Cosmic 21-cm Delensing of Microwave Background Polarization and the Minimum Detectable Energy Scale of Inflation

The curl (B) modes of cosmic microwave background (CMB) polarization anisotropies are a unique probe of the primordial background of inflationary gravitational waves (IGWs). Unfortunately, the B-mode polarization anisotropies generated by gravitational waves at recombination are confused with those generated by the mixing of gradient-mode (E-mode) and B-mode polarization anisotropies as CMB photons propagate through the Universe and are gravitationally lensed. We describe here a method for delensing CMB polarization anisotropies using observations of anisotropies in the cosmic 21-cm radiation emitted or absorbed by neutral hydrogen atoms at redshifts 10 to 200. While the detection of cosmic 21-cm anisotropies at high resolution is challenging, a combined study with a relatively low-resolution (but high-sensitivity) CMB polarization experiment could probe inflationary energy scales well below the Grand Unified Theory (GUT) scale of 10^{16} GeV -- constraining models with energy scales below 10^{15} GeV (the detectable limit derived from CMB observations alone). The ultimate theoretical limit to the detectable inflationary energy scale via this method may be as low as 3 \times 10^{14} GeV.Comment: 4 pages, 2 figures, submitted to Phys. Rev. Let

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

Solvation-guided design of fluorescent probes for discrimination of amyloids

The deposition of insoluble protein aggregates in the brain is a hallmark of many neurodegenerative diseases. While their exact role in neurodegeneration remains unclear, the presence of these amyloid deposits often precedes clinical symptoms. As a result, recent progress in imaging methods that utilize amyloid-specific small molecule probes have become a promising avenue for antemortem disease diagnosis. Here, we present a series of amino-aryl cyanoacrylate (AACA) fluorophores that show a turn-on fluorescence signal upon binding to amyloids in solution and in tissue. Using a theoretical model for environmental sensitivity of fluorescence together with ab initio computational modeling of the effects of polar environment on electron density distribution and conformational dynamics, we designed, synthesized, and evaluated a set of fluorophores that (1) bind to aggregated forms of Alzheimer's-related beta-amyloid peptides with low micromolar to high nanomolar affinities and (2) have the capability to fluorescently discriminate different amyloids based on differences in amino acid composition within the binding pocket through exploitation of their solvatochromic properties. These studies showcase the rational design of a family of amyloid-binding imaging agents that could be integrated with new optical approaches for the clinical diagnosis of amyloidoses, where accurate identification of the specific neurodegenerative disease could aid in the selection of a proper course for treatment

Diurnal patterns of soluble amyloid precursor protein metabolites in the human central nervous system

The amyloid-β (Aβ) protein is diurnally regulated in both the cerebrospinal fluid and blood in healthy adults; circadian amplitudes decrease with aging and the presence of cerebral Aβ deposits. The cause of the Aβ diurnal pattern is poorly understood. One hypothesis is that the Amyloid Precursor Protein (APP) is diurnally regulated, leading to APP product diurnal patterns. APP in the central nervous system is processed either via the β-pathway (amyloidogenic), generating soluble APP-β (sAPPβ) and Aβ, or the α-pathway (non-amyloidogenic), releasing soluble APP-α (sAPPα). To elucidate the potential contributions of APP to the Aβ diurnal pattern and the balance of the α- and β- pathways in APP processing, we measured APP proteolytic products over 36 hours in human cerebrospinal fluid from cognitively normal and Alzheimer's disease participants. We found diurnal patterns in sAPPα, sAPPβ, Aβ40, and Aβ42, which diminish with increased age, that support the hypothesis that APP is diurnally regulated in the human central nervous system and thus results in Aβ diurnal patterns. We also found that the four APP metabolites were positively correlated in all participants without cerebral Aβ deposits. This positive correlation suggests that the α- and β- APP pathways are non-competitive under normal physiologic conditions where APP availability may be the limiting factor that determines sAPPα and sAPPβ production. However, in participants with cerebral Aβ deposits, there was no correlation of Aβ to sAPP metabolites, suggesting that normal physiologic regulation of cerebrospinal fluid Aβ is impaired in the presence of amyloidosis. Lastly, we found that the ratio of sAPPβ to sAPPα was significantly higher in participants with cerebral Aβ deposits versus those without deposits. Therefore, the sAPPβ to sAPPα ratio may be a useful biomarker for cerebral amyloidosis

Chronic wasting disease prions are not transmissible to transgenic mice overexpressing human prion protein

Chronic wasting disease (CWD) is a prion disease that affects free-ranging and captive cervids, including mule deer, white-tailed deer, Rocky Mountain elk and moose. CWD-infected cervids have been reported in 14 USA states, two Canadian provinces and in South Korea. The possibility of a zoonotic transmission of CWD prions via diet is of particular concern in North America where hunting of cervids is a popular sport. To investigate the potential public health risks posed by CWD prions, we have investigated whether intracerebral inoculation of brain and spinal cord from CWD-infected mule deer transmits prion infection to transgenic mice overexpressing human prion protein with methionine or valine at polymorphic residue 129. These transgenic mice have been utilized in extensive transmission studies of human and animal prion disease and are susceptible to BSE and vCJD prions, allowing comparison with CWD. Here, we show that these mice proved entirely resistant to infection with mule deer CWD prions arguing that the transmission barrier associated with this prion strain/host combination is greater than that observed with classical BSE prions. However, it is possible that CWD may be caused by multiple prion strains. Further studies will be required to evaluate the transmission properties of distinct cervid prion strains as they are characterized

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

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

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.

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