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Abstract Varicella-zoster virus (VZV) is the etiological agent of chickenpox and shingles, diseases characterised by epidermal virus replication in skin and mucosa and the formation of blisters. We have previously shown that VZV infection has a profound effect on keratinocyte differentiation, altering the normal pattern of epidermal gene expression. In particular, VZV infection reduces expression of suprabasal keratins 1 and 10 and desmosomal proteins, disrupting epidermal structure to promote expression of a blistering phenotype. Here, we extend these findings to show that VZV infection upregulates the expression of keratin 15 (KRT15), a marker expressed by basal epidermal keratinocytes and hair follicles stem cells. We demonstrate that KRT15 is essential for VZV replication in the skin, since downregulation of KRT15 inhibits VZV replication in keratinocytes, while KRT15 exogenous overexpression supports viral replication. Importantly, our data show that VZV upregulation of KRT15 depends on the expression of the VZV immediate early gene ORF62. ORF62 is the only regulatory gene that is mutated in the live attenuated VZV vaccine and contains four of the five fixed mutations present in the VZV Oka vaccine. Our data indicate that the mutated vaccine ORF62 is not capable of upregulating KRT15, suggesting that this may contribute to the vaccine attenuation in skin. Taken together our data present a novel association between VZV and KRT15, which may open a new therapeutic window for a topical targeting of VZV replication in the skin via modulation of KRT15.

Abstract Postnatal growth failure is often attributed to dysregulated somatotropin action, however marked genetic and phenotypic heterogeneity exist. We report five patients from three families who present with short stature, immune dysfunction, atopic eczema and gastrointestinal pathology associated with recessive variants in QSOX2. QSOX2 encodes a nuclear membrane protein linked to disulphide isomerase and oxidoreductase activity. Loss of QSOX2 disrupts Growth hormone-mediated STAT5B nuclear translocation despite enhanced Growth hormone-induced STAT5B phosphorylation. Moreover, patient-derived dermal fibroblasts demonstrate Growth hormone-induced mitochondriopathy and reduced mitochondrial membrane potential. Located at the nuclear membrane, QSOX2 acts as a gatekeeper for regulating stabilisation and import of phosphorylated-STAT5B. Altogether, QSOX2 deficiency modulates human growth by impairing Growth hormone-STAT5B downstream activities and mitochondrial dynamics, which contribute to multi-system dysfunction. Furthermore, our work suggests that therapeutic recombinant insulin-like growth factor-1 may circumvent the Growth hormone-STAT5B dysregulation induced by pathological QSOX2 variants and potentially alleviate organ specific disease.

ObjectivesTo explore the demographic and clinical profile of erosive lichen planus (ELP) across multiple ethnicities within a single cohort, deepening our understanding of disease severity, progression and outcomes.MethodsA longitudinal retrospective cohort study of ELP patients in the ethnically diverse population of East London was carried out, profiling ELP (n = 57) against the milder reticular lichen planus (RLP) (n = 35).ResultsA higher prevalence of ELP was observed in white populations compared to other ethnicities. Affected females were no more likely than males to develop ELP. There was an increased time to diagnosis for ELP patients (median ELP: 452 days, RLP: 312 days), spending longer in primary care before onward referral, in particular when referred by their general medical practitioner (GP) (median dentist 313 days, GP: 606 days). Depression was more likely to occur alongside ELP. Being an ex-smoker is a risk factor for ELP while being a current smoker is associated with RLP. A higher proportion of patients with ELP were missing teeth and had periodontal disease. Multisite involvement was more common in ELP, (ELP: 68% RLP: 11.43%). 55% of ELP cases developed scarring and were less likely to respond to first line medications, requiring systemic immunosuppression. The duration of follow up was increased in the ELP who were reviewed for almost twice as long as RLP patients (ELP 71 months, RLP 35 months).ConclusionELP takes longer to diagnose, requires prolonged tertiary care and is more resistant to treatment, when compared across multiple ethnicities. These patients have increased medical and oral health needs and are at greater risk of scarring than the reticular form. A greater education amongst primary carers on its presentation, as well as a greater understanding of the cellular and molecular mechanisms driving ELP are required to improve diagnostics and identify novel therapeutic approaches.

Abstract Pityriasis rubra pilaris (PRP) is a rare skin disease which manifests as a psoriasiform dermatosis and palmoplantar keratoderma and has significant clinical‐histopathological overlap with psoriasis. Recently, several case reports have demonstrated successful treatment of PRP with anti‐IL7A and anti‐IL12/anti‐IL23 monoclonal antibodies. We report a case of atypical juvenile PRP definitively diagnosed during adulthood with presence of CARD14 mutation. This case demonstrates a dramatic improvement with ustekinumab and highlights the role of genetic testing in chronic disease of diagnostic uncertainty.

Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) is a valuable experimental tool to study the immune state in health and following immune challenges such as infectious diseases, (auto)immune diseases, and cancer. Several tools have been developed to reconstruct B cell and T cell receptor sequences from AIRR-seq data and infer B and T cell clonal relationships. However, currently available tools offer limited parallelization across samples, scalability or portability to high-performance computing infrastructures. To address this need, we developed nf-core/airrflow, an end-to-end bulk and single-cell AIRR-seq processing workflow which integrates the Immcantation Framework following BCR and TCR sequencing data analysis best practices. The Immcantation Framework is a comprehensive toolset, which allows the processing of bulk and single-cell AIRR-seq data from raw read processing to clonal inference. nf-core/airrflow is written in Nextflow and is part of the nf-core project, which collects community contributed and curated Nextflow workflows for a wide variety of analysis tasks. We assessed the performance of nf-core/airrflow on simulated sequencing data with sequencing errors and show example results with real datasets. To demonstrate the applicability of nf-core/airrflow to the high-throughput processing of large AIRR-seq datasets, we validated and extended previously reported findings of convergent antibody responses to SARS-CoV-2 by analyzing 97 COVID-19 infected individuals and 99 healthy controls, including a mixture of bulk and single-cell sequencing datasets. Using this dataset, we extended the convergence findings to 20 additional subjects, highlighting the applicability of nf-core/airrflow to validate findings in small in-house cohorts with reanalysis of large publicly available AIRR datasets.

Abstract Background Atopic eczema is a common, chronic, inflammatory skin condition with considerable heterogeneity. South Asian people living in the UK frequently have low serum vitamin D3 (25(OH)D3), and those with atopic disease can present with severe eczema. The association between vitamin D deficiency and eczema severity, and the role of vitamin D supplementation in atopic eczema is inconsistent, and under‐researched in people with Asian ancestry. Objectives This cross‐sectional study investigates the association between serum 25(OH)D3 and eczema severity in a cohort of South Asian children and young adults living in London. Methods Eligible participants were Bangladeshi children and young adults aged 0–30 years with eczema, living in London and participating in the Tower Hamlets Eczema Assessment study. Data was collected via parent/patient self‐reporting, clinical history and examination, and hospital databases. 25(OH)D3 levels were documented retrospectively, if available, from hospital databases. Eczema severity was classified by Eczema Area and Severity Index (EASI) score less than or greater than 10 (clear‐mild vs. moderate‐severe). Multivariate logistic regression was used to adjust for confounding factors. Results 681 participants were included in analyses. 25(OH)D3 results were available for 49.6% (338/681), 84.3% of which had deficient or insufficient lowest 25(OH)D3. Lowest 25(OH)D3 was inversely correlated with EASI score (Spearman's rank R2 = −0.24, p 10 and a lower median lowest and nearest 25(OH)D3. After adjustment for confounding EASI > 10 was significantly associated with a lowest 25(OH)D3

The fatigue performance of laser powder bed fusion-fabricated Ti-6Al-4V alloy was investigated using four-point bending testing. Specifically, the effects of keyhole and lack-of-fusion porosities along with various surface roughness parameters, were evaluated in the context of pore circularity and size using 2D optical metallography. Surface roughness of Sa = 15 to 7 microns was examined by SEM, and the corresponding fatigue performance was found to vary by 102 cycles to failure. The S–N curves for the various defects were also correlated with process window examination in laser beam power–velocity (P–V) space. Basquin’s stress-life relation was well fitted to the experimental S–N curves for various process parameters except keyhole porosity, indicating reduced importance for LPBF-fabricated Ti-6Al-4V alloy components.

Breast cancer is the most common type of lethal cancer in women globally. Women have a 1 in 8 chance of developing breast cancer in their lifetime. Among the four primary molecular subtypes (luminal A, luminal B, HER2+, and triple-negative), HER2+ accounts for 20–25 % of all breast cancer and is rather aggressive. Although the treatment outcome of HER2+ breast cancer patients has been significantly improved with anti-HER2 agents, primary and acquired drug resistance present substantial clinical issues, limiting the benefits of HER2-targeted treatment. MicroRNAs (miRNAs) play a central role in regulating acquired drug resistance. miRNA are single-stranded, non-coding RNAs of around 20–25 nucleotides, known for essential roles in regulating gene expression at the post-transcriptional level. Increasing evidence has demonstrated that miRNA-mediated alteration of gene expression is associated with tumorigenesis, metastasis, and tumor response to treatment. Comprehensive knowledge of miRNAs as potential markers of drug response can help provide valuable guidance for treatment prognosis and personalized medicine for breast cancer patients.

