Pushdown Compression

The pressing need for eficient compression schemes for XML documents has recently been focused on stack computation [6, 9], and in particular calls for a formulation of information-lossless stack or pushdown compressors that allows a formal analysis of their performance and a more ambitious use of the stack in XML compression, where so far it is mainly connected to parsing mechanisms. In this paper we introduce the model of pushdown compressor, based on pushdown transducers that compute a single injective function while keeping the widest generality regarding stack computation. The celebrated Lempel-Ziv algorithm LZ78 [10] was introduced as a general purpose compression algorithm that outperforms finite-state compressors on all sequences. We compare the performance of the Lempel-Ziv algorithm with that of the pushdown compressors, or compression algorithms that can be implemented with a pushdown transducer. This comparison is made without any a priori assumption on the data's source and considering the asymptotic compression ratio for infinite sequences. We prove that Lempel-Ziv is incomparable with pushdown compressors

On Weak Odd Domination and Graph-based Quantum Secret Sharing

A weak odd dominated (WOD) set in a graph is a subset B of vertices for which there exists a distinct set of vertices C such that every vertex in B has an odd number of neighbors in C. We point out the connections of weak odd domination with odd domination, [sigma,rho]-domination, and perfect codes. We introduce bounds on \kappa(G), the maximum size of WOD sets of a graph G, and on \kappa'(G), the minimum size of non WOD sets of G. Moreover, we prove that the corresponding decision problems are NP-complete. The study of weak odd domination is mainly motivated by the design of graph-based quantum secret sharing protocols: a graph G of order n corresponds to a secret sharing protocol which threshold is \kappa_Q(G) = max(\kappa(G), n-\kappa'(G)). These graph-based protocols are very promising in terms of physical implementation, however all such graph-based protocols studied in the literature have quasi-unanimity thresholds (i.e. \kappa_Q(G)=n-o(n) where n is the order of the graph G underlying the protocol). In this paper, we show using probabilistic methods, the existence of graphs with smaller \kappa_Q (i.e. \kappa_Q(G)< 0.811n where n is the order of G). We also prove that deciding for a given graph G whether \kappa_Q(G)< k is NP-complete, which means that one cannot efficiently double check that a graph randomly generated has actually a \kappa_Q smaller than 0.811n.Comment: Subsumes arXiv:1109.6181: Optimal accessing and non-accessing structures for graph protocol

DNA-methylation dynamics across short-term, exposure-containing CBT in patients with panic disorder

Interaction of genetic predispositions and environmental factors via epigenetic mechanisms have been hypothesized to play a central role in Panic Disorder (PD) aetiology and therapy. Cognitive Behavioral Therapy (CBT), including exposure interventions, belong to the most efficient treatments of PD although its biological mechanism of action remains unknown. For the first time, we explored the dynamics and magnitude of DNA-methylation and immune cell-type composition during CBT (n = 38) and the therapeutic exposure intervention (n = 21) to unravel their biological correlates and identify possible biomarkers of therapy success. We report transient regulation of the CD4 + T-Cells, Natural Killers cells, Granulocytes during exposure and a significant change in the proportions of CD4 + T cells, CD8 + T cells and B-Cells and Granulocytes during therapy. In an epigenome-wide association study we identified cg01586609 located in a CpG island and annotated to the serotonin receptor 3 A (HTR3A) to be differentially methylated during fear exposure and regulated at gene expression level with significant differences between remitters and non-remitters (p = 0.028). We moreover report cg01699630 annotated to ARG1 to undergo long lasting methylation changes during therapy (paired t test, genome-wide adj.p value = 0.02). This study reports the first data-driven biological candidates for epigenetically mediated effects of acute fear exposure and CBT in PD patients. Our results provide evidence of changes in the serotonin receptor 3 A methylation and expression during fear exposure associated with different long-term CBT trajectories and outcome, making it a possible candidate in the search of markers for therapy success. Finally, our results add to a growing body of evidence showing immune system changes associated with PD

