Carbon Aerogels for High Capacity Adsorption of CO2

Carbon aerogels are light, highly porous materials with high surface areas. Their applications have been demonstrated in a wide range of areas such as CO2 capture, gas separations, electrochemical cells, catalysis, etc. Carbon aerogels are typically made from pyrolysis of a variety of carbonizable polymeric aerogels, which in turn are synthesized via sol-gel methods. It has been argued that along with porosity and the surface structure, heteroatoms such as O and N play a decisive role on the properties of porous carbon materials, with nitrogen-containing functional groups in particular responsible for improving interaction with gases for gas adsorption applications. For these reasons, a previously-synthesized tetrahydroquinazoline (THQ) monomer was selected to be polymerized to form a PTHQ aerogel, which was then oxidized, carbonized, and etched to form a carbon aerogel. This transformation process has variable steps, which affect the characteristics of the derived aerogel. This carbon aerogel exhibits porosity favorable for high capacity of carbon dioxide, and for the selective adsorption of carbon dioxide versus other common gases, notably nitrogen and oxygen

Uptake of breast cancer preventive therapy in the UK: results from a multicentre prospective survey and qualitative interviews

Purpose: Uptake of preventive therapy for women at increased breast cancer risk in England is unknown following the introduction of UK clinical guidelines in 2013. Preventive therapy could create socioeconomic inequalities in cancer incidence if it is more readily accepted by particular socio-demographic groups. In this multicentre study, we investigated uptake of tamoxifen and evaluated socio-demographic and clinical factors associated with initiation. We explored women’s experiences of treatment decision-making using qualitative interview data. Methods: Between September 2015 and December 2016, women (n=732) attending an appointment at one of 20 centres in England to discuss breast cancer risk were approached to complete a survey containing socio-demographic details and nulliparity. Of the baseline survey respondents (n=408/732, 55.7% response rate), self-reported uptake of tamoxifen at 3-month follow-up was reported in 258 (63.2%). Sixteen women participated in semi-structured interviews. Results: One in seven (38/258=14.7%) women initiated tamoxifen. Women who had children were more likely to report use of tamoxifen than those without children (OR=5.26; 95%CI: 1.13–24.49, p=0.035). Interview data suggested that women weigh up risks and benefits of tamoxifen within the context of familial commitments, with exposure to significant other’s beliefs and experiences of cancer and medication a basis for their decision. Conclusions: Uptake of tamoxifen is low in clinical practice. There were no socio-demographic differences in uptake, suggesting that the introduction of breast cancer preventive therapy is unlikely to create socioeconomic inequalities in cancer incidence. Women’s decision-making was influenced by familial priorities, particularly having children

Polybenzodiazine Aerogels: All-Nitrogen Analogues of Polybenzoxazines Synthesis, Characterization, and High-Yield Conversion to Nanoporous Carbons

Tetrahydroquinazoline (THQ) was designed as an all-nitrogen analogue of main-stream benzoxazine monomers. THQ solutions in DMF gelled at 100 °C via HCl-catalyzed ring-opening polymerization to polybenzodiazine (PBDAZ) wet gels, which were dried in an autoclave with supercritical fluid CO2 to aerogels. These as-prepared PBDAZ-100 aerogels undergo ring-fusion aromatization at 240 °C under O2. This oxidized form is referred to as PBDAZ-240. Chemical identification of PBDAZ-100 and PBDAZ-240 relied on consideration of all nine possible polymerization pathways, in combination with elemental analysis, infrared and solid-state 13C NMR spectroscopy, and 15N NMR spectroscopy of aerogels from the selectively 15N-enriched THQ monomer. Fully oxidized PBDAZ-240 aerogels were carbonized at 800 °C under Ar to carbon aerogels with 61% w/w yield and with retention of the nanomorphology of the parent PBDAZ-100 aerogels. Direct pyrolysis of PBDAZ-100 at 800 °C, i.e., without prior oxidation, resulted in only 40% w/w yield and complete loss of the fine nanostructure. The evolution of PBDAZ-240 aerogels along pyrolysis toward carbonization was monitored using progressively higher pyrolysis temperatures from 300 to 800 °C under Ar. Aerogels received at 600 and 800 °C (referred to as PBDAZ-600 and PBDAZ-800, respectively) had relatively high surface areas (432 and 346 m2 g-1, respectively), a significant portion of which (79% in both materials) was assigned to micropores. The new polymer aerogels, together with polybenzoxazine aerogels, comprise a suitable basis set for comparing N-rich versus O-rich porous carbons as adsorbers

Repeated long-term sub-concussion impacts induce motor dysfunction in rats : a potential rodent model

