Simultaneous quantification of antioxidants paraxanthine and caffeine in human saliva by electrochemical sensing for CYP1A2 phenotyping

The enzyme CYP1A2 is responsible for the metabolism of numerous antioxidants in the body, including caffeine, which is transformed into paraxanthine, its main primary metabolite. Both molecules are known for their antioxidant and pro-oxidant characteristics, and the paraxanthine-to-caffeine molar ratio is a widely accepted metric for CYP1A2 phenotyping, to optimize dose\u2013 response effects in individual patients. We developed a simple, cheap and fast electrochemical based method for the simultaneous quantification of paraxanthine and caffeine in human saliva, by differential pulse voltammetry, using an anodically pretreated glassy carbon electrode. Cyclic voltammetry experiments revealed for the first time that the oxidation of paraxanthine is diffusion controlled with an irreversible peak at ca. +1.24 V (vs. Ag/AgCl) in a 0.1 M H2 SO4 solution, and that the mechanism occurs via the transfer of two electrons and two protons. The simultaneous quantification of paraxanthine and caffeine was demonstrated in 0.1 M H2 SO4 and spiked human saliva samples. In the latter case, limits of detection of 2.89 \ub5M for paraxanthine and 5.80 \ub5M for caffeine were obtained, respectively. The sensor is reliable, providing a relative standard deviation within 7% (n = 6). Potential applicability of the sensing platform was demonstrated by running a small scale trial on five healthy volunteers, with simultaneous quantification by differential pulse voltammetry (DPV) of paraxanthine and caffeine in saliva samples collected at 1, 3 and 6 h postdose administration. The results were validated by ultra-high pressure liquid chromatography and shown to have a high correlation factor (r = 0.994)

Pd@TiO2/carbon nanohorn electrocatalysts: reversible CO2 hydrogenation to formic acid

Direct conversion of carbon dioxide to formic acid at thermodynamic equilibrium is an advantage of enzymatic catalysis, hardly replicated by synthetic analogs, but of high priority for carbon-neutral energy schemes. The bio-mimetic potential of totally inorganic Pd@TiO2 nanoparticles is envisioned herein in combination with Single Walled Carbon NanoHorns (SWCNHs). The high surface nano-carbon entanglement templates a wide distribution of \u201chard-soft\u201d bimetallic sites where the small Pd nanoparticles (1.5 nm) are shielded within the TiO2 phase (Pd@TiO2), while being electrically wired to the electrode by the nanocarbon support. This hybrid electrocatalyst activates CO2 reduction to formic acid at near zero overpotential in the aqueous phase (onset potential at E < 120.05 V vs. RHE, pH = 7.4), while being able to evolve hydrogen via sequential formic acid dehydrogenation. The net result hints at a unique CO2 \u201ccircular catalysis\u201d where formic acid versus H2 selectivity is addressable by flow-reactor technology

The impact of urea-induced unfolding on the redox process of immobilised cytochrome c

We have studied the effect of urea-induced unfolding on the electron transfer process of yeast iso-1-cytochrome c and its mutant K72AK73AK79A adsorbed on electrodes coated by mixed 11-mercapto-1-undecanoic acid/11-mercapto-1-undecanol self-assembled monolayers. Electrochemical measurements, complemented by surface enhanced resonance Raman studies, indicate two distinct states of the adsorbed proteins that mainly differ with respect to the ligation pattern of the haem. The native state, in which the haem is axially coordinated by Met80 and His18, displays a reduction potential that slightly shifts to negative values with increasing urea concentration. At urea concentrations higher than 6 M, a second state prevails in which the Met80 ligand is replaced by an additional histidine residue. This structural change in the haem pocket is associated with an approximately 0.4 V shift of the reduction potential to negative values. These two states were found for both the wild-type protein and the mutant in which lysine residues 72, 73 and 79 had been substituted by alanines. The analysis of the reduction potentials, the reaction enthalpies and entropies as well as the rate constants indicates that these three lysine residues have an important effect on stabilising the protein structure in the adsorbed state and facilitating the electron transfer dynamics

