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Purpose: This study aims to explore the effectiveness of action learning (AL) in PA education through the action research (AR). Public administration (PA) requires training paths for its officials aimed at developing managerial skills. Training designers must construct pathways that identify goals and results to be obtained. Most importantly, they should adopt techniques that engage all stakeholders and measure training performance. This study uses the action research (AR) method to explore the effectiveness of action learning (AL) in PA education. It shows how a training project for officials of the PA can be designed and managed in a participatory and engaging manner. Design/methodology/approach: The AR approach is particularly suited to long-term training interventions in PA because it offers a means of taking shared responsibility. AR aids in building a bridge between academia and practice and solving real problems with stakeholders, students and end-clients through cyclical interactions of construction, intervention and evaluation. It focuses on AL as an innovative educational tool that links knowledge and action and theory and practice. Findings: The involvement of different stakeholders, such as teachers, students, administrators and politicians, in the design, management and evaluation process facilitates the identification of educational objectives and monitoring of outcomes in a changing public organizational context. AL is effective because it involves students as individuals and as a team, often as an organization, while trying to solve real problems. Originality/value: AL through the AR approach has not been widely used in education, especially in PA, where teaching legal and administrative content combines traditional teaching methods. The case study shows the innovative potential of AL in a traditional context such as the PA.

Introdução: No diagnóstico de Infecções Sexualmente Transmissíveis (ISTs), testes rápidos colorimétricos são frequentemente executados no Point of Care (POC), mas possuem menor sensibilidade e especificidade. Os biossensores eletroquímicos, por sua vez, associam elementos biológicos (analito e biorreceptor) em uma plataforma capaz de captar esta interação e transformar a energia desta reação em um sinal elétrico, garantindo ao diagnóstico rapidez, alta sensibilidade e especificidade. Objetivo: O objetivo dessa pesquisa foi estabelecer a prova de conceito de uma plataforma de PLA-Grafeno/Fibroína (PLA-G/F), impressa por manufatura aditiva, destinada à constituição de biossensores eletroquímicos para diagnóstico de ISTs. Método: Filamentos de PLA e PLA-G foram utilizados para a impressão de plataformas por impressão 3D. A seguir, foi depositada na região compatível com o eletrodo uma camada de Fibroína a 0,04%, 0,4% e 4%. A plataforma resultante foi submetida à caracterização química, através da Espectroscopia na Região do Infravermelho com Transformada de Fourier (FTIR) e Difração de Raios-X (DRX), e condutométrica, a fim de estabelecer o conceito proposto. Resultados: Os espectros de FT-IR de PLA, PLA-G e PLA-G/F evidenciaram presença de grupos funcionais -CH, C = O e C-O-C, característicos do PLA e PLA-G. Foi também identificada a presença das bandas correspondentes às vibrações de estiramento N-H e O-H, por sua vez correspondentes à amida I e II pertencentes ao domínio amorfo da Fibroína. Nos espectros de DRX, foram observados padrões de difração correspondentes à célula cristalina do PLA e do Grafeno oxidado. Análises de impedância em função da frequência em medições realizadas na plataforma a seco e com álcool etílico hidratado a 70° INPM sob a sua superfície demostraram que a resistência a seco concentra-se em valores entre 80 kΩ e 100 kΩ, com atividade predominante até 10 kHz. Nos testes com álcool 70%, houve aumento da resistência, atingindo de 500 kΩ a 1 MΩ, na mesma faixa de frequência. Nas duas situações foi possível caracterizar a variação da impedância na plataforma indicando a viabilidade de diagnósticos por meio de medições elétricas. Conclusão: Os resultados correspondentes à caracterização fisicoquímica das amostras sustentam a prova de conceito estabelecida a respeito da utilização da plataforma PLA-G/F para a produção de biossensores eletroquímicos, reforçando o potencial de utilização como plataforma para a obtenção sensores eletroquímicos para diagnósticos das ISTs no POC.

Abstract In recent years, there has been a growing demand for drug design approaches that incorporate a higher number of sp3-hybridized carbons, necessitating the development of innovative cross-coupling strategies to reliably introduce aliphatic fragments. Here, we present a powerful approach for the light-mediated B-alkyl Suzuki−Miyaura cross-coupling between alkyl boranes and aryl bromides. Alkyl boranes were easily generated via hydroboration from readily available alkenes, exhibiting excellent regioselectivity and enabling the selective transfer of a diverse range of primary alkyl fragments onto the arene ring under photocatalytic conditions. This methodology eliminates the need for expensive catalytic systems and sensitive organometallic compounds, operating efficiently at room temperature within just 30 min. We further demonstrate the translation of the present protocol to continuous-flow conditions, enhancing scalability, safety, and overall efficiency of the method. This versatile approach offers significant potential for accelerating drug discovery efforts by enabling the introduction of complex aliphatic fragments in a straightforward and reliable manner.

