Synthesis of 2‐[18F]Fluoro‐2‐deoxyisosorbide 5‐mononitrate and Assessment of Its in vivo Biodistribution as Determined by Dynamic Positron Emission Tomography (PET)

Herein we disclose the synthesis of 2‐fluoro‐2‐deoxyisosorbide 5‐mononitrate (2F‐IS‐5MN), a fluorinated analogue of the commonly prescribed vasodilator isosorbide 5‐mononitrate (IS‐5MN). X‐ray structural data for IS‐5MN and its C2‐epimeric congener IM‐5MN are presented together with structural data for 2F‐IS‐5MN. Radioisotope labeling of 2F‐IS‐5MN has, for the first time, allowed observation of the in vivo biodistribution of this organic nitrate by means of dynamic positron emission tomography (PET) in wild‐type mice.     

Nanomaterials for environmental studies: Classification, reference material issues, and strategies for physico-chemical characterisation

NanoImpactNet is a European Commission Framework Programme 7 (FP7) funded project that provides a forum for the discussion of current opinions on nanomaterials in relation to human and environmental issues. In September 2008, in Zurich, a NanoImpactNet environmental workshop focused on three key questions:

1.

What properties should be characterised for nanomaterials used in environmental and ecotoxicology studies?

2.

What reference materials should be developed for use in environmental and ecotoxicological studies?

3.

Is it possible to group different nanomaterials into categories for consideration in environmental studies?

Such questions have been, at least partially, addressed by other projects/workshops especially in relation to human health effects. Such projects provide a useful basis on which this workshop was based, but in this particular case these questions were reformulated in order to focus specifically on environmental studies. The workshop participants, through a series of discussion and reflection sessions, generated the conclusions listed below.The physicochemical characterisation information identified as important for environmental studies included measures of aggregation/agglomeration/dispersability, size, dissolution (solubility), surface area, surface charge, surface chemistry/composition, with the assumption that chemical composition would already be known.There is a need to have test materials for ecotoxicology, and several substances are potentially useful, including TiO₂ nanoparticles, polystyrene beads labelled with fluorescent dyes, and silver nanoparticles. Some of these test materials could then be developed into certified reference materials over time.No clear consensus was reached regarding the classification of nanomaterials into categories to aid environmental studies, except that a chemistry-based classification system was a reasonable starting point, with some modifications. It was suggested, that additional work may be required to derive criteria that can be used to generate such categories, that would also include aspects of the material structure and physical behaviour.     

Bacterial Dehydrogenases Facilitate Oxidative Inactivation and Bioremediation of Chloramphenicol

Antimicrobial resistance represents a major threat to human health and knowledge of the underlying mechanisms is therefore vital. Here, we report the discovery and characterization of oxidoreductases that inactivate the broad-spectrum antibiotic chloramphenicol via dual oxidation of the C3-hydroxyl group. Accordingly, chloramphenicol oxidation either depends on standalone glucose-methanol-choline (GMC)-type flavoenzymes, or on additional aldehyde dehydrogenases that boost overall turnover. These enzymes also enable the inactivation of the chloramphenicol analogues thiamphenicol and azidamfenicol, but not of the C3-fluorinated florfenicol. Notably, distinct isofunctional enzymes can be found in Gram-positive (e. g., Streptomyces sp.) and Gram-negative (e. g., Sphingobium sp.) bacteria, which presumably evolved their selectivity for chloramphenicol independently based on phylogenetic analyses. Mechanistic and structural studies provide further insights into the catalytic mechanisms of these biotechnologically interesting enzymes, which, in sum, are both a curse and a blessing by contributing to the spread of antibiotic resistance as well as to the bioremediation of chloramphenicol.     

Implementing a qualitative calculus to analyse moving point objects

Due to recent technological advances in position-aware devices, data about moving objects is becoming ubiquitous. Yet, it is a major challenge for spatial information systems to offer tools for the analysis of motion data, thereby evolving from static to dynamic frameworks. This paper aims to contribute to this area by introducing an implementation prototype for an information system based on the Qualitative Trajectory Calculus, a spatiotemporal calculus to represent and reason about moving point objects.     

