Characterization of a kg-scale archaeological lead-based PbWO4 cryogenic detector for the RES-NOVA experiment.

Core-collapse Supernovae (SNe) are one of the most energetic events in the Universe, during which almost all the star's binding energy is released in the form of neutrinos. These particles are direct probes of the processes occurring in the stellar core and provide unique insights into the gravitational collapse. RES-NOVA will revolutionize how we detect neutrinos from astrophysical sources, by deploying the first ton-scale array of cryogenic detectors made from archaeological lead. Pb offers the highest neutrino interaction cross-section via coherent elastic neutrino-nucleus scattering (CEνNS). Such process will enable RES-NOVA to be equally sensitive to all neutrino flavours. For the first time, we propose the use archaeological Pb as sensitive target material in order to achieve an ultra-low background level in the region of interest (O(1 keV)). All these features make possible the deployment of the first cm-scale neutrino telescope for the investigation of astrophysical sources. In this contribution, we will characterize the radiopurity level and the performance of a small-scale proof-of-principle detector of RES-NOVA, consisting in a PbWO4 crystal made from archaeological-Pb operated as cryogenic detector.

Erratum: Measurement of the 2νßß Decay Half-Life of

This corrects the article DOI: 10.1103/PhysRevLett.126.171801.

New Direct Limit on Neutrinoless Double Beta Decay Half-Life of

The Cryogenic Underground Observatory for Rare Events (CUORE) at Laboratori Nazionali del Gran Sasso of INFN in Italy is an experiment searching for neutrinoless double beta (0νßß) decay. Its main goal is to investigate this decay in ^{130}Te, but its ton-scale mass and low background make CUORE sensitive to other rare processes as well. In this Letter, we present our first results on the search for 0νßß decay of ^{128}Te, the Te isotope with the second highest natural isotopic abundance. We find no evidence for this decay, and using a Bayesian analysis we set a lower limit on the ^{128}Te 0νßß decay half-life of T_{1/2}>3.6×10^{24} yr (90% CI). This represents the most stringent limit on the half-life of this isotope, improving by over a factor of 30 the previous direct search results, and exceeding those from geochemical experiments for the first time.

An amyloid beta vaccine that safely drives immunity to a key pathological species in Alzheimer's disease: pyroglutamate amyloid beta.

Pyroglutamate amyloid beta3-42 (pGlu-Abeta3-42), a highly amyloidogenic and neurotoxic form of Abeta, is N-terminally truncated to form a pyroglutamate and has recently been proposed as a key target for immunotherapy. Optimized ACI-24, a vaccine in development for the treatment and prevention of Alzheimer's disease, focuses the antibody response on the first 15 N-terminal amino acids of Abeta (Abeta1-15). Importantly, clinical data with an initial version of ACI-24 incorporating Abeta1-15, established the vaccine's safety and tolerability with evidence of immunogenicity. To explore optimized ACI-24's capacity to generate antibodies to pGlu-Abeta3-42, pre-clinical studies were carried out. Vaccinating mice and non-human primates demonstrated that optimized ACI-24 was well-tolerated and induced an antibody response against Abeta1-42 as expected, as well as high titres of IgG reactive with pyroGlu-Abeta. Epitope mapping of the polyclonal response confirmed these findings revealing broad coverage of epitopes particularly for Abeta peptides mimicking where cleavage occurs to form pGlu-Abeta3-42. These data are in striking contrast to results obtained with other clinically tested Abeta targeting vaccines which generated restricted and limited antibody diversity. Taken together, our findings demonstrate that optimized ACI-24 vaccination represents a breakthrough to provide a safe immune response with a broader Abeta sequence recognition compared to previously tested vaccines, creating binders to pathogenic forms of Abeta important in pathogenesis including pGlu-Abeta3-42.