Whilst detrimental effects of repeated sub-concussive impacts on neurophysiological and behavioral function are increasingly reported, the underlying mechanisms are largely unknown. Here, we report that repeated sub-concussion with a light weight drop (25 g) in wild-type PVG rats for 2 weeks does not induce detectable neuromotor dysfunction assessed by beamwalk and rotarod tests. However, after 12 weeks of repeated sub-concussion, the rats exhibited moderate neuromotor dysfunction. This is the first study to demonstrate development of neuromotor dysfunction following multiple long-term sub-concussive impacts in rats. The outcomes may offer significant opportunity for future studies to understand the mechanisms of sub-concussion-induced neuropsychological changes. © Copyright © 2020 Lavender, Rawlings, Warnock, McGonigle, Hiles-Murison, Nesbit, Lam, Hackett, Fitzgerald and Takechi

Molecular Identification of a Malaria Merozoite Surface Sheddase

Proteolytic shedding of surface proteins during invasion by apicomplexan parasites is a widespread phenomenon, thought to represent a mechanism by which the parasites disengage adhesin-receptor complexes in order to gain entry into their host cell. Erythrocyte invasion by merozoites of the malaria parasite Plasmodium falciparum requires the shedding of ectodomain components of two essential surface proteins, called MSP1 and AMA1. Both are released by the same merozoite surface “sheddase,” but the molecular identity and mode of action of this protease is unknown. Here we identify it as PfSUB2, an integral membrane subtilisin-like protease (subtilase). We show that PfSUB2 is stored in apical secretory organelles called micronemes. Upon merozoite release it is secreted onto the parasite surface and translocates to its posterior pole in an actin-dependent manner, a trafficking pattern predicted of the sheddase. Subtilase propeptides are usually selective inhibitors of their cognate protease, and the PfSUB2 propeptide is no exception; we show that recombinant PfSUB2 propeptide binds specifically to mature parasite-derived PfSUB2 and is a potent, selective inhibitor of MSP1 and AMA1 shedding, directly establishing PfSUB2 as the sheddase. PfSUB2 is a new potential target for drugs designed to prevent erythrocyte invasion by the malaria parasite

5-SPICE: the application of an original framework for community health worker program design, quality improvement and research agenda setting

Introduction: Despite decades of experience with community health workers (CHWs) in a wide variety of global health projects, there is no established conceptual framework that structures how implementers and researchers can understand, study and improve their respective programs based on lessons learned by other CHW programs. Objective: To apply an original, non-linear framework and case study method, 5-SPICE, to multiple sister projects of a large, international non-governmental organization (NGO), and other CHW projects. Design: Engaging a large group of implementers, researchers and the best available literature, the 5-SPICE framework was refined and then applied to a selection of CHW programs. Insights gleaned from the case study method were summarized in a tabular format named the ‘5×5-SPICE chart’. This format graphically lists the ways in which essential CHW program elements interact, both positively and negatively, in the implementation field. Results: The 5×5-SPICE charts reveal a variety of insights that come from a more complex understanding of how essential CHW projects interact and influence each other in their unique context. Some have been well described in the literature previously, while others are exclusive to this article. An analysis of how best to compensate CHWs is also offered as an example of the type of insights that this method may yield. Conclusions: The 5-SPICE framework is a novel instrument that can be used to guide discussions about CHW projects. Insights from this process can help guide quality improvement efforts, or be used as hypothesis that will form the basis of a program's research agenda. Recent experience with research protocols embedded into successfully implemented projects demonstrates how such hypothesis can be rigorously tested

Transforming growth factor-β1 and SMAD signalling pathway in the small airways of smokers and patients with COPD: potential role in driving fibrotic type-2 epithelial mesenchymal transition

BackgroundCOPD is a common disease characterized by respiratory airflow obstruction. TGF-β1 and SMAD pathway is believed to play a role in COPD pathogenesis by driving epithelial mesenchymal transition (EMT).MethodsWe investigated TGF-β1 signalling and pSmad2/3 and Smad7 activity in resected small airway tissue from patients with; normal lung function and a smoking history (NLFS), current smokers and ex-smokers with COPD GOLD stage 1 and 2 (COPD-CS and COPD-ES) and compared these with normal non-smoking controls (NC). Using immunohistochemistry, we measured activity for these markers in the epithelium, basal epithelium, and reticular basement membrane (RBM). Tissue was also stained for EMT markers E-cadherin, S100A4 and vimentin.ResultsThe Staining of pSMAD2/3 was significantly increased in the epithelium, and RBM of all COPD groups compared to NC (p <0.0005). There was a less significant increase in COPD-ES basal cell numbers compared to NC (p= 0.02). SMAD7 staining showed a similar pattern (p <0.0001). All COPD group levels of TGF-β1 in the epithelium, basal cells, and RBM cells were significantly lower than NC (p <0.0001). Ratio analysis showed a disproportionate increase in SMAD7 levels compared to pSMAD2/3 in NLFS, COPD-CS and COPD-ES. pSMAD negatively correlated with small airway calibre (FEF25–75%; p= 0.03 r= -0.36). EMT markers were active in the small airway epithelium of all the pathological groups compared to patients with COPD.ConclusionActivation of the SMAD pathway via pSMAD2/3 is triggered by smoking and active in patients with mild to moderate COPD. These changes correlated to decline in lung function. Activation of the SMADs in the small airways is independent of TGF-β1, suggesting factors other than TGF-β1 are driving these pathways. These factors may have implications for small airway pathology in smokers and COPD through the process of EMT, however more mechanistic work is needed to prove these correlations

