Measurement of the Spectral Shape of the ß-Decay of

We report on a comparison between the theoretically predicted and experimentally measured spectra of the first-forbidden nonunique ß-decay transition ^{137}Xe(7/2^{-})→^{137}Cs(7/2^{+}). The experimental data were acquired by the EXO-200 experiment during a deployment of an AmBe neutron source. The ultralow background environment of EXO-200, together with dedicated source deployment and analysis procedures, allowed for collection of a pure sample of the decays, with an estimated signal to background ratio of more than 99 to 1 in the energy range from 1075 to 4175 keV. In addition to providing a rare and accurate measurement of the first-forbidden nonunique ß-decay shape, this work constitutes a novel test of the calculated electron spectral shapes in the context of the reactor antineutrino anomaly and spectral bump.

Search for Neutrinoless Double-ß Decay with the Complete EXO-200 Dataset.

A search for neutrinoless double-ß decay (0νßß) in ^{136}Xe is performed with the full EXO-200 dataset using a deep neural network to discriminate between 0νßß and background events. Relative to previous analyses, the signal detection efficiency has been raised from 80.8% to 96.4±3.0%, and the energy resolution of the detector at the Q value of ^{136}Xe 0νßß has been improved from σ/E=1.23% to 1.15±0.02% with the upgraded detector. Accounting for the new data, the median 90% confidence level 0νßß half-life sensitivity for this analysis is 5.0×10^{25} yr with a total ^{136}Xe exposure of 234.1 kg yr. No statistically significant evidence for 0νßß is observed, leading to a lower limit on the 0νßß half-life of 3.5×10^{25} yr at the 90% confidence level.

Search for Neutrinoless Double-Beta Decay with the Upgraded EXO-200 Detector.

Results from a search for neutrinoless double-beta decay (0νßß) of ^{136}Xe are presented using the first year of data taken with the upgraded EXO-200 detector. Relative to previous searches by EXO-200, the energy resolution of the detector has been improved to σ/E=1.23%, the electric field in the drift region has been raised by 50%, and a system to suppress radon in the volume between the cryostat and lead shielding has been implemented. In addition, analysis techniques that improve topological discrimination between 0νßß and background events have been developed. Incorporating these hardware and analysis improvements, the median 90% confidence level 0νßß half-life sensitivity after combining with the full data set acquired before the upgrade has increased twofold to 3.7×10^{25} yr. No statistically significant evidence for 0νßß is observed, leading to a lower limit on the 0νßß half-life of 1.8×10^{25} yr at the 90% confidence level.

An apparatus to manipulate and identify individual Ba ions from bulk liquid Xe.

We describe a system to transport and identify barium ions produced in liquid xenon, as part of R&D towards the second phase of a double beta decay experiment, nEXO. The goal is to identify the Ba ion resulting from an extremely rare nuclear decay of the isotope (136)Xe, hence providing a confirmation of the occurrence of the decay. This is achieved through Resonance Ionization Spectroscopy (RIS). In the test setup described here, Ba ions can be produced in liquid xenon or vacuum and collected on a clean substrate. This substrate is then removed to an analysis chamber under vacuum, where laser-induced thermal desorption and RIS are used with time-of-flight mass spectroscopy for positive identification of the barium decay product.

Search for neutrinoless double-beta decay in 136Xe with EXO-200.

We report on a search for neutrinoless double-beta decay of 136Xe with EXO-200. No signal is observed for an exposure of 32.5 kg yr, with a background of ∼1.5×10(-3) kg(-1) yr(-1) keV(-1) in the ±1σ region of interest. This sets a lower limit on the half-life of the neutrinoless double-beta decay T(1/2)(0νßß)(136Xe)>1.6×10(25) yr (90% C.L.), corresponding to effective Majorana masses of less than 140-380 meV, depending on the matrix element calculation.

Observation of two-neutrino double-beta decay in 136Xe with the EXO-200 detector.

We report the observation of two-neutrino double-beta decay in (136)Xe with T(1/2) = 2.11 ± 0.04(stat) ± 0.21(syst) × 10(21) yr. This second-order process, predicted by the standard model, has been observed for several nuclei but not for (136)Xe. The observed decay rate provides new input to matrix element calculations and to the search for the more interesting neutrinoless double-beta decay, the most sensitive probe for the existence of Majorana particles and the measurement of the neutrino mass scale.

