Estimate of the impact of background particles on the X-Ray Microcalorimeter Spectrometer on IXO

We present the results of a study on the impact of particles of galactic (GCR) and solar origin for the X-ray Microcalorimeter Spectrometer (XMS) aboard an astronomical satellite flying in an orbit at the second Lagrangian point (L2). The detailed configuration presented in this paper is the one adopted for the International X-Ray Observatory (IXO) study, however the derived estimates can be considered a conservative limit for ATHENA, that is the IXO redefined mission proposed to ESA. This work is aimed at the estimate of the residual background level expected on the focal plane detector during the mission lifetime, a crucial information in the development of any instrumental configuration that optimizes the XMS scientific performances. We used the Geant4 toolkit, a Monte Carlo based simulator, to investigate the rejection efficiency of the anticoincidence system and assess the residual background on the detector.Comment: 18 pages, 9 figure

Carbon nanotube four-terminal devices for pressure sensing applications

Carbon nanotubes (CNTs) are of high interest for sensing applications,owing to their superior mechanical strength, high Young’s modulus and low density. In this work, we report on a facile approach for the fabrication of carbon nanotube devices using a four terminal configuration. Oriented carbon nanotube films were pulled out from a CNT forest wafer and then twisted into a yarn. Both the CNT film and yarn were arranged on elastomer membranes/diaphragms which were arranged on a laser cut acrylic frame to form pressure sensors. The sensors were calibrated using a precisely controlled pressure system, showing a large change of the output voltage of approximately 50 mV at a constant supply current of 100 μA and under a low applied pressure of 15 mbar. The results indicate the high potential of using CNT films and yarns for pressure sensing applications

Natural based products for cleaning copper and copper alloys artefacts

Copper alloys objects can deteriorate their conservation state through irreversible corrosion. Since in the cultural heritage field every artefact is unique and any loss irreplaceable, solutions for conservation are needed. Hence, there is the necessity to stop the corrosion process with a suitable cleaning and conservation process to avoid further degradation processes without changing its morphological aspect. Chelating solutions are commonly used in chemical cleaning, mainly sodium salts of ethylenediaminetetraacetic acid (EDTA). However, it is resistant to water purification procedures and is not biodegradable. The goal of this study was to see if applying an ecologically friendly chelating agent as an alternative to EDTA cleaning procedures for cultural heritage was suitable. In this study were chosen six natural-based chelators that could be a new green non-toxic alternative to EDTA in corrosion-inhibiting properties. They were tested for cleaning copper artefacts exposed to atmospheric environment in polluted areas. The study considered four amino acids, a glucoheptonate (CSA) and an industrial green chelator (GLDA). The effectiveness was tested on corrosion copper compounds and on laboratory corroded copper sheets. Finally, the cleaning efficacy was tested on four Roman coins and a modern copper painting. To define the cleaning efficacy, surface analytical investigations have been carried out by means ICP-OES, UV-VIS, µ-Raman, spectro-colorimetry, XRD and FTIR. Among the amino acids, alanine was the most effective, showing an unaltered noble patina and a good effective copper recovery from corrosion patinas

Autophagy modulation in lymphocytes from COVID-19 patients. new therapeutic target in SARS-COV-2 infection

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the novel coronavirus, causing coronavirus disease 2019 (COVID-19). During virus infection, several pro-inflammatory cytokines are produced, leading to the “cytokine storm.” Among these, interleukin (IL)-6, tumor necrosis factor‐α (TNF‐α), and IL-1β seem to have a central role in the progression and exacerbation of the disease, leading to the recruitment of immune cells to infection sites. Autophagy is an evolutionarily conserved lysosomal degradation pathway involved in different aspects of lymphocytes functionality. The involvement of IL-6, TNF‐α, and IL-1β in autophagy modulation has recently been demonstrated. Moreover, preliminary studies showed that SARS-CoV-2 could infect lymphocytes, playing a role in the modulation of autophagy. Several anti-rheumatic drugs, now proposed for the treatment of COVID-19, could modulate autophagy in lymphocytes, highlighting the therapeutic potential of targeting autophagy in SARS-CoV-2 infection