Chemoreceptor responsiveness at sea level does not predict the pulmonary pressure response to high altitude

The hypoxic ventilatory response (HVR) at sea level (SL) is moderately predictive of the change in pulmonary artery systolic pressure (PASP) to acute normobaric hypoxia. However, because of progressive changes in the chemoreflex control of breathing and acid-base balance at high altitude (HA), HVR at SL may not predict PASP at HA. We hypothesized that resting peripheral oxyhemoglobin saturation (SpO2) at HA would correlate better than HVR at SL to PASP at HA. In 20 participants at SL, we measured normobaric, isocapnic HVR (L/min·-%SpO2 -1) and resting PASP using echocardiography. Both resting SpO2 and PASP measures were repeated on day 2 (n=10), days 4-8 (n=12), and 2-3 weeks (n=8) after arrival at 5050m. These data were also collected at 5050m on life-long HA residents (Sherpa; n=21). Compared to SL, SpO2 decreased from 98.6 to 80.5% (P<0.001), while PASP increased from 21.7 to 34.0mmHg (P<0.001) after 2-3 weeks at 5050m. Isocapnic HVR at SL was not related to SpO2 or PASP at any time point at 5050m (all P>0.05). Sherpa had lower PASP (P<0.01) than lowlanders on days 4-8 despite similar SpO2. Upon correction for hematocrit, Sherpa PASP was not different from lowlanders at SL, but lower than lowlanders at all HA time points. At 5050m, whilst SpO2 was not related to PASP in lowlanders at any point (all R2=0.50), there was a weak relationship in the Sherpa (R2=0.16; P=0.07). We conclude that neither HVR at SL nor resting SpO2 at HA correlates with elevations in PASP at HA

Alterations in cerebral blood flow and cerebrovascular reactivity during 14 days at 5050 m

Upon ascent to high altitude, cerebral blood flow (CBF) rises substantially before returning to sea-level values. The underlying mechanisms for these changes are unclear. We examined three hypotheses: (1) the balance of arterial blood gases upon arrival at and across 2 weeks of living at 5050 m will closely relate to changes in CBF; (2) CBF reactivity to steady-state changes in CO2 will be reduced following this 2 week acclimatisation period, and (3) reductions in CBF reactivity to CO2 will be reflected in an augmented ventilatory sensitivity to CO2. We measured arterial blood gases, middle cerebral artery blood flow velocity (MCAv, index of CBF) and ventilation () at rest and during steady-state hyperoxic hypercapnia (7% CO2) and voluntary hyperventilation (hypocapnia) at sea level and then again following 2–4, 7–9 and 12–15 days of living at 5050 m. Upon arrival at high altitude, resting MCAv was elevated (up 31 ± 31%; P < 0.01; vs. sea level), but returned to sea-level values within 7–9 days. Elevations in MCAv were strongly correlated (R2= 0.40) with the change in ratio (i.e. the collective tendency of arterial blood gases to cause CBF vasodilatation or constriction). Upon initial arrival and after 2 weeks at high altitude, cerebrovascular reactivity to hypercapnia was reduced (P < 0.05), whereas hypocapnic reactivity was enhanced (P < 0.05 vs. sea level). Ventilatory response to hypercapnia was elevated at days 2–4 (P < 0.05 vs. sea level, 4.01 ± 2.98 vs. 2.09 ± 1.32 l min−1 mmHg−1). These findings indicate that: (1) the balance of arterial blood gases accounts for a large part of the observed variability (∼40%) leading to changes in CBF at high altitude; (2) cerebrovascular reactivity to hypercapnia and hypocapnia is differentially affected by high-altitude exposure and remains distorted during partial acclimatisation, and (3) alterations in cerebrovascular reactivity to CO2 may also affect ventilatory sensitivity