Constraint-based sequence mining using constraint programming

The goal of constraint-based sequence mining is to find sequences of symbols that are included in a large number of input sequences and that satisfy some constraints specified by the user. Many constraints have been proposed in the literature, but a general framework is still missing. We investigate the use of constraint programming as general framework for this task. We first identify four categories of constraints that are applicable to sequence mining. We then propose two constraint programming formulations. The first formulation introduces a new global constraint called exists-embedding. This formulation is the most efficient but does not support one type of constraint. To support such constraints, we develop a second formulation that is more general but incurs more overhead. Both formulations can use the projected database technique used in specialised algorithms. Experiments demonstrate the flexibility towards constraint-based settings and compare the approach to existing methods.Comment: In Integration of AI and OR Techniques in Constraint Programming (CPAIOR), 201

Mapping deformations and inferring movements of masonry arch bridges using point cloud data

Many historic masonry arch bridges experience damage due to support movements during their lifetime. This damage may influence the performance of the bridge and reduce its load carrying capacity. This paper proposes a new method to quantify past support movements by investigating distortions in bridge geometry. In this method, the bridge geometry is recorded in point cloud format and segmented into different structural components (e.g. 3D piers and barrels or 2D pier and barrel cross-sections). The geometry of each component is investigated further withby fitting primitive shapes (e.g. 3D planes and cylinders or 2D lines and arcs) which represent the design intent. The discrepancy between these fitted shapes and the point clouds reveals a characteristic distortion signature. This signature is compared with theoretical distortion traces, which are obtained from kinematical analyses of the arch subjected to a range of support movements. The most likely support movement scenarios identified from these comparisons are then validated with visual indications of damage, such as crack location and size, and other geometric quantities, such as the change of the bedding joint elevations along the bridge. The proposed technique is applied to two masonry rail viaducts in the UK, which demonstrate different evidence of damage. Using the proposed method, past support movements of both bridges, which led to the observed damage, are inferred

Morphological and proteomic analysis of biofilms from the Antarctic archaeon, Halorubrum lacusprofundi

© The Author(s) 2016. Biofilms enhance rates of gene exchange, access to specific nutrients, and cell survivability. Haloarchaea in Deep Lake, Antarctica, are characterized by high rates of intergenera gene exchange, metabolic specialization that promotes niche adaptation, and are exposed to high levels of UV-irradiation in summer. Halorubrum lacusprofundi from Deep Lake has previously been reported to form biofilms. Here we defined growth conditions that promoted the formation of biofilms and used microscopy and enzymatic digestion of extracellular material to characterize biofilm structures. Extracellular DNA was found to be critical to biofilms, with cell surface proteins and quorum sensing also implicated in biofilm formation. Quantitative proteomics was used to define pathways and cellular processes involved in forming biofilms; these included enhanced purine synthesis and specific cell surface proteins involved in DNA metabolism; post-translational modification of cell surface proteins; specific pathways of carbon metabolism involving acetyl-CoA; and specific responses to oxidative stress. The study provides a new level of understanding about the molecular mechanisms involved in biofilm formation of this important member of the Deep Lake community

Exploring 4D Quantum Hall Physics with a 2D Topological Charge Pump

The discovery of topological states of matter has profoundly augmented our understanding of phase transitions in physical systems. Instead of local order parameters, topological phases are described by global topological invariants and are therefore robust against perturbations. A prominent example thereof is the two-dimensional integer quantum Hall effect. It is characterized by the first Chern number which manifests in the quantized Hall response induced by an external electric field. Generalizing the quantum Hall effect to four-dimensional systems leads to the appearance of a novel non-linear Hall response that is quantized as well, but described by a 4D topological invariant - the second Chern number. Here, we report on the first observation of a bulk response with intrinsic 4D topology and the measurement of the associated second Chern number. By implementing a 2D topological charge pump with ultracold bosonic atoms in an angled optical superlattice, we realize a dynamical version of the 4D integer quantum Hall effect. Using a small atom cloud as a local probe, we fully characterize the non-linear response of the system by in-situ imaging and site-resolved band mapping. Our findings pave the way to experimentally probe higher-dimensional quantum Hall systems, where new topological phases with exotic excitations are predicted

Increased NBCn1 expression, Na+/HCO3- co-transport and intracellular pH in human vascular smooth muscle cells with a risk allele for hypertension.

Genome-wide association studies have revealed an association between variation at the SLC4A7 locus and blood pressure. SLC4A7 encodes the electroneutral Na+/HCO3- co-transporter NBCn1 which regulates intracellular pH (pHi). We conducted a functional study of variants at this locus in primary cultures of vascular smooth muscle and endothelial cells. In both cell types, we found genotype-dependent differences for rs13082711 in DNA-nuclear protein interactions, where the risk allele is associated with increased SLC4A7 expression level, NBCn1 availability and function as reflected in elevated steady-state pHi and accelerated recovery from intracellular acidosis. However, in the presence of Na+/H+ exchange activity, the SLC4A7 genotypic effect on net base uptake and steady-state pHi persisted only in vascular smooth muscle cells but not endothelial cells. We found no discernable effect of the missense polymorphism resulting in the amino acid substitution Glu326Lys. The finding of a genotypic influence on SLC4A7 expression and pHi regulation in vascular smooth muscle cells provides an insight into the molecular mechanism underlying the association of variation at the SLC4A7 locus with blood pressure

Impact of Phenanthrene on Organic Acids Secretion and Accumulation by Perennial Ryegrass, Lolium perenne L., Root

