Physical properties of new ordered bimetallic phases M0.25Cd0.75PS3 (M = ZnII, NiII, CoII, MnII).

Four bimetallic phases of the thiophosphate family have been synthesized by the cationic exchange reaction using a freshly prepared K0.5Cd0.75PS3 precursor phase and methanolic solutions of nitrates of the divalent cations ZnII, NiII, CoII, and MnII. All the materials were characterized by FTIR, PXRD, SEM-EDXS and (in the case of the diamagnetic compounds) by solid state NMR. For the K0.5Cd0.75PS3 precursor, the X-ray powder diffraction data suggest a modification of the structure, while solid state NMR results confirm that this phase possesses an ordered arrangement of Cd vacancies. The cationic exchange reaction achieves a complete removal of potassium ions (no potassium detected by SEM-EDXS) and re-occupation of the vacancies by divalent cations. Therefore, the obtained compounds have an average composition of M0.25Cd0.75PS3 (M = ZnII, NiII, CoII, MnII) and possess an ordered distribution of the substituent cations. Even with the paramagnetic substitution level of 25%, antiferromagnetic behaviour is present in the phases with MnII, CoII and NiII, as evidenced by dc susceptibility and in the case of the MnII substituted phase by EPR. The cooperative magnetic interactions confirm the conclusion that the paramagnetic ions adopt an ordered arrangement. The analysis by broad band impedance spectroscopy allows to attribute the conductivity in these materials to charge movements in the layers due to the difference in electronegativity of the metal ions. Zn0.25Cd0.75PS3 is the phase that shows the highest conductivity values. Finally, the band gap energies of the bimetallic phases tend to be lower than those of the single-metal phases, probably due to an overlap of the band structures.

Strong intermolecular antiferromagnetic verdazyl-verdazyl coupling in the solid state.

Strong magnetic couplings are generally observed intramolecularly in organic diradicals or in systems in which they are promoted by crystal engineering strategies involving, for example, transition metal ligation. We herein present a strong intermolecularly coupling verdazyl radical in the solid state without the use of such design strategies. The crystal structure of an acetylene-substituted verdazyl radical shows a unique antiparallel face-to-face orientation of the neighboring verdazyl molecules along with verdazyl-acetylene interactions giving rise to an alternating antiferromagnetic Heisenberg chain. Single crystal structural data at 80, 100, 173, and 223 K show that one of the π-stacking distances depends on temperature, while heat capacity data indicate the absence of a phase transition. Based on this structural input, broken symmetry DFT calculations predict a change from an alternating linear Heisenberg chain with two comparable coupling constants J1 and J2 at higher temperatures towards dominant pair interactions at lower temperatures. The predicted antiferromagnetic coupling is confirmed experimentally by magnetic susceptibility, solid-state EPR and NMR spectroscopic results.

Solution structure and excitation energy transfer in phycobiliproteins of Acaryochloris marina investigated by small angle scattering.

The structure of phycobiliproteins of the cyanobacterium Acaryochloris marina was investigated in buffer solution at physiological temperatures, i.e. under the same conditions applied in spectroscopic experiments, using small angle neutron scattering. The scattering data of intact phycobiliproteins in buffer solution containing phosphate can be well described using a cylindrical shape with a length of about 225Å and a diameter of approximately 100Å. This finding is qualitatively consistent with earlier electron microscopy studies reporting a rod-like shape of the phycobiliproteins with a length of about 250 (M. Chen et al., FEBS Letters 583, 2009, 2535) or 300Å (J. Marquart et al., FEBS Letters 410, 1997, 428). In contrast, phycobiliproteins dissolved in buffer lacking phosphate revealed a splitting of the rods into cylindrical subunits with a height of 28Å only, but also a pronounced sample aggregation. Complementary small angle neutron and X-ray scattering experiments on phycocyanin suggest that the cylindrical subunits may represent either trimeric phycocyanin or trimeric allophycocyanin. Our findings are in agreement with the assumption that a phycobiliprotein rod with a total height of about 225Å can accommodate seven trimeric phycocyanin subunits and one trimeric allophycocyanin subunit, each of which having a height of about 28Å. The structural information obtained by small angle neutron and X-ray scattering can be used to interpret variations in the low-energy region of the 4.5K absorption spectra of phycobiliproteins dissolved in buffer solutions containing and lacking phosphate, respectively.

