Synthetic iron–sulfur clusters of general formulation Fe m S q L l z with core atoms Fe and S and terminal ligands L constitute a family of molecular clusters with remarkably diverse geometrical and ...electronic structures. Several structure types are also found in proteins. The large majority of research on these clusters has involved elucidation of physical properties. Here, we direct attention to reactivity in the form of cluster conversions in which the Fe m S q cores of reactants are transformed to new structures, usually of different nuclearity, in overall reactions such as self-assembly and fragment condensation and dissociation. An extensive body of core conversions, many of which have not been recognized as such, are presented including those in biological systems. All structural core types are depicted, and all core conversions are diagrammatically summarized. Clusters containing the cubane-type Fe4S4 core play a central role in conversion chemistry. The core conversion concept tends to reinforce the description of iron–sulfur cores as modular units subject to various covalent bond interactions that lead to different structures.
Lee et al report on developments in the biomimetic chemistry of cubane-type and higher nuclearity iron-sulfur clusters. They touch on general tactics in cluster synthesis, Fe4S4 clusters, ...heterometallic clusters, heteroligated cluster cores, and Fe8S7 clusters by nonpolar assembly.
Quantitative flow ratio (QFR) is a novel angiography-based method for deriving fractional flow reserve (FFR) without pressure wire or induction of hyperemia. The accuracy of QFR when assessed online ...in the catheterization laboratory has not been adequately examined to date.
The goal of this study was to assess the diagnostic performance of QFR for the diagnosis of hemodynamically significant coronary stenosis defined by FFR ≤0.80.
This prospective, multicenter trial enrolled patients who had at least 1 lesion with a diameter stenosis of 30% to 90% and a reference diameter ≥2 mm according to visual estimation. QFR, quantitative coronary angiography (QCA), and wire-based FFR were assessed online in blinded fashion during coronary angiography and re-analyzed offline at an independent core laboratory. The primary endpoint was that QFR would improve the diagnostic accuracy of coronary angiography such that the lower boundary of the 2-sided 95% confidence interval (CI) of this estimate exceeded 75%.
Between June and July 2017, a total of 308 patients were consecutively enrolled at 5 centers. Online QFR and FFR results were both obtained in 328 of 332 interrogated vessels. Patient- and vessel-level diagnostic accuracy of QFR was 92.4% (95% CI: 88.9% to 95.1%) and 92.7% (95% CI: 89.3% to 95.3%), respectively, both of which were significantly higher than the pre-specified target value (p < 0.001). Sensitivity and specificity in identifying hemodynamically significant stenosis were significantly higher for QFR than for QCA (sensitivity: 94.6% vs. 62.5%; difference: 32.0% p < 0.001; specificity: 91.7% vs. 58.1%; difference: 36.1% p < 0.001). Positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio for QFR were 85.5%, 97.1%, 11.4, and 0.06. Offline analysis also revealed that vessel-level QFR had a high diagnostic accuracy of 93.3% (95% CI: 90.0% to 95.7%).
The study met its prespecified primary performance goal for the level of diagnostic accuracy of QFR in identifying hemodynamically significant coronary stenosis. (The FAVOR Functional Diagnostic Accuracy of Quantitative Flow Ratio in Online Assessment of Coronary Stenosis II China study; NCT03191708)
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Barnacles and Biofouling Holm, Eric R
Integrative and comparative biology,
09/2012, Letnik:
52, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Biofouling, the attachment and growth of organisms on submerged, man-made surfaces, has plagued ship operators for at least 2500 years. Accumulation of biofouling, including barnacles and other ...sessile marine invertebrates, increases the frictional resistance of ships’ hulls, resulting in an increase in power and in fuel consumption required to make speed. Scientists and engineers recognized over 100 years ago that in order to solve the biofouling problem, a deeper understanding of the biology of the organisms involved, particularly with regard to larval settlement and metamorphosis and adhesives and adhesion, would be required. Barnacles have served as an important tool in pursuing this research. Over the past 20 years, the pace of these studies has accelerated, likely driven by the introduction of environmental regulations banning the most effective biofouling control products from the market. Research has largely focused on larval settlement and metamorphosis, the development of new biocides, and materials/surface science. Increased research has so far, however, failed to result in commercial applications. Two recent successes (medetomidine/Selektope®, surface-bound noradrenaline) build on our improving understanding of the role of the larval nervous system in mediating settlement and metamorphosis. New findings with regard to the curing of barnacle adhesives may pave the way to additional successes. Although the development of most current biofouling control technologies remains largely uninfluenced by basic research on, for example, the ability of settling larvae to perceive surface cues, or the nature of the interaction between organismal adhesives and the substrate, newly-developed materials can serve as useful probes to further our understanding of these processes.
