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PDF file - 380K, Ex vivo optical imaging of the BAPPA probe biodistribution

Purpose: To evaluate the potential of targeted photoacoustic imaging as a noninvasive method for detection of follicular thyroid carcinoma.Experimental Design: We determined the presence and activity of two members of matrix metalloproteinase family (MMP), MMP-2 and MMP-9, suggested as biomarkers for malignant thyroid lesions, in FTC133 thyroid tumors subcutaneously implanted in nude mice. The imaging agent used to visualize tumors was MMP-activatable photoacoustic probe, Alexa750-CXeeeeXPLGLAGrrrrrXK-BHQ3. Cleavage of the MMP-activatable agent was imaged after intratumoral and intravenous injections in living mice optically, observing the increase in Alexa750 fluorescence, and photoacoustically, using a dual-wavelength imaging method.Results: Active forms of both MMP-2 and MMP-9 enzymes were found in FTC133 tumor homogenates, with MMP-9 detected in greater amounts. The molecular imaging agent was determined to be activated by both enzymes in vitro, with MMP-9 being more efficient in this regard. Both optical and photoacoustic imaging showed significantly higher signal in tumors of mice injected with the active agent than in tumors injected with the control, nonactivatable, agent.Conclusions: With the combination of high spatial resolution and signal specificity, targeted photoacoustic imaging holds great promise as a noninvasive method for early diagnosis of follicular thyroid carcinomas. Clin Cancer Res; 19(6); 1494–502. ©2013 AACR.

PDF file - 46K

PDF file - 168K, Total and active MMP enzymes in FTC133 tumor homogenates

PDF file - 434K, Optical imaging of the probes' clearance

PDF file - 159K, Cleavage specificity

PDF file - 121K, Photoacoustic signal recorded at 680 and 750 nm

PDF file - 866K, Photoacoustic and optical imaging of the probe cleavage in tumors with different levels of MMPs: HT1080 (high MMP) and BT20 (low MMP)

PDF file - 370K, Characterization of the probes: HPLC, MS and absorbance data

Internal dose assessment intercomparison exercises are useful tools: to verify the performance of an Internal Dosimetry Service; to promote the harmonization of dose assessments; and to identify weaknesses where further improvements are necessary. However, no such international inter-comparisons have been performed for more than 10 years. In the period May 2014 - May 2016, the "Technical Recommendations for Monitoring Individuals for Occupational Intakes of Radionuclides" were developed at the initiative of the European Commission, and later published within the EC Radiation Protection series, as RP 188. In 2017 the Working Group "Internal Dosimetry" of the European Radiation Dosimetry Group (EURADOS) organised a new intercomparison action, named ICIDOSE 2017, with the main aim of testing the practical applicability of these Technical Recommendations (RP188). Four case-studies were proposed to participants: an artificially created case of inhalation of 60Co to simulate a simple special monitoring case; a real case of inhalation of 125I, with simple routine monitoring; a real and more complex case of incorporation of 234+235+238U, featuring both confirmatory and special monitoring; and a complex real case of an accidental incorporation of 241Am, including multiple administrations of DTPA. Results were received from 66 participants from 26 countries; these were compared to reference or recommended solutions, developed for each case based on the application of RP 188. The results were discussed at a workshop in October 2018, at the Federal Office for Radiation Protection (BfS, Munich, Germany). The observed spread of the submitted results was improved from those obtained from similar cases in previous intercomparison exercises, showing that the availability of RP 188 significantly contributes to the harmonization of the internal dose assessment process.