Background: among the periodontal emergencies that require immediate attention is the RAS, due to the inconvenience or complications that it causes to the patient. The use of low power laser radiation can be effective in the treatment of this entity.Objective: to determine the therapeutic effect of treatment with low-power laser radiation in patients diagnosed with recurrent aphthous stomatitis.Methods: descriptive, cross-sectional study, carried out from May/2019 to May/2021, in the Dr. Enrique Barnet polyclinic’s dental service, in Lajas municipality, Cienfuegos province, which included 46 patients diagnosed with recurrent aphthous stomatitis. Document analysis, observation and questionnaire were used; in addition to the oral examination as a diagnostic method. Patients received treatment with low-power laser radiation. The EPIDAT 3.1 program was applied for the statistical data processing.Results: the female sex predominated, the age between 19-34 years, as well as minor aphthous ulcers. The lesions were located mainly on the lip. 97.83% of the patients reported remission of the lesion on the fifth day of treatment. All treated patients evolved favorably towards healing. Only one patient presented adverse reactions.Conclusions: the results allowed us to verify the therapeutic benefits of low power laser therapy in the treatment of recurrent aphthous stomatitis.

Recessive X-linked ichthyosis (RXLI), a genetic disorder caused by deletion or point mutations of the steroid sulfatase (STS) gene, is the second most common form of ichthyosis. It is a disorder of keratinocyte cholesterol sulfate retention and the mechanism of extracutaneous phenotypes such as corneal opacities and attention deficit hyperactivity disorder are poorly understood. To understand the pathomechanisms of RXLI, the transcriptome of differentiated primary keratinocytes with STS knockdown was sequenced. The results were validated in a stable knockdown model of STS, to confirm STS specificity, and in RXLI skin. The results show that there was significantly reduced expression of genes related to epidermal differentiation and lipid metabolism, including ceramide and sphingolipid synthesis. In addition, there was significant downregulation of aldehyde dehydrogenase family members and the oxytocin receptor which have been linked to corneal transparency and behavioural disorders respectively, both of which are extracutaneous phenotypes of RXLI. These data provide a greater understanding of the causative mechanisms of RXLI’s cutaneous phenotype, and show that the keratinocyte transcriptome and lipidomics can give novel insights into the phenotype of patients with RXLI.

Sphingosine 1-phosphate lyase (SGPL1) insufficiency (SPLIS) is a syndrome which presents with adrenal insufficiency, steroid-resistant nephrotic syndrome, hypothyroidism, neurological disease, and ichthyosis. Where a skin phenotype is reported, 94% had abnormalities such as ichthyosis, acanthosis, and hyperpigmentation. To elucidate the disease mechanism and the role SGPL1 plays in the skin barrier we established clustered regularly interspaced short palindromic repeats-Cas9 SGPL1 KO and a lentiviral-induced SGPL1 overexpression (OE) in telomerase reverse-transcriptase immortalised human keratinocytes (N/TERT-1) and thereafter organotypic skin equivalents. Loss of SGPL1 caused an accumulation of S1P, sphingosine, and ceramides, while its overexpression caused a reduction of these species. RNAseq analysis showed perturbations in sphingolipid pathway genes, particularly in SGPL1_KO, and our gene set enrichment analysis revealed polar opposite differential gene expression between SGPL1_KO and _OE in keratinocyte differentiation and Ca2+ signaling genesets. SGPL1_KO upregulated differentiation markers, while SGPL1_OE upregulated basal and proliferative markers. The advanced differentiation of SGPL1_KO was confirmed by 3D organotypic models that also presented with a thickened and retained stratum corneum and a breakdown of E-cadherin junctions. We conclude that SPLIS associated ichthyosis is a multifaceted disease caused possibly by sphingolipid imbalance and excessive S1P signaling, leading to increased differentiation and an imbalance of the lipid lamellae throughout the epidermis.

In this investigation, the optimization of mechanical properties with thermal post-processing treatments was analyzed across a wide range of variants. A major aspect of additive manufacturing is the correlation between heat treatments and the effects on the mechanical properties and microstructure of the printed materials. Therefore, the present paper describes a comprehensive overview of post-process heat treatments for Laser Powder Bed Fusion fabricated AlSi10Mg alloy consisting of stress relief anneals at 190 ̊C and 285 ̊C for 2 h, hot isostatic pressing at 515 ̊C for 3 h, hot isostatic pressing + T6 treatment for 6 h, and final aging of each of these conditions at 177 ̊C for up to 1000 h. This has resulted in 40 experimental variants: 20 in the vertical and 20 in the horizontal tensile direction. After tensile testing, the resulting mechanical properties (ultimate tensile strength, yield strength, and elongation) and stress–strain curves are analyzed for comparison between all variants. Ultra-fine cellular, micro dendritic structures (0.6–1.2 μm) along with melt-band structures dominated the asbuilt and stress relief anneal conditions. In contrast, hot isostatic pressing and hot isostatic pressing + T6 conditions were dominated by ~10 μm, equiaxed, recrystallized grain structures and pseudo-eutectic silicon particles with varying sizes and size distributions. Microhardness and fractography results also corresponded to their specific heat treatment and microstructure. The comparison and correlation of the heat treatments are presented to help advance the selection of design strategies for high performance applications.

