A spectral decomposition method has been implemented to identify and quantify isotopic source terms in high-resolution gamma-ray spectroscopy in static geometry and shielding scenarios. Monte Carlo ...simulations were used to build the response matrix of a shielded high-purity germanium detector monitoring an effluent stream with a Marinelli configuration. The decomposition technique was applied to a series of calibration spectra taken with the detector using a multi-nuclide standard. These results are compared with decay-corrected values from the calibration certificate. For most nuclei in the standard ( 241 Am, 109 Cd, 137 Cs, and 60 Co), the deviations from the certificate values were generally no more than 6% with a few outliers as high as 10%. For 57 Co, the radionuclide with the lowest activity, the deviations from the standard reached as high as 25%, driven by the meager statistics in the calibration spectra. In addition, a complete treatment of error propagation for the technique is presented.
Allogeneic hematopoietic stem-cell transplantation for X-linked severe combined immunodeficiency (SCID-X1) often fails to reconstitute immunity associated with T cells, B cells, and natural killer ...(NK) cells when matched sibling donors are unavailable unless high-dose chemotherapy is given. In previous studies, autologous gene therapy with γ-retroviral vectors failed to reconstitute B-cell and NK-cell immunity and was complicated by vector-related leukemia.
We performed a dual-center, phase 1-2 safety and efficacy study of a lentiviral vector to transfer
complementary DNA to bone marrow stem cells after low-exposure, targeted busulfan conditioning in eight infants with newly diagnosed SCID-X1.
Eight infants with SCID-X1 were followed for a median of 16.4 months. Bone marrow harvest, busulfan conditioning, and cell infusion had no unexpected side effects. In seven infants, the numbers of CD3+, CD4+, and naive CD4+ T cells and NK cells normalized by 3 to 4 months after infusion and were accompanied by vector marking in T cells, B cells, NK cells, myeloid cells, and bone marrow progenitors. The eighth infant had an insufficient T-cell count initially, but T cells developed in this infant after a boost of gene-corrected cells without busulfan conditioning. Previous infections cleared in all infants, and all continued to grow normally. IgM levels normalized in seven of the eight infants, of whom four discontinued intravenous immune globulin supplementation; three of these four infants had a response to vaccines. Vector insertion-site analysis was performed in seven infants and showed polyclonal patterns without clonal dominance in all seven.
Lentiviral vector gene therapy combined with low-exposure, targeted busulfan conditioning in infants with newly diagnosed SCID-X1 had low-grade acute toxic effects and resulted in multilineage engraftment of transduced cells, reconstitution of functional T cells and B cells, and normalization of NK-cell counts during a median follow-up of 16 months. (Funded by the American Lebanese Syrian Associated Charities and others; LVXSCID-ND ClinicalTrials.gov number, NCT01512888.).
Longitudinal wobbling in 133La Biswas, S.; Palit, R.; Frauendorf, S. ...
The European physical journal. A, Hadrons and nuclei,
09/2019, Letnik:
55, Številka:
9
Journal Article
Recenzirano
.
Excited states of
133
La have been investigated to search for the wobbling excitation mode in the low-spin regime. Wobbling bands with
n
ω
=
0
and 1 are identified along with the interconnecting
Δ
...I
=
1
,
E
2 transitions, which are regarded as one of the characteristic features of wobbling motion. An increase in wobbling frequency with spin implies longitudinal wobbling for
133
La, in contrast with the case of transverse wobbling observed in
135
Pr. This is the first observation of a longitudinal wobbling band in nuclei. The experimental observations are accounted for by calculations using the quasiparticle-triaxial-rotor (QTR) model, which attribute the appearance of longitudinal wobbling to the early alignment of a
π
=
+
proton pair.
Dogs are the primary urban reservoir of Leishmania infantum and play a crucial role in the transmission of this parasite to man via sandflies. The spleen and liver are the main target organs of L. ...infantum infection, but few studies have evaluated the immune response to this infection in the canine liver. To identify the immunological mediators involved in resistance and/or susceptibility to canine visceral leishmaniosis (CVL), we selected 21 dogs naturally infected by L. infantum and classified as asymptomatic or symptomatic. Immunological parameters were analysed and correlations with clinical signs were determined. Symptomatic dogs showed higher numbers of parasites and less leucocyte infiltration in the liver compared with asymptomatic dogs. The progression of this disease was characterized not only by the down regulation of T helper (Th) 1-related cytokines, such as interferon (IFN)-γ and tumour necrosis factor (TNF)-α, but also by the down regulation of genes encoding interleukin (IL)-17A, inducible nitric oxide synthase (iNOS) and IL-10 in the spleen and liver in symptomatic dogs compared with asymptomatic dogs. Importantly, IL-17A gene transcription level was positively correlated with mRNA expression for iNOS and IFN-γ. Th1- and Th17-related cytokines therefore appear to play a role in restricting parasite growth via iNOS activation and decrease susceptibility of dogs to CVL.
