bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new method for characterizing the heat transfer capacity of the divertor and high heat flux components
Authors: Lin Qianqian , Cao Lei , Zhuang Qing , Mou Nanyu , Han Le , Yao Damao 
Published: July 2023

Abstract
The divertor is usually exposed to extreme incident heat flux conditions in nuclear fusion engineering and its ability to remove the heat is extremely crucial for the safe operation of magnetic confinement nuclear fusion device. The evaluation of the heat removal capacity of the divertor has been always based on high heat flux (HHF) tests. Yet such methods are only available for the small size of experimental components, it is more difficult to compare under different loading and cooling conditions. In order to assess the heat removal capacity in real time and accurately, a new method was developed to characterize the heat removal capacity of the divertor and other high heat load components based on the cooling water thermal decay time constant, the time constants model has also been established. The thermal decay time constant was obtained by fitting the characteristic curves of the water temperature differences with time during the cooling phase of different components under HHF tests. This index is used to quantitatively analyze, characterize and evaluate the heat transfer capacity of the system of the divertor.
Meta-learning digitized-counterdiabatic quantum optimization
Authors: Chandarana Pranav , Vieites Pablo Suárez , Hegade Narendra N , Solano Enrique , Ban Yue , Chen Xi 
Published: July 2023

Abstract
The use of variational quantum algorithms for optimization tasks has emerged as a crucial application for the current noisy intermediate-scale quantum computers. However, these algorithms face significant difficulties in finding suitable ansatz and appropriate initial parameters. In this paper, we employ meta-learning using recurrent neural networks to address these issues for the recently proposed digitized-counterdiabatic quantum approximate optimization algorithm (QAOA). By combining meta-learning and counterdiabaticity, we find suitable variational parameters and reduce the number of optimization iterations required. We demonstrate the effectiveness of our approach by applying it to the MaxCut problem and the Sherrington–Kirkpatrick model. Our method offers a short-depth circuit ansatz with optimal initial parameters, thus improving the performance of the state-of-the-art QAOA.
Decay dynamics of a giant atom in a structured bath with broken time-reversal symmetry
Authors: Du Lei , Chen Yao-Tong , Zhang Yan , Li Yong , Wu Jin-Hui 
Published: July 2023

Abstract
We study in this paper the decay dynamics of a two-level giant atom, which is coupled to a quasi-one-dimensional sawtooth lattice exposed to uniform synthetic magnetic fluxes. In the case where the two sublattices have a large detuning, the giant atom is effectively coupled to a single-band structured bath with flux-controlled energy band and time-reversal symmetry. This feature significantly affects the decay dynamics of the giant atom as well as the propagation of the emitted photon. In particular, the giant atom can exhibit chiral spontaneous emission and allow for nonreciprocal delayed light, which are however unattainable by coupling a small atom to this lattice. Giant atoms with different frequencies can be designed to emit photons towards different directions and with different group velocities. Our results pave the way towards engineering quantum networks and manipulating giant-atom interference effects.
Evaluation of electrical properties of graphene nanopowder-dispersed propylene glycol-water solutions
Authors: Surakasi Raviteja , Sekhar Gedela Chandra , Pakalapati Janaki , Pakalapati Ramya , Rafeeq Mohd 
Published: July 2023

Abstract
Nanofluids, which are suspensions of nanoparticles in base fluids, have gained significant attention in recent years due to their enhanced thermal and electrical properties. In particular, propylene glycol-water nanofluids have been extensively investigated for their electrical properties. The primary goal of this study is to evaluate the electrical characteristics of nanofluids containing graphene powder distributed in propylene glycol-water. Compositions containing 100:0, 75:25, as well as 50:50 of Propylene Glycol as well as Water were created, along with other nano fluids. Both types of base fluids were infused with graphene at quantities of 0.25 as well as 0.5 percent, respectively. The assessment of electrical characteristics in nanofluids includes the analysis of parameters like breakdown voltage, permittivity, resistivity, and electrical conductivity. With the increase in the diameter there is an increase in the value of resistivity with the dispersion of graphene nano powder whereas breakdown voltage, permittivity and electrical conductivity have been decreased with the increase in the diameter. Overall with the dispersion of graphene in nano powder the electrical properties have been enhanced. Furthermore, it discusses the underlying mechanisms and provides insights into potential applications of propylene glycol-water nanofluids in electrical and electronic systems.
Helitronics as a potential building block for classical and unconventional computing
Authors: Bechler N T , Masell J 
Published: July 2023

