448 research outputs found
Mossbauer-effect data-collection system
Automated data collection system which uses a small, general-purpose digital computer provides data acquisition from, and minor control of, four Mossbauer-effect experiments. This system is economical with no loss of versatility to the experimenter and is useful in handling large volumes of data from research experiments
Comparable High Rates of Extended-Spectrum-Beta-Lactamase-Producing Escherichia coli in Birds of Prey from Germany and Mongolia
Frequent contact with human waste and liquid manure from intensive livestock
breeding, and the increased loads of antibiotic-resistant bacteria that
result, are believed to be responsible for the high carriage rates of ESBL-
producing E. coli found in birds of prey (raptors) in Central Europe. To test
this hypothesis against the influence of avian migration, we initiated a
comparative analysis of faecal samples from wild birds found in Saxony-Anhalt
in Germany and the Gobi-Desert in Mongolia, regions of dissimilar human and
livestock population characteristics and agricultural practices. We sampled a
total of 281 wild birds, mostly raptors with primarily north-to-south
migration routes. We determined antimicrobial resistance, focusing on ESBL
production, and unravelled the phylogenetic and clonal relatedness of
identified ESBL-producing E. coli isolates using multi-locus sequence typing
(MLST) and macrorestriction analyses. Surprisingly, the overall carriage rates
(approximately 5%) and the proportion of ESBL-producers among E. coli
(Germany: 13.8%, Mongolia: 10.8%) were similar in both regions. Whereas
blaCTX-M-1 predominated among German isolates (100%), blaCTX-M-9 was the most
prevalent in Mongolian isolates (75%). We identified sequence types (STs) that
are well known in human and veterinary clinical ESBL-producing E. coli (ST12,
ST117, ST167, ST648) and observed clonal relatedness between a Mongolian avian
ESBL-E. coli (ST167) and a clinical isolate of the same ST that originated in
a hospitalised patient in Europe. Our data suggest the influence of avian
migratory species in the transmission of ESBL-producing E. coli and challenge
the prevailing assumption that reducing human influence alone invariably leads
to lower rates of antimicrobial resistance
Reference Network and Localization Architecture for Smart Manufacturing based on 5G
5G promises to shift Industry 4.0 to the next level by allowing flexible
production. However, many communication standards are used throughout a
production site, which will stay so in the foreseeable future. Furthermore,
localization of assets will be equally valuable in order to get to a higher
level of automation. This paper proposes a reference architecture for a
convergent localization and communication network for smart manufacturing that
combines 5G with other existing technologies and focuses on high-mix low-volume
application, in particular at small and medium-sized enterprises. The
architecture is derived from a set of functional requirements, and we describe
different views on this architecture to show how the requirements can be
fulfilled. It connects private and public mobile networks with local networking
technologies to achieve a flexible setup addressing many industrial use cases.Comment: 10 pages; submitted to 6th International Conference on
System-Integrated Intelligence. Intelligent, flexible and connected systems
in products and production, 7-9 September Genova, Ital
Bridging the technological divide: Stigmas and challenges with technology in digital brain health studies of older adults
The COVID-19 pandemic has increased adoption of remote assessments in clinical research. However, longstanding stereotypes persist regarding older adults\u27 technology familiarity and their willingness to participate in technology-enabled remote studies. We examined the validity of these stereotypes using a novel technology familiarity assessment
Profinite rigidity for Seifert fibre spaces
An interesting question is whether two 3-manifolds can be distinguished by
computing and comparing their collections of finite covers; more precisely, by
the profinite completions of their fundamental groups. In this paper, we solve
this question completely for closed orientable Seifert fibre spaces. In
particular, all Seifert fibre spaces are distinguished from each other by their
profinite completions apart from some previously-known examples due to Hempel.
We also characterize when bounded Seifert fibre space groups have isomorphic
profinite completions, given some conditions on the boundary
Adaptive Evolution of the Myo6 Gene in Old World Fruit Bats (Family: Pteropodidae)
PMCID: PMC3631194This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Deconvolution of monocyte responses in inflammatory bowel disease reveals an IL-1 cytokine network that regulates IL-23 in genetic and acquired IL-10 resistance.
