Characterization of high purity germanium point contact detectors with low net impurity concentration

High Purity germanium point-contact detectors have low energy thresholds and excellent energy resolution over a wide energy range, and are thus widely used in nuclear and particle physics. In rare event searches, such as neutrinoless double beta decay, the point-contact geometry is of particular importance since it allows for pulse-shape discrimination, and therefore for a significant background reduction. In this paper we investigate the pulse-shape discrimination performance of ultra-high purity germanium point contact detectors. It is demonstrated that a minimal net impurity concentration is required to meet the pulse-shape performance requirements

On Some Open Problems in Many-Electron Theory

Mel Levy and Elliott Lieb are two of the most prominent researchers who have dedicated their efforts to the investigation of fundamental questions in many-electron theory. Their results have not only revolutionized the theoretical approach of the field, but, directly or indirectly, allowed for a quantum jump in the computational treatment of realistic systems as well. For this reason, at the conclusion of our book where the subject is treated across different disciplines, we have asked Mel Levy and Elliott Lieb to provide us with some open problems, which they believe will be a worth challenge for the future also in the perspective of a synergy among the various disciplines.Comment: "Epilogue" chapter in "Many-Electron Approaches in Physics, Chemistry and Mathematics: A Multidisciplinary View", Volker Bach and Luigi Delle Site Eds. pages 411-416; Book Series: Mathematical Physics Studies, Springer International Publishing Switzerland, 2014. The original title has been modified in order to clarify the subject of the chapter out of the context of the boo

52-week efficacy and safety of telbivudine with conditional tenofovir intensification at week 24 in HBeAg-positive chronic Hepatitis B

Background and Aims: The Roadmap concept is a therapeutic framework in chronic hepatitis B for the intensification of nucleoside analogue monotherapy based on early virologic response. The efficacy and safety of this approach applied to telbivudine treatment has not been investigated. Methods: A multinational, phase IV, single-arm open-label study (ClinicalTrials.gov ID NCT00651209) was undertaken in HBeAg-positive, nucleoside-naive adult patients with chronic hepatitis B. Patients received telbivudine (600 mg once-daily) for 24 weeks, after which those with undetectable serum HBV DNA (<300 copies/mL) continued to receive telbivudine alone while those with detectable DNA received telbivudine plus tenofovir (300 mg once-daily). Outcomes were assessed at Week 52. Results: 105 patients commenced telbivudine monotherapy, of whom 100 were included in the efficacy analysis. Fifty-five (55%) had undetectable HBV DNA at Week 24 and continued telbivudine monotherapy; 45 (45%) received tenofovir intensification. At Week 52, the overall proportion of undetectable HBV DNA was 93% (93/100) by last-observation-carried-forward analysis (100% monotherapy group, 84% intensification group) and no virologic breakthroughs had occurred. ALT normalization occurred in 77% (87% monotherapy, 64% intensification), HBeAg clearance in 43% (65% monotherapy, 16% intensification), and HBeAg seroconversion in 39% (62% monotherapy, 11% intensification). Six patients had HBsAg clearance. Myalgia was more common in the monotherapy group (19% versus 7%). No decrease in the mean glomerular filtration rate occurred in either treatment group at Week 52. Conclusions: Telbivudine therapy with tenofovir intensification at Week 24, where indicated by the Roadmap strategy, appears effective and well tolerated for the treatment of chronic hepatitis B. Trial Registration: ClinicalTrials.gov NCT0065120

Neutron scattering sum rules, symmetric exchanges, and helicoidal magnetism in MnSb2O6

MnSb2O6 is based on the noncentrosymmetric P321 space group with magnetic Mn2+ (S=5/2, L≈0) spins ordering below TN=12K in a cycloidal structure. The spin rotation plane was found to be tilted away from the c axis [Kinoshita, Phys. Rev. Lett. 117, 047201 (2016)10.1103/PhysRevLett.117.047201] resulting as a helicoidal ground state, which we refer as the tilted structure. In our previous diffraction study [Chan, Phys. Rev. B 106, 064403 (2022)10.1103/PhysRevB.106.064403] we found no evidence that this tilted structure is favored over the pure cycloidal order (referred as the untilted structure). The ground-state magnetic structure, expected to be built and originate from seven nearest-neighbor Heisenberg exchange constants, has been shown to be coupled to the underlying crystallographic chirality with polar domain switching being reported. We apply neutron spectroscopy to extract these symmetric exchange constants. Given the high complexity of the magnetic exchange network, crystallographic structure and complications fitting many parameter linear spin-wave models, we take advantage of multiplexed neutron instrumentation to use the first moment sum rule of neutron scattering to estimate these symmetric exchange constants. The first moment of neutron scattering provides a way of deriving the Heisenberg exchange constant between two neighboring spins if the relative angle and distance of the two ordered spins is known. We show that the first moment sum rule combined with the known magnetic ordering wavevector fixes six of the seven exchange constants. The remaining exchange constant is not determined by this analysis because of the equal spatial bond distances present for different chiral exchange interactions. However, we find this parameter is fixed by the magnon dispersion near the magnetic zone boundary, which is not sensitive to the tilting of the global magnetic structure. We then use these parameters to calculate the low-energy spin-waves in the Néel state to reproduce the neutron response without strong antisymmetric coupling. Using Green's response functions, the stability of long-wavelength excitations in the context of our proposed untilted magnetic structures is then discussed. The results show the presence of strong symmetric exchange constants for the chiral exchange pathways and illustrate an underlying coupling between crystallographic and magnetic "chirality"through predominantly symmetric exchange. We further argue that the excitations can be consistently modelled in terms of an untilted magnetic structure in the presence of symmetric-only exchange constants

