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Digital Documentation and Analysis of Palladian Microarchitectures: From 3D Models to Knowledge-Based Information Systems
No full textChimneypieces, washbasins, well heads, and sinks by Andrea Palladio represent refined design works following architectural systems on a reduced scale, even if systematic documentation and analysis of them is still limited. This paper introduces the custom knowledge-based Information System (IS) developed to study the design patterns and proportional relationships of these microarchitectures, after their digitization. The research employed smartphone-based photogrammetry to replicate fifty-seven chimneypieces and additional microarchitectures across twenty historical buildings; digital models were collected and organized into the IS enabling systematic typological and dimensional analysis. Proportional deepening revealed recurring ratios consistent with Renaissance treatise recommendations, alongside systematic variations suggesting design flexibility within theoretical frameworks. The IS integrates 3D architectural models by metadata attributes, providing a replicable framework for heritage documentation that combines scholarly rigor with technological accessibility. This approach offers new insights into Palladian design principles while establishing a scalable model for architectural heritage documentation and analysis
Mapping the non-coding RNA landscape in ataxia telangiectasia: a scoping review of ATM dependent miRNA and lncRNA dysregulation
No full textAtaxia-Telangiectasia (A-T) is caused by biallelic Ataxia-Telangiectasia Mutated (ATM) protein mutations and is hallmarked by neurodegeneration, immunodeficiency and cancer susceptibility. Emerging work suggests that non-coding RNAs are integral to the ATM driven DNA damage response, yet the scope of non-coding RNA perturbation in A-T has not systematically mapped. This study is done to chart and synthesize all primary evidence on ncRNA dysregulation in A-T and to identify mechanistic gaps and research priorities. The evidence base comprises a total of five studies focused exclusively on microRNAs and long non-coding RNAs. Baseline sequencing of 20 patients revealed consistent downregulation of miR-195-5p, miR-30a-5p and miR-342-3p. Low dose γ-irradiation of ATM-null lymphoblastoid cell lines produced an exaggerated bidirectional shift (8 microRNAs upregulated, 6 downregulated) versus wild-type, whereas primary T-cells showed largely ATM independent rises of miR-34a-5p and miR-182-5p. A lymphoblastoid cell lines study distinguished 22 recessive or dominant radiation-responsive microRNAs. Long non-coding RNAs profiling identified 149 transcripts that require functional ATM for induction and three uniquely upregulated in A-T cells. No circular RNA study in A-T is observed till date. The ncRNA research in A-T is nascent with five studies present a miRNA dysregulation and an ATM-dependent lncRNA surge that is lost in A-T, but leave circRNAs, neuronal tissues and functional validation unexplored. Intermediate dose stress models, total and small RNA-seq under DNA damage and oxidative stress, and CRISPR rescue/knockout screens in patient derived organoids are immediate priorities for exploring the role of ncRNAs as therapeutic targets in A-T
Deep Learning-based Data Collection to Reduce Energy Consumption in Internet of Things Devices
No full textThe Internet of Things has revolutionized various industries, but the energy consumption of the devices remains a significant challenge. This paper proposes a novel approach
to reduce energy consumption using deep learning-based data collection techniques. Our proposed framework leverages deep learning models to forecast sensor data to optimize data trans-mission to adapt to dynamic environmental conditions and reduce unnecessary energy expenditure. We demonstrate the effectiveness of our approach through extensive experiments, showcasing energy savings of up to 93% with respect to the state-of-the-art methods while maintaining desired levels of data accuracy and system performance. This research contributes to the development of more energy-efficient and sustainable Internet of Things systems, paving the way for a greener future
Path-Based Nonequilibrium Binding Free Energy Estimation, from Protein–Ligand to RNA-Ligand Binding
No full textIn this study, we addressed the challenge of estimating binding free energies in complex biological systems of pharmaceutical relevance, including both protein–ligand and RNA-ligand complexes. As case studies, we examined the intricate binding of the drug Gleevec to Abl-tyrosine kinase and two ligands binding to the preQ1 RNA riboswitch. By refining our approach based on nonequilibrium steered molecular dynamics simulations and path-based collective variables, we tackled the specific difficulties posed by these systems. In particular, the Abl–Gleevec complex is characterized by significant system size and extensive conformational rearrangements of the protein, whereas the systems involving RNA are characterized by marked conformational flexibility. For the Abl–Gleevec system, our method produced binding free energy estimates closely aligned with experimental values, demonstrating its reliability. For the RNA-ligand complexes investigated, we found that the simpler water model TIP3P yields more accurate free energy estimates than the TIP4P-D model, offering practical insight for future research. In this case, the agreement with the experimental results is reasonable. Overall, this work underscores the effectiveness of the proposed path-based workflow in handling complex biomolecular systems with unique characteristics, enabling systematic binding free energy predictions across a variety of targets
