Terbium-149 production: a focus on yield and quality improvement towards preclinical application.

Terbium-149 (T1/2 = 4.1 h, Eα = 3.98 MeV (16.7%), 28 µm range in tissue) is a radionuclide with potential for targeted alpha therapy. Due to the negligible emission of α-emitting daughter nuclides, toxicity to healthy tissue may be reduced in comparison with other α-particle emitters. In this study, terbium-149 was produced via 1.4 GeV proton irradiation of a tantalum target at the CERN-ISOLDE facility. The spallation products were mass separated and implanted on zinc-coated foils and, later, radiochemically processed. Terbium-149 was separated from the co-produced isobaric radioisotopes and the zinc coating from the implantation foil, using cation-exchange and extraction chromatographic techniques, respectively. At the end of separation, up to 260 MBq terbium-149 were obtained with > 99% radionuclidic purity. Radiolabeling experiments were performed with DOTATATE, achieving 50 MBq/nmol apparent molar activity with radiochemical purity > 99%. The chemical purity was determined by inductively coupled plasma-mass spectrometry measurements, which showed lead, copper, iron and zinc only at ppb level. The radiolabeling of the somatostatin analogue DOTATATE with [149Tb]TbCl3 and the subsequent in vivo PET/CT scans conducted in xenografted mice, showing good tumor uptake, further demonstrated product quality and its ability to be used in a preclinical setting.

Muonic atom spectroscopy with microgram target material.

Muonic atom spectroscopy-the measurement of the x rays emitted during the formation process of a muonic atom-has a long standing history in probing the shape and size of nuclei. In fact, almost all stable elements have been subject to muonic atom spectroscopy measurements and the absolute charge radii extracted from these measurements typically offer the highest accuracy available. However, so far only targets of at least a few hundred milligram could be used as it required to stop a muon beam directly in the target to form the muonic atom. We have developed a new method relying on repeated transfer reactions taking place inside a 100 bar hydrogen gas cell with an admixture of 0.25% deuterium that allows us to drastically reduce the amount of target material needed while still offering an adequate efficiency. Detailed simulations of the transfer reactions match the measured data, suggesting good understanding of the processes taking place inside the gas mixture. As a proof of principle we demonstrate the method with a measurement of the 2p-1s muonic x rays from a 5  µ g gold target.

Proteomic analysis reveals rattlesnake venom modulation of proteins associated with cardiac tissue damage in mouse hearts.

Snake envenomation is a common but neglected disease that affects millions of people around the world annually. Among venomous snake species in Brazil, the tropical rattlesnake (Crotalus durissus terrificus) accounts for the highest number of fatal envenomations and is responsible for the second highest number of bites. Snake venoms are complex secretions which, upon injection, trigger diverse physiological effects that can cause significant injury or death. The components of C. d. terrificus venom exhibit neurotoxic, myotoxic, hemotoxic, nephrotoxic, and cardiotoxic properties which present clinically as alteration of central nervous system function, motor paralysis, seizures, eyelid ptosis, ophthalmoplesia, blurred vision, coagulation disorders, rhabdomyolysis, myoglobinuria, and cardiorespiratory arrest. In this study, we focused on proteomic characterization of the cardiotoxic effects of C. d. terrificus venom in mouse models. We injected venom at half the lethal dose (LD50) into the gastrocnemius muscle. Mouse hearts were removed at set time points after venom injection (1 h, 6 h, 12 h, or 24 h) and subjected to trypsin digestion prior to high-resolution mass spectrometry. We analyzed the proteomic profiles of >1300 proteins and observed that several proteins showed noteworthy changes in their quantitative profiles, likely reflecting the toxic activity of venom components. Among the affected proteins were several associated with cellular deregulation and tissue damage. Changes in heart protein abundance offer insights into how they may work synergistically upon envenomation. SIGNIFICANCE: Venom of the tropical rattlesnake (Crotalus durissus terririficus) is known to be neurotoxic, myotoxic, nephrotoxic and cardiotoxic. Although there are several studies describing the biochemical effects of this venom, no work has yet described its proteomic effects in the cardiac tissue of mice. In this work, we describe the changes in several mouse cardiac proteins upon venom treatment. Our data shed new light on the clinical outcome of the envenomation by C. d. terrificus, as well as candidate proteins that could be investigated in efforts to improve current treatment approaches or in the development of novel therapeutic interventions in order to reduce mortality and morbidity resulting from envenomation.

The Metamorphosis of Radionuclide Production and Development at Paul Scherrer Institute.

