Quantitative investigation of gamma radiation in accelerator produced ISO neutron fields.

In standard monoenergetic ISO neutron fields, the neutron yield of neutron-producing reactions was measured in combination with the prompt photon yield, including photon energies up to 10 MeV, for the purpose of comparing the two yields. Separating the photons produced by the target (direct photons) from those generated by secondary neutron reactions was achieved using the time-of-flight method. Photon and neutron ambient dose equivalent values were calculated from measured spectral energy distributions. Quasi monoenergetic neutron fields are needed to systematically test the response of measuring instruments to neutron radiation. For this reason, ISO has defined a number of reference neutron radiation fields covering a wide energy range up to 19 MeV. Because neutron detectors may also be affected by photon radiation, the photon fluence in the ISO neutron fields has to be known. This work focuses on quasi monoenergetic accelerator-produced neutron fields in the energy range of 24 keV to 19 MeV.

Synthetic polymers as substrates for a DNA-sliding clamp protein.

The clamp protein (gp45) of the DNA polymerase III of the bacteriophage T4 is known to bind to DNA and stay attached to it in order to facilitate the process of DNA copying by the polymerase. As part of a project aimed at developing new biomimetic data-encoding systems we have investigated the binding of gp45 to synthetic polymers, that is, rigid, helical polyisocyanopeptides. Molecular modelling studies suggest that the clamp protein may interact with the latter polymers. Experiments aimed at verifying these interactions are presented and discussed.

Interferometry with Bose-Einstein condensates in microgravity.

Atom interferometers covering macroscopic domains of space-time are a spectacular manifestation of the wave nature of matter. Because of their unique coherence properties, Bose-Einstein condensates are ideal sources for an atom interferometer in extended free fall. In this Letter we report on the realization of an asymmetric Mach-Zehnder interferometer operated with a Bose-Einstein condensate in microgravity. The resulting interference pattern is similar to the one in the far field of a double slit and shows a linear scaling with the time the wave packets expand. We employ delta-kick cooling in order to enhance the signal and extend our atom interferometer. Our experiments demonstrate the high potential of interferometers operated with quantum gases for probing the fundamental concepts of quantum mechanics and general relativity.

Bis-(3-methyl-1-propyl-1,3-di-hydro-1H-imidazol-2-yl-idene)silver(I) chlor-ido(5,10,15,20-tetra-phenyl-porphin-ato)cadmate(II).

The structure of the title salt, [Ag(C7H12N2)2][CdCl(C44H28N4)], at 150 K has triclinic symmetry. One of the phenyl rings bonded to the porphyrin mol-ecule and the propyl groups of both yl-idene mol-ecules coordinating to silver are disordered over two positions.

1,1'-Methyl-enebis(4-tert-butyl-pyridinium) dichloride hemihydrate.

The structure of the title hydrated salt, C19H28N2 2+·2Cl-·0.5H2O, at 150 K has monoclinic (C2/c) symmetry. The water mol-ecule is located on a twofold rotation axis.

Atomic structure of PDE4: insights into phosphodiesterase mechanism and specificity.

Cyclic nucleotides are second messengers that are essential in vision, muscle contraction, neurotransmission, exocytosis, cell growth, and differentiation. These molecules are degraded by a family of enzymes known as phosphodiesterases, which serve a critical function by regulating the intracellular concentration of cyclic nucleotides. We have determined the three-dimensional structure of the catalytic domain of phosphodiesterase 4B2B to 1.77 angstrom resolution. The active site has been identified and contains a cluster of two metal atoms. The structure suggests the mechanism of action and basis for specificity and will provide a framework for structure-assisted drug design for members of the phosphodiesterase family.

beta -Helical polymers from isocyanopeptides.

Polymerization of isocyanopeptides results in the formation of high molecular mass polymers that fold in a proteinlike fashion to give helical strands in which the peptide chains are arranged in beta-sheets. The beta-helical polymers retain their structure in water and unfold in a cooperative process at elevated temperatures. The peptide architecture in these polymers is a different form of the beta-helix motif found in proteins. Unlike their natural counterparts, which contain arrays of large beta-sheets stacked in a helical fashion, the isocyanopeptide polymers have a central helical core that acts as a director for the beta-sheet-like arrangement of the peptide side arms. The helical structure of these isocyanopeptide polymers has the potential to be controlled through tailoring of the side branches and the hydrogen-bonding network present in the beta-sheets.

