Daedalus: A hardware signal analyser for Icarus

Icarus detector [1] is a large-volume (400 cm) liquid Argon TPC that requires continuous high rate sampling signal recording on each channel (about 50 000) to produce event images quite similar to the ones from bubble chambers. In order to optimize the memory usage, a signal feature extractor, that commands memory writing only upon signal detection, has been designed in VLSI CMOS. ( 1998 Elsevier Science B.V. All rights reserved

Characterisation of La0.6Sr0.4Co0.2Fe0.8O3-\u3b4- Ba0.5Sr0.5Co0.8Fe0.2O3-\u3b4composite as cathode for solid oxide fuel cells

Mixture of La0.6Sr0.4Co0.2Fe0.8O3-\u3b4 and Ba0.5Sr0.5Co0.8Fe0.2O3-\u3b4, was investigated as promising cathode for intermediate temperature solid oxide fuel cells (IT-SOFCs). The two perovskites possess high catalytic activity for the oxygen reduction (ORR), although some problems related to their chemical and structural stability have still to be overcome in view of improving durability of the cell performance. The achievement of a stable and high-performing composite material is the aim of this study. In principle, chemical equilibrium at the LSCF-BSCF interface may be reached through ions interdiffusion during the sintering process, resulting in the chemical stabilization of the material. The composite-cathode deposited on Ce0.8Sm0.2O2-\u3b4 electrolyte was then investigated by Electrochemical Impedance Spectroscopy (EIS) as a function of temperature, overpotential and time. The results exhibited an interesting electrochemical behavior of the electrode toward oxygen reduction reaction. XRD analysis was performed to detect structural modification during thermal or operation stages and it was found that after the sintering the two starting perovskites were no longer present; a new phase with a rhombohedral La0,4Sr0,6FeO3-type structure (LSF) is formed. An improvement in composite cathode durability has been detected under the considered operating conditions (200 mAcm-2, 700 \ub0C) in comparison with the pure BSCF electrode. The results confirmed this new electrode as promising system for further investigation as IT-SOFC cathode

Application of electro-fenton process for the treatment of methylene blue

The electrochemical removal of an aqueous solution containing 0.25 mM of methylene blue (MB), one of the most important thiazine dye, has been investigated by electro-Fenton process using a graphite-felt cathode to electrogenerate in situ hydrogen peroxide and regenerate ferrous ions as catalyst. The effect of operating conditions such as applied current, catalyst concentration, and initial dye content on MB degradation has been studied. MB removal and mineralization were monitored during the electrolysis by UV\u2013Vis analysis and TOC measurements. The experimental results showed that MB was completely removed by the reaction with \u2022OH radicals generated from electrochemically assisted Fenton\u2019s reaction, and in any conditions the decay kinetic always follows a pseudo-first-order reaction. The faster MB oxidation rate was obtained applying a current of 300 mA, with 0.3 mM Fe2+at T=35 \ub0C. In these conditions, 0.25 mM MB was completely removed in 45 min and the initial TOC was removed in 90 min of electrolysis, meaning the almost complete mineralization of the organic content of the treated solution

Anti-PSMA CAR-engineered NK-92 Cells: An Off-the-shelf Cell Therapy for Prostate Cancer

Prostate cancer (PCa) has become the most common cancer among males in Europe and the USA. Adoptive immunotherapy appears a promising strategy to control the advanced stages of the disease by specifically targeting the tumor, in particular through chimeric antigen receptor T (CAR-T) cell therapy. Despite the advancements of CAR-T technology in the treatment of hematological malignancies, solid tumors still represent a challenge. To overcome current limits, other cellular effectors than T lymphocytes are under study as possible candidates for CAR-engineered cancer immunotherapy. A novel approach involves the NK-92 cell line, which mediates strong cytotoxic responses against a variety of tumor cells but has no effect on non-malignant healthy counterparts. Here, we report a novel therapeutic approach against PCa based on engineering of NK-92 cells with a CAR recognizing the human prostate-specific membrane antigen (PSMA), which is overexpressed in prostatic neoplastic cells. More importantly, the potential utility of NK-92/CAR cells to treat PCa has not yet been explored. Upon CAR transduction, NK-92/CAR cells acquired high and specific lytic activity against PSMA-expressing prostate cancer cells in vitro, and also underwent degranulation and produced high levels of IFN-\u3b3 in response to antigen recognition. Lethal irradiation of the effectors, a safety measure requested for the clinical application of retargeted NK-92 cells, fully abrogated replication but did not impact on phenotype and short-term functionality. PSMA-specific recognition and antitumor activity were retained in vivo, as adoptive transfer of irradiated NK-92/CAR cells in prostate cancer-bearing mice restrained tumor growth and improved survival. Anti-PSMA CAR-modified NK-92 cells represent a universal, off-the-shelf, renewable, and cost-effective product endowed with relevant potentialities as a therapeutic approach for PCa immunotherapy

