8 research outputs found
The Schwinger Variational Method
Variational methods have proven invaluable in theoretical physics and chemistry, both for bound state problems and for the study of collision phenomena. For collisional problems they can be grouped into two types: those based on the Schroedinger equation and those based on the Lippmann-Schwinger equation. The application of the Schwinger variational (SV) method to e-molecule collisions and photoionization has been reviewed previously. The present chapter discusses the implementation of the SV method as applied to e-molecule collisions
QDB: A new database of plasma chemistries and reactions
One of the most challenging and recurring problems when modeling plasmas is the lack of data on the key atomic and molecular reactions that drive plasma processes. Even when there are data for some reactions, complete and validated datasets of chemistries are rarely available. This hinders research on plasma processes and curbs development of industrial applications. The QDB project aims to address this problem by providing a platform for provision, exchange, and validation of chemistry datasets. A new data model developed for QDB is presented. QDB collates published data on both electron scattering and heavy-particle reactions. These data are formed into reaction sets, which are then validated against experimental data where possible. This process produces both complete chemistry sets and identifies key reactions that are currently unreported in the literature. Gaps in the datasets can be filled using established theoretical methods. Initial validated chemistry sets for SF 6 /CF 4 /O 2 and SF 6 /CF 4 /N 2 /H 2 are presented as examples
Leukotriene E4 is a full functional agonist for human cysteinyl leukotriene type 1 receptor-dependent gene expression
Leukotriene E4 (LTE4) the most stable of the cysteinyl leukotrienes (cysLTs) binds
poorly to classical type 1 (CysLT1) and 2 (CysLT2) receptors although it induces
potent responses in human airways in vivo, such as bronchoconstriction, airway
hyperresponsiveness and inflammatory cell influx suggesting the presence of a novel
receptor that preferentially responds to LTE4. To identify such a receptor two human
mast cell lines, LAD2 and LUVA, were selected that differentially responded to LTE4
when analyzed by intracellular signaling and gene expression. Comparative
transcriptome analysis and recombinant gene overexpression experiments revealed
CysLT1 as a receptor responsible for potent LTE4-induced response in LAD2 but not
in LUVA cells, an observation confirmed further by gene knockdown and selective
inhibitors. Lentiviral overexpression of CysLT1 in LUVA cells augmented
intracellular calcium signaling induced by LTE4 but did not restore full agonist
responses at the gene expression level. Our data support a model where both an
increased expression of Gαq-coupled CysLT1, and sustained intracellular calcium
mobilization and extracellular signal-regulated kinase (Erk) activation, are required
for LTE4-mediated regulation of gene expression in human cells. Our study shows for
the first time that CysLT1 expression is critically important for responsiveness to
LTE4 within a human cell system
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Derivation of ligands for the complement C3a receptor from the C-terminus of C5a
The complement cascade is a highly sophisticated network of proteins that are well regulated and directed in response to invading pathogens or tissue injury. Complement C3a and C5a are key mediators produced by this cascade, and their dysregulation has been linked to a plethora of inflammatory and autoimmune diseases. Consequently, this has stimulated interest in the development of ligands for the receptors for these complement peptides, C3a receptor, and C5a1 (C5aR/CD88). In this study we used computational methods to design novel C5a1 receptor ligands. However, functional screening in human monocyte-derived macrophages using the xCELLigence label-free platform demonstrated altered specificity of our ligands. No agonist/antagonist activity was observed at C5a1, but we instead saw that the ligands were able to partially agonize the closely related complement receptor C3a receptor. This was verified in the presence of C3a receptor antagonist SB 290157 and in a stable cell line expressing either C5a1 or C3a receptor alone. C3a agonism has been suggested to be a potential treatment of acute neutrophil-driven traumatic pathologies, and may have great potential as a therapeutic avenue in this arena
Inception of early-life allergen–induced airway hyperresponsiveness is reliant on IL-13+CD4+ T cells
Airway hyperresponsiveness (AHR) is a critical feature of wheezing and asthma in children, but the initiating immune mechanisms remain unconfirmed. We demonstrate that both recombinant interleukin-33 (rIL-33) and allergen [house dust mite (HDM) or Alternaria alternata] exposure from day 3 of life resulted in significantly increased pulmonary IL-13+CD4+ T cells, which were indispensable for the development of AHR. In contrast, adult mice had a predominance of pulmonary LinnegCD45+CD90+IL-13+ type 2 innate lymphoid cells (ILC2s) after administration of rIL-33. HDM exposure of neonatal IL-33 knockout (KO) mice still resulted in AHR. However, neonatal CD4creIL-13 KO mice (lacking IL-13+CD4+ T cells) exposed to allergen from day 3 of life were protected from AHR despite persistent pulmonary eosinophilia, elevated IL-33 levels, and IL-13+ ILCs. Moreover, neonatal mice were protected from AHR when inhaled Acinetobacter lwoffii (an environmental bacterial isolate found in cattle farms, which is known to protect from childhood asthma) was administered concurrent with HDM. A. lwoffii blocked the expansion of pulmonary IL-13+CD4+ T cells, whereas IL-13+ ILCs and IL-33 remained elevated. Administration of A. lwoffii mirrored the findings from the CD4creIL-13 KO mice, providing a translational approach for disease protection in early life. These data demonstrate that IL-13+CD4+ T cells, rather than IL-13+ ILCs or IL-33, are critical for inception of allergic AHR in early life