Satisfiability of constraint specifications on XML documents

Jose Meseguer is one of the earliest contributors in the area of Algebraic Specification. In this paper, which we are happy to dedicate to him on the occasion of his 65th birthday, we use ideas and methods coming from that area with the aim of presenting an approach for the specification of the structure of classes of XML documents and for reasoning about them. More precisely, we specify the structure of documents using sets of constraints that are based on XPath and we present inference rules that are shown to define a sound and complete refutation procedure for checking satisfiability of a given specification using tableaux.Peer ReviewedPostprint (author's final draft

Reachability in Parametric Interval Markov Chains using Constraints

Parametric Interval Markov Chains (pIMCs) are a specification formalism that extend Markov Chains (MCs) and Interval Markov Chains (IMCs) by taking into account imprecision in the transition probability values: transitions in pIMCs are labeled with parametric intervals of probabilities. In this work, we study the difference between pIMCs and other Markov Chain abstractions models and investigate the two usual semantics for IMCs: once-and-for-all and at-every-step. In particular, we prove that both semantics agree on the maximal/minimal reachability probabilities of a given IMC. We then investigate solutions to several parameter synthesis problems in the context of pIMCs -- consistency, qualitative reachability and quantitative reachability -- that rely on constraint encodings. Finally, we propose a prototype implementation of our constraint encodings with promising results

Subthreshold laser therapy with a standardized macular treatment pattern in chronic central serous chorioretinopathy

PURPOSE There is an ongoing controversial debate about the effectiveness of laser treatments in chronic central serous chorioretinopathy (cCSC). We performed a prospective non-randomized interventional study to learn about the effects of a subthreshold laser treatment (Topcon Endpoint Management™, Topcon Healthcare Inc., Tokyo, Japan) in patients with cCSC. METHODS Patients with cCSC and a minimum symptom duration of 4~months were included and treated with a standardized laser pattern covering the macular area. Retreatment was performed every 3~months if persistent subretinal fluid was observed. The primary endpoint was resolution of subretinal fluid at 6~months. Further outcome parameters included best corrected visual acuity, microperimetry, central macular and subfoveal choroidal thickness. RESULTS A total of 42 eyes of 39 patients were included. Mean patient age was 48 ± 10.6~years (range 25-67). Mean symptomatic time before inclusion into the study was 134 ± 133.4~weeks (16-518). Before inclusion, 78.6% of the patients had failed to resolve subretinal fluid under mineralocorticoid receptor antagonists and 14.3% had a recurrence after half-dose photodynamic therapy. Complete resolution of subretinal fluid was observed in 42.9% at 6~months and in 53.8% at 12~months after baseline. Central retinal thickness decreased from 398 ± 135~µm to 291 ± 68~µm (p < 0.001), subfoveal choroidal thickness changed slightly (430 ± 116~µm to 419 ± 113~µm, p = 0.026), microperimetry-derived macular function improved by 19.1 ± 4.7~dB to 21.3 ± 4.8~dB (p = 0.008) and mean BCVA improved by 4.9 ± 8.6 ETDRS letters (p < 0.001). CONCLUSION The results show that the investigated laser treatment is effective in reducing subretinal fluid and leads to an improvement of functional parameters

Separation of VUV/UV photons and reactive particles in the effluent of a He/O2 atmospheric pressure plasma jet

Cold atmospheric pressure plasmas can be used for treatment of living tissues or for inactivation of bacteria or biological macromolecules. The treatment is usually characterized by a combined effect of UV and VUV radiation, reactive species, and ions. This combination is usually beneficial for the effectiveness of the treatment but it makes the study of fundamental interaction mechanisms very difficult. Here we report on an effective separation of VUV/UV photons and heavy reactive species in the effluent of a micro scale atmospheric pressure plasma jet ($\mu$-APPJ). The separation is realized by an additional flow of helium gas under well-defined flow conditions, which deflects heavy particles in the effluent without affecting the VUV and UV photons. Both components of the effluent, the photons and the reactive species, can be used separately or in combination for sample treatment. The results of treatment of a model plasma polymer film and vegetative Bacillus subtilis and Escherichia coli cells are shown and discussed. A simple model of the He gas flow and reaction kinetics of oxygen atoms in the gas phase and at the surface is used to provide a better understanding of the processes in the plasma effluent. The new jet modification, called X-Jet for its appearance, will simplify the investigation of interaction mechanisms of atmospheric pressure plasmas with biological samples.Comment: 10 pages, 7 figures, submitted to Journal of Physics D: Applied Physic