Macroeconomic, Monetary and Class-based: Marx’s Theory of Value Beyond New and Old Interpretations
No full textAfter briefly reconstructing the debate that has developed around Marx’s theory of value since the beginning of the XXth century, this work discusses the contributions by Claudio Napoleoni and especially Augusto Graziani, comparing them with other influential interpretations proposed since the 1980s. In particular, we first address Napoleoni’s reflections on the (alleged) fatal consequences of the ‘failure’ of the so-called transformation of values into prices for Marx’s theory of exploitation. Then, we confront this view with Augusto Graziani’s reflection, according to which the Marxian theory of value could be ‘rehabilitated’ precisely as a macroeconomic theory of capitalist exploitation, where the microeconomic determination of relative prices remains in the background. In doing so, the contribution also explores the (in)consistency between Graziani’s theory and the ‘New Interpretation’ first and independently proposed by Lipietz, Duménil and Foley. Finally, a simple formal ‘reconstruction’ of Marxian theory, explicitly accounting for the monetary and class nature of capitalism in a credit-money context, is presented
3D-printed chewable Gummies: A customizable approach to formulate propranolol in the paediatric population
No full textPaediatric patients, representing over 30 % of the global population, continue to face a critical shortage of age-appropriate pharmaceutical formulations. This gap is largely attributed to the high cost and complexity of paediatric drug development, resulting in the widespread off-label use of adult medications in children—an approach that compromises safety, therapeutic efficacy, and adherence. Conventional manufacturing methods often fail to meet essential paediatric requirements such as dose flexibility, palatability, and ease of administration, all of which are pivotal for ensuring treatment adherence. Providing that the European Paediatric Formulation Initiative (EuPFI) and EMA reflection papers suggest that chewable dosage forms are generally acceptable starting at around age 3, chewables are usually considered adequate for children from about 3 to 5 years onward.
This study proposes a semisolid extrusion-based 3D printing methodology for the fabrication of chewable paediatric dosage forms—referred to as gummies—incorporating propranolol hydrochloride as a model hydrophilic drug commonly prescribed for cardiovascular and cardiac conditions in children. A hydrogel matrix consisting of 7 % w/w iota-carrageenan and 3 % w/w sodium alginate was optimized to ensure appropriate rheological properties, printability, and structural integrity. Fourier-transform infrared (FTIR) spectroscopy confirmed the uniform distribution of the active pharmaceutical ingredient within the matrix. Texture profile analysis revealed desirable mechanical properties when compared to those of commercially available gummies. Furthermore, the printed dosage units conformed to the European Pharmacopoeia quality specifications for mass uniformity and content uniformity. Notably, the simplicity and scalability of the presented approach suggest its suitability for implementation in both hospital and community pharmacy environments, facilitating decentralized manufacturing of personalized paediatric medications
Application of Deep Learning to Predict the Persistence, Bioaccumulation, and Toxicity of Pharmaceuticals
No full text: This study investigates the application of a deep learning (DL) model, specifically a message-passing neural network (MPNN) implemented through Chemprop, to predict the persistence, bioaccumulation, and toxicity (PBT) characteristics of compounds, with a focus on pharmaceuticals. We employed a clustering strategy to provide a fair assessment of the model performances. By applying the generated model to a set of pharmaceutically relevant molecules, we aim to highlight potential PBT chemicals and extract PBT-relevant substructures. These substructures can serve as structural flags, alerting drug designers to potential environmental issues from the earliest stages of the drug discovery process. Incorporating these findings into pharmaceutical development workflows is expected to drive significant advancements in creating more environmentally friendly drug candidates while preserving their therapeutic efficacy