Iridium(iii) hydrido complexes for the catalytic dehydrogenation of hydrazine borane.

The synthesis of 3,5-disubstituted cyclometalated iridium(iii) hydrido complexes of the type [3,5-R2(POCOP)IrHX] (3,5-R2(POCOP) = κ3-C5HR2-2,6-(OPtBu2)2 with R = t-Bu, COOMe; X = Cl, H) is described. All complexes were investigated in the catalytic dehydrogenation of hydrazine borane and compared with the unsubstituted compounds [(POCOP)IrHX] (X = Cl, H). All catalysts are highly active and recyclable, clearly maintaining hydrogen production activity. The dehydrogenation products were structurally characterised by solid state NMR and FTIR spectroscopy. Experimental observations were complemented by a dispersion-corrected DFT study to rationalise the mechanism of hydrazine borane dehydrogenation.

P-O-B(3) linkages in borophosphate glasses evidenced by high field (11)B/(31)P correlation NMR.

The long-standing debate about the presence of P-O-B(3) linkages in glasses has been solved by high-field scalar correlation NMR. Previously suggested by dipolar NMR methods, the presence of such species has been definitively demonstrated by (11)B((31)P) J-HMQC NMR techniques. The results indicate that borophosphate networks contain P-O-B(3) bonds and thus present a higher degree of atomic homogeneity than previously thought.

Excitation energy transfer and electron-vibrational coupling in phycobiliproteins of the cyanobacterium Acaryochloris marina investigated by site-selective spectroscopy.

In adaption to its specific environmental conditions, the cyanobacterium Acaryochloris marina developed two different types of light-harvesting complexes: chlorophyll-d-containing membrane-intrinsic complexes and phycocyanobilin (PCB) - containing phycobiliprotein (PBP) complexes. The latter complexes are believed to form a rod-shaped structure comprising three homo-hexamers of phycocyanin (PC), one hetero-hexamer of phycocyanin and allophycocyanin (APC) and probably a linker protein connecting the PBPs to the reaction centre. Excitation energy transfer and electron-vibrational coupling in PBPs have been investigated by selectively excited fluorescence spectra. The data reveal a rich spectral substructure with a total of five low-energy electronic states with fluorescence bands at 635nm, 645nm, 654nm, 659nm and a terminal emitter at about 673 nm. The electronic states at ~635 and 645 nm are tentatively attributed to PC and APC, respectively, while an apparent heterogeneity among PC subunits may also play a role. The other fluorescence bands may be associated with three different isoforms of the linker protein. Furthermore, a large number of vibrational features can be identified for each electronic state with intense phonon sidebands peaking at about 31 to 37cm⁻¹, which are among the highest phonon frequencies observed for photosynthetic antenna complexes. The corresponding Huang-Rhys factors S fall in the range between 0.98 (terminal emitter), 1.15 (APC), and 1.42 (PC). Two characteristic vibronic lines at about 1580 and 1634cm⁻¹ appear to reflect CNH⁺ and CC stretching modes of the PCB chromophore, respectively. The exact phonon and vibrational frequencies vary with electronic state implying that the respective PCB chromophores are bound to different protein environments. This article is part of a special issue entitled: photosynthesis research for sustainability: keys to produce clean energy.

Cation size effects in mixed-ion metaphosphate glasses: structural characterization by multinuclear solid state NMR spectroscopy.

