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Quantum mechanical/molecular mechanical (QM/MM) and quantum mechanical charge field (QMCF) molecular (MD) simulations have been performed to describe structural and dynamical properties of Na(I) and K(I) in water and to compare the two approaches. The first and second hydration shells were treated by ab initio quantum mechanics at the restricted Hartree-Fock (RHF) level. The structural data are in good agreement with previously published experimental and theoretical results. A considerable number of water exchange reactions were observed within the first shell during the simulation time of 12 ps. The number of exchange events in both shells is higher in the case of K(I) than Na(I) reflecting the weaker ion-ligand bond strength of K(I). Comparison of the "conventional" QM/MM framework with the QMCF method clearly indicates the latter to be advantageous, as ambiguities arising from the coupling of the subregions occurring in the QM/MM MD simulations did not evolve when the QMCF ansatz was applied.

Quantum mechanical charge field (QMCF) molecular dynamics (MD) simulations including first and second hydration shell in the QM region have been performed to describe structural and dynamical properties of Ge(II) in water. The first and second hydration shells were treated by ab initio quantum mechanics at restricted Hartree-Fock (RHF) level. The radial distribution function (RDF) showed the maximum probability of the Ge–O bond length at 2.04 A, accompanied by an extended first shell located at ∼2.8 A. A uniquely distorted hydration structure with two tri-pyramidal substructures provides a new basis for the interpretation of the kinetic properties of germanium(II) complexes.

Over the last decade several groups, including ourself, have published a series of findings on a molecule expressed in leukocytes. The molecule was termed Cybr, CYTIP or CASP for its functions and PSCDBP for its binding properties. In this review we attempt to chronicle and combine the findings on the molecule to gain an overview of its features.

The complex and labile hydration structure of the dimeric mercury ion Hg 2 2 + has been studied by means of the novel quantum mechanical charge field molecular dynamics approach (QMCF MD). This system has been chosen as a challenging target to assess and evaluate the applicability of the QMCF approach, as standard MM and QM/MM protocols face obstacles in the formulation of accurate ion–solvent interaction potentials, while the application of the QMCF approach allows to renounce these potentials as the respective contributions are all included in the quantum mechanical framework. The results of the simulation show that the Hg(I) dimer forms a very labile hydration structure. In average 3.7 ligands are bound to each of the Hg atoms, and the water molecules are exchanged on the picosecond timescale.

The structural and dynamical properties of the cis-(O-Zn-O angle approximately 90 degrees) and trans-(O-Zn-O angle approximately 180 degrees) isomers of the model diaquotriamminezinc(II) complex in aqueous solution have been evaluated using the hybrid quantum mechanical/molecular mechanical molecular dynamics simulation approach at ab initio Hartree-Fock level. In both complexes, the first hydration shell contains five ligands (two water and three ammonia molecules) arranged in a trigonal bipyramidal geometry. In the metastable cis-isomer two different bond lengths of 2.34 and 2.13 A are observed for the Zn-Oax and Zn-Oeq bonds, respectively. The trans-isomer shows the maximum of the Zn-O distance at 2.26 A. The Zn-N bond distances in both cases are approximately 2.12 A. A geometrical transformation of the cis-isomer into the trans-isomer was observed after 11.5 ps of simulation, and the trans-isomer then remained stable throughout the whole simulation time of 30 ps. A comparative study for both isomers has been performed in terms of radial distribution functions, coordination number distributions, angular distribution functions, tilt and theta angle distributions, ligands' mean residence time, ion-ligand stretching frequencies, and the vibrational and librational motions of water ligands. The results are compared with the data for the previously studied zinc-monoamine and -diamine complexes.

QMCF-MD simulations of phosphate, sulphate and perchlorate ions in aqueous solution were performed to study the anions’ librational and vibrational motions. The obtained normal modes of the tetrahedral anions are in good agreement with experimental data. The simulations also give a detailed insight into the dynamics of the these three anions in aqueous solution, in particular into ligand exchange processes and spatial distribution of water hydrogen atoms binding to the anions’ oxygens.

As a result of recent methodological developments in connection with enhanced computational capacity, theoretical methods have become increasingly valuable and reliable tools for the investigation of solutions. Simulation techniques utilizing a quantum mechanical (QM) approach for the treatment of the chemically most relevant region so-called hybrid quantum mechanical/molecular mechanical (QM/MM) simulations have reached a level of accuracy that often equals or may even surpass experimental methods. The latter is true in particular whenever ultrafast (i.e., picosecond) dynamics prevail, such as in labile hydrates or structure-breaking systems. The recent development of an improved QM/MM framework, the quantum mechanical charge field (QMCF) ansatz, enables a broad spectrum of solute systems to be elucidated. As this novel methodology does not require any solute solvent potential functions, the applicability of the QMCF method is straightforward and universal. This advantage is bought, however, at the price of a substantial increase of the QM subregion, and an attendant increase in computational periods to levels of months, and even a year, despite parallelizing high-performance computing (HPC) clusters. Molecular dynamics (MD) simulations of chemical systems showing increasing complexity have been performed, and demonstrate the superiority of the QMCF ansatz over conventional QM/MM schemes. The systems studied include Pd2+, Pt2+, and Hg2 2+, as well as composite anions such as PO4 3- and ClO4 -.