Abstract
This Consensus Document is the first of two reports summarizing the views of an expert panel organized by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) on the ...clinical use of intracoronary imaging including intravascular ultrasound (IVUS) and optical coherence tomography (OCT). The first document appraises the role of intracoronary imaging to guide percutaneous coronary interventions (PCIs) in clinical practice. Current evidence regarding the impact of intracoronary imaging guidance on cardiovascular outcomes is summarized, and patients or lesions most likely to derive clinical benefit from an imaging-guided intervention are identified. The relevance of the use of IVUS or OCT prior to PCI for optimizing stent sizing (stent length and diameter) and planning the procedural strategy is discussed. Regarding post-implantation imaging, the consensus group recommends key parameters that characterize an optimal PCI result and provides cut-offs to guide corrective measures and optimize the stenting result. Moreover, routine performance of intracoronary imaging in patients with stent failure (restenosis or stent thrombosis) is recommended. Finally, strengths and limitations of IVUS and OCT for guiding PCI and assessing stent failures and areas that warrant further research are critically discussed.
Biomimetic inorganic chemistry has as its primary goal the synthesis of molecules that approach or achieve the structures, oxidation states, and electronic and reactivity features of native ...metal-containing sites of variant nuclearity. Comparison of properties of accurate analogues and these sites ideally provides insight into the influence of protein structure and environment on intrinsic properties as represented by the analogue. For polynuclear sites in particular, the goal provides a formidable challenge for, with the exception of iron−sulfur clusters, all such site structures have never been achieved and few have even been closely approximated by chemical synthesis. This account describes the current status of the synthetic analogue approach as applied to the mononuclear sites in certain molybdoenzymes and the polynuclear sites in hydrogenases, nitrogenase, and carbon monoxide dehydrogenases.
In the present study, the overall economic impact of hull fouling on a mid-sized naval surface ship (Arleigh Burke-class destroyer DDG-51) has been analyzed. A range of costs associated with hull ...fouling was examined, including expenditures for fuel, hull coatings, hull coating application and removal, and hull cleaning. The results indicate that the primary cost associated with fouling is due to increased fuel consumption attributable to increased frictional drag. The costs related to hull cleaning and painting are much lower than the fuel costs. The overall cost associated with hull fouling for the Navy's present coating, cleaning, and fouling level is estimated to be $56M per year for the entire DDG-51 class or $1B over 15 years. The results of this study provide guidance as to the amount of money that can be reasonably spent for research, development, acquisition, and implementation of new technologies or management strategies to combat hull fouling.
The synthetic analogue approach to the metal sites in iron-sulfur proteins was initiated in the early 1970s. Iron-sulfur analogue chemistry is now a mature subject in large part.
There remain problems for chemists who choose to pursue metal clusters in biology. It remains to be seen whether the synthesis of nitrogenase clusters will precede explication of the biosynthetic ...pathways.
Novel supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) containing the poorly water-soluble drug halofantrine above equilibrium solubility (150% Seq) were compared in vitro and ...in vivo with conventional SNEDDS containing the drug below equilibrium solubility (75% Seq). Pre-concentrates comprising of either medium chain lipids (Captex 300/Capmul MCM) or long chain lipids (soybean oil/Maisine), Cremophor RH40 and ethanol were formulated maintaining the lipid-to-surfactant-to-cosolvent ratio constant (55:35:10, w/w %). The ability of super-SNEDDS to increase the absorption of halofantrine in dogs, as well as the predictivity of the dynamic in vitro lipolysis model was studied. In vitro lipolysis of SNEDDS and super-SNEDDS showed rapid drug precipitation from all formulations while the same drug concentrations in the digestion medium were found during digestion of equal amounts of SNEDDS and super-SNEDDS. Elevated halofantrine solubilisation during in vitro lipolysis was observed only when multiple capsules of conventional SNEDDS were subjected to in vitro digestion. After lipolysis the isolated super-SNEDDS pellets were characterised by XRPD revealing no crystalline halofantrine from any of the investigated formulations. Subsequent dissolution studies of the super-SNEDDS pellet in the lipolysis medium demonstrated enhanced dissolution of halofantrine suggesting that halofantrine in the pellet was amorphous. The enhanced dissolution of the amorphous halofantrine was also reflected in vivo since two capsules of conventional SNEDDS were needed to achieve similar AUC and Cmax as obtained after dosing of a single capsule of super-SNEDDS. The study demonstrated that the absorption of halofantrine was not hampered by drug precipitation. Super-SNEDDS lead to precipitation of halofantrine in an amorphous form, which can be the driving force for enhanced absorption. Since super-SNEDDS were also physically stable for at least 6months they represent a potential novel oral lipid-based drug delivery system for low aqueous soluble compounds.
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