Preparation of a porphyrinic bis(pyridyl aldehyde) and its supramolecular complexes

Shape-specific molecular assemblies require the preparation of the constituent building blocks with the necessary properties to bias exclusive formation of the proposed structures. In this work, a novel linear porphyrin dialdehyde was synthesised and used to assemble a supramolecular grid via Cu(I) heteroleptic phenanthroline/pyridyl imine complexation, and a tetrahedral cage via Fe(II) pyridyl imine coordination.We gratefully acknowledge funding from the Consejo Nacional de Ciencia y Tecnologia (CONACYT) Mexico (MAAG) and the Cambridge NanoDTC (CRG).This is the author accepted manuscript. The final version is available from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C5CC06399

Environmental assessment of Swedish clothing consumption - six garments, sustainable futures

The aim of this work was to map and understand the current environmental impact of Swedish clothing consumption. A life cycle assessment (LCA) was used to evaluate the environmental impact of six garments: a T-shirt, a pair of jeans, a dress, a jacket, a pair of socks, and a hospital uniform, using indicators of climate impact (also called “carbon footprint”), energy use, water scarcity, land use impact on soil quality, freshwater ecotoxicity, and human toxicity. The environmental impact of the six garments was then scaled up to represent Swedish national clothing consumption over one year.In addition to fulfilling this aim, the report is a unique and rich source of transparently documented inventory data on a large number of textile processes – hopefully this can be of use for other LCA practitioners. The report updates Roos et al. (2015), which was the first detailed LCA study of Swedish clothing consumption at the national level. Since the publication of the first edition, several LCA studies of textile production processes and global apparel consumption have been published, which have enabled us to refine the inventory model and benchmark the results.The work was done in Mistra Future Fashion, a cross-disciplinary research program in 2011-2019 which aimed to enable a systemic change in the Swedish fashion industry leading to sustainable development in industry and society

Towards a Quantified Design Process: bridging design and life cycle assessment

In this paper we describe how design researchers and environmental researchers are making a joint effort in overcoming the disciplinary barriers for collaboration. By comparing existing processes and identifying potential opportunities arising from inter-disciplinary collaboration the aim is to propose methods for building a bridge between disciplines. A model for “quantified design” is generated, and explored, relevant for designers, design researchers as well as LCA researchers

LCA on fast and slow garment prototypes

This report summarises the environmental assessment work done in the Mistra Future\ua0Fashion program focussed on the potential to improve the environmental performance\ua0of garments and adapt them to a circular economy. The approaches examined in this\ua0report include reducing the environmental impacts from fast-fashion trends by making\ua0garments from paper-based materials, or by extending garment life cycles.This assessment considers two paper-based garments. One is made primarily from paper pulp but enhanced with a polylactic acid polymer. This garment is worn between\ua0two to five times before being recycled as newspaper. The other fast garment is\ua0made of paper pulp, polylactic acid and nanocellulose. It has a similar life cycle but\ua0is composted after use life. These garments are compared with a standard t-shirt. The report also considers a slow-paced scenario in which a polyester garment passes between several owners and is regularly changed to maintain its appeal. It is updated\ua0with a transfer sublimation overprint three times, making the garment darker each\ua0time. Later it is joined with an outer shell of new material using laser technology tomake a cropped, box-cut jacket.The assessment was performed using environmental life cycle assessment. More\ua0particularly, the assessment was based on attributional process analysis with cutoff allocation procedures and comparison with a traditional reference garment life cycle. Key environmental effect categories considered here include climate change (greenhouse gas emissions), freshwater eutrophication, freshwater ecotoxicity and human toxicity (cancer and non-cancer).The results indicate that the environmental outcomes of the paper-based garments can be competitive with the reference garment, particularly when the user is assumed to throw away a fully functional reference garment after five uses. This assumption may be true for some users, but the number of uses is considerably lower than the typical or the potential lifespan of the reference garment. The main factor assisting the paper-based garments is the reduction in the impacts per mass associated with material manufacturing (fibres, spinning, knitting), and also their lighter masses.\ua0Avoided impacts in the use phase play a secondary role on account of their location in\ua0Sweden with its low-carbon energy mix. The long-life garments are also competitivecompared with their reference garments. This is primarily a consequence of how extending garment life avoids the production of new garments. The environmental impacts associated with transfer sublimation dye reprinting and laser processing do\ua0not significantly impact the overall environmental performance of the extended longlife\ua0garments, though confidentiality of data prevents a full assessment of these.The garments in this report are pilot products and explorative scenarios rather\ua0than attempts to model existing business or behavioural patterns. The reader\ua0should therefore take care to keep the results in context when interpreting them.\ua0Nevertheless, the results suggest the value of pursuing the potential associated with these garment life cycles. We should also bear in mind that while the reference garments in this assessment are based on typical usage patterns, other more\ua0sustainable patterns are feasible

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

NetMHCpan, a Method for Quantitative Predictions of Peptide Binding to Any HLA-A and -B Locus Protein of Known Sequence

Binding of peptides to Major Histocompatibility Complex (MHC) molecules is the single most selective step in the recognition of pathogens by the cellular immune system. The human MHC class I system (HLA-I) is extremely polymorphic. The number of registered HLA-I molecules has now surpassed 1500. Characterizing the specificity of each separately would be a major undertaking.Here, we have drawn on a large database of known peptide-HLA-I interactions to develop a bioinformatics method, which takes both peptide and HLA sequence information into account, and generates quantitative predictions of the affinity of any peptide-HLA-I interaction. Prospective experimental validation of peptides predicted to bind to previously untested HLA-I molecules, cross-validation, and retrospective prediction of known HIV immune epitopes and endogenous presented peptides, all successfully validate this method. We further demonstrate that the method can be applied to perform a clustering analysis of MHC specificities and suggest using this clustering to select particularly informative novel MHC molecules for future biochemical and functional analysis.Encompassing all HLA molecules, this high-throughput computational method lends itself to epitope searches that are not only genome- and pathogen-wide, but also HLA-wide. Thus, it offers a truly global analysis of immune responses supporting rational development of vaccines and immunotherapy. It also promises to provide new basic insights into HLA structure-function relationships. The method is available at http://www.cbs.dtu.dk/services/NetMHCpan

Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.

Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health

Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.

Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.Peer reviewe

Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery