Classifying and Formally Verifying Integer Constant Folding

Constant folding is a well-known optimization of compilers which evaluates constant expressions already at compile time. Constant folding is valid only if the results computed by the compiler are exactly the same as the results which would be computed at run-time by the target machine arithmetic. We classify different arithmetics by deriving a general condition under which a target-machine arithmetic can be replaced by a compiler arithmetic. Furthermore, we consider integer arithmetics as a special case. They can be described by residue class arithmetics. We show that these arithmetics form a lattice. Using the order relation in this lattice, we establish a necessary and sufficient criterion under which constant folding can be done in a residue class arithmetic that is different from the one of the target machine. Concerning formal verification, we have formalized our proofs in the Isabelle/HOL system. As examples, we discuss the Java and C integer arithmetics and show which compiler arithmetics are valid for constant folding. This discussion reveals also potential sources of incorrect behavior of C compilers.     

The vapor pressure and thermodynamic activities of zinc in solid alpha brasses

The vapor pressures of zinc over solid alpha brasses were determined for six alloys ranging in composition from approximately 5 to 30 pct zinc. The absorption spectra method was utilized for obtaining the vapor pressure data. Activities and activity coefficients are given for zinc for the six alloys investigated.     

The Functional Characterization of GCaMP3.0 Variants Specifically Targeted to Subcellular Domains

Calcium (Ca²⁺) ions play a pivotal role in physiology and cellular signaling. The intracellular Ca²⁺ concentration ([Ca²⁺]_i) is about three orders of magnitude lower than the extracellular concentration, resulting in a steep transmembrane concentration gradient. Thus, the spatial and the temporal dynamics of [Ca²⁺]_i are ideally suited to modulate Ca²⁺-mediated cellular responses to external signals. A variety of highly sophisticated methods have been developed to gain insight into cellular Ca²⁺ dynamics. In addition to electrophysiological measurements and the application of synthetic dyes that change their fluorescent properties upon interaction with Ca²⁺, the introduction and the ongoing development of genetically encoded Ca²⁺ indicators (GECI) opened a new era to study Ca²⁺-driven processes in living cells and organisms. Here, we have focused on one well-established GECI, i.e., GCaMP3.0. We have systematically modified the protein with sequence motifs, allowing localization of the sensor in the nucleus, in the mitochondrial matrix, at the mitochondrial outer membrane, and at the plasma membrane. The individual variants and a cytosolic version of GCaMP3.0 were overexpressed and purified from E. coli cells to study their biophysical properties in solution. All versions were examined to monitor Ca²⁺ signaling in stably transfected cell lines and in primary cortical neurons transduced with recombinant Adeno-associated viruses (rAAV). In this comparative study, we provide evidence for a robust approach to reliably trace Ca²⁺ signals at the (sub)-cellular level with pronounced temporal resolution.     

Cloning and Functional Characterization of Dog OCT1 and OCT2: Another Step in Exploring Species Differences in Organic Cation Transporters

OCT1 and OCT2 are polyspecific membrane transporters that are involved in hepatic and renal drug clearance in humans and mice. In this study, we cloned dog OCT1 and OCT2 and compared their function to the human and mouse orthologs. We used liver and kidney RNA to clone dog OCT1 and OCT2. The cloned and the publicly available RNA-Seq sequences differed from the annotated exon-intron structure of OCT1 in the dog genome CanFam3.1. An additional exon between exons 2 and 3 was identified and confirmed by sequencing in six additional dog breeds. Next, dog OCT1 and OCT2 were stably overexpressed in HEK293 cells and the transport kinetics of five drugs were analyzed. We observed strong differences in the transport kinetics between dog and human orthologs. Dog OCT1 transported fenoterol with 12.9-fold higher capacity but 14.3-fold lower affinity (higher K_M) than human OCT1. Human OCT1 transported ipratropium with 5.2-fold higher capacity but 8.4-fold lower affinity than dog OCT1. Compared to human OCT2, dog OCT2 showed 10-fold lower transport of fenoterol and butylscopolamine. In conclusion, the functional characterization of dog OCT1 and OCT2 reported here may have implications when using dogs as pre-clinical models as well as for drug therapy in dogs.     

