LE STUDIUM Multidisciplinary Journal

Wen Chen1,3, Da-Yan Liu2, and Driss Boutat2
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This work is the first of its kind to present a fractional-order learning observer for diagnosing individual battery faults in a battery string. There are no voltage measurements to each individual battery cell on this string; instead, a sensor is mounted at the two ends of the string to measure the total of the voltage values for all cells on the same string. To accurately model a battery cell, the constant phase element is used in the electric circuit model. Because it has the fractional-order characteristic, the battery cell is modeled as a fractional-order system. Based on the fractional-order model of the battery string, a fractional-order learning observer is designed to diagnose the faults from battery controller signals and internal short circuit to achieve industrial risk management. Simulation studies are conducted to verify the effectiveness of the proposed fractional-order learning observer.
 

Alessandro Turbil 1, 2, 3
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Since the Renaissance, Western societies have shown a profound fascination with the Middle Ages, and although it is generally assumed that the transmission of the medieval cultural and literary heritage came to an end with the beginning of this new 'age', recent critical advances have demonstrated the enduring presence of medieval literature in the book markets of the 16th, 17th and 18th centuries. However, the publishing and reading practices that shaped the transmission and reception of this cultural heritage remain largely unexamined. The research project Medieval Lyric Heritage in the French Printing and Bookselling Network (1470-1600): A Bibliographical and Ontological Preliminary Study, supported by the Institute for Advanced Studies LeStudium at the Centre d’Études Supérieures de la Renaissance (University of Tours), addressed significant methodological challenges and sought to develop an ontology focusing on the circulation of written cultural artefacts in print, with particular emphasis on the reuse of textual, iconographic and material elements within the printing ecosystem.

Erminia Ardissino1,2,3 , Elise Boillet3
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The European Renaissance saw a deep renewal of the form and content of prayer. Even before the Reformation (whether Protestant or Catholic), the growing role played by lay people, women and men, in the religious sphere created new forms of worship, developing new practices and new texts. The renewal became even more intense during the 16th and 17th centuries, two centuries defined and devastated by changing confessional identities, but also vitalized by the printing press and confraternal activities. The project intended to study, from a multidisciplinary perspective, the changes which took place in this everyday and universal practice in the early modern period. The results offer an important contribution to knowledge on the topic for two reasons: first, it goes beyond existing studies on prayer, which do not go later than the 15th century and are focused on monastic prayer and books of hours; second, because it took into account under-studied aspects, such as domestic practices, the contributions of women, devotional images, books of prayer, catechisms, and parodies, offering a truly new picture that may suggest much further research. Moreover, having involved scholars who specialise in the fields being studied, the results offer an unparalleled academic contribution on the various topics considered.

H. Arthur Woods1,3 and Jérôme Casas2
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Insects transport respiratory gases in air-filled tracheal tubes, and a fundamental problem over the past century has been to understand how insects transport gases rapidly enough to support their metabolic rates under highly variables regimes of supply and demand. Here, using a mix of mathematical and physical models, we evaluate the roles that carbon dioxide plays in shaping tracheal structure and function in caterpillars. We first evaluate whether CO2 trapping by midgut fluids drives convective flows of oxygen toward tracheal tips. We then evaluate whether and how CO2 is recycled, via the tracheal system, between the highly alkaline midguts of caterpillars and their acidic hindguts. We conclude that, for caterpillars, there is only weak evidence for CO2-driven convective gas flows. Nevertheless, the models suggest that caterpillars can use convection driven by oxygen absorption to move CO2 rapidly from posterior to anterior parts of the tracheal system. Our results also suggest new approaches to key problems in microfluidics – namely, how to control the movements of gases and liquids within small channels.

Anielka Zehnaker 1, Amandine Vallet 1, Juliette Gourdon 1, Caterina Sarti 1, Vinesh Jugnarain 1, Maya Haj Hassan 1, Laetitia Mathias 1, Camille Gauthier 1, Pauline Raynaud 1, Thomas Boulo 1, Linda Beauclair 1, Yves Bigot 1, Livio Casarini 1 2 5, Pascale C
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In this study, we tackled the challenge of developing modulatory antibodies against G protein-coupled receptors, with a specific focus on the follicle-stimulating hormone receptor (FSHR), a pivotal regulator of reproduction. Leveraging variable domains of heavy chain-only antibodies (VHHs), we constructed two immune VHH libraries and implemented multiplexed phage display techniques. Our methodology integrated Multiplexed Phage Display, High-Throughput Sequencing, and Functional Assays to identify modulatory VHHs targeting FSHR. Following library construction, next-generation sequencing identified 34 clusters of specifically enriched sequences. These sequences underwent functional assessment in a primary screen based on a cAMP response element (CRE)-dependent reporter gene assay. Impressively, 23 VHHs displayed either negative or positive modulation of FSH-induced responses, indicating a high success rate for the multiplexed strategy. Subsequently, we focused on the largest identified cluster, PRC1, which exhibited positive modulation of FSH action. We provided evidence that PRC1 specifically binds to human FSHR and the FSHR/FSH complex, enhancing FSH-induced cAMP production and Gs recruitment. In conclusion, our study showcases an improved selection strategy that effectively identifies functionally active VHHs and can be adapted to target other challenging membrane receptors. Notably, this investigation led to the discovery of PRC1, the first potential positive modulator VHH reported for the human FSHR.

Neil C. Sturchio1,3, Daniel Hube2, Patrick Ollivier2
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The present study was conducted to elucidate the connections of modern groundwater pollution to specific munitions materials used and destroyed during and after World War I (WWI).  Large quantities of unexploded munitions are still present in the tunnels and soils of former battlefields. We performed analyses of the isotopic compositions of nitroaromatics, nitrate, and perchlorate in samples of munition and contaminated groundwater collected at three sites along the WWI battlefront in northern France. The isotopic data from these samples indicates a direct connection between the groundwater contamination and the WWI munitions. Potential adverse effects on public health from munitions compounds in groundwater indicate an urgent need for further evaluation of the continuing presence of legacy WWI munitions and their contribution to chronic groundwater pollution in the region.

