Possible structure in the GRB sky distribution at redshift two

Context. Research over the past three decades has revolutionized cosmology while supporting the standard cosmological model. However, the cosmological principle of Universal homogeneity and isotropy has always been in question, since structures as large as the survey size have always been found each time the survey size has increased. Until 2013, the largest known structure in our Universe was the Sloan Great Wall, which is more than 400 Mpc long located approximately one billion light years away. Aims. Gamma-ray bursts are the most energetic explosions in the Universe. As they are associated with the stellar endpoints of massive stars and are found in and near distant galaxies, they are viable indicators of the dense part of the Universe containing normal matter. The spatial distribution of gamma-ray bursts can thus help expose the large scale structure of the Universe. Methods. As of July 2012, 283 GRB redshifts have been measured. Subdividing this sample into nine radial parts, each containing 31 GRBs, indicates that the GRB sample having 1.6 < z < 2.1 differs significantly from the others in that 14 of the 31 GRBs are concentrated in roughly 1/8 of the sky. A two-dimensional Kolmogorov-Smirnov test, a nearest-neighbour test, and a Bootstrap Point-Radius Method explore the significance of this clustering. Results. All tests used indicate that there is a statistically significant clustering of the GRB sample at 1.6 < z < 2.1. Furthermore, this angular excess cannot be entirely attributed to known selection biases, making its existence due to chance unlikely. Conclusions. This huge structure lies ten times farther away than the Sloan Great Wall, at a distance of approximately ten billion light years. The size of the structure defined by these GRBs is about 2000-3000 Mpc, or more than six times the size of the Sloan Great Wall.Comment: accepted for publication in Astronomy & Astrophysic

Near-integrated GARCH sequences

Motivated by regularities observed in time series of returns on speculative assets, we develop an asymptotic theory of GARCH(1,1) processes {y_k} defined by the equations y_k=\sigma_k\epsilon_k, \sigma_k^2=\omega +\alpha y_{k-1}^2+\beta \sigma_{k-1}^2 for which the sum \alpha +\beta approaches unity as the number of available observations tends to infinity. We call such sequences near-integrated. We show that the asymptotic behavior of near-integrated GARCH(1,1) processes critically depends on the sign of \gamma :=\alpha +\beta -1. We find assumptions under which the solutions exhibit increasing oscillations and show that these oscillations grow approximately like a power function if \gamma \leq 0 and exponentially if \gamma >0. We establish an additive representation for the near-integrated GARCH(1,1) processes which is more convenient to use than the traditional multiplicative Volterra series expansion.Comment: Published at http://dx.doi.org/10.1214/105051604000000783 in the Annals of Applied Probability (http://www.imstat.org/aap/) by the Institute of Mathematical Statistics (http://www.imstat.org

Amyloid Fibers of α-Synuclein Catalyze Chemical Reactions

Amyloid fibers of the protein α-synuclein, found in Lewy body deposits, are hallmarks of Parkinson’s disease. We here show that α-synuclein amyloids catalyze biologically relevant chemical reactions in vitro. Amyloid fibers, but not monomers, of α-synuclein catalyzed hydrolysis of the model ester para-nitrophenyl acetate and dephosphorylation of the model phosphoester para-nitrophenyl-orthophosphate. When His50 was replaced with Ala in α-synuclein, dephosphorylation but not esterase activity of amyloids was diminished. Truncation of the protein’s C-terminus had no effect on fiber catalytic efficiency. Catalytic activity of α-synuclein fibers may be a new gain-of-function that plays a role in Parkinson’s disease

Cosmology with Gamma-Ray Bursts Using k-correction

In the case of Gamma-Ray Bursts with measured redshift, we can calculate the k-correction to get the fluence and energy that were actually produced in the comoving system of the GRB. To achieve this we have to use well-fitted parameters of a GRB spectrum, available in the GCN database. The output of the calculations is the comoving isotropic energy E_iso, but this is not the endpoint: this data can be useful for estimating the {\Omega}M parameter of the Universe and for making a GRB Hubble diagram using Amati's relation.Comment: 4 pages, 6 figures. Presented as a talk on the conference '7th INTEGRAL/BART Workshop 14 -18 April 2010, Karlovy Vary, Czech Republic'. Published in Acta Polytechnic

Estimation in nonstationary random coefficient autoregressive models

We investigate the estimation of parameters in the random coefficient autoregressive model. We consider a nonstationary RCA process and show that the innovation variance parameter cannot be estimated by the quasi-maximum likelihood method. The asymptotic normality of the quasi-maximum likelihood estimator for the remaining model parameters is proven so the unit root problem does not exist in the random coefficient autoregressive model.Comment: 21 page

Macromolecular crowding modulates α-synuclein amyloid fiber growth

The crowdedness of living cells, hundreds of milligrams per milliliter of macromolecules, may affect protein folding, function, and misfolding. Still, such processes are most often studied in dilute solutions in vitro. To assess consequences of the in vivo milieu, we here investigated the effects of macromolecular crowding on the amyloid fiber formation reaction of α-synuclein, the amyloidogenic protein in Parkinson\u27s disease. For this, we performed spectroscopic experiments probing individual steps of the reaction as a function of the macromolecular crowding agent Ficoll70, which is an inert sucrose-based polymer that provides excluded-volume effects. The experiments were performed at neutral pH at quiescent conditions to avoid artifacts due to shaking and glass beads (typical conditions for α-synuclein), using amyloid fiber seeds to initiate reactions. We find that both primary nucleation and fiber elongation steps during α-synuclein amyloid formation are accelerated by the presence of 140 and 280 mg/mL Ficoll70. Moreover, in the presence of Ficoll70 at neutral pH, secondary nucleation appears favored, resulting in faster overall α-synuclein amyloid formation. In contrast, sucrose, a small-molecule osmolyte and building block of Ficoll70, slowed down α-synuclein amyloid formation. The ability of cell environments to modulate reaction kinetics to a large extent, such as severalfold faster individual steps in α-synuclein amyloid formation, is an important consideration for biochemical reactions in living systems

Crosstalk Between Alpha-Synuclein and Other Human and Non-Human Amyloidogenic Proteins: Consequences for Amyloid Formation in Parkinson\u27s Disease

It was recently shown (Sampson et al., Elife9, 2020) that an amyloidogenic protein, CsgA, present in E. coli biofilms in the gut can trigger Parkinson\u27s disease in mice. This study emphasizes the possible role of the gut microbiome in modulation (and even initiation) of human neurodegenerative disorders, such as Parkinson\u27s disease. As the CsgA protein was found to accelerate alpha-synuclein (the key amyloidogenic protein in Parkinson\u27s disease) amyloid formation in vitro, this result suggests that also other amyloidogenic proteins from gut bacteria, and even from the diet (such as stable allergenic proteins), may be able to affect human protein conformations and thereby modulate amyloid-related diseases. In this review, we summarize what has been reported in terms of in vitro cross-reactivity studies between alpha-synuclein and other amyloidogenic human and non-human proteins. It becomes clear from the limited data that exist that there is a fine line between acceleration and inhibition, but that cross-reactivity is widespread, and it is more common for other proteins (among the studied cases) to accelerate alpha-synuclein amyloid formation than to block it. It is of high importance to expand investigations of cross-reactivity between amyloidogenic proteins to both reveal underlying mechanisms and links between human diseases, as well as to develop new treatments that may be based on an altered gut microbiome

Response to crowded conditions reveals compact nucleus for amyloid formation of folded protein

Although the consequences of the crowded cell environments may affect protein folding, function and misfolding reactions, these processes are often studied in dilute solutions in vitro. We here used biophysical experiments to investigate the amyloid fibril formation process of the fish protein apo-β-parvalbumin in solvent conditions that mimic steric and solvation aspects of the in vivo milieu. Apo-β-parvalbumin is a folded protein that readily adopts an amyloid state via a nucleation-elongation mechanism. Aggregation experiments in the presence of macromolecular crowding agents (probing excluded volume, entropic effects) as well as small molecule osmolytes (probing solvation, enthalpic effects) revealed that both types of agents accelerate overall amyloid formation, but the elongation step was faster with macromolecular crowding agents but slower in the presence of osmolytes. The observations can be explained by the steric effects of excluded volume favoring assembled states and that amyloid nucleation does not involve monomer unfolding. In contrast, the solvation effects due to osmolyte presence promote nucleation but not elongation. Therefore, the amyloid-competent nuclei must be compact with less osmolytes excluded from the surface than either the folded monomers or amyloid fibers. We conclude that, in contrast to other amyloidogenic folded proteins, amyloid formation of apo-β-parvalbumin is accelerated by crowded cell-like conditions due to a nucleation process that does not involve large-scale protein unfolding