Measurement of the Charge Collection Efficiency after Heavy Non-Uniform Irradiation in BaBar Silicon Detectors

We have investigated the depletion voltage changes, the leakage current increase and the charge collection efficiency of a silicon microstrip detector identical to those used in the inner layers of the BaBar Silicon Vertex Tracker (SVT) after heavy non-uniform irradiation. A full SVT module with the front-end electronics connected has been irradiated with a 0.9 GeV electron beam up to a peak fluence of 3.5 x 10^14 e^-/cm^2, well beyond the level causing substrate type inversion. We irradiated one of the two sensors composing the module with a non-uniform profile with sigma=1.4 mm that simulates the conditions encountered in the BaBar experiment by the modules intersecting the horizontal machine plane. The position dependence of the charge collection properties and the depletion voltage have been investigated in detail using a 1060 nm LED and an innovative measuring technique based only on the digital output of the chip.Comment: 7 pages, 13 figures. Presented at the 2004 IEEE Nuclear Science Symposium, October 18-21, Rome, Italy. Accepted for publication by IEEE Transactions on Nuclear Scienc

Light Ions Response of Silicon Carbide Detectors

Silicon carbide (SiC) Schottky diodes 21 mum thick with small surfaces and high N-dopant concentration have been used to detect alpha particles and low energy light ions. In particular 12C and 16O beams at incident energies between 5 and 18 MeV were used. The diode active-region depletion-thickness, the linearity of the response, energy resolution and signal rise-time were measured for different values of the applied reverse bias. Moreover the radiation damage on SiC diodes irradiated with 53 MeV 16O beam has been explored. The data show that SiC material is radiation harder than silicon but at least one order of magnitude less hard than epitaxial silicon diodes. An inversion in the signal was found at a fluence of 10^15 ions/cm^2.Comment: 20 pages, 16 figures, submitted for publication to Nuclear Instruments and Methods in Physics Research

Effect of soy on metabolic syndrome and cardiovascular risk factors : a randomized controlled trial

Background: Cardiovascular diseases are currently the commonest cause of death worldwide. Different strategies for their primary prevention have been planned, taking into account the main known risk factors, which include an atherogenic lipid profile and visceral fat excess. Methods: The study was designed as a randomized, parallel, single-center study with a nutritional intervention duration of 12 weeks. Whole soy foods corresponding to 30 g/day soy protein were given in substitution of animal foods containing the same protein amount. Results: Soy nutritional intervention resulted in a reduction in the number of MetS features in 13/26 subjects. Moreover, in the soy group we observed a significant improvement of median percentage changes for body weight ( 121.5 %) and BMI ( 121.5 %), as well as for atherogenic lipid markers, namely TC ( 124.85 %), LDL-C ( 125.25 %), non-HDL-C ( 127.14 %) and apoB ( 1214.8 %). Since the majority of the studied variables were strongly correlated, three factors were identified which explained the majority (52 %) of the total variance in the whole data set. Among them, factor 1, which loaded lipid and adipose variables, explained the 22 % of total variance, showing a statistically significant difference between treatment arms (p = 0.002). Conclusions: The inclusion of whole soy foods (corresponding to 30 g/day protein) in a lipid-lowering diet significantly improved a relevant set of biomarkers associated with cardiovascular risk

The RIG-I agonist M8 triggers cell death and natural killer cell activation in human papillomavirus-associated cancer and potentiates cisplatin cytotoxicity

Although the activation of innate immunity to treat a wide variety of cancers is gaining increasing attention, it has been poorly investigated in human papillomavirus (HPV)-associated malignancies. Because these tumors harbor a severely impaired cGAS-STING axis, but they still retain a largely functional RIG-I pathway, another critical mediator of adaptive and innate immune responses, we asked whether RIG-I activation by the 5'ppp-RNA RIG-I agonist M8 would represent a therapeutically viable option to treat HPV+ cancers. Here, we show that M8 transfection of two cervical carcinoma-derived cell lines, CaSki and HeLa, both expressing a functional RIG-I, triggers intrinsic apoptotic cell death, which is significantly reduced in RIG-I KO cells. We also demonstrate that M8 stimulation potentiates cisplatin-mediated cell killing of HPV+ cells in a RIG-I dependent manner. This combination treatment is equally effective in reducing tumor growth in a syngeneic pre-clinical mouse model of HPV16-driven cancer, where enhanced expression of lymphocyte-recruiting chemokines and cytokines correlated with an increased number of activated natural killer (NK) cells in the tumor microenvironment. Consistent with a role of RIG-I signaling in immunogenic cell killing, stimulation of NK cells with conditioned medium from M8-transfected CaSki boosted NK cell proliferation, activation, and migration in a RIG-I-dependent tumor cell-intrinsic manner. Given the highly conserved molecular mechanisms of carcinogenesis and genomic features of HPV-driven cancers and the remarkably improved prognosis for HPV+ oropharyngeal cancer, targeting RIG-I may represent an effective immunotherapeutic strategy in this setting, favoring the development of de-escalating strategies

IRST SiPM characterizations and application studies

This paper reports on work undertaken, in collaboration with ITC-IRST at Trento, to characterize and test the silicon photomultiplers produced by them, with a view to their future application in high energy and astrophysics experiments. Results of static and dynamic measurents with various IRST devices under controlled climatic conditions, together with measurements with SiPMs from other distributors are reported and discussed with emphasis on progress in the understanding of operational principles and the reduction of noise. Results from the test beam application of the SiPMs are also reported and future plans are discusse

Human metapneumovirus establishes persistent infection in lung microvascular endothelial cells and primes a th2-skewed immune response

Human metapneumovirus (HMPV) is a major cause of lower respiratory tract infections. HMPV infection has been hypothesized to alter dendritic cell (DC) immune response; however, many questions regarding HMPV pathogenesis within the infected lung remain unanswered. Here, we show that HMPV productively infects human lung microvascular endothelial cells (L-HMVECs). The release of infectious virus occurs for up to more than 30 days of culture without producing overt cytopathic effects and medium derived from persistently HMPV-infected L-HMVECs (secretome) induced monocyte-derived DCs to prime naïve CD4 T-cells toward a Th2 phenotype. Moreover, we demonstrated that infected secretomes trigger DCs to up-regulate OX40L expression and OX40L neutralization abolished the pro-Th2 effect that is induced by HMPV-secretome. We clarified secretome from HMPV by size exclusion and ultracentrifugation with the aim to characterize the role of viral particles in the observed pro-Th2 effect. In both cases, the percentage of IL-4-producing cells and expression of OX40L returned at basal levels. Finally, we showed that HMPV, per se, could reproduce the ability of secretome to prime pro-Th2 DCs. These results suggest that HMPV, persistently released by L-HMVECs, might take part in the development of a skewed, pro-Th2 lung microenvironment