Simultaneous Planck, Swift, and Fermi observations of X-ray and gamma-ray selected blazars

We present simultaneous Planck, Swift, Fermi, and ground-based data for 105 blazars belonging to three samples with flux limits in the soft X-ray, hard X-ray, and gamma-ray bands. Our unique data set has allowed us to demonstrate that the selection method strongly influences the results, producing biases that cannot be ignored. Almost all the BL Lac objects have been detected by Fermi-LAT, whereas ~40% of the flat-spectrum radio quasars (FSRQs) in the radio, soft X-ray, and hard X-ray selected samples are still below the gamma-ray detection limit even after integrating 27 months of Fermi-LAT data. The radio to sub-mm spectral slope of blazars is quite flat up to ~70GHz, above which it steepens to ~-0.65. BL Lacs have significantly flatter spectra than FSRQs at higher frequencies. The distribution of the rest-frame synchrotron peak frequency (\nupS) in the SED of FSRQs is the same in all the blazar samples with =10^13.1 Hz, while the mean inverse-Compton peak frequency, , ranges from 10^21 to 10^22 Hz. The distributions of \nupS and of \nupIC of BL Lacs are much broader and are shifted to higher energies than those of FSRQs and strongly depend on the selection method. The Compton dominance of blazars ranges from ~0.2 to ~100, with only FSRQs reaching values >3. Its distribution is broad and depends strongly on the selection method, with gamma-ray selected blazars peaking at ~7 or more, and radio-selected blazars at values ~1, thus implying that the assumption that the blazar power is dominated by high-energy emission is a selection effect. Simple SSC models cannot explain the SEDs of most of the gamma-ray detected blazars in all samples. The SED of the blazars that were not detected by Fermi-LAT may instead be consistent with SSC emission. Our data challenge the correlation between bolometric luminosity and \nupS predicted by the blazar sequence.Comment: Version accepted by A&A. Joint Planck, Swift, and Fermi collaborations pape

Planck 2013 results. XXII. Constraints on inflation

We analyse the implications of the Planck data for cosmic inflation. The Planck nominal mission temperature anisotropy measurements, combined with the WMAP large-angle polarization, constrain the scalar spectral index to be ns = 0:9603 _ 0:0073, ruling out exact scale invariance at over 5_: Planck establishes an upper bound on the tensor-to-scalar ratio of r < 0:11 (95% CL). The Planck data thus shrink the space of allowed standard inflationary models, preferring potentials with V00 < 0. Exponential potential models, the simplest hybrid inflationary models, and monomial potential models of degree n _ 2 do not provide a good fit to the data. Planck does not find statistically significant running of the scalar spectral index, obtaining dns=dln k = 0:0134 _ 0:0090. We verify these conclusions through a numerical analysis, which makes no slowroll approximation, and carry out a Bayesian parameter estimation and model-selection analysis for a number of inflationary models including monomial, natural, and hilltop potentials. For each model, we present the Planck constraints on the parameters of the potential and explore several possibilities for the post-inflationary entropy generation epoch, thus obtaining nontrivial data-driven constraints. We also present a direct reconstruction of the observable range of the inflaton potential. Unless a quartic term is allowed in the potential, we find results consistent with second-order slow-roll predictions. We also investigate whether the primordial power spectrum contains any features. We find that models with a parameterized oscillatory feature improve the fit by __2 e_ _ 10; however, Bayesian evidence does not prefer these models. We constrain several single-field inflation models with generalized Lagrangians by combining power spectrum data with Planck bounds on fNL. Planck constrains with unprecedented accuracy the amplitude and possible correlation (with the adiabatic mode) of non-decaying isocurvature fluctuations. The fractional primordial contributions of cold dark matter (CDM) isocurvature modes of the types expected in the curvaton and axion scenarios have upper bounds of 0.25% and 3.9% (95% CL), respectively. In models with arbitrarily correlated CDM or neutrino isocurvature modes, an anticorrelated isocurvature component can improve the _2 e_ by approximately 4 as a result of slightly lowering the theoretical prediction for the ` <_ 40 multipoles relative to the higher multipoles. Nonetheless, the data are consistent with adiabatic initial conditions

