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"Hansen, R"
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Transatlantic spread of highly pathogenic avian influenza H5N1 by wild birds from Europe to North America in 2021
Highly pathogenic avian influenza (HPAI) viruses of the A/Goose/Guangdong/1/1996 lineage (GsGd), which threaten the health of poultry, wildlife and humans, are spreading across Asia, Europe, Africa and North America but are currently absent from South America and Oceania. In December 2021, H5N1 HPAI viruses were detected in poultry and a free-living gull in St. John’s, Newfoundland and Labrador, Canada. Our phylogenetic analysis showed that these viruses were most closely related to HPAI GsGd viruses circulating in northwestern Europe in spring 2021. Our analysis of wild bird migration suggested that these viruses may have been carried across the Atlantic via Iceland, Greenland/Arctic or pelagic routes. The here documented incursion of HPAI GsGd viruses into North America raises concern for further virus spread across the Americas by wild bird migration.
Journal Article
Advances in Development of Antimicrobial Peptidomimetics as Potential Drugs
The rapid emergence of multidrug-resistant pathogens has evolved into a global health problem as current treatment options are failing for infections caused by pan-resistant bacteria. Hence, novel antibiotics are in high demand, and for this reason antimicrobial peptides (AMPs) have attracted considerable interest, since they often show broad-spectrum activity, fast killing and high cell selectivity. However, the therapeutic potential of natural AMPs is limited by their short plasma half-life. Antimicrobial peptidomimetics mimic the structure and biological activity of AMPs, but display extended stability in the presence of biological matrices. In the present review, focus is on the developments reported in the last decade with respect to their design, synthesis, antimicrobial activity, cytotoxic side effects as well as their potential applications as anti-infective agents. Specifically, only peptidomimetics with a modular structure of residues connected via amide linkages will be discussed. These comprise the classes of α-peptoids (N-alkylated glycine oligomers), β-peptoids (N-alkylated β-alanine oligomers), β3-peptides, α/β3-peptides, α-peptide/β-peptoid hybrids, α/γ N-acylated N-aminoethylpeptides (AApeptides), and oligoacyllysines (OAKs). Such peptidomimetics are of particular interest due to their potent antimicrobial activity, versatile design, and convenient optimization via assembly by standard solid-phase procedures.
Journal Article
Correlation between hemolytic activity, cytotoxicity and systemic in vivo toxicity of synthetic antimicrobial peptides
The use of non-standard toxicity models is a hurdle in the early development of antimicrobial peptides towards clinical applications. Herein we report an extensive in vitro and in vivo toxicity study of a library of 24 peptide-based antimicrobials with narrow spectrum activity towards veterinary pathogens. The haemolytic activity of the compounds was evaluated against four different species and the relative sensitivity against the compounds was highest for canine erythrocytes, intermediate for rat and human cells and lowest for bovine cells. Selected peptides were additionally evaluated against HeLa, HaCaT and HepG2 cells which showed increased stability towards the peptides. Therapeutic indexes of 50–500 suggest significant cellular selectivity in comparison to bacterial cells. Three peptides were administered to rats in intravenous acute dose toxicity studies up to 2–8 × MIC. None of the injected compounds induced any systemic toxic effects in vivo at the concentrations employed illustrating that the correlation between the different assays is not obvious. This work sheds light on the in vitro and in vivo toxicity of this class of promising compounds and provides insights into the relationship between the different toxicity models often employed in different manners to evaluate the toxicity of novel bioactive compounds in general.
Journal Article
Forever Young : a life of adventure in air and space
The autobiography of astronaut John Young.
Book
A forecast comparison of volatility models: does anything beat a GARCH(1,1)?
We compare 330 ARCH-type models in terms of their ability to describe the conditional variance. The models are compared out-of-sample using DM-$ exchange rate data and IBM return data, where the latter is based on a new data set of realized variance. We find no evidence that a GARCH(1,1) is outperformed by more sophisticated models in our analysis of exchange rates, whereas the GARCH(1,1) is clearly inferior to models that can accommodate a leverage effect in our analysis of IBM returns. The models are compared with the test for superior predictive ability (SPA) and the reality check for data snooping (RC). Our empirical results show that the RC lacks power to an extent that makes it unable to distinguish 'good' and 'bad' models in our analysis.
Journal Article
Dear Neil Armstrong : letters to the first man on the moon from all mankind
\"In the years between the historic first moon landing by Apollo 11 on July 20, 1969, and his death at age 82 on August 25, 2012, Neil Armstrong received hundreds of thousands of cards and letters from all over the world, congratulating him, praising him, requesting pictures and autographs, and asking him what must have seemed to him to be limitless-and occasionally intrusive-questions. Of course, all the famous astronauts received fan mail, but the sheer volume Armstrong had to deal with for more than four decades after his moon landing was staggering. Today, the preponderance of those letters-some 75,000 of them-are preserved in the archives at Purdue University in West Lafayette, Indiana. Dear Neil Armstrong: Letters to the First Man from All Mankind publishes a careful sampling of these letters-roughly 400-reflecting the various kinds of correspondence that Armstrong received along with representative samples of his replies. Selected and edited by James R. Hansen, Armstrong's authorized biographer and author of the New York Times best seller First Man: The Life of Neil A. Armstrong, this collection sheds light on Armstrong's enduring impact and offers an intimate glimpse into the cultural meanings of human spaceflight. Readers will explore what the thousands of letters to Neil Armstrong meant not only to those who wrote them, but as a snapshot of one of humankind's greatest achievements in the twentieth century. They will see how societies and cultures projected their own meanings onto one of the world's great heroes and iconic figures\"-- Provided by publisher.
BOOK
Systematic Localization of Common Disease-Associated Variation in Regulatory DNA
Genome-wide association studies have identified many noncoding variants associated with common diseases and traits. We show that these variants are concentrated in regulatory DNA marked by deoxyribonuclease I (DNase I) hypersensitive sites (DHSs). Eighty-eight percent of such DHSs are active during fetal development and are enriched in variants associated with gestational exposure—related phenotypes. We identified distant gene targets for hundreds of variant-containing DHSs that may explain phenotype associations. Disease-associated variants systematically perturb transcription factor recognition sequences, frequently alter allelic chromatin states, and form regulatory networks. We also demonstrated tissue-selective enrichment of more weakly disease-associated variants within DHSs and the de novo identification of pathogenic cell types for Crohn's disease, multiple sclerosis, and an electrocardiogram trait, without prior knowledge of physiological mechanisms. Our results suggest pervasive involvement of regulatory DNA variation in common human disease and provide pathogenic insights into diverse disorders.
Journal Article