OBJECTIVE: Dysregulated immune responses are the cause of IBDs. Studies in mice and humans suggest a central role of interleukin (IL)-23-producing mononuclear phagocytes in disease pathogenesis. Mechanistic insights into the regulation of IL-23 are prerequisite for selective IL-23 targeting therapies as part of personalised medicine. DESIGN: We performed transcriptomic analysis to investigate IL-23 expression in human mononuclear phagocytes and peripheral blood mononuclear cells. We investigated the regulation of IL-23 expression and used single-cell RNA sequencing to derive a transcriptomic signature of hyperinflammatory monocytes. Using gene network correlation analysis, we deconvolved this signature into components associated with homeostasis and inflammation in patient biopsy samples. RESULTS: We characterised monocyte subsets of healthy individuals and patients with IBD that express IL-23. We identified autosensing and paracrine sensing of IL-1α/IL-1β and IL-10 as key cytokines that control IL-23-producing monocytes. Whereas Mendelian genetic defects in IL-10 receptor signalling induced IL-23 secretion after lipopolysaccharide stimulation, whole bacteria exposure induced IL-23 production in controls via acquired IL-10 signalling resistance. We found a transcriptional signature of IL-23-producing inflammatory monocytes that predicted both disease and resistance to antitumour necrosis factor (TNF) therapy and differentiated that from an IL-23-associated lymphocyte differentiation signature that was present in homeostasis and in disease. CONCLUSION: Our work identifies IL-10 and IL-1 as critical regulators of monocyte IL-23 production. We differentiate homeostatic IL-23 production from hyperinflammation-associated IL-23 production in patients with severe ulcerating active Crohn's disease and anti-TNF treatment non-responsiveness. Altogether, we identify subgroups of patients with IBD that might benefit from IL-23p19 and/or IL-1α/IL-1β-targeting therapies upstream of IL-23
Immunodeficiency, autoimmune thrombocytopenia and enterocolitis caused by autosomal recessive deficiency of PIK3CD-encoded phosphoinositide 3-kinase δ.
Phosphoinositide 3-kinase δ (PI3Kδ), a lipid kinase consisting of a catalytic (p110δ, encoded by PIK3CD) and a regulatory subunit (p85, encoded by PIK3R1), generates the second messenger phosphatidylinositol (3,4,5)-trisphosphate (PIP3) in the plasma membrane of leukocytes downstream of antigen and cytokine receptors.1 Signaling via PDK1, AKT, mTOR and downstream targets such as FOXO1, contributes to the metabolic and transcriptional changes required for the expansion, differentiation and effector function of lymphocytes. Activating germline mutations in PIK3CD cause the immune dysregulatory disease activated PI3Kδ syndrome (APDS), usually presenting
with recurrent sinopulmonary infections in childhood, herpesvirus infections and CD4+ lymphopenia, underscoring the important role of balanced p110δ activity in human adaptive immunity.
Ablation of p110δ in mice leads to aberrant T cell responses and intestinal inflammation. In humans, immune dysregulation including severe colitis is present in many cancer patients who are treated with the p110δ-specific inhibitor Idelalisib. Recently, one patient with autosomal recessive deficiency of p85α and two patients with loss-of function mutations in p110δ have been described who developed humoral immunodeficiency and colitis
Hermansky-Pudlak syndrome type 1 causes impaired anti-microbial immunity and inflammation due to dysregulated immunometabolism
Hermansky-Pudlak syndrome (HPS) types 1 and 4 are caused by defective vesicle trafficking. The mechanism for Crohn's disease-like inflammation, lung fibrosis, and macrophage lipid accumulation in these patients remains enigmatic. The aim of this study is to understand the cellular basis of inflammation in HPS-1. We performed mass cytometry, proteomic and transcriptomic analyses to investigate peripheral blood cells and serum of HPS-1 patients. Using spatial transcriptomics, granuloma-associated signatures in the tissue of an HPS-1 patient with granulomatous colitis were dissected. In vitro studies were conducted to investigate anti-microbial responses of HPS-1 patient macrophages and cell lines. Monocytes of HPS-1 patients exhibit an inflammatory phenotype associated with dysregulated TNF, IL-1α, OSM in serum, and monocyte-derived macrophages. Inflammatory macrophages accumulate in the intestine and granuloma-associated macrophages in HPS-1 show transcriptional signatures suggestive of a lipid storage and metabolic defect. We show that HPS1 deficiency leads to an altered metabolic program and Rab32-dependent amplified mTOR signaling, facilitated by the accumulation of mTOR on lysosomes. This pathogenic mechanism translates into aberrant bacterial clearance, which can be rescued with mTORC1 inhibition. Rab32-mediated mTOR signaling acts as an immuno-metabolic checkpoint, adding to the evidence that defective bioenergetics can drive hampered anti-microbial activity and contribute to inflammation
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