X-Ray microcalorimeter detectors - Technology developments for high energy astrophysics space missions

Improvements in the design, fabrication, and performance of astronomical detectors has ushered in the so-called era of multi messenger astrophysics, in which several different signals (electromagnetic waves, gravitational waves, neutrinos, cosmic rays) are processed to obtain detailed descriptions of their sources. Soft x-ray instrumentation has been developed in the last decades and used on board numerous space missions. This has allowed a deep understanding of several physical phenomena taking place in astrophysical sources of different scales from normal stars to galaxy clusters and huge black holes. On the other hand, imaging and spectral capabilities in the the hard x-rays are still lagging behind with high potentials of discovery area. Modern cryogenic microcalorimeters have two orders of magnitude or more better energy resolution with respect to CCD detectors at the same energy in the whole X-ray band. This significant improvement will permit important progress in high energy astrophysics thanks to the data that will be provided by future missions adopting this detector technology such as the ESA L2 mission Athena, the JAXA/NASA mission XRISM, both under development, or the NASA LYNX mission presently under investigation. The JAXA/NASA mission Hitomi, launched in 2016 and failed before starting normal operation, has already given a hint of the high potential of such detectors. Due to their very high sensitivity, X-ray cryogenic microcalorimeters need to be shielded from out of band radiation by the use of efficient thin filters. These microcalorimeters work by measuring the temperature increase caused by a photon that hits an X-ray absorber. In neutron transmutation doped germanium (NTD Ge) devices the temperature increase in the absorber is measured by a semiconductor thermometer made of germanium doped by the neutron transmutation doping technique. They are characterized by relatively low specific heat and low sensitivity to external magnetic fields. These characteristics make them promising detectors for hard X-ray detectors for space and laboratory applications. Research groups of the the X-ray Astronomy Calibration and Testing (XACT) Laboratory of the Osservatorio Astronomico di Palermo – Istituto Nazionale di Astrofisica (INAF-OAPA), and of the Dipartimento di Fisica e Chimica “Emilio Segrè” (DiFC) of the Università di Palermo have already developed experience related to the design, fabrication and testing of NTD Ge microcalorimeters. Furthermore, the research group has participated for many years in the design and development of filters for x-ray detectors in different space missions. This thesis concerns the development of materials and technologies for high energy microcalorimeters. In particular its aim is to design and fabricate thick bismuth absorbers for NTD germanium microcalorimeter arrays to extend their detection band toward hard X-ray energies. Filters for shielding microcalorimeters from different background radiation arriving on the detectors were also studied. The design and fabrication of thick bismuth absorbers for hard x-rays detection (20 keV ≤ E ≤ 100 keV) is part of an ongoing effort to develop arrays of NTD Ge microcalorimeters by planar technologies for astrophysical applications. One potential application of such detectors is in the high spectral resolution (∆E ~ 50 eV) investigation of the hard X-ray emission from the solar corona, which is the goal of a stratospheric balloon borne experiment concept named MIcrocalorimeters STratospheric ExpeRiment for solar hard X rays (MISTERX) presently under study at INAF-OAPA. The characterization activity of filters for microcalorimeters in also related to the implementation of the European Space Agency high energy mission named Athena (Advanced Telescopes for High Energy Astrophysics). This thesis describes the design, fabrication, and characterization of the bismuth absorbers, as well as the characterization of filters for Athena. Chapter one summarizes the working principles of NTD Ge microcalorimeters and their applications. Chapter 2 describes the design of the bismuth absorber array on suitable substrates. Chapter 3 focuses on the electroplating process for the bismuth layer deposition, with details about the design and fabrication of the microlithographic mask for the array patterning, and about the development of the microlithographic process for the array fabrication on the chosen substrates. The fabrication of 4 x 4 absorber arrays is also described. Chapter 4 reports on the characterization activity of deposited bismuth layers by different techniques; their morphology was investigated by scanning electron microscopy. The electrochemical impedance spectroscopy technique was used to increase grown layer quality. Fabricated arrays were also characterized. Chapter 5 describes the characterization activity for different filter prototype samples developed for Athena. Mechanical robustness, radio frequency attenuation and radiation damage caused by protons were evaluated. Radiation damage effects at different doses were in particular investigated on silicon nitride filters by scanning electron microscopy (SEM), atomic force microscopy (AFM), UV-Vis-IR spectroscopy and x-ray attenuation measurements. Details on both technical detector requirements and different sensor types are given in the Appendix

