284 research outputs found
Ab initio study of beryllium-decorated fullerenes for hydrogen storage
We have found that a beryllium (Be) atom on nanostructured materials with H2
molecules generates a Kubas-like dihydrogen complex [H. Lee et al.
arXiv:1002.2247v1 (2010)]. Here, we investigate the feasibility of Be-decorated
fullerenes for hydrogen storage using ab initio calculations. We find that the
aggregation of Be atoms on pristine fullerenes is energetically preferred,
resulting in the dissociation of the dihydrogen. In contrast, for boron
(B)-doped fullerenes, Be atoms prefer to be individually attached to B sites of
the fullerenes, and a maximum of one H2 molecule binds to each Be atom in a
form of dihydrogen with a binding energy of ~0.3 eV. Our results show that
individual dispersed Be-decorated B-doped fullerenes can serve as a
room-temperature hydrogen storage medium.Comment: 11 pages, 3 figures, Accepted for publication in Journal of Applied
Physic
The use of decomposition methods in real-world treatment benefits evaluation for patients with type 2 diabetes initiating different injectable therapies: findings from the Initiator study
Onur Başer (MEF Author)Background: Determining characteristics of patients likely to benefit from a particular treatment could help physicians set personalized targets. OBJECTIVES: To use decomposition methodology on real-world data to identify the relative contributions of treatment effects and patients' baseline characteristics. METHODS: Decomposition analyses were performed on data from the Initiation of New Injectable Treatment Introduced after Antidiabetic Therapy with Oral-only Regimens (INITIATOR) study, a real-world study of patients with type 2 diabetes started on insulin glargine (GLA) or liraglutide (LIRA). These analyses investigated relative contributions of differences in baseline characteristics and treatment effects to observed differences in 1-year outcomes for reduction in glycated hemoglobin A1c (HbA1c) and treatment persistence. RESULTS: The greater HbA1c reduction seen with GLA compared with LIRA (-1.39% vs. -0.74%) was primarily due to differences in baseline characteristics (HbA1c and endocrinologist as prescribing physician; P < 0.050). Patients with baseline HbA1c of 9.0% or more or evidence of diagnosis codes related to mental illness achieved greater HbA1c reductions with GLA, whereas patients with baseline polypharmacy (6-10 classes) or hypogylcemia achieved greater reductions with LIRA. Decomposition analyses also showed that the higher persistence seen with GLA (65% vs. 49%) was mainly caused by differences in treatment effects (P < 0.001). Patients 65 years and older, those with HbA1c of 9.0% or more, those taking three oral antidiabetes drugs, and those with polypharmacy of more than 10 classes had higher persistence with GLA; patients 18 to 39 years and those with HbA1c of 7.0% to less than 8.0% had higher persistence with LIRA. CONCLUSIONS: Although decomposition does not demonstrate causal relationships, this method could be useful for examining the source of differences in outcomes between treatments in a real-world setting and could help physicians identify patients likely to respond to a particular treatment. Copyright (C) 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.WOS:000419245600004Scopus - Affiliation ID: 60105072PMID: 29241884Science Citation Index Expanded - Social Sciences Citation IndexQ1ArticleUluslararası işbirliği ile yapılan - EVETAralık2017YÖK - 2017-1
A Synthetic Agonist to Vasoactive Intestinal Peptide Receptor-2 Induces Regulatory T Cell Neuroprotective Activities in Models of Parkinson\u27s Disease