Introducing functional classification theory to land use planning by means of decision tables

This paper contributes to the conceptualisation and analysis of double-sided matching problems, taking the land use planning problem as an example. It does so by introducing functional classification theory at the knowledge level, the symbol level and the system level of a DSS. This theory explicitly expresses the methodological viewpoint of relational realism. At the knowledge level this implies defining knowledge on the basis of matching the intension and extension of concepts. At the symbol level it deals with knowledge representation and here decision tables are advanced and formally introduced. At the system level the formalism used at the symbol level is implemented to develop a relational matching DSS.     

Heterogeneous oligonucleotide-hybridization assay based on hot electron-induced electrochemiluminescence of a rhodamine label at oxide-coated aluminum and silicon electrodes

This paper describes a heterogeneous oligonucleotide-hybridization assay based on hot electron-induced electrochemiluminescence (HECL) of a rhodamine label. Thin oxide-film coated aluminum and silicon electrodes were modified with an aminosilane layer and derivatized with short, 15-mer oligonucleotides via diisothiocyanate coupling. Target oligonucleotides were conjugated with tetramethylrhodamine (TAMRA) dye at their amino modified 5′ end and hybridization was detected using HECL of TAMRA. Preliminary results indicate sensitivity down to picomolar level and low nonspecific adsorption. The sensitivity was better on oxide-coated silicon compared to oxide-coated aluminum electrodes and two-base pair mismatched hybrids were successfully discriminated. The experimental results presented here might be useful for the design of disposable electrochemiluminescent DNA biosensors.     

The role of the hyperpolarization-activated inward current If in arrhythmogenesis: a computer model study.

Atrial fibrillation is the most common cardiac arrhythmia. Structural cardiac defects such as fibrosis and gap junction remodeling lead to a reduced cellular electrical coupling and are known to promote atrial fibrillation. It has been observed that the expression of the hyperpolarization-activated current If is increased under pathological conditions. Recent experimental data indicate a possible contribution of If to arrhythmogenesis. In this paper, the role of If in action potential propagation in normal and in pathological tissue is investigated by means of computer simulations. The effect of diffuse fibrosis and gap junction remodeling is simulated by reducing cellular coupling nonuniformly. As expected, the conduction velocity decreases when cellular coupling is reduced. In the presence of If the conduction velocity increases both in normal and in pathological tissue. In our simulations, ectopic activity is present in regions with high expression of If and is facilitated by cellular uncoupling. We conclude that an increased If may facilitate propagation of the action potential. Hence, If may prevent conduction slowing and block. Overexpression of If may lead to ectopic activity, especially when cellular coupling is reduced under pathological conditions.     

Generation of digital terrain models with a ground-based SAR system

A novel technique for the retrieval of a digital terrain model (DTM) with a ground-based synthetic aperture radar (GB-SAR) system is described. A set of SAR images collected over a test site located at Salice d'Ulzio, Italy, is used to validate experimentally the proposed DTM retrieval technique. The topographic height is obtained using an algorithm specifically tailored for a GB-SAR system equipped with two receive antennas. The comparison with an existing DTM of the test site area shows that the retrieved DTM is accurate, with root mean square height differences between the two DTMs below 5 m.     

Data driven analysis of functional brain networks in fMRI for schizophrenia investigation

The purpose of this article is to present a methodology to identify the sources of activity in brain networks from functional magnetic resonance imaging (fMRI) data using the multiset canonical correlation analysis algorithm. The aim is to lay the foundations for a screening marker to be used as indicator of mental diseases. Group analysis blind source separation methods have proved reliable to extract the latent sources underlying the brain activities but currently there is no recognized biomarker for mental disorders. Recent studies have identified alterations in the so called default mode network (DMN) that are common to several neuropsychiatric disorders, including schizophrenia. In particular, here we account for the hypothesis that the alterations in the DMN activity can be effectively highlighted by analyzing the transient states between two different tasks. A set of fMRI data acquired from 18 subjects performing working memory tasks is investigated for such purpose. Subjects are patients affected by schizophrenia for one half and healthy control subjects for the other. Under these conditions, the proposed methodology provides high discrimination performances in terms of classification error, thereby providing promising results for a preliminary tool able to monitor the disease state or to perform a prescreening for patients at risk for schizophrenia. © 2014 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 24, 239–248, 2014