Radionuclide production and development has a long history at the Paul Scherrer Institute (PSI) and dates back to the founding times of its forerunner institutions: the Federal Institute for Reactor Research and the Swiss Institute for Nuclear Research. The facilities used for this purpose have evolved substantially over the last five decades. Many radiometals in use today, as radiopharmaceuticals, are for the diagnosis and treatment of disease, with the most popular means of detection being Positron Emission Tomography. These positron emitters are easily produced at low proton energies using medical cyclotrons, however, developments at these facilities are lacking. Currently, the fixed 72 MeV proton beam at PSI is degraded at IP2 irradiation station to provide the desired energy to irradiate targets to produce the likes of 44Sc, 43Sc and 64Cu as a proof of principle, which are of great interest to the nuclear medicine community. This development work can then be implemented at facilities containing medical cyclotrons. A history of the development of radionuclides at PSI, along with current development and projects with partner institutions, is described.

Characterization of the Axial Jet Separator with a CO2/Helium Mixture: Toward GC-AMS Hyphenation.

Development of interfaces for sample introduction from high pressures is important for real-time online hyphenation of chromatographic and other separation devices with mass spectrometry (MS) or accelerator mass spectrometry (AMS). Momentum separators can reduce unwanted low-density gases and introduce the analyte into the vacuum. In this work, the axial jet separator, a new momentum interface, is characterized by theory and empirical optimization. The mathematical model describes the different axial penetration of the components of a jet-gas mixture and explains the empirical results for injections of CO2 in helium into MS and AMS instruments. We show that the performance of the new interface is sensitive to the nozzle size, showing good qualitative agreement with the mathematical model. Smaller nozzle sizes are more preferable due to their higher inflow capacity. The CO2 transmission efficiency of the interface into a MS instrument is ∼ 14% (CO2/helium separation factor of 2.7). The interface receives and delivers flows of ∼ 17.5 mL/min and ∼ 0.9 mL/min, respectively. For the interfaced AMS instrument, the ionization and overall efficiencies are 0.7-3% and 0.1-0.4%, respectively, for CO2 amounts of 4-0.6 µg C, which is only slightly lower compared to conventional systems using intermediate trapping. The ionization efficiency depends on to the carbon mass flow in the injected pulse and is suppressed at high CO2 flows. Relative to a conventional jet separator, the transmission efficiency of the axial jet separator is lower, but its performance is less sensitive to misalignments.

Nuclear chemistry. Synthesis and detection of a seaborgium carbonyl complex.

Experimental investigations of transactinoide elements provide benchmark results for chemical theory and probe the predictive power of trends in the periodic table. So far, in gas-phase chemical reactions, simple inorganic compounds with the transactinoide in its highest oxidation state have been synthesized. Single-atom production rates, short half-lives, and harsh experimental conditions limited the number of experimentally accessible compounds. We applied a gas-phase carbonylation technique previously tested on short-lived molybdenum (Mo) and tungsten (W) isotopes to the preparation of a carbonyl complex of seaborgium, the 106th element. The volatile seaborgium complex showed the same volatility and reactivity with a silicon dioxide surface as those of the hexacarbonyl complexes of the lighter homologs Mo and W. Comparison of the product's adsorption enthalpy with theoretical predictions and data for the lighter congeners supported a Sg(CO)6 formulation.

Chemical characterization of element 112.

The heaviest elements to have been chemically characterized are seaborgium (element 106), bohrium (element 107) and hassium (element 108). All three behave according to their respective positions in groups 6, 7 and 8 of the periodic table, which arranges elements according to their outermost electrons and hence their chemical properties. However, the chemical characterization results are not trivial: relativistic effects on the electronic structure of the heaviest elements can strongly influence chemical properties. The next heavy element targeted for chemical characterization is element 112; its closed-shell electronic structure with a filled outer s orbital suggests that it may be particularly susceptible to strong deviations from the chemical property trends expected within group 12. Indeed, first experiments concluded that element 112 does not behave like its lighter homologue mercury. However, the production and identification methods used cast doubt on the validity of this result. Here we report a more reliable chemical characterization of element 112, involving the production of two atoms of (283)112 through the alpha decay of the short-lived (287)114 (which itself forms in the nuclear fusion reaction of 48Ca with 242Pu) and the adsorption of the two atoms on a gold surface. By directly comparing the adsorption characteristics of (283)112 to that of mercury and the noble gas radon, we find that element 112 is very volatile and, unlike radon, reveals a metallic interaction with the gold surface. These adsorption characteristics establish element 112 as a typical element of group 12, and its successful production unambiguously establishes the approach to the island of stability of superheavy elements through 48Ca-induced nuclear fusion reactions with actinides.