Biocatalytic oxidation by chloroperoxidase from Caldariomyces fumago in polymersome nanoreactors.

The encapsulation of chloroperoxidase from Caldariomyces fumago (CPO) in block copolymer polymersomes is reported. Fluorescence and electron microscopy show that when the encapsulating conditions favour self-assembly of the block copolymer, the enzyme is incorporated with concentrations that are 50 times higher than the enzyme concentration before encapsulation. The oxidation of two substrates by the encapsulated enzyme was studied: i) pyrogallol, a common substrate used to assay CPO enzymatic activity and ii) thioanisole, of which the product, (R)-methyl phenyl sulfoxide, is an important pharmaceutical intermediate. The CPO-loaded polymersomes showed distinct reactivity towards these substrates. While the oxidation of pyrogallol was limited by diffusion of the substrate into the polymersome, the rate-limiting step for the oxidation of thioansiole was the turnover by the enzyme.

Reported fatigue, difficulty, and cardiovascular response to a memory challenge.

Female undergraduates were presented the opportunity to earn a small chance of winning a modest prize by memorizing in 2 min two or six nonsense trigrams (meaningless series of three letters, such as AED). Analysis of cardiovascular measures taken during the work period indicated that systolic blood pressure responses first rose and then fell with self-reported fatigue in the two trigram condition. By contrast, the responses declined with self-reported fatigue in the six trigram condition, starting relatively high and ending low. Whereas systolic blood pressure responses were stronger for Six Trigram participants where fatigue was low, they tended to be stronger for Two Trigram participants where fatigue was moderate and were weak for both trigram groups where fatigue was high. Response patterns for diastolic blood pressure and, especially, mean arterial blood pressure, were similar. The blood pressure findings conceptually replicate and extend previous fatigue study results and provide further support for a recent conceptual analysis of fatigue influence on effort and associated cardiovascular responses.

Transfection by cationic gemini lipids and surfactants.

Diseases that are linked to defective genes or mutations can in principle be cured by gene therapy, in which damaged or absent genes are either repaired or replaced by new DNA in the nucleus of the cell. Related to this, disorders associated with elevated protein expression levels can be treated by RNA interference via the delivery of siRNA to the cytoplasm of cells. Polynucleotides can be brought into cells by viruses, but this is not without risk for the patient. Alternatively, DNA and RNA can be delivered by transfection, i.e. by non-viral vector systems such as cationic surfactants, which are also referred to as cationic lipids. In this review, recent progress on cationic lipids as transfection vectors will be discussed, with special emphasis on geminis, surfactants with 2 head groups and 2 tails connected by a spacer.

AT THE PHYSICS-BIOLOGY INTERFACE: THE NEUTRON AFFAIR.

We present predictions of neutron relative biological effectiveness (RBE) for cell irradiations with neutron beams at PTB-Braunschweig. A neutron RBE model is adopted to evaluate initial DNA damage induction given the neutron-induced charged particle field. RBE values are predicted for cell exposures to quasi-monoenergetic beams (0.56 MeV, 1.2 MeV) and to a broad energy distribution neutron field with dose-averaged energy of 5.75 MeV. Results are compared to what obtained with our RBE predictions for neutrons at similar energies, when a 30-cm sphere is irradiated in an isotropic neutron field. RBE values for experimental conditions are higher for the lowest neutron energies, because, as expected, target geometry determines the weight of the low-effectiveness photon component of the neutron dose. These results highlight the importance of characterizing neutron fields in terms of physical interactions, to fully understand neutron-induced biological effects, contributing to risk estimation and to the improvement of radiation protection standards.

Macrophage behavior on multilayered DNA-coatings in vitro.

