Inflammation as a Central Mechanism in Alzheimer\u27s Disease

Alzheimer\u27s disease (AD) is a progressive neurodegenerative disorder that is characterized by cognitive decline and the presence of two core pathologies, amyloid β plaques and neurofibrillary tangles. Over the last decade, the presence of a sustained immune response in the brain has emerged as a third core pathology in AD. The sustained activation of the brain\u27s resident macrophages (microglia) and other immune cells has been demonstrated to exacerbate both amyloid and tau pathology and may serve as a link in the pathogenesis of the disorder. In the following review, we provide an overview of inflammation in AD and a detailed coverage of a number of microglia-related signaling mechanisms that have been implicated in AD. Additional information on microglia signaling and a number of cytokines in AD are also reviewed. We also review the potential connection of risk factors for AD and how they may be related to inflammatory mechanisms

The Emergence of the Modern Universe: Tracing the Cosmic Web

This is the report of the Ultraviolet-Optical Working Group (UVOWG) commissioned by NASA to study the scientific rationale for new missions in ultraviolet/optical space astronomy approximately ten years from now, when the Hubble Space Telescope (HST) is de-orbited. The UVOWG focused on a scientific theme, The Emergence of the Modern Universe, the period from redshifts z = 3 to 0, occupying over 80% of cosmic time and beginning after the first galaxies, quasars, and stars emerged into their present form. We considered high-throughput UV spectroscopy (10-50x throughput of HST/COS) and wide-field optical imaging (at least 10 arcmin square). The exciting science to be addressed in the post-HST era includes studies of dark matter and baryons, the origin and evolution of the elements, and the major construction phase of galaxies and quasars. Key unanswered questions include: Where is the rest of the unseen universe? What is the interplay of the dark and luminous universe? How did the IGM collapse to form the galaxies and clusters? When were galaxies, clusters, and stellar populations assembled into their current form? What is the history of star formation and chemical evolution? Are massive black holes a natural part of most galaxies? A large-aperture UV/O telescope in space (ST-2010) will provide a major facility in the 21st century for solving these scientific problems. The UVOWG recommends that the first mission be a 4m aperture, SIRTF-class mission that focuses on UV spectroscopy and wide-field imaging. In the coming decade, NASA should investigate the feasibility of an 8m telescope, by 2010, with deployable optics similar to NGST. No high-throughput UV/Optical mission will be possible without significant NASA investments in technology, including UV detectors, gratings, mirrors, and imagers.Comment: Report of UV/O Working Group to NASA, 72 pages, 13 figures, Full document with postscript figures available at http://casa.colorado.edu/~uvconf/UVOWG.htm

Sharing Social Network Data: Differentially Private Estimation of Exponential-Family Random Graph Models

Motivated by a real-life problem of sharing social network data that contain sensitive personal information, we propose a novel approach to release and analyze synthetic graphs in order to protect privacy of individual relationships captured by the social network while maintaining the validity of statistical results. A case study using a version of the Enron e-mail corpus dataset demonstrates the application and usefulness of the proposed techniques in solving the challenging problem of maintaining privacy \emph{and} supporting open access to network data to ensure reproducibility of existing studies and discovering new scientific insights that can be obtained by analyzing such data. We use a simple yet effective randomized response mechanism to generate synthetic networks under $\epsilon$-edge differential privacy, and then use likelihood based inference for missing data and Markov chain Monte Carlo techniques to fit exponential-family random graph models to the generated synthetic networks.Comment: Updated, 39 page

El Niño and health risks from landscape fire emissions in southeast Asia

Emissions from landscape fires affect both climate and air quality. Here, we combine satellite-derived fire estimates and atmospheric modelling to quantify health effects from fire emissions in southeast Asia from 1997 to 2006. This region has large interannual variability in fire activity owing to coupling between El Niño-induced droughts and anthropogenic land-use change. We show that during strong El Niño years, fires contribute up to 200 μg m−3 and 50 ppb in annual average fine particulate matter (PM2.5) and ozone surface concentrations near fire sources, respectively. This corresponds to a fire contribution of 200 additional days per year that exceed the World Health Organization 50 μg m−3 24-hr PM2.5 interim target and an estimated 10,800 (6,800–14,300)-person (~ 2%) annual increase in regional adult cardiovascular mortality. Our results indicate that reducing regional deforestation and degradation fires would improve public health along with widely established benefits from reducing carbon emissions, preserving biodiversity and maintaining ecosystem services

Evolution of Second-Order Cosmological Perturbations and Non-Gaussianity

We present a second-order gauge-invariant formalism to study the evolution of curvature perturbations in a Friedmann-Robertson-Walker universe filled by multiple interacting fluids. We apply such a general formalism to describe the evolution of the second-order curvature perturbations in the standard one-single field inflation, in the curvaton and in the inhomogeneous reheating scenarios for the generation of the cosmological perturbations. Moreover, we provide the exact expression for the second-order temperature anisotropies on large scales, including second-order gravitational effects and extend the well-known formula for the Sachs-Wolfe effect at linear order. Our findings clarify what is the exact non-linearity parameter f_NL entering in the determination of higher-order statistics such as the bispectrum of Cosmic Microwave Background temperature anisotropies. Finally, we compute the level of non-Gaussianity in each scenario for the creation of cosmological perturbations.Comment: 14 pages, LaTeX file. Further comments adde

Ribbons on the CBR Sky: A Powerful Test of a Baryon Symmetric Universe

If the Universe consists of domains of matter and antimatter, annihilations at domain interfaces leave a distinctive imprint on the Cosmic Background Radiation (CBR) sky. The signature is anisotropies in the form of long, thin ribbons of width $\theta_W\sim 0.1^\circ$, separated by angle $\theta_L\simeq 1^\circ(L/100h^{-1}{Mpc})$ where L is the characteristic domain size, and y-distortion parameter $y \approx 10^{-6}$. Such a pattern could potentially be detected by the high-resolution CBR anisotropy experiments planned for the next decade, and such experiments may finally settle the question of whether or not our Hubble volume is baryon symmetric.Comment: LaTeX, 10 pages, 4 figures in epsf. Revised version corrects a couple of relevant mistake

Completing Natural Inflation

If the inflaton is a pseudo-scalar axion, the axion shift symmetry can protect the flatness of its potential from too large radiative corrections. This possibility, known as natural inflation, requires an axion scale which is greater than the (reduced) Planck scale. It is unclear whether such a high value is compatible with an effective field theoretical description, and if the global axionic symmetry survives quantum gravity effects. We propose a mechanism which provides an effective large axion scale, although the original one is sub-Planckian. The mechanism is based on the presence of two axions, with a potential provided by two anomalous gauge groups. The effective large axion scale is due to an almost exact symmetry between the couplings of the axions to the anomalous groups. We also comment on a possible implementation in heterotic string theory.Comment: 9 pages, 1 figur

The Lyth Bound and the End of Inflation

We derive an extended version of the well-known Lyth Bound on the total variation of the inflaton field, incorporating higher order corrections in slow roll. We connect the field variation $\Delta\phi$ to both the spectral index of scalar perturbations and the amplitude of tensor modes. We then investigate the implications of this bound for ``small field'' potentials, where the field rolls off a local maximum of the potential. The total field variation during inflation is {\em generically} of order $m_{\rm Pl}$, even for potentials with a suppressed tensor/scalar ratio. Much of the total field excursion arises in the last e-fold of inflation and in single field models this problem can only be avoided via fine-tuning or the imposition of a symmetry. Finally, we discuss the implications of this result for inflationary model building in string theory and supergravity.Comment: 10 pages, RevTeX, 2 figures (V3: version accepted for publication by JCAP