Molecular basis for passive immunotherapy of Alzheimer's disease

Amyloid aggregates of the amyloid-{beta} (A{beta}) peptide are implicated in the pathology of Alzheimer's disease. Anti-A{beta} monoclonal antibodies (mAbs) have been shown to reduce amyloid plaques in vitro and in animal studies. Consequently, passive immunization is being considered for treating Alzheimer's, and anti-A{beta} mAbs are now in phase II trials. We report the isolation of two mAbs (PFA1 and PFA2) that recognize A{beta} monomers, protofibrils, and fibrils and the structures of their antigen binding fragments (Fabs) in complex with the A{beta}(1–8) peptide DAEFRHDS. The immunodominant EFRHD sequence forms salt bridges, hydrogen bonds, and hydrophobic contacts, including interactions with a striking WWDDD motif of the antigen binding fragments. We also show that a similar sequence (AKFRHD) derived from the human protein GRIP1 is able to cross-react with both PFA1 and PFA2 and, when cocrystallized with PFA1, binds in an identical conformation to A{beta}(1–8). Because such cross-reactivity has implications for potential side effects of immunotherapy, our structures provide a template for designing derivative mAbs that target A{beta} with improved specificity and higher affinity

A roadmap for China to peak carbon dioxide emissions and achieve a 20% share of non-fossil fuels in primary energy by 2030

As part of its Paris Agreement commitment, China pledged to peak carbon dioxide (CO2) emissions around 2030, striving to peak earlier, and to increase the non-fossil share of primary energy to 20% by 2030. Yet by the end of 2017, China emitted 28% of the world's energy-related CO2 emissions, 76% of which were from coal use. How China can reinvent its energy economy cost-effectively while still achieving its commitments was the focus of a three-year joint research project completed in September 2016. Overall, this analysis found that if China follows a pathway in which it aggressively adopts all cost-effective energy efficiency and CO2 emission reduction technologies while also aggressively moving away from fossil fuels to renewable and other non-fossil resources, it is possible to not only meet its Paris Agreement Nationally Determined Contribution (NDC) commitments, but also to reduce its 2050 CO2 emissions to a level that is 42% below the country's 2010 CO2 emissions. While numerous barriers exist that will need to be addressed through effective policies and programs in order to realize these potential energy use and emissions reductions, there are also significant local environmental (e.g., air quality), national and global environmental (e.g., mitigation of climate change), human health, and other unquantified benefits that will be realized if this pathway is pursued in China

Measuring the 3D Clustering of Undetected Galaxies Through Cross Correlation of their Cumulative Flux Fluctuations from Multiple Spectral Lines

We discuss a method for detecting the emission from high redshift galaxies by cross correlating flux fluctuations from multiple spectral lines. If one can fit and subtract away the continuum emission with a smooth function of frequency, the remaining signal contains fluctuations of flux with frequency and angle from line emitting galaxies. Over a particular small range of observed frequencies, these fluctuations will originate from sources corresponding to a series of different redshifts, one for each emission line. It is possible to statistically isolate the fluctuations at a particular redshift by cross correlating emission originating from the same redshift, but in different emission lines. This technique will allow detection of clustering fluctuations from the faintest galaxies which individually cannot be detected, but which contribute substantially to the total signal due to their large numbers. We describe these fluctuations quantitatively through the line cross power spectrum. As an example of a particular application of this technique, we calculate the signal-to-noise ratio for a measurement of the cross power spectrum of the OI(63 micron) and OIII(52 micron) fine structure lines with the proposed Space Infrared Telescope for Cosmology and Astrophysics. We find that the cross power spectrum can be measured beyond a redshift of z=8. Such observations could constrain the evolution of the metallicity, bias, and duty cycle of faint galaxies at high redshifts and may also be sensitive to the reionization history through its effect on the minimum mass of galaxies. As another example, we consider the cross power spectrum of CO line emission measured with a large ground based telescope like CCAT and 21-cm radiation originating from hydrogen in galaxies after reionization with an interferometer similar in scale to MWA, but optimized for post-reionization redshifts.Comment: 21 pages, 6 figures; Replaced with version accepted by JCAP; Added an example of cross correlating CO line emission and 21cm line emission from galaxies after reionizatio

The Gross--Llewellyn Smith Sum Rule in the Analytic Approach to Perturbative QCD

We apply analytic perturbation theory to the Gross--Llewellyn Smith sum rule. We study the $Q^2$ evolution and the renormalization scheme dependence of the analytic three-loop QCD correction to this sum rule, and demonstrate that the results are practically renormalization scheme independent and lead to rather different $Q^2$ evolution than the standard perturbative correction possesses.Comment: 17 pages, 9 eps figures, REVTe

SMASH 1 : A VERY FAINT GLOBULAR CLUSTER DISRUPTING in the OUTER REACHES of the LMC?

