Time-Resolved Data Acquisition for In Situ Subsurface Planetary Geochemistry

The current gamma-ray/neutron instrumentation development effort at NASA Goddard Space Flight Center aims to extend the use of active pulsed neutron interrogation techniques to probe the subsurface geochemistry of planetary bodies in situ. All previous NASA planetary science missions, that used neutron and/or gamma-ray spectroscopy instruments, have relied on a constant neutron source produced from galactic cosmic rays. One of the distinguishing features of this effort is the inclusion of a high intensity 14.1 MeV pulsed neutron generator synchronized with a custom data acquisition system to time each event relative to the pulse. With usually only one opportunity to collect data, it is difficult to set a priori time-gating windows to obtain the best possible results. Acquiring time-tagged, event-by-event data from nuclear induced reactions provides raw data sets containing channel/energy, and event time for each gamma ray or neutron detected. The resulting data set can be plotted as a function of time or energy using optimized analysis windows after the data are acquired. Time windows can now be chosen to produce energy spectra that yield the most statistically significant and accurate elemental composition results that can be derived from the complete data set. The advantages of post-processing gamma-ray time-tagged event-by-event data in experimental tests using our prototype instrument will be demonstrated

Doping evolution of superconducting gaps and electronic densities of states in Ba(Fe1-xCox)2As2 iron pnictides

An extensive calorimetric study of the normal- and superconducting-state properties of Ba(Fe1-xCox)2As2 is presented for 0 < x < 0.2. The normal-state Sommerfeld coefficient increases (decreases) with Co doping for x 0.06), which illustrates the strong competition between magnetism and superconductivity to monopolize the Fermi surface in the underdoped region and the filling of the hole bands for overdoped Ba(Fe1-xCox)2As2. All superconducting samples exhibit a residual electronic density of states of unknown origin in the zero-temperature limit, which is minimal at optimal doping but increases to the normal-state value in the strongly under- and over-doped regions. The remaining specific heat in the superconducting state is well described using a two-band model with isotropic s-wave superconducting gaps.Comment: Submitted to Europhysics Letter

A sensitive mass spectrometric assay for mitochondrial CoQ pool redox state in vivo

Coenzyme Q (CoQ) is an essential cofactor, primarily found in the mitochondrial inner membrane where it functions as an electron carrier in the respiratory chain, and a lipophilic antioxidant. The redox state of the CoQ pool is the ratio of its oxidised (ubiquinone) and reduced (ubiquinol) forms, and is a key indicator of mitochondrial bioenergetic and antioxidant status. However, the role of CoQ redox state in vivo is poorly understood, because determining its value is technically challenging due to redox changes during isolation, extraction and analysis. To address these problems, we have developed a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay that enables us to extract and analyse both the CoQ redox state and the magnitude of the CoQ pool with negligible changes to redox state from small amounts of tissue. This will enable the physiological and pathophysiological roles of the CoQ redox state to be investigated in vivo

A sensitive mass spectrometric assay for mitochondrial CoQ pool redox state in vivo.

Coenzyme Q (CoQ) is an essential cofactor, primarily found in the mitochondrial inner membrane where it functions as an electron carrier in the respiratory chain, and as a lipophilic antioxidant. The redox state of the CoQ pool is the ratio of its oxidised (ubiquinone) and reduced (ubiquinol) forms, and is a key indicator of mitochondrial bioenergetic and antioxidant status. However, the role of CoQ redox state in vivo is poorly understood, because determining its value is technically challenging due to redox changes during isolation, extraction and analysis. To address these problems, we have developed a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay that enables us to extract and analyse both the CoQ redox state and the magnitude of the CoQ pool with negligible changes to redox state from small amounts of tissue. This will enable the physiological and pathophysiological roles of the CoQ redox state to be investigated in vivo

Altered emotional experiences attributed to antipsychotic medications - A potential link with estimated dopamine D-2 receptor occupancy

Altered emotional experiences in response to antipsychotics may increase the burden of disease in patients with schizophrenia. In a large cross-sectional study, patients with schizophrenia completed the Subjects Reaction to Antipsychotics questionnaire (SRA) to assess whether they attributed altered emotional experiences (flattened affect or depressive symptoms) to their antipsychotics. Association with antipsychotic D-2 receptor affinity and occupancy was examined using logistic regression. We compared antipsychotic-attributed emotional experiences between patients using antipsychotic monotherapy and combination therapy. Of the 1298 included patients, 23% attributed flattened affect to their anti psychotics and 16% attributed depressive symptoms to their antipsychotics, based on the SRA. No differences were observed between antipsychotics in patients on monotherapy. We discuss that within these patients' relatively low dose range, altered emotional experiences did not appear to relate to the level of D-2 receptor affinity of antipsychotic monotherapy. Patients using antipsychotic combination therapy (22%) were more likely to attribute depressive symptoms to their antipsychotics than patients using antipsychotic monotherapy (OR [95%CI]=1.443 [1.033-2.015]); possibly due to higher D-2 receptor occupancies as estimated by dose equivalents. (C) 2016 Published by Elsevier Ireland Ltd