A key assumption in studies of cortical functions is that excitatory principal neurons, but not inhibitory cells express calcium/calmodulin-dependent protein kinase II subunit α (CaMKIIα) resulting in a widespread use of CaMKIIα promoter-driven protein expression for principal cell manipulation and monitoring their activities. Using neuroanatomical and electrophysiological methods we demonstrate that in addition to pyramidal neurons, multiple types of cortical GABAegic cells are targeted by adeno-associated viral vectors (AAV) driven by the CaMKIIα promoter in both male and female mice. We tested the AAV5 and AAV9 serotype of viruses with either Channelrhodopsin 2 (ChR2)-mCherry or Archaerhodopsin-T-green fluorescent protein (GFP) constructs, with different dilutions. We show that in all cases, the reporter proteins can visualize a large fraction of different interneuron types, including parvalbumin (PV), somatostatin (SST), neuronal nitric oxide synthase (nNOS), neuropeptide Y (NPY), and cholecystokinin (CCK)-containing GABAergic cells, which altogether cover around 60% of the whole inhibitory cell population in cortical structures. Importantly, the expression of the excitatory opsin Channelrhodopsin 2 in the interneurons effectively drive spiking of infected GABAergic cells even if the immunodetectability of reporter proteins is ambiguous. Thus, our results challenge the use of CaMKIIα promoter-driven protein expression as a selective tool in targeting cortical glutamatergic neurons using viral vectors.

The applicability of capillary electrophoresis (CE) with light-emitting diode-induced fluorescence detection (LEDIF) for the separation of sugars in honey samples was studied. An amount of 25 mM ammonium acetate (pH 4.5) with 0.3% polyethylene oxide (PEO) was found to be optimal for the efficient separation of carbohydrates. 8-aminopyrene-1,3,6-trisulfonic acid (APTS) was used for the labeling of the carbohydrate standards and honey sugars for fluorescence detection. The optimized method was applied in the quantitative analysis of fructose and glucose by direct injection of honey samples. Apart from the labeling reaction, no other sample preparation was performed. The mean values of the fructose/glucose ratio for phacelia honey, acacia honey and honeydew honey were 0.86, 1.61 and 1.42, respectively. The proposed method provides high separation efficiency and sensitive detection within a short analysis time. Apart from the labeling reaction, it enables the injection of honeys without sample pretreatment. This is the first time that fluorescence detection has been applied for the CE analysis of sugars in honeys.

A Me3Si-protected P7 cage reacts with N-heterocyclic-carbene complexes of coinage metals to yield a mononuclear Cu(i) complex featuring a Cu(η4-P7) core and a trinuclear Au(i) complex with linearly coordinated metal ions attached to the P7 cluster.

The nitroxyl radical 1-methyl-2-azaadamantane N-oxyl (Me-AZADO) exhibits magnetic bistability arising from a radical/dimer interconversion. The transition from the rotationally disordered paramagnetic plastic crystal, Me-AZADO, to the ordered diamagnetic crystalline phase, (Me-AZADO)2, has been conclusively demonstrated by crystal structure determination from high-resolution powder diffraction data and by solid-state NMR spectroscopy. The phase change is characterized by a wide thermal hysteresis with high sensitivity to even small applied pressures. The molecular dynamics of the phase transition from the plastic crystal to the conventional crystalline phase has been tracked by solid-state (1H and 13C) NMR and EPR spectroscopies.

A synthetic strategy featuring dicyanometalates [M(CN)2]- (M = Ag, Au) as N-coordinating ditopic linkers connecting partially blocked FeII centers has been employed to produce heterometallic hexanuclear complexes, which exhibit spin-crossover (SCO) behavior at the FeII sites. The reaction between tris(2-pyridylmethyl)amine (tpma)-capped FeII ions and [Ag(CN)2]- proceeded with partial decomposition of the dicyanoargentate and led to the formation of {[Fe(tpma)]4(μ-CN)2[μ-Ag(CN)2]2}(ClO4)4·3H2O (1), in which both [Ag(CN)2]- and CN- act as bridging ligands, and the opposite [Ag(CN)2]- bridges are engaged in a pronounced argentophilic d10-d10 interaction. In an analogous synthesis, the more stable [Au(CN)2]- species remained intact and furnished the complex {[Fe(tpma)]2[μ-Au2(CN)4]2} (2), which features two FeII centers bridged by two [Au2(CN)4]2- dimers. The use of S,S'-bis(2-pyridylmethyl)-1,2-thioethane (bpte) as a mixed-donor, N2S2-coordinating capping ligand yielded {[Fe(bpte)]2[μ-Au2(CN)4]2} (3), with a structure analogous to that of 2. Variable-temperature magnetic susceptibility measurements revealed that complexes 1-3 exhibit an onset of SCO above 350 K. Measurements above 400 K further confirmed the occurrence of a gradual spin-state conversion for complex 2.