In vitro sugarcane plants (Saccharum spp.) are susceptible to environmental changes in theacclimatization phase, which affects their growth and development. The objective of thiswork was to evaluate the effect of the biostimulant Enerplant® on the survival and growth ofin vitro plants of sugarcane cv. C97-445 inex vitro acclimatization. Three solutions (0.6, 0.8and 1.0 ml l-1) of Enerplant® were evaluated and compared with the biostimulant VIUSID Agro®0.8 ml l-1. Two daily applications were made, the first three days after transplant and thenonce a week. The experiments were carried out in the dry season. The variables evaluatedwere survival at 15 days and morphophysiological at 55 days after transplantation. It wasverified that the application of Enerplant® increases the survival of sugarcanein vitroplantsand improves their growth. Treatment with 0.8 ml l-1 of this biostimulant had the greatest effect onin vitroplant growth underex vitro acclimatization conditions.

Este trabalho objetiva analisar as contribuições da teoria pedagógica de Paulo Freire e da concepção construtivista de Antoni Zabala para a promoção da ginástica laboral com vistas à formação humana na perspectiva da politecnia. A partir de um estudo qualitativo de cunho bibliográfico com obras que versam sobre a ginástica laboral, a politecnia, a teoria de Paulo Freire e a concepção construtivista de Antoni Zabala. Constatou-se que a teoria de Paulo Freire e a concepção construtivista de Antoni Zabala contribuem na transformação das ações com a ginástica laboral com vistas ao desenvolvimento de ações contextualizadas e que promovam a autonomia e formação crítica dos aprendizes, para além do fazer prático. Desta forma, a presente revisão de literatura contribui com as discussões sobre a prática da ginástica laboral em uma perspectiva didática, pautada no diálogo entre os envolvidos para o desenvolvimento de ações que promovam a Qualidade de Vida no Trabalho, e construa um ambiente profissional cada vez mais humanizado, algo que colabora para a execução das tarefas trabalhistas de maneira mais qualitativa.

O processo de ensino e aprendizagem de Matemática, nos anos iniciais do ensino fundamental, tem sido uma questão tratada e estudada cuidadosamente por pesquisadores e educadores, sempre posicionando o aprendiz no centro de todo processo educacional. O presente trabalho tem como objetivo apresentar uma proposta para o ensino e aprendizagem de frações, através de uma ressignificação nos princípios e relações Matemáticas que conduzem aos conceitos de números fracionários. A estratégia de ensino e aprendizagem de frações foi aplicada em uma turma de25 alunos, entre 9 e 11 anos, do 5º ano do ensino fundamental de uma escola pública municipal da cidade de Rio Largo. A ressignificação do processo de ensino e aprendizagem dos conceitos de fração determinou implicações positivas que foram manifestadas pelo bom desempenho dos alunos nas questões recomendadas. Espera-se que pesquisas futuras envolvendo o ensino e aprendizagem de Matemática, por ressignificação de conceitos, sejam conduzidas, nos diversos níveis de ensino, para melhor execução e compreensão de modelos matemáticos.

The propagation of sugarcane (Saccharum spp.) Requires seed with physiological and phytosanitary quality. The work was carried out with the objective of establishing a bank of sugarcane mother plants under semi-controlled conditions to guarantee the efficiency of in vitro propagation with plants free of Xanthomonas albilineans. A greenhouse was modified and the structure was remodeled, a Sarán shade mesh (50%) and a sprinkler irrigation system were placed. The plants were grown in plastic containers (20 m3 volume) with a mixture of cachaça compost and zeolite 3:1. Stems of cultivars C98-357, C97-445 and C86-156, without symptoms of leaf scald and with six months of culture, were cut into segments with a bud. Hydrothermal treatment was applied and subsequently the biostimulant VIUSID Agro® (0.8 ml l-1) before the buds planting. At three months of culture, a serological diagnosis was made to detect the presence of X. albilineans. The negative plants were treated with biostimulants and the response of the in vitro establishment was evaluated. Adequate plant growth was achieved under the conditions described. The establishment of a bank of sugarcane mother plants under semi-controlled conditions and its management guaranteed that microbial contamination and phenolic oxidation decreased in the in vitro establishment phase. The effectiveness of the hydrothermal treatment combined with the semi-controlled conditions and the management of the plants make it possible to reduce the incidence of X. albilineans.

