6 TH INTERNATIONAL CONFERENCE ON COMPOSITE MATERIALS NON-AUTOCLAVE PROCESSING OF SANDWICH STRUCTURES: THE ROLE OF PREPREG THROUGH THICKNESS AIR PERMEABILITY

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Aluminum alloy production for the reinforcement of the CMS conductor

The Compact Muon Solenoid (CMS) is one of the general-purpose detectors to be provided for the Large Hadron Collider (LHC) project at CERN. The design field of the CMS superconducting magnet is 4 T, the magnetic length is 12.5 m and the free bore is 6 m. To reinforce the high-purity (99.998%) Al-stabilized conductor of the magnet against the magnetic loadings experienced during operation at 4.2 K, two continuous sections of Al-alloy (AA) reinforcement are Electron Beam (EB) welded to it. The reinforcements have a section of 24*18 mm and are produced in continuous 2.55 km lengths. The alloy EN AW-6082 has been selected for the reinforcement due to its excellent extrudability, high strength in the precipitation hardened states, high toughness and strength at cryogenic temperature and good EB weldability. Each of the continuous lengths of the reinforcement is extruded billet on billet and press quenched on-line from the extrusion temperature in an industrial extrusion plant. In order to insure the ready EB weldability of the reinforcement onto the pure aluminum of the insert, tight dimensional tolerances and proper surface finish of the reinforcement are required in the as-extruded state. As well, in order to facilitate the winding operation of the conductor, the uniformity of the mechanical properties of the extruded reinforcement, especially at the billet on billet joints, is critical. To achieve these requirements in an industrial environment, substantial effort was made to refine existing production techniques and to monitor critical extrusion parameters during production. This paper summarizes the main results obtained during the establishment of the extrusion line and of the production phase of the reinforcement. (10 refs)

Design, construction, and quality tests of the large Al-alloy mandrels for the CMS coil

The Compact Muon Solenoid (CMS) is one of the general-purpose detectors to be provided for the LHC project at CERN. The design field of the CMS superconducting magnet is 4 T, the magnetic length is 12.5 m and the free bore is 6 m. Almost all large indirectly cooled solenoids constructed to date (e.g., Zeus, Aleph, Delphi, Finuda, Babar) comprise Al-alloy mandrels fabricated by welding together plates bent to the correct radius. The external cylinder of CMS will consist of five modules having an inner diameter of 6.8 m, a thickness of 50 mm and an individual length of 2.5 m. It will be manufactured by bending and welding thick plates (75 mm) of the strain hardened aluminum alloy EN AW-5083-H321. The required high geometrical tolerances and mechanical strength (a yield strength of 209 MPa at 4.2 K) impose a critical appraisal of the design, the fabrication techniques, the welding procedures and the quality controls. The thick flanges at both ends of each module will be fabricated as seamless rolled rings, circumferentially welded to the body of the modules. The developed procedures and manufacturing methods will be validated by the construction of a prototype mandrel of full diameter and reduced length (670 mm). (7 refs)

Possible fabrication techniques and welding specifications for the external cylinder of the CMS coil

The Compact Muon Solenoid (CMS) is one of the experiments, which are being designed in the framework of the Large Hadron Collider (LHC) project at CERN. The design field of the CMS magnet is 4 T, the magnetic length is 12.5 m and the free aperture is 6 m in diameter. This is achieved with a 4 layer and 5 module superconducting Al- stabilized coil energized at a nominal current of 20 kA at 4.5 K. In the CMS coil the structural function is ensured, unlike in other existing Al-stabilized thin solenoids, both by the Al-alloy reinforced conductor and the external cylinder. The calculated stress level in the cylinder at operating conditions is particularly severe. In this paper the different possible fabrication techniques are assessed and compared and a possible welding specification for this component is given. (9 refs)