We present the discovery of a very faint stellar system, SMASH 1, that is potentially a satellite of the Large Magellanic Cloud. Found within the Survey of the Magellanic Stellar History (SMASH), SMASH 1 is a compact (rh=9.1-3.4+5.9pc) and very low luminosity (Mv=-1.0±0.9,Lv=102.3±0.4L⊙ ) stellar system that is revealed by its sparsely populated main sequence and a handful of red giant branch candidate member stars. The photometric properties of these stars are compatible with a metal-poor ([Fe/H]=-2.2) and old (13 Gyr) isochrone located at a distance modulus of ∼18.8, i.e., a distance of . Situated at 11.°3 from the LMC in projection, its three-dimensional distance from the Cloud is 13 kpc, consistent with a connection to the LMC, whose tidal radius is at least . Although the nature of SMASH 1 remains uncertain, its compactness favors it being a stellar cluster and hence dark-matter free. If this is the case, its dynamical tidal radius is only ≲19 pc at this distance from the LMC, and smaller than the system's extent on the sky. Its low luminosity and apparent high ellipticity (ϵ=0.62-0.21+0.17) with its major axis pointing toward the LMC may well be the tell-tale sign of its imminent tidal demise.Peer reviewe

The bearable lightness of being

How are philosophical questions about what kinds of things there are to be understood and how are they to be answered? This paper defends broadly Fregean answers to these questions. Ontological categories-such as object, property, and relation-are explained in terms of a prior logical categorization of expressions, as singular terms, predicates of varying degree and level, etc. Questions about what kinds of object, property, etc., there are are, on this approach, reduce to questions about truth and logical form: for example, the question whether there are numbers is the question whether there are true atomic statements in which expressions function as singular terms which, if they have reference at all, stand for numbers, and the question whether there are properties of a given type is a question about whether there are meaningful predicates of an appropriate degree and level. This approach is defended against the objection that it must be wrong because makes what there depend on us or our language. Some problems confronting the Fregean approach-including Frege's notorious paradox of the concept horse-are addressed. It is argued that the approach results in a modest and sober deflationary understanding of ontological commitments

Strong Coupling Constant with Flavour Thresholds at Four Loops in the MS-bar Scheme

We present in analytic form the matching conditions for the strong coupling constant alpha_s^(n_f)(mu) at the flavour thresholds to three loops in the modified minimal-subtraction scheme. Taking into account the recently calculated coefficient beta_3 of the Callan-Symanzik beta function of quantum chromodynamics, we thus derive a four-loop formula for alpha_s^(n_f)(mu) together with appropriate relationships between the asymptotic scale parameters Lambda^(n_f) for different numbers of flavours n_f.Comment: 10 pages (Latex), 3 figures (Postscript

The Clustering of Massive Halos

The clustering properties of dark matter halos are a firm prediction of modern theories of structure formation. We use two large volume, high-resolution N-body simulations to study how the correlation function of massive dark matter halos depends upon their mass and formation history. We find that halos with the lowest concentrations are presently more clustered than those of higher concentration, the size of the effect increasing with halo mass; this agrees with trends found in studies of lower mass halos. The clustering dependence on other characterizations of the full mass accretion history appears weaker than the effect with concentration. Using the integrated correlation function, marked correlation functions, and a power-law fit to the correlation function, we find evidence that halos which have recently undergone a major merger or a large mass gain have slightly enhanced clustering relative to a randomly chosen population with the same mass distribution.Comment: 10 pages, 8 figures; text improved, references and one figure added; accepted for publication in Ap

Chirality in Bare and Passivated Gold Nanoclusters

Chiral structures have been found as the lowest-energy isomers of bare (Au$_{28}$ and Au$_{55}) and thiol-passivated (Au$_{28}(SCH$_{3})$_{16}$and Au$_{38}(SCH_{3})_{24}) gold nanoclusters. The degree of chirality existing in the chiral clusters was calculated using the Hausdorff chirality measure. We found that the index of chirality is higher in the passivated clusters and decreases with the cluster size. These results are consistent with the observed chiroptical activity recently reported for glutahione-passivated gold nanoclusters, and provide theoretical support for the existence of chirality in these novel compounds.Comment: 5 pages, 1 figure. Submitted to PR

Meson-meson scattering within one loop Chiral Perturbation Theory and its unitarization

We present the complete one-loop calculation of all the two meson scattering amplitudes within the framework of SU(3) Chiral Perturbation Theory, which includes pions, kaons and the eta. In addition, we have unitarized these amplitudes with the coupled channel Inverse Amplitude Method, which ensures simultaneously the good low energy properties of Chiral Perturbation Theory and unitarity. We show how this method provides a remarkable description of meson-meson scattering data up to 1.2 GeV including the scattering lengths and the generation of seven light resonances, which is consistent with previous determination of the chiral parameters. Particular attention is paid to discuss the differences and similarities of this work with previous analysis in the literature.Comment: 20 pages, 5 figures. Comments on sigma, kappa and eta', as well as some references added. Final version to appear in Phys.Rev.