A Comprehensive Approach to Improve Performance and Stability of State-of-the- Art Air Electrodes for Intermediate Temperature Reversible Cells: An Impedance Spectroscopy Analysis

Solid oxide fuel cells (SOFC) are devices for the transformation of chemical energy in electrical energy. SOFC appear very promising for their very high efficiency, in addition to the capability to work in reverse mode, which makes them suitable for integration in production units powered with renewables. Research efforts are currently addressed to find chemically and structurally stable materials, in order to improve performance stability during long-term operation. In this work, we examine different approaches for improving stability of two state-of-the-art perovskite materials, La0.6Sr0.4Co0.2Fe0.8O3-\uf064 (LSCF) and Ba0.5Sr0.5Co0.8Fe0.2O3-\uf064 (BSCF), very promising as air electrodes. Two different systems are considered: (i) LSCF and BSCF porous electrodes impregnated by a nano-sized La0.8Sr0.2MnO3-\uf064 layer and (ii) LSCF-BSCF composites with the two phases in different volume proportions. The study considers the results obtained by electrochemical impedance spectroscopy investigation, observing the polarisation resistance (Rp) of each system to evaluate performance in typical SOFC operating conditions. Furthermore, the behaviour of polarisation resistance under the effect of a net current load (cathodic) circulating for hundreds of hours is examined, as parameter to evaluate long-term performance stability

Adoptive cell therapy of triple negative breast cancer with redirected cytokine-induced killer cells

Cytokine-Induced Killer (CIK) cells share several functional and phenotypical properties of both T and natural killer (NK) cells. They represent an attractive approach for cell-based immunotherapy, as they do not require antigen-specific priming for tumor cell recognition, and can be rapidly expanded in vitro. Their relevant expression of Fc\u3b3RIIIa (CD16a) can be exploited in combination with clinical-grade monoclonal antibodies (mAbs) to redirect their lytic activity in an antigen-specific manner. Here, we report the efficacy of this combined approach against triple negative breast cancer (TNBC), an aggressive tumor that still requires therapeutic options. Different primitive and metastatic TNBC cancer mouse models were established in NSG mice, either by implanting patient-derived TNBC samples or injecting MDA-MB-231 cells orthotopically or intravenously. The combined treatment consisted in the repeated intratumoral or intravenous injection of CIK cells and cetuximab. Tumor growth and metastasis were monitored by bioluminescence or immunohistochemistry, and survival was recorded. CIK cells plus cetuximab significantly restrained primitive tumor growth in mice, either in patient-derived tumor xenografts or MDA-MB-231 cell line models. Moreover, this approach almost completely abolished metastasis spreading and dramatically improved survival. The antigen-specific mAb favored tumor and metastasis tissue infiltration by CIK cells, and led to an enrichment of the CD16a+ subset. Data highlight the potentiality of this novel immunotherapy strategy where a nonspecific cytotoxic cell population can be converted into tumor-specific effectors with clinical-grade antibodies, thus providing not only a therapeutic option for TNBC but also a valid alternative to more complex approaches based on chimeric antigen receptor-engineered cells. List of abbreviations: ACT, Adoptive Cell Transfer; ADCC, Antibody-Dependent Cell-mediated Cytotoxicity; ADP, Adenosine diphosphate; BLI, Bioluminescence Imaging; CAR, Chimeric Antigen Receptor; CIK, Cytokine Induced Killer cells; CTX, Cetuximab; DMEM, Dulbecco\u2019s Modified Eagle Medium; EGFR, Human Epidermal Growth Factor 1; ER, Estrogen; FBS, Fetal Bovine Serum; FFPE, Formalin-Fixed Paraffin-Embedded; GMP, Good Manufacturing Practices; GVHD, Graft Versus Host Disease; HER2, Human Epidermal Growth Factor 2; HRP, Horseradish Peroxidase; IFN-\u3b3, Interferon-\u3b3; IHC, Immunohistochemistry; IL-2, Interleukin-2; ISO, Irrelevant antibody; i.t., intratumoral; i.v., intravenous, mAbs, Monoclonal Antibodies; mIHC, Multiplex Fluorescence Immunohistochemistry; MHC, Major Histocompatibility Complex; NK, Natural Killer; NKG2D, Natural-Killer group 2 member D; NSG, NOD/SCID common \u3b3 chain knockout; PARP, Poly ADP-ribose polymerase; PBMCs, Peripheral Blood Mononuclear Cells; PBS, Phosphate-buffered saline; PDX, Patient-derived xenograft; PR, Progesterone; rhIFN-\u3b3, Recombinant Human Interferon-\u3b3; RPMI, Roswell Park Memorial Institute; STR, Short tandem Repeat; TCR, T Cell Receptor; TNBC, Triple Negative Breast Cancer; TSA, Tyramide Signal Amplification