Metaphosphate glasses with two monovalent species A(1-x)B(x)PO3 (0 ≤x≤ 1) show mixed-ion effects (MIE) in the dc conductivities and glass transition temperatures, which are strongly dependent on the cation size mismatch between the two mobile species. In the present contribution, mixed-ion metaphosphate glasses based on the cation combinations Cs-Li, Rb-Li, and Cs-Ag, exhibiting particularly large size mismatches, are analyzed by (31)P, (87)Rb, (109)Ag and (133)Cs NMR to determine possible correlations between this mismatch and some of the structural properties critical to the development of the MIE: the local environments around the mobile species and their spatial distribution relative to each other. The results are compared with those obtained in the Na-Ag metaphosphate series, which serves as a reference system, with minimized cation mismatch MIE. The local coordination environments of the Ag(+), Rb(+) and Cs(+) ions follow analogous compositional trends as previously observed in Na-based mixed-ion metaphosphate glasses: for a given cation species A, the average A-O distance shows an expansion/compression when this cation is replaced by a second species B with smaller/bigger ionic radius, respectively. This compositional differentiation of the structural sites for the mobile species may contribute to the MIE. Concerning the relative spatial distribution of the mobile ions, results from (7)Li-(133)Cs (SEDOR) experiments indicate a random mixture of Cs and Li in Cs-Li metaphosphate glasses. While this result is in agreement with one of the fundamental hypotheses of the models proposed to describe the MIE, it is at variance with the observation of various partial cation segregation phenomena observed in Na-based mixed alkali glasses. This result suggests that cation size mismatch is not the decisive parameter in determining segregation or non-statistical mixing of cations in the glass. In the Cs-Ag and Na-Ag glasses, (109)Ag spin-echo NMR reveals a progressive slowing down of the Ag(+) diffusion dynamics as this species is replaced by Cs(+) or Na(+). The substitution by the bigger Cs(+) ion causes a strong reduction in Ag(+) mobility suggesting the existence of separated diffusion pathways for these cations. In contrast, substitution by the similarly-sized Na(+) causes a much weaker mobility reduction consistent with the existence of Ag-Na cooperative hopping.

Direct correlation between nonrandom ion hopping and network structure in ion-conducting borophosphate glasses.

We present temperature-dependent conductivity spectra of sodium borophosphate glasses with a varying borate/phosphate ratio but a constant sodium oxide content which can be mapped into time-dependent mean square displacements. For the first time, we show that characteristic lengths of ion transport derived thereof are directly linked to features of network structure, viz., the number of boron oxide tetrahedra. Our results also shed light on the mixed network former effect.

[Quality management in a combined clinic - the quality management system according to DIN EN ISO 9001 of the The German Association of Spa Accommodation Resorts e. V. (VdKB)]. / Qualitätsmanagement im Klinikverbund - das QM-System nach DIN EN ISO 9001 des Verbands der Kurbeherbergungsbetriebe Deutschlands e. V. (VdKB).

The implementation of a quality system in health care organizations offers huge potentials for improvement and development. But the realization of such systems necessitates high investments, which small companies and family businesses often are unable to raise. The German Association of Spa Accommodation Resorts (VdKB) commissioned two consultants to develop a reasonably priced implementation concept of a DIN EN ISO 9001 quality system specially adjusted to small companies and family businesses in medical spa and rehabilitation services, which was successfully accredited in May 2003. This paper describes fundamental requirements in combine management systems, considers the pros and cons of management combines and demonstrates the practical realization of combine requirements on the example of the VdKB-combine system.

Two-dimensional 109Ag NMR and random-walk simulation studies of silver dynamics in glassy silver ion conductors.

By applying one- and two-dimensional 109Ag NMR, we demonstrate that silver diffusion in silver iodide/silver phosphate glasses is governed by a very broad, continuous distribution of correlation times G(lg tau). As a consequence, over a wide temperature range, the 109Ag NMR spectra can be described by a weighted superposition of a Gaussian and a Lorentzian where these line-shape components result from the slow and the fast silver ions in G(lg tau), respectively. For the 109Ag NMR two-time correlation functions F2(t), measured as a stimulated echo, a very stretched decay to F2SS(t(m)) = 0 is observed. When fitting to a Kohlrausch function, exp[-(t/tau)beta], a stretching parameter beta approximately = 0.2 is found. The temperature dependence of the mean correlation time of silver dynamics is described by an Arrhenius law where the activation energy is consistent with the one reported for the dc conductivity sigma(dc). In addition, it is shown that the effect of complex dynamical processes on NMR multi-time correlation functions can easily be calculated when performing random-walk simulations for schematic models such as the random-barrier model and the random-energy model. Based on these models it is possible to simulate various NMR observables and the mean square displacement, thus revealing the information content of multi-dimensional NMR experiments on solid ion conductors.

[Quality management in German rehabilitation clinics - a stratified representative survey]. / Qualitätsmanagement in Rehabilitationseinrichtungen in der Bundesrepublik Deutschland - Eine stratifizierte repräsentative Studie zum Stand der Umsetzung.