A solution culture experiment was performed to investigate the impact of phenanthrene (PHE) on organic acids secretion and accumulation by Lolium perenne L. root. Data showed that, oxalic acid was the dominant composition of organic acids in root and root exudates. In root exudates, increased levels of PHE resulted in higher oxalic acid and its secrete proportion; oxalic acid arranged from 3.00 to 4.72 mg/g FW under spiked PHE treatments, in control, it was 2.33 mg/g FW. In root, oxalic acid rose to 25.61 mg/g FW at 1 mg/L PHE treatment, while the PHE concentration was continuously increasing, organic acids in root decreased

The FPR2-induced rise in cytosolic calcium in human neutrophils relies on an emptying of intracellular calcium stores and is inhibited by a gelsolin-derived PIP2-binding peptide

<p>Abstract</p> <p>Background</p> <p>The molecular basis for neutrophil recognition of chemotactic peptides is their binding to specific G-protein-coupled cell surface receptors (GPCRs). Human neutrophils express two pattern recognition GPCRs, FPR1 and FPR2, which belong to the family of formyl peptide receptors. The high degree of homology between these two receptors suggests that they share many functional and signal transduction properties, although they exhibit some differences with respect to signaling. The aims of this study were to determine whether FPR2 triggers a unique signal that allows direct influx of extracellular calcium without the emptying of intracellular calcium stores, and whether the gelsolin-derived PIP₂-binding peptide, PBP10, selectively inhibits FPR2-mediated transient rise in intracellular Ca²⁺.</p> <p>Results</p> <p>The transient rise in intracellular Ca²⁺induced by agonists for FPR1 or FPR2 in human neutrophils occurred also in the presence of a chelator of Ca²⁺(EGTA). PBP10 inhibited not only FPR2-induced oxidase activity, but also the transient rise in intracellular Ca²⁺.</p> <p>Conclusions</p> <p>Ca²⁺signaling mediated <it>via </it>FPR2 follows the same route as FPR1, which involves initial emptying of the intracellular stores. PBP10 inhibits selectively the signals generated by FPR2, both with respect to NADPH-oxidase activity and the transient rise in intracellular Ca²⁺induced by agonist exposure.</p

Quantitative super-resolution imaging of pathological aggregates reveals distinct toxicity profiles in different synucleinopathies.

Protein aggregation is a hallmark of major neurodegenerative disorders. Increasing data suggest that smaller aggregates cause higher toxic response than filamentous aggregates (fibrils). However, the size of small aggregates has challenged their detection within biologically relevant environments. Here, we report approaches to quantitatively super-resolve aggregates in live cells and ex vivo brain tissues. We show that Amytracker 630 (AT630), a commercial aggregate-activated fluorophore, has outstanding photophysical properties that enable super-resolution imaging of α-synuclein, tau, and amyloid-β aggregates, achieving ∼4 nm precision. Applying AT630 to AppNL-G-F mouse brain tissues or aggregates extracted from a Parkinson's disease donor, we demonstrate excellent agreement with antibodies specific for amyloid-β or α-synuclein, respectively, confirming the specificity of AT630. Subsequently, we use AT630 to reveal a linear relationship between α-synuclein aggregate size and cellular toxicity and discovered that aggregates smaller than 450 ± 60 nm (aggregate450nm) readily penetrated the plasma membrane. We determine aggregate450nm concentrations in six Parkinson's disease and dementia with Lewy bodies donor samples and show that aggregates in different synucleinopathies demonstrate distinct potency in toxicity. We further show that cell-penetrating aggregates are surrounded by proteasomes, which assemble into foci to gradually process aggregates. Our results suggest that the plasma membrane effectively filters out fibrils but is vulnerable to penetration by aggregates of 450 ± 60 nm. Together, our findings present an exciting strategy to determine specificity of aggregate toxicity within heterogeneous samples. Our approach to quantitatively measure these toxic aggregates in biological environments opens possibilities to molecular examinations of disease mechanisms under physiological conditions

Impact of Age and Body Site on Adult Female Skin Surface pH

Background: pH is known as an important parameter in epidermal barrier function and homeostasis. Aim: The impact of age and body site on skin surface pH (pH(SS)) of women was evaluated in vivo. Methods: Time domain dual lifetime referencing with luminescent sensor foils was used for pH(SS) measurements. pH(SS) was measured on the forehead, the temple, and the volar forearm of adult females (n = 97, 52.87 +/- 18.58 years, 20-97 years). Every single measurement contained 2,500 pH values due to the luminescence imaging technique used. Results: pH(SS) slightly increases with age on all three investigated body sites. There are no significant differences in pH(SS) between the three investigated body sites. Conclusion: Adult pH(SS) on the forehead, the temple and the volar forearm increases slightly with age. This knowledge is crucial for adapting medical skin care products. Copyright (C) 2012 S. Karger AG, Base

An intelligent multi-agent memory assistant

World population is ageing and increasingly scarce resources are required to cover the needs of everyone adequately. Medical conditions, especially memory problems, restrict the daily life of a broad slice of the elderly population, affect their independence. To prevent this, providing the right care and assistance while having in mind the costs implicated is essential. One possible path is to work with resources that we already have today and create innovative solutions to achieve the required level of support. There are not many solution either technological or not to prevent memory loss. In this work we present a possible solution aimed at restoring or maintaining the independence of elderly people, through the use of so-called Memory Assistants. We thus present an Intelligent Multi-Agent Memory Assistant designed to help people with memory problems remember their events and activities. The implementation of an event manager, free time manger, medication remainder and a sensory system, to manage and monitor the user, we aim to improve their quality of life and increase their independence