Background: The timing for heart surgery following cerebral embolization after cardiac valve vegetation is vital to postoperative recovery being uneventful, additionally Covid-19 may negatively affect the outcome. Minimally invasive methods and upgraded surgical instruments maximize the benefits of surgery also in complex cardiac revision cases with substantial perioperative risk. Case Presentation: A 68 y.o. patient, 10 years after previous sternotomy for OPCAB was referred to cardiac surgery on the 10th postoperative day after neurosurgical intervention with suspected mitral valve endocarditis. Mitral valve vegetation, tricuspid valve insufficiency and coronary stenosis were diagnosed and treated by minimally invasive revision cardiac surgery. Conclusion: The present clinical case demonstrates for the first time that the minimally invasive approach via right anterior mini-thoracotomy can be safely used for concomitant complex mitral valve reconstruction, tricuspid valve repair and aorto-coronary bypass surgery, even as a revision procedure in the presence of florid endocarditis after recent neurosurgical intervention. The Covid-19 pandemic and prophylactic patient isolation slow down the efficacy of pulmonary weaning and mobilisation and prolong the need for ICU treatment, without adversely affecting long-term outcome.

We report the first series of homoleptic phosphido iron complexes synthesized by treating either the β-diketiminato complex [(Dippnacnac)FeCl2Li(dme)2] (Dippnacnac = HC[(CMe)N(C6H3-2,6-iPr2)]2) or [FeBr2(thf)2] with an excess of phosphides R2PLi (R = tBu, tBuPh, Cy, iPr). Reaction outcomes depend strongly on the bulkiness of the phosphido ligands. The use of tBu2PLi precursor led to an anionic diiron complex 1 encompassing a planar Fe2P2 core with two bridging and two terminal phosphido ligands. An analogous reaction employing less sterically demanding phosphides, tBuPhPLi and Cy2PLi yielded diiron anionic complexes 2 and 3, respectively, featuring a short Fe–Fe interaction supported by three bridging phosphido groups and one additional terminal R2P− ligand at each iron center. Further tuning of the P-substrates bulkiness gave a neutral phosphido complex 4 possessing a tetrahedral Fe4 cluster core held together by six bridging iPr2P moieties. Moreover, we also describe the first homoleptic phosphanylphosphido iron complex 5, which features an iron center with low coordination provided by three tBu2P-P(SiMe3)− ligands. The structures of compounds 1–5 were determined by single-crystal X-ray diffraction and 1–3 by 1H NMR spectroscopy. Moreover, the electronic structures of 1–3 were interrogated using zero-field Mossbauer spectroscopy and DFT methods.

Reactions between red phosphorus (Pred) and potassium ethoxide in various organic solvents under reflux convert this rather inert form of the element to soluble polyphosphides. The activation is hypothesized to proceed via a nucleophilic attack by ethoxide on the polymeric structure of Pred, leading to disproportionation of the latter, as judged from observation of P(OEt)3 in the reaction products. A range of solvents has been probed, revealing that different polyphosphide anions (P73-, P162-, P213-, and P5-) can be stabilized depending on the combination of the boiling point and dielectric constant (polarity) of the solvent. The effectiveness of activation also depends on the nature of nucleophile, with the rate of reaction between Pred and KOR increasing in the order t-Bu < n-Hex < Et < Me, which is in agreement with the increasing order of nucleophilic strength. Thiolates and amides were also examined as potential activators, but the reaction with these nucleophiles were substantially slower; nonetheless, all reactions between Pred and NaSR yielded exclusively P162- as a soluble polyphosphide product.

