8-Methoxypsoralen Levels in Blood of Vitiligo Patients and in Skin, Ophthalmic Fluids, and Ocular Tissues of the Guinea Pig

8-Methoxypsoralen (8-MOP) levels in the blood of vitiligo patients were determined through the use of a reverse- phase high-performance liquid chromatographic method. The overall recovery of the internal standards was 85-94%, with the lower detection limit of 8-MOP at 2ng. Peak blood levels as low as 130ng/ml and as high as 3892 ng/ml were obtained in patients at 1-3h following the oral administration of 0.6mg/kg body weight of Oxsoralen capsules (Elder Pharmaceuticals Co.). These results are consistent with the clinical observation that maximum response in phototherapy is obtained at about 2h after oral administration of the drug. Two hours after oral administration of 0.6mg/kg of Oxsoralen, 8-MOP levels in the epidermis, dermis, and whole skin of the guinea pig (inng/g) were: epidermis, 330 ± 20; dermis, 89 ± 16; whole skin, 379 ± 19. Also detected were 8-MOP levels of 441 ± 22ng/ml in aqueous humor, 166 ± 18ng/ml in vitreous gel, 355 ± 15ng/g in lens, and 410 ± 26ng/g in retina. These results point to the fact that the eyes of the patient must be protected from exposure to sunlight after psoralen UV treatment, and that 8-MOP is absorbed in blood unevenly and varies from patient to patient. The fact that only 50-60% of the patients responded to psoralen photochemotherapy for vitiligo may be related to the variation of absorption of the drug in individual patients

Rhodium(II) Proximity-Labeling Identifies a Novel Target Site on STAT3 for Inhibitors with Potent Anti-Leukemia Activity

Nearly 40 % of children with acute myeloid leukemia (AML) suffer relapse arising from chemoresistance, often involving upregulation of the oncoprotein STAT3 (signal transducer and activator of transcription 3). Herein, rhodium(II)-catalyzed, proximity-driven modification identifies the STAT3 coiled-coil domain (CCD) as a novel ligand-binding site, and we describe a new naphthalene sulfonamide inhibitor that targets the CCD, blocks STAT3 function, and halts its disease-promoting effects in vitro, in tumor growth models, and in a leukemia mouse model, validating this new therapeutic target for resistant AML

High Velocity Impact and Blast Loading of Composite Sandwich Panels with Novel Carbon and Glass Construction

This research investigates whether the layup order of the carbon-fibre/glass-fibre skins in hybrid composite sandwich panels has an effect on impact response. Composite sandwich panels with carbon-fibre/glass-fibre hybrid skins were subjected to impact at velocities of 75 ± 3 and 90 ± 3 m s−1. Measurements of the sandwich panels were made using high-speed 3D digital image correlation (DIC), and post-impact damage was assessed by sectioning the sandwich panels. It was concluded that the introduction of glass-fibre layers into carbon-fibre laminate skins reduces brittle failure compared to a sandwich panel with carbon-fibre reinforced polymer skins alone. Furthermore, if the impact surface is known, it would be beneficial to select an asymmetrical panel such as Hybrid-(GCFGC) utilising glass-fibre layers in compression and carbon-fibre layers in tension. This hybrid sandwich panel achieves a specific deflection of 0.322 mm kg−1 m2 and specific strain of 0.077% kg−1 m2 under an impact velocity of 75 ± 3 m s−1. However, if the impact surface is not known, selection of a panel with a symmetric yet more dispersed hybridisation would be effective. By distributing the different fibre layers more evenly within the skin, less surface and core damage is achieved. The distributed hybrid investigated in this research, Hybrid-(GCGFGCG), achieved a specific deflection of 0.394 mm kg−1 m2 and specific strain of 0.085% kg−1 m2 under an impact velocity of 75 ± 3 m s−1. Blast loading was performed on a large scale version of Hybrid-(GCFGC) and it exhibited a maximum deflection of 75 mm following a similar deflection profile to those observed for the impact experiments