Protection of Melanized Cryptococcus neoformans from Lethal Dose Gamma Irradiation Involves Changes in Melanin\u27s Chemical Structure and Paramagnetism

Certain fungi thrive in highly radioactive environments including the defunct Chernobyl nuclear reactor. Cryptococcus neoformans (C. neoformans), which uses L-3,4-dihydroxyphenylalanine (L-DOPA) to produce melanin, was used here to investigate how gamma radiation under aqueous aerobic conditions affects the properties of melanin, with the aim of gaining insight into its radioprotective role. Exposure of melanized fungal cell in aqueous suspensions to doses of γ-radiation capable of killing 50 to 80% of the cells did not lead to a detectable loss of melanin integrity according to EPR spectra of melanin radicals. Moreover, upon UV-visible (Xe-lamp) illumination of melanized cells, the increase in radical population was unchanged after γ-irradiation. Gamma-irradiation of frozen cell suspensions and storage of samples for several days at 77 K however, produced melanin modification noted by a reduced radical population and reduced photoresponse. More direct evidence for structural modification of melanin came from the detection of soluble products with absorbance maxima near 260 nm in supernatants collected after γ-irradiation of cells and cell-free melanin. These products, which include thiobarbituric acid (TBA)-reactive aldehydes, were also generated by Fenton reagent treatment of cells and cell-free melanin. In an assay of melanin integrity based on the metal (Bi+3) binding capacity of cells, no detectable loss in binding was detected after γ-irradiation. Our results show that melanin in C. neoformans cells is susceptible to some damage by hydroxyl radical formed in lethal radioactive aqueous environments and serves a protective role in melanized fungi that involves sacrificial breakdown

Incidence and survival of patients with oligometastatic esophagogastric cancer: A multicenter cohort study

urpose/objective: This multicenter study assessed the incidence and survival of patients with esophagogastric cancer and oligometastatic disease (OMD) in two tertiary referral cancer centers in The Netherlands and Switzerland. Materials/methods: Between 2010 and 2021, patients with metastatic esophagogastric cancer were identified. Patients with de-novo OMD were included (first-time diagnosis of ≤5 distant metastases on 18F-FDG-PET/CT). Control of the primary tumor was considered in patients who underwent primary tumor resection or definitive chemoradiotherapy without locoregional recurrence. Treatment of OMD was categorized into (1) systemic therapy, (2) local treatment (stereotactic body radiotherapy or metastasectomy), (3) local plus systemic therapy, or (4) best supportive care. The primary outcomes were overall survival (OS) and independent prognostic factors for OS. Independent prognostic factors for OS were analyzed using multivariable Cox proportional hazard models. Results: In total, 830 patients with metastatic esophagogastric cancer were identified of whom 200 patients with de-novo OMD were included (24%). The majority of included patients had esophageal cancer (73%) with adenocarcinoma histology (79%) and metachronous OMD (52%). The primary tumor was controlled in 68%. Treatment of OMD was systemic therapy (25%), local treatment (43%), local plus systemic therapy (13%), or best supportive care (18%). Median follow-up was 14 months (interquartile range: 7-27). Median OS was 16 months (95% CI: 13-21). Improved OS was independently associated with local plus systemic therapy compared with systemic therapy alone (hazard ratio [HR] 0.47, 95% confidence interval [CI]: 0.25-0.87). Worse OS was independently associated with squamous cell carcinoma (HR 1.70, 95% CI: 1.07-2.74), bone oligometastases (HR 2.44, 95% CI: 1.28-4.68), brain oligometastases (HR 1.98, 95% CI: 1.05-4.69), and two metastatic locations (HR 2.07, 95% CI: 1.04-4.12). Median OS after local plus systemic therapy was 35 months (95% CI: 22-NA) as compared with 13 months (95% CI: 9-21, p < 0.001) after systemic therapy alone for OMD. Conclusion: Patients with metastatic esophagogastric cancer present in 25% with de-novo OMD. Local treatment of OMD plus systemic therapy was independently associated with long-term OS and independently improved OS when compared with systemic therapy alone. Randomized controlled trials are warranted to confirm these results. Keywords: Esophageal neoplasms; Gastric neoplasms; Lymphatic metastasis; Metastasectomy; Neoplasm metastasis; Radiosurgery