Multimodal X-ray imaging of nanocontainer-treated macrophages and calcium distribution in the perilacunar bone matrix

Studies of biological systems typically require the application of several complementary methods able to yield statistically-relevant results at a unique level of sensitivity. Combined X-ray fluorescence and ptychography offer excellent elemental and structural imaging contrasts at the nanoscale. They enable a robust correlation of elemental distributions with respect to the cellular morphology. Here we extend the applicability of the two modalities to higher X-ray excitation energies, permitting iron mapping. Using a long-range scanning setup, we applied the method to two vital biomedical cases. We quantified the iron distributions in a population of macrophages treated with Mycobacterium-tuberculosis-targeting iron-oxide nanocontainers. Our work allowed to visualize the internalization of the nanocontainer agglomerates in the cytosol. From the iron areal mass maps, we obtained a distribution of antibiotic load per agglomerate and an average areal concentration of nanocontainers in the agglomerates. In the second application we mapped the calcium content in a human bone matrix in close proximity to osteocyte lacunae (perilacunar matrix). A concurrently acquired ptychographic image was used to remove the mass-thickness effect from the raw calcium map. The resulting ptychography-enhanced calcium distribution allowed then to observe a locally lower degree of mineralization of the perilacunar matrix

Solving Constraints in Model Transformations

Constraint programming holds many promises for model driven software development (MDSD). Up to now, constraints have only started to appear in MDSD modeling languages, but have not been properly reflected in model transformation. This paper introduces constraint programming in model transformation, shows how constraint programming integrates with QVT Relations - as a pathway to wide spread use of our approach - and describes the corresponding model transformation engine. In particular, the paper will illustrate the use of constraint programming for the specification of attribute values in target models, and provide a qualitative evaluation of the benefit drawn from constraints integrated with QVT Relations

Inductive Proof Outlines for Monitors in Java

Abstract. The research concerning Java’s semantics and proof theory has mainly focussed on various aspects of sequential sub-languages. Java, however, integrates features of a class-based object-oriented language with the notion of multi-threading, where multiple threads can concurrently execute and exchange information via shared instance variables. Furthermore, each object can act as a monitor to assure mutual exclusion or to coordinate between threads. In this paper we present a sound and relatively complete assertional proof system for Java’s monitor concept, which generates verification conditions for a concurrent sublanguage JavaMT of Java. This work extends previous results by incorporating Java’s monitor methods

High-speed fixed-target serial virus crystallography

We report a method for serial X-ray crystallography at X-ray free-electron lasers (XFELs), which allows for full use of the current 120-Hz repetition rate of the Linear Coherent Light Source (LCLS). Using a micropatterned silicon chip in combination with the high-speed Roadrunner goniometer for sample delivery, we were able to determine the crystal structures of the picornavirus bovine enterovirus 2 (BEV2) and the cytoplasmic polyhedrosis virus type 18 polyhedrin, with total data collection times of less than 14 and 10 min, respectively. Our method requires only micrograms of sample and should therefore broaden the applicability of serial femtosecond crystallography to challenging projects for which only limited sample amounts are available. By synchronizing the sample exchange to the XFEL repetition rate, our method allows for most efficient use of the limited beam time available at XFELs and should enable a substantial increase in sample throughput at these facilities