We recently introduced a family of 6-NHC-Cu(I) catalysts that exhibit highest selectivities (regio- and enantio-) exclusively when aryl ethers are used as the leaving group. Understanding the match ­between a catalyst and leaving group remains elusive. We sought to increase our understanding of this system by comparing our catalyst’s ­activity with other catalysts using substrates that contain different leaving groups. Our objective is to better understand the regioselectivity–leaving group combinations. We also observed that our catalyst functioned best when methanol was used as an additive. We examined the selectivities as a function of other protic additives. Finally, we wanted to understand the regioselectivity–enantioselectivity relationship with regards to internal versus terminal leaving groups. Overall, we demonstrate that matching leaving group and catalyst is important and that for our extended aromatic ligand the use of aromatic leaving groups is a unique pairing. We also demonstrate that the leaving group is also critical for controlling both types of selectivity.

Oxidation of distorted square-planar perfluoropinacolate Co compound [CoII(pinF)2]2−, 1, to [CoIII(pinF)2]1−, 2, is reported. Rigidly square-planar 2 has an intermediate-spin, S = 1, ground state and very large zero-field splitting (ZFS) with D = 67.2 cm−1; |E| = 18.0 cm−1, (E/D = 0.27), g⊥ = 2.10, g‖ = 2.25 and χTIP = 1950 × 10−6 cm3 mol−1. This Co(III) species, 2, reacts with ROS to oxidise two (pinF)2− ligands to form tetrahedral [CoII(Hpfa)4]2−, 3.

This work describes a series of iron(II) phosphanylphosphido complexes. These compounds were obtained by reacting lithiated diphosphanes R2PP(SiMe3)Li (R = t-Bu, i-Pr) with an iron(II) β-diketiminate complex, [LFe(μ2-Cl)2Li(DME)2] (1), where DME = 1,2-dimethoxyethane and L = Dippnacnac (β-diketiminate). While the reaction of 1 with t-Bu2PP(SiMe3)Li yields [LFe(η1-Me3SiPP-t-Bu2)] (2), that of 1 with equimolar amounts of i-Pr2PP(SiMe3)Li, in DME, leads to [LFe(η2-i-Pr2PPSiMe3)] (3). In contrast, the reaction of 1 with (i-Pr2N)2PP(SiMe3)Li provides not an iron-containing complex but 1-[(diisopropylamino)phosphine]-2,4-bis(diisopropylamino)-3-(trimethylsilyl)tetraphosphetane (4). The structures of 2–4 were determined using diffractometry. Thus, 2 exhibits a three-coordinate iron site and 3 a four-coordinate iron site. The increase in the coordination number is induced by the change from an anticlinal to a synclinal conformation of the phoshpanylphosphido ligands. The electronic structures of 2 and 3 were asse...

Soluble polyphosphide anions were successfully generated in a number of organic solvents by the reaction between shelf-stable red phosphorus and potassium ethoxide. The species were identified by (31)P NMR spectroscopy in solution and by X-ray crystal-structure determination of (Bu4N)2P16 in the solid state. The reaction was scaled up to gram quantities by using a flow-chemistry process.

Oxidation of distorted square-planar perfluoropinacolate Co compound [CoII(pinF)2]2-, 1, to [CoIII(pinF)2]1-, 2, is reported. Rigidly square-planar 2 has an intermediate-spin, S = 1, ground state and very large zero-field splitting (ZFS) with D = 67.2 cm-1; |E| = 18.0 cm-1, (E/D = 0.27), g⊥ = 2.10, g‖ = 2.25 and χTIP = 1950 × 10-6 cm3 mol-1. This Co(iii) species, 2, reacts with ROS to oxidise two (pinF)2- ligands to form tetrahedral [CoII(Hpfa)4]2-, 3.