Measurement of the 2νßß Decay Half-Life of

We measured two-neutrino double beta decay of ^{130}Te using an exposure of 300.7 kg yr accumulated with the CUORE detector. Using a Bayesian analysis to fit simulated spectra to experimental data, it was possible to disentangle all the major background sources and precisely measure the two-neutrino contribution. The half-life is in agreement with past measurements with a strongly reduced uncertainty: T_{1/2}^{2ν}=7.71_{-0.06}^{+0.08}(stat)_{-0.15}^{+0.12}(syst)×10^{20} yr. This measurement is the most precise determination of the ^{130}Te 2νßß decay half-life to date.

Improved Limit on Neutrinoless Double-Beta Decay in

We report new results from the search for neutrinoless double-beta decay in ^{130} Te with the CUORE detector. This search benefits from a fourfold increase in exposure, lower trigger thresholds, and analysis improvements relative to our previous results. We observe a background of (1.38±0.07)×10^{-2} counts/(keV kg yr)) in the 0νßß decay region of interest and, with a total exposure of 372.5 kg yr, we attain a median exclusion sensitivity of 1.7×10^{25} yr. We find no evidence for 0νßß decay and set a 90% credibility interval Bayesian lower limit of 3.2×10^{25} yr on the ^{130} Te half-life for this process. In the hypothesis that 0νßß decay is mediated by light Majorana neutrinos, this results in an upper limit on the effective Majorana mass of 75-350 meV, depending on the nuclear matrix elements used.

Galectin-1 suppression delineates a new strategy to inhibit myeloma-induced angiogenesis and tumoral growth in vivo.

Galectin-1 (Gal-1) is involved in tumoral angiogenesis, hypoxia and metastases. Actually the Gal-1 expression profile in multiple myeloma (MM) patients and its pathophysiological role in MM-induced angiogenesis and tumoral growth are unknown. In this study, we found that Gal-1 expression by MM cells was upregulated in hypoxic conditions and that stable knockdown of hypoxia inducible factor-1α significantly downregulated its expression. Therefore, we performed Gal-1 inhibition using lentivirus transfection of shRNA anti-Gal-1 in human myeloma cell lines (HMCLs), and showed that its suppression modified transcriptional profiles in both hypoxic and normoxic conditions. Interestingly, Gal-1 inhibition in MM cells downregulated proangiogenic genes, including MMP9 and CCL2, and upregulated the antiangiogenic ones SEMA3A and CXCL10. Consistently, Gal-1 suppression in MM cells significantly decreased their proangiogenic properties in vitro. This was confirmed in vivo, in two different mouse models injected with HMCLs transfected with anti-Gal-1 shRNA or the control vector. Gal-1 suppression in both models significantly reduced tumor burden and microvascular density as compared with the control mice. Moreover, Gal-1 suppression induced smaller lytic lesions on X-ray in the intratibial model. Overall, our data indicate that Gal-1 is a new potential therapeutic target in MM blocking angiogenesis.

Search for Neutrinoless Double-Beta Decay of (130)Te with CUORE-0.

We report the results of a search for neutrinoless double-beta decay in a 9.8 kg yr exposure of (130)Te using a bolometric detector array, CUORE-0. The characteristic detector energy resolution and background level in the region of interest are 5.1±0.3 keV FWHM and 0.058±0.004(stat)±0.002(syst)counts/(keV kg yr), respectively. The median 90% C.L. lower-limit half-life sensitivity of the experiment is 2.9×10(24) yr and surpasses the sensitivity of previous searches. We find no evidence for neutrinoless double-beta decay of (130)Te and place a Bayesian lower bound on the decay half-life, T(1/2)(0ν)>2.7×10(24) yr at 90% C.L. Combining CUORE-0 data with the 19.75 kg yr exposure of (130)Te from the Cuoricino experiment we obtain T(1/2)(0ν)>4.0×10(24) yr at 90% C.L. (Bayesian), the most stringent limit to date on this half-life. Using a range of nuclear matrix element estimates we interpret this as a limit on the effective Majorana neutrino mass, m(ßß)<270-760 meV.

Uptake and acute toxicity of cerium in the lichen Xanthoria parietina.