Bleeding and vascular infections are serious potential complications during abdominal general surgery. The management of bleeding depends on the extent and localization and can range from the application of hemostatics to vascular sutures, interpositioning and ligatures. The use of prosthetic biomaterials implanted endoluminally or during open reconstruction permits palliation of potentially fatal conditions. The overall incidence of infections involving vascular prostheses is relatively low because of routine antibiotic prophylaxis prior to surgery, refinements in sterilization and packaging of devices and careful adherence to aseptic procedural and surgical techniques. When infections occur detection and definitive therapy of the vascular prosthesis are often delayed and the management is complex and tedious. Infections involving vascular prostheses are difficult to eradicate and in general, surgical therapy is required often coupled with excision of the prosthesis. Keys to success include accurate diagnostics to identify the organism and extent of graft infections, specific long-term antibiotic therapy and well-planned surgical interventions to excise and replace the infected graft and sterilize the local tissue. Regardless of the technique used to eradicate graft infections, success is measured by patient survival, freedom from recurrent infection and patency of revascularization. Even when treatment is successful, the morbidity associated with vascular graft infections is considerable. Aortoenteric fistulas (AEF) are a rare (incidence 1.5 %) but often fatal complication. Primary diagnosis of AEF remains difficult. Computed tomography (CT) and fluorodeoxyglucose positron emission tomography CT (FDG-PET-CT) are the diagnostic tools of choice. Therapy consists of an urgent individualized interdisciplinary surgical approach with primary axillofemoral bypass and secondary prosthesis explantation or in situ replacement and subsequent bowel resection. Endovascular aortic repair (EVAR) is reserved for primary aortoenteric fistulas in patients with no signs of infection or in emergency cases as a bridging method.

EnMAP (Environmental Mapping and Analysis Program) is a German hyperspectral earth observation satellite. Its spectral measurements will be used to obtain a diagnostic characterization of the earth's surface and to derive quantitative surface parameters on the status of terrestrial and aquatic ecosystems and the changes they undergo. EnMAP data will supply a basis for quantifying and modeling crucial ecosystem processes, thereby making a major contribution toward understanding the complexities of the Earth system. The satellite system is being developed entirely in Germany under the aegis of the Space Administration of the German Aerospace Center (DLR), with the launch scheduled for 2018. EnMAP carries a push broom type hyperspectral instrument with 30 km swath width at a ground sampling distance of 30 m, covering the full range of strong solar irradiation from 420 nm to 2450 nm with two spectrometers, one each for the VNIR and SWIR range. It will be operated for five years on a sun-synchronous orbit with a local time descending node (LTDN) at 11:00. At near nadir orientation (±5°) the repeat rate of EnMAP is 27 days. Using the across track platform pointing capability of ±30° enables frequent access to any global site within four days, allowing short term evolutions of ecosystems to be studied with high precision. Data takes can be acquired with an accumulated length of 5000 km along track per day, with individual segments ranging from 30 km to 1000 km. Image data are down linked via the Neustrelitz ground station using an X-band link at 320 MBit/s.

The pharmacologically and industrially important palladium(II) ion is usually characterised as square-planar structure in aqueous solution, similar to the platinum(II) ion. Our investigations by means of the most modern experimental and theoretical methods give clear indications, however, that the hydrated palladium(II) ion is hexa-coordinated, with four ligands arranged in a plane at 2.0 A plus two additional ligands in axial positions showing an elongated bond distance of 2.7–2.8 A. The second shell consists in average of 8.0 ligands at a mean distance of 4.4 A. This structure provides a new basis for the interpretation of the kinetic properties of palladium(II) complexes.

For more than a decade Kayser-Threde, a medium-sized enterprise of the German space industry, has been involved in astrobiology research in partnership with a variety of scientific institutes from all over Europe. Previous projects include exobiology research platforms in low Earth orbit on retrievable carriers and onboard the Space Station. More recently, exobiology payloads for in situ experimentation on Mars have been studied by Kayser-Threde under ESA contracts, specifically the ExoMars Pasteur Payload. These studies included work on a sample preparation and distribution systems for Martian rock/regolith samples, instrument concepts such as Raman spectroscopy and a Life Marker Chip, advanced microscope systems as well as robotic tools for astrobiology missions. The status of the funded technical studies and major results are presented. The reported industrial work was funded by ESA and the German Aerospace Center (DLR). (c) 2007 Published by Elsevier Ltd.

We simultaneously studied the impact of top-down (protistan grazing) and bottom-up (phosphorus availability) factors on the numbers and biomasses of bacteria from various phylogenetic lineages, and on their growth and activity parameters in the oligo-mesotrophic Piburger See, Austria. Enhanced grazing resulted in decreased proportions of bacteria with high nucleic acid content (high-NA bacteria) and lower detection rates by FISH. There was a change in the composition of the bacterial assemblage, whereby Betaproteobacteria were heavily grazed while Alphaproteobacteria and Cytophaga-Flavobacterium-Bacteroides were less affected by predators. Changes in bacterial assemblage composition were also apparent in the treatments enriched with phosphorus, and even more pronounced in the incubations in dialysis tubes (allowing relatively free nutrient exchange). Here, Betaproteobacteria became dominant and appeared to act as successful opportunistic competitors for nutrients. In contrast, Actinobacteria did not respond to surplus phosphorus by population growth, and, moreover, maintained their small size, which resulted in a very low biomass contribution. In addition, significant relationships between high-NA bacteria and several bacterial phylogenetic clades were found, indicating an enhanced activity status. By combining several single-cell methods, new insight is gained into the competitive abilities of freshwater bacteria from a variety of phylogenetic lineages under contrasting sets of bottom-up and top-down constraints.

