373 research outputs found
Holography and Variable Cosmological Constant
An effective local quantum field theory with UV and IR cutoffs correlated in
accordance with holographic entropy bounds is capable of rendering the
cosmological constant (CC) stable against quantum corrections. By setting an IR
cutoff to length scales relevant to cosmology, one easily obtains the currently
observed rho_Lambda ~ 10^{-47} GeV^4, thus alleviating the CC problem. It is
argued that scaling behavior of the CC in these scenarios implies an
interaction of the CC with matter sector or a time-dependent gravitational
constant, to accommodate the observational data.Comment: 7 pages, final version accepted by PR
Eccentric lamellar keratolimbal grafts harvested with a manually guided microkeratome
Background: To perform lamellar keratolimbal allograft transplantation in a one- step procedure with a single graft, we investigated the feasibility of harvesting eccentric lamellar keratolimbal grafts from conventionally processed corneoscleral buttons using a manually guided microkeratome in conjunction with an artificial anterior chamber system. Methods: We used the Moria LSK- One microkeratome and the automated lamellar therapeutic keratoplasty ( ALTK) system ( Antony, France). Ten human donor eyes were used to obtain single- piece lamellar keratolimbal grafts. Specimens were processed for light and electron microscopy. Results: Eccentric keratolimbal grafts could be obtained from all human donor buttons. Grafts include a crescent- shaped limbal and a large corneal portion. No visible damage to the limbal region was discernible. Conclusion: Our data show that the LSK- One microkeratome in conjunction with the ALTK system allows harvesting eccentric keratolimbal grafts from donor corneoscleral buttons. Copyright (c) 2007 S. Karger AG, Basel
The Running of the Cosmological and the Newton Constant controlled by the Cosmological Event Horizon
We study the renormalisation group running of the cosmological and the Newton
constant, where the renormalisation scale is given by the inverse of the radius
of the cosmological event horizon. In this framework, we discuss the future
evolution of the universe, where we find stable de Sitter solutions, but also
"big crunch"-like and "big rip"-like events, depending on the choice of the
parameters in the model.Comment: 14 pages, 7 figures, minor improvements, references adde
N-glycans of Human Protein C Inhibitor: Tissue-Specific Expression and Function
Protein C inhibitor (PCI) is a serpin type of serine protease inhibitor that is found in many tissues and fluids in human, including blood plasma, seminal plasma and urine. This inhibitor displays an unusually broad protease specificity compared with other serpins. Previous studies have shown that the N-glycan(s) and the NH2-terminus affect some blood-related functions of PCI. In this study, we have for the first time determined the N-glycan profile of seminal plasma PCI, by mass spectrometry. The N-glycan structures differed markedly compared with those of both blood-derived and urinary PCI, providing evidence that the N-glycans of PCI are expressed in a tissue-specific manner. The most abundant structure (m/z 2592.9) had a composition of Fuc3Hex5HexNAc4, consistent with a core fucosylated bi-antennary glycan with terminal Lewisx. A major serine protease in semen, prostate specific antigen (PSA), was used to evaluate the effects of N-glycans and the NH2-terminus on a PCI function related to the reproductive tract. Second-order rate constants for PSA inhibition by PCI were 4.3±0.2 and 4.1±0.5 M−1s−1 for the natural full-length PCI and a form lacking six amino acids at the NH2-terminus, respectively, whereas these constants were 4.8±0.1 and 29±7 M−1s−1 for the corresponding PNGase F-treated forms. The 7–8-fold higher rate constants obtained when both the N-glycans and the NH2-terminus had been removed suggest that these structures jointly affect the rate of PSA inhibition, presumably by together hindering conformational changes of PCI required to bind to the catalytic pocket of PSA
Scalar-Tensor Models of Normal and Phantom Dark Energy
We consider the viability of dark energy (DE) models in the framework of the
scalar-tensor theory of gravity, including the possibility to have a phantom DE
at small redshifts as admitted by supernova luminosity-distance data. For
small , the generic solution for these models is constructed in the form of
a power series in without any approximation. Necessary constraints for DE
to be phantom today and to cross the phantom divide line at small
are presented. Considering the Solar System constraints, we find for the
post-Newtonian parameters that and for
the model to be viable, and (but very close to 1) if the model
has a significantly phantom DE today. However, prospects to establish the
phantom behaviour of DE are much better with cosmological data than with Solar
System experiments. Earlier obtained results for a -dominated universe
with the vanishing scalar field potential are extended to a more general DE
equation of state confirming that the cosmological evolution of these models
rule them out. Models of currently fantom DE which are viable for small can
be easily constructed with a constant potential; however, they generically
become singular at some higher . With a growing potential, viable models
exist up to an arbitrary high redshift.Comment: 30 pages, 4 figures; Matches the published version containing an
expanded discussion of various point
DOR/Tp53inp2 and Tp53inp1 Constitute a Metazoan Gene Family Encoding Dual Regulators of Autophagy and Transcription