Abstract
Magnetic textures are promising candidates for unconventional computing due to their non-linear dynamics. We propose to investigate the rich variety of seemingly trivial lamellar magnetic phases, e.g. helical, spiral, stripy phase, or other one-dimensional soliton lattices. These are the natural stray field-free ground states of almost every magnet. The order parameters of these phases may be of potential interest for both classical and unconventional computing, which we refer to as helitronics. For the particular case of a chiral magnet and its helical phase, we use micromagnetic simulations to demonstrate the working principles of all-electrical (i) classical binary memory cells and (ii) memristors and artificial synapses, based on the orientation of the helical stripes.
LPF: a framework for exploring the wing color pattern formation of ladybird beetles in Python
Authors: Lee Daewon 
Published: July 2023

Abstract

Summary
Biological pattern formation is one of the complex system phenomena in nature, requiring theoretical analysis based on mathematical modeling and computer simulations for in-depth understanding. We propose a Python framework named LPF to systematically explore the highly diverse wing color patterns of ladybirds using reaction-diffusion models. LPF supports GPU-accelerated array computing for numerical analysis of partial differential equation models, concise visualization of ladybird morphs, and evolutionary algorithms for searching mathematical models with deep learning models for computer vision.

Availability and implementation
LPF is available on GitHub at https://github.com/cxinsys/lpf.
O04 HPV8 E6 leads to Lrig1+ keratinocyte stem cell expansion
Authors: Shorning Boris , Morgan Huw J , Olivero Carlotta , Borgogna Cinzia , Gariglio Marisa , Akgul Baki , Patel Girish K 
Published: July 2023

Abstract
Actinic keratoses (AKs) represent the precursor skin lesions in the pathogenesis of up to 82% of cutaneous squamous cell carcinoma (cSCCs). However, current treatment of AK lesions leads, at best, to only a 75% reduction in cSCCs for 1 year, and relies on therapies using topical chemotherapy, immune stimulants or surgical destruction. We have previously shown that 44% of AK tissue sample histologies contain koilocytes, and genotyping universally identified human papillomavirus 8 (HPV8). To determine the cell signalling basis for HPV8 Lrig1 hair follicle junctional zone keratinocyte stem cell proliferation and expansion, we sought to identify the integral early region gene(s). Skin histology of HPVtg mice expressing individual early-region genes (E2, E4, E6 and E7) identified both E2 and E6 mouse skin as having broadened hair follicle infundibulum. Whole-mount immunofluorescent labelling demonstrated Lrig1 proliferation and expansion in E6 mice only, which we confirmed by flow cytometric analysis. Compared to wild-type (WT) mice, E6 mice Lrig1 flow-sorted cells had lower expression of the differentiation marker keratin 10 but comparable levels of Sox9 and cMyc, consistent with expansion of keratinocyte stem cells, as confirmed by colony-forming efficiency assay (WT 0.05 ± 0.043 vs. E6 0.24 ± 0.11). E6-transduced, but not E7-transduced, HaCaT keratinocytes demonstrated reduced differentiation and increased p63 expression with induced differentiation using calcium shift. Compared to vector control and E7-transduced, E6-transduced HaCaT keratinocytes demonstrated increased migration and colony-forming efficiency but similar proliferation, consistent with greater expression of pSTAT3 and ΔNP63. Ingenuity pathway analysis of previously determined E6 binding partners identified p300 as a regulator of STAT3 activation. Small interfering RNA targeting P300 in E6-transduced HaCaT cells led to a reduction in pSTAT3 and ΔNP63. Pull-down experiments show that E6 bound acetylated p300, which, in turn, led to increased expression of STAT3 regulated genes. The E6K137N mutation in transgenic mice, wherein E6 does not bind p300, do not develop papilloma or cSCC. Our findings show that E6, not E7, as often observed in α-serotype HPV, was responsible for HPV8-induced Lrig1 hair follicle junctional zone keratinocyte stem cell expansion.
O08 Using single-cell transcriptomics to characterize early mechanisms of psoriasis resolution
Authors: Francis Luc , McCluskey Daniel , Ganier Clarisse  , Du-Harpur Xinyi , Baudry David , Dhami Pawan  , Barker Jonathon , Smith Catherine , Capon Francesca  , Mahil Satveer 
Published: July 2023