BACKGROUND: As of January 1, 2000 rehabilitation clinics in Germany are obliged to implement and develop a quality management system. OBJECTIVE: This study aims to depict the implementation of quality management (QM), to trace the preferred QM models, identify the reasons for and experience with the introducing quality management, and inquire into the quality tools used in rehabilitation clinics. METHODS: Postal study of a representatively selected random sample of 298 rehabilitation clinics, stratified along the criteria state, number of beds and financially responsible agency, using six questions with nominally scaled items. Questionnaire design provided no clues as to the responding clinics. The study was designed along the Total Design Method. RESULTS: 89 % of the responding clinics have implemented a QM system, or are about to or planning to do so. Only 11 % reject quality management. 59 % implemented their system in 1998, 1999 or 2000. Among the reasons for implementing a QM system, items related to potentials of quality management predominate, whereas demands by third parties are given only very rarefy. DISCUSSION: The response rate was 59 %, i. e., the study can be considered representative. The high share of clinics taking a positive view on quality management is however somewhat modified by the fact that 40.4 % of the clinics have adopted or are planning far traditional quality assurance methods. Whether these systems will satisfy the legal requirements in place (SGB V) is doubtful. Adjusted, responses show that 48.9 % of the clinics are running QM systems, are about to or planning to implement one. CONCLUSIONS: Many of the responding clinics have already implemented a QM system or are about to do so. A majority of the clinics however rely on traditional quality assurance methods. Whether quality assurance will satisfy the legal requirements in place (SGB V) re an internal quality management system must be awaited.

Optimization of retroviral vector generation for clinical application.

BACKGROUND: For many inherited and acquired diseases of the blood system, gene transfer into hematopoietic cells is a promising strategy to alleviate disease-related symptoms or even correct genetic alterations. In clinical gene therapy applications, low transduction efficiencies have been a major limitation mainly because of insufficient effective titers of the retroviral supernatants used. Thus, optimization of clinical-grade vector production under current 'Good Manufacturing Practice' (GMP) conditions is a prerequisite for successful gene therapy trials. METHODS: We established stable retroviral producer clones with single integrations of a retroviral vector encoding for the multidrug-resistance gene 1 (MDR1). Optimization of vector production in multi-tray cell factories (MTCFs) was studied with particular regard to harvest medium, cell density and harvest time point. RESULTS: We demonstrated that high-titer vector stocks could be produced in serum-free medium. By reducing the volume of harvest medium, titers could be increased up to four-fold. Plating optimal cell densities of 1 x 10(4) cells/cm2, repetitive harvests of vector supernatant were feasible over four consecutive days. Combining the most advantageous culture and harvest parameters tested, we were able to produce large quantities of serum-free vector supernatant in 40-tray MTCFs. Highly efficient gene transfer into primary human CD34+ progenitor cells demonstrated the quality of these vector stocks. CONCLUSION: The large-scale vector-production protocol in MTCFs described here is easy to handle, is applicable to a wide range of adherent producer cell lines and, most importantly, complies with current GMP guidelines.

Improved post-transcriptional processing of an MDR1 retrovirus elevates expression of multidrug resistance in primary human hematopoietic cells.

We describe the functional analysis of a novel retroviral vector, SF91m3, which was designed for improved expression of the in vivo selectable marker, multidrug resistance 1 gene (MDR1), in hematopoietic cells. SF91m3 combines several promising features. The vector backbone lacks viral coding sequences and AUG-start codons 5' of the MDR1 cDNA. A point mutation of a cryptic splice acceptor of the MDR1 cDNA increases the probability of transferring an intact provirus. The titer of a PG13 packaging cell clone containing a single proviral integration is high (>2 x 10(6) particles/ml from frozen stocks of serum-free vector harvests). Human hematopoietic cells transduced with SF91m3 reliably express MDR1 before and after passage through NOD/SCID mice, as shown by quantitative PCR and efflux assays with rhodamine 123 or Hoechst 33342. Finally, SF91m3 mediates resistance to escalated doses of cytotoxic agents, as shown by survival and differentiation of transduced colony-forming cells in the presence of colchicine at 48 ng/ml (>10 x IC(50)). Thus, SF91m3 may represent an interesting candidate for future trials addressing the safety and utility of MDR1 gene transfer; moreover, this study demonstrates that sequence alterations improving post-transcriptional processing of retroviral vectors have a substantial impact for gene expression in hematopoietic cells.