A magnetically driven piston pump for ultra-clean applications.

A magnetically driven piston pump for xenon gas recirculation is presented. The pump is designed to satisfy extreme purity and containment requirements, as is appropriate for the recirculation of isotopically enriched xenon through the purification system and large liquid xenon time projection chamber of EXO-200. The pump, using sprung polymer gaskets, is capable of pumping more than 16 standard liters per minute of xenon gas with 750 Torr differential pressure.

A simple radionuclide-driven single-ion source.

We describe a source capable of producing single barium ions through nuclear recoils in radioactive decay. The source is fabricated by electroplating (148)Gd onto a silicon α-particle detector and vapor depositing a layer of BaF(2) over it. (144)Sm recoils from the alpha decay of (148)Gd are used to dislodge Ba(+) ions from the BaF(2) layer and emit them in the surrounding environment. The simultaneous detection of an α particle in the substrate detector allows for tagging of the nuclear decay and of the Ba(+) emission. The source is simple, durable, and can be manipulated and used in different environments. We discuss the fabrication process, which can be easily adapted to emit most other chemical species, and the performance of the source.

Highly specific interactions between botulinum neurotoxins and synaptic vesicle proteins.

Despite its extreme toxicity, botulinum neurotoxin is widely utilized in low doses as a treatment for several neurological disorders; higher doses cause the neuroparalytic syndrome botulism. The toxin blocks neurotransmitter release by preferentially attaching to pre-synaptic membrane receptors at neuromuscular junctions and subsequently delivering a Zn2+-dependent protease component to presynaptic neuronal cytosol. These highly specialized enzymes exclusively hydrolyze peptide bonds within SNARE (soluble N-ethylmaleiamide sensitive factor attachment protein receptor) proteins. In this review we discuss the structural basis for botulinum toxin's exquisite specificity for its neuronal cell-surface receptors and intracellular SNARE targets.

Current developments in adenovirus-based cancer gene therapy.

Adenovirus (Ad)-based cancer gene therapy is a promising, novel approach for treating cancer resistant to established treatment modalities. Unfortunately, the efficacy of nonreplicative first generation Ads was low and data from clinical trials were disappointing. To address this problem, conditionally replicating Ads have been constructed. Infection of tumor cells with conditionally replicating Ads results in tumor-specific replication, subsequent oncolysis and release of the virus progeny. Recently, it has been suggested that the low expression of the coxsackie-Ad receptor is the rate-limiting factor for infectivity with serotype 5 (Ad5). Unfortunately, coxsackie-Ad receptor expression is highly variable and often low on many tumor types. Consequently, molecular strategies have been applied for the development of coxsackie-Ad receptor-independent oncolytic Ads. This review describes recent developments of Ad-based cancer gene therapy, including novel engineering techniques of the Ad capsid for efficient tumor targeting, as well as targeting techniques, to restrict transgene expression to cancer cells.

Direct measurements of Ab and Ac using vertex and kaon charge tags at the SLAC detector.

Exploiting the manipulation of the SLAC Linear Collider electron-beam polarization, we present precise direct measurements of the parity-violation parameters A(c) and A(b) in the Z-boson-c-quark and Z-boson-b-quark coupling. Quark-antiquark discrimination is accomplished via a unique algorithm that takes advantage of the precise SLAC Large Detector charge coupled device vertex detector, employing the net charge of displaced vertices as well as the charge of kaons that emanate from those vertices. From the 1996-1998 sample of 400 000 Z decays, produced with an average beam polarization of 73.4%, we find A(c)=0.673+/-0.029(stat)+/-0.023(syst) and A(b)=0.919+/-0.018(stat)+/-0.017(syst).

Differential indication for histological evaluation of endometrial fluid in postmenopause.