FRI0376 EFFECT OF CARBAMYLATED LOW-DENSITY LIPOPROTEINS ON BONE CELLS HOMEOSTASIS

Background:Carbamylation is a post-translational modification occurring under several conditions such as uremia, smoking and chronic inflammation as in rheumatoid arthritis (RA). Low-density lipoproteins (LDL) represent a target of carbamylation. Carbamylated-LDL (cLDL) have an increased inflammatory and atherogenic potential. Growing evidence supports an influence of modified lipids on bone cells homeostasis. However, the role of cLDL on bone cells physiology is still unknown.Objectives:Considering the rate of carbamylation and the role of anti-carbamylated proteins antibodies as markers of erosive disease in RA, the purpose of this study is to investigate the effect of cLDL on bone homeostasis.Methods:In-vitrocarbamylation of LDL was performed as previously described by Ok et al. (Kidney Int. 2005). Briefly, native LDL (nLDL) were treated with potassium cyanate (KOCN) for 4 hours, followed by excessive dialysis for 36 hours to remove KOCN. Both osteoclasts (OCs) and osteoblasts (OBLs) were treated at baseline with 20 μg/ml, 100 μg/ml and 200 μg/ml of cLDL or nLDL. To induce osteoclast differentiation, CD14+ monocytes were isolated from peripheral blood of healthy donors by magnetic microbeads separation and then cultured on a 96-wells plate in DMEM media supplemented with RANKL and M-CSF. After 10 days cells were fixed, stained for tartrate-resistant acid phosphatase (TRAP), a marker of OC differentiation, and counted. OBLs were isolated from bone specimens of 3 patients who had undergone to knee or hip arthroplasty for osteoarthritis and treated for 5 days with different concentrations of cLDL and nLDL. OBLs were fixed and stained for alkaline phosphatase positive activity (ALP), a marker of osteogenic differentiation. Total RNA was extracted from cell lysates. Copies of single-stranded complementary DNA (cDNA) were synthesized and analyzed by real-time PCR to evaluate RANKL and Osteoprotegerin (OPG) mRNA expression levels.Results:In OCLs culture, cLDL significantly decreased the number of OC compared to untreated cells (200 μg/ml p=0,0015) and nLDL treated cells (200 μg/ml p= 0,011; 20 μg/ml p= 0,0014) (Fig 1). Moreover, treatment with cLDL induced an increase of not terminally differentiated OCs, reduced dimensions of OCs, less intense TRAP staining and vacuolization (Fig 2). In OBLs culture, cLDL (20, 100 μg/ml) significantly reduced the ALP activity of OBLs compared with untreated cells (p<0.05) (Fig 3). nLDL did not affect the ALP expression. Treatment with cLDL stimulated RANKL mRNA expression in osteoblasts increasing the RANKL/OPG ratio (Fig 4).Fig 1.Fig 2.Fig 3.Fig 4.Conclusion:cLDL induce a significant depression of OC and OBL differentiation. Moreover, cLDL increase RANKL expression in OBL, unbalancing bone tissue turnover towards bone resorption. Accordingly, cLDL could be implicated in the bone loss characterizing several conditions associated to an increased carbamylation, such as RADisclosure of Interests:Bruno Lucchino: None declared, Martina Leopizzi: None declared, Tania Colasanti: None declared, Valeria Di Maio: None declared, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi, Manuela Di Franco: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lill

L-DOPA preloading increases the uptake of borophenylalanine in C6 glioma rat model: a new strategy to improve BNCT efficacy.

Purpose: Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on 10B(n,a)7Li reaction, for the treatment of malignant gliomas. One of the main limitations for BNCT effectiveness is the insufficient intake of 10B nuclei in the tumor cells. This work was aimed at investigating the use of L-DOPA as a putative enhancer for 10B-drug 4-dihydroxy-borylphenylalanine (BPA) uptake in the C6-glioma model. The investigation was first per- formed in vitro and then extended to the animal model. Methods and Materials: BPA accumulation in C6-glioma cells was assessed using radiowave dielectric spectros- copy, with and without L-DOPA preloading. Two L-DOPA incubation times (2 and 4 hours) were investigated, and the corresponding effects on BPA accumulation were quantified. C6-glioma cells were also implanted in the brain of 32 rats, and tumor growth was monitored by magnetic resonance imaging. Rats were assigned to two experimental branches: (1) BPA administration; (2) BPA administration after pretreatment with L-DOPA. All an- imals were sacrificed, and assessments of BPA concentrations in tumor tissue, normal brain, and blood samples were performed using high-performance liquid chromatography. Results: L-DOPA preloading induced a massive increase of BPA concentration in C6-glioma cells only after a 4-hour incubation. In the animal model, L-DOPA pretreatment produced a significantly higher accumulation of BPA in tumor tissue but not in normal brain and blood samples. Conclusions: This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malig- nant gliomas eligible for BNCT. L-DOPA preloading effect is discussed in terms of membrane transport mechanisms

Monte-Carlo Simulations of the Suzaku-XRS Residual Background Spectrum

Cryogenic micro-calorimeters are suitable to detect small amounts of energy deposited by electromagnetic and nuclear interactions, which makes them attractive in a variety of applications on ground and in space. The only X-ray microcalorimeter that operated in orbit to date is the X-Ray Spectrometer on-board of the Japanese Suzaku satellite. We discuss the analysis of the components of its residual background spectrum with the support of Monte-Carlo simulations

Anti-D4GDI antibodies activate platelets in vitro. a possible link with thrombocytopenia in primary antiphospholipid syndrome