Abstract
The use of biological drugs targeting the interleukin (IL)-23/IL-17 axis has greatly improved outcomes in people with psoriasis, with an increasing number achieving clear skin (‘remission’). However, the early mechanisms of biologic-induced psoriasis resolution are yet to be fully explored. Longitudinal sampling of resolving disease tissue provides the opportunity to uncover the dynamic cellular and molecular events triggered by these powerful treatments. Identifying the early sequence of events and key drivers underpinning psoriasis resolution may help to guide future treatment strategies. We performed single-cell RNA sequencing (scRNA-seq) on skin biopsies from five individuals with psoriasis who achieved remission upon treatment with the exemplar IL23p19 inhibitor biologic risankizumab. We profiled whole skin at baseline, and at days 3 and 14 of treatment. We filtered, integrated, scaled and normalized the scRNA-seq data set using R. Ingenuity pathway analysis and the CellChat R package were used to explore canonical pathways and receptor–ligand interactions, respectively. RNA in situ hybridization (RNA ISH) was used to identify the spatial context of cell populations of interest using three independently ascertained patients, sampled at days 0 and 14 of risankizumab treatment. The final scRNA-seq data set comprised 164 741 cells We identified 39 clusters in whole skin, including keratinocyte, fibroblast, myeloid cell and T-cell subsets. We found marked differences in transcript levels between day 0 and day 3 of biological treatment using differential gene expression analysis, with the largest number of modulated genes observed among fibroblast and myeloid cell types. We identified a novel fibroblast population which was reduced in relative abundance at day 14 of treatment in lesional psoriasis skin and absent in nonlesional skin. Pathway analysis of this fibroblast population showed an association with inflammatory signalling, and receptor–ligand interaction analysis revealed proinflammatory cytokine signalling to differentiated keratinocytes. The presence of this fibroblast population in psoriasis skin was validated by deconvolution of independent, publicly available bulk RNA sequencing data sets. Finally, we confirmed the localization of this fibroblast population in the upper dermis of psoriasis skin and the reduced abundance after 14 days of risankizumab treatment using RNA ISH of lesional skin from three independently ascertained patients. Our findings provide a high-resolution atlas of the early changes in the skin microenvironment of resolving psoriasis. We identify a response in a novel fibroblast population in the early stages of biological treatment. We are currently exploring the role of this fibroblast population as a driver cell type in psoriasis resolution.
O13 JAK inhibitors to restore skin barrier function in ARCI
Authors: Giusto Elena , Enjalbert Florence , Rognoni Emanuel  , Caley Matthew , O’Toole Edel  
Published: July 2023

Abstract
The autosomal recessive congenital ichthyoses (ARCI) are a group of chronic conditions where there is unmet therapeutic need. Harlequin ichthyosis (HI) is the most severe form of ARCI, with aberrant differentiation of the epidermis leading to a severe barrier defect. It is caused by mutations in ABCA12, a lipid transporter involved in the transport of glucosylceramides from the lamellar body to the lipid lamellae. Lamellar ichthyosis is caused by mutations in TGM1. Several Janus kinase (JAK) inhibitors (JAKi) inhibiting the JAK–STAT pathway are now licensed for atopic dermatitis. Previous work from our group in an in vitro HI model showed that tofacitinib had a restorative effect on the lipid barrier. We hypothesized that JAKi A, B and C could restore the epidermal barrier in both HI three-dimensional (3D) organotypic models (OTs) made using ABCA12 CrispR-Cas9 knockout and wild-type keratinocytes and ARCI 3D OTs generated with short hairpin RNA knock down of TGM1. The JAKi were tested at three concentrations in the 3D models (20, 50 and 500 nmol L–1 for JAKiA; 10, 50 and 250 nmol L–1 for JAKiB; 2, 25 and 125 nmol L–1 for JAKiC) and vehicle only was used as the control. The OTs were stained with haematoxylin and eosin, Nile red and differentiation markers such as K10, K14, transglutaminase 1 (TGM1) and involucrin. All three JAKi had a positive effect on the epidermal barrier. The epidermal structure looked more organized and uniform, with an increase in neutral and polar lipids in the upper epidermis. The differentiation markers showed normalization of the expression of involucrin, K10 and TGM1 at the same drug concentrations. These results suggest that JAKi have a generalized positive effect on the skin barrier and will be further investigated in an in vivo mouse model of HI.
P02 Potential for the loss of endothelial AMBRA1 expression in the tumour microenvironment to identify high-risk patient subsets with nonulcerated AJCC stage I/II melanoma
Authors: Stout Roisin , Best Katie , Cosgarea Ioana , Lovat Penny  , Armstrong Jane 
Published: July 2023

