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Objective/background The objective was to examine trends in abdominal aortic and iliac aneurysm repairs in Norway from 2001 to 2013, and study regional variations and organizational developments in this type of vascular surgery. Methods This was a retrospective study on aortic and iliac aneurysm repairs using data from the Norwegian Patient Register. The vascular centers were categorized by yearly volume of repairs into small (<18), medium (18–49) and large (≥50). Incidence rates were assessed per 100,000 ≥ 60 years. The percentage of endovascular aneurysm repairs (EVAR) was calculated among the conducted repairs at the three categories of centers and the South-Eastern, Western, Central, and Northern Norway Regional Health Authority (NRHA). Results The national incidence rates of intact repairs per 100,000 ≥ 60 years increased from 57.4 to 65.7 ( p < .01). Ruptured repairs decreased from 19.7 to 9.2 ( p < .01). The rate of EVAR increased from 6.0 to 29.9 ( p < .01) in intact and from 0.4 to 2.5 ( p < .01) in ruptured repairs. The vascular centers were reduced from 25 to 16. The rate of EVAR was 27.1% ( p < .01) higher at large centers and 7.9% ( p < .03) higher at medium centers compared with small centers, and from 11.1% to 15.7% higher ( p < .01) at the Central, Western, and Northern NRHA compared with the South-Eastern NRHA, which had the most centers (also in the large category). The national increase in intact EVAR from 10.6% to 43.3% was less compared with many other Western countries. Conclusion During the study period the rates of intact repairs increased while the ruptured repairs decreased. EVAR was associated with centers performing high volumes of abdominal aortic and iliac aneurysm repairs and regional authorities organized with few centers. [ABSTRACT FROM AUTHOR]

A novel type of resonance ionization laser ion source (RILIS) is under development, which combines the advantages of laser ionization with those of a source-implemented ion trap. This laser ion source trap (LIST) system, based on a gas-filled linear radio-frequency quadrupole ion trap, decouples the evaporation and ionization process by introduction of a primary surface ion repeller. Apart from significantly enhancing the selectivity in radioactive ion beam production, optimum control on the temporal pulse structure and the emittance of the generated laser ion bunch is obtained. A variety of operational modes from quasi-dc to microseconds-bunched ion beams with variable repetition rate can be set. Principles and layout of individual components of the LIST are presented on the basis of atom and ion trajectory simulations and resulting performance parameters are discussed. [Copyright &y& Elsevier]

Abstract: The long-lived radio isotope 237Np is generated within the nuclear fuel cycle and represents a major hazard in the final disposal of nuclear waste. Related geochemical research requires sensitive methods for the detection of ultratrace amounts of neptunium in environmental samples. Resonance ionization mass spectrometry (RIMS) has proven to be one of the most sensitive methods for the detection of plutonium. A precondition for the application of RIMS to ultratrace analysis of neptunium is the knowledge of an efficient and selective scheme for optical excitation and ionization. Therefore, a multitude of medium to high-lying atomic levels in neptunium was located by applying in-source resonance ionization spectroscopy. By using excitation via six previously known first excited, intermediate levels of odd parity, a set of twelve so far unknown high-lying levels of even parity were identified and studied further for their suitability in resonant excitation/ionization schemes. Autoionizing resonances for efficient ionization of neptunium atoms were subsequently accessed spectroscopically. Altogether five resonance ionization schemes were investigated and characterized concerning their saturation behavior and relative efficiency. Applying a calibrated sample, an overall efficiency of 0.3% was determined. [Copyright &y& Elsevier]

Abstract: Near-infrared fluorophore (NIRF)-labeled imaging probes are becoming increasingly important in bio-molecular imaging applications, that is, in animal models for tumor imaging or inflammation studies. In this study we showed that the previously introduced chemical concept of ‘Reverse Design’ represents an efficient strategy for the generation of selective probes for cysteine proteases from chemically optimized protease inhibitors for investigations in proteomic lysates as well as for in vivo molecular imaging studies. The newly developed activity-based probe AW-091 was demonstrated to be highly selective for cathepsin S in vitro and proved useful in monitoring cysteine cathepsin activity in vivo, that is, in zymosan-induced mouse model of inflammation. AW-091 showed higher signal-to-background ratios at earlier time points than the commercially available polymer-based ProSense680 (VisEn Medical) and thus represents an efficient new tool for studying early proteolytic processes leading to various diseases, including inflammation, cancer, and rheumatoid arthritis. In addition, the fluorescent signal originating from the cleaved AW-091 was shown to be reduced by the administration of an anti-inflammatory drug, dexamethasone and by the cathepsin inhibitor E-64, providing a valuable system for the evaluation of small-molecule inhibitors of cathepsins. [Copyright &y& Elsevier]

Fibroblast growth factor (FGF) signaling regulates mammalian development and metabolism, and its dysregulation is implicated in many inherited and acquired diseases, including cancer. Heparan sulfate glycosaminoglycans (HSGAGs) are essential for FGF signaling as they promote FGF⋅FGF receptor (FGFR) binding and dimerization. Using novel organic synthesis protocols to prepare homogeneously sulfated heparin mimetics (HM), including hexasaccharide (HM6), octasaccharide (HM8), and decasaccharide (HM10), we tested the ability of these HM to support FGF1 and FGF2 signaling through FGFR4. Biological assays show that both HM8 and HM10 are significantly more potent than HM6 in promoting FGF2-mediated FGFR4 signaling. In contrast, all three HM have comparable activity in promoting FGFI⋅FGFR4 signaling. To understand the molecular basis for these differential activities in FGF1/2⋅FGFR4 signaling, we used NMR spectroscopy, isothermal titration calorimetry, and size-exclusion chromatography to characterize binding interactions of FGF1/2 with the isolated Ig-domain 2 (D2) of FGFR4 in the presence of HM, and binary interactions of FGFs and D2 with HM. Our data confirm the existence of both a secondary FGFI⋅FGFR4 interaction site and a direct FGFR4⋅FGFR4 interaction site thus supporting the formation of the symmetric mode of FGF⋅FGFR dimerization in solution. Moreover, our results show that the observed higher activity of HMs relative to HM6 in stimulating FGF2⋅FGFR4 signaling correlates with the higher affinity of HM8 to bind and dimerize FGF2. Notably FGF2⋅HM8 exhibits pronounced positive binding cooperativity. Based on our findings we propose a refined symmetric FGF⋅FGFR dimerization model, which incorporates the differential ability of HM to dimerize FGFs. [ABSTRACT FROM AUTHOR]

Mature thrombin-activable fibrinolysis inhibitor (TAFIa) is a highly unstable metallocarboxypeptidase that stabilizes blood clots by clipping C-terminal lysine residues from partially degraded fibrin. In accordance with its in vitro antifibrinolytic activity, animal studies have reported that inhibition of mature TAFI aids in the prevention of thrombosis. The level of TAFI activity is stringently regulated through (i) controlled proteolytic truncation of the zymogen (TAFI), generating the mature enzyme, TAFIa, and (ii) the short half-life of TAFIa. TAFI itself exhibits an intrinsic enzymatic activity, which is likely required to provide a baseline level of antifibrinolytic activity. The novel crystal structure presented here reveals that the active site of TAFI is accessible, providing the structural explanation for the its intrinsic activity. It also supports the notion that an "instability region" exists, in agreement with site-directed mutagenesis studies. Sulfate ions, bound to this region, point toward a potential heparin-binding site and could explain how heparin stabilizes TAFIa. [ABSTRACT FROM AUTHOR]

The autoionization (AI) spectrum of gadolinium between the first and second limits has been investigated by triple-resonance excitation with high-resolution cw lasers. A large number of narrow AI resonances have been observed and assigned total angular momentum J values. The resonances are further divided into members of AI Rydberg series converging to the second limit or other ‘interloping’ levels. Fine structure in the Rydberg series has been identified and interpreted in terms of Jcj coupling. A number of detailed studies have been performed on the interloping resonances: these include lifetime determination by line-shape analysis, isotope shifts, hyperfine structure, and photoionization saturation parameters. The electronic structure of the interloping levels is discussed in terms of these studies. Line-widths generally decrease with increasing total angular momentum and the J=7 resonances are extremely narrow with Lorentzian widths ranging from <1 MHz up to 157 MHz. The strongest resonances are found to have cross-sections of ∼10−12 cm2 and photoionization can be saturated with powers available from cw diode lasers. [Copyright &y& Elsevier]