A coherent polarimeter array for the Large Scale Polarization Explorer balloon experiment

We discuss the design and expected performance of STRIP (STRatospheric Italian Polarimeter), an array of coherent receivers designed to fly on board the LSPE (Large Scale Polarization Explorer) balloon experiment. The STRIP focal plane array comprises 49 elements in Q band and 7 elements in W-band using cryogenic HEMT low noise amplifiers and high performance waveguide components. In operation, the array will be cooled to 20 K and placed in the focal plane of a $\sim 0.6$ meter telescope providing an angular resolution of $\sim1.5$ degrees. The LSPE experiment aims at large scale, high sensitivity measurements of CMB polarization, with multi-frequency deep measurements to optimize component separation. The STRIP Q-band channel is crucial to accurately measure and remove the synchrotron polarized component, while the W-band channel, together with a bolometric channel at the same frequency, provides a crucial cross-check for systematic effects.Comment: In press on the Proceedings of the SPIE Conference Astronomical Telescopes + instrumentation 2012, Amsterdam, paper 8446-27

BeyondPlanck II. CMB map-making through Gibbs sampling

We present a Gibbs sampling solution to the map-making problem for CMB measurements, building on existing destriping methodology. Gibbs sampling breaks the computationally heavy destriping problem into two separate steps; noise filtering and map binning. Considered as two separate steps, both are computationally much cheaper than solving the combined problem. This provides a huge performance benefit as compared to traditional methods, and allows us for the first time to bring the destriping baseline length to a single sample. We apply the Gibbs procedure to simulated Planck 30 GHz data. We find that gaps in the time-ordered data are handled efficiently by filling them with simulated noise as part of the Gibbs process. The Gibbs procedure yields a chain of map samples, from which we may compute the posterior mean as a best-estimate map. The variation in the chain provides information on the correlated residual noise, without need to construct a full noise covariance matrix. However, if only a single maximum-likelihood frequency map estimate is required, we find that traditional conjugate gradient solvers converge much faster than a Gibbs sampler in terms of total number of iterations. The conceptual advantages of the Gibbs sampling approach lies in statistically well-defined error propagation and systematic error correction, and this methodology forms the conceptual basis for the map-making algorithm employed in the BeyondPlanck framework, which implements the first end-to-end Bayesian analysis pipeline for CMB observations.Comment: 11 pages, 10 figures. All BeyondPlanck products and software will be released publicly at http://beyondplanck.science during the online release conference (November 18-20, 2020). Connection details will be made available at the same website. Registration is mandatory for the online tutorial, but optional for the conferenc

BeyondPlanck VII. Bayesian estimation of gain and absolute calibration for CMB experiments

We present a Bayesian calibration algorithm for CMB observations as implemented within the global end-to-end BeyondPlanck (BP) framework, and apply this to the Planck Low Frequency Instrument (LFI) data. Following the most recent Planck analysis, we decompose the full time-dependent gain into a sum of three orthogonal components: One absolute calibration term, common to all detectors; one time-independent term that can vary between detectors; and one time-dependent component that is allowed to vary between one-hour pointing periods. Each term is then sampled conditionally on all other parameters in the global signal model through Gibbs sampling. The absolute calibration is sampled using only the orbital dipole as a reference source, while the two relative gain components are sampled using the full sky signal, including the orbital and Solar CMB dipoles, CMB fluctuations, and foreground contributions. We discuss various aspects of the data that influence gain estimation, including the dipole/polarization quadrupole degeneracy and anomalous jumps in the instrumental gain. Comparing our solution to previous pipelines, we find good agreement in general, with relative deviations of -0.84% (-0.67%) for 30 GHz, -0.14% (0.02%) for 44 GHz and -0.69% (-0.08%) for 70 GHz, compared to Planck 2018 (NPIPE). The deviations we find are within expected error bounds, and we attribute them to differences in data usage and general approach between the pipelines. In particular, the BP calibration is performed globally, resulting in better inter-frequency consistency. Additionally, WMAP observations are used actively in the BP analysis, which breaks degeneracies in the Planck data set and results in better agreement with WMAP. Although our presentation and algorithm are currently oriented toward LFI processing, the procedure is fully generalizable to other experiments.Comment: 18 pages, 15 figures. All BeyondPlanck products and software will be released publicly at http://beyondplanck.science during the online release conference (November 18-20, 2020). Connection details will be made available at the same website. Registration is mandatory for the online tutorial, but optional for the conferenc