OBJECTIVES: The endometrium carcinoma is the most frequent malignancy of the female genital tract. Approximately, 10-20% of all patients with an endometrial carcinoma are free of symptoms until the time of diagnosis. The frequent occurrence of an endometrial carcinoma in connection with intrauterine cavity fluid collection (sero- or mucometra) has been discussed controversially in literature. What are the hysteroscopic and histological findings in patients with sonographically determined endometrial fluid in postmenopause, and how should these findings be interpreted? METHODS: 74 patients, in whom endometrial fluid without bleeding disorders had been diagnosed during routine transvaginal sonography, underwent hysteroscopy conducted with a 4.5 mm optics and dilatation and curettage (D&C). The median age of the patients was 68 years with a range of 32 years. RESULTS: The simple thickness of the endometrium, i.e. single layer measured sonographically at the point of maximal thickness, was on average 5.7 mm +/- 3.6 mm (2-15 mm). Hysteroscopically, an endometrium polyp was found in 23 cases (31.1%), endometrium hyperplasia in 12 (16.2%), and an atrophy in 35 cases (47.3%). In four cases (5.4%), an endometrial carcinoma was suspected. The histological results were consistent with the hysteroscopic findings. In all instances, in which the simple endometrial thickness amounted to 3 mm or less, an atrophic endometrium was found. The frequency of intrauterine pathologies increased significantly with a greater thickness of the endometrium. In 80% of patients, a cervical stenosis existed. CONCLUSIONS: Endometrial fluid by itself, without assessment of the endometrium, does not indicate the requirement for additional histological clarification. As diagnostics, the authors suggest especially the endometrial morphology.

Mesothelin-mediated targeting of adenoviral vectors for ovarian cancer gene therapy.

Adenoviruses (Ads) are efficient gene transfer vehicles, but Ad-mediated gene therapy for ovarian cancer remains limited in vivo by inefficient and nonspecific gene transfer. Mesothelin (MSLN), a cell surface glycoprotein, is overexpressed in ovarian cancer but not in normal tissues except mesothelial cells. Therefore, MSLN is an attractive candidate for transcriptional and transductional targeting in the context of ovarian cancer gene therapy. We evaluated the expression of MSLN mRNA and MSLN surface protein in ovarian cancer cells. Ads containing the MSLN promoter driving reporter gene expression were created and tested in ovarian cancer cell lines and purified ovarian cancer cells isolated from patients. To evaluate transductional targeting, we used an Ad vector containing an Fc-binding domain within the fiber protein, which served as a docking domain for binding with anti-MSLN immunoglobulins. Both RT-PCR and flow cytometry revealed high MSLN gene and protein expression in ovarian cancer cells. The MSLN promoter was activated in ovarian cancer cells, but showed significantly reduced activity in normal control cells. Transductional targeting of Ads via anti-MSLN antibody increased transgene expression in ovarian cancer cells. This report describes the use of MSLN for transcriptional as well as transductional targeting strategies for ovarian cancer gene therapy.

Preeclamptic women are deficient of interleukin-10 as assessed by cytokine release of trophoblast cells in vitro.

BACKGROUND: It is well known that the acceptance of the fetoplacental unit in human pregnancy requires maternal immune tolerance, which is thought to be regulated locally by the placenta. Therefore an anti-inflammatory cytokine such as IL-10 plays a critical role in different pregnancy disorders including preeclampsia. In the present study, we examined the expression of both proinflammatory (TNF-alpha, IL-1beta, IL-2) and immunoregulatory (IL-6, IL-10) cytokines from normal term and preeclamptic patients in human trophoblast cultures. METHODS: Eleven patients with preeclampsia and 11 patients with a normal pregnancy at term were included in the study. Trophoblast cells isolated from placentas were cultured up to 48 h under standard tissue culture conditions and cytokine release was determined by ELISA. IL-10 synthesis was significantly decreased in the third trimester in preeclamptic patients in comparison with the control group. RESULTS: There were no significant differences in IL-1beta, IL-2, IL-6 or TNF-alpha expression but a significant alteration in IL-10 release in trophoblast cultures in vitro in term placentas from preeclamptic patients compared with normal pregnancy. CONCLUSIONS: Because IL-10 is a potent regulator of anti-inflammatory immune response these abnormalities may be associated with the inadequate placental development in preeclampsia.

Improved direct measurement of the parity-violation parameter Ab using a mass tag and momentum-weighted track charge.

We present an improved direct measurement of the parity-violation parameter A(b) in the Z boson-b-quark coupling using a self-calibrating track-charge technique applied to a sample enriched in Z-->bb events via the topological reconstruction of the B hadron mass. Manipulation of the Stanford Linear Collider electron-beam polarization permits the measurement of A(b) to be made independently of other Z-pole coupling parameters. From the 1996-1998 sample of 400,000 hadronic Z decays, produced with an average beam polarization of 73.4%, we find A(b)=0.906+/-0.022(stat)+/-0.023(syst).