Human DOR/TP53INP2 displays a unique bifunctional role as a modulator of autophagy and gene transcription. However, the domains or regions of DOR that participate in those functions have not been identified. Here we have performed structure/function analyses of DOR guided by identification of conserved regions in the DOR gene family by phylogenetic reconstructions. We show that DOR is present in metazoan species. Invertebrates harbor only one gene, DOR/Tp53inp2, and in the common ancestor of vertebrates Tp53inp1 may have arisen by gene duplication. In keeping with these data, we show that human TP53INP1 regulates autophagy and that different DOR/TP53INP2 and TP53INP1 proteins display transcriptional activity. The use of molecular evolutionary information has been instrumental to determine the regions that participate in DOR functions. DOR and TP53INP1 proteins share two highly conserved regions (region 1, aa residues 28–42; region 2, 66–112 in human DOR). Mutation of conserved hydrophobic residues in region 1 of DOR (that are part of a nuclear export signal, NES) reduces transcriptional activity, and blocks nuclear exit and autophagic activity under autophagy-activated conditions. We also identify a functional and conserved LC3-interacting motif (LIR) in region 1 of DOR and TP53INP1 proteins. Mutation of conserved acidic residues in region 2 of DOR reduces transcriptional activity, impairs nuclear exit in response to autophagy activation, and disrupts autophagy. Taken together, our data reveal DOR and TP53INP1 as dual regulators of transcription and autophagy, and identify two conserved regions in the DOR family that concentrate multiple functions crucial for autophagy and transcription
Hubble expansion and structure formation in the "running FLRW model" of the cosmic evolution
A new class of FLRW cosmological models with time-evolving fundamental
parameters should emerge naturally from a description of the expansion of the
universe based on the first principles of quantum field theory and string
theory. Within this general paradigm, one expects that both the gravitational
Newton's coupling, G, and the cosmological term, Lambda, should not be strictly
constant but appear rather as smooth functions of the Hubble rate. This
scenario ("running FLRW model") predicts, in a natural way, the existence of
dynamical dark energy without invoking the participation of extraneous scalar
fields. In this paper, we perform a detailed study of these models in the light
of the latest cosmological data, which serves to illustrate the
phenomenological viability of the new dark energy paradigm as a serious
alternative to the traditional scalar field approaches. By performing a joint
likelihood analysis of the recent SNIa data, the CMB shift parameter, and the
BAOs traced by the Sloan Digital Sky Survey, we put tight constraints on the
main cosmological parameters. Furthermore, we derive the theoretically
predicted dark-matter halo mass function and the corresponding redshift
distribution of cluster-size halos for the "running" models studied. Despite
the fact that these models closely reproduce the standard LCDM Hubble
expansion, their normalization of the perturbation's power-spectrum varies,
imposing, in many cases, a significantly different cluster-size halo redshift
distribution. This fact indicates that it should be relatively easy to
distinguish between the "running" models and the LCDM cosmology using realistic
future X-ray and Sunyaev-Zeldovich cluster surveys.Comment: Version published in JCAP 08 (2011) 007: 1+41 pages, 6 Figures, 1
Table. Typos corrected. Extended discussion on the computation of the
linearly extrapolated density threshold above which structures collapse in
time-varying vacuum models. One appendix, a few references and one figure
adde
Cardiac Insulin Resistance in Subjects With Metabolic Syndrome Traits and Early Subclinical Atherosclerosis.
OBJECTIVE
Experimental evidence suggests that metabolic syndrome (MetS) is associated with changes in cardiac metabolism. Whether this association occurs in humans is unknown.
RESEARCH DESIGN AND METHODS
821 asymptomatic individuals from the Progression of Early Subclinical Atherosclerosis (PESA) study (50.6 [46.9-53.6] years, 83.7% male) underwent two whole-body 18F-fluorodeoxyglucose positron emission tomography-magnetic resonance (18F-FDG PET-MR) 4.8 ± 0.6 years apart. Presence of myocardial 18F-FDG uptake was evaluated qualitatively and quantitatively. No myocardial uptake was grade 0, while positive uptake was classified in grades 1-3 according to target-to-background ratio tertiles.
RESULTS
One hundred fifty-six participants (19.0%) showed no myocardial 18F-FDG uptake, and this was significantly associated with higher prevalence of MetS (29.0% vs. 13.9%, P < 0.001), hypertension (29.0% vs. 18.0%, P = 0.002), and diabetes (11.0% vs. 3.2%, P < 0.001), and with higher insulin resistance index (HOMA-IR, 1.64% vs. 1.23%, P < 0.001). Absence of myocardial uptake was associated with higher prevalence of early atherosclerosis (i.e., arterial 18F-FDG uptake, P = 0.004). On follow-up, the associations between myocardial 18F-FDG uptake and risk factors were replicated, and MetS was more frequent in the group without myocardial uptake. The increase in HOMA-IR was associated with a progressive decrease in myocardial uptake (P < 0.001). In 82% of subjects, the categorization according to presence/absence of myocardial 18F-FDG uptake did not change between baseline and follow-up. MetS regression on follow-up was associated with a significant (P < 0.001) increase in myocardial uptake.
CONCLUSIONS
Apparently healthy individuals without cardiac 18F-FDG uptake have higher HOMA-IR and higher prevalence of MetS traits, cardiovascular risk factors, and early atherosclerosis. An improvement in cardiometabolic profile is associated with the recovery of myocardial 18F-FDG uptake at follow-up.The PESA study is funded by the
Centro Nacional de Investigaciones Cardiovasculares (CNIC) and Santander Bank. B.I. is supported by the European Commission (grant
numbers 819775 and 945118), by the Spanish
Ministry of Science and Innovation (PID2019-
110369RB-I00), and by the Red Madrilena de ~
Nanomedicina en Imagen Molecular-Comunidad
de Madrid (S2017/BMD-3867 RENIM-CM). A.D.
is an Alfonso Martin Escudero fellow and is scientifically supported by La Caixa Foundation.
The CNIC is supported by the Instituto de Salud
Carlos III (ISCIII), the Ministerio de Ciencia e Innovacion (MCIN), and the Pro CNIC Foundation,
and is a Severo Ochoa Center of Excellence
(grant CEX2020-001041-S funded by MICIN/AEI/
10.13039/501100011033).S
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