Measuring the Primordial Deuterium Abundance During the Cosmic Dark Ages

We discuss how measurements of fluctuations in the absorption of cosmic microwave background (CMB) photons by neutral gas during the cosmic dark ages, at redshifts z ~ 7--200, could reveal the primordial deuterium abundance of the Universe. The strength of the cross-correlation of brightness-temperature fluctuations due to resonant absorption of CMB photons in the 21-cm line of neutral hydrogen with those due to resonant absorption of CMB photons in the 92-cm line of neutral deuterium is proportional to the fossil deuterium to hydrogen ratio [D/H] fixed during big bang nucleosynthesis (BBN). Although technically challenging, this measurement could provide the cleanest possible determination of [D/H], free from contamination by structure formation processes at lower redshifts, and has the potential to improve BBN constraints to the baryon density of the Universe \Omega_{b} h^2. We also present our results for the thermal spin-change cross-section for deuterium-hydrogen scattering, which may be useful in a more general context than we describe here.Comment: 4 pages, 3 figures, submitted to Phys. Rev. Let

Charged-particle decay and suppression of small-scale power

We study the suppression of the small-scale power spectrum due to the decay of charged matter to dark matter prior to recombination. Prior to decay, the charged particles couple to the photon-baryon fluid and participate in its acoustic oscillations. However, after decaying to neutral dark matter the photon-baryon fluid is coupled only gravitationally to the newly-created dark matter. This generically leads to suppression of power on length scales that enter the horizon prior to decay. For decay times of approximately 3.5 years this leads to suppression of power on subgalactic scales, bringing the observed number of Galactic substructures in line with observation. Decay times of a few years are possible if the dark matter is purely gravitationally interacting, such as the gravitino in supersymmetric models or a massive Kaluza-Klein graviton in models with universal extra dimensions.Comment: 4 pages, 3 figures, submitted to Phys. Rev. Let

Complex folding and misfolding effects of deer-specific amino acid substitutions in the β2-α2 loop of murine prion protein

The β2–α2 loop of PrPC is a key modulator of disease-associated prion protein misfolding. Amino acids that differentiate mouse (Ser169, Asn173) and deer (Asn169, Thr173) PrPC appear to confer dramatically different structural properties in this region and it has been suggested that amino acid sequences associated with structural rigidity of the loop also confer susceptibility to prion disease. Using mouse recombinant PrP, we show that mutating residue 173 from Asn to Thr alters protein stability and misfolding only subtly, whilst changing Ser to Asn at codon 169 causes instability in the protein, promotes oligomer formation and dramatically potentiates fibril formation. The doubly mutated protein exhibits more complex folding and misfolding behaviour than either single mutant, suggestive of differential effects of the β2–α2 loop sequence on both protein stability and on specific misfolding pathways. Molecular dynamics simulation of protein structure suggests a key role for the solvent accessibility of Tyr168 in promoting molecular interactions that may lead to prion protein misfolding. Thus, we conclude that ‘rigidity’ in the β2–α2 loop region of the normal conformer of PrP has less effect on misfolding than other sequence-related effects in this region

A status report on the observability of cosmic bubble collisions

In the picture of eternal inflation as driven by a scalar potential with multiple minima, our observable universe resides inside one of many bubbles formed from transitions out of a false vacuum. These bubbles necessarily collide, upsetting the homogeneity and isotropy of our bubble interior, and possibly leading to detectable signatures in the observable portion of our bubble, potentially in the Cosmic Microwave Background or other precision cosmological probes. This constitutes a direct experimental test of eternal inflation and the landscape of string theory vacua. Assessing this possibility roughly splits into answering three questions: What happens in a generic bubble collision? What observational effects might be expected? How likely are we to observe a collision? In this review we report the current progress on each of these questions, improve upon a few of the existing results, and attempt to lay out directions for future work.Comment: Review article; comments very welcome. 24 pages + 4 appendices; 19 color figures. (Revised version adds two figures, minor edits.

Cosmic 21-cm Fluctuations as a Probe of Fundamental Physics

Fluctuations in high-redshift cosmic 21-cm radiation provide a new window for observing unconventional effects of high-energy physics in the primordial spectrum of density perturbations. In scenarios for which the initial state prior to inflation is modified at short distances, or for which deviations from scale invariance arise during the course of inflation, the cosmic 21-cm power spectrum can in principle provide more precise measurements of exotic effects on fundamentally different scales than corresponding observations of cosmic microwave background anisotropies.Comment: 8 pages, 2 figure

A single dose of the γ-secretase inhibitor semagacestat alters the cerebrospinal fluid peptidome in humans

BACKGROUND: In Alzheimer’s disease, beta-amyloid peptides in the brain aggregate into toxic oligomers and plaques, a process which is associated with neuronal degeneration, memory loss, and cognitive decline. One therapeutic strategy is to decrease the production of potentially toxic beta-amyloid species by the use of inhibitors or modulators of the enzymes that produce beta-amyloid from amyloid precursor protein (APP). The failures of several such drug candidates by lack of effect or undesired side-effects underscore the importance to monitor the drug effects in the brain on a molecular level. Here we evaluate if peptidomic analysis in cerebrospinal fluid (CSF) can be used for this purpose. METHODS: Fifteen human healthy volunteers, divided into three groups, received a single dose of placebo or either 140 mg or 280 mg of the γ-secretase inhibitor semagacestat (LY450139). Endogenous peptides in CSF, sampled prior to administration of the drug and at six subsequent time points, were analyzed by liquid chromatography coupled to mass spectrometry, using isobaric labeling based on the tandem mass tag approach for relative quantification. RESULTS: Out of 302 reproducibly detected peptides, 11 were affected by the treatment. Among these, one was derived from APP and one from amyloid precursor-like protein 1. Nine peptides were derived from proteins that may not be γ-secretase substrates per se, but that are regulated in a γ-secretase-dependent manner. CONCLUSIONS: These results indicate that a CSF peptidomic approach may be a valuable tool both to verify target engagement and to identify other pharmacodynamic effects of the drug. Data are available via ProteomeXchange with identifier PXD003075. TRIAL REGISTRATION: NCT00765115, registered 30/09/2008. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13195-016-0178-x) contains supplementary material, which is available to authorized users

The Quintessential CMB, Past & Future

The past, present and future of cosmic microwave background (CMB) anisotropy research is discussed, with emphasis on the Boomerang and Maxima balloon experiments. These data are combined with large scale structure (LSS) information and high redshift supernova (SN1) observations to explore the inflation-based cosmic structure formation paradigm. Here we primarily focus on a simplified inflation parameter set, {omega_b,omega_{cdm},Omega_{tot}, Omega_Q,w_Q, n_s,tau_C, sigma_8}. After marginalizing over the other cosmic and experimental variables, we find the current CMB+LSS+SN1 data gives Omega_{tot}=1.04\pm 0.05, consistent with (non-baroque) inflation theory. Restricting to Omega_{tot}=1, we find a nearly scale invariant spectrum, n_s =1.03 \pm 0.07. The CDM density, omega_{cdm}=0.17\pm 0.02, is in the expected range, but the baryon density, omega_b=0.030\pm 0.004, is slightly larger than the current nucleosynthesis estimate. Substantial dark energy is inferred, Omega_Q\approx 0.68\pm 0.05, and CMB+LSS Omega_Q values are compatible with the independent SN1 estimates. The dark energy equation of state, parameterized by a quintessence-field pressure-to-density ratio w_Q, is not well determined by CMB+LSS (w_Q<-0.3 at 95%CL), but when combined with SN1 the resulting w_Q<-0.7 limit is quite consistent with the w_Q=-1 cosmological constant case. Though forecasts of statistical errors on parameters for current and future experiments are rosy, rooting out systematic errors will define the true progress.Comment: 14 pages, 3 figs., in Proc. CAPP-2000 (AIP), CITA-2000-6

CMB Analysis of Boomerang & Maxima & the Cosmic Parameters {Omega_tot,Omega_b h^2,Omega_cdm h^2,Omega_Lambda,n_s}

We show how estimates of parameters characterizing inflation-based theories of structure formation localized over the past year when large scale structure (LSS) information from galaxy and cluster surveys was combined with the rapidly developing cosmic microwave background (CMB) data, especially from the recent Boomerang and Maxima balloon experiments. All current CMB data plus a relatively weak prior probability on the Hubble constant, age and LSS points to little mean curvature (Omega_{tot} = 1.08\pm 0.06) and nearly scale invariant initial fluctuations (n_s =1.03\pm 0.08), both predictions of (non-baroque) inflation theory. We emphasize the role that degeneracy among parameters in the L_{pk} = 212\pm 7 position of the (first acoustic) peak plays in defining the $\Omega_{tot}$ range upon marginalization over other variables. Though the CDM density is in the expected range (\Omega_{cdm}h^2=0.17\pm 0.02), the baryon density Omega_bh^2=0.030\pm 0.005 is somewhat above the independent 0.019\pm 0.002 nucleosynthesis estimate. CMB+LSS gives independent evidence for dark energy (Omega_\Lambda=0.66\pm 0.06) at the same level as from supernova (SN1) observations, with a phenomenological quintessence equation of state limited by SN1+CMB+LSS to w_Q<-0.7 cf. the w_Q=-1 cosmological constant case.Comment: 11 pages, 3 figs., in Proc. IAU Symposium 201 (PASP), CITA-2000-6

Limits on the ultra-bright Fast Radio Burst population from the CHIME Pathfinder

We present results from a new incoherent-beam Fast Radio Burst (FRB) search on the Canadian Hydrogen Intensity Mapping Experiment (CHIME) Pathfinder. Its large instantaneous field of view (FoV) and relative thermal insensitivity allow us to probe the ultra-bright tail of the FRB distribution, and to test a recent claim that this distribution's slope, $\alpha\equiv-\frac{\partial \log N}{\partial \log S}$, is quite small. A 256-input incoherent beamformer was deployed on the CHIME Pathfinder for this purpose. If the FRB distribution were described by a single power-law with $\alpha=0.7$, we would expect an FRB detection every few days, making this the fastest survey on sky at present. We collected 1268 hours of data, amounting to one of the largest exposures of any FRB survey, with over 2.4\,$\times$\,10$^5$\,deg$^2$\,hrs. Having seen no bursts, we have constrained the rate of extremely bright events to $<\!13$\,sky$^{-1}$\,day$^{-1}$ above $\sim$\,220$\sqrt{(\tau/\rm ms)}$ Jy\,ms for $\tau$ between 1.3 and 100\,ms, at 400--800\,MHz. The non-detection also allows us to rule out $\alpha\lesssim0.9$ with 95$\%$ confidence, after marginalizing over uncertainties in the GBT rate at 700--900\,MHz, though we show that for a cosmological population and a large dynamic range in flux density, $\alpha$ is brightness-dependent. Since FRBs now extend to large enough distances that non-Euclidean effects are significant, there is still expected to be a dearth of faint events and relative excess of bright events. Nevertheless we have constrained the allowed number of ultra-intense FRBs. While this does not have significant implications for deeper, large-FoV surveys like full CHIME and APERTIF, it does have important consequences for other wide-field, small dish experiments