bluuebunny/crossref_metadata_2025_split huggingface dataset:
Turkey meat semi-finished products enriched with flax and flaxseed oil for the prevention of cardiovascular diseases of the population of the Smolensk region
Authors: Borisova V L , Stefanova I L , Sazonova E A , Kurskaya Yu A , Nikonorova A A 
Published: July 2023

Abstract
The article provides information about the impact of nutrition on human health and the formation of nutritional diseases. Irrational nutrition is typical for the population of Russia, in particular of the Smolensk region. The article provides an overview of the functional properties of flax seeds and linseed oil in terms of fatty acid composition and functional properties. The data of studies on the determination of fatty acid composition in samples enriched with flax seeds, flaxseed oil compared to the control sample (initial minced turkey breast meat) are presented. The introduction of functional ingredients improved the fatty acid composition and increased the efficiency of enriched semi-finished products. The positive effect of oilseed flax and flaxseed oil on the organoleptic characteristics of the developed chopped semi-finished products was noted. Improving the Omega-3: Omega-6 ratio in the developed semi-finished products allows to consider enriched semi-finished products as a functional food product.
Ways to increase the efficiency of industrial production of combined feed
Authors: Pavlidis Victoria , Chkalova Marina 
Published: July 2023

Abstract
This paper aims at finding a solution to the main problem of feed production: increasing the efficiency of the production process while improving the quality of products. The article aims to develop an adequate mathematical model of the technological process of combined feed industrial production. The authors have developed the theoretical background for describing this process on the basis of flow models within the framework of the original “three effects” concept, a stochastic model has been created taking into account the preservation of the exergy balance of the technological system. The main research tool is the apparatus of system analysis and the theory of random processes. An engineering-mathematical calculation of the parameters of the constructed model was performed, verification of the stochastic model of the technological process of preparing compound feeds in laboratory conditions was carried out. As a result of the research, the authors established the possibility of controlling the stochastic feed flow in all subsystems of the production technological system, outlined ways to solve the problem of increasing the efficiency of feed production by reducing energy costs and improving the output product granulometric composition.
New approaches to increasing the nutritional value of bread products based on the use of non-traditional cereals and biologically active substances with detoxifying properties
Authors: Altynbayeva G K , Azimova S T , Konarbayeva Z K , Tautaeva A T , Aidarkhanov A M 
Published: July 2023

Abstract
A practical solution to the problem of increasing the nutritional value of bread is the use of high-protein soy seeds and pumpkin processing product - pectin, the potential of which is to improve the quality of bread, intensify the technological process, enhance the detoxification properties of finished products, including easily fermentable sugars, nitrogenous and mineral substances, vitamins, dietary fiber. The possibility of using whole-ground soy flour in the production of poly-strain starter culture is shown, which contributes to the improvement of the vital activity of lactic acid bacteria. The introduction of poly-strain soy sourdough and 0.5% by weight of dry pumpkin pectin flour into the bread intensifies the dough making process due to easily fermentable sugars, improves the quality of the finished bread, provides it with an increased content of protein, dietary fiber, nitrogenous and mineral substances, vitamins, giving bread detoxifying properties and increasing its freshness.
CFD and experimental investigation of AM surfaces with different build orientations
Authors: Mandloi Kuldeep , Allen Angela , Cherukuri Harish , Miller Jimmie , Duttrer Brian , Raquet Jeff 
Published: July 2023