Environmental cerium (Ce) levels are likely to increase in the near future and monitoring of its biological effects will therefore be necessary. The aim of this study was to test if treatment of the lichen Xanthoria parietina with Ce-containing solutions (0.1mM, 1mM, 10mM and 100mM) causes Ce bioaccumulation (both extra- and intra-cellularly) as well as physiological (sample viability, membrane lipids peroxidation, photosynthetic performance, water-soluble proteins content) and ultrastructural alterations. The results showed that treatment with Ce solutions induces Ce bioaccumulation, both extra-cellularly and intra-cellularly, which in turn causes an acute toxicity, evident as decreased sample viability, marked decrease in the photosynthetic performance and important changes in the ultrastructure.

Antimony toxicity in the lichen Xanthoria parietina (L.) Th. Fr.

In this paper we tested if treating the lichen Xanthoria parietina with Sb-containing solutions causes Sb bioaccumulation as well as physiological and ultrastructural changes. Total and intracellular antimony content in Sb-treated samples increased progressively with increasing concentration in the treatment solutions. Incubation of X. parietina thalli with Sb at concentrations as low as 0.1mM caused a decrease in sample viability, measured as intensity of respiratory activity, and damage to cell membranes, expressed in terms of membrane lipid peroxidation, as well as ultrastructural changes such as plasmolysis, impairment of the thylakoid system of the alga and cytoplasmic lipid droplets. The photosynthetic system hardly responded, at least under the tested experimental conditions.

Physiological response of the epiphytic lichen Evernia prunastri (L.) Ach. to ecologically relevant nitrogen concentrations.

This study investigated the physiological response of the epiphytic lichen Evernia prunastri to ecologically relevant concentrations of nitrogen compounds. Lichen samples were sprayed for 4 weeks either with water or 50, 150 and 500 µM NH(4)Cl. The integrity of cell membranes and chlorophyll a fluorescence emission (F(V)/F(M) and PI(ABS)) were analyzed. No membrane damage occurred after the exposure period. F(V)/F(M), a classical fluorescence indicator, decreased during the second week of treatment with 500 µM NH(4)Cl and the third week with 50 and 150 µM NH(4)Cl. PI(ABS), an overall index of the photosynthetic performance, was more sensitive and decreased already during the first week with 500 µM NH(4)Cl and the second week with 150 µM NH(4)Cl. Since E. prunastri has been exposed to ammonium loads corresponding to real environmental conditions, these findings open the way to an effective use of this species as early indicators of environmental nitrogen excess.

Measurement of airborne 131I, 134)Cs and 137Cs due to the Fukushima reactor incident in Milan (Italy).

After the earthquake and the tsunami occurred in Japan on March 2011, four of the Fukushima reactors had released in air a large amount of radioactive isotopes that diffused all over the world. The presence of airborne (131)I, (134)Cs, and (137)Cs in air particulate due to this accident were detected and measured in the Low Radioactivity Laboratory operating in the Department of Environmental Sciences of the University of Milano-Bicocca. The sensitivity of the detecting apparatus is of 0.2 uBq/m(3) of air. Concentration and time distribution of these radiocontaminations ranging from a few to 400 uBq/m(3) for the (131)I and of a few tens of uBq/m(3) for the (137)Cs and (134)Cs.

ARFI elastography in patients with chronic autoimmune liver diseases: A preliminary study.

OBJECTIVE: Acoustic radiation force impulse (ARFI) is a new software-based technique that evaluates liver stiffness during B-mode ultrasonography. The purpose of this study was to evaluate the accuracy of ARFI in distinguishing patients with chronic autoimmune liver disease from healthy subjects. MATERIAL AND METHODS: We enrolled 9 adult patients (8 women, 1 man; age 48.1 ± 12.8 years) with chronic autoimmune disease (primary biliary cirrhosis (PBC, n = 3), autoimmune hepatitis (AIH, n = 2), primary sclerosing cholangitis (PSC, n = 1) and overlap syndromes, (n = 3) who underwent a liver biopsy and 11 healthy volunteers (age 34.7 ± 10.4 years; 7 women, 4 men). Liver stiffness was evaluated and expressed as the shear wave velocity (SWV) in m/sec. We used a US scanner Siemens-Acuson S2000, evaluating the right liver lobe and the left liver lobe. RESULTS: THE SWV WAS SIGNIFICANTLY HIGHER IN CASES (RIGHT LOBE: 1.51 ± 0.44; left lobe: 1.57 ± 0.40) than in controls (right lobe: 1.08 ± 0.10; left lobe: 1.12 ± 0.13) (right lobe: P = 0.002; left lobe: P = 0.013). We found no significant correlation between right and left lobe SWVs in cases (P = 0.779) or controls (P = 0.385). The SWV cut-off that best distinguished cases from controls was 1.25 m/sec (accuracy: AUC=0.885; sensitivity: 70.6%; specificity: 95.5%). CONCLUSIONS: ARFI elastography is a noninvasive ultrasonographic technique that can differentiate healthy subjects from patients with fibrotic stages of chronic liver disease.

