224 research outputs found
Optimal stochastic modelling with unitary quantum dynamics
Identifying and extracting the past information relevant to the future
behaviour of stochastic processes is a central task in the quantitative
sciences. Quantum models offer a promising approach to this, allowing for
accurate simulation of future trajectories whilst using less past information
than any classical counterpart. Here we introduce a class of phase-enhanced
quantum models, representing the most general means of causal simulation with a
unitary quantum circuit. We show that the resulting constructions can display
advantages over previous state-of-art methods - both in the amount of
information they need to store about the past, and in the minimal memory
dimension they require to store this information. Moreover, we find that these
two features are generally competing factors in optimisation - leading to an
ambiguity in what constitutes the optimal model - a phenomenon that does not
manifest classically. Our results thus simultaneously offer new quantum
advantages for stochastic simulation, and illustrate further qualitative
differences in behaviour between classical and quantum notions of complexity.Comment: 9 pages, 5 figure
Measures of distinguishability between stochastic processes
Quantifying how distinguishable two stochastic processes are lies at the
heart of many fields, such as machine learning and quantitative finance. While
several measures have been proposed for this task, none have universal
applicability and ease of use. In this Letter, we suggest a set of requirements
for a well-behaved measure of process distinguishability. Moreover, we propose
a family of measures, called divergence rates, that satisfy all of these
requirements. Focussing on a particular member of this family -- the
co-emission divergence rate -- we show that it can be computed efficiently,
behaves qualitatively similar to other commonly-used measures in their regimes
of applicability, and remains well-behaved in scenarios where other measures
break down
Visual scoping operations for physical assembly
Planning is hard. The use of subgoals can make planning more tractable, but
selecting these subgoals is computationally costly. What algorithms might
enable us to reap the benefits of planning using subgoals while minimizing the
computational overhead of selecting them? We propose visual scoping, a strategy
that interleaves planning and acting by alternately defining a spatial region
as the next subgoal and selecting actions to achieve it. We evaluated our
visual scoping algorithm on a variety of physical assembly problems against two
baselines: planning all subgoals in advance and planning without subgoals. We
found that visual scoping achieves comparable task performance to the subgoal
planner while requiring only a fraction of the total computational cost.
Together, these results contribute to our understanding of how humans might
make efficient use of cognitive resources to solve complex planning problems
Static chaos and scaling behaviour in the spin-glass phase
We discuss the problem of static chaos in spin glasses. In the case of
magnetic field perturbations, we propose a scaling theory for the spin-glass
phase. Using the mean-field approach we argue that some pure states are
suppressed by the magnetic field and their free energy cost is determined by
the finite-temperature fixed point exponents. In this framework, numerical
results suggest that mean-field chaos exponents are probably exact in finite
dimensions. If we use the droplet approach, numerical results suggest that the
zero-temperature fixed point exponent is very close to
. In both approaches is the lower critical dimension in
agreement with recent numerical simulations.Comment: 28 pages + 6 figures, LateX, figures uuencoded at the end of fil
Chaotic, memory and cooling rate effects in spin glasses: Is the Edwards-Anderson model a good spin glass?