Abstract
Additive manufacturing (AM) surfaces offer the possibility of novel cooling channel geometries for high temperature applications. AM processes can optimize the internal geometry of cooling channels, which is generally constrained by limitations of conventional machining processes. The AM process gives rise to surface textures that depend on the build and scan orientations that also potentially contribute to heat-transfer characteristics and provide additional considerations for optimization. The motivation behind this research work is to explore the correlation between AM roughness characteristics (build-orientations, density of spatter deposits and their sizes, amplitudes/wavelengths, etc) and the resulting effect on heat transfer and pressure drop across cooling channels. In this study, the actual AM surfaces with different build angles were fabricated using Laser powder bed fusion (LPBF) and the roughness data of these surfaces were acquired. These measured surface topographies were used for developing simplified surfaces for the purposes of CFD simulations. Modeled AM surfaces with different build orientations were used to analyze the effect of built orientation and spatter deposits in terms of heat transfer for different flow conditions. The CFD simulations also informed the design of the experimental set-up for the validation of computational results. For the comparison, a reference smooth surface is machined from forged Inconel-625 for experiments and CFD simulations were also carried out for the validation. Results from CFD simulations show that the surface features (such as build angles and spatter deposits) significantly affect the heat transfer and fluid flow in terms of Nusselt number and pressure drop and the surface area impact on heat transfer is minimal in all the cases for both laminar and turbulent flow conditions. Under turbulent flow conditions, transverse track alignment shows the highest efficiency in terms of the Nusselt number and adding particles improves heat transfer efficiency for smooth and parallel-tracked surfaces. However, when the flow becomes laminar, reversed behavior is observed and surfaces show downside effects in terms of Nu. Also we define a performance factor that assesses the combined effects of both the thermal and the fluid flow characteristics to differentiate the performance of the AM channels.
Flexible resistive memory device based on agar
Authors: Chang Yu-Chi , Liu Hao-Jung , Chen Bo-Jhang 
Published: July 2023

Abstract
Potential applications of natural materials in environmentally friendly electronics include for information storage. In this work, natural material–agar was used to fabricate a flexible resistive memory device. Agar is one of the most widely used biomaterials for tissue engineering, medicine and other biotechnological applications. Agar is a suitable material for flexible electronics due to its good film formation, biocompatibility, low-temperature solution processability, transparency and flexibility. The flexible agar memory device described in this article exhibits an ON/OFF ratio of 103 under a bending radius of 5 mm, good bending endurance and a stable data retention time of over 104 s. Moreover, the agar could easily use a leaf as a substrate to make a fully biodegradable device. Agar, due to its exceptional flexibility, is emerging as a promising candidate for wearable and skin-compatible electronics, particularly in memory devices.
Microstructural characterization and mechanical properties of Inconel 625 wall fabricated by GTAW-based WAAM using stringer bead and circular weave pattern
Authors: Akash P , Puviyarasan M , Senthil T S , Rathinasuriyan C , Sindhiya S 
Published: July 2023

Abstract
In this work, Inconel 625 alloy was used to manufacture walls using the Wire Arc Additive Manufacturing (WAAM) technology, which is based on Gas Tungsten Arc Welding (GTAW). The wall was fabricated using a circular weave and stringer bead pattern. Microstructural analysis and tensile characteristics were evaluated for both walls. Using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and elemental mapping, the fracture zones of the tensile specimens were examined. The microstructure is mostly made up of equiaxed dendrites, with the rare presence of continuous and discontinuous cellular dendrites along the cross-section. In tensile tests, circular weaved walls performed better than stringer bead walls. The circular weave specimen had an ultimate tensile strength (UTS) of 762 MPa in the horizontal and 722 MPa in the vertical orientations. Also, the Inconel 625 wall showed anisotropic behavior (5.3%) during tensile testing. The fracture morphology analysis revealed that all the specimens were fractured as a result of large plastic deformation, corresponding to ductile failure. Based on the EDS results, the fracture zone mainly consists of Ni and Cr with a small percentage of Nb and Mo. The absence of laves phases makes the fracture mode ductile. The elemental mapping shows uniform dispersion of Ni and Cr within the fracture region, further supporting the ductile failure mode.
Semi-equivariant conditional normalizing flows, with applications to target-aware molecule generation
Authors: Rozenberg Eyal , Freedman Daniel 
Published: July 2023

Abstract
Learning over the domain of 3D graphs has applications in a number of scientific and engineering disciplines, including molecular chemistry, high energy physics, and computer vision. We consider a specific problem in this domain, namely: given one such 3D graph, dubbed the base graph, our goal is to learn a conditional distribution over another such graph, dubbed the complement graph. Due to the three-dimensional nature of the graphs in question, there are certain natural invariances such a distribution should satisfy: it should be invariant to rigid body transformations that act jointly on the base graph and the complement graph, and it should also be invariant to permutations of the vertices of either graph. We propose a general method for learning the conditional probabilistic model, the central part of which is a continuous normalizing flow. We establish semi-equivariance conditions on the flow which guarantee the aforementioned invariance conditions on the conditional distribution. Additionally, we propose a graph neural network architecture which implements this flow, and which is designed to learn effectively despite the typical differences in size between the base graph and the complement graph. We demonstrate the utility of our technique in the molecular setting by training a conditional generative model which, given a receptor, can generate ligands which may successfully bind to that receptor. The resulting model, which has potential applications in drug design, displays high quality performance in the key ΔBinding metric.
O09 Dynamic impact of chronic inflammation on epidermal autophagy pathway
Authors: Uddin Nazia , Ostano Paola , Chiorino Giovanna , di Domizio Jeremy , Gilliet Michel , Philpott Mike , Hannen Rosalind , Bergamaschi Daniele 
Published: July 2023

Abstract
Chronic inflammatory signalling significantly affects epidermal homeostasis leading to different types of skin conditions characterized by a deregulated stratification of epidermal keratinocytes. Our project aims to investigate how chronic inflammation mechanistically influences autophagy signalling in the epidermis. We have previously reported impairment of the autophagic flux in an established psoriatic keratinocyte model (PSA cells) when compared to corresponding controls from healthy skin (KT2 and NTERT cells). To understand the dynamic impact of chronic inflammation on the epidermal autophagy pathway we have custom made a cytokine cocktail which induces interleukin-1β release at different times in keratinocyte cultures and stimulates keratinocyte proliferation. Stimulation of healthy keratinocytes with chronic inflammatory cocktail-induced activation of initial steps of the autophagy process. This is confirmed by the protein expression of key components of ULK1 and VPS34 complexes. Analysis of the elongation-stage markers confirmed the activation and correct proceeding of the pathway, until we observed LC3-I accumulation. In autophagy, the phospholipid phosphatidylethanolamine (PE) is crucial for LC3-I conversion to LC3-II. Changes in phospholipid metabolism have been reported in inflammatory skin conditions, including PE downregulation in psoriatic keratinocytes. By increasing PE expression in inflamed keratinocytes, we show increased LC3-II lipidation and restoration of the autophagy pathway functionality. Moreover, inflammation-induced p62 upregulation (a cargo degraded by the lysosomal autophagy compartment) and deregulated the lysosomal membrane permeability integrity, as confirmed by the expression of glycosylated and deglycosylated lysosomal protein (LAMP1, LAMP2 and LAMP3) expression. Our data are supported by independent transcriptomic data analysis from the GEO database, comparing autophagy gene expression in psoriatic and healthy matched or nonmatched controls. Spatial transcriptomic mapping of autophagic genes in lesional psoriatic skin provided further insight into the epidermal autophagy pathway regulation in inflammatory skin conditions. Immunofluorescence staining of both healthy and psoriatic human skin samples finally translate the differences in key autophagy marker expression observed in our two- and three-dimensional cell models, including deregulation of LC3, p62 and lysosomal membrane protein expression. Overall, our results exhibit a comprehensive and mechanistical analysis of how chronic inflammation could affect the integrity of this metabolic pathway, which significantly regulates epidermal homeostasis. Our data provide novel targets for therapeutic strategies and supports autophagy stimulation as viable modes of treatment to counteract chronic inflammatory skin conditions.
P03 Hydroxypyridone antifungals induce myofibroblast apoptosis in an in vitro model of hypertrophic scars
Authors: Lapthorn Alice , Ilg Marcus , Sullivan Justine , Dziewulski Peter , Cellek Selim 
Published: July 2023