Logics for Unranked Trees: An Overview

Labeled unranked trees are used as a model of XML documents, and logical languages for them have been studied actively over the past several years. Such logics have different purposes: some are better suited for extracting data, some for expressing navigational properties, and some make it easy to relate complex properties of trees to the existence of tree automata for those properties. Furthermore, logics differ significantly in their model-checking properties, their automata models, and their behavior on ordered and unordered trees. In this paper we present a survey of logics for unranked trees

Ranibizumab non-response in pachychoroid neovasculopathy: Effects of switching to aflibercept

Non-response to intravitreal ranibizumab represents a frequent problem in pachychoroid neovasculopathy (PNV). To investigate the effectivity of switching to aflibercept, the database of the Ludwig Maximilians University, Munich, was screened for patients fulfilling the following inclusion criteria: (i) diagnosis of PNV;(ii) inadequate response to >= 3 ranibizumab injections, in spite of monthly dosing, defined as persistence of subretinal-fluid four weeks after the last ranibizumab injection;(iii) resulting switch to aflibercept administered as three monthly injections. Primary outcome measure was percentage of eyes with a dry macula four weeks after the third aflibercept injection. Secondary outcome measures included changes in maximum subretinal fluid (SRF), central subfield thickness (CST) and subfoveal choroidal thickness (SFCT). In total, 14 eyes of 14 patients were included. Mean age was 64.1 +/- 7.5 (range: 51-78) years. Switching to aflibercept was performed after mean 8.4 +/- 4.1 (3-15) ranibizumab injections. While no eye (0%) achieved a dry macula status during ranibizumab treatment, switching to aflibercept achieved a dry macula status in eight eyes (57.1%) after three injections. While both ranibizumab and aflibercept showed an effect on CST (p=0.027, p=0.003), only aflibercept showed a significant effect on SRF (p=0.0009) and SFCT (p=0.044). In cases of PNV not responding to intravitreal ranibizumab, switching treatment to aflibercept induces a favorable short-term response resolving persistent fluid and achieving a dry macula. Further studies with longer follow-up are warranted

Vanishing pachy-choroid in pachychoroid neovasculopathy under long-term anti-vascular endothelial growth factor therapy

BACKGROUND To investigate the diagnostic value of choroidal thickness in the definition of pachychoroid neovasculopathy (PNV), especially in eyes treated with anti-vascular endothelial growth factor (VEGF) therapy. METHODS Twenty-two consecutive eyes of 11 patients with uni- or bilateral PNV were analyzed. Anti-VEGF treatment was correlated with changes in choroidal thickness on enhanced depth imaging optical coherence tomography. RESULTS There were 14 eyes with PNV and 8 non-neovascular partner eyes. Mean age was 64.2 ± 4.0 (range: 60-72), total follow-up was 1.8 ± 0.4 (1-2) years. In PNV eyes, choroidal thickness at baseline was 400 ± 58 (269-485) μm. After two years and 13 anti-VEGF injections on average, a mean reduction of - 39 ± 10 (- 26 to - 56) % to final 241 ± 52 (162-327) μm was observed (p~ 0.13 for all comparisons). A significant correlation of choroidal thinning and anti-VEGF injection rate was observed at year one (r = - 0.79; R2~= 0.63; p~= 0.00073) and two (r = - 0.69; R2~= 0.48; p~= 0.019). While 85.7% of PNV eyes exceeded a pachychoroid threshold of ≥350 μm at baseline, this figure dropped to 21.4% at year one and 0% at year two. CONCLUSION In PNV, choroidal thickness significantly decreases with anti-VEGF therapy, resembling a \textquotedblvanishing pachy-choroid\textquotedbl, and thus does not represent a valid long-term diagnostic criterium, especially when differentiating PNV from nAMD