Infiltration of surface water constitutes an important pillar in artificial groundwater recharge. However, insufficient transformation of organic carbon and nutrients, as well as clogging of sediments often cause major problems. The attenuation efficiency of dissolved organic carbon (DOC), nutrients and pathogens versus the risk of bioclogging for intermittent recharge were studied in an infiltration basin covered with different kinds of macrovegetation. The quality and concentration of organic carbon, major nutrients, as well as bacterial biomass, activity and diversity in the surface water, the porewater, and the sediment matrix were monitored over one recharge period. Additionally, the numbers of viral particles and Escherichia coli were assessed. Our study showed a fast establishment of high microbial activity. DOC and nutrients have sustainably been reduced within 1.2 m of sediment passage. Numbers of E. coli, which were high in the topmost centimetres of sediment porewater, dropped below the detection limit. Reed cover was found to be advantageous over bushes and trees, since it supported higher microbial activities along with a good infiltration and purification performance. Short-term infiltration periods of several days followed by a break of similar time were found suitable for providing high recharge rates, and good water purification without the risk of bioclogging.

An implementation strategy for a dissociative water potential in hybrid QM/MM simulations is outlined. As the knowledge of the time-dependent topology is crucial for the assignment of solvent molecules to the QM or MM subregion, proton transfer events and the associated change of the molecular composition have to be monitored as the simulation is progressing. A simple and effective update criterion is proposed, which was found to be an efficient tool to identify sustained proton transfer reactions. The resulting topology data enable the application of the dissociative solvent model in QM/MM simulations and serve as a reference for the analysis of time-dependent properties such as the proton hopping rate and the diffusion coefficient. For the latter, an interpolation scheme is proposed linking subsequent proton transfer events into a single diffusive entity. Suitable settings of key parameters for the topology update and the interpolation scheme have been determined by analyzing MD trajectories of an excess proton in water and 1 M HCl. The resulting values for the proton hopping rate and the diffusion coefficient are well within the range estimated by EVB models and CPMD approaches. An investigation of the hydrolytic conversion of As(III) to [As(OH)2](+) serves as an exemplary application of the dissociative model in a QM/MM simulation study.

In the hospital, human resource planning has to consider the needs and preferences of personnel and planners as well as the financial interest of the hospital. Additionally, staff planning has become more complex due to a growing number of part-time doctors as well as a variety of working shifts.The aim of the study was to describe existing human resource planning in German anesthesiology departments. Furthermore, we evaluated existing software solutions supporting human resource planning.Anesthesiology departments of German university hospitals were enrolled in the study. The aspects covered were tools and time needed for planning, amount of conflicts while planning, components of the software solutions and the efficiency and satisfaction according to the users. This was evaluated for short-, intermediate- and long-term planning. Two groups were compared: departments with and without software exchanging information among the three planning periods.Out of 35 university anesthesiology departments, 23 took part in the survey. On average they employed 105.8 ± 27.8 doctors who had to cover 13.5 ± 6.3 different shifts during a weekday. Personnel planning is mostly done by senior physicians. In some departments, other staff, such as residents and junior doctors, were involved as well. Software that exchanged information between short-, intermediate- and long-term planning was used in 53 % of the departments (12 out of 23). Five departments used commercially available planning software: Polypoint Deutschland (PolypointDeutschland), Atoss (Atoss AG) and SP Expert (Interflex Datensysteme). The time needed for short-term planning was slightly reduced in the exchanging software group. No difference was shown for the intermediate planning period. The use of this software led to a slight reduction in planning conflicts and increased the self-estimated efficiency of the users (p = 0.02). Throughout all groups, the major complaint was missing interfaces, for example between the software and human resources department. The ideal planning software should reduce time needed for planning and prevent planning conflicts according to the interviewed physicians. Furthermore it should be flexible and transparent for all involved staff.This study analyzed structures established in human resource planning in the anesthesiology departments for the first time. Time for planning varies significantly in comparable departments indicating suboptimal processes. Throughout Germany, the requirements for human resources planning are similar; for example, the software should integrate all aspects of HR planning. Different approaches are under evaluation but so far no software solution has prevailed. The used solutions vary substantially and therefore a comparison is difficult. There is no software solution with wide adoption.

The title compound is hydrothermally synthesized from a mixture of KNO3, B2O3, and Ce(NO3)3·6H2O with a molar ratio of 1:1:0.07 (autoclave, 513 K, 3 d).

Structure and dynamics of [MgEDTA](2-) and [CaEDTA](2-) complexes in aqueous solution have been investigated via quantum mechanical/molecular mechanical (QM/MM) simulations. While for the first a 6-fold octahedral complex has been observed, the presence of an additional coordinating water ligand has been observed in the latter case. Because of rapidly exchanging water molecules, this 7-fold coordination complex was found to form pentagonal bipyramidal as well as capped trigonal prismatic configurations along the simulation interchanging on the picosecond time scale. Also in the case of [MgEDTA](2-) a trigonal prismatic configuration has been observed for a very short time period of approximately 1 ps. This work reports for the first time the presence of trigonal prismatic structures observed in the coordination sphere of [MgEDTA](2-) and [CaEDTA](2-) complexes in aqueous solution. In addition to the detailed characterization of structure and dynamics of the systems, the prediction of the associated infrared spectra indicates that the ion-water vibrational mode found at approximately 250 cm(-1) provides a distinctive measure to experimentally detect the presence of the coordinating water molecule via low-frequency IR setups.