Background: Thrombocytopenia is a manifestation associated with primary antiphospholipid syndrome (PAPS), and many studies have stressed the leading role played by platelets in the pathogenesis of antiphospholipid syndrome (APS). Platelets are highly specialized cells, and their activation involves a series of rapid rearrangements of the actin cytoskeleton. Recently, we described the presence of autoantibodies against D4GDI (Rho GDP dissociation inhibitor beta, ARHGDIB) in the serum of a large subset of SLE patients, and we observed that anti-D4GDI antibodies activated the cytoskeleton remodeling of lymphocytes by inhibiting D4GDI and allowing the upregulation of Rho GTPases, such as Rac1. Proteomic and transcriptomic studies indicate that D4GDI is very abundant in platelets, and small GTPases of the RHO family are critical regulators of actin dynamics in platelets. Methods: We enrolled 38 PAPS patients, 15 patients carrying only antiphospholipid antibodies without clinical criteria of APS (aPL carriers) and 20 normal healthy subjects. Sera were stored at - 20 °C to perform an ELISA test to evaluate the presence of anti-D4GDI antibodies. Then, we purified autoantibodies anti-D4GDI from patient sera. These antibodies were used to conduct in vitro studies on platelet activation. Results: We identified anti-D4GDI antibodies in sera from 18/38 (47%) patients with PAPS, in sera from 2/15(13%) aPL carriers, but in no sera from normal healthy subjects. Our in vitro results showed a significant 30% increase in the activation of integrin αIIbβ3 upon stimulation of platelets from healthy donors preincubated with the antibody anti-D4GDI purified from the serum of APS patients. Conclusions: In conclusion, we show here that antibodies anti-D4GDI are present in the sera of PAPS patients and can prime platelet activation, explaining, at least in part, the pro-thrombotic state and the thrombocytopenia of PAPS patients. These findings may lead to improved diagnosis and treatment of APS

Management of infants with brief resolved unexplained events (Brue) and apparent life-threatening events (alte): A rand/ucla appropriateness approach

Unexpected events of breath, tone, and skin color change in infants are a cause of consider-able distress to the caregiver and there is still debate on their appropriate management. The aim of this study is to survey the trend in prevention, decision-making, and management of brief resolved unexplained events (BRUE)/apparent life-threatening events (ALTE) and to develop a shared proto-col among hospitals and primary care pediatricians regarding hospital admission criteria, work-up and post-discharge monitoring of patients with BRUE/ALTE. For the study purpose, a panel of 54 experts was selected to achieve consensus using the RAND/UCLA appropriateness method. Twelve scenarios were developed: one addressed to primary prevention of ALTE and BRUE, and 11 focused on hospital management of BRUE and ALTE. For each scenario, participants were asked to rank each option from ‘1’ (extremely inappropriate) to ‘9’ (extremely appropriate). Results derived from panel meeting and discussion showed several points of agreement but also disagreement with different opinion emerged and the need of focused education on some areas. However, by combining previous recommendations with expert opinion, the application of the RAND/UCLA appropriateness permit-ted us to drive pediatricians to reasoned and informed decisions in term of evaluation, treatment and follow-up of infants with BRUE/ALTE, reducing inappropriate exams and hospitalisation and highlighting priorities for educational interventions

ORIGIN: Metal Creation and Evolution from the Cosmic Dawn

ORIGIN is a proposal for the M3 mission call of ESA aimed at the study of metal creation from the epoch of cosmic dawn. Using high-spectral resolution in the soft X-ray band, ORIGIN will be able to identify the physical conditions of all abundant elements between C and Ni to red-shifts of z=10, and beyond. The mission will answer questions such as: When were the first metals created? How does the cosmic metal content evolve? Where do most of the metals reside in the Universe? What is the role of metals in structure formation and evolution? To reach out to the early Universe ORIGIN will use Gamma-Ray Bursts (GRBs) to study their local environments in their host galaxies. This requires the capability to slew the satellite in less than a minute to the GRB location. By studying the chemical composition and properties of clusters of galaxies we can extend the range of exploration to lower redshifts (z approx. 0.2). For this task we need a high-resolution spectral imaging instrument with a large field of view. Using the same instrument, we can also study the so far only partially detected baryons in the Warm-Hot Intergalactic Medium (WHIM). The less dense part of the WHIM will be studied using absorption lines at low redshift in the spectra for GRBs. The ORIGIN mission includes a Transient Event Detector (coded mask with a sensitivity of 0.4 photon/sq cm/s in 10 s in the 5-150 keV band) to identify and localize 2000 GRBs over a five year mission, of which approx.65 GRBs have a redshift >7. The Cryogenic Imaging Spectrometer, with a spectral resolution of 2.5 eV, a field of view of 30 arcmin and large effective area below 1 keV has the sensitivity to study clusters up to a significant fraction of the virial radius and to map the denser parts of the WHIM (factor 30 higher than achievable with current instruments). The payload is complemented by a Burst InfraRed Telescope to enable onboard red-shift determination of GRBs (hence securing proper follow up of high-z bursts) and also probes the mildly ionized state of the gas. Fast repointing is achieved by a dedicated Controlled Momentum Gyro and a low background is achieved by the selected low Earth orbit