114 research outputs found
Critical role for polar residues in coupling leukotriene B4 binding to signal transduction in BLT1.
Event-by-Event Fluctuations in Heavy Ion Collisions and the QCD Critical Point
The event-by-event fluctuations of suitably chosen observables in heavy ion
collisions at SPS, RHIC and LHC can tell us about the thermodynamic properties
of the hadronic system at freeze-out. By studying these fluctuations as a
function of varying control parameters, it is possible to learn much about the
phase diagram of QCD. As a timely example, we stress the methods by which
present experiments at the CERN SPS can locate the second-order critical
endpoint of the first-order transition between quark-gluon plasma and hadron
matter. Those event-by-event signatures which are characteristic of freeze-out
in the vicinity of the critical point will exhibit nonmonotonic dependence on
control parameters. We focus on observables constructed from the multiplicity
and transverse momenta of charged pions. We first consider how the
event-by-event fluctuations of such observables are affected by Bose-Einstein
correlations, by resonances which decay after freeze-out and by fluctuations in
the transverse flow velocity. We compare our thermodynamic predictions for such
noncritical event-by-event fluctuations with NA49 data, finding broad
agreement. We then focus on effects due to thermal contact between the observed
pions and a heat bath with a given (possibly singular) specific heat, and due
to the direct coupling between the critical fluctuations of the sigma field and
the observed pions. We also discuss the effect of the pions produced in the
decay of sigma particles just above threshold after freeze-out on the inclusive
pion spectrum and on multiplicity fluctuations. We estimate the size of these
nonmonotonic effects which appear near the critical point, including
restrictions imposed by finite size and finite time, and conclude that they
should be easily observable.Comment: 58 pages, 2 figures; to appear in Phys. Rev.
Slowing Out of Equilibrium Near the QCD Critical Point
The QCD phase diagram may feature a critical end point at a temperature T and
baryon chemical potential which is accessible in heavy ion collisions.
The universal long wavelength fluctuations which develop near this Ising
critical point result in experimental signatures which can be used to find the
critical point. The magnitude of the observed effects depends on how large the
correlation length becomes. Because the matter created in a heavy ion
collision cools through the critical region of the phase diagram in a finite
time, critical slowing down limits the growth of , preventing it from
staying in equilibrium. This is the fundamental nonequilibrium effect which
must be calculated in order to make quantitative predictions for experiment. We
use universal nonequilibrium dynamics and phenomenologically motivated values
for the necessary nonuniversal quantities to estimate how much the growth of
is slowed.Comment: 21 pages, 5 figures, reference added, typo corrected, to appear in
Phys. Rev.
Bridging flavour violation and leptogenesis in SU(3) family models
We reconsider basic, in the sense of minimal field content, Pati-Salam x
SU(3) family models which make use of the Type I see-saw mechanism to reproduce
the observed mixing and mass spectrum in the neutrino sector. The goal of this
is to achieve the observed baryon asymmetry through the thermal decay of the
lightest right-handed neutrino and at the same time to be consistent with the
expected experimental lepton flavour violation sensitivity. This kind of models
have been previously considered but it was not possible to achieve a
compatibility among all of the ingredients mentioned above. We describe then
how different SU(3) messengers, the heavy fields that decouple and produce the
right form of the Yukawa couplings together with the scalars breaking the SU(3)
symmetry, can lead to different Yukawa couplings. This in turn implies
different consequences for flavour violation couplings and conditions for
realizing the right amount of baryon asymmetry through the decay of the
lightest right-handed neutrino. Also a highlight of the present work is a new
fit of the Yukawa textures traditionally embedded in SU(3) family models.Comment: 26 pages, 5 figures, Some typos correcte
Baculovirus Capsid Display Potentiates OVA Cytotoxic and Innate Immune Responses
Baculoviruses (BV) are DNA viruses that are pathogenic for insects. Although BV infect a range of mammalian cell types, they do not replicate in these cells. Indeed, the potential effects of these insect viruses on the immune responses of mammals are only just beginning to be studied. We show in this paper that a recombinant Autographa californica multiple nuclear polyhedrosis virus carrying a fragment of ovalbumin (OVA) on the VP39 capsid protein (BV-OVA) has the capacity to act as an adjuvant and vector of antigens in mice, thereby promoting specific CD4 and cytotoxic T cell responses against OVA. BV also induced in vivo maturation of dendritic cells and the production of inflammatory cytokines, thus promoting innate and adaptive immune responses. The OVA-specific response induced by BV-OVA was strong enough to reject a challenge with OVA-expressing melanoma cells (MO5 cells) and effectively prolonged survival of MO5 bearing mice. All these findings, together with the absence of pre-existing immunity to BV in humans and the lack of viral gene expression in mammalian cells, make BV a candidate for vaccination
Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people
The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 x 10(-8)) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits.Peer reviewe
Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.
Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability
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