Mathematics in elementary school provides a whole foundation of knowledge that the student will need to expand more abstract contexts, establishing competencies and skills necessary to reason and think mathematically. Mathematical games have been an essential tool to minimize these distortions between theory and practice in learning mathematics.This study, carried out in 2019, aimed to present a memory game formed by Pythagorean suits, belonging to a kit of mathematical games produced by the research group GALC -Geometry, Algebra, Combinatory and Logic. Methodologically, the proposal aims to propose this game as an alternative in educational practice in the teaching and learning process of mathematics in basic education. The use of new methodologies for the act of learning and teaching mathematics has strengthened the student's creativity in basic education, stimulating teachers to realign all their pedagogical practice in favor of a more motivating and current mathematics teaching

A wide range of post process hot isostatic pressing (HIP) studies of electron beam additively manufactured Ti-6Al-4V in this research program have shown that cooling rates of 103 °C/min from temperatures above and below the beta transus produced acicular alpha-prime martensite characteristic elongations < 10%. Optimum yield strength (0.9 GPa), UTS (1.0 GPa), and elongation (∼14%) were achieved for slow cooling (at 102 °C/min) from 850 °C HIP which produced a dense, Widmanstatten alpha structure within the retained, as-fabricated columnar grains by alpha-prime decomposition. These results suggest that manipulation of AM process parameters to produce a small-grain, equiaxed microstructure, HIPed below the beta transus and slow cooled, will have a wide range of superior, isotropic mechanical properties corresponding to a Widmanstatten alpha microstructure within the equiaxed grains.

In today's contemporary world, the beginning of the 21st century, scientific and technological changes are accelerating and exponential growth so the nursery school needs to create the means to adapt to this whole evolutionary process of humanity. The objective of this work is to suggest innovative practices for the teaching of mathematics in children's education under the perspective of the child's creativity. The teaching of mathematics in children's education must be balanced with activities that can awaken in the child the creativity necessary to reach the solution of the problem proposed. Given this argument and for better learning of mathematics in children's education, we propose some activities associated with children's abilities, among them, numerical, verbal and spatial. It is hoped that this model of teaching and learning mathematics in early childhood education, through the three skills, is connected with the reality of the apprentice child.

Atopic eczema is a common and complex disease. Missing genetic hereditability and increasing prevalence in industrializing nations point toward an environmental driver. We investigated the temporal association of weather and pollution parameters with eczema severity. This cross-sectional clinical study was performed between May 2018 and March 2020 and is part of the Tower Hamlets Eczema Assessment. All participants had a diagnosis of eczema, lived in East London, were of Bangladeshi ethnicity, and were aged 10 after previous ambient exposure to commonly studied meteorological variables and pollutants. There were 430 participants in the groups with Eczema Area and Severity Index ≤ 10 and 149 in those with Eczema Area and Severity Index > 10. Using logistic generalized additive models and a model selection process, we found that tropospheric ozone averaged over the preceding 270 days was strongly associated with eczema severity alongside the exposure to fine particles with diameters of 2.5 μm or less (fine particulate matter) averaged over the preceding 120 days. In our models and analyses, fine particulate matter appeared to largely act in a supporting role to ozone. We show that long-term exposure to ground-level ozone at high levels has the strongest association with eczema severity.

No mundo contemporâneo diversas pesquisas são realizadas em busca de uma solução eficaz no processo ensino e aprendizagem de matemática, tendo como foco as suas novas técnicas da educação matemática. Este trabalho tem como objetivo apresentar uma proposta metodológica para o ensino e aprendizagem de matemática na educação básica, através da resolução de problemas utilizando o método de Polya. O método de Polya consiste em três etapas: Compreender o problema, Designar um plano, Executar o plano e Retrospecto do problema. Metodologicamente serão apresentados três problemas matemáticos cuja resolução seguirá o método de Polya. Está sugestão, Resolução de Problemas através do método de Polya, como prática educacional no processo de ensino e aprendizagem de matemática possibilita ao professor facilitador e ao aluno aprendiz desenvolver novas habilidades no intuito de fortalecer o pensamento crítico e o raciocínio lógico.

