73 research outputs found
Cosmic distance-duality as probe of exotic physics and acceleration
In cosmology, distances based on standard candles (e.g. supernovae) and
standard rulers (e.g. baryon oscillations) agree as long as three conditions
are met: (1) photon number is conserved, (2) gravity is described by a metric
theory with (3) photons travelling on unique null geodesics. This is the
content of distance-duality (the reciprocity relation) which can be violated by
exotic physics. Here we analyse the implications of the latest cosmological
data sets for distance-duality. While broadly in agreement and confirming
acceleration we find a 2-sigma violation caused by excess brightening of SN-Ia
at z > 0.5, perhaps due to lensing magnification bias. This brightening has
been interpreted as evidence for a late-time transition in the dark energy but
because it is not seen in the d_A data we argue against such an interpretation.
Our results do, however, rule out significant SN-Ia evolution and extinction:
the "replenishing" grey-dust model with no cosmic acceleration is excluded at
more than 4-sigma despite this being the best-fit to SN-Ia data alone, thereby
illustrating the power of distance-duality even with current data sets.Comment: 6 pages, 4 colour figures. Version accepted as a Rapid Communication
in PR
Application of Pulsed Field Gel Electrophoresis to Determine γ-ray-induced Double-strand Breaks in Yeast Chromosomal Molecules
The frequency of DNA double-strand breaks (dsb) was determined in yeast cells exposed to γ-rays under anoxic conditions. Genomic DNA of treated cells was separated by pulsed field gel electrophoresis, and two different approaches for the evaluation of the gels were employed: (1) The DNA mass distribution profile obtained by electrophoresis was compared to computed profiles, and the number of DSB per unit length was then derived in terms of a fitting procedure; (2) hybridization of selected chromosomes was performed, and a comparison of the hybridization signals in treated and untreated samples was then used to derive the frequency of dsb
Charge Deficiency, Charge Transport and Comparison of Dimensions
We study the relative index of two orthogonal infinite dimensional
projections which, in the finite dimensional case, is the difference in their
dimensions. We relate the relative index to the Fredholm index of appropriate
operators, discuss its basic properties, and obtain various formulas for it. We
apply the relative index to counting the change in the number of electrons
below the Fermi energy of certain quantum systems and interpret it as the
charge deficiency. We study the relation of the charge deficiency with the
notion of adiabatic charge transport that arises from the consideration of the
adiabatic curvature. It is shown that, under a certain covariance,
(homogeneity), condition the two are related. The relative index is related to
Bellissard's theory of the Integer Hall effect. For Landau Hamiltonians the
relative index is computed explicitly for all Landau levels.Comment: 23 pages, no figure
Model-independent dark energy test with sigma_8 using results from the Wilkinson Microwave Anisotropy Probe
By combining the recent WMAP measurements of the cosmic microwave background
anisotropies and the results of the recent luminosity distance measurements to
type-Ia supernovae, we find that the normalization of the matter power spectrum
on cluster scales, sigma_8, can be used to discriminate between dynamical
models of dark energy (quintessence models) and a conventional cosmological
constant model (LCDM).Comment: 5 pages, 6 figures. Additional discussion and reference, matches PRD
accepted versio
Small, seeding-competent huntingtin fibrils are prominent aggregate species in brains of zQ175 Huntington's disease knock-in mice
The deposition of mutant huntingtin (mHTT) protein aggregates in neurons of patients is a pathological hallmark of Huntington’s disease (HD). Previous investigations in cell-free and cell-based disease models showed mHTT exon-1 (mHTTex1) fragments with pathogenic polyglutamine (polyQ) tracts (>40 glutamines) to self-assemble into highly stable, β-sheet-rich protein aggregates with a fibrillar morphology. HD knock-in mouse models have not been extensively studied with regard to mHTT aggregation. They endogenously produce full-length mHTT with a pathogenic polyQ tract as well as mHTTex1 fragments. Here, we demonstrate that seeding-competent, fibrillar mHTT aggregates can be readily detected in brains of zQ175 knock-in HD mice. To do this, we applied a highly sensitive FRET-based protein amplification assay that is capable of detecting seeding-competent mHTT aggregate species down to the femtomolar range. Furthermore, we show that fibrillar structures with an average length of ∼200 nm can be enriched with aggregate-specific mouse and human antibodies from zQ175 mouse brain extracts through immunoprecipitations, confirming that such structures are formed in vivo. Together these studies indicate that small, fibrillar, seeding-competent mHTT structures are prominent aggregate species in brains of zQ175 mice
Non-parametric Dark Energy Degeneracies
We study the degeneracies between dark energy dynamics, dark matter and
curvature using a non-parametric and non-perturbative approach. This allows us
to examine the knock-on bias induced in the reconstructed dark energy equation
of state, w(z), when there is a bias in the cosmic curvature or dark matter
content, without relying on any specific parameterisation of w. Even assuming
perfect Hubble, distance and volume measurements, we show that for z > 1, the
bias in w(z) is up to two orders of magnitude larger than the corresponding
errors in Omega_k or Omega_m. This highlights the importance of obtaining
unbiased estimators of all cosmic parameters in the hunt for dark energy
dynamics.Comment: 10 pages, 8 figures. Invited Review for special issue of General
Relativity and Gravitation issue on Dark Energy, eds. G. F.R Ellis et a
Evaluation of presumably disease causing SCN1A variants in a cohort of common epilepsy syndromes
Objective: The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. Methods: We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. Results and Interpretation: We identified 8 known missense mutations, previously reported as path
Variation of mutation and recombination frequencies over a range of thymidylate concentrations in a diploid thymidylate auxotroph.
A diploid yeast thymidylate auxotroph was grown under conditions of thymidylate stress ranging from depletion to excess levels of the nucleotide. High concentrations of thymidylate were mutagenic and recombinagenic whereas starvation for thymine nucleotides was recombinagenic and only slightly mutagenic. These results are discussed in relation to possible mutagenic and recombinagenic mechanisms of nucleotide pool imbalances
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