2,406 research outputs found
Inflation on the Brane with Vanishing Gravity
Many existing models of brane inflation suffer from a steep irreducible
gravitational potential between the branes that causes inflation to end too
early. Inspired by the fact that point masses in 2+1 D exert no gravitational
force, we propose a novel unwarped and non-supersymmetric setup for inflation,
consisting of 3-branes in two extra dimensions compactified on a sphere. The
size of the sphere is stabilized by a combination of a bulk cosmological
constant and a magnetic flux. Computing the 4D effective potential between
probe branes in this background, we find a non-zero contribution only from
exchange of level-1 KK modes of the graviton and radion. Identifying antipodal
points on the 2-sphere projects out these modes, eliminating entirely the
troublesome gravitational contribution to the inflationary potential.Comment: 19 pages, 11 figures, JHEP forma
Human helminth therapy to treat inflammatory disorders - where do we stand?
Parasitic helminths have evolved together with the mammalian immune system over many millennia and as such they have become remarkably efficient modulators in order to promote their own survival. Their ability to alter and/or suppress immune responses could be beneficial to the host by helping control excessive inflammatory responses and animal models and pre-clinical trials have all suggested a beneficial effect of helminth infections on inflammatory bowel conditions, MS, asthma and atopy. Thus, helminth therapy has been suggested as a possible treatment method for autoimmune and other inflammatory disorders in humans
Heteroreceptor complexes formed by dopamine D1, histamine H3 and N-methyl-D-aspartate glutamate receptors as targets to prevent neuronal death in Alzheimer's disease
Alzheimer’s disease (AD) is a neurodegenerative disorder causing progressive memory loss and cognitive dysfunction. Anti-AD strategies targeting cell receptors consider them as isolated units. However, many cell surface receptors cooperate and physically contact each other forming complexes having different biochemical properties than individual receptors. We here report the discovery of dopamine D , histamine H , and N-methylD-aspartate (NMDA) glutamate receptor heteromers in heterologous systems and in rodent brain cortex. Heteromers were detected by coimmunoprecipitation and in situ proximity ligation assays (PLA) in the rat cortex where H receptor agonists, via negative cross-talk, and H receptor antagonists, via cross-antagonism, decreased D receptor agonist signaling determined by ERK1/2 or Akt phosphorylation and counteracted D receptormediated excitotoxic cell death. Both D and H receptor antagonists also counteracted NMDA toxicity suggesting a complex interaction between NMDA receptors and D -H receptor heteromer function. Likely due to heteromerization, H receptors act as allosteric regulator for D and NMDA receptors. By bioluminescence resonance energy transfer (BRET), we demonstrated that D or H receptors form heteromers with NR1A/NR2B NMDA receptor subunits. D -H -NMDA receptor complexes were confirmed by BRET combined with fluorescence complementation. The endogenous expression of complexes in mouse cortex was determined by PLA and similar expression was observed in wild-type and APP/PS1 mice. Consistent with allosteric receptor-receptor interactions within the complex, H receptor antagonists reduced NMDA or D receptor-mediated excitotoxic cell death in cortical organotypic cultures. Moreover, H receptor antagonists reverted the toxicity induced by ß -amyloid peptide. Thus, histamine H receptors in D -H -NMDA heteroreceptor complexes arise as promising targets to prevent neurodegeneration
Understanding Galaxy Formation and Evolution
The old dream of integrating into one the study of micro and macrocosmos is
now a reality. Cosmology, astrophysics, and particle physics intersect in a
scenario (but still not a theory) of cosmic structure formation and evolution
called Lambda Cold Dark Matter (LCDM) model. This scenario emerged mainly to
explain the origin of galaxies. In these lecture notes, I first present a
review of the main galaxy properties, highlighting the questions that any
theory of galaxy formation should explain. Then, the cosmological framework and
the main aspects of primordial perturbation generation and evolution are
pedagogically detached. Next, I focus on the ``dark side'' of galaxy formation,
presenting a review on LCDM halo assembling and properties, and on the main
candidates for non-baryonic dark matter. It is shown how the nature of
elemental particles can influence on the features of galaxies and their
systems. Finally, the complex processes of baryon dissipation inside the
non-linearly evolving CDM halos, formation of disks and spheroids, and
transformation of gas into stars are briefly described, remarking on the
possibility of a few driving factors and parameters able to explain the main
body of galaxy properties. A summary and a discussion of some of the issues and
open problems of the LCDM paradigm are given in the final part of these notes.Comment: 50 pages, 10 low-resolution figures (for normal-resolution, DOWNLOAD
THE PAPER (PDF, 1.9 Mb) FROM http://www.astroscu.unam.mx/~avila/avila.pdf).