Abstract
Despite being the most common complication following burn injury, there are no medications to prevent the formation of hypertrophic scars. Myofibroblasts are key cells involved in scar formation, responsible for producing excessive amounts of extracellular matrix and have been shown to be resistant to apoptosis. We have previously shown that hydroxypyridone antifungals can inhibit the transformation of fibroblasts to myofibroblasts, and exhibit other antifibrotic effects. This study aimed to investigate the effect of these drugs on established myofibroblasts. Primary human dermal fibroblasts, derived from scars of patients with burns, were exposed to 10 ng mL–1 transforming growth factor (TGF)-β1 to induce myofibroblast transformation. The In-Cell enzyme-linked immunosorbent assay method was used to measure α-smooth muscle actin (α-SMA), with DRAQ5 staining used to measure cell viability. Concentration–response curves for the three hydroxypyridone antifungals (ciclopirox, ciclopirox ethanolamine and piroctone olamine) were constructed (0.03–300 µmol L–1) to see if the drugs could reverse myofibroblast transformation. TUNEL staining was used to investigate if the drugs (at 10 µmol L–1) induced apoptosis in the myofibroblasts. When applied to established myofibroblasts, the hydroxypyridone antifungals did not reverse myofibroblast transformation. Instead, the drugs exhibited a concentration-dependent decrease in myofibroblast cell viability. A 22% reduction in myofibroblast cell viability was observed at 10 µmol L–1, compared to fibroblasts treated in coincubation with TGF-β1 and the hydroxypyridones. To see if this reduction in cell viability was due to the induction of apoptosis in the myofibroblasts, TUNEL staining was used. TUNEL staining confirmed that the hydroxypyridone antifungals induced apoptosis in myofibroblasts after 72 h of treatment. This affect was not seen in the fibroblasts treated in coincubation with TGF-β1 and the hydroxypyridone antifungals. This is the first study to show that hydroxypyridone antifungals can induce apoptosis in established myofibroblasts, derived from burn scar tissue. Together with our previous results, this suggests that hydroxypyridone antifungals can prevent scar formation by tackling continuous myofibroblast transformation and myofibroblast persistence.
P05 Inducible MDM2 ablation increases p53 expression to block papillomatogenesis in HK1.ras transgenic mice
Authors: Crispini Ana Gutierrez , Slosarska Aleksandra , Greenhalgh David 
Published: July 2023

Abstract
Previously, p53 loss was a consistent theme in skin carcinogenesis driven by activated rasHa/fos expression (HK1.ras/fos) and ablation of phosphatase and tensin homolog (PTEN)-mediated Akt regulation (K14.creP/Δ5PTENflx), leading to well-differentiated squamous cell carcinoma. Given that MDM2 is a ubiquitin ligase that targets p53 for degradation, the potential efficacy of MDM2 functional knockout to protect p53 levels and thus inhibit tumour formation was investigated. Initial experiments investigated the inhibition of benign papilloma formation in HK1.ras mice as analysis of endogenous MDM2 status showed that activated p-MDM2166 activity was confined to suprabasal layers, resulting in strong nuclear p53 expression in basal layers that inhibited conversion. Yet, earlier hyperplasia expressed only sporadic p53/MDM2, suggesting that should MDM2 activity be inhibited, increased p53 in hyperplasia may inhibit papilloma formation. Therefore, loss of MDM2-mediated p53 degradation was investigated via inducible ablation of MDM2 exons 5 and 6, which bind p53 and chaperone for ubiquitination, employing K14-driven Cre/lox-P and treatment with topical RU486 (K14cre-Δ5/6MDM2flx/flx). In control, RU486-treated K14cre-Δ5/6MDM2flx/flx littermates, surprisingly few effects were observed, as normal epidermis expressed only sporadic p53/MDM2 as keratinocytes divided. Similarly, early HK1.ras hyperplasia displayed sporadic p53/MDM2 coexpression, suggesting an epidermis was relatively tolerant of Ras-mediated proliferation, where p53 overexpression risks problems of barrier maintenance due to excess apoptosis. With time, HK1.ras papillomas increased nuclear basal layer p53; p-MDM2166 also increased but remained suprabasal – alongside p-Akt1473 – possibly geared to maintain barrier functions from potential p53-mediated apoptosis. Conversely, in RU486-treated HK1.ras-Δ5/6MDM2flx/flx littermates, while hyperplasia histotype appeared unaffected, expression analysis found strong, elevated p53 expression in all compartments, consistent with loss of MDM2 inhibition. Moreover, this level of basal layer p53 in early hyperplasia apparently blocked papilloma formation and fed back to inhibit p-Akt1, whereas heterozygous MDM2 HK1.ras-Δ5/6MDM2flx/wt littermates exhibited a papillomatogenesis identical to wild-type HK1.ras littermates, with suprabasal p-MDM2166 and p-Akt1473. These findings suggest that MDM2 inhibition can inhibit benign tumour formation via maintaining p53 levels; however, with time (&gt; 20 weeks), small papillomas did appear, showing that this inhibition can be circumvented.
P07 Optimizing DNA specificity and applicability of base and prime editors on COL7A1 variants causing recessive dystrophic epidermolysis bullosa
Authors: Brooks Imogen , Rudnytska Maria , Gebrezgabher Ruta  , Laczmanski Lukasz , Newby Gregory  , Liu David , McGrath John , Jackow Joanna 
Published: July 2023