Abstract
With the recent inclusion of adjuvant therapy for the management of patients with AJCC stage II melanomas there is increased emphasis on the identification of both prognostic and companion biomarkers for early-stage tumours. The expression of AMBRA1 and loricrin (AMBLor) in the epidermis overlying early-stage nonulcerated primary melanomas has recently been identified as a prognostic biomarker able to identify genuinely low-risk tumour subsets. Pilot data also show that loss of AMBLor is associated with loss of AMBRA1 expression in the surrounding tumour endothelium. The aim of the present study was therefore to define the potential of endothelial AMBRA1 expression to identify AJCC stage I/II melanomas at risk of metastasis. Endothelial AMBRA1 expression was determined in a cohort of 48 AJCC stage I/II melanomas previously subjected to automated immunohistochemical analysis for AMBRA1 expression and defined as tumours with loss of AMBLor. Endothelial AMBRA1 expression determined by positive pixel count using Aperio Image-Scope and normalized to vessel area, revealed variable AMBRA1 expression in the intra- and/or peritumoral vessels within 500 µm of the tumour mass. Further analysis revealed a significantly increased proportion of intra-/peritumoral vessels (23.7%) with low AMBRA1 (&lt; 50% of mean total vessel expression) in melanomas that metastasized vs. 12.4% of vessels with low AMBRA1 expression in tumours that remained localized (P = 0.002). Kaplan–Meier analysis additionally demonstrated a significant reduction in 5-year recurrence-free survival (RFS) to 33% for patients with melanomas with &gt; 12% intra-/peritumoral vessels with reduced AMBRA1 expression vs. 76% RFS for patients with &lt; 12% intra-/peritumoral vessels in which AMBRA1 expression was reduced (hazard ratio 5.16, 95% confidence interval 2.05–13; P = 0.003). Collectively, these data suggest that endothelial AMBRA1 expression may serve as a prognostic and companion biomarker to identify and stratify high-risk subsets of patients with early-stage melanoma for adjuvant treatment.
P04 Skin concentration of 7-dehydrocholesterol is not a limiting factor for vitamin D3 synthesis in older versus younger adults, and a similar response occurs to UVR in these age groups
Authors: Borecka Oktawia , Dutton John J , Tang Jonathan C Y   , Fraser William D , Rhodes Lesley E 
Published: July 2023

Abstract
Skin exposure to ultraviolet radiation (UVR) triggers conversion of precursor 7-dehydrocholesterol (7DHC) to vitamin D3, which then enters the bloodstream. The aim of this study was to assess if skin 7DHC concentration differs between younger and older adults, and to explore the impact of solar-simulated UVR (SSR) on 7DHC (in skin) and vitamin D3 (cholecalciferol; in serum) in these age groups. Younger (n = 10, 18–40 years) and older (n = 11; 65–89 years) adults of skin phototype I–III were exposed to a suberythemal dose of SSR (95% UVA, 5% UVB, 1.3 standard erythemal dose) over 35% body surface area in the UK winter. Six 5-mm buttock skin punch biopsies were taken: two from unexposed skin, two immediately post-UVR and two at 24 h post-UVR. Blood was taken at baseline, 24 h and 7 days post-UVR. Skin and serum samples were assayed using high-performance liquid chromatography–tandem mass spectrometry. Baseline mean (SD) 7DHC concentrations were 0.22 (0.07) µg mg–1 and 0.25 (0.08) µg mg–1 in younger and older adults, respectively. Immediately post-UVR, 7DHC concentrations were 0.27 (0.10) µg mg–1 and 0.22 (0.08) µg mg–1 in younger and older adults, respectively, and 24 h post-UVR they were 0.27 (0.08) µg mg–1 and 0.28 (0.13) µg mg–1, respectively. Baseline serum vitamin D3 concentrations in younger adults were 1.5 (1.5) nmol L–1 vs. 1.5 (1.7) nmol L–1 in older adults; 24 h post-UVR they were 3.1 (2.0) nmol L–1 in younger adults vs. 2.5 (2.0) nmol L–1 in older adults and 7 days post-UVR they were 2.0 (2.1) vs. 1.7 (1.2) nmol L–1, respectively. No significant difference was seen in any parameter between age groups. Thus, in contrast to previous assumptions, skin 7DHC concentration is not a limiting factor for vitamin D3 synthesis in healthy older adults relative to younger adults. The early vitamin D3 biosynthetic pathway does not appear to differ between these age groups.
P20 Engineered peptide for KLK5 inhibition – therapeutic intervention for atopic dermatitis
Authors: Mah Jeffrey , Macmillan Derek , Di Wei-Li 
Published: July 2023

