831 research outputs found
Navigating Copper-Atom-Pair Structural Effect inside a Porous Organic Polymer Cavity for Selective Hydrogenation of Biomass-Derived 5-Hydroxymethylfurfural
In recent times, selective hydrogenation of biomass-derived 5-hydroxymethylfurfural (5-HMF) to produce the novel difuranic polyol scaffold 2,5-dihydroxymethylfuran (DHMF) has attracted the interest of the many researchers due to its peculiar symmetrical structure and its widespread application as a monomer for the preparation of cross-linked polyesters and polyurethane. Copper-based catalysts have been explored for selective catalytic hydrogenation; however, hurdles are still associated with the strongly reducing H2 atmosphere and oxidizing C–O bond that make the Cu0 and Cux+ surface active species unstable, limiting the rational design of highly efficient integrated catalyst systems. To address this, herein, we built catalytic systems for 5-HMF hydrogenation with stable and balanced Cu0 and Cux+ active surface species inside the nanocage of a catechol-based porous organic polymer (POP) endowed with large surface areas, impressive stabilities, and spatial restriction inhibiting nanoparticle aggregation. Batch reactor screening identified that a superior catalytic performance (DHMF selectivity of 98%) has been achieved with our newly designed Cu@C-POP at 150 °C temperature and 20 bar H2 pressure, which was also higher than that of other reported copper catalysts. Comprehensive characterization understanding with H2-TPR and X-ray photoelectron spectroscopy (XPS) study revealed that substantially boosted activity is induced by the presence of the bulk CuOx phase and atomically dispersed Cu species incorporating isolated Cu ions, which are further confirmed through the positive binding energy shift of Cu 2p3/2 XPS spectra (∼0.4 eV). The Cu environment in our catalytic systems comprises a predominantly square planar geometry (probably Jahn–Teller distorted OH), which we gleaned from the extended X-ray absorption for fine structure (EXAFS) analysis featuring two adjacent copper atoms with the valence state in between of 0 and +2, as validated by XANES absorption edge positions. EXAFS studies further revealed a lowering of the Cu coordination number for the most active Cu@C-POP-B catalyst, suggesting the presence of metal vacancies. Density functional theory calculations showed that the presence of Cu metal vacancies stabilized the reaction intermediates formed during 5-HMF hydrogenation and decreased the hydrogenation barriers, resulting in an enhanced catalytic activity of the Cu@C-POP-B catalyst
Protocol for a human in vivo model of acute cigarette smoke inhalation challenge in smokers with COPD: monitoring the nasal and systemic immune response using a network biology approach
Introduction: Cigarette smoke contributes to a diverse
range of diseases including chronic obstructive
pulmonary disease (COPD), cardiovascular disorders
and many cancers. There currently is a need for
human challenge models, to assess the acute effects of
a controlled cigarette smoke stimulus, followed by
serial sampling of blood and respiratory tissue for
advanced molecular profiling. We employ precision
sampling of nasal mucosal lining fluid by absorption to
permit soluble mediators measurement in eluates.
Serial nasal curettage was used for transcriptomic
analysis of mucosal tissue.
Methods and analysis: Three groups of strictly
defined patients will be studied: 12 smokers with
COPD (GOLD Stage 2) with emphysema, 12 matched
smokers with normal lung function and no evidence of
emphysema, and 12 matched never smokers with
normal spirometry. Patients in the smoking groups are
current smokers, and will be given full support to stop
smoking immediately after this study. In giving a
controlled cigarette smoke stimulus, all patients will
have abstained from smoking for 12 h, and will smoke
two cigarettes with expiration through the nose in a
ventilated chamber. Before and after inhalation of
cigarette smoke, a series of samples will be taken from
the blood, nasal mucosal lining fluid and nasal tissue
by curettage. Analysis of plasma nicotine and
metabolites in relation to levels of soluble inflammatory
mediators in nasal lining fluid and blood, as well as
assessing nasal transcriptomics, ex vivo blood platelet
aggregation and leucocyte responses to toll-like
receptor agonists will be undertaken.
Implications: Development of acute cigarette smoke
challenge models has promise for the study of
molecular effects of smoking in a range of pathological
processes.This study was funded by the Wellcome Trust and Dainippon Sumitomo Pharma Co Ltd, Osaka, Japan. Supported by: Dainippon Sumitomo Pharma Co Ltd, Osaka, Japan National Institute of Healthcare Research (Grant No: R3101002), NIHR Imperial Biomedical Research Centre (NIHR BMRC), Imperial Academic Health Science Centre (AHSC), Imperial Centre for Respiratory Infection (CRI, Grant No: 083567/Z/07/Z), Wellcome Trust (Grant No: 083429/Z/07/Z)
Semantic diversity:A measure of contextual variation in word meaning based on latent semantic analysis
Thrombosis Is Reduced by Inhibition of COX-1, but Unaffected by Inhibition of COX-2, in an Acute Model of Platelet Activation in the Mouse
This 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
A Study of Problem Solving Using Blocks Vehicle in a STEAM Course for Lower Elementary Levels
STEAM education is currently one of the most important parts of the elementary school curriculum. If STEAM learning can cultivate good problem-solving ability, it will also help improve judgment and thinking abilities. Several voices in the literature have argued for cooperative learning in STEAM courses. Although the effectiveness of course learning often is evaluated using course feedback forms, there is comparatively little emphasis on whether a course succeeds in realizing cooperative learning. For a course involving self-propelled toy-brick cars, there is little research on the application of low-grade pupils. Therefore, based on the integration of STEAM courses into self-propelled toy-brick car learning, this study applied two learning strategies of cooperative learning and individual learning to low-grade pupils in the second grade in elementary schools. After completing the course problem-solving ability indicators were measured and analyzed using the problem-solving ability test. The results show that the mean score of the experimental group in the problem-solving ability test was higher than that of the control group. In the problem-solving ability test, the scores of the two groups were also significantly different, which suggests that cooperative learning is more effective than individual learning strategies.acceptedVersio
Symptoms and quality of life in late stage Parkinson syndromes: a longitudinal community study of predictive factors
BACKGROUND
Palliative care is increasingly offered earlier in the cancer trajectory but rarely in Idiopathic Parkinson's Disease(IPD), Progressive Supranuclear Palsy(PSP) or Multiple System Atrophy(MSA). There is little longitudinal data of people with late stage disease to understand levels of need. We aimed to determine how symptoms and quality of life of these patients change over time; and what demographic and clinical factors predicted changes.