We investigate chaotic, memory and cooling rate effects in the three
dimensional Edwards-Anderson model by doing thermoremanent (TRM) and AC
susceptibility numerical experiments and making a detailed comparison with
laboratory experiments on spin glasses. In contrast to the experiments, the
Edwards-Anderson model does not show any trace of re-initialization processes
in temperature change experiments (TRM or AC). A detailed comparison with AC
relaxation experiments in the presence of DC magnetic field or coupling
distribution perturbations reveals that the absence of chaotic effects in the
Edwards-Anderson model is a consequence of the presence of strong cooling rate
effects. We discuss possible solutions to this discrepancy, in particular the
smallness of the time scales reached in numerical experiments, but we also
question the validity of the Edwards-Anderson model to reproduce the
experimental results.Comment: 17 pages, 10 figures. The original version of the paper has been
split in two parts. The second part is now available as cond-mat/010224
Epigenetic upregulation of FKBP5 by aging and stress contributes to NF-kappa B-driven inflammation and cardiovascular risk
Aging and psychosocial stress are associated with increased inflammation and disease risk, but the underlying molecular mechanisms are unclear. Because both aging and stress are also associated with lasting epigenetic changes, a plausible hypothesis is that stress along the lifespan could confer disease risk through epigenetic effects on molecules involved in inflammatory processes. Here, by combining large-scale analyses in human cohorts with experiments in cells, we report that FKBP5, a protein implicated in stress physiology, contributes to these relations. Across independent human cohorts (total n > 3,000), aging synergized with stress-related phenotypes, measured with childhood trauma and major depression questionnaires, to epigenetically up-regulate FKBP5 expression. These age/stress-related epigenetic effects were recapitulated in a cellular model of replicative senescence, whereby we exposed replicating human fibroblasts to stress (glucocorticoid) hormones. Unbiased genome-wide analyses in human blood linked higher FKBP5 mRNA with a proinflammatory profile and altered NF-kappa B-related gene networks. Accordingly, experiments in immune cells showed that higher FKBP5 promotes inflammation by strengthening the interactions of NF-kappa B regulatory kinases, whereas opposing FKBP5 either by genetic deletion (CRISPR/Cas9-mediated) or selective pharmacological inhibition prevented the effects on NF-kappa B. Further, the age/stress-related epigenetic signature enhanced FKBP5 response to NF-kappa B through a positive feedback loop and was present in individuals with a history of acute myocardial infarction, a disease state linked to peripheral inflammation. These findings suggest that aging/stress-driven FKBP5-NF-kappa B signaling mediates inflammation, potentially contributing to cardiovascular risk, and may thus point to novel biomarker and treatment possibilities.Peer reviewe
CD40L Deficiency Attenuates Diet-Induced Adipose Tissue Inflammation by Impairing Immune Cell Accumulation and Production of Pathogenic IgG-Antibodies
BACKGROUND: Adipose tissue inflammation fuels the metabolic syndrome. We recently reported that CD40L--an established marker and mediator of cardiovascular disease--induces inflammatory cytokine production in adipose cells in vitro. Here, we tested the hypothesis that CD40L deficiency modulates adipose tissue inflammation in vivo. METHODOLOGY/PRINCIPAL FINDINGS: WT or CD40L(-/-) mice consumed a high fat diet (HFD) for 20 weeks. Inflammatory cell recruitment was impaired in mice lacking CD40L as shown by a decrease of adipose tissue macrophages, B-cells, and an increase in protective T-regulatory cells. Mechanistically, CD40L-deficient mice expressed significantly lower levels of the pro-inflammatory chemokine MCP-1 both, locally in adipose tissue and systemically in plasma. Moreover, levels of pro-inflammatory IgG-antibodies against oxidized lipids were reduced in CD40L(-/-) mice. Also, circulating low-density lipoproteins and insulin levels were lower in CD40L(-/-) mice. However, CD40L(-/-) mice consuming HFD were not protected from the onset of diet-induced obesity (DIO), insulin resistance, and hepatic steatosis, suggesting that CD40L selectively limits the inflammatory features of diet-induced obesity rather than its metabolic phenotype. Interestingly, CD40L(-/-) mice consuming a low fat diet (LFD) showed both, a favorable inflammatory and metabolic phenotype characterized by diminished weight gain, improved insulin tolerance, and attenuated plasma adipokine levels. CONCLUSION: We present the novel finding that CD40L deficiency limits adipose tissue inflammation in vivo. These findings identify CD40L as a potential mediator at the interface of cardiovascular and metabolic disease