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We previously disclosed the discovery of rationally designed N-((1-(4-(propylsulfonyl)piperazin-1-yl)cycloalkyl)methyl)benzamide inhibitors of glycine transporter-1 (GlyT-1), represented by analogues ...10 and 11. We describe herein further structure-activity relationship exploration of this series via an optimization strategy that primarily focused on the sulfonamide and benzamide appendages of the scaffold. These efforts led to the identification of advanced leads possessing a desirable balance of excellent in vitro GlyT-1 potency and selectivity, favorable ADME and in vitro pharmacological profiles, and suitable pharmacokinetic and safety characteristics. Representative analogue (+)-67 exhibited robust in vivo activity in the cerebral spinal fluid glycine biomarker model in both rodents and nonhuman primates. Furthermore, rodent microdialysis experiments also demonstrated that oral administration of (+)-67 significantly elevated extracellular glycine levels within the medial prefrontal cortex (mPFC).
Loco-regional recurrence in 50% of oral squamous cell carcinoma (OSCC) patients poses major challenge for oncologists. Lack of biomarkers that can predict disease aggressiveness and recurrence risk ...makes the scenario more dismal. On the basis of our earlier global proteomic analyses we identified five differentially expressed proteins in OSCC. This study aimed to develop protein biomarkers-based prognostic risk prediction model for OSCC. Sub-cellular expression of five proteins, S100A7, heterogeneous nuclear ribonucleoproteinK (hnRNPK), prothymosin α (PTMA), 14-3-3ζ and 14-3-3σ was analyzed by immunohistochemistry in test set (282 Indian OSCCs and 209 normal tissues), correlated with clinic-pathological parameters and clinical outcome over 12 years to develop a risk model for prediction of recurrence-free survival. This risk classifier was externally validated in 135 Canadian OSCC and 96 normal tissues. Biomarker signature score based on PTMA, S100A7 and hnRNPK was associated with recurrence free survival of OSCC patients (hazard ratio=1.11; 95% confidence interval 1.08, 1.13, P<0.001, optimism-corrected c-statistic=0.69) independent of clinical parameters. Biomarker signature score stratified OSCC patients into high- and low-risk groups with significant difference for disease recurrence. The high-risk group had median survival 14 months, and 3-year survival rate of 30%, whereas low-risk group survival probability did not reach 50%, and had 3-year survival rate of 71%. As a powerful predictor of 3-year recurrence-free survival in OSCC patients, the newly developed biomarkers panel risk classifier will facilitate patient counseling for personalized treatment.
The PROSPECT reactor antineutrino experiment Ashenfelter, J.; Balantekin, A.B.; Baldenegro, C. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
04/2019, Letnik:
922
Journal Article
Recenzirano
Odprti dostop
The Precision Reactor Oscillation and Spectrum Experiment, PROSPECT, is designed to make both a precise measurement of the antineutrino spectrum from a highly-enriched uranium reactor and to probe ...eV-scale sterile neutrinos by searching for neutrino oscillations over meter-long baselines. PROSPECT utilizes a segmented6Li-doped liquid scintillator detector for both efficient detection of reactor antineutrinos through the inverse beta decay reaction and excellent background discrimination. PROSPECT is a movable 4-ton antineutrino detector covering distances of 7m to 13m from the High Flux Isotope Reactor core. It will probe the best-fit point of the ν̄e disappearance experiments at 4σ in 1 year and the favored regions of the sterile neutrino parameter space at more than 3σ in 3 years. PROSPECT will test the origin of spectral deviations observed in recent θ13 experiments, search for sterile neutrinos, and address the hypothesis of sterile neutrinos as an explanation of the reactor anomaly. This paper describes the design, construction, and commissioning of PROSPECT and reports first data characterizing the performance of the PROSPECT antineutrino detector.
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