A Search for the Double-Beta Decay of Xe-136 to an Excited State of Ba-136 with EXO-200

This thesis presents a search for the two neutrino double beta decay (ββ2ν) of 136Xe to the 0+1 excited state of 136Ba using data from the EXO-200 detector collected between 2011 and 2012. The ββ2ν decay to the excited state is a process that have been observed for other double beta decay nuclei. An observation of this decay would shed some light on the validities of the various nuclear physics models. Located at the Waste Isolation Pilot Plant (WIPP) near Carlsbad, NM, EXO-200 is a liquid xenon time projection chamber filled with 200 kg of 80.6% isotopically enriched 136Xe. The liquid xenon serves both as the decay source and the detection medium. Maximum likelihood fits of the sum energy spectra based on Monte Carlo simulations are used to constrain the number of ββ2ν decay to the 0+1 excited state of 136Ba. A half-life lower limit on this decay of 1.2 · 1023 year at 90% C.L is set, still a couple orders of magnitude from our expected theoretical rate of 2.5 · 1025 year from the applying the calculated phase space factor and the nuclear matrix element suppressions on the measured ββ2ν decay to the ground state. A developing analysis using a new energy variable designed specifically for the search of the decay to the excited state is also discussed

The mature EV71 virion induced a broadly cross-neutralizing VP1 antibody against subtypes of the EV71 virus.

Enterovirus 71 (EV71) has emerged as a neurological virus causing life-threatening diseases in young children and infants. Although EV71 vaccines in development have presented promising results in several clinical trials, the identified key antigen for improving the broad protective efficacy of EV71 vaccines has not been well investigated. In this report, we show that different multiplicities of infection (MOIs) of the B4(E59) virus significantly affect EV71 vaccine production in a serum-free microcarrier bioreactor system. The antigens produced from high MOIs of 10-1 and 10-2 exhibited higher yield and more infectious full particle (FP) contents in the EV71 vaccines than those produced with low MOIs of 10-4 and 10-6, leading to better cross-neutralizing efficacy. The C4(E36) neutralization results showed that only antisera raised from EV71 FPs provided substantial neutralizing titers against C4(E36), whereas empty particles (EPs) of EV71 conferred no efficacy. Competitive ELISA showed that anti-FP mainly binds to FPs and that 20% of antibodies bind to EPs, whereas most anti-EP binds EPs, with only 10% antibodies binding to FPs. VP1-adsorbed anti-FP lost most of the virus neutralization efficiency, suggesting that the VP1 subunit of FP is the major immunogenic antigen determining the ability of the EV71 vaccine to elicit cross-neutralizing antibodies against EV71 virus subtypes. These findings demonstrate that the high-MOI production approach is significantly correlated with FP productivity, thereby improving the cross-neutralization efficacy of an EV71 vaccine and providing the basis for a better vaccine design against widespread EV71 viruses

Development of a highly sensitive glycan microarray for quantifying AFP-L3 for early prediction of hepatitis B virus-related hepatocellular carcinoma.