Influence of multiplicity of infection and protein stability on retroviral vector-mediated gene expression in hematopoietic cells.

Using retroviral vectors encoding enhanced green fluorescent protein (EGFP), we addressed to what extent expression of retroviral transgenes in hematopoietic cells depends on the multiplicity of infection (MOI) and on the half-life of the encoded protein. We show that an elevation of the MOI not only elevates the frequency of transduced cells, but also increases transgene expression levels and reduces interanimal variability in vivo (hematopoietic cells of C57BL/6J mice analyzed 13 weeks after transplantation). This suggests that the MOI has to be carefully controlled and should be adapted as desired for clinical studies when evaluating vector performance in preclinical models. The impact of protein stability is demonstrated by comparing vectors expressing EGFP or a destabilized variant with a C-terminal PEST-sequence, d2EGFP. The loss of expression with d2EGFP was more pronounced in terminally differentiated cells of the peripheral blood (>30 fold) than in progenitor cells (five- to 10-fold), indicating a stronger transcription of the retroviral promoter in progenitor cells and a predominant role of protein inheritance over de novo synthesis of transgenic protein in mature blood cells. This analysis reveals an important and differentiation-dependent contribution of protein half-life to the expression of retroviral vectors in hematopoietic cells, establishes d2EGFP as a more accurate reporter for determination of vector transcription, and also suggests that preclinical data obtained under conditions of high transduction rates or with vectors expressing stable reporter proteins require careful interpretation.

Effect of monochromatic UV-B radiation on electron transfer reactions of Photosystem II.

The adverse effect of low intensity, small band UV-B irradiation (lambda = 305 +/- 5 nm, I = 300 mW m(-2)) on PS II has been studied by comparative measurements of laser flash-induced changes of the absorption at 325 nm, DeltaA(325)(t), as an indicator of redox changes in Q(A), and of the relative fluorescence quantum yield, F(t)/F(o), in PS II membrane fragments. The properties of untreated control were compared with those of samples where the oxygen evolution rate under illumination with continuous saturating light was inhibited by up to 95%. The following results were obtained: a) the detectable initial amplitude (at a time resolution of 30 mus) of the 325 nm absorption changes, DeltaA(325), remained virtually invariant whereas the relaxation kinetics exhibit significant changes, b) the 300 mus kinetics of DeltaA(325) dominating the relaxation in UV-B treated samples was largely replaced by a 1.3 ms kinetics after addition of MnCl(2), c) the extent of the flash induced rise of the relative fluorescence quantum yield was severely diminished in UV-B treated PS II membrane fragments but the relaxation kinetics remain virtually unaffected. Based on these results the water oxidizing complex (WOC) is inferred to be the primary target of UV-B impairment of PS II while the formation of the 'stable' radical pair P680(+*)Q(A) (-) (*) is almost invariant to this UV-B treatment.

Development of the family therapy enactment rating scale.

This report describes the development of a new scale designed to establish how therapists intervene and clients respond during effective enactments in family therapy sessions. The Family Therapy Enactment Rating Scale (FTERS) was developed by clinically trained investigators who observed 27 videotaped family therapy sessions and listed therapist interventions and client responses during four phases of enactments: pre-enactment preparation, initiation, facilitation, and closing commentary. Interrater reliabilities for the FTERS were calculated by training 6 undergraduate volunteers to rate independently a sample of 12 enactments. When reliabilities were found to be relatively low, a second study was conducted in which the FTERS was revised and reliabilities were calculated with a different sample of 21 videotaped enactments and a new group of 6 undergraduate raters. Reliability for the FTERS was found to be sufficiently robust to make this measure of therapist interventions and client responses a useful instrument for evaluating what takes place during enactments. Findings on the FTERS were used to offer tentative guidelines for effective initiation and facilitation of enactments in family therapy sessions.

Dipolar coupling information in multispin systems: application of a compensated REDOR NMR approach to inorganic phosphates. Rotational echo double resonance.