Weekly carboplatin and docetaxel for locally advanced primary and recurrent cervical cancer: a phase I study.

OBJECTIVE: The aim of this study was to determine the dose-limiting toxicities (DLTs) and maximum tolerated doses (MTDs) of a docetaxel-carboplatin regimen in patients with locally advanced cervical cancer (LACC) or recurrent cervical cancer. The regimen was administered weekly, with a maximum of 12 courses. PATIENTS AND METHODS: Twenty patients were treated with with a total of 145 cycles of weekly carboplatin and docetaxel. The starting dose of docetaxel was 25 mg/m(2) with increments of 5 mg/m(2) until a final dose of 35 mg/m(2) was reached. Dose-escalation of docetaxel was followed by carboplatin at AUC 2, AUC 2.5, and AUC 3, respectively. Defined dose-limiting toxicities were WHO grade (G) 3 hematotoxicity, G4 mucositis, and G2 neurotoxicity. The response status of the patients was assessed using the common ECOG response criteria. RESULTS: Two of four patients developed a DLT at dose level 4. Nonhematological toxicity was generally mild, except for ubiquitous complete alopecia. The MTD was reached at docetaxel 35 mg/m(2) and carboplatin AUC 2 mg/mL.min. The overall response rate was 65% in the entire group of evaluable patients and 77% in patients with primary LACC, with two cases of pathological complete response. CONCLUSION: This dose-dense regimen was well-tolerated and could be administered on an outpatient basis.

Improved direct measurement of A(b) and A(c) at the Z(0) pole using a lepton tag.

The parity violation parameters A(b) and A(c) of the Zb(b) and Zc(c) couplings have been measured directly, using the polar angle dependence of the polarized cross sections at the Z(0) pole. Bottom and charmed hadrons were tagged via their semileptonic decays. Both the electron and muon analyses take advantage of new multivariate techniques to increase the analyzing power. Based on the 1993-1998 SLD sample of 550,000 Z(0) decays produced with highly polarized electron beams, we measure A(b) = 0.919+/-0.030(stat)+/-0.024(syst), and A(c) = 0.583+/-0.055(stat)+/-0.055(syst).

First symmetry tests in polarized Z0 decays to bbg.

We have made the first direct symmetry tests in the decays of polarized Z0 bosons into fully identified bbg states, collected in the SLD experiment at SLAC. We searched for evidence of parity violation at the bbg vertex by studying the asymmetries in the b-quark polar- and azimuthal-angle distributions, and for evidence of T-odd, CP-even or CP-odd, final-state interactions by measuring angular correlations between the three-jet plane and the Z0 polarization. We found results consistent with standard model expectations and set 95% C. limits on anomalous contributions.

Improved direct measurement of leptonic coupling asymmetries with polarized Z bosons.

We present final measurements of the Z boson-lepton coupling asymmetry parameters A(e), A(mu), and A(tau) with the complete sample of polarized Z bosons collected by the SLD detector at the SLAC Linear Collider. From the left-right production and decay polar angle asymmetries in leptonic Z decays we measure A(e) = 0.1544+/-0.0060, A(mu) = 0.142+/-0.015, and A(tau) = 0.136+/-0.015. Combined with our left-right asymmetry measured from hadronic decays, we find A(e) = 0.1516+/-0.0021. Assuming lepton universality, we obtain a combined effective weak mixing angle of sin (2)theta(eff)(W) = 0.230 98+/-0.000 26.

High-precision measurement of the left-right Z Boson cross-section asymmetry.

We present a measurement of the left-right cross-section asymmetry ( A(LR)) for Z boson production by e(+)e(-) collisions. The measurement includes the final data taken with the SLD detector at the SLAC Linear Collider during the period 1996-1998. Using a sample of 383 487 Z decays collected during the 1996-1998 runs we measure the pole value of the asymmetry, A(0)(LR), to be 0.150 56+/-0.002 39 which is equivalent to an effective weak mixing angle of sin (2)straight theta(eff)(W) = 0.231 07+/-0.000 30. Our result for the complete 1992-1998 data set comprising approximately 537 000 Z decays is sin (2)straight theta(eff)(W) = 0.230 97+/-0.000 27.