Experimental examples of as-built microstructures and associated microindentation hardnesses (HV) for a wide range of metal additive manufacturing (AM) processes for Inconel 625 alloy are presented in this research paper. These processes included cold spray, laser powder bed fusion, wire arc additive manufacturing, electron beam directed energy deposition, laser hot wire, binder jetting, laser power directed energy deposition, electron beam melting, and laser wire directed energy deposition. Microstructures ranged from impact bonded, flattened 625 alloy grains containing microdendrites and dislocations, having a microindentation hardness of HV 590 for cold spray, to large, equiaxed grains for binder jet-printed components having a microindentation hardness of HV 180. Electron and laser beam melt-related processes, including wire and powder feeds, produced varying sizes of columnar grains with parallel and cellular arrays of microdendrites, having microindentation hardnesses ranging from HV 304 to HV 228. Delta phase precipitate needles were also produced in laser-powered directed energy deposition microstructures along with columns of gamma double-prime precipitates for electron beam melting. The results demonstrate a range of AM processes applications and strategies to produce as-built and surface-modified Inconel 625 alloy products and components. These results demonstrate differences in the microstructure from the various AM processes and considerations for use in end use applications.

This research program investigated the effects of layer thickness (50 µm and 100 µm) on the microstructure and mechanical properties of electron beam powder bed fusion (EBPBF) additive manufacturing of Inconel 625 alloy. The as-built 50 µm and 100 µm layer thickness components were also heat treated at temperatures above 1100 °C which produced a recrystallized grain structure containing annealing twins in the 50 µm layer thickness components, and a duplex grain structure consisting of islands of very small equiaxed grains dispersed in a recrystallized, large-grain structure containing annealing twins. The heat-treated components of the microstructures and mechanical properties were compared with the as-built components in both the build direction (vertical) and perpendicular (horizontal) to the build direction. Vickers microindentation hardness (HV) values for the vertical and horizontal geometries averaged 227 and 220 for the as-built 50 µm and 100 µm layer components, respectively, and 185 and 282 for the corresponding heat-treated components. The yield stress values were 387 MPa and 365 MPa for the as-built horizontal and vertical 50 µm layer geometries, and 330 MPa and 340 MPa for the as-built 100 µm layer components. For the heat-treated 50 µm components, the yield stress values were 340 and 321 MPa for the horizontal and vertical geometries, and 581 and 489 MPa for the 100 µm layer components, respectively. The elongation for the 100 µm layer as-built horizontal components was 28% in contrast with 65% for the corresponding 100 µm heat-treated layer components, an increase of 132% for the duplex grain structure.

This study examines and compares the microstructures, Vickers microindentation hardness, and mechanical properties for additively manufactured (AM) samples built by a variety of AM processes: wire arc AM (WAAM), electron beam powder bed fusion (EB-PBF), laser wire direct energy deposition (LW-DED), electron beam direct energy deposition (EB-DED), laser-powered direct energy deposition (LP-DED), and laser powder bed fusion (L-PBF). These AM process samples were post-processed and heat-treated by stress relief annealing at 1066 °C, HIP at 1163 °C, and solution annealing treatment at 1177 °C. The resulting microstructures and corresponding microindentation hardnesses were examined and compared with the as-built AM process microstructures and hardnesses. Fully heat-treated AM process samples were mechanically tested to obtain tensile properties and were also evaluated and compared. Principal findings in this study were that high-temperature heat treatment >1100 °C of AM process-built samples was dominant and exhibited recrystallized, equiaxed grains containing fcc {111} annealing twins and second phase particles independent of the AM process, in contrast to as-built columnar/dendritic structures. The corresponding yield stress values ranged from 285 MPa to 371 MPa, and elongations ranged from 52% to 70%, respectively. Vickers microindentation hardnesses (HV) over this range of heat-treated samples varied from HV 190 to HV 220, in contrast to the as-built samples, which varied from HV 191 to HV 304.

Decifrar um modelo das coisas perpassa por três circunstâncias observáveis: intuição, deliberação e tomada de decisão. Segundo Jaques Lacan, o tempo lógico é definido em três atos: o instante de ver, o tempo de compreender e o momento de concluir. A interpretação de um modelo matemático segue em três partes analisáveis: a noção intuitiva, o pensamento matemático e a resolução do problema. Este estudo objetivou identificar as verdadeiras relações entre os princípios da descodificação de um modelo da natureza, as etapas de execução do tempo lógico de Lacan e a as fases da explicação de um modelo matemático. A ordem é ressignificar o processo de ensino e aprendizagem de matemática utilizando uma abordagem Lacaniana. Abordagens pedagógicas que fortalecem a intuição e o pensamento matemático são indispensáveis para aprimorar o desenvolvimento metacognitivo do sujeito envolvido.

