The interplay of inflammation and cardiovascular disease in systemic lupus erythematosus

Patients with systemic lupus erythematosus have up to a 50-fold increased risk of developing atherosclerotic cardiovascular disease. Recent advances in the etiology of vascular damage in this disease stress the interplay of lupus-specific inflammatory factors with traditional cardiac risk factors, leading to increased endothelial damage. This review analyzes the putative role that immune dysregulation and lupus-specific factors may play in the pathogenesis of premature vascular damage in this disease. The potential role of various cytokines, in particular type I interferons, in the development of accelerated atherosclerosis is examined. Potential therapeutic targets are discussed

Advances in Disease Mechanisms and Translational Technologies: Clinicopathologic Significance of Inflammasome Activation in Autoimmune Diseases

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154483/1/art41127.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154483/2/art41127_am.pd

A modulated cocrystal:<i>N</i>′-(propan-2-ylidene)nicotinohydrazide and sebacic acid

n/

Comparison of ultracold neutron sources for fundamental physics measurements

Ultracold neutrons (UCNs) are key for precision studies of fundamental parameters of the neutron and in searches for new CP violating processes or exotic interactions beyond the Standard Model of particle physics. The most prominent example is the search for a permanent electric dipole moment of the neutron (nEDM). We have performed an experimental comparison of the leading UCN sources currently operating. We have used a 'standard' UCN storage bottle with a volume of 32 liters, comparable in size to nEDM experiments, which allows us to compare the UCN density available at a given beam port.Comment: 20 pages, 30 Figure

Solid-State Forms of β-Resorcylic Acid: How Exhaustive Should a Polymorph Screen Be?

An extensive experimental screen, coupled with a computational study, revealed seven new solid-state forms of β-resorcylic acid. The known, stable polymorph II° shows a reversible phase transformation to the new, kinetically stable, probably disordered high temperature form I. The study provides a consistent picture of the solid-state of β-resorcylic acid

Dysfunction of endothelial progenitor cells is associated with the type I IFN pathway in patients with polymyositis and dermatomyositis

Objective. Alterations in phenotype and function of endothelial progenitor cells (EPCs) have been associated with poor vascular outcomes and impaired vascular repair in various conditions. Our hypothesis was that patients with PM and DM have dysregulation of EPCs driven by type I IFN and IL-18 similar to other autoimmune diseases. Methods. Quantification of circulating EPCs was performed by flow cytometry in patients with PM/DM and matched healthy controls. The ability of EPCs to differentiate into mature endothelial cells was investigated by light and fluorescence microscopy quantification in the presence or absence of PM/DM or control serum, neutralizing antibodies to type I IFN receptor or IL-18. Serum type I IFN activity was quantified by induction of type I IFN-inducible genes in HeLa cells. Circulating IL-18 concentrations were assessed by ELISA. Results. Circulating EPCs were significantly lower in PM/DM patients compared with controls. PM/DM EPCs displayed a decreased capacity to differentiate into mature endothelial cells and PM/DM serum significantly inhibited differentiation of control EPCs. This effect was reversed in the majority of samples with neutralizing antibodies to IL-18 or to type I IFN receptor or by a combination of these antibodies. Patients with associated impairments in EPC function had higher type I IFN serum activity. Conclusion. PM/DM is associated with dysregulation of EPC phenotype and function that may be attributed, at least in part, to aberrant IL-18 and type I IFN pathways. The implication of these vasculopathic findings for disease prognosis and complications remains to be determined

Extensive sequential polymorphic interconversion in the solid-state: Two hydrates and ten anhydrous phases of hexamidine diisethionate

Crystal polymorphism and solvent inclusion is a dominant research area in the pharmaceutical industry and continues to unveil complex systems. Here, we present the solid-state system of hexamidine diisethionate (HDI), an antiseptic drug compound forming a dimorphic dihydrate as well as ten anhydrous polymorphs. The X-ray and neutron crystal structures of the hydrated crystal forms and related interaction energies show no direct interaction between the cation and water but very strong interactions between cation and anion, and anion and water. This is observed macroscopically as high stability of the hydrate against dehydration by temperature and humidity. The anhydrous polymorphs reveal a rare case of sequential and reversible polymorphic transformations, which are characterized by thermal analysis and variable-temperature powder X-ray diffraction (PXRD). While most transitions are accompanied by significant structural changes, the low-energy transitions can only be detected as slight changes in the reflection positions with temperature. HDI thus represents a model compound to investigate polymorphic transitions with small structural changes

τ\tauSPECT: A spin-flip loaded magnetic ultracold neutron trap for a determination of the neutron lifetime

The confinement of ultracold neutrons (UCNs) in a three dimensional magnetic field gradient trap allows for a measurement of the free neutron lifetime with superior control over spurious loss channels and can provide a large kinetic energy acceptance to enhance statistical sensitivity. In this paper, we present the first successful implementation of a pulsed spin-flip based loading scheme for a three-dimensional magnetic UCN trap. The measurements with the $\tau$SPECT experiment were performed at the pulsed UCN source of the research reactor TRIGA Mainz. We report on detailed investigations of major systematic effects influencing the neutron storage time, statistically limited by the size of the recorded data set. The extracted neutron storage time constant of $\tau = 859(16)\mathrm{s}$ is compatible with, but not to be interpreted as, a measurement of the free neutron lifetime.Comment: 15 pages, 19 figure