Hyaluronan is a natural and effective immunological adjuvant for protein-based vaccines

One of the main goals of vaccine research is the development of adjuvants that can enhance immune responses and are both safe and biocompatible. We explored the application of the natural polymer hyaluronan (HA) as a promising immunological adjuvant for protein-based vaccines. Chemical conjugation of HA to antigens strongly increased their immunogenicity, reduced booster requirements, and allowed antigen dose sparing. HA-based bioconjugates stimulated robust and long-lasting humoral responses without the addition of other immunostimulatory compounds and proved highly efficient when compared to other adjuvants. Due to its intrinsic biocompatibility, HA allowed the exploitation of different injection routes and did not induce inflammation at the inoculation site. This polymer promoted rapid translocation of the antigen to draining lymph nodes, thus facilitating encounters with antigen-presenting cells. Overall, HA can be regarded as an effective and biocompatible adjuvant to be exploited for the design of a wide variety of vaccines

Measurement of the muon decay spectrum with the ICARUS liquid Argon TPC

Examples are given which prove the ICARUS detector quality through relevant physics measurements. We study the muon decay energy spectrum from a sample of stopping muon events acquired during the test run of the ICARUS T600 detector. This detector allows the spatial reconstruction of the events with fine granularity, hence, the precise measurement of the range and dE/dx of the muon with high sampling rate. This information is used to compute the calibration factors needed for the full calorimetric reconstruction of the events. The Michel rho parameter is then measured by comparison of the experimental and Monte Carlo simulated muon decay spectra, obtaining rho = 0.72 +/- 0.06(stat.) +/- 0.08(syst.). The energy resolution for electrons below ~50 MeV is finally extracted from the simulated sample, obtaining (Emeas-Emc)/Emc = 11%/sqrt(E[MeV]) + 2%.Comment: 16 pages, 8 figures, LaTex, A4. Some text and 1 figure added. Final version as accepted for publication in The European Physical Journal

Multi-centre phase II clinical trial of yttrium-90 resin microspheres alone in unresectable, chemotherapy refractory colorectal liver metastases

Background:This multi-centre phase II clinical trial is the first prospective evaluation of radioembolisation of patients with colorectal liver metastases (mCRC) who failed previous oxaliplatin-and irinotecan-based systemic chemotherapy regimens.Methods:Eligible patients had adequate hepatic, haemopoietic and renal function, and an absence of major hepatic vascular anomalies and hepato-pulmonary shunting. Gastroduodenal and right gastric arteries were embolised before hepatic arterial administration of yttrium-90 resin microspheres (median activity, 1.7 GBq; range, 0.9-2.2).Results:Of 50 eligible patients, 38 (76%) had received 654 lines of chemotherapy. Most presented with synchronous disease (72%), <4 hepatic metastases (58%), 25-50% replacement of total liver volume (60%) and bilateral spread (70%). Early and intermediate (<48 h) WHO G1-2 adverse events (mostly fever and pain) were observed in 16 and 22% of patients respectively. Two died due to renal failure at 40 days or liver failure at 60 days respectively. By intention-to-treat analysis using Response Evaluation Criteria in Solid Tumours, 1 patient (2%) had a complete response, 11 (22%) partial response, 12 (24%) stable disease, 22 (44%) progressive disease; 4 (8%) were non-evaluable. Median overall survival was 12.6 months (95% CI, 7.0-18.3); 2-year survival was 19.6%.Conclusion: Radioembolisation produced meaningful response and disease stabilisation in patients with advanced, unresectable and chemorefractory mCRC. \ua9 2010 Cancer Research UK All rights reserved