Predictors of disease burden in patients with untreated transthyretin amyloid cardiomyopathy and their caregivers: a post hoc analysis of an international survey
No full textIntroduction: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive condition with debilitating symptoms. The self-reported burden of ATTR-CM on patients and their caregivers was previously evaluated in an international, multicenter, real-world survey study. Methods: This post hoc analysis used univariate and multivariate models to evaluate survey items as predictors of ATTR-CM burden. The final multivariate models were optimized using forward selection and CV Press criteria with 8-fold cross-validation to include only the best predictors. Hierarchical linear regression analyses were used to explore potential moderators of the relationship between patient health status and caregiver burden. Results: The original survey included 208 patients with ATTR-CM, naïve to disease-modifying treatment, and their unpaid primary caregivers from international amyloidosis centers of excellence in 7 countries between July 2021 and August 2022. Most patients were male (86%), elderly (median age, 81 years), and had untreated wild-type ATTR-CM (91% of 155 with genetic testing). Patients reported fair to good health status overall [Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) median score, 68]. Most (60%) of the 199 patients with a New York Heart Association (NYHA) classification were class II (18% class I; 22% class III). Optimized multivariate models for several measures found symptomatic heart failure (NYHA class II or III), having "weakness, especially in the legs," older age, and female sex, were independent predictors of higher patient-reported burden. The majority of caregivers were female (85%) and the spouse (59%) or adult child (37%) of the patient. The median duration of caregiving was 1.5 years. In the final optimized multivariate model, only the patient's KCCQ-OS score was a significant predictor of caregiver burden. This relationship was not clinically moderated by other patient or caregiver variables. Conclusions: Our analysis showed that heart failure symptoms, weakness, especially in the legs, older age, and female sex, are independent predictors of higher disease burden in patients with ATTR-CM. A higher caregiver burden was best predicted by poorer health status in the patient, even in the presence of potential moderators. Implementing strategies to reduce the physical symptoms experienced by patients with ATTR-CM may help to reduce their burden, and that experienced by caregivers
Alessandro Serpieri and his seismographs: innovations in late nineteenth-century Italian seismology
No full textThe paper examines the historical development and context of several seismographs preserved in the Physics Laboratory and Museum of Science and Technology at the University of Urbino Carlo Bo. In the second half of the nineteenth century, these instruments were used by Alessandro Serpieri (1823–1885), a Scolopian priest and a pioneer of Italian seismology. Following a brief biographical overview of the scientist, the study examines three principal instruments currently on display in the museum: the “protoseismograph” by Michele Stefano De Rossi (1878) and two seismographs designed by the Urbino-based instrument-maker Achille Scateni (c. 1882). In addition to these surviving instruments, the study also discusses a seismograph invented by Serpieri in 1873, known only through contemporary descriptions and illustrations. This study re-examines their history and mechanical functioning using archival documents, publications from the period, and direct analysis of the instruments, focusing on Luigi Palmieri’s influence on Serpieri’s seismograph design. It highlights the scientific heritage of Urbino’s Physics Laboratory and the pivotal collaboration between Serpieri and Scateni, locating their advancements in Italian instrumental seismology within the context of the birth of quantitative seismometry which complemented continuing observational methods in the late nineteenth century. In particular, it suggests how the interplay between local instrumental innovation and national scientific networks fostered the development of modern seismometry in Italy
Ad oceanum, gli archi liminali di Rimini, Ancona e Fano
No full textEste capítulo examina tres monumentos bien conocidos
en el centro de Italia adriática, dos arcos, los arcos proto-augusteos de
Rímini y el arco trajaneo de Ancona, y una puerta, la Puerta augustea de
Fano. Estos tres arcos cumplen funciones tanto urbanas como fronterizas;
los arcos de Rímini y Fano son partes integrales de las respectivas
murallas de la ciudad, sirviendo como entradas principales. Además,
están conectados al sistema de calzadas, enlazados con la vía consular
Flaminia, una arteria especialmente favorecida por Augusto. Él realizó
importantes trabajos de renovación en ella, como se documenta en la
Res Gestae y la inscripción en el Arco de Rímini. En contraste, el Arco de
Ancona está estrechamente asociado con uno de los principales puertos
del mar Adriático, designado como el ‘accessus Italiae’, como se indica en
la inscripción en el ático