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This study proposes a generalized nth-order perturbation method based on (isogeometric) boundary element methods for uncertainty analysis in 3D acoustic scattering problems. In this paper, for the first time, we derive nth-order Taylor expansions of 3D acoustic boundary integral equations, taking incident wave frequency as a random input variable. In addition, subdivision surface basis functions used in geometric modeling are employed to discretize the generalized nth-order derivative boundary integral equations, in order to avoid cumbersome meshing procedure and retain geometric accuracy. Moreover, the fast multipole method is introduced to accelerate the stochastic perturbation analysis with boundary element methods. Numerical examples are given to demonstrate the accuracy and efficiency of the proposed uncertainty quantification algorithm.

The Werner syndrome RecQ helicase WRN was identified as a synthetic lethal target in cancer cells with microsatellite instability (MSI) by several genetic screens1–6. Despite advances in treatment with immune checkpoint inhibitors7–10, there is an unmet need in the treatment of MSI cancers11–14. Here we report the structural, biochemical, cellular and pharmacological characterization of the clinical-stage WRN helicase inhibitor HRO761, which was identified through an innovative hit-finding and lead-optimization strategy. HRO761 is a potent, selective, allosteric WRN inhibitor that binds at the interface of the D1 and D2 helicase domains, locking WRN in an inactive conformation. Pharmacological inhibition by HRO761 recapitulated the phenotype observed by WRN genetic suppression, leading to DNA damage and inhibition of tumour cell growth selectively in MSI cells in a p53-independent manner. Moreover, HRO761 led to WRN degradation in MSI cells but not in microsatellite-stable cells. Oral treatment with HRO761 resulted in dose-dependent in vivo DNA damage induction and tumour growth inhibition in MSI cell- and patient-derived xenograft models. These findings represent preclinical pharmacological validation of WRN as a therapeutic target in MSI cancers. A clinical trial with HRO761 (NCT05838768) is ongoing to assess the safety, tolerability and preliminary anti-tumour activity in patients with MSI colorectal cancer and other MSI solid tumours.

The synthesis and pharmacological activity of a new series of isoxazolylpyrimidines as sigma-2 receptor (σ2R) ligands are reported. Modification of a new hit retrieved in an HTS campaign allowed the identification of the compound WLB-89462 (20c) with good σ2R affinity (Ki= 13 nM) and high selectivity vs both the σ1R (Ki= 1777 nM) and a general panel of 180 targets. It represents one of the first σ2R ligands with drug-like properties, linked to a good physicochemical and ADMET profile (good solubility, no CYP inhibition, good metabolic stability, high permeability, brain penetration, and high oral exposure in rodents). Compound 20cshows neuroprotective activity in vitro and improves short-term memory impairment induced by hippocampal injection of amyloid β peptide in rats. Together with the promising effects in the chronic models where 20cis currently being evaluated, these results pave the way toward its clinical development as a neuroprotective agent.

In this paper, we present a set of improved algorithms for recovering computer aided design (CAD-type) surface models from three-dimensional (3D) images. The goal of the proposed framework is to generate B-spline or non-uniform rational B-spline (NURBS) surfaces, which are standard mathematical representations of solid objects in digital engineering. To create a NURBS surface, we first compute a control network (a quadrilateral mesh) from a triangular mesh using the Marching Cubes algorithm and Discrete Morse theory. To create a NURBS surface, we first compute a triangular mesh using the Marching Cubes algorithm, then the control network (a quadrilateral mesh) is determined from the triangular mesh by using Discrete Morse theory. Discrete Morse theory uses the critical points of a specific scalar field defined over the triangulation to generate a quad mesh. Such a scalar field is obtained by solving a graph Laplacian eigenproblem over the triangulation. However, the resulting surface is not optimal. We therefore introduce an optimization algorithm to better approximate the geometry of the object. In addition, we propose a statistical method for selecting the most appropriate eigenfunction of the graph Laplacian to generate a control network that is neither too coarse nor too fine, given the precision of the 3D image. To do this, we set up a regression model and use an information criterion to choose the best surface. Finally, we extend our approach by taking into account both model and data uncertainty using probabilistic regression and sampling the posterior distribution with Hamiltonian Markov Chain Monte Carlo.Graphical Abstract

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We describe the SOniCS (SOFA + FEniCS) plugin to help develop an intuitive understanding of complex biomechanics systems. This new approach allows the user to experiment with model choices easily and quickly without requiring in-depth expertise. Constitutive models can be modified by one line of code only. This ease in building new models makes SOniCS ideal to develop surrogate, reduced order models and to train machine-learning algorithms for enabling real-time patient-specific simulations. SOniCS is thus not only a tool that facilitates the development of surgical training simulations but also, and perhaps more importantly, paves the way to increase the intuition of users or otherwise non-intuitive behaviors of (bio)mechanical systems. The plugin uses new developments of the FEniCSx project enabling automatic generation with FFCx of finite-element tensors, such as the local residual vector and Jacobian matrix. We verify our approach with numerical simulations, such as manufactured solutions, cantilever beams, and benchmarks provided by FEBio. We reach machine precision accuracy and demonstrate the use of the plugin for a real-time haptic simulation involving a surgical tool controlled by the user in contact with a hyperelastic liver. We include complete examples showing the use of our plugin for simulations involving Saint Venant–Kirchhoff, Neo-Hookean, Mooney–Rivlin, and Holzapfel Ogden anisotropic models as supplementary material.

This paper presents a new non-boundary-fitted-grid numerical technique for solving partial differential equations (PDEs) in multi-hole domains. A multiply-connected domain is converted into a simply-connected domain of rectangular or non-rectangular shape that is discretised using a Cartesian grid. Compact radial basis function (RBF) stencils, which are constructed through integration rather than the conventional differentiation, are used to discretise the field variables. The imposition of inner boundary conditions is conducted by means of body forces that are derived from satisfying the governing equations and prescribed boundary conditions in small subregions. Salient features of the proposed method include: (i) simple pre-processing (Cartesian grid), (ii) high rates of convergence of the solution accuracy with respect to grid refinement achieved with compact integrated-RBF stencils, where both nodal function and derivative values are included in the approximations, (iii) the system matrix kept unchanged for the case of moving holes, and (iv) no interpolation between Lagrange and Euler meshes required. Several linear and nonlinear problems, including rotating-cylinder flows and buoyancy-driven flows in eccentric and concentric annuli, are simulated to verify the proposed technique. • This paper presents a new non-boundary-fitted-grid method. • The field variables are approximated using compact integrated-RBF stencils. • Body forces are derived from satisfying the PDEs and boundary conditions in subregions. • Interpolation between the two Euler and Lagrange systems is not required. • Multiply-connected domains with moving holes are considered in verification. [ABSTRACT FROM AUTHOR]

AbstractThis essay challenges the equity of eco-cosmopolitism, which Patrick Hayden defines as a socio-political “world environmental citizenship” (2010, 368). Isabelle Stengers, among others, recommends an ecological “cosmopolitical proposal”– a global checks and balances system (2005, 1003). In response, I argue that eco-cosmopolitism merely dredges up the same criticism of inequality and social injustice already problematized against Kant’s “civil commons.” Examining Malik Sajad’s Munnu: A Boy from Kashmir(2015), I explore the cultural narrative concerning the hazardous disposal of waste in Kashmir. I suggest that eco-cosmopolitism is a neo-imperialist hegemonic construct that glosses over both the lived experiences and the complicated history of Kashmir. Ideological visions of a global environmentalism are easy to imagine when one occupies the privilege of sanitary waste management and relative political stability; however, in contested territories of violence, one’s concern for the environment is guided less by planetary liberal-universalist environmentalism than by ownership of local land. Examining Munnu’srepresentation of Kashmir’s sanitation infrastructure, I argue that India wrestles against its own colonial history while also employing tenets of colonialism in the eco-colonization of Kashmir, which I pair with international apathy toward Kashmir. By analyzing British blueprints of colonial latrines for South Asia, drafted in 1906, I argue that Munnuconfronts global indifference to the humanitarian crisis and the environmental degradation of Kashmir’s datedconcerns and municipal infrastructure.

ObjectiveWe assessed past-season, pre-season and in-season risk factors to investigate their association with an in-season groin problem in male amateur football players.MethodsPast-season groin-pain information and pre-season short-lever and long-lever adductor squeeze strength were obtained at baseline, together with anthropometrics (weight, lower limb lever length) and player age. In-season hip-related and groin-related sporting function was monitored every 4 weeks using the Sports and Recreation (Sport) subscale from the Hip And Groin Outcome Score questionnaire (HAGOS (Sport)). Groin problems, including time-loss groin injuries and groin pain irrespective of time loss, were collected over a 39-week competitive in-season. We estimated relative risk (RR), and 95% credibility interval (ICr) from logistic regressions fitted in a Bayesian framework.ResultsPlayers (n=245) suffering from groin pain during the past-season had 2.4 times higher risk of experiencing a groin problem in the new season (2.40 RR; 95% ICr 1.5 to 3.7). This risk was reduced by 35% (0.65 RR; 95% ICr 0.42 to 0.99) per unit (N·m/kg) increase in the long-lever adductor squeeze test. Player age, short-lever squeeze test and the HAGOS (Sport) scores were not associated with the risk of a groin problem.ConclusionsPast-season groin pain increased the risk of a groin problem in the new in-season. This risk was reduced by higher pre-season long-lever adductor squeeze strength. Past-season groin-pain information and long-lever adductor squeeze strength can be quickly obtained during pre-season to identify players with an elevated risk of in-season groin problems. This may be key to reduce these problems in the new season.

In this paper we develop a framework for solving inverse deformation problems using the FEniCS Project finite-element software. We validate our approach with experimental imaging data acquired from a soft silicone beam under gravity. In contrast with inverse iterative algorithms that require multiple solutions of a standard elasticity problem, the proposed method can compute the undeformed configuration by solving only one modified elasticity problem. This modified problem has a complexity comparable to the standard one. The framework is implemented within an open-source pipeline enabling the direct and inverse deformation simulation directly from imaging data. We use the high-level unified form language (UFL) of the FEniCS Project to express the finite-element model in variational form and to automatically derive the consistent Jacobian. Consequently, the design of the pipeline is flexible: for example, it allows the modification of the constitutive models by changing a single line of code. We include a complete working example showing the inverse deformation of a beam deformed by gravity as supplementary material.

Bispecific antibodies (BsAbs) can induce long-term responses in patients with refractory and relapsed B-cell lymphoma. Nevertheless, response rates across patients are heterogeneous, and the factors determining quality and duration of responses are poorly understood. To identify key determinants of response to BsAbs, we established a primary, autologous culture model allowing us to mimic treatment with CD3xCD19 and CD3xCD20 BsAbs within the lymph node microenvironment ex vivo. T cell–mediated killing of lymphoma cells and proliferation of T cells varied significantly among patients but highly correlated between BsAbs targeting CD20 or CD19. Ex vivo response to BsAbs was significantly associated with expansion of T cells and secretion of effector molecules (eg, granzyme B, perforin) but not with expression of T-cell exhaustion (eg, PD1, TIM3) or activation markers (eg, CD25, CD69) or formation of intercellular contacts. In addition, we identified a distinct phenotype of regulatory T cells that was linked to ex vivo response independently from T-cell frequency at baseline. High expression levels of Aiolos (IKZF1), ICOS, and CXCR5 were positively associated with ex vivo response, whereas strong expression of Helios (IKZF2) had an unfavorable impact on ex vivo response to BsAbs. We further showed that lenalidomide, nivolumab, and atezolizumab improved ex vivo response to BsAbs by potentiating T-cell effector functions. In summary, our ex vivo study identified a distinct regulatory T-cell phenotype as a potential contributor to treatment failure of BsAbs and suggests drug combinations of high clinical relevance that could improve the efficacy of BsAbs.

Bispecific antibodies (BsAbs) can induce long-term responses in patients with refractory and relapsed B-cell lymphoma. Nevertheless, response rates across patients are heterogeneous, and the factors determining quality and duration of responses are poorly understood. To identify key determinants of response to BsAbs, we established a primary, autologous culture model allowing us to mimic treatment with CD3xCD19 and CD3xCD20 BsAbs within the lymph node microenvironment ex vivo. T cell–mediated killing of lymphoma cells and proliferation of T cells varied significantly among patients but highly correlated between BsAbs targeting CD20 or CD19. Ex vivo response to BsAbs was significantly associated with expansion of T cells and secretion of effector molecules (eg, granzyme B, perforin) but not with expression of T-cell exhaustion (eg, PD1, TIM3) or activation markers (eg, CD25, CD69) or formation of intercellular contacts. In addition, we identified a distinct phenotype of regulatory T cells that was linked to ex vivo response independently from T-cell frequency at baseline. High expression levels of Aiolos (IKZF1), ICOS, and CXCR5 were positively associated with ex vivo response, whereas strong expression of Helios (IKZF2) had an unfavorable impact on ex vivo response to BsAbs. We further showed that lenalidomide, nivolumab, and atezolizumab improved ex vivo response to BsAbs by potentiating T-cell effector functions. In summary, our ex vivo study identified a distinct regulatory T-cell phenotype as a potential contributor to treatment failure of BsAbs and suggests drug combinations of high clinical relevance that could improve the efficacy of BsAbs.

The transcription factor eomesodermin (EOMES) promotes interleukin (IL)-10 expression in CD4+T cells, which has been linked to immunosuppressive and cytotoxic activities. We detected cytotoxic, programmed cell death protein-1 (PD-1) and EOMES co-expressing CD4+T cells in lymph nodes (LNs) of patients with chronic lymphocytic leukemia (CLL) or diffuse large B-cell lymphoma. Transcriptome and flow cytometry analyses revealed that EOMES does not only drive IL-10 expression, but rather controls a unique transcriptional signature in CD4+T cells, that is enriched in genes typical for T regulatory type 1 (TR1) cells. The TR1 cell identity of these CD4+T cells was supported by their expression of interferon gamma and IL-10, as well as inhibitory receptors including PD-1. TR1 cells with cytotoxic capacity accumulate also in Eµ-TCL1 mice that develop CLL-like disease. Whereas wild-type CD4+T cells control TCL1 leukemia development after adoptive transfer in leukopenic Rag2−/−mice, EOMES-deficient CD4+T cells failed to do so. We further show that TR1 cell-mediated control of TCL1 leukemia requires IL-10 receptor (IL-10R) signaling, as Il10rb-deficient CD4+T cells showed impaired antileukemia activity. Altogether, our data demonstrate that EOMES is indispensable for the development of IL-10-expressing, cytotoxic TR1 cells, which accumulate in LNs of CLL patients and control TCL1 leukemia in mice in an IL-10R-dependent manner.

A new series of propionamide derivatives was developed as dual μ-opioid receptor agonists and σ1receptor antagonists. Modification of a high-throughput screening hit originated a series of piperazinylcycloalkylmethyl propionamides, which were explored to overcome the challenge of achieving balanced dual activity and convenient drug-like properties. The lead compound identified, 18g, showed good analgesic effects in several animal models of both acute (paw pressure) and chronic (partial sciatic nerve ligation) pain, with reduced gastrointestinal effects in comparison with oxycodone.

ABSTRACTObjectivesdifferent active and passive post-exercise recovery techniques such as massage, foam rolling, stretching or ice baths among others, are used by elite athletes to promote effective physiological, physical, and mental restoration. However, limited research is available investigating the use of recovery strategies in professional soccer. As such, we aimed to explore and describe the use of strategies by professional teams throughout the season, describing competitive and preparatory phases.Methodsthe present study collected data from all professional Spanish soccer teams who played in ‘LaLiga’ (The Spanish first division), during the season 2018–2019 (n = 20) and the ones promoted for the season 2019–2020 (n = 3). A six-section online survey was responded once.Resultsteams used different recovery protocols and combinations, although natural and physical strategies such as sleep/nap, food/fluid replacement, cold/ice bath/shower/immersion, and massage were always present. However, there is no agreement in the protocols and timings employed. Three physical strategies showed a higher presence in the recovery protocols after competition: cold/ice bath/shower/immersion, massage and foam rolling; always used by seventeen teams (74%), sixteen (70%) and thirteen (57%) respectively. The design and supervision of recovery are multidisciplinary tasks in 87% of the teams. Our findings also demonstrate that although there is a body of scientific evidence on recovery, a gap between theory and practice exists with 13% of the teams acknowledging that insufficient logistics and economic resources limit the use of some strategies, and two teams (9%) not periodizing or individualizing recovery.Conclusionthe investigation provided insight into the current use of recovery strategies by ‘LaLiga’ teams, highlighting that all clubs used them to one extent or another, but also that significant variability responding to individualized perceptions exists. Moreover, this study provides relevant contextual information that may be useful for professional soccer staff concerning the use of recovery strategies.

Genome-wide association studies identified a single-nucleotide polymorphism (SNP) affecting the transcription factor Eomesodermin (EOMES) associated with a significantly increased risk to develop chronic lymphocytic leukemia (CLL). Epigenetic analyses, RNA sequencing, and flow cytometry revealed that EOMES is not expressed in CLL cells, but in CD8+T cells for which EOMES is a known master regulator. We thus hypothesized that the increased CLL risk associated with the EOMESSNP might be explained by its negative impact on CD8+T-cell-mediated immune control of CLL. Flow cytometry analyses revealed a higher EOMES expression in CD8+T cells of CLL patients compared to healthy individuals, and an accumulation of PD-1+EOMES+CD8+T cells in lymph nodes rather than blood or bone marrow in CLL. This was in line with an observed expansion of EOMES+CD8+T cells in the spleen of leukemic Eµ-TCL1 mice. As EOMES expression was highest in CD8+T cells that express inhibitory receptors, an involvement of EOMES in T-cell exhaustion and dysfunction seems likely. Interestingly, Eomes-deficiency in CD8+T cells resulted in their impaired expansion associated with decreased CLL control in mice. Overall, these observations suggest that EOMES is essential for CD8+T-cell expansion and/or maintenance, and therefore involved in adaptive immune control of CLL.

In this study, we use a large-scale parameter analysis and linear regression method to characterize the static stability of Kiewitt-sunflower-type single-layer reticulated spherical shell. Based on more than 15,000 numerical cases of elastic–plastic load–displacement process, and the investigations on the influence of buckling and instability mode, rise-span and ring-numbers ratio, efficiency of the structure, load distribution, support conditions, size of the initial geometric imperfection and distribution patterns are proceeded. We summarize the key effect for stable performance of structure, and develop the formulation to calculate the ultimate capacity of stability. The results show that Kiewitt-sunflower type single-layer reticulated spherical shell is sensitive to defect, and different distribution patterns of geometry defect lead to different structural buckling. The ultimate stability bearing capacity can be improved by increasing the rise-span and ring-numbers ratio. The asymmetrical load distribution has little effect on the stability. The most unfavorable eigenmode is arbitrary, and it is generally not the lowest order. We summarize the key effect for stable performance of structure, and develop the formulation to calculate the ultimate capacity of stability.

The synthesis and pharmacological activity of a new series of 4-alkyl-1-oxa-4,9-diazaspiro[5.5]undecane derivatives as potent dual ligands for the σ1receptor (σ1R) and the μ-opioid receptor (MOR) are reported. A lead optimization program over the initial 4-aryl analogues provided 4-alkyl derivatives with the desired functionality and good selectivity and ADME profiles. Compound 14u(EST73502) showed MOR agonism and σ1R antagonism and a potent analgesic activity, comparable to the MOR agonist oxycodone in animal models of acute and chronic pain after single and repeated administration. Contrary to oxycodone, 14uproduces analgesic activity with reduced opioid-induced relevant adverse events, like intestinal transit inhibition and naloxone-precipitated behavioral signs of opiate withdrawal. These results provide evidence that dual MOR agonism and σ1R antagonism may be a useful strategy for obtaining potent and safer analgesics and were the basis for the selection of 14uas a clinical candidate for the treatment of pain.

Tumour heterogeneity encompasses both the malignant cells and their microenvironment. While heterogeneity between individual patients is known to affect the efficacy of cancer therapy, most personalized treatment approaches do not account for intratumour heterogeneity. We addressed this issue by studying the heterogeneity of nodal B-cell lymphomas by single-cell RNA-sequencing and transcriptome-informed flow cytometry. We identified transcriptionally distinct malignant subpopulations and compared their drug-response and genomic profiles. Malignant subpopulations from the same patient responded strikingly differently to anti-cancer drugs ex vivo, which recapitulated subpopulation-specific drug sensitivity during in vivo treatment. Infiltrating T cells represented the majority of non-malignant cells, whose gene-expression signatures were similar across all donors, whereas the frequencies of T-cell subsets varied significantly between the donors. Our data provide insights into the heterogeneity of nodal B-cell lymphomas and highlight the relevance of intratumour heterogeneity for personalized cancer therapy.

