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.

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.

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.

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.

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.

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.

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.

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.

Tumor necrosis factor alpha and human Schwann cells: signalling and phenotype modulation without cell death.

The aim of the study was to evaluate the biological response of human Schwann cells (SC) to tumor necrosis factor alpha (TNFalpha) in vitro and to the inflammatory milieu of chronic inflammatory demyelinating polyradiculoneuritis (CIDP). By immunocytochemical and functional assays, we found that SC expressed TNF receptors and that TNFalpha promoted in SC cultures transient activation of transcription factors NFkappaB and c-jun in the absence of apoptosis. In addition, TNFalpha significantly increased the proportion of non-myelin-forming SC expressing the p75 nerve growth factor receptor. Such phenotypic effect was dose-dependent and partially mediated by NFkappaB, as assessed by functional blockage with acetylsalicylic acid. We then extended our study to a human disease in which SC are exposed to TNFalpha. Increased signals for NFkappaB, but not c-jun, molecules were observed by immunohistochemistry on SC nuclei in nerve biopsies from patients with CIDP, as compared with controls. Irrespective of the presence of nerve inflammation, SC showed no evidence of apoptosis. Taken together, our results suggested that SC are potential targets of TNFalpha and that this cytokine exerted no cytotoxic effects either in vivo or in vitro. Rather, TNFalpha may influence the fate of SC by activating transcriptional pathways and modulating their phenotype.

HTLV type IIIB infection of human thymic epithelial cells: viral expression correlates with the induction of NF-kappa B-binding activity in cells activated by cell adhesion.

Productive infection by the LAV strain has been demonstrated in T cell precursors at different stages of intrathymic development, while viral replication in thymic epithelial cells is still controversial. In this article we show that epithelial cell cultures derived from the medullary component of normal thymus are infectable by HTLV-IIIB virus through cell-free and lymphoid-mediated transmission. Free virus inoculum results in the integration of proviral copies undergoing poor replication, whereas lymphoid-mediated transmission leads to substantial viral expression and the production of viral progeny able to secondary infect lymphoid cells. Interleukin 6 production and phenotype changes (increased expression of MHC class I and ICAM-1) were induced in TE cells by contact with free virus or by adhesion to infected lymphoid cells. By contrast, NF-kappa B-binding activity on the HIV-1 LTR kappa B enhancer element was upregulated only by contact with infected lymphoid cells, but not with virus. The viral replication observed in TE cells after lymphoid-mediated transmission correlates with the upregulation of NF-kappa B-binding activity. Interleukin 6 increased production and phenotype changes and increased NF-kappa B-binding activity were also induced by adhesion to uninfected lymphoid cells, demonstrating that lymphoepithelial cell contacts can activate TE cells. These results demonstrate that thymic epithelial cells are permissive to HIV infection and that viral replication in this cell lineage can be modulated by intracellular signals delivered by adhesive contacts.

[Lambert-Eaton myasthenic syndrome. Physiopathological aspects and therapeutic modalities]. / Syndrome myasthénique de Lambert-Eaton. Aspects physiopathologiques et modalités thérapeutiques.

A 68-year old man experienced a progressive proximal tetraparesis with anhidrosis and a single episode of horizontal diplopia before presenting exertional dyspnea; pulmonary investigations revealed a small cell carcinoma of the lung. Clinical and electrophysiological investigations with abnormal SFEMG, repetitive stimulations and autonomic assessment pointed to a pre-synaptic neuromuscular dysfunction compatible with a Lambert-Eaton syndrome. Antibodies to acetylcholine receptors and calcium channels were negative. Thoracic radiotherapy combined with chemotherapy produced marked improvement: repeated electrophysiological evaluations showed a strong correlation between median nerve CMAP amplitude and clinical course. This case prompted us to discuss current concepts of pre-synaptic dysfunction, and paraneoplastic syndrome, and to review therapeutic strategies, in the light of recent studies of Lambert-Eaton syndrome.

[Surgical repair of pectus excavatum by internal metal strut fixation. Clinical experience in 51 cases]. / Riparazione chirurgica del petto escavato mediante fissazione interna con barre metalliche. Esperienza clinica su 51 casi.

BACKGROUND: Broad is the spectrum of congenital chest wall deformities. Fortunately the severe life-threatening deformities (i.e. ectopia cordis and Jeune's disease) are rarer than the more frequent pectus excavatum and carinatum. Funnel chest is the most common anterior chest wall deformity, it results from posterior depression of the sternum and cartilages, from the third to the eighth; it occurs more frequently in boys than in girls (4:1 ratio). While the deformity may be recognizable at birth, especially during crying spells, it progressively worsens during childhood, producing, sometimes, respiratory and cardiac impairment. METHODS: The authors report their experience, from April 1970 to December 1998, in correction of Pectus Excavatum using a single surgical technique, at the Borgo Roma Hospital of Verona. During this period 51 patients (mean age 14 years) affected by this deformity, were treated performing a sterno-chondroplasty with internal fixation. Most of the patients (94%) required operation for the esthetic and psychological reasons only. The grade of funnel chest (according to the Chin Classification) was: type I in 59.6% of patients, type II in 31.4% and type III in 11.7%. The surgical technique consisted in the modification of the Ravitch's technique (subperichondrial cartilage resection, transverse osteotomy with internal stainless steel strut fixation). We considered the intervention advisable to correct an existing defect or to prevent its progression. We don't think, in fact, that spontaneous recession of the deformity may occur. RESULTS: The follow-up varied from 4 to 18 years. The result was classified according to the classification of Humphreys and it was excellent in 64.7%, good in 17.7%, fair in 9.8% and poor in 7.8%. CONCLUSIONS: This technique proved to be safe and effective, it can be performed with no mortality, very low complication rate and satisfactory results.

[Transitory carotid ischemic attacks: clinical and pathogenic aspects]. / Accidents ischémiques transitoires carotidiens: aspects cliniques et pathogéniques.

The aim of this study is to describe the clinical characteristics and the pathological mechanisms of carotid transient ischemic attacks (TIA) in 117 patients which were hospitalised for such symptoms. Our results show a male predominance, except for age group under 40 and over 79 years. The principal cardiovascular index and risk factors are: arterial hypertension, smoking, hyperlipidemia, vascular intermittent claudication and hematocrit greater than 46%. Amongst our patients, 17% with hemispherical and mixed TIAs had a cerebral infarction proved by CT-Scan, the recent aspect and localisation of which were compatible with symptoms. The atherosclerotic causes are more frequently associated with mixed and retinal TIAs than hemispheric TIAs. This fact may be attributed to a larger proportion of stenotic atherosclerotic lesions by mixed TIAs than hemispheric ones. The cardiac embolic pathogenic mechanism is responsible for 11% of TIAs if considered individually; of 5% if associated with carotid atherosclerosis.

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.

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.

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.