The proton transfer properties of the dissociative water potential developed by Garofalini et al. were closely examined by carefully analyzing the pairwise screening functions of the three-body interaction. It was shown that a simultaneous adjustment of the exponential screening factor and the three-body cutoff distance enables a selective adjustment of the diffusive properties of an excess proton, while at the same time structural and other dynamical data remain unaffected to a large extend. To investigate proton transfer properties without the influence of nuclear quantum effects, deuterated systems have been investigated in addition to their hydrogen counterparts. It was shown that the suggested parameter set A leads to significantly improved diffusion coefficients and proton hopping rates. Comparison of proton transfer correlation functions to simulation data obtained from Car-Parrinello molecular dynamics simulations confirms the improved performance of the adjusted parametrization.

Cost effectiveness has been demonstrated for traditional lumbar discectomy, lumbar laminectomy as well as for instrumented and noninstrumented arthrodesis. While emerging evidence suggests that minimally invasive spine surgery reduces morbidity, duration of hospitalization, and accelerates return to activites of daily living, data regarding cost effectiveness of these novel techniques is limited. The current study analyzes all available data on minimally invasive techniques for lumbar discectomy, decompression, short-segment fusion and deformity surgery. In general, minimally invasive spine procedures appear to hold promise in quicker patient recovery times and earlier return to work. Thus, minimally invasive lumbar spine surgery appears to have the potential to be a cost-effective intervention. Moreover, novel less invasive procedures are less destabilizing and may therefore be utilized in certain indications that traditionally required arthrodesis procedures. However, there is a lack of studies analyzing the economic impact of minimally invasive spine surgery. Future studies are necessary to confirm the durability and further define indications for minimally invasive lumbar spine procedures.

Dynamic properties of hydrated aluminium(III) ion have been investigated by ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations at Hartree–Fock level including only the first or first plus second hydration shell into the QM region. The octahedral Al–O frequencies and ligand exchange processes between second shell and bulk have been evaluated. The results show that quantum effects play a non-negligible role also in the interaction of first and second shell and that inclusion of the latter into the QM region improves the values of sensitive dynamical data.

Dynamic properties of the hydrated Pb(II) ion have been investigated by ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations at Hartree Fock quantum mechanical level. Librational as well as vibrational motions of first and second shell and the bulk as well as the frequencies of rotations have been evaluated by means of velocity auto correlation functions (VACF). The time evolution of the Pb–O distances and selected O–Pb–O angles in the first shell was evaluated. A lower limit of the mean ligand residence time of water molecules in the first shell was estimated as 0.23 ns, in the second shell a mean residence time of 5.6 ps was observed.

When T cells are primed by dendritic cells (DCs) to initiate antigen-specific immune responses screening for matching antigen receptor-MHC/peptide pairs takes place in DC-T-cell conjugates. For an immune response DC-T-cell conjugates formed during priming events need to dissolve. Although detailed knowledge on molecules involved in the conjugate formation is available, dissolving of them has not been considered to be an active process. Here, we identify CYTIP (cytohesin-interacting protein) to mediate DC-T-cell deattachment. CYTIP, which is induced during maturation of DCs, shortly accumulates to the contact zones with T cells within the first hour of coculture. Specific silencing of CYTIP results in stronger adhesion of DCs to T cells and to fibronectin. When a need for deattachment is created in a T-cell priming assay by only partially loading DCs with antigen, CYTIP silencing causes reduced priming capacity. Thus, CYTIP allows DCs to actively control DC-T-cell interactions.

The progress of computational chemistry in the treatment of liquid systems is outlined, and the combination of the statistical methods (Monte Carlo, MC, and molecular dynamics, MD) with quantum mechanics as the main foundation of this progress is emphasized. The difficulties of experimental studies of liquid systems without having obtained sophisticated theoretical models describing the structural entities and the dynamical behavior of these liquids demonstrate that chemistry research is in a transition phase, where theory and high-performance computing have not only become a valuable supplement, but an essential and almost indispensable component to secure a correct interpretation of measured data.

A new formalism for quantum mechanical / molecular mechanical (QM/MM) dynamics of chemical species in solution has been developed, which does not require the construction of any other potential functions except those for solvent–solvent interactions, maintains all the advantages of large simulation boxes and ensures the accuracy of ab initio quantum mechanics for all forces acting in the chemically most relevant region. Interactions between solute and more distant solvent molecules are incorporated by a dynamically adjusted force field corresponding to the actual molecular configuration of the simulated system and charges derived from the electron distribution in the solvate. The new formalism has been tested with some examples of hydrated ions, for which accurate conventional ab initio QM/MM simulations have been previously performed, and the comparison shows equivalence and in some aspects superiority of the new method. As this simulation procedure does not require any tedious construction of two-and three-body interaction potentials inherent to conventional QM/MM approaches, it opens the straightforward access to ab initio molecular dynamics simulations of any kind of solutes, such as metal complexes and other composite species in solution.