The present study used the adult earthworm Aporrectodea trapezoides as a bioindicator species to look into the possible dangers of ammonium sulfate (AS) fertilizer. Two complementary toxicity tests were conducted to determine the LC50values, growth rate inhibition, morphological alterations, and histopathological texture of worms. The lethality test included four increasing concentrations of AS fertilizer (ranging from 2500 to 7500 mg/kg of dry soil weight (d.w.)), while sub-lethal concentrations were based on 10%, 30%, 40%, and 50% of the 14-day median lethal concentration (LC50), with a control group included for both tests. The LC(50) values for AS fertilizer were significantly higher at 7 days (4831.13 mg/kg d.w.) than at 14 days (2698.67 mg/kg d.w.) of exposure. Notably, earthworms exhibited significant growth rate inhibition under exposure to various concentrations and time durations (14/28 exposure days). Morphological alterations such as clitellar swelling, bloody lesions, whole body coiling and constriction, body strangulation, and fragmentation were accentuated steadily, with higher concentrations. Histopathological manifestations included severe injuries to the circular and longitudinal muscular layers, vacuolation, muscle layer atrophy, degradation of the chloragogenous tissue in the intestine, collapsed digestive epithelium of the pharynx with weak reserve inclusion, and fibrosis of blood vessels. These effects were primarily influenced by increasing concentrations of fertilizer and time exposure. The study highlights the strong relationship between concentration and exposure time responses and underscores the potential of A. trapezoides earthworms as valuable biological control agents against acidic ammonium sulfate fertilizer. Importantly, this research contributes to the use of such biomarkers in evaluating soil toxicity and the biological control of environmental risk assessment associated with chemical fertilizers.

In this paper, the coupled dynamics of the floating platform and the wind turbine rotor are analyzed. In particular, the damping is explicitly derived from the coupled equations of the rotor and floating platform. The analysis of the damping leads to the study of instability phenomena, thus obtaining the explicit conditions that lead to the non-minimum phase zero (NMPZ). Two NMPZs are analyzed, one related to the rotor dynamics and the other one to the platform pitch dynamics. The latter introduces a novelty, and an explicit condition is provided in this work for its verification. In the second part of the paper, from the analysis of the damping of the floating platform, a new strategy for the control of floating offshore wind turbines (FOWTs) is proposed. This strategy allows one to impose on the controller an explicit level of damping in the platform pitch motion that adapts with wind speed and operating conditions without changing the period of platform pitching. Finally the new strategy is compared to one without compensation and one with a non-adapting compensation by performing aero-hydro-servo-elastic numerical simulations of a reference FOWT. Generated power, motions, blade pitch and tower base fatigue are compared, showing that the new control strategy can reduce fatigue in the structure without affecting the power production.

Skin secretions from Patagonian ground frogs, Eupsophus vertebralis, have previously been reported as a potent proteinaceous adhesive with potential biomedical applications. Here, we conducted a rheological analysis indicating the mechanical robustness of these secretions, with a storage modulus ranging from 1 to 10 Pa. In addition, antimicrobial and cytotoxicity assays were performed, revealing no antimicrobial activity against both the Gram-positive and Gram-negative bacteria. The cytotoxicity results were intriguing, as three samples showed no harm, and one exhibited a severe cytotoxic effect on the human cell line MG63. These properties, as indicated by these preliminary results, reinforce their potential for practical applications in the industrial and medical sectors.

Abstract Background The activities of MYC, the androgen receptor, and its associated pioneer factors demonstrate substantial reprogramming between early and advanced prostate cancer. Although previous studies have shown a shift in cellular metabolic requirements associated with prostate cancer progression, the epigenetic regulation of these processes is incompletely described. Here, we have integrated chromatin immunoprecipitation sequencing (ChIP-seq) and whole-transcriptome sequencing to identify novel regulators of metabolism in advanced prostate tumors characterized by elevated MYC activity. Results Using ChIP-seq against MYC, HOXB13, and AR in LNCaP cells, we observed redistribution of co-bound sites suggestive of differential KMT2A activity as a function of MYC expression. In a cohort of 177 laser-capture microdissected foci of prostate tumors, KMT2A expression was positively correlated with MYC activity, AR activity, and HOXB13 expression, but decreased with tumor grade severity. However, KMT2A expression was negatively correlated with these factors in 25 LuCaP patient-derived xenograft models of advanced prostate cancer and 99 laser-capture microdissected foci of metastatic castration-resistant prostate cancer. Stratified by KMT2A expression, ChIP-seq against AR and HOXB13 in 15 LuCaP patient-derived xenografts showed an inverse association with sites involving genes implicated in lipid metabolism, including the arachidonic acid metabolic enzyme PLA2G4F. LuCaP patient-derived xenograft models grown as organoids recapitulated the inverse association between KMT2A expression and fluorine-18 labeled arachidonic acid uptake in vitro. Conclusions Our study demonstrates that the epigenetic activity of transcription factor oncogenes exhibits a shift during prostate cancer progression with distinctive phenotypic effects on metabolism. These epigenetically driven changes in lipid metabolism may serve as novel targets for the development of novel imaging agents and therapeutics.