Gamma-ray emitting binaries (GREBs) are complex systems. Its study became in the last years a major endeavour for the high-energy astrophysics community, both from an observational and a theoretical perspective. Whereas the accumulation of observation time for most Galactic gamma-ray sources is typically leading to highly accurate descriptions of their steadyphenomenology, GREBs keep providing “exceptions to the rule” either through long-term monitoring of known systems or in the discovery of new sources of this class. Moreover, many GREBs have been identified as powerful radio, optical and X-ray emitters, and may significantly contribute as well to the Galactic cosmic-ray sea. Their understanding implies, therefore, solving a puzzle in a broad-band and multi-messenger context. In these proceedings we will summarise our current understanding of GREBs, emphasising the most relevant observational results and reviewing a number of controversial properties.

Ulnar artery thrombosis in Guyon’s canal can lead to vascular insufficiency in the fingers. The recommended treatment is resection and reconstruction of the pathological area. A bypass may be necessary, which may be venous or arterial. Arterial bypasses have better long-term patency; however, they are a source of donor-site complications.

The synthesis and pharmacological activity of a new series of thieno[2,3-d]pyrimidin-4(3H)-one derivatives as sigma-1 receptor (σ1R) ligands are reported. A hit from a high-throughput screening program was evolved into a highly potent and selective σ1R agonist (14qR) that contains a free NH group as positive ionizable moiety, not fulfilling the usual pharmacophoric features of the σ1R. The compound shows good physicochemical and ADMET characteristics, displays an agonist profile in the binding immunoglobulin protein/σ1R association assay, induces neuron viability in an in vitro model of β-amyloid peptide intoxication, and presents positive results against recognition memory impairment induced by hippocampal injection of Aβ peptide in rats after oral treatment, altogether making 14qR(WLB-87848) an interesting candidate for neuroprotection.

•Preadult dietary patterns of human individuals from Central Andes have been object of sporadic studies.•The site of Huaca 20 (620–780 CE), a residential sector of Maranga, the main urban center in the lower Rimac Valley of the Peruvian Central Coast, provides an impar opportunity to assess the nuances of fishing-farming preadult diets for this period.•Despite poor-preservation issues, δ13C and δ15N isotopes from dentine segments and quantitative paleodietary reconstruction with Bayesian Mixing Models show that Huaca 20 preadults relied on a mixed diet based on plants, especially maize, complemented with marine protein in proportions that varied with age.•We can observe evidence of specific infant feeding strategies in Huaca 20.

•Elevated levels of the kappa free light chains index (FKLCi) have emerged as a predictor for Therapeutic Failure (TF), defined as the occurrence of a second relapse, two or more T2 lesions, or PIRA.•An FKLCi exceeding 130 was associated with TF in both univariate and multivariate analyses, adjusted for sex, age, presence of acute inflammatory activity, EDSS at the time of sampling, administered line of treatment, and time from CSF analysis to treatment initiation.•Initiating second-line disease-modifying therapies in patients with elevated FKLCi levels would be advisable, as they have shown to be a robust protective factor against TF.•Age emerged as a weak protective factor against TF.•In contrast to findings from other studies, Oligoclonal IgM Bands, Chitinase-3 Like-1, and serum Neurofilament (analyzed as either raw values or age-adjusted Z-scores) were not associated with worse disease outcomes.

Ni-based superalloy 718 fabricated viaarc plasma direct energy deposition (IN718 AP-DED) exhibit a limited response to heat treatment due to its coarse primary microstructure and interdendritic segregation, which may prevent its use in high-integrity applications. Thus, dedicated heat treatments for IN718 AP-DED must possess a homogenization temperature as high as possible to significantly dissolve the eutectics and increase the γ′′-former elements in solid-solution. The present work proposed heat treatments for IN718 AP-DED (homogenization – 1050, 1100, 1142, and 1185 °C / 2h – followed by aging – 718 °C / 8h, cooling at 56 °C / h, and 621 °C / 8h). The as-built IN718 AP-DED showed the typical coarse and oriented (cube texture) microstructure with eutectics (Laves and MC-typical carbides) in the interdendritic region, which were significantly dissolved during the homogenization, promoting a high-volume fraction of hardening phase (γ′′ and γ′) and outstanding quasi-static mechanical properties after the aging step. The present work showed that IN718 AP-DED mechanical properties can be optimized through dedicated heat treatments, meeting the ductility and yield strength requirements (room temperature) of AMS 5662. Furthermore, the heat treatments did not alter the grain morphology and texture aspect, inducing a lower Young’s modulus compared to the non-oriented material.