Extensive telomere erosion is consistent with localised clonal expansions in Barrett’s metaplasia

Barrett’s oesophagus is a premalignant metaplastic condition that predisposes patients to the development of oesophageal adenocarcinoma. However, only a minor fraction of Barrett’s oesophagus patients progress to adenocarcinoma and it is thus essential to determine bio-molecular markers that can predict the progression of this condition. Telomere dysfunction is considered to drive clonal evolution in several tumour types and telomere length analysis provides clinically relevant prognostic and predictive information. The aim of this work was to use high-resolution telomere analysis to examine telomere dynamics in Barrett’s oesophagus. Telomere length analysis of XpYp, 17p, 11q and 9p, chromosome arms that contain key cancer related genes that are known to be subjected to copy number changes in Barrett’s metaplasia, revealed similar profiles at each chromosome end, indicating that no one specific telomere is likely to suffer preferential telomere erosion. Analysis of patient matched tissues (233 samples from 32 patients) sampled from normal squamous oesophagus, Z-line, and 2 cm intervals within Barrett’s metaplasia, plus oesophago-gastric junction, gastric body and antrum, revealed extensive telomere erosion in Barrett’s metaplasia to within the length ranges at which telomere fusion is detected in other tumour types. Telomere erosion was not uniform, with distinct zones displaying more extensive erosion and more homogenous telomere length profiles. These data are consistent with an extensive proliferative history of cells within Barrett’s metaplasia and are indicative of localised clonal growth. The extent of telomere erosion highlights the potential of telomere dysfunction to drive genome instability and clonal evolution in Barrett’s metaplasia

Precise Measurement of the Tau Lifetime

The τ lifetime was measured with the Mark II vertex detector at the storage ring PEP. ττ=(3.20±0.41±0.35)×10-13 sec was found, which agrees well with e-μ-τ university. © 1983 The American Physical Society

Macrophage Migration Inhibitory Factor Antagonist Blocks the Development of Endometriosis In Vivo

Endometriosis, a disease of reproductive age women, is a major cause of infertility, menstrual disorders and pelvic pain. Little is known about its etiopathology, but chronic pelvic inflammation is a common feature in affected women. Beside symptomatic treatment of endometriosis-associated pain, only two main suboptimal therapeutic approaches (hormonal and invasive surgery) are generally recommended to patients and no specific targeted treatment is available. Our studies led to the detection of a marked increase in the expression of macrophage migration inhibitory factor (MIF) in the eutopic endometrium, the peripheral blood and the peritoneal fluid of women with endometriosis, and in early, vascularized and active endometriotic lesions. Herein, we developed a treatment model of endometriosis, where human endometrial tissue was first allowed to implant into the peritoneal cavity of nude mice, to assess in vivo the effect of a specific antagonist of MIF (ISO-1) on the progression of endometriosis and evaluate its efficacy as a potential therapeutic tool. Administration of ISO-1 led to a significant decline of the number, size and in situ dissemination of endometriotic lesions. We further showed that ISO-1 may act by significantly inhibiting cell adhesion, tissue remodeling, angiogenesis and inflammation as well as by altering the balance of pro- and anti-apoptotic factors. Actually, mice treatment with ISO-1 significantly reduced the expression of cell adhesion receptors αv and ß3 integrins (P<0.05), matrix metalloproteinases (MMP) 2 and 9 (P<0.05), vascular endothelial cell growth factor (VEGF) (P<0.01), interleukin 8 (IL8) (P<0.05), cyclooxygenease (COX)2 (P<0.001) and the anti-apoptotic protein Bcl2 (P<0.01), but significantly induced the expression of Bax (P<0.05), a potent pro-apoptotic protein. These data provide evidence that specific inhibition of MIF alters endometriotic tissue growth and progression in vivo and may represent a promising potential therapeutic avenue

First search for Lorentz and CPT violation in double beta decay with EXO-200

A search for Lorentz- and CPT-violating signals in the double beta decay spectrum of Xe-136 has been performed using an exposure of 100 kg . yr with the EXO-200 detector. No significant evidence of the spectral modification due to isotropic Lorentz -violation was found, and a two-sided limit of -2.65 x 10(-5) GeV < (a)(of),(,3r) < 7.60 x 10(-6) GeV (90% C.L.) is placed on the relevant coefficient within the Standard -Model Extension (SME). This is the first experimental study of the effect of the SME-defined oscillation -free and momentum-independent neutrino coupling operator on the double beta decay process. © 2016 American Physical Society112111sciescopu

Limits on new-lepton pairs (L-,L0) with arbitrary neutrino mass.

We have searched 205 pb-1 of s =29 GeV data from the Mark II detector at the SLAC e+e- storage ring PEP for events which may signify the existence of a new lepton pair (L-,L0) where the L0 may be massive, but does not exceed the L- mass. Three event signatures for L+L- decay are examined: (i) e, (ii) (e or)(+4), and (iii) (e or )(3+0). The numbers of signature events are found to be in good agreement with Monte Carlo simulations of known background sources. The ranges of L- and L0 masses for which new lepton pairs are excluded are obtained using a likelihood-ratio method to compare the number of observed signature events to the expected background, and to the expected background plus Monte Carlo predictions of (L-,L0) signals. © 1989 The American Physical Society

Kiloton-scale xenon detectors for neutrinoless double beta decay and other new physics searches

Large detectors employing xenon are a leading technology in existing and planned searches for new physics, including searches for neutrinoless double beta decay (0νββ) and dark matter. While upcoming detectors will employ target masses of a ton or more, further extending gas- or liquid-phase Xe detectors to the kton scale would enable extremely sensitive next-generation searches for rare phenomena. The key challenge to extending this technology to detectors well beyond the ton scale is the acquisition of the Xe itself. We describe the motivation for extending Xe time-projection chambers to the kton scale and possible avenues for Xe acquisition that avoid existing supply chains. If acquisition of Xe in the required quantities is successful, kton-scale detectors of this type could enable a new generation of experiments, including searches for 0νββ at half-life sensitivities as long as 1030 yr