Chemical investigation of hassium (element 108).

The periodic table provides a classification of the chemical properties of the elements. But for the heaviest elements, the transactinides, this role of the periodic table reaches its limits because increasingly strong relativistic effects on the valence electron shells can induce deviations from known trends in chemical properties. In the case of the first two transactinides, elements 104 and 105, relativistic effects do indeed influence their chemical properties, whereas elements 106 and 107 both behave as expected from their position within the periodic table. Here we report the chemical separation and characterization of only seven detected atoms of element 108 (hassium, Hs), which were generated as isotopes (269)Hs (refs 8, 9) and (270)Hs (ref. 10) in the fusion reaction between (26)Mg and (248)Cm. The hassium atoms are immediately oxidized to a highly volatile oxide, presumably HsO(4), for which we determine an enthalpy of adsorption on our detector surface that is comparable to the adsorption enthalpy determined under identical conditions for the osmium oxide OsO(4). These results provide evidence that the chemical properties of hassium and its lighter homologue osmium are similar, thus confirming that hassium exhibits properties as expected from its position in group 8 of the periodic table.

The tetraheme cytochrome c NrfH is required to anchor the cytochrome c nitrite reductase (NrfA) in the membrane of Wolinella succinogenes.

The electron-transport chain that catalyzes nitrite respiration with formate in Wolinella succinogenes consists of formate dehydrogenase, menaquinone and the nitrite reductase complex. The latter catalyzes nitrite reduction by menaquinol and is made up of NrfA and NrfH, two c-type cytochromes. NrfA is the catalytic subunit; its crystal structure is known. NrfH belongs to the NapC/NirT family of membrane-bound c-type cytochromes and mediates electron transport between menaquinol and NrfA. It is demonstrated here by MALDI MS that four heme groups are attached to NrfH. A Delta nrfH deletion mutant of W. succinogenes was constructed by replacing the nrfH gene with a kanamycin-resistance gene cartridge. This mutant did not form the NrfA protein, probably because of a polar effect of the mutation on nrfA expression. The nrfHAIJ gene cluster was restored by integration of an nrfH-containing plasmid into the genome of the Delta nrfH mutant. The resulting strain had wild-type properties with respect to growth by nitrite respiration and nitrite reductase activity. A mutant (stopH) that contained the nrfHAIJ locus with nrfH modified by two artificial stop codons near its 5' end produced wild-type amounts of NrfA in the absence of the NrfH protein. NrfA was located exclusively in the soluble cell fraction of the stopH mutant, indicating that NrfH acts as the membrane anchor of the NrfHA complex in wild-type bacteria. The stopH mutant did not grow by nitrite respiration and did not catalyze nitrite reduction by formate, indicating that the electron transport is strictly dependent on NrfH. The NrfH protein seems to be an unusual member of the NapC/NirT family as it forms a stable complex with its redox partner protein NrfA.

Evidence for new isotopes of element 107: 266Bh and 267Bh

New neutron rich isotopes 267107Bh and 266107Bh were produced in bombardments of a 249Bk target with 117-MeV and 123-MeV 22Ne ions at the Lawrence Berkeley National Laboratory 88-Inch Cyclotron. Identification was made by observation of correlated alpha-particle decays between the Bh isotopes and their Db and Lr daughters using a rotating wheel system. 267Bh was produced with a cross section of approximately 70 pb and decays with a 17(+14)(-6) s half life by emission of alpha particles with an average energy of 8.83+/-0.03 MeV. One atom of 266Bh was observed, decaying within 1 s by emission of a 9.29-MeV alpha particle.

Chemical characterization of bohrium (element 107)

The arrangement of the chemical elements in the periodic table highlights resemblances in chemical properties, which reflect the elements' electronic structure. For the heaviest elements, however, deviations in the periodicity of chemical properties are expected: electrons in orbitals with a high probability density near the nucleus are accelerated by the large nuclear charges to relativistic velocities, which increase their binding energies and cause orbital contraction. This leads to more efficient screening of the nuclear charge and corresponding destabilization of the outer d and f orbitals: it is these changes that can give rise to unexpected chemical properties. The synthesis of increasingly heavy elements, now including that of elements 114, 116 and 118, allows the investigation of this effect, provided sufficiently long-lived isotopes for chemical characterization are available. In the case of elements 104 and 105, for example, relativistic effects interrupt characteristic trends in the chemical properties of the elements constituting the corresponding columns of the periodic table, whereas element 106 behaves in accordance with the expected periodicity. Here we report the chemical separation and characterization of six atoms of element 107 (bohrium, Bh), in the form of its oxychloride. We find that this compound is less volatile than the oxychlorides of the lighter elements of group VII, thus confirming relativistic calculations that predict the behaviour of bohrium, like that of element 106, to coincide with that expected on the basis of its position in the periodic table.