Chelating Polymers for Targeted Decontamination of Actinides: Application of PEI-MP to Hydroxyapatite-Th(IV)

In case of an incident in the nuclear industry or an act of war or terrorism, the dissemination of plutonium could contaminate the environment and, hence, humans. Human contamination mainly occurs via inhalation and/or wounding (and, less likely, ingestion). In such cases, plutonium, if soluble, reaches circulation, whereas the poorly soluble fraction (such as small colloids) is trapped in alveolar macrophages or remains at the site of wounding. Once in the blood, the plutonium is delivered to the liver and/or to the bone, particularly into its mineral part, mostly composed of hydroxyapatite. Countermeasures against plutonium exist and consist of intravenous injections or inhalation of diethylenetetraminepentaacetate salts. Their effectiveness is, however, mainly confined to the circulating soluble forms of plutonium. Furthermore, the short bioavailability of diethylenetetraminepentaacetate results in its rapid elimination. To overcome these limitations and to provide a complementary approach to this common therapy, we developed polymeric analogs to indirectly target the problematic retention sites. We present herein a first study regarding the decontamination abilities of polyethyleneimine methylcarboxylate (structural diethylenetetraminepentaacetate polymer analog) and polyethyleneimine methylphosphonate (phosphonate polymeric analog) directed against Th(IV), used here as a Pu(IV) surrogate, which was incorporated into hydroxyapatite used as a bone model. Our results suggest that polyethylenimine methylphosphonate could be a good candidate for powerful bone decontamination action.     

Impact of enzymatic mash maceration and storage on anthocyanin and color retention of pasteurized strawberry purées

Strawberry purées were prepared using a commercial polygalacturonase (PG) and a highly purified pectinesterase (PE) preparation, respectively. To elucidate the effect of pectin on color stability following enzymatic pulp maceration, pectin composition was studied by isolating and fractionating the alcohol-insoluble residue from the strawberry purées. The purées were stored at +20 and +4 °C in the dark over a period of 24 weeks monitoring the amounts of monomeric and polymeric anthocyanins as well as antioxidant activities (FRAP, TEAC). Individual anthocyanins were analyzed by HPLC–DAD–MS ⁿ , and color measurements were obtained in the CIE L*a*b* system. Pectin composition was significantly modified following enzymatic maceration of the purées. While PG treatment generally resulted in pectin losses, oxalate-soluble pectins were increased in PE-treated purées. After 24 weeks of storage, the best anthocyanin retention was observed in PE-treated purées. Such products also revealed greatest anthocyanin half-life values and lowest proportion of polymeric pigments. Compared to an untreated control, enzymatic purée maceration using the PG was also beneficial for pigment retention, but less effective than PE. In contrast, color and antioxidant activity were independent of both enzymatic treatments. An initial heating step (90 °C, 10 s) for immediate inactivation of native enzymes such as polyphenoloxidases slightly improved pigment stability, while lowered temperature during mash maceration was less effective. However, by far best color and pigment retention were achieved when the purées were stored at 4 °C in the dark.     

Influence of Surface Modifications on the Spatiotemporal Microdistribution of Quantum Dots In Vivo

For biomedical applications of nanoconstructs, it is a general prerequisite to efficiently reach the desired target site. In this regard, it is crucial to determine the spatiotemporal distribution of nanomaterials at the microscopic tissue level. Therefore, the effect of different surface modifications on the distribution of microinjected quantum dots (QDs) in mouse skeletal muscle tissue has been investigated. In vivo real‐time fluorescence microscopy and particle tracking reveal that carboxyl QDs preferentially attach to components of the extracellular matrix (ECM), whereas QDs coated with polyethylene glycol (PEG) show little interaction with tissue constituents. Transmission electron microscopy elucidates that carboxyl QDs adhere to collagen fibers as well as basement membranes, a type of ECM located on the basolateral side of blood vessel walls. Moreover, carboxyl QDs have been found in endothelial junctions as well as in caveolae of endothelial cells, enabling them to translocate into the vessel lumen. The in vivo QD distribution is confirmed by in vitro experiments. The data suggest that ECM components act as a selective barrier depending on QD surface modification. For future biomedical applications, such as targeting of blood vessel walls, the findings of this study offer design criteria for nanoconstructs that meet the requirements of the respective application.     

Accurate junction detection and characterization in line-drawing images

In this paper, we present a new approach for junction detection and characterization in line-drawing images. We formulate this problem as searching for optimal meeting points of median lines. In this context, the main contribution of the proposed approach is three-fold. First, a new algorithm for the determination of the support region is presented using the linear least squares technique, making it robust to digitization effects. Second, an efficient algorithm is proposed to detect and conceptually remove all distorted zones, retaining reliable line segments only. These line segments are then locally characterized to form a local structure representation of each crossing zone. Finally, a novel optimization algorithm is presented to reconstruct the junctions. Junction characterization is then simply derived. The proposed approach is very highly robust to common geometry transformations and can resist a satisfactory level of noise/degradation. Furthermore, it works very efficiently in terms of time complexity and requires no prior knowledge of the document content. Extensive evaluations have been performed to validate the proposed approach using other baseline methods. An application of symbol spotting is also provided, demonstrating quite good results.