In the Coulomb gauge, the Hamiltonian of QCD contains terms of order ħ 2 , identified by Christ and Lee, which are non-local but instantaneous. The question is addressed how do these terms fit in with BRST invariance. Our discussion is confined to the simplest, O ( g 4 ) , example.

A new pedestrian crossing opened in August 2015 to visitors of Harlech Castle providing level access to the castle from the newly opened visitor centre. The installation of the new footbridge was possibly the most ambitious construction project to take place at Harlech since the building of the castle itself. The paper tells the story of how this new footbridge came about, its design development from a two-span simple assembly into a three-span, modern, elegant Z-shaped structure which has captured the imagination of many. The footbridge has been nicknamed the “floating bridge”. The paper also discusses the place of the footbridge within the history of the site, the positive and negative reactions that it received and how it has become part of the much-loved landmark site, featuring on newly commissioned souvenirs.

Heteroleptic complexes [Fe(bpte)(bim)]X

Purpose: To evaluate the potential of targeted photoacoustic imaging as a noninvasive method for detection of follicular thyroid carcinoma. Experimental Design: We determined the presence and activity of two members of matrix metalloproteinase family (MMP), MMP-2 and MMP-9, suggested as biomarkers for malignant thyroid lesions, in FTC133 thyroid tumors subcutaneously implanted in nude mice. The imaging agent used to visualize tumors was MMP-activatable photoacoustic probe, Alexa750-CXeeeeXPLGLAGrrrrrXK-BHQ3. Cleavage of the MMP-activatable agent was imaged after intratumoral and intravenous injections in living mice optically, observing the increase in Alexa750 fluorescence, and photoacoustically, using a dual-wavelength imaging method. Results: Active forms of both MMP-2 and MMP-9 enzymes were found in FTC133 tumor homogenates, with MMP-9 detected in greater amounts. The molecular imaging agent was determined to be activated by both enzymes in vitro, with MMP-9 being more efficient in this regard. Both optical and photoacoustic imaging showed significantly higher signal in tumors of mice injected with the active agent than in tumors injected with the control, nonactivatable, agent. Conclusions: With the combination of high spatial resolution and signal specificity, targeted photoacoustic imaging holds great promise as a noninvasive method for early diagnosis of follicular thyroid carcinomas. Clin Cancer Res; 19(6); 1494–502. ©2013 AACR.

The perisomatic region of principal neurons in cortical regions is innervated by three types of GABAergic interneuron, including parvalbumin-containing basket cells (PVBCs) and axo-axonic cells (AACs), as well as cholecystokinin and type 1 cannabinoid receptor-expressing basket cells (CCK/CB1BCs). These perisomatic inhibitory cell types can also be found in the basal nucleus of the amygdala, however, their output properties are largely unknown. Here, we performed whole-cell recordings in morphologically identified interneurons in slices prepared from transgenic mice, in which the GABAergic cells could be selectively targeted. Investigating the passive and active membrane properties of interneurons located within the basal amygdala revealed that the three interneuron types have distinct single-cell properties. For instance, the input resistance, spike rate, accommodation in discharge rate, or after-hyperpolarization width at the half maximal amplitude separated the three interneuron types. Furthermore, we performed paired recordings from interneurons and principal neurons to uncover the basic features of unitary inhibitory postsynaptic currents (uIPSCs). Although we found no difference in the magnitude of responses measured in the principal neurons, the uIPSCs originating from the distinct interneuron types differed in rise time, failure rate, latency, and short-term dynamics. Moreover, the asynchronous transmitter release induced by a train of action potentials was typical for the output synapses of CCK/CB1BCs. Our results suggest that, despite the similar uIPSC magnitudes originating from the three perisomatic inhibitory cell types, their distinct release properties together with the marked differences in their spiking characteristics may contribute to accomplish specific functions in amygdala network operation.

