Annealing-enhanced birefringence and aggregation in MEH-PPV : a spectroscopic ellipsometry study

Funding: UK EPSRC (GR/S62628/01) and Royal Society Wolfson Research Merit Award (I.D.W.S.).We have used absorption, photoluminescence (PL) and variable angle spectroscopic ellipsometry (VASE) measurements to investigate the structural changes that take place upon high temperature annealing in spin-coated films of the prototypical conjugated polymer (CP) poly[2-(2’-ethylhexyloxy)-5-methoxy-1,4-phenylenevinylene] (MEH-PPV). Absorption and VASE measurements reveal that the birefringence of the films increases by approximately a factor of two upon heating, which indicates significant increase in the alignment of the conjugated polymer (CP) strands within the film plane. Absorption and PL spectra indicate the formation in annealed films of interchain species having lower energy transitions. But these measurements alone do not reveal the type of interchain species formed, such as excimers or aggregates. VASE measurements were used to investigate this feature and clearly reveal a new, low energy, feature with a shoulder at 650 nm in the dispersion relations of the extraordinary (out-of-plane) extinction and absorption coefficients of annealed films, which we assign to aggregate absorption. Thus, our work shows that VASE is a sensitive enough technique to measure aggregate absorption in CP films. In the case of the ordinary (in-plane) extinction and absorption coefficients, there is increased amplitude of the lower energy peak upon heating, owing to increased uniaxial anisotropy, along with a broadening and a longer red-tail, but the well-resolved red-shifted absorption band seen for the extraordinary absorption coefficient, is not observed. Therefore, we conclude that while in-plane and out-of-plane aggregation occurs in annealed spin-coated films of MEH-PPV, aggregate absorption is only clearly observed when the aggregate electronic transition dipole is oriented preferentially in a direction perpendicular to the film plane. This conclusion is consistent with the usual observation that aggregate absorption in MEH-PPV films is not easily observed using absorption spectra alone, which are typically measured at normal incidence.PostprintPeer reviewe

Self-Generated Magnetic Fields in Galactic Cooling Flows

Interstellar magnetic fields in elliptical galaxies are assumed to have their origin in stellar fields that accompany normal mass loss from an evolving population of old stars. The seed fields are amplified by interstellar turbulence driven by stellar mass loss and supernova events. These disordered fields are further amplified by time-dependent compression in the inward moving galactic cooling flow and are expected to dominate near the galactic core. Under favorable circumstances, fields similar in strength to those observed $B \sim 1-10~(r/10~kpc)^{-1.2}\mu$G can be generated solely from these natural galactic processes. In general the interstellar field throughout elliptical galaxies is determined by the outermost regions in the interstellar gas where the turbulent dynamo process can occur. Because of the long hydrodynamic flow times in galactic cooling flows, currently observed magnetic fields may result from periods of intense turbulent field amplification that occurred in the outer galaxy in the distant past. Particularly strong fields in ellipticals may result from ancient galactic mergers or shear turbulence introduced at the boundary between the interstellar gas and ambient cluster gas.Comment: 21 pages in AASTEX LaTeX with 2 figures; accepted by Astrophysical Journa

Evaluation of the Algorithms and Parameterizations for Ground Thawing and Freezing Simulation in Permafrost Regions

Ground thawing and freezing depths (GTFDs) strongly influence the hydrology and energy balances of permafrost regions. Current methods to simulate GTFD differ in algorithm type, soil parameterization, representation of latent heat, and unfrozen water content. In this study, five algorithms (one semiempirical, two analytical, and two numerical), three soil thermal conductivity parameterizations, and three unfrozen water parameterizations were evaluated against detailed field measurements at four field sites in Canada’s discontinuous permafrost region. Key findings include: (1) de Vries’ parameterization is recommended to determine the thermal conductivity in permafrost soils; (2) the three unfrozen water parameterization methods exhibited little difference in terms of GTFD simulations, yet the segmented linear function is the simplest to be implemented; (3) the semiempirical algorithm reasonably simulates thawing at permafrost sites and freezing at seasonal frost sites with site-specific calibration. However, large interannual and intersite variations in calibration coefficients limit its applicability for dynamic analysis; (4) when driven by surface forcing, analytical algorithms performed marginally better than the semiempirical algorithm. The inclusion of bottom forcing improved analytical algorithm performance, yet their results were still poor compared with those achieved by numerical algorithms; (5) when supplied with the optimal inputs, soil parameterizations, and model configurations, the numerical algorithm with latent heat treated as an apparent heat capacity achieved the best GTFD simulations among all algorithms at all sites. Replacing the observed bottom temperature with a zero heat flux boundary condition did not significantly reduce simulation accuracy, while assuming a saturated profile caused large errors at several sites