A latent trait approach to measuring HIV/AIDS related stigma in healthcare professionals: application of mokken scaling technique

The attitudes of healthcare professionals towards HIV positive patients and high risk groups are central to the quality of care and therefore to the management of HIV/AIDS related stigma in health settings. Extant HIV/AIDS stigma scales that measure stigmatising attitudes towards people living with HIV/AIDS have been developed using scaling techniques such as principal component analysis. This approach has resulted in instruments that are often long. Mokken scale analysis is a nonparametric hierarchical scaling technique that can be used to develop unidimensional cumulative scales. This technique is advantageous over the other approaches; as the scales are usually shorter, while retaining acceptable psychometric properties. Moreover, Mokken scales also make no distributional assumptions about the underlying data, other than that the data are capable of being ordered by item and by person. In this study we aimed at developing a precise and concise measure of HIV/AIDS related stigma among health care professionals, using Mokken scale analysis

Friedreich ataxia patient tissues exhibit increased 5-hydroxymethylcytosine modification and decreased CTCF binding at the FXN locus

© 2013 Al-Mahdawi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Friedreich ataxia (FRDA) is caused by a homozygous GAA repeat expansion mutation within intron 1 of the FXN gene, which induces epigenetic changes and FXN gene silencing. Bisulfite sequencing studies have identified 5-methylcytosine (5 mC) DNA methylation as one of the epigenetic changes that may be involved in this process. However, analysis of samples by bisulfite sequencing is a time-consuming procedure. In addition, it has recently been shown that 5-hydroxymethylcytosine (5 hmC) is also present in mammalian DNA, and bisulfite sequencing cannot distinguish between 5 hmC and 5 mC.The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement number 242193/EFACTS (CS), the Wellcome Trust [089757] (SA) and Ataxia UK (RMP) to MAP

Identification of chemokine receptors as potential modulators of endocrine resistance in oestrogen receptor–positive breast cancers

Introduction Endocrine therapies target oestrogenic stimulation of breast cancer (BC) growth, but resistance remains problematic. Our aims in this study were (1) to identify genes most strongly associated with resistance to endocrine therapy by intersecting global gene transcription data from patients treated presurgically with the aromatase inhibitor anastrazole with those from MCF7 cells adapted to long-term oestrogen deprivation (LTED) (2) to assess the clinical value of selected genes in public clinical data sets and (3) to determine the impact of targeting these genes with novel agents. Methods Gene expression and Ki67 data were available from 69 postmenopausal women with oestrogen receptor–positive (ER+) early BC, at baseline and 2 weeks after anastrazole treatment, and from cell lines adapted to LTED. The functional consequences of target genes on proliferation, ER-mediated transcription and downstream cell signalling were assessed. Results By intersecting genes predictive of a poor change in Ki67 with those upregulated in LTED cells, we identified 32 genes strongly correlated with poor antiproliferative response that were associated with inflammation and/or immunity. In a panel of LTED cell lines, C-X-C chemokine receptor type 7 (CXCR7) and CXCR4 were upregulated compared to their wild types (wt), and CXCR7, but not CXCR4, was associated with reduced relapse-free survival in patients with ER+ BC. The CXCR4 small interfering RNA variant (siCXCR4) had no specific effect on the proliferation of wt-SUM44, wt-MCF7 and their LTED derivatives. In contrast, siCXCR7, as well as CCX733, a CXCR7 antagonist, specifically suppressed the proliferation of MCF7-LTED cells. siCXCR7 suppressed proteins associated with G1/S transition and inhibited ER transactivation in MCF7-LTED, but not wt-MCF7, by impeding association between ER and proline-, glutamic acid– and leucine-rich protein 1, an ER coactivator. Conclusions These data highlight CXCR7 as a potential therapeutic target warranting clinical investigation in endocrine-resistant BC

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