METHODS
We recruited 82 patients into a longitudinal study, consenting patients with a diagnosis of IPD, MSA or PSP, stages 3-5 Hoehn and Yahr(H&Y). At baseline and then on up to 3 occasions over one year, we collected self-reported demographic, clinical, symptom, palliative and quality of life data, using Parkinson's specific and generic validated scales, including the Palliative care Outcome Scale (POS). We tested for predictors using multivariable analysis, adjusting for confounders.
FINDINGS
Over two thirds of patients had severe disability, over one third being wheelchair-bound/bedridden. Symptoms were highly prevalent in all conditions - mean (SD) of 10.6(4.0) symptoms. More than 50% of the MSA and PSP patients died over the year. Over the year, half of the patients showed either an upward (worsening, 24/60) or fluctuant (8/60) trajectory for POS and symptoms. The strongest predictors of higher levels of symptoms at the end of follow-up were initial scores on POS (AOR 1.30; 95%CI:1.05-1.60) and being male (AOR 5.18; 95% CI 1.17 to 22.92), both were more predictive than initial H&Y scores.
INTERPRETATION
The findings point to profound and complex mix of non-motor and motor symptoms in patients with late stage IPD, MSA and PSP. Symptoms are not resolved and half of the patients deteriorate. Palliative problems are predictive of future symptoms, suggesting that an early palliative assessment might help screen for those in need of earlier intervention
The role of the RACK1 ortholog Cpc2p in modulating pheromone-induced cell cycle arrest in fission yeast
The detection and amplification of extracellular signals requires the involvement of multiple protein components. In mammalian cells the receptor of activated C kinase (RACK1) is an important scaffolding protein for signal transduction networks. Further, it also performs a critical function in regulating the cell cycle by modulating the G1/S transition. Many eukaryotic cells express RACK1 orthologs, with one example being Cpc2p in the fission yeast Schizosaccharomyces pombe. In contrast to RACK1, Cpc2p has been described to positively regulate, at the ribosomal level, cells entry into M phase. In addition, Cpc2p controls the stress response pathways through an interaction with Msa2p, and sexual development by modulating Ran1p/Pat1p. Here we describe investigations into the role, which Cpc2p performs in controlling the G protein-mediated mating response pathway. Despite structural similarity to Gβ-like subunits, Cpc2p appears not to function at the G protein level. However, upon pheromone stimulation, cells overexpressing Cpc2p display substantial cell morphology defects, disorientation of septum formation and a significantly protracted G1 arrest. Cpc2p has the potential to function at multiple positions within the pheromone response pathway. We provide a mechanistic interpretation of this novel data by linking Cpc2p function, during the mating response, with its previous described interactions with Ran1p/Pat1p. We suggest that overexpressing Cpc2p prolongs the stimulated state of pheromone-induced cells by increasing ste11 gene expression. These data indicate that Cpc2p regulates the pheromone-induced cell cycle arrest in fission yeast by delaying cells entry into S phase
Pre-cooling for endurance exercise performance in the heat: a systematic review.
PMCID: PMC3568721The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/10/166.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Endurance exercise capacity diminishes under hot environmental conditions. Time to exhaustion can be increased by lowering body temperature prior to exercise (pre-cooling). This systematic literature review synthesizes the current findings of the effects of pre-cooling on endurance exercise performance, providing guidance for clinical practice and further research
Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer
<p>Aims: DDX3 is an RNA helicase that has antiapoptotic properties, and promotes proliferation and transformation. In addition, DDX3 was shown to be a direct downstream target of HIF-1α (the master regulatory of the hypoxia response) in breast cancer cell lines. However, the relation between DDX3 and hypoxia has not been addressed in human tumors. In this paper, we studied the relation between DDX3 and the hypoxic responsive proteins in human breast cancer.</p>
<p>Methods and Results: DDX3 expression was investigated by immunohistochemistry in breast cancer in comparison with hypoxia related proteins HIF-1α, GLUT1, CAIX, EGFR, HER2, Akt1, FOXO4, p53, ERα, COMMD1, FER kinase, PIN1, E-cadherin, p21, p27, Transferrin receptor, FOXO3A, c-Met and Notch1. DDX3 was overexpressed in 127 of 366 breast cancer patients, and was correlated with overexpression of HIF-1α and its downstream genes CAIX and GLUT1. Moreover, DDX3 expression correlated with hypoxia-related proteins EGFR, HER2, FOXO4, ERα and c-Met in a HIF-1α dependent fashion, and with COMMD1, FER kinase, Akt1, E-cadherin, TfR and FOXO3A independent of HIF-1α.</p>
<p>Conclusions: In invasive breast cancer, expression of DDX3 was correlated with overexpression of HIF-1α and many other hypoxia related proteins, pointing to a distinct role for DDX3 under hypoxic conditions and supporting the oncogenic role of DDX3 which could have clinical implication for current development of DDX3 inhibitors.</p>
- …