A pivotal factor to consider in the development of biomaterials and biomaterial coatings is the inflammatory response to these materials. The insertion of implants is followed by protein adsorption and subsequent interactions with cellular components of the biological surroundings, in which macrophages play a dominant role through the production of a myriad of signaling molecules. In view of this, the aims of the present study were to evaluate (i) gross protein adsorption to, and (ii) in vitro behavior of macrophages on novel biomaterial coatings, composed of poly-D-lysine (PDL) or poly(allylamine hydrochloride) (PAH) and DNA, and to compare these coatings with negative (noncoated glass) and positive controls (noncoated glass + LPS-stimulation). The results demonstrate that multilayered DNA-coatings do not affect gross protein adsorption compared to noncoated controls. Cell culture experiments showed that the attachment to, and viability and morphology of two types of macrophages cultured on multilayered DNA-coatings is comparable to noncoated controls. Still, macrophages repeatedly showed decreased secretion levels of the proinflammatory cytokine TNF-alpha on multilayered DNA-coatings, whereas no differences were observed in the secretion of IL-1beta, IL-10, and TGF-beta1. Appropriate animal studies are required to elucidate if these in vitro indications have clinical effects on the inflammatory and wound healing processes around implants.

Multilayered DNA coatings: in vitro bioactivity studies and effects on osteoblast-like cell behavior.

This study describes the effect of multilayered DNA coatings on (i) the formation of mineralized depositions from simulated body fluids (SBF); and (ii) osteoblast-like cell behavior with and without pretreatment in SBF. DNA coatings were generated using electrostatic self-assembly, with poly-d-lysine or poly(allylamine hydrochloride) as cationic polyelectrolytes, on titanium substrates. Coated substrates and non-coated controls were immersed in SBF with various compositions. The deposition of calcium phosphate was enhanced on multilayered DNA coatings as compared with non-coated controls, and was dependent on the type of cationic polyelectrolyte used in the build-up of the DNA coatings. Further analysis showed that the depositions consisted of carbonated apatite. Non-pretreated DNA coatings were found to have no effect on osteoblast-like cell behavior compared with titanium controls. On the other hand, SBF-pretreatment of DNA coatings affected the differentiation of osteoblast-like cells through an increased deposition of osteocalcin. The results of this study are indicative of the bone-bonding capacities of DNA coatings. Nevertheless, future animal experiments are required to provide conclusive evidence for the bioactivity of DNA coatings.

Biological responses to multilayered DNA-coatings.

This study was performed to evaluate the basic biological response to deoxyribonucleic acid (DNA)-based coatings for soft tissue implants. To that end, in vitro experiments were used to study their cytocompatibility, and in vivo subcutaneous implantation studies with transponders in a rat model were performed to evaluate their histocompatibility. The DNA-based coatings were fabricated using the electrostatic self-assembly technique using cationic poly-D-lysine or poly-allylamine hydrochloride and anionic DNA. Noncoated substrates served as controls. In vitro, the behavior of primary rat dermal fibroblasts was assessed in terms of cell proliferation and morphology. Both types of multilayered DNA-coatings significantly increased rat dermal fibroblast proliferation without altering the morphological appearance of the cells. The tissue response to multilayered DNA-coatings was assessed using an in vivo rat model, in which transponders were inserted subcutaneously for 4 and 12 weeks. No macroscopic signs of inflammation or adverse tissue reactions were observed at implant retrieval. Histological analyses demonstrated a uniform tissue response to all types of implants. All implants were encapsulated in a fibrous tissue capsule without intervening inflammatory cells at the implant surface. Histomorphometrically, multilayered DNA-coatings induced fibrous tissue capsules with similar quality and thickness compared to noncoated controls. In addition, all fibrous tissue capsules showed similar expression of alpha-smooth muscle actin. This study demonstrates that multilayered DNA-coatings are cytocompatible and histocompatible, and justifies further research on their functionalization with biologically active compounds to modulate tissue responses.

Calibration of personal dosemeters in mixed neutron-photon fields: some problems and their solution.

In neutron reference radiation fields, the conventional true value of the personal dose equivalent, H(p)(10), is derived from the spectral neutron fluence and recommended conversion coefficients. This procedure requires the phantom on which the personal dosemeter is mounted to be irradiated with a broad and parallel beam. In many practical situations, the change of the neutron fluence and/or the energy distribution over the surface of the phantom may not be neglected. For a selection of typical irradiation conditions in neutron reference radiation fields, the influence of this effect has been analysed using numerical methods. A further problem, which is of relevance for the calibration of dosemeters measuring both the neutron and the photon component of mixed fields, is the 'double counting' of the dose equivalent due to neutron-induced photons. The relevance of this conceptual problem for calibrations in mixed-field dosimetry was analysed.

The neutron component of two high-energy photon reference fields.