Continuous EB welding of the reinforcement of the CMS conductor

The Compact Muon Solenoid (CMS) is one of the general-purpose detectors to be provided for the LHC project at CERN. The design field of the CMS superconducting magnet is 4 T, the magnetic length is 12.5 m and the free bore is 6 m. In order to withstand the electro-mechanical forces during the operation of the CMS magnet, the superconducting cable embedded in a 99.998% pure aluminum matrix is reinforced with two sections of aluminum alloy EN AW-6082 assembled by continuous Electron Beam Welding (EBW). A dedicated production line has been designed by Techmeta, a leading company in the field of EBW. The production line has a total length of 70 m. Non-stop welding of each of the 20 lengths of 2.5 km, required to build the coil, will last 22 hours. EBW is the most critical process involved in the production line. The main advantage of the EBW process is to minimize the Heat Affected Zone; this is particularly important for avoiding damage to the superconducting cable located only 4.7 mm from the welded joints. Two welding guns of 20 kW each operate in parallel in a vacuum chamber fitted with dynamic airlocks. After welding, the conductor is continuously machined on the four faces and on each corner to obtain the required dimensions and surface finish. Special emphasis has been put on quality monitoring. All significant production parameters are recorded during operation and relevant samples are taken from each produced length for destructive testing purposes. In addition, a continuous phased array ultrasonic checking device is located immediately after the welding unit for the continuous welding quality control, along with a dimension laser measurement unit following the machining. (8 refs)

Pyruvate Dehydrogenase Complex Deficiency: Updating the Clinical, Metabolic and Mutational Landscapes in a Cohort of Portuguese Patients

Background: The pyruvate dehydrogenase complex (PDC) catalyzes the irreversible decarboxylation of pyruvate into acetyl-CoA. PDC deficiency can be caused by alterations in any of the genes encoding its several subunits. The resulting phenotype, though very heterogeneous, mainly affects the central nervous system. The aim of this study is to describe and discuss the clinical, biochemical and genotypic information from thirteen PDC deficient patients, thus seeking to establish possible genotype-phenotype correlations. Results: The mutational spectrum showed that seven patients carry mutations in the PDHA1 gene encoding the E1α subunit, five patients carry mutations in the PDHX gene encoding the E3 binding protein, and the remaining patient carries mutations in the DLD gene encoding the E3 subunit. These data corroborate earlier reports describing PDHA1 mutations as the predominant cause of PDC deficiency but also reveal a notable prevalence of PDHX mutations among Portuguese patients, most of them carrying what seems to be a private mutation (p.R284X). The biochemical analyses revealed high lactate and pyruvate plasma levels whereas the lactate/pyruvate ratio was below 16; enzymatic activities, when compared to control values, indicated to be independent from the genotype and ranged from 8.5% to 30%, the latter being considered a cut-off value for primary PDC deficiency. Concerning the clinical features, all patients displayed psychomotor retardation/developmental delay, the severity of which seems to correlate with the type and localization of the mutation carried by the patient. The therapeutic options essentially include the administration of a ketogenic diet and supplementation with thiamine, although arginine aspartate intake revealed to be beneficial in some patients. Moreover, in silico analysis of the missense mutations present in this PDC deficient population allowed to envisage the molecular mechanism underlying these pathogenic variants. Conclusion: The identification of the disease-causing mutations, together with the functional and structural characterization of the mutant protein variants, allow to obtain an insight on the severity of the clinical phenotype and the selection of the most appropriate therapy.info:eu-repo/semantics/publishedVersio