Real-time elastography as a noninvasive technique for quantification of fibrosis in patients with chronic viral liver disease: Preliminary findings.

INTRODUCTION: Real-time elastography (RTE) is a novel technique for measuring tissue elasticity. The aims of this study were to prospectively measure liver stiffness with RTE in patients with chronic viral hepatitis and to evaluate the possible correlation between RTE data and the extent of fibrosis based on liver biopsy findings (Ishak score). MATERIAL AND METHODS: Between February and October 2011, 26 patients (18M, 8F, mean age 41 ± 13 [standard deviation], range 22-62) with chronic viral hepatitis were prospectively evaluated with ultrasonography (US) that included RTE. All patients then underwent US-guided percutaneous liver biopsy (right lobe) for evaluation of fibrosis. Examinations were performed with a iU22 scanner (Philips, Bothell, WA, USA); a convex transducer (C5-1) was used for the US examination, and a linear transducer (L12-5) for RTE. In the RTE images, relative tissue stiffness is expressed according to a color scale with soft areas represented in green/red and hard areas in blue. Patients were examined in the supine position in suspended normal respiration; three loops of 20 RTE frames were recorded for each case. For each patient, we calculated the mean strain ratio (MSR) for the 3 loops. The Spearman correlation coefficient was used to assess correlation between the ASR and fibrosis stage (F) reflected by the Ishak score. RESULTS: The Spearman coefficient showed significant correlation between the MSR and F (Rho = 0.470, p = 0.015). CONCLUSIONS: RTE appears to be a useful tool for noninvasive evaluation of fibrosis in patients with chronic viral hepatitis although these findings need to be confirmed in larger case series.

Autoimmune enteropathy and rheumatoid arthritis: a new association in the field of autoimmunity.

We report the case of a 35-year-old woman with a diagnosis of coeliac disease at the age of 32 due to a severe malabsorption and flat mucosa without endomysial and tissue transglutaminase antibodies. The lack of clinical and histological improvement after 1 year of a gluten-free diet led to a diagnosis of refractory sprue. She had a good clinical response to steroids that were stopped after 3 months when she became pregnant. After delivery, she again started to complain of malabsorption with arthritis. Positivity for enterocyte autoantibodies together with a flat mucosa persistence allowed to identify a condition of autoimmune enteropathy; moreover, a rheumatological assessment gave evidence of an associated rheumatoid arthritis. Treatment by steroids and methotrexate brought to the remission of intestinal and articular symptoms together with an improvement of duodenal histology. This is the first description of an autoimmune enteropathy associated with rheumatoid arthritis. Autoimmune enteropathy should be always ruled out in patients with a villous atrophy unresponsive to a gluten-free diet, autoimmune manifestations and negativity of coeliac disease markers.

Gene transfer of RANTES and MCP-1 chemokine antagonists prolongs cardiac allograft survival.