Cis-epistasis at the LPA locus and risk of cardiovascular diseases

AIMS Coronary artery disease (CAD) has a strong genetic predisposition. However, despite substantial discoveries made by genome-wide association studies (GWAS), a large proportion of heritability awaits identification. Non-additive genetic-effects might be responsible for part of the unaccounted genetic variance. Here we attempted a proof-of-concept study to identify non-additive genetic effects, namely epistatic interactions, associated with CAD. METHODS AND RESULTS We tested for epistatic interactions in ten CAD case-control studies and UK Biobank with focus on 8,068 SNPs at 56 loci with known associations with CAD risk. We identified a SNP pair located in cis at the LPA locus, rs1800769 and rs9458001, to be jointly associated with risk for CAD (odds ratio OR=1.37, p = 1.07 $\times$ 10-11), peripheral arterial disease (OR = 1.22, p = 2.32 $\times$ 10-4), aortic stenosis (OR = 1.47, p = 6.95 $\times$ 10-7), hepatic lipoprotein(a) (Lp(a)) transcript levels (beta = 0.39, p = 1.41 $\times$ 10-8), and Lp(a) serum levels (beta = 0.58, p = 8.7 $\times$ 10-32), while individual SNPs displayed no association. Further exploration of the LPA locus revealed a strong dependency of these associations on a rare variant, rs140570886, that was previously associated with Lp(a) levels. We confirmed increased CAD risk for heterozygous (relative OR = 1.46, p = 9.97 $\times$ 10-32) and individuals homozygous for the minor allele (relative OR = 1.77, p = 0.09) of rs140570886. Using forward model selection, we also show that epistatic interactions between rs140570886, rs9458001, and rs1800769 modulate the effects of the rs140570886 risk allele. CONCLUSIONS These results demonstrate the feasibility of a large-scale knowledge-based epistasis scan and provide rare evidence of an epistatic interaction in a complex human disease. We were directed to a variant (rs140570886) influencing risk through additive genetic as well as epistatic effects. In summary, this study provides deeper insights into the genetic architecture of a locus important for cardiovascular diseases. TRANSLATIONAL PERSPECTIVE Genetic variants identified by GWAS studies explain about a quarter of the heritability of coronary artery disease by additive genetic effects. Our study demonstrates that non-additive effects contribute to the genetic architecture of the disease as well and identifies complex interaction patterns at the LPA locus, which affect LPA expression, Lp(a) plasma levels and risk of atherosclerosis. This proof-of-concept study encourages systematic searches for epistatic interactions in further studies to shed new light on the aetiology of the disease

Association of inflammation with depression and anxiety: evidence for symptom-specificity and potential causality from UK Biobank and NESDA cohorts.

Funder: Partially supported by the Complex Trait Genetics programme of Amsterdam NeuroscienceFunder: Supported by the International Max Planck Research School of Translational Psychiatry (IMPRS-TP)Funder: MQ: Transforming Mental Health (MQ); doi: https://doi.org/10.13039/501100008162; Grant(s): MQDS17/40, MQDS17/40, MQDS17/40Funder: EC | EC Seventh Framework Programm | FP7 People: Marie-Curie Actions (FP7-PEOPLE - Specific Programme "People" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011264; Grant(s): PCIG12-GA-2012-334065Funder: BMA Foundation (J Moulton grant 2019)We examined whether inflammation is uniformly associated with all depressive and anxiety symptoms, and whether these associations are potentially causal. Data was from 147,478 individuals from the UK Biobank (UKB) and 2,905 from the Netherlands Study of Depression and Anxiety (NESDA). Circulating C-reactive protein (CRP) was measured in both cohorts and interleukin-6 (IL-6) in NESDA. Genetic instruments for these proteins were obtained from published GWAS and UKB. Depressive and anxiety symptoms were assessed with self-report questionnaires. In NESDA, neurovegetative (appetite, sleep, psychomotor) symptoms were disaggregated as increased vs. decreased. In joint analyses, higher CRP was associated with depressive symptoms of depressed mood (OR = 1.06, 95% CI = 1.05-1.08), altered appetite (OR = 1.25, 95%CI = 1.23-1.28), sleep problems (OR = 1.05, 95%CI = 1.04-1.06), and fatigue (OR = 1.12, 95% CI = 1.11-1.14), and with anxiety symptoms of irritability (OR = 1.06, 95% CI = 1.05-1.08) and worrying control (OR = 1.03, 95% CI = 1.02-1.04). In NESDA, higher IL-6 was additionally associated with anhedonia (OR = 1.30, 95% CI = 1.12-1.52). Higher levels of both CRP (OR = 1.27, 95% CI = 1.13-1.43) and IL-6 (OR = 1.26, 95% CI = 1.07-1.49) were associated with increased sleep. Higher CRP was associated with increased appetite (OR = 1.21, 95% CI = 1.08-1.35) while higher IL-6 with decreased appetite (OR = 1.45, 95% CI = 1.18-1.79). In Mendelian Randomisation analyses, genetically predicted higher IL-6 activity was associated with increased risk of fatigue (estimate = 0.25, SE = 0.08) and sleep problems (estimate = 0.19, SE = 0.07). Inflammation was associated with core depressive symptoms of low mood and anhedonia and somatic/neurovegetative symptoms of fatigue, altered sleep and appetite changes. Less consistent associations were found for anxiety. The IL-6/IL-6R pathway could be causally linked to depression. Experimental studies are required to further evaluate causality, mechanisms, and usefulness of immunotherapies for depressive symptoms