Recent developments in computer speed and capacity have opened the access to highly accurate molecular dynamics simulations based on quantum mechanically calculated forces for the chemically relevant region around ions in solution (QM/MM formalism). This accuracy, although still extremely consuming (30–300 days of CP time per simulation), is needed for reliable structural details and ligand exchange rates. A large number of main group and transition metal ions have been investigated by this approach, giving very detailed insight into the properties of these ions in solution and allowing to classify the ions by various characteristics. Most first-row transition metal ions have a very stable first hexa-coordinated solvation shell, whose vibrational distortions, however, strongly influence the dynamics of the second shell. The dynamical Jahn–Teller effect – shown to be a femto- and picosecond phenomenon – can strongly influence ligand coordination and exchange dynamics. A large number of ions with very labile solvation shell such as most main group ions, but also transition metal ions, e.g. Ag(I) and Hg(II), can change their coordination within the picosecond scale, leading to an almost simultaneous presence of several species hardly accessible by present experimental techniques. Among these ions, the structure breakers are of particular interest, and it could be shown that there are two types of them, one with a large and very labile first coordination shell such as Cs(I), the other characterised by a small first but an unusually large second solvation shell such as Au(I). Investigations of metal ions coordinated to ammonia ligands have shown that coordination to hetero-atoms can accelerate the ligand exchange reaction rates by several orders of magnitude, e.g. for Cu(II) and Ni(II). Simulations of ions in aqueous ammonia gave a very detailed picture of the complexity of species almost simultaneously present and illustrate the enormous difficulties encountered when trying to fit X-ray or neutron diffraction data for such systems. In general, ligand exchange rates situated in the picosecond range are far below the NMR scale, and as femtosecond laser pulse spectroscopy could not be applied so far to ionic solutions, accurate simulations have become a very important tool to access structure and dynamics of solvated ions. A number of VIDEO clips supplied on the Web as supporting material illustrates the processes occurring in solutions of the metal ions.

Activins are members of the transforming growth factor-beta (TGF-beta) family and are important for skin morphogenesis and wound healing. TGF-beta1 is necessary for the population of the epidermis with Langerhans cells (LC). However, a role for activin in LC biology is not known. To address this question, we analyzed skin from transgenic mice overexpressing the activin antagonist follistatin in the epidermis. Using immunofluorescence, we observed a striking decrease in the number of LC in the epidermis of transgenic mice in comparison to wild-type mice. Nevertheless, these LC expressed normal levels of major histocompatibility complex (MHC)-class II and Langerin/ CD207 in situ. In explant cultures of whole ear skin the number of dendritic cells (DC), which migrated into the culture medium, was reduced. This reduction was even more pronounced in cultures of epidermal sheets. Virtually all emigrated cutaneous DC displayed typical morphology with cytoplasmic "veils", showed translocation of MHC-class II to the surface membrane, and expressed the maturation marker 2A1. Thus, cutaneous DC from transgenic mice seemed to mature normally. These results demonstrate that overexpression of follistatin in the epidermis affects LC trafficking but not maturation and suggest a novel role of the follistatin-binding partner activin in LC biology.

Structural properties of the hydrated Ba(II) ion have been investigated by ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations at double zeta HF quantum mechanical level. The first shell coordination number was found to be 9.3, and several other structural parameters such as angular distribution functions, radial distribution functions and tilt- and θ-angle distributions allowed the full characterization of the hydration structure of the Ba(II) ion in dilute aqueous solution. Velocity autocorrelation functions were used to calculate librational and vibrational motions, ion–ligand motions as well as reorientation times. Different dynamical parameters such as water reorientation, mean ligand residence time, the number of ligand exchange processes and rate constants were also analyzed and the ligand exchange rate constant for the first shell was determined as k = 5.3 × 1010 s−1.

A molecular dynamics simulation employing three-body corrected pair potentials to describe the ion–water interaction has been performed to investigate the structural and dynamical properties of Bi(III) in dilute aqueous solution. A first shell hydration complex forming a tri-capped trigonal prism was observed. The second shell consists in average of 21 water molecules, the mean ligand residence time of the second shell was evaluated as 8.5 ps.

Structural properties of the hydrated Al(III) ion have been investigated by ab initio quantum mechanical/ molecular mechanical (QM/MM) molecular dynamics (MD) simulations at double zeta HF quantum mechanical level including only the first and first plus second hydration shell into the QM region. The coordination number in the first shell was found to be 6.0 in both cases, but the inclusion of the second shell into the QM region causes significant changes in the properties of the hydrate. Several structural parameters such as angular distribution functions, radial distribution functions and tilt- and theta-angle distributions were used to fully characterise the hydration structure of Al(III).

This paper summarizes the content of four Technical Notes that were established within a study contracted by the European Space Agency concerning the possibility of applying Raman spectroscopy in the field of remote imaging. An overview of the scientific demands and Raman spectroscopy from the user’s point of view is provided together with a few key aspects in the field of planetary research. Laboratory Raman experiments were used for establishing a basis for the subsequent extrapolation to remote Raman spectroscopy. A detailed numerical simulator was used to derive numbers concerning link budgets and overall remote Raman spectroscopy instrument performance for a number of different scenarios. A summary of subsystem technologies and criticalities is also presented together with the necessary R&D efforts. Copyright  2004 John Wiley & Sons, Ltd.

