ADC Nonlinearity Correction for the Majorana Demonstrator

Imperfections in analog-to-digital conversion (ADC) cannot be ignored when signal digitization requirements demand both wide dynamic range and high resolution, as is the case for the Majorana Demonstrator 76Ge neutrinoless double-beta decay search. Enabling the experiment's high-resolution spectral analysis and efficient pulse shape discrimination required careful measurement and correction of ADC nonlinearities. A simple measurement protocol was developed that did not require sophisticated equipment or lengthy data-taking campaigns. A slope-dependent hysteresis was observed and characterized. A correction applied to digitized waveforms prior to signal processing reduced the differential and integral nonlinearities by an order of magnitude, eliminating these as dominant contributions to the systematic energy uncertainty at the double-beta decay Q value

Results of the MAJORANA DEMONSTRATOR's Search for Double-Beta Decay of 76Ge to Excited States of 76Se

The MAJORANA DEMONSTRATOR is searching for double-beta decay of 76Ge to excited states (E.S.) in 76Se using a modular array of high purity Germanium detectors. 76Ge can decay into three E.S.s of 76Se. The E.S. decays have a clear event signature consisting of a ββ-decay with the prompt emission of one or two γ-rays, resulting in with high probability in a multi-site event. The granularity of the DEMONSTRATOR detector array enables powerful discrimination of this event signature from backgrounds. Using 21.3 kg-y of isotopic exposure, the DEMONSTRATOR has set world leading limits for each E.S. decay, with 90% CL lower half-life limits in the range of (0.56 2.1) ⋅ 1024 y. In particular, for the 2v transition to the first 0+ E.S. of 76Se, a lower half-life limit of 0.68 ⋅ 1024 at 90% CL was achieved

Observation of Coherent Elastic Neutrino-Nucleus Scattering

The coherent elastic scattering of neutrinos off nuclei has eluded detection for four decades, even though its predicted cross-section is the largest by far of all low-energy neutrino couplings. This mode of interaction provides new opportunities to study neutrino properties, and leads to a miniaturization of detector size, with potential technological applications. We observe this process at a 6.7-sigma confidence level, using a low-background, 14.6-kg CsI[Na] scintillator exposed to the neutrino emissions from the Spallation Neutron Source (SNS) at Oak Ridge National Laboratory. Characteristic signatures in energy and time, predicted by the Standard Model for this process, are observed in high signal-to-background conditions. Improved constraints on non-standard neutrino interactions with quarks are derived from this initial dataset

Characterisation and testing of CHEC-M—A camera prototype for the small-sized telescopes of the Cherenkov telescope array

The Compact High Energy Camera (CHEC) is a camera design for the Small-Sized Telescopes (SSTs; 4 m diameter mirror) of the Cherenkov Telescope Array (CTA). The SSTs are focused on very-high-energy γ-ray detection via atmospheric Cherenkov light detection over a very large area. This implies many individual units and hence cost-effective implementation, as well as shower detection at large impact distance, and hence large field of view (FoV), and efficient image capture in the presence of large time gradients in the shower image detected by the camera. CHEC relies on dual-mirror optics to reduce the plate-scale and make use of 6 × 6 mm2pixels, leading to a low-cost (∼150 k€), compact (0.5 m × 0.5 m), and light (∼45 kg) camera with 2048 pixels providing a camera FoV of ∼9 degrees. The CHEC electronics are based on custom TARGET (TeV array readout with GSa/s sampling and event trigger) application-specific integrated circuits (ASICs) and field programmable gate arrays (FPGAs) sampling incoming signals at a gigasample per second, with flexible camera-level triggering within a single backplane FPGA. CHEC is designed to observe in the γ-ray energy range of 1–300 TeV, and at impact distances up to ∼500 m. To accommodate this and provide full flexibility for later data analysis, full waveforms with 96 samples for all 2048 pixels can be read out at rates up to ∼900 Hz. The first prototype, CHEC-M, based on multi-anode photomultipliers (MAPMs) as photosensors, was commissioned and characterised in the laboratory and during two measurement campaigns on a telescope structure at the Paris Observatory in Meudon. In this paper, the results and conclusions from the laboratory and on-site testing of CHEC-M are presented. They have provided essential input on the system design and on operational and data analysis procedures for a camera of this type. A second full-camera prototype based on Silicon photomultipliers (SiPMs), addressing the drawbacks of CHEC-M identified during the first prototype phase, has already been built and is currently being commissioned and tested in the laboratory

Expression of Osteopontin in oesophageal squamous cell carcinoma

Osteopontin is a multifunctional 34 kDa extracellular matrix protein with a cell-binding domain. It is involved cell adhesion and cell migration and is therefore considered to influence tumorigenesis and/or metastasis. The purpose of the present study was to evaluate the clinical significance of Osteopontin expression in oesophageal squamous cell carcinoma (ESCC). In the present study, we immunohistochemically investigated the relationship between Osteopontin expression and clinicopathological factors including prognosis in surgical specimens of primary tumours in 175 patients with ESCC. Osteopontin was expressed in 48% of 175 patients. Osteopontin expression was significantly correlated with lymph node metastasis, lymphatic invasion, and stage (P=0.0015, 0.037 and 0.033, respectively). Tumours with expressing Osteopontin exhibited more lymph node metastasis, lymphatic invasion and advanced stage than the tumour with negative Osteopontin expression. Five-year survival rate was better in patients with negative Osteopontin expression than in those with positive Osteopontin expression (P=0.035). However, multivariate analysis revealed that Osteopontin expression was not an independent prognostic factor. As our findings suggest that Osteopontin may play an important role in progress of ESCC, the evaluation of Osteopontin expression is useful for predicting the malignant properties of ESCC