Flammability reduction in a pressurised water electrolyser based on a thin polymer electrolyte membrane through a Pt-alloy catalytic approach

Various Pt-based materials (unsupported Pt, PtRu, PtCo) were investigated as catalysts for recombining hydrogen and oxygen back into water. The recombination performance correlated well with the surface Pt metallic state. Alloying cobalt to platinum was observed to produce an electron transfer favouring the occurrence of a large fraction of the Pt metallic state on the catalyst surface. Unsupported PtCo showed both excellent recombination performance and dynamic behaviour. In a packed bed catalytic reactor, when hydrogen was fed at 4% vol. in the oxygen stream (flammability limit), 99.5% of the total H 2 content was immediately converted to water in the presence of PtCo thus avoiding safety issues. The PtCo catalyst was thus integrated in the anode of the membrane-electrode assembly of a polymer electrolyte membrane electrolysis cell. This catalyst showed good capability to reduce the concentration of hydrogen in the oxygen stream under differential pressure operation (1-20 bar), in the presence of a thin (90 µm) Aquivion® membrane. The modified system showed lower hydrogen concentration in the oxygen flow than electrolysis cells based on state-of-the-art thick polymer electrolyte membranes and allowed to expand the minimum current density load down to 0.15 A cm -2 . The electrolysis cell equipped with a dual layer PtCo/IrRuOx oxidation catalyst achieved a high operating current density (3 A cm -2 ) as requested to decrease the system capital costs, under high efficiency conditions (about 77% efficiency at 55°C and 20 bar). Moreover, the electrolysis system showed reduced probability to reach the flammability limit under both high differential pressure (20 bar) and partial load operation (5%), as needed to properly address grid-balancing service

Deformation analysis of ATHENA test filters made of plastic thin films supported by a mesh under differential static pressure

Within ESA Cosmic Vision 2015-2025 Science Program, ATHENA was selected to be a Large-class high energy astrophysics space mission. The observatory will be equipped with two interchangeable focal plane detectors named X-Ray Integral Field Unit (X-IFU) and Wide Field Imager (WFI). In order to optimally exploit the detector sensitivity, X-ray transparent filters are required. Such filters need to be extremely thin to maximize the X-ray transparency, that is, no more than a few tens of nm, still they must be able to sustain the severe stresses experienced during launch. Partially representative test filters were made with a thin polypropylene film, coated with Ti, and supported by a thin highly transparent mesh either in stainless steel or niobium. Differential static pressure experiments were carried out on two filter samples. In addition, the roles of the mesh on the mechanical deformation is studied, adopting a finite element model (FEM). The numerical analysis is compared with experimental results and found in good agreement. The FEM is a promising tool that allows to characterize materials and thicknesses in order to optimize the design

Chemotherapy cardiotoxicity: cardioprotective drugs and early identification of cardiac dysfunction.

Background: Chemotherapy cardiotoxicity is an emerging problem and it is very important to prevent cardiac dysfunction caused by anticancer drugs. The aim of this study was to assess the alterations of the cardiac function induced by chemotherapy in a follow-up of 2 years and to evaluate the cardioprotective role of angiotensin-converting enzyme inhibitors (ACEIs) in the prevention of cardiac dysfunction. Methods: A prospective study was carried out using patients with breast cancer (85 women; median age 57W12years) and other inclusion and exclusion criteria. On the basis of treatment, patients were divided into six groups: fluorouracil-epirubicincyclophosphamide, FEC (group A); FEC and trastuzumab (B); trastuzumab (C); FEC and taxotere (D); FEC, paclitaxel and trastuzumab (E); and chemotherapy and cardioprotective drugs (F). Cardiological evaluation including electrocardiogram and conventional echocardiogram with tissue Doppler imaging (TDI) was carried out at T0 (before starting chemotherapy), T1 (after 6months from the start of chemotherapy) and T2 (2 years after the end of chemotherapy). Results: Significant changes in the TDI parameters of systolic and diastolic function were observed at T1 and T2 in all patients. A significant reduction of left ventricular ejection fraction (LVEF) was observed only at T2. In the patients treated with ACEI (F), these changes were less significant than in other groups and they do not have significant changes in the indices of diastolic function. Conclusion: TDI is more sensitive than conventional echocardiogram in the early diagnosis of cardiac dysfunction and ACEIs seem to have an important role in the prevention of cardiotoxicity