Maternal haemoglobin levels in pregnancy and child DNA methylation : a study in the pregnancy and childhood epigenetics consortium
Altered maternal haemoglobin levels during pregnancy are associated with pre-clinical and clinical conditions affecting the fetus. Evidence from animal models suggests that these associations may be partially explained by differential DNA methylation in the newborn with possible long-term consequences. To test this in humans, we meta-analyzed the epigenome-wide associations of maternal haemoglobin levels during pregnancy with offspring DNA methylation in 3,967 newborn cord blood and 1,534 children and 1,962 adolescent whole-blood samples derived from 10 cohorts. DNA methylation was measured using Illumina Infinium Methylation 450K or MethylationEPIC arrays covering 450,000 and 850,000 methylation sites, respectively. There was no statistical support for the association of maternal haemoglobin levels with offspring DNA methylation either at individual methylation sites or clustered in regions. For most participants, maternal haemoglobin levels were within the normal range in the current study, whereas adverse perinatal outcomes often arise at the extremes. Thus, this study does not rule out the possibility that associations with offspring DNA methylation might be seen in studies with more extreme maternal haemoglobin levels.Peer reviewe
Hypertensive Disorders of Pregnancy and DNA Methylation in Newborns Findings From the Pregnancy and Childhood Epigenetics Consortium
Hypertensive disorders of pregnancy (HDP) are associated with low birth weight, shorter gestational age, and increased risk of maternal and offspring cardiovascular diseases later in life. The mechanisms involved are poorly understood, but epigenetic regulation of gene expression may play a part. We performed meta-analyses in the Pregnancy and Childhood Epigenetics Consortium to test the association between either maternal HDP (10 cohorts; n=5242 [cases=476]) or preeclampsia (3 cohorts; n=2219 [cases=135]) and epigenome-wide DNA methylation in cord blood using the Illumina HumanMethylation450 BeadChip. In models adjusted for confounders, and with Bonferroni correction, HDP and preeclampsia were associated with DNA methylation at 43 and 26 CpG sites, respectively. HDP was associated with higher methylation at 27 (63%) of the 43 sites, and across all 43 sites, the mean absolute difference in methylation was between 0.6% and 2.6%. Epigenome-wide associations of HDP with offspring DNA methylation were modestly consistent with the equivalent epigenome-wide associations of preeclampsia with offspring DNA methylation (R-2=0.26). In longitudinal analyses conducted in 1 study (n=108 HDP cases; 550 controls), there were similar changes in DNA methylation in offspring of those with and without HDP up to adolescence. Pathway analysis suggested that genes located at/near HDP-associated sites may be involved in developmental, embryogenesis, or neurological pathways. HDP is associated with offspring DNA methylation with potential relevance to development.Peer reviewe
Association between DNA methylation and ADHD symptoms from birth to school age: a prospective meta-analysis
Attention-deficit and hyperactivity disorder (ADHD) is a common childhood disorder with a substantial genetic
component. However, the extent to which epigenetic mechanisms play a role in the etiology of the disorder is
unknown. We performed epigenome-wide association studies (EWAS) within the Pregnancy And Childhood
Epigenetics (PACE) Consortium to identify DNA methylation sites associated with ADHD symptoms at two methylation
assessment periods: birth and school age. We examined associations of both DNA methylation in cord blood with
repeatedly assessed ADHD symptoms (age 4–15 years) in 2477 children from 5 cohorts and of DNA methylation at
school age with concurrent ADHD symptoms (age 7–11 years) in 2374 children from 9 cohorts, with 3 cohorts
participating at both timepoints. CpGs identified with nominal significance (p < 0.05) in either of the EWAS were
correlated between timepoints (ρ = 0.30), suggesting overlap in associations; however, top signals were very different.
At birth, we identified nine CpGs that predicted later ADHD symptoms (p < 1 × 10–7
), including ERC2 and CREB5.
Peripheral blood DNA methylation at one of these CpGs (cg01271805 in the promoter region of ERC2, which regulates
neurotransmitter release) was previously associated with brain methylation. Another (cg25520701) lies within the gene
body of CREB5, which previously was associated with neurite outgrowth and an ADHD diagnosis. In contrast, at school
age, no CpGs were associated with ADHD with p < 1 × 10−7
. In conclusion, we found evidence in this study that DNA
methylation at birth is associated with ADHD. Future studies are needed to confirm the utility of methylation variation
as biomarker and its involvement in causal pathways
- …