A paradigm shift has emerged in Parkinson\u27s disease (PD) highlighting the prominent role of CD4+ Tregs in pathogenesis and treatment. Bench to bedside research, conducted by others and our own laboratories, advanced a neuroprotective role for Tregs making pharmacologic transformation of immediate need. Herein, a vasoactive intestinal peptide receptor-2 (VIPR2) peptide agonist, LBT-3627, was developed as a neuroprotectant for PD-associated dopaminergic neurodegeneration. Employing both 6-hydroxydopamine (6-OHDA) and α-synuclein (α-Syn) overexpression models in rats, the sequential administration of LBT-3627 increased Treg activity without altering cell numbers both in naïve animals and during progressive nigrostriatal degeneration. LBT-3627 administration was linked to reductions of inflammatory microglia, increased survival of dopaminergic neurons, and improved striatal densities. While α-Syn overexpression resulted in reduced Treg activity, LBT-3627 rescued these functional deficits. This occurred in a dose-dependent manner closely mimicking neuroprotection. Taken together, these data provide the basis for the use of VIPR2 agonists as potent therapeutic immune modulating agents to restore Treg activity, attenuate neuroinflammation, and interdict dopaminergic neurodegeneration in PD. The data underscore an important role of immunity in PD pathogenesis
Severe fever with thrombocytopenia syndrome phlebovirus non-structural protein activates TPL2 signalling pathway for viral immunopathogenesis
Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV), listed in the World Health Organization Prioritized Pathogens, is an emerging phlebovirus with a high fatality . Owing to the lack of therapies and vaccines , there is a pressing need to understand SFTSV pathogenesis. SFSTV non-structural protein (NSs) has been shown to block type I interferon induction and facilitate disease progression . Here, we report that SFTSV-NSs targets the tumour progression locus 2 (TPL2)-A20-binding inhibitor of NF-κB activation 2 (ABIN2)-p105 complex to induce the expression of interleukin-10 (IL-10) for viral pathogenesis. Using a combination of reverse genetics, a TPL2 kinase inhibitor and Tpl2 mice showed that NSs interacted with ABIN2 and promoted TPL2 complex formation and signalling activity, resulting in the marked upregulation of Il10 expression. Whereas SFTSV infection of wild-type mice led to rapid weight loss and death, Tpl2 mice or Il10 mice survived an infection. Furthermore, SFTSV-NSs P A and SFTSV-NSs K R that lost the ability to induce TPL2 signalling and IL-10 production showed drastically reduced pathogenesis. Remarkably, the exogenous administration of recombinant IL-10 effectively rescued the attenuated pathogenic activity of SFTSV-NSs P A, resulting in a lethal infection. Our study demonstrates that SFTSV-NSs targets the TPL2 signalling pathway to induce immune-suppressive IL-10 cytokine production as a means to dampen the host defence and promote viral pathogenesis
Europium-doped cerium oxide nanoparticles for microglial Aβ clearance and homeostasis
Alzheimer’s disease (AD) is the most common neurodegenerative disorder. Pathologically, it is characterized by the deposition of amyloid beta (Aβ) plaques and presence of neurofibrillary tangles. These drive microglia neuroinflammation and consequent neurodegeneration. While the means to affect Aβ plaque accumulation was achieved how it affects disease outcomes remains uncertain. Cerium oxide (CeO2) reduces Aβ plaques, oxidative stress, inflammation, and Alzheimer’s disease (AD) signs and symptoms. Specifically, CeO2 nanoparticles (CeO2NPs) induces free radical scavenging and cell protective intracellular signaling. This can ameliorate the pathobiology of an AD-affected brain. In order to investigate, CeO2NPs affects for microglia neurotoxic responses a novel formulation of europium doped CeO2NPs (EuCeO2NPs) was synthesized. We then tested EuCeO2NPs for its’ abilities to generate cellular immune homeostasis in AD models. EuCeO2NPs attenuated microglia BV2 inflammatory activities after Aβ1–42 exposure by increasing the cells’ phagocytic and Aβ degradation activities. These were associated with increases in the expression of the CD36 scavenger receptor. EuCeO2NPs facilitated Aβ endolysosomal trafficking and abrogated microglial inflammatory responses. We posit that EuCeO2NPs may be developed as an AD immunomodulator
Elevated expression of Nodal and YAP1 is associated with poor prognosis of gastric adenocarcinoma
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