Neutron reflection study on soluble and insoluble poly[2-(2 '-ethylhexyloxy)-5-methoxy-1,4-phenylenevinylene) films

Neutron reflection (NR) has been utilized to study the physical structure of the light-emitting polymer poly[2-(2'-ethylhexyloxy)-5-methoxy-1,4-phenylenevinylene) (MEHPPV). Films of soluble MEHPPV (S-MEHPPV) and insoluble MEHPPV (I-MEHPPV) prepared via a chloro precursor polymer were investigated. For S-MEHPPV spin-coated films were found to contain two layers, one of low-density and thickness of approximate to1360 Angstrom with the second layer being thinner, approximate to240 Angstrom, but denser. The thicker layer only covered about 30% of the substrate surface. In contrast, I-MEHPPV formed uniform films across the substrate. We found that during the thermal conversion of the chloro precursor polymer the film thickness was maintained and it was only on cooling that the films contracted. Importantly, the thermal expansion and contraction of I-MEHPPV was reversible. NR showed that thermal annealing of I-MEHPPV had little affect on the films physical structure while for S-MEHPPV only the thinner layer was changed and became more dense. Photoluminescence spectra of S-MEHPPV before and after annealing showed that the densification observed in the neutron reflection measurements was mirrored in the emission properties of the polymer film. (C) 2002 American Institute of Physics

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis clinical trials

OBJECTIVE: To assess whether genetic subgroups in recent amyotrophic lateral sclerosis (ALS) trials responded to treatment with lithium carbonate, but that the treatment effect was lost in a large cohort of nonresponders. METHODS: Individual participant data were obtained from 3 randomized trials investigating the efficacy of lithium carbonate. We matched clinical data with data regarding the UNC13A and C9orf72 genotype. Our primary outcome was survival at 12 months. On an exploratory basis, we assessed whether the effect of lithium depended on the genotype. RESULTS: Clinical data were available for 518 of the 606 participants. Overall, treatment with lithium carbonate did not improve 12-month survival (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.7-1.4; p = 0.96). Both the UNC13A and C9orf72 genotype were independent predictors of survival (HR 2.4, 95% CI 1.3-4.3; p = 0.006 and HR 2.5, 95% CI 1.1-5.2; p = 0.032, respectively). The effect of lithium was different for UNC13A carriers (p = 0.027), but not for C9orf72 carriers (p = 0.22). The 12-month survival probability for UNC13A carriers treated with lithium carbonate improved from 40.1% (95% CI 23.2-69.1) to 69.7% (95% CI 50.4-96.3). CONCLUSIONS: This study incorporated genetic data into past ALS trials to determine treatment effects in a genetic post hoc analysis. Our results suggest that we should reorient our strategies toward finding treatments for ALS, start focusing on genotype-targeted treatments, and standardize genotyping in order to optimize randomization and analysis for future clinical trials

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Aspects of microbial communities in peatland carbon cycling under changing climate and land use pressures

This is the final version. Available on open access from the Finnish Peatland Society via the DOI in this record. Globally, major efforts are being made to restore peatlands to maximise their resilience to anthropogenic climate change, which puts continuous pressure on peatland ecosystems and modifies the geography of the environmental envelope that underpins peatland functioning. A probable effect of climate change is reduction in the waterlogged conditions that are key to peatland formation and continued accumulation of carbon (C) in peat. C sequestration in peatlands arises from a delicate imbalance between primary production and decomposition, and microbial processes are potentially pivotal in regulating feedbacks between environmental change and the peatland C cycle. Increased soil temperature, caused by climate warming or disturbance of the natural vegetation cover and drainage, may result in reductions of long-term C storage via changes in microbial community composition and metabolic rates. Moreover, changes in water table depth alter the redox state and hence have broad consequences for microbial functions, including effects on fungal and bacterial communities especially methanogens and methanotrophs. This article is a perspective review of the effects of climate change and ecosystem restoration on peatland microbial communities and the implications for C sequestration and climate regulation. It is authored by peatland scientists, microbial ecologists, land managers and non-governmental organisations who were attendees at a series of three workshops held at The University of Manchester (UK) in 2019–2020. Our review suggests that the increase in methane flux sometimes observed when water tables are restored is predicated on the availability of labile carbon from vegetation and the absence of alternative terminal electron acceptors. Peatland microbial communities respond relatively rapidly to shifts in vegetation induced by climate change and subsequent changes in the quantity and quality of below-ground C substrate inputs. Other consequences of climate change that affect peatland microbial communities and C cycling include alterations in snow cover and permafrost thaw. In the face of rapid climate change, restoration of a resilient microbiome is essential to sustaining the climate regulation functions of peatland systems. Technological developments enabling faster characterisation of microbial communities and functions support progress towards this goal, which will require a strongly interdisciplinary approach.Natural Environment Research Council (NERC

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification