Structure and properties of crystalline inclusions trapped in minerals

This thesis deals with the characterization of mineral inclusions by means of various non-destructive techniques. Two type of inclusions are analyzed: inclusions in diamonds and inclusions in metamorphic rocks, in particular the host-inclusion pair quartz in garnet. The work on inclusion in diamonds focuses on rare inclusions of magnetic minerals, such as iron oxides, and employs a multi-analytical approach: X-ray diffraction, Raman spectroscopy, magnetometry, and X-ray tomography. Magnetic properties can help in the identification of the composition of the inclusions and thus of the environment in which the host-inclusion system grew. X-ray tomography was employed to locate the inclusions in the samples, asses the presence of fractures, and support the identification of the phases. The characterization of the quartz-in-garnet pair is focused on the determination of the stress state of the inclusions and the influence of such stress on the structure and properties of the system. It is shown how to characterize the crystal structure of inclusions in-situ by means of X-ray diffraction. A thorough characterization of the polarized Raman scattering of quartz as a function of pressure and temperature was performed to guide the interpretation of the results from inclusions. The high-pressure Raman experiment verifies the validity of the approach based on the phonon-mode Grüneisen tensor to calculate the pressure in the inclusions, also for the E modes. Furthermore, it points out that strong multiphonon interactions can contribute to the stability of alpha-quartz at ambient conditions and provides new pressure calibrations. The heating experiment performed in situ by Raman spectroscopy shows that the quartz inclusion in garnet does not undergo the alpha-beta phase transition. The comparison of the free and trapped crystal data clearly shows a different response to heating and the applied models cannot reproduce the experimental data. It can be shown that the disagreement between the data and the prediction is due to the elastic anisotropy of quartz, suggesting that at a new model taking into account elastic anisotropy is needed

Cubic or Not Cubic? Combined Experimental and Computational Investigation of the Short-Range Order of Tin Halide Perovskites

Tin-based metal halide perovskites with a composition of ASnX3 (where A= MA or FA and X = I or Br) have been investigated by means of X-ray total scattering techniques coupled to pair distribution function (PDF) analysis. These studies revealed that that none of the four perovskites has a cubic symmetry at the local scale and that a degree of increasing distortion is always present, in particular when the cation size is increased, i.e., from MA to FA, and the hardness of the anion is increased, i.e., from Br- to I-. Electronic structure calculations provided good agreement with experimental band gaps for the four perovskites when local dynamical distortions were included in the calculations. The averaged structure obtained from molecular dynamics simulations was consistent with experimental local structures determined via X-ray PDF, thus highlighting the robustness of computational modeling and strengthening the correlation between experimental and computational results

Fossil subduction recorded by quartz from the coesite stability field

Metamorphic rocks are the records of plate tectonic processes whose reconstruction relies on correct estimates of the pressures and temperatures (P-T) experienced by these rocks through time. Unlike chemical geothermobarometry, elastic geobarometry does not rely on chemical equilibrium between minerals, so it has the potential to provide information on overstepping of reaction boundaries and to identify other examples of non-equilibrium behavior in rocks. Here we introduce a method that exploits the anisotropy in elastic properties of minerals to determine the unique P and T of entrapment from a single inclusion in a mineral host. We apply it to preserved quartz inclusions in garnet from eclogite xenoliths hosted in Yakutian kimberlites (Russia). Our results demonstrate that quartz trapped in garnet can be preserved when the rock reaches the stability field of coesite (the high-pressure and hightemperature polymorph of quartz) at 3 GPa and 850 \ub0C. This supports a metamorphic origin for these xenoliths and sheds light on the mechanisms of craton accretion from a subducted crustal protolith. Furthermore, we show that interpreting P and T conditions reached by a rock from the simple phase identification of key inclusion minerals can be misleading

Deep learning-based algorithm for postoperative glioblastoma MRI segmentation: a promising new tool for tumor burden assessment

Objective: Clinical and surgical decisions for glioblastoma patients depend on a tumor imaging-based evaluation. Artificial Intelligence (AI) can be applied to magnetic resonance imaging (MRI) assessment to support clinical practice, surgery planning and prognostic predictions. In a real-world context, the current obstacles for AI are low-quality imaging and postoperative reliability. The aim of this study is to train an automatic algorithm for glioblastoma segmentation on a clinical MRI dataset and to obtain reliable results both pre- and post-operatively. Methods: The dataset used for this study comprises 237 (71 preoperative and 166 postoperative) MRIs from 71 patients affected by a histologically confirmed Grade IV Glioma. The implemented U-Net architecture was trained by transfer learning to perform the segmentation task on postoperative MRIs. The training was carried out first on BraTS2021 dataset for preoperative segmentation. Performance is evaluated using DICE score (DS) and Hausdorff 95% (H95). Results: In preoperative scenario, overall DS is 91.09 (± 0.60) and H95 is 8.35 (± 1.12), considering tumor core, enhancing tumor and whole tumor (ET and edema). In postoperative context, overall DS is 72.31 (± 2.88) and H95 is 23.43 (± 7.24), considering resection cavity (RC), gross tumor volume (GTV) and whole tumor (WT). Remarkably, the RC segmentation obtained a mean DS of 63.52 (± 8.90) in postoperative MRIs. Conclusions: The performances achieved by the algorithm are consistent with previous literature for both pre-operative and post-operative glioblastoma's MRI evaluation. Through the proposed algorithm, it is possible to reduce the impact of low-quality images and missing sequences

The Evolving Scenario in the Assessment of Radiological Response for Hepatocellular Carcinoma in the Era of Immunotherapy: Strengths and Weaknesses of Surrogate Endpoints

Hepatocellular carcinoma (HCC) is a challenging malignancy characterised by clinical and biological heterogeneity, independent of the stage. Despite the application of surveillance programs, a substantial proportion of patients are diagnosed at advanced stages when curative treatments are no longer available. The landscape of systemic therapies has been rapidly growing over the last decade, and the advent of immune-checkpoint inhibitors (ICIs) has changed the paradigm of systemic treatments. The coexistence of the tumour with underlying cirrhosis exposes patients with HCC to competing events related to tumour progression and/or hepatic decompensation. Therefore, it is relevant to adopt proper clinical endpoints to assess the extent of treatment benefit. While overall survival (OS) is the most accepted endpoint for phase III randomised controlled trials (RCTs) and drug approval, it is affected by many limitations. To overcome these limits, several clinical and radiological outcomes have been used. For instance, progression-free survival (PFS) is a useful endpoint to evaluate the benefit of sequential treatments, since it is not influenced by post-progression treatments, unlike OS. Moreover, radiological endpoints such as time to progression (TTP) and objective response rate (ORR) are frequently adopted. Nevertheless, the surrogacy between these endpoints and OS in the setting of unresectable HCC (uHCC) remains uncertain. Since most of the surrogate endpoints are radiology-based (e.g., PFS, TTP, ORR), the use of standardised tools is crucial for the evaluation of radiological response. The optimal way to assess the radiological response has been widely debated, and many criteria have been proposed over the years. Furthermore, none of the criteria have been validated for immunotherapy in advanced HCC. The coexistence of the underlying chronic liver disease and the access to several lines of treatments highlight the urgent need to capture early clinical benefit and the need for standardised radiological criteria to assess cancer response when using ICIs in mono- or combination therapies. Here, we review the most commonly used clinical and radiological endpoints for trial design, as well as their surrogacy with OS. We also review the criteria for radiological response to treatments for HCC, analysing the major issues and the potential future perspectives

Super-Resolution Microscopy Using a Bioorthogonal-Based Cholesterol Probe Provides Unprecedented Capabilities for Imaging Nanoscale Lipid Heterogeneity in Living Cells

Despite more than 20 years of work since the lipid raft concept was proposed, the existence of these nanostructures remains highly controversial due to the lack of noninvasive methods to investigate their native nanorganization in living unperturbed cells. There is an unmet need for probes for direct imaging of nanoscale membrane dynamics with high spatial and temporal resolution in living cells. In this paper, a bioorthogonal-based cholesterol probe (chol-N-3) is developed that, combined with nanoscopy, becomes a new powerful method for direct visualization and characterization of lipid raft at unprecedented resolution in living cells. The chol-N-3 probe mimics cholesterol in synthetic and cellular membranes without perturbation. When combined with live-cell super-resolution microscopy, chol-N-3 demonstrates the existence of cholesterol-rich nanodomains of <50 nm at the plasma membrane of resting living cells. Using this tool, the lipid membrane structure of such subdiffraction limit domains is identified, and the nanoscale spatiotemporal organization of cholesterol in the plasma membrane of living cells reveals multiple cholesterol diffusion modes at different spatial localizations. Finally, imaging across thick organ samples outlines the potential of this new method to address essential biological questions that were previously beyond reach.M.L., O.T., and J.A.N.-G. contributed equally to this work. This work was supported by grants from the Spanish Ministry of Science Innovation and Universities, (Grant No. BFU-2015-68981-P) and the Basque Government (Grant No. IT1264-19) to F.-X.C. and M.L.. The authors thank J. M. Gonzalez Manas and Sergio Perez Acebron for helful comments on the manuscript. The authors thank the technical and human support provided by the analytical and high-resolution microscopy facility (SGIker) of UPV/EHU and European funding (ERDF and ESF). J.B.d.l.S. acknowledges funding from the Bill and Melinda Gates Foundation and the BBSRC (Grant Nos. INV-016631 and BB/V019791/1, respectively). This work was supported in part by the Fundacion Biofisica Bizkaia (FBB) and the Basque Excellence Research Centre (BERC) program of the Basque Government. J.A.N.-G. was supported by a FI predoctoral fellowship from the Basque Government and currently by FBB. Documen

Zbornik I. skupa hrvatske ranokršćanske arheologije (HRRANA)

Episkopalno središte, tri slavne nekropole Salone i Eufrazijeva bazilika u Poreču su najpoznatiji ranokršćanski lokaliteti u Hrvatskoj. Oni, međutim, nisu i jedini – uz njih su pronađeni brojni drugi, ne manje važni, ranokršćanski objekti, crkve, nekropole i pokretni nalazi. O njihovom značaju govori i činjenica da je više njih relevantno i u međunarodnom istraživanju određenih arheoloških tema. K tomu, nakon gotovo stoljeća i pol arheoloških iskopavanja, znanost uvijek iznova dolazi do novih otkrića. Takva poticajna situacija potaknula je znanstvenike sa Katedre za antičku provincijalnu i ranokršćansku arheologiju Odsjeka za arheologiju Filozofskog fakulteta u Zagrebu na organizaciju prvog nacionalnog ranokršćanskog arheološkog skupa. Slijedom toga je u Zagrebu od 15. do 17. ožujka 2018. održan prvi hrvatski skup ranokršćanske arheologije. Prvi cilj skupa, čiji akronim po početnim slovima naslova glasi HRRANA, je bio prezentiranje aktualnog stanja, i možebitno unaprjeđivanje, te važne znanstvene discipline. Objavom ovog zbornika radova nastoji se promovirati ne samo hrvatske ranokršćanske lokalitete, spomenike, arhitekturu, krajobraze, ikonografiju, epigrafiju i recentna arheološka istraživanja, nego i uputiti na različite istraživačke i metodološke probleme u istraživanju ranokršćanske arheologije u Hrvatskoj kroz rasprave, ispitivanja, znanstvena i praktična pitanja.Episkopalno središte, tri slavne nekropole Salone i Eufrazijeva bazilika u Poreču su najpoznatiji ranokršćanski lokaliteti u Hrvatskoj. Oni, međutim, nisu i jedini – uz njih su pronađeni brojni drugi, ne manje važni, ranokršćanski objekti, crkve, nekropole i pokretni nalazi. O njihovom značaju govori i činjenica da je više njih relevantno i u međunarodnom istraživanju određenih arheoloških tema. K tomu, nakon gotovo stoljeća i pol arheoloških iskopavanja, znanost uvijek iznova dolazi do novih otkrića. Takva poticajna situacija potaknula je znanstvenike sa Katedre za antičku provincijalnu i ranokršćansku arheologiju Odsjeka za arheologiju Filozofskog fakulteta u Zagrebu na organizaciju prvog nacionalnog ranokršćanskog arheološkog skupa. Slijedom toga je u Zagrebu od 15. do 17. ožujka 2018. održan prvi hrvatski skup ranokršćanske arheologije. Prvi cilj skupa, čiji akronim po početnim slovima naslova glasi HRRANA, je bio prezentiranje aktualnog stanja, i možebitno unaprjeđivanje, te važne znanstvene discipline. Objavom ovog zbornika radova nastoji se promovirati ne samo hrvatske ranokršćanske lokalitete, spomenike, arhitekturu, krajobraze, ikonografiju, epigrafiju i recentna arheološka istraživanja, nego i uputiti na različite istraživačke i metodološke probleme u istraživanju ranokršćanske arheologije u Hrvatskoj kroz rasprave, ispitivanja, znanstvena i praktična pitanja

Zbornik I. skupa hrvatske ranokršćanske arheologije (HRRANA)

Episkopalno središte, tri slavne nekropole Salone i Eufrazijeva bazilika u Poreču su najpoznatiji ranokršćanski lokaliteti u Hrvatskoj. Oni, međutim, nisu i jedini – uz njih su pronađeni brojni drugi, ne manje važni, ranokršćanski objekti, crkve, nekropole i pokretni nalazi. O njihovom značaju govori i činjenica da je više njih relevantno i u međunarodnom istraživanju određenih arheoloških tema. K tomu, nakon gotovo stoljeća i pol arheoloških iskopavanja, znanost uvijek iznova dolazi do novih otkrića. Takva poticajna situacija potaknula je znanstvenike sa Katedre za antičku provincijalnu i ranokršćansku arheologiju Odsjeka za arheologiju Filozofskog fakulteta u Zagrebu na organizaciju prvog nacionalnog ranokršćanskog arheološkog skupa. Slijedom toga je u Zagrebu od 15. do 17. ožujka 2018. održan prvi hrvatski skup ranokršćanske arheologije. Prvi cilj skupa, čiji akronim po početnim slovima naslova glasi HRRANA, je bio prezentiranje aktualnog stanja, i možebitno unaprjeđivanje, te važne znanstvene discipline. Objavom ovog zbornika radova nastoji se promovirati ne samo hrvatske ranokršćanske lokalitete, spomenike, arhitekturu, krajobraze, ikonografiju, epigrafiju i recentna arheološka istraživanja, nego i uputiti na različite istraživačke i metodološke probleme u istraživanju ranokršćanske arheologije u Hrvatskoj kroz rasprave, ispitivanja, znanstvena i praktična pitanja.Episkopalno središte, tri slavne nekropole Salone i Eufrazijeva bazilika u Poreču su najpoznatiji ranokršćanski lokaliteti u Hrvatskoj. Oni, međutim, nisu i jedini – uz njih su pronađeni brojni drugi, ne manje važni, ranokršćanski objekti, crkve, nekropole i pokretni nalazi. O njihovom značaju govori i činjenica da je više njih relevantno i u međunarodnom istraživanju određenih arheoloških tema. K tomu, nakon gotovo stoljeća i pol arheoloških iskopavanja, znanost uvijek iznova dolazi do novih otkrića. Takva poticajna situacija potaknula je znanstvenike sa Katedre za antičku provincijalnu i ranokršćansku arheologiju Odsjeka za arheologiju Filozofskog fakulteta u Zagrebu na organizaciju prvog nacionalnog ranokršćanskog arheološkog skupa. Slijedom toga je u Zagrebu od 15. do 17. ožujka 2018. održan prvi hrvatski skup ranokršćanske arheologije. Prvi cilj skupa, čiji akronim po početnim slovima naslova glasi HRRANA, je bio prezentiranje aktualnog stanja, i možebitno unaprjeđivanje, te važne znanstvene discipline. Objavom ovog zbornika radova nastoji se promovirati ne samo hrvatske ranokršćanske lokalitete, spomenike, arhitekturu, krajobraze, ikonografiju, epigrafiju i recentna arheološka istraživanja, nego i uputiti na različite istraživačke i metodološke probleme u istraživanju ranokršćanske arheologije u Hrvatskoj kroz rasprave, ispitivanja, znanstvena i praktična pitanja