Diversas pesquisas são realizadas anualmente na Educação Matemática com o propósito de apresentar alternativas para o ensino de matemática em ambientes computacionais. A transformação tecnológica do mundo moderno proporcionou uma mudança metodológica na prática de ensinar e aprender matemática. Atualmente, o uso de tecnologias educacionais, em sala de aula, é requisito primordial para aproximar o aprendiz dos conteúdos de matemática Este trabalho objetivou apresentar o comportamento das funções polinomiais através de um conjunto de pontos, chamado Interpolação Polinomial, em um ambiente computacional. Uma pesquisa de campo foi realizada com 16 estudantes da Educação Técnica de uma Escola Pública Federal para comprovar que o grau de motivação e de interesse pela matemática aumentou com a utilização de um ambiente computacional. Espera-se que outros trabalhos dessa magnitude sejam desenvolvidos, no meio acadêmico, e que possamos minimizar as defasagens entre a teoria matemática e sua prática por intermédio de novas tecnologias.

As dificuldades na compreensão de conceitos matemáticos na educação básica são evidentes no desempenho escolar dos educandos, especialmente pelas propostas educacionais suplantadas e que não conseguem aproximar nenhum interesse do aprendiz pelos conteúdos recomendados. Este trabalho tem como objetivo afrontar essas indagações e inquietudes de pesquisadores da Educação Matemática, estabelecendo três pressupostos indispensáveis para minimizar questionamentos sobre o ensino e aprendizagem de matemática: Problema, Causa e Paradigma. Metodologicamente, a proposta fundamenta-se em oferecer uma ferramenta intuitiva para resolução de sistemas lineares do 1º grau com duas equações e duas incógnitas e coeficiente positivos, por intermédio de problemas matemáticos, utilizando uma tabela de dados. Quatro problemas matemáticos serão investigados. Não basta exclusivamente resolver o problema matemático indicado, no entanto descobrir um caminho para desvendar padrões e estabelecer relações. Espera-se que este trabalho possa auxiliar professores e alunos no processo de ensino e aprendizagem de matemática, utilizando uma estratégia de observar um problema matemático por meio de uma resolução não tradicional com ínfimas abstrações, provocando chances de perceber um evento por outro referencial.

Inherited monogenic palmoplantar keratodermas are a heterogeneous group of conditions characterised by persistent epidermal thickening of the palmoplantar skin. Palmoplantar keratodermas are grouped depending on the morphology of the keratoderma into diffuse, focal/striate or papular/punctate. Some palmoplantar keratodermas just affect the skin of the palms and soles and others have associated syndromic features which include changes in hair, teeth, nails, hearing loss or cardiomyopathy. Next generation sequencing has helped discover genes involved in many of these conditions and has led to reclassification of some palmoplantar keratodermas. In this review, we discuss the diagnostic features of palmoplantar keratodermas and management options.

Com todo avanço tecnológico, percebe-se que o fracasso no ensino de matemática na educação básica, muitas vezes, está vinculado à prática pedagógica adotada pelos professores. Este artigo tem como objetivo apresentar uma nova proposta de ensino e aprendizagem de matemática na educação básica, chamado Processo – RICA. A base deste processo fundamenta-se em quatro pilares educacionais: Raciocínio Lógico, Inteligência matemática, Criatividade e Aprendizagem. Os dados foram levantados, a partir, de um estudo de caso com seis alunos voluntários de um curso técnico de informática do Instituto Federal de Alagoas e a análise desses dados evidenciou que o processo - RICA é uma proposta metodológica visivelmente adaptável, moderna e inovadora para o entendimento dos tópicos de matemática e contribui para obter novas possibilidades para assimilação desta ciência tão provocativa e essencial para a explicação dos fenômenos da natureza.

Abstract Sebaceous gland carcinoma (SGC) is a rare, but life-threatening condition with a predilection for the periocular region. Eyelid SGC can be broadly categorised into two subtypes, namely either nodular or pagetoid with the latter being more aggressive and requiring radical excision to save life. We have identified key altered microRNAs (miRNA) involved in SGC shared by both subtypes, hsa-miR-34a-5p and hsa-miR-16-5p. However, their gene targets BCL2 and MYC were differentially expressed with both overexpressed in pagetoid but unchanged in nodular suggesting different modes of action of these two miRNAs on BCL/MYC expression. Hsa-miR-150p is nodular-specifically overexpressed, and its target ZEB1 was significantly downregulated in nodular SGC suggesting a tumour suppressor role. Invasive pagetoid subtype demonstrated specific overexpression of hsa-miR-205 and downregulation of hsa-miR-199a. Correspondingly, miRNA gene targets, EZH2 (by hsa-miR-205) and CD44 (by hsa-miR-199a), were both overexpressed in pagetoid SGC. CD44 has been identified as a potential cancer stem cell marker in head and neck squamous cell carcinoma and its overexpression in pagetoid cells represents a novel treatment target. Aberrant miRNAs and their gene targets have been identified in both SGC subtypes, paving the way for better molecular understanding of these tumours and identifying new treatment targets.