Structural and dynamical properties of the hydrated Cs+ ion have been investigated by performing ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations at different quantum mechanical levels (HF, B3LYP and BP86). The first shell coordination number was found to be ∼8 in the HF and ∼9 in the B3LYP and BP86 case and several other structural parameters such as angular distribution functions, radial distribution functions, and tilt- and θ-angle distributions allowed to fully characterize the hydration structure of the Cs+ ion. Velocity autocorrelation functions were used to calculate librational and vibrational motions, ion−ligand motions, as well as reorientation times. The strong “structure breaking” effect of Cs+ can be interpreted on the basis of different dynamical parameters such as accelerated water reorientation, mean ligand residence time, and the number of ligand exchange processes.

Background High doses (10(-6)-10(-8) M) of tacrolimus (FK506) were reported to induce a type-2 T-helper cell (Th2)-promoting function in developing dendritic cells (DC). We used a therapeutic dose (2.4 x 10(-9 )M) of tacrolimus to investigate its effect on human monocyte-derived DC. Methods Using untreated and treated immature and mature DC we compared T cell-activating capacity, surface marker expression, T cell and DC cytokine profile and transcription of genes coding for a panel of DC function-related molecules. Results Tacrolimus-treated mature DC had reduced T-cell stimulatory capacity. Although interleukin (IL)-12 production of DC was impaired, they did not promote Th2 development as T cells activated by tacrolimus-treated DC produced less interferon (IFN)-gamma, IL-4 and IL-10. The up-regulation of the T-cell activation marker CD69 and the production of IL-2 were impaired. In addition, tacrolimus-treated DC produced less IP-10 (CXCL10), which is known to be involved in allograft rejection. Other molecules related to DC function remained unchanged. Conclusions Tacrolimus treatment reduces the ability of DC to stimulate T cells and the impaired production of DC-derived IP-10 (CXCL10) and IL-12 might play a role in the immunosuppressive action of tacrolimus.

We present a new method to design the energy level scheme of quantum dot (QD) structures by combining band gap engineering with the self-organized growth of (QDs). With the embedding of QDs in two-dimensional supperlattices optical transition energies, ionization energies and the absorption properties of this system can be adjusted. This scheme is applied for novel photodetectors made of InAs QDs embedded in an AlAs/GaAs superlattice, and the absorption energy is tailored by changing the superlattice period. Moreover, the dark current of these devices is reduced by more than one order of magnitude compared to devices without a superlattice.

Due to the increasing number of long-term cancer survivors, physicians of all specialties are confronted with the need to prevent side effects of the applied oncologic treatments. In the field of reproductive medicine fertility preservation has gained importance as most oncologic treatments have detrimental immediate or long-term impacts on male and female fertility. The American Society of Clinical Oncology and the American Society for Reproductive Medicine, as well as the recently founded International Society for Fertility Preservation propose several established and investigational options for fertility preservation. This review aims to summarize currently available techniques for fertility preservation and future perspectives in this field, as well as to provide recommendations for patient follow-up after cancer and during pregnancy.

A combined theoretical and experimental study was performed to elucidate the structural and dynamical properties of the isolated aqueous hexacyanoferrate(II) ion as well as in the presence of potassium counterions. It is shown that in absence of counterions, the highly negatively charged hexacyanoferrate(II) complex is not stable in aqueous solution. However, if the high negative charge is compensated by potassium counterions, a stable complex is observed, which is proven by theoretical simulations as well as by extended X-ray absorption fine structure (EXAFS) experiments. From the simulation it is found that potassium ions surrounding the complex are highly mobile and thus cannot be observed via EXAFS experiments. The structure of aqueous hexacyanoferrate(II) in the presence of potassium ions is identical to that of the solid-state structure, but the mobility of potassium ions is significantly increased in the liquid. These highly mobile potassium ions circulating the complex are the reason for the very short lifetime of hydrogen bonds between solvent water molecules and cyanide ligands being on the femtosecond scale.

The classical modeling of proton transfer reactions in chemical simulations requires the application of reactive force field formulations. A common feature of these dissociative potential models of aqueous systems is the possibility to transfer protons between water, oxonium and hydroxide ions. Since molecules undergo a change of their composition as the simulation progresses, the respective topology defining which atoms form a molecular unit at a given configuration becomes time-dependent. Knowledge of this variable topology is a key prerequisite to apply dissociative models in the framework of hybrid quantum mechanical/molecular mechanical (QM/MM) simulation studies. In order to effectively execute QM/MM simulations, the simulation software has to be able to independently monitor all occurring bond formation and cleavage events and automatically adjust the respective topology information, thereby discriminating between short-time fluctuations and sustained proton transfer events. The properties of a simple yet effective automated topology update criterion developed for excess protons are presented and its performance for hydroxide containing solutions and systems containing excess protons is compared. Furthermore, the influence of deuteration of the different systems is discussed. The data clearly demonstrates that it is possible to apply a global setting for the automated topology update of both proton and proton-hole migration.

Raman imaging on different types of meteorite surfaces was performed. Three different surface textures on a chondritic meteorite from the Dhofar 005 strewnfield and a fourth surface with a very rough texture on a goethite mineral have been investigated. The Raman measurements were made with and without autofocus. The influence of the surface texture on the quality of the Raman spectra was analyzed. The percentage of the informative Raman spectra obtained from every sampled area were sufficient to assert the local mineral composition. For obtaining a spatial distribution of minerals (in the micrometer range), an autofocus device needed to be employed. It was found that approximately 85% of all Raman spectra taken at λ ext =633 nm show sufficient information to establish a clear assignment to a certain mineral. In the case of the rough goethite surface, measured without an autofocus device approx. 60% of the recorded spectra could be assigned.

