Elongated semiconductor nanocrystals with oriented transition dipoles, such as nanorods (NRs) and elongated nanoplatelets (NPLs), can exhibit emission anisotropy when confined in thin films. In this work, we report the effect of nanocrystal alignment on thin polymer film optical properties including absorbance, fluorescence polarisation and light guiding. We find that changes in absorbance after stretching films containing elongated nanocrystals are associated with changes in nanocrystal alignment. Stretching the NPL films induces fluorescence anisotropy, which follows an exponential trend that can be approximated as linear within a moderate range of true strain values. This empirical relationship provides a means to monitor strain in polymers undergoing deformation. The light guiding properties of polymer films containing luminescent nanocrystals are also investigated by applying experimental and Monte Carlo simulation methodologies developed for the luminescent solar concentrator field. We show that drop cast polymer films containing spherical quantum dots, with isotropic fluorescence, more effectively guide light to the film edges compared with elongated nanocrystals. The elongated nanocrystals are aligned in the film plane by both stretching and drop casting processes, resulting in increased fluorescence emission from the film faces due to escape cone losses.

Introduction and Hypothesis: Through the production of prostacyclin (PGI2), cyclooxygenase (COX)-2 protects the cardio-renal system. Restraining methylarginines (ADMA, SDMA), which are biomarkers of renal and cardiovascular disease and inhibitors (ADMA) of cardioprotective endothelial nitric oxide synthase (eNOS), has been suggested as a contributory pathway. However, the relationship between renal function, COX-2 and methylarginines remains unclear. Methods: Using plasma from genetically modified mice with germline global deletion of COX-2 or PGI 2 synthase (PGIS) and human plasma from a unique individual lacking COX-derived prostaglandins due to a loss of cPLA 2 , before and after receiving a cPLA 2 -replete transplanted donor kidney, we measured methylarginines, arginine and citrulline using UHPLC-MS/MS. Renal function was assessed by measuring cystatin C by ELISA. To eliminate the impact of renal function in vivo , methylarginine and PGI 2 release from organotypic kidney slices in culture were quantified by ELISA. Results: Plasma ADMA, SDMA, citrulline and cystatin C, were similarly elevated in samples from the patient lacking COX/PGI 2 capacity compared to levels in healthy volunteers. Renal function, ADMA, SDMA and citrulline returned towards normal range when the patient received a genetically normal kidney, capable of COX/PGI 2 activity. Cystatin C correlated with ADMA, SDMA and citrulline. Loss of COX-2 or PGIS in mice increased plasma levels of ADMA, SDMA and cystatin C. As in human, SDMA, ADMA and citrulline but not arginine positively correlated with cystatin C. Levels of analytes in conditioned media of kidney slices (24h) were not altered in tissue from COX-2 KO (6-keto=14.0±1.8, ADMA=1.0±0.06, SDMA=0.30±0.05; n=8) compared to wildtype mice (66-keto=15.0±1.7, ADMA=0.98±0.06, SDMA=0.24±0.01; n=12). Conclusions: COX-2 and PGI2 are critical regulators of renal function. Plasma methylarginines are integrally linked to renal homeostasis.

Recent efforts to synchronise laboratory protocols for measuring luminescent solar concentrator (LSC) efficiencies, and to use consistent terminology, has been driven by a prior lack of consensus on both terminology and the reporting of experimental results. This analysis seeks to understand how terminology in the field of luminescent solar concentrators has been used in the past, and to recommend the most clear and consistent terminology that should be used for future publications. LSCs for electrical power generation, referred to as luminescent solar concentrator photovoltaics (LSC-PV), should be treated as integrated photovoltaic cells. Consequently, the power conversion efficiency (PCE) and external quantum efficiency (EQELSC(λ)) should be reported, as they would be with any other photovoltaic device. The term "optical efficiency" has been defined inconsistently throughout the literature, with several different efficiency expressions, and thus it should be interpreted with great care. The highest values for the three most common LSC efficiency metrics have been examined in detail and their validity and significance have been assessed. Among the examined results, it has been assessed that the highest reliable results are a PCE of 7.1%, an optical power efficiency (ηopt) of 7.8% and an external photon efficiency (ηext) of 6.8%. A significant number of highest efficiencies reported have used questionable calculation methods meaning those efficiency values should not be used as a comparison for current and future publications. Additionally, reporting optical power efficiency is not recommended unless optical power is relevant to the device application.