Fluticasone furoate maintains epithelial homeostasis via leptin/leptin receptor pathway in nasal cells

Leptin is involved in the lung epithelial homeostasis. Its role in the nasal tract is largely unknown. Allergic rhinitis (AR) is induced by the allergen exposure leading to consequential structural abnormalities in the nasal epithelium. Topical corticosteroids are recommended as first-line therapy in AR. Parietaria pollen is one of the most important allergenic sources in the southern Europe. In vitro, in human nasal epithelial cell line RPMI 2650, we aimed to determine whether allergen stimulation acts on leptin/leptin receptor pathway and how fluticasone furoate (FF) influences this pathway. The effects of the major allergen recombinant Par j 1 (rPar j 1), of FF, of leptin, and of TGF-b1 on cell proliferation, on leptin/leptin receptor expression and modulation (by clonogenic test, by RT-q- RT-PCR, by immunocytochemistry and by flow-cytometry), and on STAT-3 activation (assessing nuclear translocation by western blot analysis) were assessed. We found that rPar j 1 and TGF-b1 significantly decreased cell proliferation and down-regulated the leptin/leptin receptor pathway, whereas FF and leptin reverted them, both alone and in combination. Furthermore, rPar j 1 reduced, while leptin and FF increased STAT-3 activation. In conclusion, FF and leptin itself are able to preserve nasal epithelial homeostasis restoring the leptin/leptin receptor pathway altered by rPar j 1 exposure

Partially Purified Extracts of Sea Anemone Anemonia viridis Affect the Growth and Viability of Selected Tumour Cell Lines

In the last few years, marine species have been investigated for the presence of natural products with anticancer activity. Using reversed phase chromatography, low molecular weight proteins were fractionated from the sea anemone Anemonia viridis. Four different fractions were evaluated for their cytotoxic activity by means of erythrocyte haemolysis test, MTS, and LDH assays. Finally, the antiproliferative activities of three of these fractions were studied on PC3, PLC/PRF/5, and A375 human cancer cell lines. Our analysis revealed that the four fractions showed different protein contents and diverse patterns of activity towards human PBMC and cancer cell lines. Interestingly, fractions III and IV exerted cytotoxic effects on human cells. Conversely, fractions I and II displayed very low toxic effects associated with antiproliferative activities on cancer cell lines

A New Genetic Risk Score to Predict the Outcome of Locally Advanced or Metastatic Breast Cancer Patients Treated With First-Line Exemestane: Results From a Prospective Study

Currently there are no reliable biomarkers to predict outcome of exemestane treatment. We designed a prospective study to investigate whether constitutive genetic background might affect response to therapy. In a population of 302 advanced breast cancer patients treated with exemestane we showed that a 5-polymorphism-based genetic score could be used to identify patients with different risks of progression and death.Introduction: Approximately 50% of locally advanced or metastatic breast cancer (MBC) patients treated with first-line exemestane do not show objective response and currently there are no reliable biomarkers to predict the outcome of patients using this therapy. The constitutive genetic background might be responsible for differences in the outcome of exemestane-treated patients. We designed a prospective study to investigate the role of germ line polymorphisms as biomarkers of survival. Patients and Methods: Three hundred two locally advanced or MBC patients treated with first-line exemestane were genotyped for 74 germ line polymorphisms in 39 candidate genes involved in drug activity, hormone balance, DNA replication and repair, and cell signaling pathways. Associations with progression-free survival (PFS) and overall survival (OS) were tested with multivariate Cox regression. Bootstrap resampling was used as an internal assessment of results reproducibility. Results: Cytochrome P450 19A1-rs10046TC/CC, solute carrier organic anion transporter 1B1-rs4149056TT, adenosine triphosphate binding cassette subfamily G member 2-rs2046134GG, fibroblast growth factor receptor-4-rs351855TT, and X-ray repair cross complementing 3-rs861539TT were significantly associated with PFS and then combined into a risk score (0-1, 2, 3, or 4-6 risk points). Patients with the highest risk score (4-6 risk points) compared with ones with the lowest score (0-1 risk points) had a median PFS of 10 months versus 26.3 months (adjusted hazard ratio [AdjHR], 3.12 [95% confidence interval (CI), 2.18-4.48]; P < .001) and a median OS of 38.9 months versus 63.0 months (AdjHR, 2.41 [95% CI, 1.22-4.79], P = .012), respectively. Conclusion: In this study we defined a score including 5 polymorphisms to stratify patients for PFS and OS. This score, if validated, might be translated to personalize locally advanced or MBC patient treatment and management