Locally advanced cutaneous malignancy of the scalp and forehead is a disease that requires an aggressive approach to resection and reconstruction. Free flap reconstruction in these sites has been advocated because of the advantages of importing large amounts of well-vascularized tissue into a recipient site, which has often been compromised by previous surgery or radiotherapy. A consecutive series of 32 free flap reconstructions in 29 patients with cutaneous malignancy of the scalp and forehead was reviewed. The flap failure rate was 6% (two flaps) and the major complication rate was 10%. Of the surviving flaps, 97% (N = 29) were successful in reconstructing a challenging group of defects. Three patients developed local recurrence of the primary malignancy (mean follow-up, 21 months). The use of a broad repertoire of free tissue transfers in reconstruction of the scalp and forehead defects has allowed effective treatment of locally advanced malignancy of this region. Critical analysis of the results, however, indicates that microsurgical reconstruction is not without morbidity and that there are refinements in the diagnostic and operative steps of management that can maximize the functional and aesthetic results.

We investigate the energy levels of self-assembled InAs/GaAs quantum dot stacks by photoluminescence and vertical photocurrent spectroscopy. This leads to a photodetector with two response peaks at 55 and 253 meV due to interdot and dot-continuum transitions. Two samples are used for the investigations: one without and one with AlAs barriers between the dot layers to restrict the vertical current. These barriers have a strong influence on the signal height of the room temperature photoluminescence. They make—due to the lower dark current and lower noise—the interdot transitions visible in photocurrent spectroscopy and increase the dot-continuum photocurrent energy by the amount of the first miniband energy level of the AlAs/GaAs superlattice.

In systemic lymphoma, a secondary CNS involvement (secondary CNS lymphoma, SCNSL) occurs in 2-5% of patients. With conventional therapy the prognosis of SCNSL is poor with median overall survival (OS) in most series of approx. 6 months. The optimal therapeutic management has not been established; long-term control seems possible only with intensive chemotherapy including high-dose chemotherapy with autologous stem-cell transplantation (HD-ASCT). Since 2011, data on SCNSL patients have been prospectively collected in a multicenter international registry. Thus far, 173 immunocompetent patients with CNS involvement at diagnosis (cohort I, n=30) or at progression/relapse (cohort II, n=143) from 41 centers have been included. The median age was 63 years (26-86), 111 (64%) were male. The median time to CNS involvement in cohort II was 10.6 months Of 155 patients with data available, 122 (79%) had aggressive B-cell lymphoma, 25 (16%) indolent lymphoma, 5 (3%) mantle cell lymphoma and 3 (2%) T-cell lymphoma. Lymphoma localization in the CNS was brain parenchyma in 84 (54%), meningeal compartment in 37 (24%), spinal cord in 2 (1%) and a combination of these compartments in 32 (21%). Simultaneous systemic involvement was found in 42% of patients in cohort II. Therapy for CNS involvement and outcome was analyzed in 99 patients thus far (16 in cohort I and 83 in cohort II). Systemic therapy alone was given to 48 (49%), systemic + intrathecal therapy to 43 (43%), intrathecal therapy alone to 5 (5%), radiotherapy alone to 2 (2%); one patient did not receive any treatment. Systemic chemotherapy was high-dose methotrexate-based in 81 (89%) and high-dose cytarabine-based in 53 (58%); 61 (61% of all) patients received rituximab systemically. Liposomal cytarabine was the most frequent intrathecal therapy given in 30 out of 48 patients (63%). HD-ASCT was performed in 25 (25%) patients. The median progression-free survival (PFS) was 5.9 months (95% CI 3.1-8.7), the median OS 18.6 months (95% CI 10.3-26.9). On univariate analysis, CNS lymphoma at diagnosis, no meningeal involvement, better ECOG performance status, treatment with rituximab, HD-ASCT and response to therapy were associated with better outcome. Multivariate analysis was done using blockwise variable selection, starting with demographic data and findings at first diagnosis, and subsequently enlarging the model by findings at CNS involvement, therapy of CNS involvement and outcome of CNS therapy. Here, a probable prognostic role for cohort I and HD-ASCT (for OS) and no meningeal involvement (for both PFS and OS) was found with response to CNS therapy being the dominating prognostic factor (for both OS and PFS). This is the largest prospective series on SCNSL in the era of modern lymphoma therapies. The results underscore the role of intensive therapy for long-term control of SCNSL. At the meeting, an updated analysis will be presented.

Several bioanalytical enrichment techniques are based on the interactions of phosphopeptides with Ln(III) ions. In order to gain an improved understanding of these complexes and the respective ion–peptide interactions, hybrid quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations of La(III) coordinating to the phosphopeptide VPQLEIVPNSpAEER were conducted. Simulations of di- as well as monoanionic phosphate groups were carried out. The La(III) ion and its first hydration layer, including the sidechain of the phosphoserine residue were treated quantum mechanically at RI-MP2/triple zeta level, whereas the remaining part of the system was treated with classical potentials. The simulation of the dianionic phosphopeptide revealed a 9-fold coordinated La(III) ion, with the phosphopeptide binding bi- as well as monodentate. The mean residence times (τ) of the first shell water molecules were 82 ps and 37 ps for the bi- and monodentate complexes, respectively, which is much higher compared to free La(III) in aqueous solution (τ = 17 ps). The simulation of the monoanionic La(III)–phosphopeptide complex revealed a bidentate coordination throughout the 80 ps sampling period. An intramolecular hydrogen bond between the hydrogen of the phosphate group and the backbone was observed and a τ value of 14 ps was obtained, which is much lower as for the dianionic complex.