Abstract
Epidermal proteases, such as human tissue kallikrein-related peptidase, regulate skin barrier function through keratinocyte desquamation, antimicrobial defence, inflammatory response and barrier maintenance. It has been reported that the activity of kallikreins (KLKs) is upregulated in inflammatory skin disorders, including atopic dermatitis (AD; eczema). AD is a very common, chronic and relapsing inflammatory skin disease affecting 15–20% of children in the UK. Studies have shown that enhanced KLK5 results in AD-like skin architecture with an impaired skin barrier function. In this study, we aimed to develop a potent and selective inhibitor that targets KLK5 and restores epidermal barrier dysfunction in AD. Nature-based sunflower trypsin inhibitor 1 (SFTI), a small, circular peptide exhibiting wide-ranging serine protease inhibition can be engineered and modified to become a potent inhibitor specific for tissue kallikreins; our previous study also indicated that it was able to permeate through the outermost layer to exert its inhibitory action on serine proteases. In this study, we wanted to develop a more potent and specific inhibitor of KLK5 based on a lead SFTI analogue (‘analogue 6’) that was previously developed by our research group. Computer modelling was employed to assess the structure and binding affinity between KLK5 and SFTI-1. Designed SFTI analogues were then synthesized using solid phase peptide synthesis. The inhibitory effect was evaluated by its half maximal inhibitory concentration (IC50) against KLK5 using a 7-amido-4-methylcoumarin assay and further tested by protease-activated receptor 2-dependent intracellular calcium influx assay in keratinocytes. Computer modelling then indicated that an endogenous inhibitor was comparable with the analogue 6 we developed previously. Analogue 6 was further modified, based on the endogenous inhibitor structure, and synthesized. The new analogue achieved an IC50 of 14 nmol L–1 for KLK5, which was a fourfold increase in potency compared to analogue 6 (IC50 56 nmol L–1) and a 16-fold increase vs. SFTI-1 wild type (IC50 230 nmol L–1). Further, the new analogue could inhibit proteinase-activated receptor 2 (PAR2)-dependent intracellular calcium influx by modulating the activation of PAR2 receptor, a KLK5 downstream molecule in keratinocytes at a minimum inhibitor-to-enzyme molar ratio of 1:1. The novel potent inhibitor for KLK5 could be a potential therapeutic intervention for AD and other inflammatory skin conditions with enhanced KLK5.
P23 Inducible E-cadherin ablation drives malignant progression in HK1.ras.fos.PTENflx/flx carcinogenesis and induces conversion of HK1.fos.PTENflx/flx keratoacanthoma
Authors: Zaweia Rema , Alyamani Abdullah , McMenemy Carol  , Quinn Jean , Greenhalgh David  
Published: July 2023

Abstract
Inducible ablation of E-cadherin expression has been investigated in mouse skin carcinogenesis driven by Ras and Fos activation (HK1.ras; HK1.fos), and conditional (cre/lox) PTEN knockout exclusively in the epidermis. Previously, analysis of endogenous E-cadherin expression in stage-specific HK1.ras/fos/Δ5PTEN tumours showed E-cadherin expression became reduced at the invasive front of well-differentiated squamous cell carcinomas (wdSCCs) following p53 loss, and where retention of p21 minimized Akt activation and further progression. To validate stage-specific causality of E-cadherin loss, RU486-inducible conditional E-cadherin knockout was introduced into HK1.ras/fos/Δ5PTENflx/flx genotypes employing the cre/LoxP system (K14cre-ΔE-cadflx/flx). Initial observations in RU486-treated compound HK1.ras/fos/ΔPTENflx/flx-ΔE-cadflx/flx mice found that E-cadherin ablation appeared to accelerate malignant conversion, again associated with p53 loss; however, the main effect was on malignant progression and invasion, as wdSCCs displayed rapid progression to aggressive SCCs. Malignant progression also implicated β-catenin activation, finding increased nuclear expression, alongside loss of membranous expression, in the invasive basal layer keratinocytes, together with loss of p21 and increased p-Akt1 activity. In addition, preliminary data for E-cadherin loss in HK1.fos/Δ5PTEN keratoacanthoma aetiology now showed malignant conversion to invasive wdSCC, again associated with increased β-catenin activation. These wdSCCs may have retained a degree of correct adhesion signalling, as basal layer HK1.fos/Δ5PTEN-ΔE-cadflx/flx keratinocytes exhibited both membranous and nuclear p-β-catenin expression; hence, in the absence of Ras, progression stalled at wdSCC. Collectively, these data show that, in some contexts (hyperplasia/papillomas), E-cadherin loss can be tolerated via increased differentiation, while in carcinogenesis, following overt tumour appearance, conditional ablation of E-cadherin drives invasion and malignant progression, consistent with roles in cell–cell adhesion and deregulated signalling to β-catenin.