Lectures given at the IV Mexican School of Astrophysics, July 18-25, 2005
(submitted to the Editors on March 15, 2006
The stellar halo of the Galaxy
Stellar halos may hold some of the best preserved fossils of the formation
history of galaxies. They are a natural product of the merging processes that
probably take place during the assembly of a galaxy, and hence may well be the
most ubiquitous component of galaxies, independently of their Hubble type. This
review focuses on our current understanding of the spatial structure, the
kinematics and chemistry of halo stars in the Milky Way. In recent years, we
have experienced a change in paradigm thanks to the discovery of large amounts
of substructure, especially in the outer halo. I discuss the implications of
the currently available observational constraints and fold them into several
possible formation scenarios. Unraveling the formation of the Galactic halo
will be possible in the near future through a combination of large wide field
photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes.
Full-resolution version available at
http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd
Low and High Expressing Alleles of the LMNA Gene: Implications for Laminopathy Disease Development
Today, there are at least a dozen different genetic disorders caused by mutations within the LMNA gene, and collectively, they are named laminopathies. Interestingly, the same mutation can cause phenotypes with different severities or even different disorders and might, in some cases, be asymptomatic. We hypothesized that one possible contributing mechanism for this phenotypic variability could be the existence of high and low expressing alleles in the LMNA locus. To investigate this hypothesis, we developed an allele-specific absolute quantification method for lamin A and lamin C transcripts using the polymorphic rs4641C/T LMNA coding SNP. The contribution of each allele to the total transcript level was investigated in nine informative human primary dermal fibroblast cultures from Hutchinson-Gilford progeria syndrome (HGPS) and unaffected controls. Our results show differential expression of the two alleles. The C allele is more frequently expressed and accounts for ∼70% of the lamin A and lamin C transcripts. Analysis of samples from six patients with Hutchinson-Gilford progeria syndrome showed that the c.1824C>T, p.G608G mutation is located in both the C and the T allele, which might account for the variability in phenotype seen among HGPS patients. Our method should be useful for further studies of human samples with mutations in the LMNA gene and to increase the understanding of the link between genotype and phenotype in laminopathies
The Search for Invariance: Repeated Positive Testing Serves the Goals of Causal Learning
Positive testing is characteristic of exploratory behavior, yet it seems to be at odds with the aim of information seeking. After all, repeated demonstrations of one’s current hypothesis often produce the same evidence and fail to distinguish it from potential alternatives. Research on the development of scientific reasoning and adult rule learning have both documented and attempted to explain this behavior. The current chapter reviews this prior work and introduces a novel theoretical account—the Search for Invariance (SI) hypothesis—which suggests that producing multiple positive examples serves the goals of causal learning. This hypothesis draws on the interventionist framework of causal reasoning, which suggests that causal learners are concerned with the invariance of candidate hypotheses. In a probabilistic and interdependent causal world, our primary goal is to determine whether, and in what contexts, our causal hypotheses provide accurate foundations for inference and intervention—not to disconfirm their alternatives. By recognizing the central role of invariance in causal learning, the phenomenon of positive testing may be reinterpreted as a rational information-seeking strategy
Large Scale Structure of the Universe
Galaxies are not uniformly distributed in space. On large scales the Universe
displays coherent structure, with galaxies residing in groups and clusters on
scales of ~1-3 Mpc/h, which lie at the intersections of long filaments of
galaxies that are >10 Mpc/h in length. Vast regions of relatively empty space,
known as voids, contain very few galaxies and span the volume in between these
structures. This observed large scale structure depends both on cosmological
parameters and on the formation and evolution of galaxies. Using the two-point
correlation function, one can trace the dependence of large scale structure on
galaxy properties such as luminosity, color, stellar mass, and track its
evolution with redshift. Comparison of the observed galaxy clustering
signatures with dark matter simulations allows one to model and understand the
clustering of galaxies and their formation and evolution within their parent
dark matter halos. Clustering measurements can determine the parent dark matter
halo mass of a given galaxy population, connect observed galaxy populations at
different epochs, and constrain cosmological parameters and galaxy evolution
models. This chapter describes the methods used to measure the two-point
correlation function in both redshift and real space, presents the current
results of how the clustering amplitude depends on various galaxy properties,
and discusses quantitative measurements of the structures of voids and
filaments. The interpretation of these results with current theoretical models
is also presented.Comment: Invited contribution to be published in Vol. 8 of book "Planets,
Stars, and Stellar Systems", Springer, series editor T. D. Oswalt, volume
editor W. C. Keel, v2 includes additional references, updated to match
published versio
- …