Antibody-drug conjugates (ADCs) are a promising targeted cancer therapy; however, patient selection based solely on target antigen expression without consideration for cytotoxic payload vulnerabilities has plateaued clinical benefits. Biomarkers to capture patients who might benefit from specific ADCs have not been systematically determined for any cancer. We present a comprehensive therapeutic and biomarker analysis of a B7H3-ADC with pyrrolobenzodiazepine(PBD) payload in 26 treatment- resistant, metastatic prostate cancer (mPC) models. B7H3 is a tumor-specific surface protein widely expressed in mPC, and PBD is a DNA cross-linking agent. B7H3 expression was necessary but not sufficient for B7H3-PBD-ADC responsiveness. RB1 deficiency and/or replication stress, characteristics of poor prognosis, and conferred sensitivity were associated with complete tumor regression in both neuroendocrine (NEPC) and androgen receptor positive (ARPC) prostate cancer models, even with low B7H3 levels. Non-ARPC models, which are currently lacking efficacious treatment, demonstrated the highest replication stress and were most sensitive to treatment. In RB1 WT ARPC tumors, SLFN11 expression or select DNA repair mutations in SLFN11 nonexpressors governed response. Importantly, WT TP53 predicted nonresponsiveness (7 of 8 models). Overall, biomarker-focused selection of models led to high efficacy of in vivo treatment. These data enable a paradigm shift to biomarker-driven trial designs for maximizing clinical benefit of ADC therapies., Introduction Metastatic prostate cancer (mPC) remains a lethal disease accounting for more than 30,000 deaths annually in the United States (1). The use of androgen deprivation therapy (ADT) and androgen [...]

An overview is presented of the progress since 2021 in the construction and scientific programme preparation of the Divertor Tokamak Test (DTT) facility. Licensing for building construction has been granted at the end of 2021. Licensing for Cat. A radiologic source has been also granted in 2022. The construction of the toroidal field magnet system is progressing. The prototype of the 170 GHz gyrotron has been produced and it is now under test on the FALCON facility. The design of the vacuum vessel, the poloidal field coils and the civil infrastructures has been completed. The shape of the first DTT divertor has been agreed with EUROfusion to test different plasma and exhaust scenarios: single null, double null, X-divertor and negative triangularity plasmas. A detailed research plan is being elaborated with the involvement of the EUROfusion laboratories.

Glycogen storage disease Type III (GSD III) is an autosomal recessive disease due to the deficiency of the debranching enzyme, which has two main consequences: a reduced availability of glucose due to the incomplete degradation of glycogen, and the accumulation of abnormal glycogen in liver and cardiac/skeletal muscle. The role of dietary lipid manipulations in the nutritional management of GSD III is still debated. A literature overview shows that low-carbohydrate (CHO) / high-fat diets may be beneficial in reducing muscle damage. We present a 24-year GSD IIIa patient with severe myopathy and cardiomyopathy in whom a gradual shift from a high-CHO diet (61% total energy intake), low-fat (18%), high-protein (21%) to a low-CHO (32 %) high-fat (45%) / high-protein (23%) diet was performed. CHO was mainly represented by high-fiber, low glycemic index food, and fat consisted prevalently of mono and polyunsaturated fatty acids. After a 2-year follow-up, all biomarkers of muscle and heart damage markedly decreased (by 50–75%), glucose levels remained within the normal range and lipid profile was unchanged. At echocardiography, there was an improvement in geometry and left ventricular function. A low -CHO, high-fat, high-protein diet seems to be safe, sustainable and effective in reducing muscle damage without worsening cardiometabolic profile in GSDIIIa. This dietary approach could be started as early as possible in GSD III displaying skeletal/cardiac muscle disease in order to prevent/minimize organ damage.