Preterm Birth in Caucasians Is Associated with Coagulation and Inflammation Pathway Gene Variants

Spontaneous preterm birth (<37 weeks gestation—PTB) occurs in ∼12% of pregnancies in the United States, and is the largest contributor to neonatal morbidity and mortality. PTB is a complex disease, potentially induced by several etiologic factors from multiple pathophysiologic pathways. To dissect the genetic risk factors of PTB a large-scale high-throughput candidate gene association study was performed examining 1536 SNP in 130 candidate genes from hypothesized PTB pathways. Maternal and fetal DNA from 370 US Caucasian birth-events (172 cases and 198 controls) was examined. Single locus, haplotype, and multi-locus association analyses were performed separately on maternal and fetal data. For maternal data the strongest associations were found in genes in the complement-coagulation pathway related to decidual hemorrhage in PTB. In this pathway 3 of 6 genes examined had SNPs significantly associated with PTB. These include factor V (FV) that was previously associated with PTB, factor VII (FVII), and tissue plasminogen activator (tPA). The single strongest effect was observed in tPA marker rs879293 with a significant allelic (p = 2.30×10−3) and genotypic association (p = 2.0×10−6) with PTB. The odds ratio (OR) for this SNP was 2.80 [CI 1.77–4.44] for a recessive model. Given that 6 of 8 markers in tPA were statistically significant, sliding window haplotype analyses were performed and revealed an associating 4 marker haplotype in tPA (p = 6.00×10−3). The single strongest effect in fetal DNA was observed in the inflammatory pathway at rs17121510 in the interleukin-10 receptor antagonist (IL-10RA) gene for allele (p = 0.01) and genotype (p = 3.34×10−4). The OR for the IL-10RA genotypic additive model was 1.92 [CI 1.15–3.19] (p = 2.00×10−3). Finally, exploratory multi-locus analyses in the complement and coagulation pathway were performed and revealed a potentially significant interaction between a marker in FV (rs2187952) and FVII (rs3211719) (p<0.001). These results support a role for genes in both the coagulation and inflammation pathways, and potentially different maternal and fetal genetic risks for PTB

Biomass and Burning Characteristics of Sugar Pine Cones

We investigated the physical and burning characteristics of sugar pine (Pinus lambertiana Douglas) cones and their contribution to woody surface fuel loadings. Field sampling was conducted at the Yosemite Forest Dynamics Plot (YFDP), a 25.6 ha mapped study plot in Yosemite National Park, California, USA. We developed a classification system to describe sugar pine cones of different sizes and decay conditions, and examined differences among cone classes in biomass, bulk density, flame length, burning time, consumption, and relative contribution to surface fuel loads. Sugar pine cones comprised 601 kg ha-1 of surface fuels. Mature cones comprised 54% of cone biomass, and aborted juvenile cones accounted for 44%. Cone biomass, diameter, and bulk density differed among cone condition classes, as did burning characteristics (one-way ANOVA, P \u3c 0.001 in all cases). Flame lengths ranged from 5 cm to 94 cm for juvenile cones, and 71 cm to 150 cm for mature cones. Our results showed that the developmental stage at which sugar pine cones become surface fuels determines their potential contribution to surface fire behavior in Sierra Nevada mixed-conifer forests. Sugar pine cones burn with greater flame lengths and flame times than the cones of other North American fire-tolerant pine species studied to date, indicating that cones augment the surface fire regime of sugar pine forests, and likely do so to a greater degree than do cones of other pine species

Molecular imaging of glioblastoma multiforme using anti-insulin-like growth factor-binding protein-7 single-domain antibodies

BACKGROUND: Insulin-like growth factor-binding protein 7 (IGFBP7) is an abundant, selective and accessible biomarker of glioblastoma multiforme (GBM) tumour vessels. In this study, an anti-IGFBP7 single-domain antibody (sdAb) was developed to target GBM vessels for molecular imaging applications. METHODS: Human GBM was modelled in mice by intracranial implantation of U87MG.EGFRvIII cells. An anti-IGFBP7 sdAb, isolated from an immune llama library by panning, was assessed in vitro for its binding affinity using surface plasmon resonance and by ex vivo immunobinding on mouse and human GBM tissue. Tumour targeting by Cy5.5-labelled anti-IGFBP7 sdAb as well as by anti-IGFBP7 sdAb conjugated to PEGylated Fe3O4 nanoparticles (NPs)-Cy5.5 were assessed in U87MG.EGFRvIII tumour-bearing mice in vivo using optical imaging and in brain sections using fluorescent microscopy. RESULTS: Surface plasmon resonance analyses revealed a medium affinity (KD\ufffd40\ufffd50 nM) binding of the anti-IGFBP7 sdAb to the purified antigen. The anti-IGFBP7 sdAb also selectively bound to both mouse and human GBM vessels, but not normal brain vessels in tissue sections. In vivo, intravenously injected anti-IGFBP7 sdAb-Cy5.5 bound to GBM vessels creating high imaging signal in the intracranial tumour. Similarly, the anti-IGFBP7 sdAb-functionalised PEGylated Fe3O4 NP-Cy5.5 demonstrated enhanced tumour signal compared with non-targeted NPs. Fluorescent microscopy confirmed the presence of anti-IGFBP7 sdAb and anti-IGFBP7 sdAb- PEGylated Fe3O4 NPs selectively in GBM vessels. CONCLUSIONS: Anti-IGFBP7 sdAbs are novel GBM vessel-targeting moieties suitable for molecular imaging.Peer reviewed: YesNRC publication: Ye