4,005 research outputs found
Fakeons, quantum gravity and the correspondence principle
The correspondence principle made of unitarity, locality and
renormalizability has been very successful in quantum field theory. Among the
other things, it helped us build the standard model. However, it also showed
important limitations. For example, it failed to restrict the gauge group and
the matter sector in a powerful way. After discussing its effectiveness, we
upgrade it to make room for quantum gravity. The unitarity assumption is better
understood, since it allows for the presence of physical particles as well as
fake particles (fakeons). The locality assumption is applied to an interim
classical action, since the true classical action is nonlocal and emerges from
the quantization and a later process of classicization. The renormalizability
assumption is refined to single out the special role of the gauge couplings. We
show that the upgraded principle leads to an essentially unique theory of
quantum gravity. In particular, in four dimensions, a fakeon of spin 2,
together with a scalar field, is able to make the theory renormalizable while
preserving unitarity. We offer an overview of quantum field theories of
particles and fakeons in various dimensions, with and without gravity.Comment: Proceedings of the conference "Progress and Visions in Quantum Theory
in View of Gravity: Bridging foundations of physics and mathematics", Max
Planck Institute for Mathematics in the Sciences, Leipzig, October 2018 - to
appear in a book with the same title edited by F. Finster, D. Giulini, J.
Kleiner and J. Tolksdorf - 21 page
Distinct RNA profiles in subpopulations of extracellular vesicles: apoptotic bodies, microvesicles and exosomes
Introduction: In recent years, there has been an exponential increase in the number of studies aiming to understand the biology of exosomes, as well as other extracellular vesicles. However, classification of membrane vesicles and the appropriate protocols for their isolation are still under intense discussion and investigation. When isolating vesicles, it is crucial to use systems that are able to separate them, to avoid cross-contamination. Method: EVs released from three different kinds of cell lines: HMC-1, TF-1 and BV-2 were isolated using two centrifugation-based protocols. In protocol 1, apoptotic bodies were collected at 2,000×g, followed by filtering the supernatant through 0.8 µm pores and pelleting of microvesicles at 12,200×g. In protocol 2, apoptotic bodies and microvesicles were collected together at 16,500×g, followed by filtering of the supernatant through 0.2 µm pores and pelleting of exosomes at 120,000×g. Extracellular vesicles were analyzed by transmission electron microscopy, flow cytometry and the RNA profiles were investigated using a Bioanalyzer®. Results: RNA profiles showed that ribosomal RNA was primary detectable in apoptotic bodies and smaller RNAs without prominent ribosomal RNA peaks in exosomes. In contrast, microvesicles contained little or no RNA except for microvesicles collected from TF-1 cell cultures. The different vesicle pellets showed highly different distribution of size, shape and electron density with typical apoptotic body, microvesicle and exosome characteristics when analyzed by transmission electron microscopy. Flow cytometry revealed the presence of CD63 and CD81 in all vesicles investigated, as well as CD9 except in the TF-1-derived vesicles, as these cells do not express CD9. Conclusions: Our results demonstrate that centrifugation-based protocols are simple and fast systems to distinguish subpopulations of extracellular vesicles. Different vesicles show different RNA profiles and morphological characteristics, but they are indistinguishable using CD63-coated beads for flow cytometry analysis
Interactions between the Nse3 and Nse4 Components of the SMC5-6 Complex Identify Evolutionarily Conserved Interactions between MAGE and EID Families
The SMC5-6 protein complex is involved in the cellular response to DNA damage. It is composed of 6-8 polypeptides, of which Nse1, Nse3 and Nse4 form a tight sub-complex. MAGEG1, the mammalian ortholog of Nse3, is the founding member of the MAGE (melanoma-associated antigen) protein family and Nse4 is related to the EID (E1A-like inhibitor of differentiation) family of transcriptional repressors.Using site-directed mutagenesis, protein-protein interaction analyses and molecular modelling, we have identified a conserved hydrophobic surface on the C-terminal domain of Nse3 that interacts with Nse4 and identified residues in its N-terminal domain that are essential for interaction with Nse1. We show that these interactions are conserved in the human orthologs. Furthermore, interaction of MAGEG1, the mammalian ortholog of Nse3, with NSE4b, one of the mammalian orthologs of Nse4, results in transcriptional co-activation of the nuclear receptor, steroidogenic factor 1 (SF1). In an examination of the evolutionary conservation of the Nse3-Nse4 interactions, we find that several MAGE proteins can interact with at least one of the NSE4/EID proteins.We have found that, despite the evolutionary diversification of the MAGE family, the characteristic hydrophobic surface shared by all MAGE proteins from yeast to humans mediates its binding to NSE4/EID proteins. Our work provides new insights into the interactions, evolution and functions of the enigmatic MAGE proteins
Differential hippocampal shapes in posterior cortical atrophy patients: A comparison with control and typical AD subjects.
Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by predominant visual deficits and parieto-occipital atrophy, and is typically associated with Alzheimer's disease (AD) pathology. In AD, assessment of hippocampal atrophy is widely used in diagnosis, research, and clinical trials; its utility in PCA remains unclear. Given the posterior emphasis of PCA, we hypothesized that hippocampal shape measures may give additional group differentiation information compared with whole-hippocampal volume assessments. We investigated hippocampal volume and shape in subjects with PCA (n = 47), typical AD (n = 29), and controls (n = 48). Hippocampi were outlined on MRI scans and their 3D meshes were generated. We compared hippocampal volume and shape between disease groups. Mean adjusted hippocampal volumes were ∼8% smaller in PCA subjects (P < 0.001) and ∼22% smaller in tAD subject (P < 0.001) compared with controls. Significant inward deformations in the superior hippocampal tail were observed in PCA compared with controls even after adjustment for hippocampal volume. Inward deformations in large areas of the hippocampus were seen in tAD subjects compared with controls and PCA subjects, but only localized shape differences remained after adjusting for hippocampal volume. The shape differences observed, even allowing for volume differences, suggest that PCA and tAD are each associated with different patterns of hippocampal tissue loss that may contribute to the differential range and extent of episodic memory dysfunction in the two groups. Hum Brain Mapp, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc
Simultaneous disruption of two DNA polymerases, Polη and Polζ, in Avian DT40 cells unmasks the role of Polη in cellular response to various DNA lesions
Replicative DNA polymerases are frequently stalled by DNA lesions. The resulting replication blockage is released by homologous recombination (HR) and translesion DNA synthesis (TLS). TLS employs specialized TLS polymerases to bypass DNA lesions. We provide striking in vivo evidence of the cooperation between DNA polymerase η, which is mutated in the variant form of the cancer predisposition disorder xeroderma pigmentosum (XP-V), and DNA polymerase ζ by generating POLη−/−/POLζ−/− cells from the chicken DT40 cell line. POLζ−/− cells are hypersensitive to a very wide range of DNA damaging agents, whereas XP-V cells exhibit moderate sensitivity to ultraviolet light (UV) only in the presence of caffeine treatment and exhibit no significant sensitivity to any other damaging agents. It is therefore widely believed that Polη plays a very specific role in cellular tolerance to UV-induced DNA damage. The evidence we present challenges this assumption. The phenotypic analysis of POLη−/−/POLζ−/− cells shows that, unexpectedly, the loss of Polη significantly rescued all mutant phenotypes of POLζ−/− cells and results in the restoration of the DNA damage tolerance by a backup pathway including HR. Taken together, Polη contributes to a much wide range of TLS events than had been predicted by the phenotype of XP-V cells
Wilson-loop formalism for Reggeon exchange in soft high-energy scattering
We derive a nonperturbative expression for the non-vacuum,
qqbar-Reggeon-exchange contribution to the meson-meson elastic scattering
amplitude at high energy and low momentum transfer, in the framework of QCD.