An experimental strategy has been developed for measuring multiple dipole-dipole interactions in inorganic compounds using the technique of rotational echo double resonance (REDOR) NMR. Geometry-independent information about the dipole couplings between the observe nuclear species S (arbitrary quantum number) and the heteronuclear species I (spin-12) can be conveniently obtained from the experimental curve of DeltaS/S(0) versus dipolar evolution time by limiting the analysis to the initial data range 0 < delta S/S(0) < 0.30. Numerical simulations have been carried out on a three-spin system of type SI(2) in order to assess the effect of the I-I homonuclear dipole-dipole coupling and the influence of experimental imperfections such as finite pulse length and misadjustments of the 180 degrees pulses applied to the I-spin species. The simulations show further that within the initial data range the effects of such misadjustments can be internally compensated by a modified sequence having an additional 180 degrees pulse on the I channel in the middle of the dipolar evolution periods. Experimental (27)Al¿(31)P¿ REDOR results on the multispin systems Al(PO(3))(3), AlPO(4), [AlPO(4)](12)(C(3)H(7))(4)NF, and Na(3)PO(4) confirm the general utility of this approach. Thus, for applications to unknown systems the compensation strategy obviates calibration procedures with model compounds.

MDR1 gene expression in NOD/SCID repopulating cells after retroviral gene transfer under clinically relevant conditions.

We have adapted a recently published protocol for retroviral gene transfer into hematopoietic cells [A. J. Schilz et al. (1998) Blood 92: 3163-3171] with respect to clinical requirements such as large-volume vector stock generation, adequate cell source, high cell numbers, and serum-free conditions. We present data on transduction efficacy and expression of the multidrug resistance 1 (MDR1) gene in human CD34(+) cells from mobilized peripheral blood (PB) mediated by a gibbon ape leukemia virus (GALV)-pseudotyped retroviral vector. Using a 1-day cytokine-mediated prestimulation, consisting of human interleukin (IL)-3, IL-6, stem cell factor (SCF), Flt-3 ligand (FL), and thrombopoietin (TPO), followed by a 3-day transduction procedure, we were able to detect up to 51% CD34(+) cells expressing MDR1. Xenotransplantation of transduced cells into NOD/LtSz-scid/scid (NOD/SCID) mice resulted in a mean engraftment level of 23% (0.1 to 87%). As shown by quantitative PCR analysis, a mean of 12.7% (range 0.3 to 55%) of the engrafted human cells in the bone marrow of chimeric mice contained the MDR1 cDNA. Furthermore, enhanced expression of MDR1 above control levels was detected in up to 15% of the engrafted human cell population. Our data suggest that NOD/SCID repopulating cells derived from mobilized PB can be transduced efficiently with existing retroviral vector systems under clinically applicable conditions.

[Reform of the Law DIN EN ISO 9001:2000. Commentary on the new requirements on quality management systems]. / Die Reform der DIN EN ISO 9001:2000. Ein Kommentar zu den neuen Anforderungen an Qualitätsmanagement-Systeme.

Since January this year the German translation of the third draft to the reform of the DIN EN ISO 9000 is available. The draft reveals an approximation to the models of Business Excellence. Most important changes are a far stronger customer orientation, orientation on the processes and resource management. The norms DIN EN ISO 9002 and 9003 have been removed, ISO 8402 has been integrated in the reformed DIN EN ISO 9000. Apart from that the compatibility with other management systems has been improved. It was the aim of the reform to improve the applicability for all types of business, products and services.

The effects of dose, route of administration, drug scheduling and MDR-1 gene transfer on the genotoxicity of etoposide in bone marrow.

We have used the bone marrow micronucleus assay (BMMN) as a measure of clastogenicity, in response to etoposide exposure in murine bone marrow. Oral delivery of etoposide resulted in a reduced number of micronucleated polychromatic erythrocytes (MPE) relative to the same dose delivered intraperitoneally (P < 0.001). Daily fractionation of the oral schedule of etoposide led to a more than six-fold increase in cumulative MPE frequency over that observed with the same total, unfractionated dose, with the potency of the response increasing with serial exposure (r = 0.79). Retrovirally-mediated expression of MDR1 in murine bone marrow resulted in partial protection against the clastogenic activity of etoposide relative to mock transduced control mice. The model system developed has indicated a variety of factors able to influence the genotoxicity of etoposide. It should now be possible to further exploit this model in order to define other factors governing haemopoietic sensitivity to etoposide.