 negatively influenced OS and DFS (RR 1:2, p = 0.03, and RR 1:2.75, p = 0.05). Parameters capturing the pre-treatment glycolytic volume and metabolic activity of [(18)F]FDG-positive disease provide important prognostic information in patients with CC treated with CRT. The post-therapy [(18)F]FDG-PET/CT uptake (partial tumor metabolic response) is predictive of disease outcome

Crafting Critical Heritage Discourses into Interactive Exhibition Design

This paper argues how a more reflective design practice that embraces critical discourses can transform interactive exhibition design and therefore the museum visiting experience. Four framing arguments underpin our exhibition design making: the value of materiality, visiting as an aesthetic experience, challenging the authorized voice, and heritage as a process. These arguments were embodied through design, art and craft practice into one interactive exhibition at a house museum. We draw from our design process discussing the implications that adopting an approach informed by critical heritage debates has on exhibition design and suggest three sensitizing concepts (polyvocal narratives, dialogical interaction, interweaving time and space) bridging the practice of interactive exhibition design and critical heritage theory

An intermediate-effect size variant in UMOD confers risk for chronic kidney disease

The kidney-specific gene UMOD encodes for uromodulin, the most abundant protein excreted in normal urine. Rare large-effect variants in UMOD cause autosomal dominant tubulointerstitial kidney disease (ADTKD), while common low-impact variants strongly associate with kidney function and the risk of chronic kidney disease (CKD) in the general population. It is unknown whether intermediate-effect variants in UMOD contribute to CKD. Here, candidate intermediate-effect UMOD variants were identified using large-population and ADTKD cohorts. Biological and phenotypical effects were investigated using cell models, in silico simulations, patient samples, and international databases and biobanks. Eight UMOD missense variants reported in ADTKD are present in the Genome Aggregation Database (gnomAD), with minor allele frequency (MAF) ranging from 10(−5) to 10(−3). Among them, the missense variant p.Thr62Pro is detected in ∼1/1,000 individuals of European ancestry, shows incomplete penetrance but a high genetic load in familial clusters of CKD, and is associated with kidney failure in the 100,000 Genomes Project (odds ratio [OR] = 3.99 [1.84 to 8.98]) and the UK Biobank (OR = 4.12 [1.32 to 12.85). Compared with canonical ADTKD mutations, the p.Thr62Pro carriers displayed reduced disease severity, with slower progression of CKD and an intermediate reduction of urinary uromodulin levels, in line with an intermediate trafficking defect in vitro and modest induction of endoplasmic reticulum (ER) stress. Identification of an intermediate-effect UMOD variant completes the spectrum of UMOD-associated kidney diseases and provides insights into the mechanisms of ADTKD and the genetic architecture of CKD