Abstract
Base and prime editors are novel CRISPR variants that reduce the risk of off-target effects by avoiding double-stranded DNA cleavage, bypassing the need for homology-directed repair. These tools offer great therapeutic potential for inherited skin diseases such as recessive dystrophic epidermolysis bullosa (RDEB). Biallelic loss-of-function mutations in COL7A1 cause RDEB, resulting from loss of functional type VII collagen (C7) in the basement membrane zone. Current therapies for RDEB are limited, but ex vivo and in vivo COL7A1 base or prime editing therapies can potentially restore normal protein production with a single intervention treatment. This study compared DNA editing specificity, safety and efficiency on RDEB fibroblasts harbouring a homozygous c.4448 G&gt;A (p.Gly1483Asp) mutation in COL7A1. Firstly, transfected adenine base editor (ABE8e) mRNA together with single guide RNA (sgRNA) were introduced into patient primary fibroblasts with Lipofectamine MessengerMax. By varying concentrations and ratios of guide RNA and ABE8e mRNA, we have achieved 100% biallelic correction without introducing any bystander mutations using 200 ng ABE8e and 28 ng sgRNA by transfecting 100 000 cells. Initial prime editing experiments are underway with PEmax plasmid and engineered prime editing guide RNAs (epegRNA) to optimize the guide design and to compare PE2max and PE4max editing systems. The functionality of the 100% biallelic correction using ABE8e is being evaluated with Western blot and in three-dimensional skin models. These early experiments demonstrate the potential value of base editing as a gene-editing tool in RDEB therapeutics; however, more functional work and off-target analyses are needed.
P18 KLICK syndrome is a hyperproliferative inflammatory skin disorder
Authors: Cherry Hannah , Parsons Maddy , Rastrick Joe , Hardman-Smart Jonathan , DiMeglio Paola , McGrath John 
Published: July 2023

Abstract
Keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK) syndrome is an ultra-rare genodermatosis. Clinical manifestations include linear hyperkeratotic papules in the flexures, palmoplantar keratoderma and pseudoainhum. To date, all affected individuals carry a homozygous pathogenic variant, c.-95delC in POMP, which encodes for proteasome maturation protein. Disease pathophysiology is not well understood, resulting in nonspecific and limited treatment options. However, clinically, the phenotype shows erythema and inflammation, indicating that there may be uncharacterized inflammatory pathways in KLICK syndrome, similar to some other ichthyoses. The aim of this work was to characterize KLICK syndrome at the cellular and molecular level. A lesional skin biopsy was obtained, following informed consent, from a 32-year-old woman with KLICK syndrome. Sanger sequencing confirmed the presence of the homozygous single nucleotide deletion in the 5′ untranslated region in POMP. Skin architecture was assessed using immunostaining, which revealed dynamic proliferative keratinocytes, precocious expression of involucrin and loricrin, and retention of loricrin in the stratum corneum. Lymphocytic infiltrates in the upper dermis were suggestive of inflammation and imaging mass cytometry was used to visualize and identify the immune subsets present. RNA sequencing revealed dysregulated pathways relating to keratinocyte differentiation, keratinization, cornification, and interferon signalling. Functional classification of differentially expressed genes using PANTHER additionally implicated WNT signalling, EGFR signalling and inflammatory signalling pathways as dysregulated in KLICK syndrome. KLICK syndrome can therefore be characterized as a hyperproliferative inflammatory skin disorder. Using a reverse transcriptomics approach, epidermal growth factor receptor (EGFR) inhibition and phosphoinositide 3-kinase (PI3K) inhibition were identified as potential treatment options that warrant further investigation. Understanding the pathobiology of KLICK syndrome may yield novel mechanisms driving inflammatory skin disease, which may be therapeutically targetable in patients with currently limited treatment options.