Describing the mesons in terms of colourless qqbar dipoles, the problem is
reduced to the two-fermion-exchange contribution to the dipole-dipole
scattering amplitudes, which is expressed as a path integral, over the
trajectories of the exchanged fermions, of the expectation value of a certain
Wilson loop. We also show how the resulting expression can be reconstructed
from a corresponding quantity in the Euclidean theory, by means of analytic
continuation. Finally, we make contact with previous work on Reggeon exchange
in the gauge/gravity duality approach.Comment: A few misprints in the expressions for the relevant Wilson loops have
been corrected. 55 pages, 7 figure
Warped Riemannian metrics for location-scale models
The present paper shows that warped Riemannian metrics, a class of Riemannian
metrics which play a prominent role in Riemannian geometry, are also of
fundamental importance in information geometry. Precisely, the paper features a
new theorem, which states that the Rao-Fisher information metric of any
location-scale model, defined on a Riemannian manifold, is a warped Riemannian
metric, whenever this model is invariant under the action of some Lie group.
This theorem is a valuable tool in finding the expression of the Rao-Fisher
information metric of location-scale models defined on high-dimensional
Riemannian manifolds. Indeed, a warped Riemannian metric is fully determined by
only two functions of a single variable, irrespective of the dimension of the
underlying Riemannian manifold. Starting from this theorem, several original
contributions are made. The expression of the Rao-Fisher information metric of
the Riemannian Gaussian model is provided, for the first time in the
literature. A generalised definition of the Mahalanobis distance is introduced,
which is applicable to any location-scale model defined on a Riemannian
manifold. The solution of the geodesic equation is obtained, for any Rao-Fisher
information metric defined in terms of warped Riemannian metrics. Finally,
using a mixture of analytical and numerical computations, it is shown that the
parameter space of the von Mises-Fisher model of -dimensional directional
data, when equipped with its Rao-Fisher information metric, becomes a Hadamard
manifold, a simply-connected complete Riemannian manifold of negative sectional
curvature, for . Hopefully, in upcoming work, this will be
proved for any value of .Comment: first version, before submissio
The Generation of Forces and Moments during Visual-Evoked Steering Maneuvers in Flying Drosophila
Sideslip force, longitudinal force, rolling moment, and pitching moment generated by tethered fruit flies, Drosophila melanogaster, were measured during optomotor reactions within an electronic flight simulator. Forces and torques were acquired by optically measuring the angular deflections of the beam to which the flies were tethered using a laser and a photodiode. Our results indicate that fruit flies actively generate both sideslip and roll in response to a lateral focus of expansion (FOE). The polarity of this behavior was such that the animal's aerodynamic response would carry it away from the expanding pattern, suggesting that it constitutes an avoidance reflex or centering response. Sideslip forces and rolling moments were sinusoidal functions of FOE position, whereas longitudinal force was proportional to the absolute value of the sine of FOE position. Pitching moments remained nearly constant irrespective of stimulus position or strength, with a direction indicating a tonic nose-down pitch under tethered conditions. These experiments expand our understanding of the degrees of freedom that a fruit fly can actually control in flight
Motor features in posterior cortical atrophy and their imaging correlates
Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by impaired higher visual processing skills; however, motor features more commonly associated with corticobasal syndrome may also occur. We investigated the frequency and clinical characteristics of motor features in 44 PCA patients and, with 30 controls, conducted voxel-based morphometry, cortical thickness, and subcortical volumetric analyses of their magnetic resonance imaging. Prominent limb rigidity was used to define a PCA-motor subgroup. A total of 30% (13) had PCA-motor; all demonstrating asymmetrical left upper limb rigidity. Limb apraxia was more frequent and asymmetrical in PCA-motor, as was myoclonus. Tremor and alien limb phenomena only occurred in this subgroup. The subgroups did not differ in neuropsychological test performance or apolipoprotein E4 allele frequency. Greater asymmetry of atrophy occurred in PCA-motor, particularly involving right frontoparietal and peri-rolandic cortices, putamen, and thalamus. The 9 patients (including 4 PCA-motor) with pathology or cerebrospinal fluid all showed evidence of Alzheimer's disease. Our data suggest that PCA patients with motor features have greater atrophy of contralateral sensorimotor areas but are still likely to have underlying Alzheimer's disease
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