Soluble polyphosphide anions were successfully generated in a number of organic solvents by the reaction between shelf-stable red phosphorus and potassium ethoxide. The species were identified by 31P NMR spectroscopy in solution and by X-ray crystal-structure determination of (Bu4N)2P16 in the solid state. The reaction was scaled up to gram quantities by using a flow-chemistry process.

A selenium analogue of amino-D-luciferin, aminoseleno-D-luciferin, is synthesized and shown to be a competent substrate for the firefly luciferase enzyme. It has a red-shifted bioluminescence emission maximum at 600 nm and is suitable for bioluminescence imaging studies in living subjects.

The microenvironment as an integral part of cells plays critical roles in their physiology, structure and function. There are continuously increasing interests in understanding how the microenvironment controls the behavior and fate of stem cells,1, 2 and the initiation, progression and metastasis of tumors.3–5 Molecular characterization of the extracellular microenvironment is usually performed in vitro through identification of the secreted proteins in cultured cells6 and analysis of gene expression in purified components of normal and malignant tissues.7 The great complexity of the extracellular microenvironment and our current incomplete understanding of the biological factors involved present a big challenge in recreating an ex vivo counterpart. In vivo imaging can shed light into the biological processes within their native microenvironment through tracking the movement of cells genetically labeled with fluorescent proteins.8–14 It is, however, presently challenging to directly image specific signaling molecules in the extracellular microenvironment involved in the cell-to-cell and cell-to-matrix interactions because of the lack of methods that can stably present the designed reporters in the extracellular microenvironment in vivo. To meet this critical need, we report here a simple, general strategy to deliver and immobilize synthetic reporters for creating a reporting system in animals for in vivo imaging of molecular signaling and interactions in the microenvironment. Our strategy takes advantage of the ubiquitous distribution of collagen proteins, which are a major component of the extracellular matrix inside the mammalian body. Collagens provide an ideal harbor for the reporters because of their abundance (they are the most abundant proteins in the body, representing about 30% of total proteins) and relative physiological stability. In our design, a reporter is immobilized onto the collagens in extracellular microenvironment through a collagen-binding protein (Fig. 1a). Unlike targeting to the cell surface, which often leads to internalization of the reporters, binding of the reporters to collagens will prevent them from being internalized into cells, and retain them in the extracellular microenvironment for effective sensing. With this strategy we were able to create a mouse with reporters embedded throughout the body. The distribution, stability and function of the immobilized reporters were evaluated by successfully mapping extracellular enzyme activity in tumor-bearing mice. We further evaluated the immobilized reporter for imaging enzyme activity in an inflammation site in a mouse model to demonstrate the general applicability of the reporter immobilization strategy for various biological models. Fig. 1 A reporter immobilization strategy for in vivo imaging. (a) Schematic of reporter immobilization over the body through binding ubiquitous collagens for imaging the extracellular microenvironment. (b) In vivo bioluminescence imaging of CB-Luc, a fusion ...

The structure of linear energy divergences is analysed on the example of one graph to 3-loop order. Such dangerous divergences do cancel when all graphs are added, but next to leading divergences do not cancel out., Comment: 6 pages, 1 figure

A comparative study of TiO2 powders prepared by sol–gel methods is presented. Titanium tetraisopropoxide was used as the precursor for the sol–gel processes. The effects of the annealing treatment on phase, crystallite size, porosity and photodegradation of dyes (methyl orange and methylene blue) were studied. The phase structure, microstructure and surface properties of the films were characterized by using X-ray diffraction (XRD) and Atomic Force Microscopy (AFM). The X-ray diffraction was used for crystal phase identification, for the accurate estimation of the anatase–rutile ratio and for the crystallite size evaluation of each polymorph in the samples. It was found that the only TiO2 anatase phase of the synthesized TiO2 develops below 500 °C, between 600 and 800 °C the anatase coexist with rutile and above 800 °C only the rutile phase was found in the samples. Attention has been paid not only to crystal structures, but also to the porosity, the particle size and the photocatalytic properties. However, the annealing temperature was found to have significant influence on the photocatalytic properties. Different TiO2 doctor blade thin films were obtained mixing the sol gel powder (100% anatase) and TiO2 Aldrich with TiO2 Degussa P25. The surfactant (Triton X100 or sodium dodecyl sulfate) affects the packing density of the particles during deposition and the photocatalytic degradation efficiency of the dyes. The photocatalytic degradation kinetics of methyl orange and methylene blue using TiO2 thin film were investigated.