Production of CXC and CC chemokines by human antigen-presenting cells in response to Lassa virus or closely related immunogenic viruses, and in cynomolgus monkeys with lassa fever.

International audienceThe pathogenesis of Lassa fever (LF), a hemorrhagic fever endemic to West Africa, remains unclear. We previously compared Lassa virus (LASV) with its genetically close, but nonpathogenic homolog Mopeia virus (MOPV) and demonstrated that the strong activation of antigen-presenting cells (APC), including type I IFN production, observed in response to MOPV probably plays a crucial role in controlling infection. We show here that human macrophages (MP) produce large amounts of CC and CXC chemokines in response to MOPV infection, whereas dendritic cells (DC) release only moderate amounts of CXC chemokines. However, in the presence of autologous T cells, DCs produced CC and CXC chemokines. Chemokines were produced in response to type I IFN synthesis, as the levels of both mediators were strongly correlated and the neutralization of type I IFN resulted in an inhibition of chemokine production. By contrast, LASV induced only low levels of CXCL-10 and CXCL-11 production. These differences in chemokine production may profoundly affect the generation of virus-specific T-cell responses and may therefore contribute to the difference of pathogenicity between these two viruses. In addition, a recombinant LASV (rLASV) harboring the NP-D389A/G392A mutations, which abolish the inhibition of type I IFN response by nucleoprotein (NP), induced the massive synthesis of CC and CXC chemokines in both DC and MP, confirming the crucial role of arenavirus NP in immunosuppression and pathogenicity. Finally, we confirmed, using PBMC samples and lymph nodes obtained from LASV-infected cynomolgus monkeys, that LF was associated with high levels of CXC chemokine mRNA synthesis, suggesting that the very early synthesis of these mediators may be correlated with a favourable outcome

Pushdown compression

24 pagesInternational audienceThe pressing need for efficient compression schemes for XML documents has recently been focused on stack computation (Hariharan and Shankar 2006, League and Eng 2007), and in particular calls for a formulation of information-lossless stack or pushdown compressors that allows a formal analysis of their performance and a more ambitious use of the stack in XML compression, where so far it is mainly connected to parsing mechanisms. In this paper we introduce the model of pushdown compressor, based on pushdown transducers that compute a single injective function while keeping the widest generality regarding stack computation. The celebrated Lempel-Ziv algorithm LZ78 was introduced as a general purpose compression algorithm that outperforms finite-state compressors on all sequences. We compare the performance of the Lempel-Ziv algorithm with that of the pushdown compressors, or compression algorithms that can be implemented with a pushdown transducer. This comparison is made without any a priori assumption on the data's source and considering the asymptotic compression ratio for infinite sequences. We prove that Lempel-Ziv is incomparable with pushdown compressors

Method and apparatus for generating three-dimensional patterned soft structures and uses thereof

A method for generating a three-dimensional patterned soft structure, including the steps of providing a soft supporting substrate, providing a drop-on-demand system with a device for varying the velocity of the jetted droplets, providing a liquid ink, jetting the liquid ink towards the soft supporting substrate with the drop-on-demand system, controlling an injection depth of the liquid ink into the soft supporting substrate by varying a jetting velocity of the liquid ink; and depositing droplets of the liquid ink over a volume of the soft supporting substrate, thereby generating the three-dimensional patterned soft structure