The super-LHC

We review here the prospects of a long-term upgrade programme for the Large Hadron Collider (LHC), CERN laboratory's new proton-proton collider. The super-LHC, which is currently under evaluation and design, is expected to deliver of the order of ten times the statistics of the LHC. In addition to a non-technical summary of the principal physics arguments for the upgrade, I present a pedagogical introduction to the technological challenges on the accelerator and experimental fronts, and a review of the current status of the planning.Comment: To appear in Contemporary Physic

Extended peptide-based inhibitors efficiently target the proteasome and reveal overlapping specificities of the catalytic β-subunits

AbstractBackground: The 26S proteasome is responsible for most cytosolic proteolysis, and is an important protease in major histocompatibility complex class I-mediated antigen presentation. Constitutively expressed proteasomes from mammalian sources possess three distinct catalytically active species, β1, β2 and β5, which are replaced in the γ-interferon-inducible immunoproteasome by a different set of catalytic subunits, β1i, β2i and β5i, respectively. Based on preferred cleavage of short fluorogenic peptide substrates, activities of the proteasome have been assigned to individual subunits and classified as ‘chymotryptic-like’ (β5), ‘tryptic-like’ (β2) and ‘peptidyl-glutamyl peptide hydrolyzing’ (β1). Studies with protein substrates indicate a far more complicated, less strict cleavage preference. We reasoned that inhibitors of extended size would give insight into the extent of overlapping substrate specificity of the individual activities and subunits.Results: A new class of proteasome inhibitors, considerably extended in comparison with the commonly used fluorescent substrates and peptide-based inhibitors, has been prepared. Application of the safety catch resin allowed the generation of the target compounds using a solid phase protocol. Evaluation of the new compounds revealed a set of highly potent proteasome inhibitors that target all individual active subunits with comparable affinity, unlike the other inhibitors described to date. Modification of the most active compound, adamantane-acetyl-(6-aminohexanoyl)3-(leucinyl)3-vinyl-(methyl)-sulfone (AdaAhx3L3VS), itself capable of proteasome inhibition in living cells, afforded a new set of radio- and affinity labels.Conclusions: N-terminal extension of peptide vinyl sulfones has a profound influence on both their efficiency and selectivity as proteasome inhibitors. Such extensions greatly enhance inhibition and largely obliterate selectivity towards the individual catalytic activities. We conclude that for the interaction with larger substrates, there appears to be less discrimination of different substrate sequences for the catalytic activities than is normally assumed based on the use of small peptide-based substrates and inhibitors. The compounds described here are readily accessible synthetically, and are more potent inhibitors in living cells than their shorter peptide vinyl sulfone counterparts

Response of neovascular central serous chorioretinopathy to an extended upload of anti-VEGF agents

Purpose To determine the anatomical and functional outcomes of an extended 6-month intravitreal anti-vascular endothelial growth factor (anti-VEGF) upload in choroidal neovascularization (CNV) secondary to chronic central serous chorioretinopathy (CSCR). Methods A retrospective database analysis was performed applying the following inclusion criteria: (1) diagnosis of CSCR, (2) diagnosis of secondary CNV, and (3) treatment of at least six consecutive injections of anti-VEGF. Outcome measures included the change of central retinal subfield thickness, remodeling of the pigment epithelium detachments, and change in visual function. Results Twenty-one eyes of 21 patients were included. Mean patient age was 65 ± 8.3 years, and 35% of the patients (n = 8) were female. Mean disease duration before diagnosis of CNV was 48 ± 25.3 months. Mean central retinal thickness decreased from 346 ± 61 to 257 ± 57 μm (p < 0.01) after the sixth injection while mean visual acuity improved from 0.65 ± 0.35 to 0.49 ± 0.29 (logMAR; p < 0.01). Of note, an extended upload of six as opposed to three injections yielded an additional mean central retinal thickness reduction (280 ± 46 μm vs. 257 ± 57 μm, p = 0.038). Significant CNV remodeling was observed as a decrease in pigment epithelium detachment (PED) vertical (p = 0.021) and horizontal diameter (p = 0.024) as well as PED height (p < 0.01). Conclusion An extended anti-VEGF upload of six consecutive injections seems to be effective in inducing CNV remodeling and fluid resorption in CNV complicating chronic CSCR