The α-fetoprotein fraction L3 (AFP-L3), which is synthesized by malignant cells and incorporates a fucosylated oligosaccharide, has been investigated as a diagnostic and prognostic marker for hepatocellular carcinoma (HCC). Quantification of AFP-L3 by conventional enzyme-linked immunosorbent assay (ELISA) has not always produced reliable results for serum samples with low AFP, and thus we evaluated the clinical utility of quantifying AFP-L3 using a new and highly sensitive glycan microarray assay. Sera from 9 patients with chronic hepatitis B and 32 patients with hepatitis B virus (HBV)-related HCC were tested for AFP-L3 level using the glycan microarray. Additionally, we compared receiver operator characteristic curves for the ELISA and glycan microarray methods for determination of the AFP-L3: AFP-L1 ratio in patient samples. This ratio was calculated for 8 HCC patients who underwent transarterial embolization therapy pre- or post-treatment with AFP-L3. Glycan microarrays showed that the AFP-L3 ratio of HBV-related HCC patients was significantly higher than that measured for chronic hepatitis B patients. Overall parameters for estimating AFP-L3% in HCC samples were as follows: sensitivity, 53.13%; specificity, 88.89%; and area under the curve, 0.75. The elevated AFP-L3% in the 8 patients with HBV-related HCC was strongly associated with HCC progression. Following one month of transarterial embolization therapy, the relative mean AFP-L3% decreased significantly. In addition, we compared Fut8 gene expression between paired tumor and non-tumor tissues from 24 patients with HBV-related HCC. The Fut8 mRNA expression was significantly increased in tumorous tissues in these patients than that in non-tumor tissue controls. Higher expression of Fut8 mRNA in tumorous tissues in these patients was associated with poor differentiation than well and moderate differentiation. Our results describe a new glycan microarray for the sensitive and rapid quantification of fucosylated AFP; this method is potentially applicable to screening changes in AFP-L3 level for assessment of HCC progression

Values for reactivity of AFP-L3% and AFP at different times for patients with HCC.

<p>(A) Dynamic changes of AFP-L3% in each HCC patient. The results of the assay showed that AFP-L3% level had increased significantly at point in late time (n = 8; *<i>P</i><0.05). (B) AFP-L3% and AFP values at different time points for patients with HCC.</p

Psoas muscle area is an independent survival prognosticator in patients undergoing surgery for long‐bone metastases

Abstract Background Predictive analytics is gaining popularity as an aid to treatment planning for patients with bone metastases, whose expected survival should be considered. Decreased psoas muscle area (PMA), a morphometric indicator of suboptimal nutritional status, has been associated with mortality in various cancers, but never been integrated into current survival prediction algorithms (SPA) for patients with skeletal metastases. This study investigates whether decreased PMA predicts worse survival in patients with extremity metastases and whether incorporating PMA into three modern SPAs (PATHFx, SORG‐NG, and SORG‐MLA) improves their performance. Methods One hundred eighty‐five patients surgically treated for long‐bone metastases between 2014 and 2019 were divided into three PMA tertiles (small, medium, and large) based on their psoas size on CT. Kaplan–Meier, multivariable regression, and Cox proportional hazards analyses were employed to compare survival between tertiles and examine factors associated with mortality. Logistic regression analysis was used to assess whether incorporating adjusted PMA values enhanced the three SPAs' discriminatory abilities. The clinical utility of incorporating PMA into these SPAs was evaluated by decision curve analysis (DCA). Results Patients with small PMA had worse 90‐day and 1‐year survival after surgery (log‐rank test p 0.5 after the addition of adjusted PMA to these SPAs. Conclusions Decreased PMA on CT is associated with worse survival in surgically treated patients with extremity metastases, even after controlling for three contemporary SPAs. Physicians should consider the additional prognostic value of PMA on survival in patients undergoing consideration for operative management due to extremity metastases

The glycan microarray utilized in the study.

<p>(A) Schematic of chemically synthesized oligosaccharides (AFP-L1 and AFP-L3 fragments). (B) Illustration of the characterization and quantification of the oligosaccharides immobilized on the supporting surface. Cy3-labeled antibody is added and binds to the captured analyte. (C) Readout by fluorescence scanner.</p

Comparison of AFP-L3% at pre- and post-TAE treatment.

<p>Post-treatment AFP-L3% values (0.38±0.09) were significantly lower than the pre-treatment point time (0.57±0.16) in different patients (n = 8; *<i>P</i><0.05).</p

Fut8 expression is increased in HCC tumor tissues.

<p>(A) The Fut8 mRNA levels were evaluated in HCC tumor tissue compared normal liver tissue from the same patients (n = 24; *, <i>P</i><0.05). (B) Association between Fut8 levels and histologic grade (*, <i>P</i><0.05).</p