Effect of tumor necrosis factor antagonism on allergen-mediated asthmatic airway inflammation

SummaryObjectiveTo assess whether tumor necrosis factor (TNF) antagonism can attenuate eosinophilic airway inflammation in patients with mild-to-moderate allergic asthma.DesignRandomized, double-blind, placebo-controlled trial.SettingNational Institutes of Health (NIH) Clinical Center.PatientsTwenty-six patients with mild-to-moderate allergic asthma, receiving only inhaled β-2-agonists, who demonstrated both an early and late phase response to inhalational allergen challenge.InterventionInjection of a soluble TNF receptor (TNFR:Fc, etanercept, Enbrel) or placebo, 25mg subcutaneously, twice weekly for 2 weeks, followed by a bronchoscopic segmental allergen challenge.MeasurementsThe primary outcome measure was whether TNFR:Fc can access the lung and inhibit TNF bioactivity. Secondary outcome measures included pulmonary eosinophilia, Th2-type cytokines, and airway hyperresponsiveness.ResultsAnti-TNF therapy was associated with transient hemiplegia in one patient, which resulted in suspension of the study. Data from the 21 participants who completed the study were analyzed. Following treatment, patients receiving anti-TNF therapy had significantly increased TNFR2 levels in epithelial lining fluid (ELF) (P<0.001), consistent with delivery of TNFR:Fc to the lung. TNF antagonism did not attenuate pulmonary eosinophilia and was associated with an increase in ELF IL-4 levels (P=0.033) at 24h following segmental allergen challenge. TNF antagonism was not associated with a change in airway hyperresponsiveness to methacholine.ConclusionsTNF antagonism may not be effective for preventing allergen-mediated eosinophilic airway inflammation in mild-to-moderate asthmatics. Transient hemiplegia, which may mimic an evolving stroke, may be a potential toxicity of anti-TNF therapy

Cryptocurrency Competition and Market Concentration in the Presence of Network Effects

When network products and services become more valuable as their userbase grows (network effects), this tendency can become a major determinant of how they compete with each other in the market and how the market is structured. Network effects are traditionally linked to high market concentration, early-mover advantages, and entry barriers, and in the market they have also been used as a valuation tool. The recent resurgence of Bitcoin has been partly attributed to network effects, too. We study the existence of network effects in six cryptocurrencies from their inception to obtain a high-level overview of the application of network effects in the cryptocurrency market. We show that, contrary to the usual implications of network effects, they do not serve to concentrate the cryptocurrency market, nor do they accord any one cryptocurrency a definitive competitive advantage, nor are they consistent enough to be reliable valuation tools. Therefore, while network effects do occur in cryptocurrency networks, they are not (yet) a defining feature of the cryptocurrency market as a whole

Photoluminescent, upconversion luminescent and nonlinear optical metal-organic frameworks: From fundamental photophysics to potential applications

Metal-organic frameworks (MOFs) are a class of porous materials prepared by the self-assembly of metal ions or clusters with organic ligands. The unique characteristics of MOFs, including structural tunability, high surface areas, low densities and tailored pore surface functionalization, have made them leading contenders as high-performance porous materials, alongside the established zeolites and activated carbons. Consequently, the permanent porosity of MOFs has been extensively exploited for gas capture and separation and catalysis. In recent years, the field has been expanded towards new applications and many studies of MOFs are venturing into unexplored avenues. A large number of studies have been focused on photoluminescent, upconversion luminescent, and nonlinear optical MOFs for applications in areas such as white-light emission, bioimaging, sensing, and photocatalysis. Within the first half of this tutorial review, we present the fundamental principles of luminescence, including detailed scientific discussions on the luminescence origin of different materials such as organic dyes, transition metal complexes, quantum dots, and lanthanide compounds. Principles and important parameters for the applications of luminescent MOFs are introduced, followed by a summary of recent interesting publications for each application. In the second half, we introduce nonlinear optical effects including second harmonic generation and two-photon absorption, and upconversion of luminescence, followed by detailed examples of MOFs that exhibit these phenomena. Finally, insights about the remaining challenges and future directions are discussed. (C) 2018 Elsevier B.V. All rights reserved

On the Hausdorff and packing measures of typical compact metric spaces

We study the Hausdorff and packing measures of typical compact metric spaces belonging to the Gromov–Hausdorff space (of all compact metric spaces) equipped with the Gromov–Hausdorff metric.Publisher PDFPeer reviewe

Making a HIIT: study protocol for assessing the feasibility and effects of co-designing high-intensity interval training workouts with students and teachers