A Monte-Carlo ray tracing simulator with a graphical user interface (MCRTS-GUI) has been developed to provide a quantitative description, performance evaluation and photon loss analysis of luminescent solar concentrators (LSCs). The algorithm is applied to several practical LSC device structures including multiple dyes in the same waveguiding layer, and structures where a dye layer is sandwiched between clear substrates. The effect of the host matrix absorption and the influence of the neighboring layers are investigated. Validations demonstrate that the MCRTS-GUI developed provides a reliable and accurate description of LSC performance. Code for the mixed-dye single layer configuration is converted into a ray-tracing package with a user-friendly interface and is made available as open source software.

The effect of quantum dot (QD) aggregation on scattering in luminescent solar concentrators (LSCs) was investigated to improve device efficiency. LSCs have the potential to expand the solar collection capacity of structures in applications such as solar harvesting windows or sound barriers. LSCs suffer from low efficiencies and one major efficiency loss in QD-based LSCs is light scattering, caused by QD aggregates. Dispersion of QDs in acrylic monomers was investigated using dynamic light scattering (DLS) to find optimal parameters for fabricating scatter-free polymer sheets containing QDs. The monomers investigated were methyl methacrylate (MMA), lauryl methacrylate (LMA) and ethylene glycol dimethacrylate (EGDMA). Three monomer compositions have been described which can be polymerised into matrices which encapsulate QDs with good dispersion.

Introduction: Thromboxane A2 [TxA2] is generated from arachidonic acid by cyclooxigenase-1 (COX-1) (prostaglandin H synthase-1) and thromboxane synthase. Aspirin, which irreversibly inhibits COX-1, is a widely used antiplatelet therapy with proven clinical efficacy. Inherited platelet disorders (IPD) are rare diseases caused by alterations of relevant genes in platelet formation and/or function. Despite the relevance of the TxA2 pathway in platelet physiology, few patients with mutations in PTGS1, the gene encoding COX-1, have been identified (<5 cases worldwide). Objective: Characterization of a patient with aspirin-like platelet defect and moderate bleeding, enrolled in the Spanish multicentric project "Functional and molecular characterization of patients with IPD". Methods: The index case is a 13-year-old adopted girl of Asian origin, referred because of moderate chronic bleeding (BAT-ISTH=6) and an aspirin-like platelet dysfunction. No coagulation defect or other relevant clinical symptoms were present. Platelet phenotyping included: blood count, PFA-100; platelet aggregation [LTA], glycoproteins (GP), activation and secretion of granules by flow cytometry (FC), TxA2 synthesis by enzyme-immunoassay, synthesis of eicosanoids by tandem gas chromatography with mass spectrometry (LC-MS), western-blot (WB) of platelet lysates, and immunofluorescence (IF) assays. The patient's DNA was analyzed with a HTS-gene panel (Bastida et al, Haematologica 2018). A HEK 293T cell transfection model was established to further assess the pathogenicity of the candidate variant found in the patient. Results: The index case has normal platelet size and count (206x109/L; 11.4 fL). PFA-100 times were normal for COL-ADP and prolonged for COL-EPI (>300s). The FC analysis showed normal expression of GPs (Ib/IX, IIb/IIIa, Ia, GPVI) and reduced fibrinogen*488 binding (20-30%) in response to ADP, TRAP and low dose CRP (2ug/mL). P-selectin and CD63 secretion with agonists was comparable to those of controls. LTA was normal with ristocetin (1.25mg/mL) and TRAP (25uM), reduced by 40-50% with ADP (10uM) and collagen (3ug/mL) and absent with epinephrine (10uM), low dose collagen (1ug/mL) and arachidonic acid (1.6mM). LTA with U46619 (5uM), a direct agonist of the TxA2 receptor, was normal, suggesting a defect in TxA2 synthesis. Indeed, TxA2 levels in LTA supernatants in the patient were very low (5ng/mL; <10% vs. two controls). A significant reduction (50-90%) in TxA2 production was confirmed in the patient whole blood stimulated with collagen or TRAP, as measured by LC-MS. HTS analysis revealed that the patient is a heterozygous carrier of the variant c.428A>G, [p.Asn143Ser] in PTGS1. This variant, not previously described, affects a conserved residue in the catalytic domain of COX-1, which is one of the three N-glycosylation sites in the enzyme. The variant was not associated with reduced COX-1 expression as evaluated by WB in platelet lysates, and by IF in spread washed platelets and leukocytes. HEK 293T cells transfected with wild-type COX-1 construct (validated by RT-PCR and WB), displayed substantial TxA2 synthesis (500ng/mL; 2.5x105 transfected cells) in response to arachidonic acid. In contrast, similar transfection of p.143Ser COX-1 mutant almost abrogated this TxA2 production (≈50-75ng/mL in 2.5x105 transfected cells). Conclusion: We have identified a novel autosomal dominant COX-1 variant, p.Asn143Ser, associated with functional haploinsufficiency of the enzyme and platelet aggregation defects. To our knowledge, this case represents the third description of variants in PTGS1 (Nance, JTH 2016; Sivapalaratnam, Blood 2018), which cause platelet dysfunction and bleeding. Disclosures Almarza: Rocket Pharmaceuticals: Equity Ownership, Patents & Royalties, Research Funding. Bueren:Rocket Pharmaceuticals, Inc.: Consultancy, Equity Ownership, Patents & Royalties: Inventor on patents on lentiviral vectors filled by CIEMAT, CIBERER and F.J.D and may be entitled to receive financial benefits from the licensing of such patents, Research Funding.