Vascularized organ allografts are rapidly destroyed by host immune cells that are recruited along chemokine gradients. Among chemokines, Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES) CC chemokine ligand (CCL5) and monocyte chemoattractant protein (MCP)-1 (CCL2) are upregulated in rejecting cardiac allografts. To antagonize these chemokines, we constructed adenoviral vectors expressing NH(2)-terminal deletion (8ND) mutants of the respective genes. Using the F344-to-LEW rat model, intragraft gene transfer of chemokine analogs prolonged cardiac allograft survival from 10.1+/-0.7 and 10.4+/-0.7 days using non-coding adenovirus and vehicle alone, respectively, to 17.0+/-0.7 days for 8ND-RANTES (P<0.001) and 14.2+/-0.8 days for 8ND-MCP-1 (P<0.01). 8ND-RANTES reduced graft infiltration by monocytes/macrophages, cluster of differentiation (CD) 8alpha(+) and T-cell receptor alphabeta(+) cells, while 8ND-MCP-1 reduced monocytes/macrophages. In mixed leukocyte reactions in vitro, proliferation of host lymphocytes from regional lymph nodes in response to donor splenocytes was unaffected by 8ND-RANTES gene transfer. Using a two-gene approach, the contribution of 8ND-MCP-1 was negligible, consistent with available evidence that 8ND-RANTES inhibits both RANTES and MCP-1 activities. 8ND-RANTES gene transfer and a short course of low-dose cyclosporine A synergistically prolonged graft survival to 37.8+/-5.5 vs 15.4+/-0.5 days with cyclosporine alone (P<0.001). These results suggest a role for anti-chemokine gene therapy as an adjuvant therapy in heart transplantation.

Anti-ganglioside antibodies in coeliac disease with neurological disorders.

BACKGROUND: Anti-ganglioside antibodies have been described in sera of coeliac patients with peripheral neuropathy and cerebellar ataxia. AIMS: To investigate the correlation between anti-ganglioside antibodies and neurological involvement in coeliac disease before and after gluten-free diet. PATIENTS AND METHODS: Twenty-two untreated coeliac patients with neurological dysfunction and 30 untreated coeliacs without neurological dysfunction, 20 patients with neurological disorders, 50 autoimmune disease and 20 blood donors were tested for anti-GM1, anti-GD1b and anti-GQ1b IgG and IgM antibodies by enzyme-linked immunosorbent assay. RESULTS: IgG antibodies to at least one of the three antigens tested were positive in 64% of coeliac patients with neurological symptoms compared to 30% of coeliacs without neurological dysfunction (P=0.02), 50% of patients with neurological disorders (P=ns), 20% with autoimmune diseases (P=0.003) and none of blood donors (P=0.0001). A strict gluten-free diet determined anti-ganglioside antibody disappearance in about half of coeliacs. CONCLUSIONS: A significant correlation between anti-ganglioside antibodies and neurological disorders in patients with an underlying coeliac disease has been found. Anti-ganglioside antibodies may represent a new immunological marker to identify neurological impairment in patients with coeliac disease.

Measurement of the p to s wave branching ratio of 187Re beta decay from beta environmental fine structure.

The mixed occurrence of s-wave and p-wave contributions in a first forbidden unique Gamow-Teller beta decay has been investigated for the first time by measuring the beta environmental fine structure (BEFS) in a 187Re crystalline compound. The experiment has been carried out with an array of eight AgReO4 thermal detectors operating at a temperature of approximately 100 mK. A fit of the observed BEFS spectrum indicates the p-wave electron emission as the dominant channel. The complete understanding of the BEFS distortion of the 187Re beta decay spectrum is crucial for future experiments aiming at the precise calorimetric measurement of the antineutrino mass.

New limit on the neutrinoless betabeta decay of 130Te.

We report the present results of CUORICINO, a search for neutrinoless double-beta (0nu betabeta) decay of 130Te. The detector is an array of 62 TeO2 bolometers with a total active mass of 40.7 kg. The array is cooled by a dilution refrigerator shielded from environmental radioactivity and energetic neutrons, operated at approximately 8 mK in the Gran Sasso Underground Laboratory. No evidence for (0nu betabeta) decay was found and a new lower limit, T(1/2)(0nu) > or = 1.8 x 10(24) yr (90% C.L.) is set, corresponding to [m(nu)] < or = 0.2 to 1.1 eV, depending on the theoretical nuclear matrix elements used in the analysis.