Vapor grown carbon nanofiber based cotton fabrics with negative thermoelectric power

Vapor grown carbon nanofiber (CNF) based ink dispersions were used to dip-coat woven cotton fabrics with different constructional parameters, and their thermoelectric (TE) properties studied at room temperature. Unlike the positive thermoelectric power (TEP) observed in TE textile fabrics produced with similar carbon-based nanostructures, the CNF-based cotton fabrics showed negative TEP, caused by the compensated semimetal character of the CNFs and the highly graphitic nature of their outer layers, which hinders the p-type doping with oxygen groups onto them. A dependence of the electrical conductivity (r) and TEP as a function of the woven cotton fabric was also observed. The cotton fabric with the largest linear density (tex) showed the best performance with negative TEP values around - 8 lV K-1 , a power factor of 1.65 9 10-3 lW m-1 K-2 , and a figure of merit of 1.14 9 10-6 . Moreover, the possibility of a slight e- charge transfer or n-doping from the cellulose onto the most external CNF graphitic shells was also analysed by computer modelling. This study presents n-type carbon-based TE textile fabrics produced easily and without any functionalization processes to prevent the inherent doping with oxygen, which causes the typical p-type character found in most carbon-based TE materialsFEDER funds through COMPETE and by national funds through FCT – Foundation for Science and Technology within the project POCI-01-0145- FEDER-007136. E. M. F. Vieira is grateful for financial support through FCT with CMEMS-UMinho Strategic Project UIDB/ 04436/202

Synergistic toughening of composite fibres by self-alignment of reduced graphene oxide and carbon nanotubes

The extraordinary properties of graphene and carbon nanotubes motivate the development of methods for their use in producing continuous, strong, tough fibres. Previous work has shown that the toughness of the carbon nanotube-reinforced polymer fibres exceeds that of previously known materials. Here we show that further increased toughness results from combining carbon nanotubes and reduced graphene oxide flakes in solution-spun polymer fibres. The gravimetric toughness approaches 1,000 J g−1, far exceeding spider dragline silk (165 J g−1) and Kevlar (78 J g−1). This toughness enhancement is consistent with the observed formation of an interconnected network of partially aligned reduced graphene oxide flakes and carbon nanotubes during solution spinning, which act to deflect cracks and allow energy-consuming polymer deformation. Toughness is sensitive to the volume ratio of the reduced graphene oxide flakes to the carbon nanotubes in the spinning solution and the degree of graphene oxidation. The hybrid fibres were sewable and weavable, and could be shaped into high-modulus helical springs

Virus Replication Strategies and the Critical CTL Numbers Required for the Control of Infection

Vaccines that elicit protective cytotoxic T lymphocytes (CTL) may improve on or augment those designed primarily to elicit antibody responses. However, we have little basis for estimating the numbers of CTL required for sterilising immunity at an infection site. To address this we begin with a theoretical estimate obtained from measurements of CTL surveillance rates and the growth rate of a virus. We show how this estimate needs to be modified to account for (i) the dynamics of CTL-infected cell conjugates, and (ii) features of the virus lifecycle in infected cells. We show that provided the inoculum size of the virus is low, the dynamics of CTL-infected cell conjugates can be ignored, but knowledge of virus life-histories is required for estimating critical thresholds of CTL densities. We show that accounting for virus replication strategies increases estimates of the minimum density of CTL required for immunity over those obtained with the canonical model of virus dynamics, and demonstrate that this modeling framework allows us to predict and compare the ability of CTL to control viruses with different life history strategies. As an example we predict that lytic viruses are more difficult to control than budding viruses when net reproduction rates and infected cell lifetimes are controlled for. Further, we use data from acute SIV infection in rhesus macaques to calculate a lower bound on the density of CTL that a vaccine must generate to control infection at the entry site. We propose that critical CTL densities can be better estimated either using quantitative models incorporating virus life histories or with in vivo assays using virus-infected cells rather than peptide-pulsed targets