Associations between the Complement System and Choroidal Neovascularization in Wet Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is the leading cause of blindness affecting the elderly in the Western world. The most severe form of AMD, wet AMD (wAMD), is characterized by choroidal neovascularization (CNV) and acute vision loss. The current treatment for these patients comprises monthly intravitreal injections of anti-vascular endothelial growth factor (VEGF) antibodies, but this treatment is expensive, uncomfortable for the patient, and only effective in some individuals. AMD is a complex disease that has strong associations with the complement system. All three initiating complement pathways may be relevant in CNV formation, but most evidence indicates a major role for the alternative pathway (AP) and for the terminal complement complex, as well as certain complement peptides generated upon complement activation. Since the complement system is associated with AMD and CNV, a complement inhibitor may be a therapeutic option for patients with wAMD. The aim of this review is to (i) reflect on the possible complement targets in the context of wAMD pathology, (ii) investigate the results of prior clinical trials with complement inhibitors for wAMD patients, and (iii) outline important considerations when developing a future strategy for the treatment of wAMD.     

Precipitation and pinning in Ca and Sr-Rich High-Tc superconducting “Bi2Sr2CaCu2O8” ceramics

From a consideration of the phase equilibrium diagram of the system Bi₂O₃-SrO-CaO-CuO, a simple annealing procedure was developed to precipitate Bi_2+xSr_2+xCuO_6+d, Sr₁₄Cu₂₄O_41−x, and Bi₂Sr₃O₆ in high-temperature superconducting Sr-rich “Bi₂Sr₂CaCu₂O₈” ceramics and Ca₂CuO₃ and a liquid in Ca-rich “Bi₂Sr₂CaCu₂O₈” ceramics. The transformation results in an increase of the critical current density of which is believed to express improved pinning properties of the superconducting crystals, in particular an increased pinning energy, which reduces the probability for thermally activated depinning. Possible pinning centers which were introduced during precipitation of the second phases are the surface of the precipitates.     

Thermodynamic data of the formation of titanium nitride in iron

The solubility of titanium nitride in liquid iron is described by the solubility product log([%Ti][%N])₁ = ?17040/T + 6.40 reported by Turkdogan. The solubility in δ ferrite measured by Kunze is log<[%Ti][%N])_δ = ?17205/T + 5.56. Combining the solubilities in both phases and the solubilities of nitrogen the distribution equilibrium of titanium can be derived. It is characterized by the thermodynamic distribution coefficient k^δ/I_o,Ti = [%Ti]_δ/[%Ti] = 0.40. By zone melting and secondary ion mass spectrometry of the titanium distribution k^δ/I_Ti = 0.53 was measured. An analysis of all known data led to k^δ/I_o,Ti = 0.40…0.50. Measurements of the TiN solubility in austenite by heat treatment were not significant. They led to distribution coefficients between 0.07 and > 1. By zone melting in a carburizing atmosphere a distribution coefficient k^γ/I_Ti = 0.12 was measured. From a thermodynamic analysis performed by Ohtani et al., from the TiN solubility in the melt, and from the solubilities of nitrogen k^γ/I_o,Ti = 0.13 was deduced. Basing on the distribution equilibria of titanium and nitrogen and on the measured temperature dependence the solubility product log([%Ti][%N])_γ = ?15000/T + 4.06 was obtained.     

Computing change and specificity with equational logic programs

Recent deductive approaches to reasoning about action and chance allow us to model objects and methods in a deductive framework. In these approaches, inheritance of methods comes for free, whereas overriding of methods is unsupported. In this paper, we present an equational logic framework for objects, methods, inheritance and overriding of methods. Overriding is achieved via the concept of specificity, which states that more specific methods are preferred to less specific ones. Specificity is computed with the help of negation as failure. We specify equational logic programs and show that their completed versions behave as intended. Furthermore, we prove that SLDENF-resolution is complete if the equational theory is finitary, the completed programs are consistent and no derivation flounders or is infinite. Moreover, we give syntactic conditions which guarantee that no derivation flounders or is infinite. Finally, we discuss how the approach can be extended to reasoning about the past in the context of incompletely specified objects or situations. It will turn out that constructive negation is needed to solve these problems.     

On case-based learnability of languages

Case-based reasoning is deemed an important technology to alleviate the bottleneck of knowledge acquisition in Artificial Intelligence (AI). In case-based reasoning, knowledge is represented in the form of particular cases with an appropriate similarity measure rather than any form of rules. The case-based reasoning paradigm adopts the view that an Al system is dynamically changing during its life-cycle which immediately leads to learning considerations. Within the present paper, we investigate the problem of case-based learning of indexable classes of formal languages. Prior to learning considerations, we study the problem of case-based representability and show that every indexable class is case-based representable with respect to a fixed similarity measure. Next, we investigate several models of case-based learning and systematically analyze their strengths as well as their limitations. Finally, the general approach to case-based learnability of indexable classes of formal languages is prototypically applied to so-called containmet decision lists, since they seem particularly tailored to case-based knowledge processing.     

Preface: Volume 70, Issue 1

This paper defines reduction on derivations in the strict intersection type assignment system of [2], by generalising cutelimination, and shows a strong normalisation result for this reduction. Using this result, new proofs are given for the approximation theorem and the characterisation of normalisability using intersection types.