Inherited defects of platelet function disorders are rare and difficult to diagnose due to lack of standardized platelet tests. An aspirin-like platelet defect is characterised by reduced thromboxane A2 (TXA2) signalling due to a defect in the arachidonic acid (AA) pathway in platelets. Patients with aspirin-like defect present with mild to moderate bleeding symptoms and impaired platelet aggregation responses to AA and ADP. This is similar to the irreversible effect of aspirin on platelets, which is mediated through inhibition of prostaglandin H synthase-1 also known as cyclooxygenase-1 (PTGS1/COX1). We for the first time report platelet function disorders due to autosomal recessive inheritance of variants in PTGS1.

Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat the condition of rheumatoid arthritis, where levels of prostaglandin E2 (PGE2) and granulocyte macrophage-colony stimulating factor (GM-CSF) are elevated in the synovial fluid. NO-NSAIDs are a new class of cyclooxygenase (COX)-inhibitors developed by coupling a nitric oxide (NO)-donating moiety to conventional NSAIDs. We show that, in cytokine-treated synoviocytes (from non-rheumatic patients), NO-naproxen and NO-flurbiprofen like their parent compounds concentration-dependently reduce the levels of PGE2 (an index of COX-2 activity), with a corresponding rise in the release of GM-CSF. Unlike acetylsalicylic acid (ASA), NO-ASA reduces the levels of PGE2, without increasing GM-CSF release, although cell viability is reduced at the highest concentration (1 mM). The effects of NSAIDs and NO-NSAIDs on GM-CSF release were attributable to the PGE2 mediated cyclic (c) AMP pathway because PGE2 reversed the effects of COX blockade. Second, phosphodiesterase inhibitors 3-isobutyl-1-methylxanthine (IBMX) and Ro-201724 (both of which elevate cAMP levels) decreased GM-CSF release, in the presence of PGE2. Finally, neither sodium nitroprusside nor zaprinast (both of which elevate cGMP levels) affected GM-CSF or PGE2 release. Our findings demonstrate that GM-CSF is regulated by NSAIDs and NO-NSAIDs via inhibition of COX and appears to be mediated via the cAMP pathway. NO-ASA is the exception, because it does not increase GM-CSF release, although at millimolar concentrations cell viability is reduced.

Mechanical forces are key regulators of cell function, particularly of cells within the arterial wall that are exposed to the shear stress and pulsatile pressure of flowing blood. The finding by Chang and colleagues in this issue of Clinical Science that cell stretch can up-regulate the expression of hypoxia-inducible factor-1alpha and vascular endothelial growth factor, which is a key regulator of blood vessel remodelling, provides us with further insight into the mechanisms underlying remodelling at sites of occlusive disease within the cardiovascular system.

ABSTRACT: Coronary artery disease is the leading cause of mortality in the West with over 1.2 million angioplasties performed annually. Despite the introduction of stents, restenosis occurs in 30–40% of vessels, which until recently has only been treated effectively by coronary artery bypass surgery. Coronary artery brachytherapy appears to provide an alternative, less invasive remedy. The mechanisms of restenosis and how these are inhibited by radiation are described here. The practicalities of radiation delivery and the history of the development of intravascular radiation as an effective clinical tool are outlined. Finally, the pitfalls of the current technology and the areas in which future research must be targeted for the field to develop are discussed. Copyright 2002 The Royal College of Radiologists. Published by Elsevier Science Ltd. All rights reserved.