This is the final version. Available on open access from BMC via the DOI in this recordBACKGROUND: High-intensity interval training (HIIT) is an effective strategy for improving a variety of health outcomes within the school setting. However, there is limited research on the implementation of school-based HIIT interventions and the integration of HIIT within the Health and Physical Education (HPE) curriculum. The aims of the Making a HIIT study are to: 1) describe the methodology and evaluate the feasibility of co-designing HIIT workouts with students and teachers in HPE; 2) determine the effect of co-designed HIIT workouts on cardiorespiratory and muscular fitness, and executive function; 3) understand the effect of co-design on students' motivation, enjoyment, and self-efficacy towards the workouts; and 4) evaluate the implementation of the intervention. METHODS: Three schools will participate. Within each school, three different groups will be formed from Year 7 and 8 classes: 1) Co-Designers; 2) HIIT Only; and 3) Control. The study will include two phases. In phase one, Group 1 will co-design HIIT workouts as part of the HPE curriculum using an iterative process with the researcher, teacher, and students as collaborators. This process will be evaluated using student discussions, student surveys, and teacher interviews. In phase two, Groups 1 and 2 will use the co-designed 10-minute HIIT workouts in HPE for 8-weeks. Group 3 (control) will continue their regular HPE lessons. All students will participate in cardiorespiratory fitness, muscular fitness, and executive function assessments before and after the HIIT program or control period. Students will complete questionnaires on their motivation, enjoyment, and self-efficacy of the workouts. Differences between groups will be assessed using linear regressions to account for covariates. Heart rate and rating of perceived exertion will be collected during each HIIT session. The implementation will be evaluated using the Framework for Effective Implementation. Ethical approval was granted by the University of Queensland Human Research Ethics Committee and other relevant bodies. DISCUSSION: This study will be the first to co-design HIIT workouts with teachers and students within the HPE curriculum. As this study relies on co-design, each HIIT workout will differ, which will add variability between HIIT workouts but increase the ecological validity of the study. TRIAL REGISTRATION: ACTRN, ACTRN12622000534785, Registered 5 April 2022 - Retrospectively registered, https://www.anzctr.org.au/ACTRN12622000534785.aspx.QUEX Institute for Global ExcellenceSports Medicine Australia

Genetical genomics: spotlight on QTL hotspots

No abstract available

Incarceration of Iodine in a Pyrene-Based Metal-Organic Framework

A pyrene-based metal-organic framework (MOF) SION-8 captured iodine (I-2) vapor with a capacity of 460 and 250 mg g(MOF)(-1) at room temperature and 75 degrees C, respectively. Single-crystal X-ray diffraction analysis and van-der-Waals-corrected density functional theory calculations confirmed the presence of I-2 molecules within the pores of SION-8 and their interaction with the pyrene-based ligands. The I-2-pyrene interactions in the I-2-loaded SION-8 led to a 10(4)-fold increase of its electrical conductivity compared to the bare SION-8. Upon adsorption, >= 95 % of I-2 molecules were incarcerated and could not be washed out, signifying the potential of SION-8 towards the permanent capture of radioactive I-2 at room temperature

Selective CO₂ capture in metal-organic frameworks with azine-functionalized pores generated by mechanosynthesis

Two new three-dimensional porous Zn(II)-based metal-organic frameworks, containing azine-functionalized pores, have been readily and quickly isolated via mechanosynthesis, by using a nonlinear dicarboxylate and linear N-donor ligands. The use of nonfunctionalized and methyl-functionalized N-donor ligands has led to the formation of frameworks with different topologies and metal-ligand connectivities and therefore different pore sizes and accessible volumes. Despite this, both metal-organic frameworks (MOFs) possess comparable BET surface areas and CO₂ uptakes at 273 and 298 K at 1 bar. The network with narrow and interconnected pores in three dimensions shows greater affinity for CO compared to the network with one-dimensional and relatively large pores-attributable to the more effective interactions with the azine groups

Immune-Complex Mimics as a Molecular Platform for Adjuvant-Free Vaccine Delivery

Protein-based vaccine development faces the difficult challenge of finding robust yet non-toxic adjuvants suitable for humans. Here, using a molecular engineering approach, we have developed a molecular platform for generating self-adjuvanting immunogens that do not depend on exogenous adjuvants for induction of immune responses. These are based on the concept of Immune Complex Mimics (ICM), structures that are formed between an oligomeric antigen and a monoclonal antibody (mAb) to that antigen. In this way, the roles of antigens and antibodies within the structure of immune complexes are reversed, so that a single monoclonal antibody, rather than polyclonal sera or expensive mAb cocktails can be used. We tested this approach in the context of Mycobacterium tuberculosis (MTB) infection by linking the highly immunogenic and potentially protective Ag85B with the oligomeric Acr (alpha crystallin, HspX) antigen. When combined with an anti-Acr monoclonal antibody, the fusion protein formed ICM which bound to C1q component of the complement system and were readily taken up by antigen-presenting cells in vitro. ICM induced a strong Th1/Th2 mixed type antibody response, which was comparable to cholera toxin adjuvanted antigen, but only moderate levels of T cell proliferation and IFN-γ secretion. Unfortunately, the systemic administration of ICM did not confer statistically significant protection against intranasal MTB challenge, although a small BCG-boosting effect was observed. We conclude that ICM are capable of inducing strong humoral responses to incorporated antigens and may be a suitable vaccination approach for pathogens other than MTB, where antibody-based immunity may play a more protective role