First Measurement of a Thermochemical Property of a Seaborgium Compound.

With only a few atoms of seaborgium (Sg, element 106), in the form of volatile SgO(2)Cl(2), it was possible to determine the sublimation enthalpy of this compound using gas chromatography. Furthermore, it was demonstrated that in Group 6 Sg is chemically more similar to W than to Mo.

[Technical adaptation of impulse oscillometry to special research conditions]. / Technische Adaption der Impuls-Oszillometrie an spezielle Untersuchungsbedingungen.

The technical adaptation of the Impulse-Oscillometry (IOS) to different conditions of measurement allows a wide range of applications so that even questions of peripheral user groups using lung function tests can be answered. Thus, the variable connection of the IOS head via fold hose opens the field of bedside measurements and additional applications in pediatrics, intensive care and veterinary medicine. Rhinomanometric examinations are possible with little expenditure and high practicability using nasal tips.

Relative strength of central and peripheral fusion as a function of stimulus parameters.

We investigated the role of various stimulus parameters that influence motor fusion responses for peripheral as compared to central fusional stimuli. Results from the initial experiment indicated that a central stimulus equal in size to a peripheral fusion stimulus dominated the response independent of the amount of retinal eccentricity of the peripheral target. A second experiment indicated that the central stimulus dominated even when the peripheral stimulus was larger. However, when the peripheral stimulus was changed in shape so that it became an annulus surrounding the central stimulus, the peripheral stimulus was always stronger. In another phase of the experiment, we found that the extent to which a peripheral stimulus surrounded the central one determined which controlled the response. We concluded that the surrounding perceptual gestalt produced by the peripheral stimulus was the most significant variable determining the relative strengths of central and peripheral fusion stimuli. Clinical implications are discussed.

[Osteoma of the mid-face area--a rare site]. / Osteom des Mittelgesichts--Eine seltene Lokalisation.

Osteomas are benign, symptomless, slowly growing tumors that are usually found incidentally. The most frequent site of origin is a paranasal sinus. We report a 17 year old man with an osteoma of the middle face. The history, clinical findings and surgical procedure are described. Aetiological factors and possible complications of paranasal osteomas are discussed.

Program priorities of crippled children's agencies: a survey.

State Crippled Children's (CC) programs are known for their diversity in organization and varying coverage of diagnostic categories. Relatively little information is available concerning the programmatic priorities of CC agencies. To identify the activities central to the mission of State CC agencies, a survey was undertaken. Results from the survey revealed considerable unanimity among CC directors in identifying activities deemed to be very important to their agencies' missions. However, CC program directors indicated that their agencies were unable to spend sufficient amounts of time working on many of these activities. With few exceptions, the same activities were accorded high priority regardless of the particular organizational type of CC program and regardless of the tenure of the director. Directors of CC programs were also consistent in identifying activities that were relatively less important to their agencies' missions, including activities related to community-based care. Together with improvements in the treatment of childhood chronic illness, changes in the availability and financing of specialty medical care have substantially altered the problems that now face State CC programs. Despite major differences across the State CC programs, survey results reflect a broad consensus among CC directors concerning the current role of their agencies in the care of children with special health needs. Such a consensus may be an important element in gaining the additional resources needed to address current problems and to ensure high quality of care for these children and their families.

[Leukocyte migration inhibition test in multiple sclerosis - results of a migration technic according to Clausen using brain specific antigens]. / Leukozytenmigrations-Inhibitionstest bei Multipler Sklerose - Ergebnisse mit der Migrationstechnik nach Clausen bei Anwendung hirhtypischer Antigene.

The leukocyte migration inhibitory factor (LIF) was examined in 57 test persons--27 patients with multiple sclerosis (MS) and 30 normals--with the indirect and the direct leucocyte migration inhibition test in agarose (LMIAT). The stimulation of lymphocytes was carried out by the application of myelin basic protein (BP) and a membrane-associated antigen of normal brain (NTA). The mean value of controls +/- 2 s and the migration index less than or equal to 0,80 were used for limiting. In the indirect technique could be established significant group effects (NTA- and BP-values of MS cases compared to the controls) after 10 hours of incubation. The direct method showed in MS patients a significant lowered migration-index on an average after stimulation with the NTA; controls gave negative findings (except two cases). The valence of the test system and prospective modifications for further results were indicated.