The 4.4 MeV photon reference field described in ISO 4037 is produced by the (12)C(p,p')(12)C (E(x) = 4.4389 MeV) reaction using a thick elemental carbon target and a proton beam with an energy of 5.7 MeV. The relative abundance of the isotope (13)C in elemental carbon is 1.10%. Therefore, the 4.4 MeV photon field is contaminated by neutrons produced by the (13)C(p,n) (13)N reaction (Q = -3.003 MeV). The ambient dose equivalent H*(10) produced by these neutrons is of the same order of magnitude as the ambient dose equivalent produced by the 4.4 MeV photons. For the calibration of dosemeters, especially those also sensitive to neutrons, the spectral fluence distribution of these neutrons has to be known in detail. On the other hand, a mixed photon/neutron field is very useful for the calibration of tissue-equivalent proportional counters (TEPC), if this field combines a high-linear energy transfer (LET) component produced by low-energy neutrons and a low-LET component resulting from photons with about the same ambient dose equivalent and energies up to 7 MeV. Such a mixed field was produced at the PTB accelerator facility using a thin CaF(2) + (nat)C target and a 5.7 MeV proton beam.

Measurement of the fluence response of the GSI neutron ball dosemeter in the energy range from thermal to 19 MeV.

At high-energy particle accelerators, area monitoring needs to be performed in a wide range of neutron energies. In principle, neutrons occur from thermal energies up to the energy of the accelerated ions, which is for the present GSI (Gesellschaft für Schwerionenforschung) accelerator facility approximately 1-2 GeV per nucleon. There are no passive dosemeters available, which are designed for the use at high-energy accelerators. At GSI, a neutron dosemeter was developed, which is suitable for the measurement of high-energy neutron radiation by the insertion of a lead layer around Thermoluminescence (TL) detection elements (pairs of TL 600/700) at the centre of the dosemeter. The design of the sphere was derived from the construction of the extended range rem-counters for the measurement of ambient dose equivalent H(10). In this work, the dosemeter fluence response was measured in the quasi-monoenergetic neutron fields of the accelerator facility of the PTB in Braunschweig and in the thermal neutron field of the GKSS research reactor FRG-1 in Geesthacht. For the accelerator measurements, the reactions (7)Li(p,n)(7)Be, (3)H(p,n)(3)He and (2)H(d,n)(3)He were used to produce neutron fields with energy peaks between 144 keV and 19 MeV. The measured fluence responses are 27% too low for thermal energies and show an agreement with approximately 14% for the accelerator produced neutron fields related to the computed fluence responses (MCNP, FLUKA calculations). The measured as well as the computed fluence responses of the dosemeter are compared with the corresponding conversion coefficients.

A monitor for neutron flux measurements up to 20 MeV.

A liquid scintillation detector aimed for neutron energy and fluence measurements in the energy region <20 MeV has been calibrated using monoenergetic and white spectrum neutron fields. Careful measurements of the proton light output function and the response matrix have been performed allowing for the application of unfolding techniques using existing codes. The response matrix is used to characterise monoenergetic neutron fields produced by the T(d,n) at a low-energy deuteron accelerator installed at the Swedish Defense Research Agency (FOI).

Photon contribution to ambient dose equivalent H(10) in the wide-spectrum neutron reference fields of the IRSN.

The photon contribution to ambient dose equivalent in several wide-spectrum reference neutrons fields of the Institute for Radiological Protection and Nuclear Safety were measured using a Geiger-Müller counter. For the investigated fields, the ratio of photon to neutron ambient dose equivalent ranged between 0.03 and 0.20. The results show that the Geiger-Müller tube is a versatile instrument for dosimetry in mixed photon-neutron fields if sufficient information for the calculation of corrections is available.

A compact high-energy neutron spectrometer.

A compact liquid organic neutron spectrometer based on a single NE213 liquid scintillator (5 cm diameter x 5 cm) is described. The spectrometer is designed to measure neutron fluence spectra over the energy range 2-200 MeV and is suitable for use in neutron fields having any type of time structure. Neutron fluence spectra are obtained from measurements of two-parameter distributions (counts versus pulse-height and pulse shape) using the Bayesian unfolding code MAXED. Calibration and test measurements made using a pulsed neutron beam with a continuous energy spectrum are described and the application of the spectrometer to radiation dose measurements is discussed.