Molecular determinants of the SARS-CoV-2 fusion peptide activity

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, emerged in late 2019 and quickly spread worldwide, resulting in over 125 million infections and 2.7 million deaths as of March 2021 accordingly to the World Health Organization. Despite the great advances achieved by the scientific community in providing crucial information about this virus, we are still far from completely understanding it. SARS-CoV-2 is an enveloped virus, meaning that it is encapsulated by a lipid membrane, which needs to be fused to the host membrane to begin the infection process. Fusion between viral and host membrane is catalyzed by the spike (S) glycoprotein. The S-protein is composed of essential elements for the infection mechanism, namely the receptor-binding domain known to bind to angiotensin-converting enzyme 2 during the viral entry pathway. Another important region, known as the fusion peptide (FP), plays an essential part in the fusion mechanism, by inserting into and disturbing the host membrane. There is still not a consensus among scientists in terms of the fusion peptide location on the S-protein sequence, with two major candidate regions having been proposed. We recently used a machine learning-based tool developed by us to identify viral FPs with accuracies over 85%. With this tool a putative FP, previously suggested in the literature, has been identified, as well as other proposals including the requirement of more than one FP. To further address this question, we are performing a systematic analysis of the SARS-CoV-2 putative FPs, using Molecular Dynamics (MD) simulations, which provide a detailed perspective of how these peptides insert and interact with the membrane. In parallel, we are characterizing these systems experimentally. Additionally we are exploring therapeutic strategies targeting these regions. Given the major role of the FP in the virus infection process, this work provides relevant insights and contributes to the fight against COVID-19.info:eu-repo/semantics/publishedVersio

The CMS conductor

The Compact Muon Solenoid (CMS) is one of the experiments, which are being designed in the framework of the Large Hadron Collider (LHC) project at CERN, the design field of the CMS magnet is 4 T, the magnetic length is 13 m and the aperture is 6 m. This high magnetic field is achieved by means of a 4 layer, 5 modules superconducting coil. The coil is wound from an Al-stabilized Rutherford type conductor. The nominal current of the magnet is 20 kA at 4.5 K. In the CMS coil the structural function is ensured, unlike in other existing Al-stabilized thin solenoids, both by the Al-alloy reinforced conductor and the external former. In this paper the retained manufacturing process of the 50-km long reinforced conductor is described. In general the Rutherford type cable is surrounded by high purity aluminium in a continuous co-extrusion process to produce the Insert. Thereafter the reinforcement is joined by Electron Beam Welding to the pure Al of the insert, before being machined to the final dimensions. During the manufacture the bond quality between the Rutherford cable and the high purity aluminium as well as the quality of the EB welding are continuously controlled by a novel ultrasonic phased array system. The dimensions of the insert and the final conductor are measured by laser micrometer. (8 refs)

Transmural Remission Improves Clinical Outcomes Up to 5 years in Crohn's Disease

Introduction: Evidence supporting transmural remission (TR) as a long-term treatment target in Crohn's disease (CD) is still unavailable. Less stringent but more reachable targets such as isolated endoscopic (IER) or radiologic remission (IRR) may also be acceptable options in the long-term. Methods: Multicenter retrospective study including 404 CD patients evaluated by magnetic resonance enterography and colonoscopy. Five-year rates of hospitalization, surgery, use of steroids, and treatment escalation were compared between patients with TR, IER, IRR, and no remission (NR). Results: 20.8% of CD patients presented TR, 23.3% IER, 13.6% IRR and 42.3% NR. TR was associated with lower risk of hospitalization (odds-ratio [OR] 0.244 [0.111-0.538], p < 0.001), surgery (OR 0.132 [0.030-0.585], p = 0.008), steroid use (OR 0.283 [0.159-0.505], p < 0.001), and treatment escalation (OR 0.088 [0.044-0.176], p < 0.001) compared to no NR. IRR resulted in lower risk of hospitalization (OR 0.333 [0.143-0.777], p = 0.011) and treatment escalation (OR 0.260 [0.125-0.540], p < 0.001), while IER reduced the risk of steroid use (OR 0.442 [0.262-0.745], p = 0.002) and treatment escalation (OR 0.490 [0.259-0.925], p = 0.028) compared to NR. Conclusions: TR improved clinical outcomes over 5 years of follow-up in CD patients. Distinct but significant benefits were seen with IER and IRR. This suggests that both endoscopic and radiologic remission should be part of the treatment targets of CD.info:eu-repo/semantics/publishedVersio