We report here a new small molecule fluorogen and RNA aptamer pair for RNA labeling. The small-molecule fluorogen is designed on the basis of fluorescently quenched sulforhodamine dye. The SELEX (Systematic Evolution of Ligands by EXponential enrichment) procedure and fluorescence screening in E. coli have been applied to discover the aptamer that can specifically activate the fluorogen with micromolar binding affinity. The systematic mutation and truncation study on the aptamer structure determined the minimum binding domain of the aptamer. A series of rationally modified fluorogen analogues have been made to probe the interacting groups of fluorogen with the aptamer. These results led to the design of a much improved fluorogen ASR 7 that displayed a 33-fold increase in the binding affinity for the selected aptamer in comparison to the original ASR 1 and an 88-fold increase in the fluorescence emission after the aptamer binding. This study demonstrates the value of combining in vitro SELEX and E. coli fluorescence screening with rational modifications in discovering and optimizing new fluorogen-RNA aptamer labeling pairs.

We study to one-loop order the renormalization of QCD in the Coulomb gauge using the Hamitonian formalism. Divergences occur which might require counter-terms outside the Hamiltonian formalism, but they can be cancelled by a redefinition of the Yang-Mills electric field., Comment: 21 pages, 31 figures

Furin, a proprotein convertases family endoprotease, processes numerous physiological substrates and is overexpressed in cancer and inflammatory conditions. Noninvasive imaging of furin activity will offer a valuable tool to probe furin function over the course of tumor growth and migration in the same animals in real time and directly assess the inhibition efficacy of drugs in vivo. Here, we report successful bioluminescence imaging of furin activity in xenografted MBA-MB-468 breast cancer tumors in mice with bioluminogenic probes. The probes are conjugates of furin substrate, a consensus amino acid motif R-X-K/R-R (X, any amino acid), with the firefly luciferase substrate D-aminoluciferin. In the presence of the luciferase reporter, the probes are unable to produce bioluminescent emission without furin activation. Blocking experiments with a furin inhibitor and control experiments with a scrambled probe showed that the bioluminescence emission in the presence of firefly luciferase is furin-dependent and specific. After furin activation, a 30-fold increase in the bioluminescent emission was observed in vitro, and on average, a 7-8-fold contrast between the probe and control was seen in the same tumor xenografts in mice. Direct imaging of furin activity may facilitate the study of furin function in tumorigenicity and the discovery of new drugs for furin-targeted cancer therapy.

The CONRAD Project is a Coordinated Network for Radiation Dosimetry funded by the European Commission 6th Framework Programme. The activities developed within CONRAD Work Package 5 ('Coordination of Research on Internal Dosimetry') have contributed to improve the harmonisation and reliability in the assessment of internal doses. The tasks carried out included a study of uncertainties and the refinement of the IDEAS Guidelines associated with the evaluation of doses after intakes of radionuclides. The implementation and quality assurance of new biokinetic models for dose assessment and the first attempt to develop a generic dosimetric model for DTPA therapy are important WP5 achievements. Applications of voxel phantoms and Monte Carlo simulations for the assessment of intakes from in vivo measurements were also considered. A Nuclear Emergency Monitoring Network (EUREMON) has been established for the interpretation of monitoring data after accidental or deliberate releases of radionuclides. Finally, WP5 group has worked on the update of the existing IDEAS bibliographic, internal contamination and case evaluation databases. A summary of CONRAD WP5 objectives and results is presented here.