BeyondPlanck XII. Cosmological parameter constraints with end-to-end error propagation

We present cosmological parameter constraints as estimated using the Bayesian BeyondPlanck (BP) analysis framework. This method supports seamless end-to-end error propagation from raw time-ordered data to final cosmological parameters. As a first demonstration of the method, we analyze time-ordered Planck LFI observations, combined with selected external data (WMAP 33-61GHz, Planck HFI DR4 353 and 857GHz, and Haslam 408MHz) in the form of pixelized maps which are used to break critical astrophysical degeneracies. Overall, all results are generally in good agreement with previously reported values from Planck 2018 and WMAP, with the largest relative difference for any parameter of about 1 sigma when considering only temperature multipoles between 29<l<601. In cases where there are differences, we note that the BP results are generally slightly closer to the high-l HFI-dominated Planck 2018 results than previous analyses, suggesting slightly less tension between low and high multipoles. Using low-l polarization information from LFI and WMAP, we find a best-fit value of tau=0.066 +/- 0.013, which is higher than the low value of tau=0.051 +/- 0.006 derived from Planck 2018 and slightly lower than the value of 0.069 +/- 0.011 derived from joint analysis of official LFI and WMAP products. Most importantly, however, we find that the uncertainty derived in the BP processing is about 30% larger than when analyzing the official products, after taking into account the different sky coverage. We argue that this is due to marginalizing over a more complete model of instrumental and astrophysical parameters, and this results in both more reliable and more rigorously defined uncertainties. We find that about 2000 Monte Carlo samples are required to achieve robust convergence for low-resolution CMB covariance matrix with 225 independent modes.Comment: 13 pages, 10 figure

BeyondPlanck X. Planck LFI frequency maps with sample-based error propagation

We present Planck LFI frequency sky maps derived within the BeyondPlanck framework. This framework draws samples from a global posterior distribution that includes instrumental, astrophysical and cosmological parameters, and the main product is an entire ensemble of frequency sky map samples. This ensemble allows for computationally convenient end-to-end propagation of low-level instrumental uncertainties into higher-level science products. We show that the two dominant sources of LFI instrumental systematic uncertainties are correlated noise and gain fluctuations, and the products presented here support - for the first time - full Bayesian error propagation for these effects at full angular resolution. We compare our posterior mean maps with traditional frequency maps delivered by the Planck collaboration, and find generally good agreement. The most important quality improvement is due to significantly lower calibration uncertainties in the new processing, as we find a fractional absolute calibration uncertainty at 70 GHz of $\delta g_{0}/g_{0} =5 \cdot 10^{-5}$, which is nominally 40 times smaller than that reported by Planck 2018. However, the original Planck 2018 estimate has a non-trivial statistical interpretation, and this further illustrates the advantage of the new framework in terms of producing self-consistent and well-defined error estimates of all involved quantities without the need of ad hoc uncertainty contributions. We describe how low-resolution data products, including dense pixel-pixel covariance matrices, may be produced directly from the posterior samples without the need for computationally expensive analytic calculations or simulations. We conclude that posterior-based frequency map sampling provides unique capabilities in terms of low-level systematics modelling and error propagation, and may play an important role for future CMB B-mode experiments. (Abridged.)Comment: 32 pages, 23 figures, data available from https://www.cosmoglobe.uio.no