Surgical revision strategies in the event of biomechanical failure associated with tibial tuberosity advancement (TTA)

Il legamento crociato craniale (LCCr) rappresenta la principale struttura anatomica di stabilizzazione dell'articolazione del ginocchio. La rottura del legamento crociato craniale è una delle patologie ortopediche di maggior riscontro clinico. La sua rottura, parziale o completa, determina instabilità articolare, con progressivo sviluppo di osteoartrosi e possibili lesioni meniscali. La manifestazione clinica principale è rappresentata da zoppia, più o meno evidente, dell'arto pelvico. Nonostante sia una patologia studiata da molti anni, non è stato ancora definito un percorso patogenetico univoco ed universalmente accettato. Nella maggior parte dei casi si tratta di un processo degenerativo-progressivo caratterizzato da una cascata di eventi, quali indebolimento, degenerazione e rottura parziale, che esitano nella rottura totale del legamento. Molte tecniche chirurgiche sono state proposte per il trattamento della rottura del LCCr. In particolare, l'avanzamento della tuberosità tibiale (Tibial Tuberosity Advancement, TTA) e l'osteotomia livellante del piatto tibiale (Tibial Plateau Levelling Osteotomy, TPLO) risultano essere le più studiate ed utilizzate. Nonostante siano delle tecniche ad alta percentuale di successo (superiore al 90-95%), non è possibile escludere l'eventualità di fallimenti o insuccessi biomeccanici. L'insuccesso biomeccanico di avanzamento della tuberosità tibiale (TTA) si verifica in seguito a complicazioni tipiche quali collasso del cage, cedimento dell'impianto, frattura della tibia o della tuberosità tibiale, esecuzione della linea di osteotomia in posizione eccessivamente craniale, applicazione della TTA in animali sovrappeso o con angolo del piatto tibiale (TPA) molto elevato. In questi casi è possibile mettere a punto delle strategie di revisione chirurgica con l'obiettivo di risolvere, in maniera definitiva, la patologia.The cranial cruciate ligament (CrCL) represents the main anatomic structure for the knee joint stabilization. The rupture of the cranial cruciate ligament is the most clinically relevant among orthopedic pathologies. The partial or complete rupture, which determines joint instability, may lead to osteoarthritis and possible meniscal injuries. The main clinical manifestation is represented by lameness, more or less evident, of the pelvic limb. Although this pathology has been studied for many years, a unique and universally accepted pathogenetic path has not been defined yet. In most cases it is a degenerative-progressive process characterized by a cascade of events such as weakness, degeneration and partial rupture, which lead to complete rupture of the ligament. Many surgical techniques have been proposed for the treatment of the CrCL rupture. Particularly the Tibial Tuberosity Advancement (TTA) and the Tibial Plateau Levelling Osteotomy (TPLO) are the most studied and used. Even if these techniques have a very high success rate (more than 90-95%), it is not possible to exclude the possibility of biomechanical failure. Biomechanical failure of Tibial Tuberosity Advancement occurs as a result of complications like cage collapse, implant failure, tibia or tibial tuberosity fracture, execution of the osteotomy line in an excessive cranial position, application of TTA in overweight animals or in animals with very high tibial plateau angle (TPA). In these cases, it's possible to develop surgical revision strategies in order to solve the pathology definitively