Mahenina Jaovita Manase1, 2 and Emilie Destandau3
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Ravenala or Traveller's Tree (STRELITZIACEAE) and Litchi (SAPINDACEAE) are two species widely distributed in Madagascar. Particularly, on the one hand, the Litchi fruit is exploited by the local agri-food industry and offers valuable co-products. On the other hand, some part of Ravenala enters the preparation of traditional remedy used by the Malagasy. In this research project focused on the valorisation of plant and co-product, our strategy is to characterize active compounds. Our study consists of developing analytical analysis methods and performing biological tests to identify the active compounds. Since the Institute of Organic and Analytical Chemistry - ICOA UMR7311 is at the cutting edge of technology and has internationally renowned expertise in natural substances for cosmetic uses. Our cooperation can easily meet our objectives. Thus, we would have found in plants widely distributed in Madagascar biosourced ingredients.

Georg von Samson-Himmelstjerna2,4 , Abdallah Harmache1, Oceane Lénhof1, Jürgen Krücken2, Alexandre Vernudachi3, Cédric Neveu1
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Helminth infections represent a major health threat for both humans and animals. In the latter they occur at often very high prevalences and on a global scale. Due to a near complete lack of immuno-prophylactic measures the metaphylactic use of chemotherapeutics i.e. the anthelmintics is the corner stone of worm control since decades. This has resulted in widespread anthelmintic resistance in a range of helminth species. Particularly the gastrointestinal nematodes and amongst them also so called roundworms or ascarids have evolved resistance. This results in an increasing clinical issue as like in horses the Parascaris spp. as well as in pigs or humans the Ascarais spp. often cause considerable clinical symptoms. To improve the sustainable use and provide solutions for the resistance problem it is important to understand the molecular mechanisms of anthelmintic resistance. In the present project the P-glycoprotein (Pgp) based drug efflux as a non-drug target associated mechanism of resistance is being addressed in Parascaris. To this end, the model nematode Caenorhabditis elegans was employed and the specific role of the Pgp3 was  examined. The pharmacological profile of a Pgp3 knock out C. elegans line (VC 2338) was established using a panel of anthelmintic compounds and compared with the N2 wildtype strain. Furthermore, the Parascaris Pgp3 coding sequence was injected into the VC2338 to achieve recombinant expression under an intestinal promotor (ges1) as we have done it successfully with another Parascaris Pgp recently. Our results suggest that the Parascaris Pgp3 overexpression in C. elegans interferes with the development of the worm and ongoing investigations attempt to further elucidate the specific role of Pgp3 in the worms homoeostasis.

Bilal Haider Abbasi, Tehreem Mahmood, Arnaud Lanoue, Nathalie Giglioli Guivarch
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One of the Asteraceae family's most significant therapeutic herbs is Echinacea purpurea (L.) Moench. The plant is extremely rich in anti inflammatory and antioxidant chemicals, that can be produced effectively and sustainably by in vitro cultures, which are often enhanced by the inclusion of an elicitor in the culture media. In the present investigation, TDZ was effectively utilized to induce E. purpurea callus cultures. Additionally, different melatonin dosages were evaluated for their impact on biomass accumulation, antioxidant capability, and secondary metabolite synthesis. In callus treated with 25μM melatonin, the highest biomass accumulation, total phenolic output, and total flavonoid production were noted. At the same moderate concentration, the best DPPH radical scavenging activity and overall antioxidant capacity were also observed. A positive association was reflected between biomass and these factors. Notable inhibitory effects were seen against pancreatic lipase, alpha-glucosidase, and alpha-amylase after administration with exogenous melatonin, respectively, during the investigation of the potential of callus cultures. These results emphasized the need to look into the existing strategy in more detail in order to identify novel approaches to treating diabetes and obesity. In HPLC analysis, maximum amounts of metabolites resulted at concentrations of 25–50 μM, except amino acids that were associated with the lowest melatonin concentration. Our research showed that TDZ can be used for efficient callus induction of E. purpurea, and elicitation with melatonin may be a useful tactic for boosting biomass, phenolic compounds, flavonoids, and antioxidant capacity as well as numerous enzyme inhibitory effects.

Magdalena Mizerska-Kowalska, Samia Aci-Sèche, Stéphane Bourg, Elżbieta Łastawiecka, Pascal Bonnet
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Constitutive activation of ERK1/2 pathway drives the proliferation and survival of many cancer cell types. Therefore, the new approaches, i.e. small molecular weight compounds targeting directly hyperactivated ERK 1/2, are widely explored as anticancer compounds. Recently, new molecules based on a 1,1-dioxido-2,5-dihydrothiophen-3-yl 4-benzenesulfonate scaffold (targeting the FRS domain of ERK2) were synthesized. These new molecules, indicated as compounds 4 and 6, contain modifications of the arylamine substituent at the 4-position of the heterocyclic scaffold. To gain insight into molecular mechanisms of their activity, the study was focused on the exploration of potential interaction of these new compounds with ERK2 by means of in silico study, i.e. molecular docking. The docking procedure was carried out within both substrate docking sites, DRS and FRS, and ATP binding sites, and by means of Molecular Operating Environment (MOE) system. The 4gt3, 
high-resolution ERK2 structure available in the Protein Data Bank (RCSB PDB) was chosen for this purpose. The analysis indicated that both compounds 4 and 6 bound with similar efficiency within both substrate docking sites, DRS and FRS, but not in the ATP binding site.