This work presents a hybrid ab initio quantum mechanical/molecular mechanical simulation at the RI-MP2 level of theory investigating the hydrolysis process of arsenic(III), ultimately leading to arsenous acid (H3AsO3). A newly implemented dissociative water model has been applied to treat the interactions in the classical region, which is capable of describing non-neutral water species such as hydroxide and oxonium ions. Three stages of hydrolysis have been observed during the simulation and besides profound dynamical considerations, detailed insights into structural changes and atomic partial charge shifts are presented. In particular, the geometrical properties of H-bonds involved in each of the three proton transfer events and subsequent proton hopping reactions are discussed. A Laguerre tessellation analysis has been employed to estimate the molecular volume of H3AsO3. Estimations of pKa values of the arsenic(III)-aquo-complexes have been obtained at the G4 and CBS-Q//B3 levels of theory using a thermodynamic cycle, whereas rate constants for the final hydrolysis step have been determined via reaction path optimization and transition state theory. Newly recorded Fourier transform infrared (FT-IR) spectroscopy measurements have been compared to power spectra obtained from the simulation data, confirming its quality. The simulation findings, as well as results from computational spectroscopic calculations utilizing the PT2-VSCF methodology, proved valuable for the interpretation of the experimental FT-IR data, elucidating the particularities of the strongly observed IR Raman noncoincidence effect.

Metformin-induced lactic acidosis is a rare but severe disease for the individual patients. A case of a 64-year-old patient with diabetes mellitus type 2 suffering from this disease is presented where metformin accumulation was caused by prerenal acute kidney failure. The clinical evaluation up to the final diagnosis, the pathophysiology and the appropriate therapy are presented in detail. Additionally, the current guidelines regarding the perioperative management of metformin administration are summarized. The case described aims to direct attention to the rare but, nevertheless, severe symptoms of metformin-induced lactic acidosis.

Sepsis and related complications are a challenge for intensive care medicine. Despite many advances in antibiotic therapy sepsis remains one of the most common diseases of patients in intensive care units and is designated as the main cause of death in critically ill patients. Persisting sepsis leads to impaired immunity, resulting in immunosuppression. Unspecific predictive signs complicate an early diagnosis; however, an early initiation of adequate therapy is of crucial importance for the prognosis. Scoring systems can be applied for the initial evaluation but are controversially discussed concerning the monitoring of disease progression and therapy as well as outcome prediction. Biomarkers are considered as a complementary approach.

SUMMARY 1. Virus-like particle (VLP) 3 abundances in nine freshwater to saline lakes in the Vestfold Hills, Eastern Antarctica (68∞ S) were determined in December 1999. In the ultraoligotrophic to oligotrophic freshwater lakes, VLP abundances ranged from 1.01 to 3.28 · 10 6 mL ‐1 in the top 6 m of the water column. In the saline lakes the range was between 6.76 and 36.5 · 10 6 mL ‐1 . The lowest value was found in meromictic Ace Lake and the highest value in hypersaline Lake Williams. Virus to bacteria ratios (VBR) were lowest in the freshwater lakes and highest in the saline lakes, with a maximum of 23.4 in the former and 50.3 in the latter. 2. A range of morphologies among VLP was observed, including phages with short (Podoviridae) and long tails, icosahedric viruses of up to 300 nm and star-like particles of about 80 nm diameter. 3. In these microbially dominated ecosystems there was no correlation between VLP and either bacterial numbers or chlorophyll a. There was a significant correlation between VLP abundances and dissolved organic carbon concentration (ra 0.845, P< 0.01). 4. The data suggested that viruses probably attack a spectrum of bacteria and protozoan species. Virus-like particle numbers in the freshwater lakes were lower than values reported for lower latitude systems. Those in the saline lakes were comparable with abundances reported from other Antarctic lakes, and were higher than most values published for lower latitude lakes and many marine systems. Across the salinity spectrum from freshwater through brackish to hypersaline, VLP concentrations increased roughly in relation to increasing trophy. 5. Given that Antarctic lakes have a plankton almost entirely made up of bacteria and protists, and that VLP abundances are high, it is likely that viruses play a pivotal role in carbon cycling in these extreme ecosystems.

In this article, the role of the clinical nurse specialist (CNS) at the University Hospital Insel in Bern, Switzerland, is described using four examples from daily practice. The first describes how the CNS may influence patient care by direct care, bedside teaching, or case reviews. Therefore, this form of co-operation with the nursing teams is a very important factor for improving nursing care. The second example is about wound care. Although the CNS work as generalists on the wards, they also have their specialist fields, where they have in-depth knowledge, skills and expertise. The third example describes how a CNS initiated an interprofessional working group with the aim of improving palliative care and palliative medicine throughout the hospital. Although such knowledge already existed in the hospital, it was not easily accessible to all the health care professionals. The fourth example is about project management. A CNS acted as a project leader of a multiprofessional group for pain assessment and management in babies, children and adolescents. This example also shows how a problem occurring in daily practice can be worked out and resolved.