A sucessão de Fibonacci é uma das sequências matemáticas mais conhecidas e bastante utilizada para explicar modelos da natureza. Diversas aplicações no ramo da computação, da biologia, das finanças, das artes, entre outras, tem a sucessão de Fibonacci como referencial. As linhas de Tendência são gráficos gerados por equações matemáticas que se ajustam a um conjunto de dados no intuito de estimar resultados futuros. Objetivou-se como este artigo avaliar o comportamento da Sucessão de Fibonacci através de diversas Linhas de Tendência utilizando como ferramenta a Regressão do Software Excel. Metodologicamente, a ideia é apresentar para cada Linha de Tendência sua equação matemática de Regressão e seu coeficiente de correlação Quatro Linhas de Tendências serão apresentadas: Linear, Exponencial, Logarítmica e Potência. A pergunta a ser respondida é: qual o melhor modelo de regressão que se ajusta a sucessão de Fibonacci? Desta forma, espera-se que este trabalho possa contribuir na aprendizagem de modelos de regressão nos diversos níveis de ensino da Educação Básica. PALAVRAS-CHAVE: Sucessão de Fibonacci, Regressão no Excel, Linhas de Tendência

An unmodified, non-spherical, hydride-dehydride (HDH) Ti-6Al-4V powder having a substantial economic advantage over spherical, atomized Ti-6Al-4V alloy powder was used to fabricate a range of test components and aerospace-related products utilizing laser beam powder-bed fusion processing. The as-built products, utilizing optimized processing parameters, had a Rockwell-C scale (HRC) hardness of 44.6. Following heat treatments which included annealing at 704 °C, HIP at ~926 °C (average), and HIP + anneal, the HRC hardnesses were observed to be 43.9, 40.7, and 40.4, respectively. The corresponding tensile yield stress, UTS, and elongation for these heat treatments averaged 1.19 GPa, 1.22 GPa, 8.7%; 1.03 GPa, 1.08 GPa, 16.7%; 1.04 GPa, 1.09 GPa, 16.1%, respectively. The HIP yield strength and elongation of 1.03 GPa and 16.7% are comparable to the best commercial, wrought Ti-6Al-4V products. The corresponding HIP component microstructures consisted of elongated small grains (~125 microns diameter) containing fine, alpha/beta lamellae.

The sulphide acid coolers are tube and shell jacketed heat exchangers designed to cool down the produced gas from 416,15 K to 310,15 K in addition to separate the sulphur carried over by the outlet gas from the reactor tower. The investigation was carried out by applying the passive experimentation process in an online cooler set in order to determine the heat transfer rates and fouling based on heat resistance. It was corroborated that the operation of this equipment outside design parameters increases outlet gas temperature and liquid sulphur carryovers. Efficiency loss is caused by fouling elements in the fluid, which results in changes in the overall heat transfer rate. The linear tendency of the fouling heat resistance based on time for three gas flowrates.

Arts partnerships involving teachers, artists and arts organizations continue to be popular as a means of delivering arts education. Acting as an intermediary between schools and artists, arts brokers can be crucial to the successful implementation of these partnerships. Characterized as individuals who can act as channels for innovative practice, arts brokers can potentially support teachers to take risks, build capacity for reflection and develop agency as arts practitioners. This article examines the role of the Creative Associate -- an arts broker within an Irish arts partnership ("Creative Schools-Scoileanna ldánacha"). Data was collected using semi-structured interviews in a purposive sample of eight Irish primary schools. Using a framework put forward by Sinclair et al., the support provided by the arts broker is critically analyzed. The establishment and development of stakeholder relationships is explored while emerging challenges are debated and discussed. Findings from this study indicated that the success of the arts broker is underpinned by their ability to build and nurture relationships. By 'bridging the gap' between teachers, schools and artists, this article argues that arts brokers can ensure partnerships have a sustained, meaningful impact on the enhancement of arts education in schools.

The induction period is a frequently discussed element in a teacher's career. While there is a recognised need for support during induction, the access to support is not available to all newly qualified teachers (NQTs). However, little is known about the micro-political processes of NQTs' access to support in the workplace. The purpose of this study is to investigate experiences of support during NQTs' first year in teaching, using concepts from micro-political theory. The findings show that NQTs experience reactive support, a lack of formal support, and self-initiated informal peer support. The findings are based on a thematic analysis of written accounts collected from 15 NQTs in Norwegian secondary schools every month during their first year, as well as individual interviews at the end of the year. The study concludes that the use of power in interactions among members of the school organisation impact NQTs' access to induction-support.