Resonance Raman measurements of carotenoids using light emitting diodes

We report on the development of a compact commercial instrument for measuring carotenoids in skin tissue. The instrument uses two light emitting diodes (LEDs) for dual-wavelength excitation and four photomultiplier tubes for multichannel detection. Bandpass filters are used to select the excitation and detection wavelengths. The f/1.3 optical system has high optical throughput and single photon sensitivity, both of which are crucial in LED-based Raman measurements. We employ a signal processing technique that compensates for detector drift and error. The sensitivity and reproducibility of the LED Raman instrument compares favorably to laser-based Raman spectrometers. This compact, portable instrument is used for non-invasive measurement of carotenoid molecules in human skin with a repeatability better than 10%.Comment: Accepted for publication by the Journal of Biomedical Optic

Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy - the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial

Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of 'personalized' therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160 mg/ sulfamethoxazole 800 mg twice a day plus folic acid 5 mg daily or doxycycline 100 mg once daily if body weight is < 50 kg or 100 mg twice daily if ≥50 kg) for the participant prior to randomization. Participants randomized to antimicrobial therapy will receive a voucher to help cover the additional prescription drug costs. Additionally, those participants will have 4-5 scheduled blood draws over the initial 24 months of therapy for safety monitoring. Blood sampling for DNA sequencing and genome wide transcriptomics will be collected before therapy. Blood sampling for transcriptomics and oral and fecal swabs for determination of the microbiome communities will be collected before and after study completion. As a pragmatic study, participants in both treatment arms will have limited in-person visits with the enrolling clinical center. Visits are limited to assessments of lung function and other clinical parameters at time points prior to randomization and at months 12, 24, and 36. All participants will be followed until the study completion for the assessment of clinical endpoints related to hospitalization and mortality events. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02759120

Evidence for oxygenic photosynthesis half a billion years before the Great Oxidation Event

The early Earth was characterized by the absence of oxygen in the ocean–atmosphere system, in contrast to the well-oxygenated conditions that prevail today. Atmospheric concentrations first rose to appreciable levels during the Great Oxidation Event, roughly 2.5–2.3 Gyr ago. The evolution of oxygenic photosynthesis is generally accepted to have been the ultimate cause of this rise, but it has proved difficult to constrain the timing of this evolutionary innovation. The oxidation of manganese in the water column requires substantial free oxygen concentrations, and thus any indication that Mn oxides were present in ancient environments would imply that oxygenic photosynthesis was ongoing. Mn oxides are not commonly preserved in ancient rocks, but there is a large fractionation of molybdenum isotopes associated with the sorption of Mo onto the Mn oxides that would be retained. Here we report Mo isotopes from rocks of the Sinqeni Formation, Pongola Supergroup, South Africa. These rocks formed no less than 2.95 Gyr ago in a nearshore setting. The Mo isotopic signature is consistent with interaction with Mn oxides. We therefore infer that oxygen produced through oxygenic photosynthesis began to accumulate in shallow marine settings at least half a billion years before the accumulation of significant levels of atmospheric oxygen

Controls on uranium isotope fractionation in the Late Paleoproterozoic ocean

Uranium isotope data from Proterozoic carbonates (δ238Ucarb) and black shales (δ238Uauth) are enigmatic. Average Proterozoic δ238Ucarb (approximating Proterozoic seawater, δ238Usw) is similar to modern river/seawater δ238U, and Proterozoic black shales do not always record highly fractionated δ238Uauth compared to contemporaneous δ238Ucarb. However, very light δ238Ucarb and heavy δ238Uauth for the widely anoxic Proterozoic oceans was expected because large isotope fractionations accompany U reduction in anoxic environments. To address this enigma, we report black shale δ238Uauth through a well-characterised multi-core transect in the late Paleoproterozoic Animikie Basin, North America. There is a wide range of δ238Uauth, from –0.52‰ to 0.53‰, that generally correlates with organic carbon enrichments. Heavy δ238Uauth in organic-rich shallow shelf sediments within and near a euxinic wedge are attributed to enhanced productivity with vigorous sediment microbial activity, neutrally charged aqueous U species that slow reaction kinetics, and redoxcline fluctuations. In less organic-rich sediments of the anoxic-ferruginous deep shelf environment, characterized by lower productivity and plentiful reduced iron availability, light δ238Uauth may reflect rapid U reduction or adsorption to solid Fe/Mn species. Hence, for the widely anoxic Proterozoic oceans, we propose that large isotopic fractionations (0.4 to 1.2‰) were associated with highly productive areas on anoxic continental margins, and muted isotopic fractionations (–0.1 to 0.4‰) occurred in anoxic deep-ocean environments. Low-productivity Proterozoic oceans yielded sediments with δ238Ucarb and δ238Uauth close to modern river/seawater values, whereas higher-productivity basins (e.g., Animikie Basin) resulted in lower δ238Ucarb and more variable δ238Uauth.</p

Geochemical alteration of felsic Archean rocks by Gunflint Formation-derived fluids, Quetico–Superior region, northwest Ontario

Alteration of ferromagnesian minerals in felsic Archean rocks apparently was accomplished by diffusion of Gunflint Formation-derived fluids across the Proterozoic–Archean contact. The geochemical evidence documented here is consistent with slow mineral–fluid exchanges under diagenetic or low-grade metamorphic conditions. Chemical changes in mafic minerals include additions of iron, manganese, and water and losses of silica, calcium, and magnesium. The reaction layer extends ~3 m into felsic rocks immediately underlying the Proterozoic–Archean contact. From the evidence presented and the experimental information available it is concluded that these chemical changes occurred as Gunflint Formation-derived, iron-rich fluids diffused into underlying rock over a time frame of 105–107 years. The thermal energy for the reactions was most likely generated by the weight of the overlying sediments and water column. </jats:p