Self-assembly of focal point oligo-catechol ethylene glycol dendrons on titanium oxide surfaces: adsorption kinetics, surface characterization, and nonfouling properties

This work covers the synthesis of second-generation, ethylene glycol dendrons covalently linked to a surface anchor that contains two, three, or four catechol groups, the molecular assembly in aqueous buffer on titanium oxide surfaces, and the evaluation of the resistance of the monomolecular adlayers against nonspecific protein adsorption in contact with full blood serum. The results were compared to those of a linear poly(ethylene glycol) (PEG) analogue with the same molecular weight. The adsorption kinetics as well as resulting surface coverages were monitored by ex situ spectroscopic ellipsometry (VASE), in situ optical waveguide lightmode spectroscopy (OWLS), and quartz crystal microbalance with dissipation (QCM-D) investigations. The expected compositions of the macromolecular films were verified by X-ray photoelectron spectroscopy (XPS). The results of the adsorption study, performed in a high ionic strength ("cloud-point") buffer at room temperature, demonstrate that the adsorption kinetics increase with increasing number of catechol binding moieties and exceed the values found for the linear PEG analogue. This is attributed to the comparatively smaller and more confined molecular volume of the dendritic macromolecules in solution, the improved presentation of the catechol anchor, and/or their much lower cloud-point in the chosen buffer (close to room temperature). Interestingly, in terms of mechanistic aspects of "nonfouling" surface properties, the dendron films were found to be much stiffer and considerably less hydrated in comparison to the linear PEG brush surface, closer in their physicochemical properties to oligo(ethylene glycol) alkanethiol self-assembled monolayers than to conventional brush surfaces. Despite these differences, both types of polymer architectures at saturation coverage proved to be highly resistant toward protein adsorption. Although associated with higher synthesis costs, dendritic macromolecules are considered to be an attractive alternative to linear polymers for surface (bio)functionalization in view of their spontaneous formation of ultrathin, confluent, and nonfouling monolayers at room temperature and their outstanding ability to present functional ligands (coupled to the termini of the dendritic structure) at high surface densities.

[Adapted and Standardised Patient Management in the Treatment of Neovascular AMD in the Outpatient Setting of a University Eye Hospital.]

Visual results in treating neovascular age-related macular degeneration (AMD) using intravitreal injected anti-VEGF (IVT) clearly depend on injection frequency. Regarding to the European approval Ranibizumab has to be used only in cases of recurrent visual loss after the loading phase. In contrast monthly treatment--as also provided in the ANCHOR and MARINA studies--is generally allowed in Switzerland. However, it is commonly tried to reduce the injection frequency because of the particular cost situation in all health systems and of cause also due to the necessary strict monitoring and reinjection regimes, which raise management problems with increasing patient numbers. In this article the special treatment regimes of our University Eye Hospital is presented, in which a reduced injection frequency basically leads to the same increased and stable visual results as in ANCHOR and MARINA; however, needing significantly more injections as generally provided in other countries of Europe. The main focus for achieving this in a large number of patients is placed on re-structuring our outpatient flow for IVT patients with particular emphasis on patient separation and standardisation of treatment steps leading to significantly reduced time consumption per patient. Measurements of timing and patient satisfaction before and after restructuring underline its importance in order to be able to treat more patients at a high quality even in the future. The exceptional importance of spectral domain OCT measurements as the most important criterium for indicating re-treatment is illustrated.

Biotreibstoffe aus Entwicklungsländern: Eine Lebenszyklusbetrachtung

Das Kyoto-Protokoll zur Treibhausgasreduktion und steigende Ölpreise, aber auch Lobbyarbeit vom Landwirtschaftssektor und von der Automobilindustrie haben global zu einem Boom der Biotreibstoffe geführt. Aufgrund des durch die Agrarflächen beschränkten Mengen-Potenzials, der absehbaren Konkurrenz zur Nahrungsmittelproduktion und den oftmals hohen Umweltauswirkungen liegt das nachhaltige Marktpotenzial von Biotreibstoffen deutlich unter 10% des gesamten weltweiten Treibstoffkonsums. Trotz dieser Nachteile existieren gerade in Entwicklungsländern auch Nischen für die nachhaltige Produktion von Bioenergie. Oftmals ist es dabei sinnvoller, Biomasse für lokale Strom- und Wärmeproduktion zu nutzen, statt Biotreibstoffe für den Export zu produzieren.

Diffusion-driven transport in clayrock formations

Clay mineral-rich sedimentary formations are currently under investigation to evaluate their potential use as host formations for installation of deep underground disposal facilities for radioactive waste (e.g. Boom Clay (BE), Opalinus Clay (CH), Callovo-Oxfordian argillite (FR)). The ultimate safety of the corresponding repository concepts depends largely on the capacity of the host formation to limit the flux towards the biosphere of radionuclides (RN) contained in the waste to acceptably low levels. Data for diffusion-driven transfer in these formations shows extreme differences in the measured or modelled behaviour for various radionuclides, e. g. between halogen RN (Cl-36, I-129) and actinides (U-238,U-235, Np-237, Th-232, etc.), which result from major differences between RN of the effects on transport of two phenomena: diffusion and sorption. This paper describes recent research aimed at improving understanding of these two phenomena, focusing on the results of studies carried out during the EC Funmig IP on clayrocks from the above three formations and from the Boda formation (HU). Project results regarding phenomena governing water, cation and anion distribution and mobility in the pore volumes influenced by the negatively-charged surfaces of clay minerals show a convergence of the modelling results for behaviour at the molecular scale and descriptions based on electrical double layer models. Transport models exist which couple ion distribution relative to the clay-solution interface and differentiated diffusive characteristics. These codes are able to reproduce the main trends in behaviour observed experimentally, e.g. D-e(anion) < D-e(HTO) < D-e(cation) and D-e(anion) variations as a function of ionic strength and material density. These trends are also well-explained by models of transport through ideal porous matrices made up of a charged surface material. Experimental validation of these models is good as regards monovalent alkaline cations, in progress for divalent electrostatically-interacting cations (e.g. Sr2+) and still relatively poor for 'strongly sorbing', high K-d cations. Funmig results have clarified understanding of how clayrock mineral composition, and the corresponding organisation of mineral grain assemblages and their associated porosity, can affect mobile solute (anions, HTO) diffusion at different scales (mm to geological formation). In particular, advances made in the capacity to map clayrock mineral grain-porosity organisation at high resolution provide additional elements for understanding diffusion anisotropy and for relating diffusion characteristics measured at different scales. On the other hand, the results of studies focusing on evaluating the potential effects of heterogeneity on mobile species diffusion at the formation scale tend to show that there is a minimal effect when compared to a homogeneous property model. Finally, the results of a natural tracer-based study carried out on the Opalinus Clay formation increase confidence in the use of diffusion parameters measured on laboratory scale samples for predicting diffusion over geological time-space scales. Much effort was placed on improving understanding of coupled sorption-diffusion phenomena for sorbing cations in clayrocks. Results regarding sorption equilibrium in dispersed and compacted materials for weakly to moderately sorbing cations (Sr2+, Cs+, Co2+) tend to show that the same sorption model probably holds in both systems. It was not possible to demonstrate this for highly sorbing elements such as Eu(III) because of the extremely long times needed to reach equilibrium conditions, but there does not seem to be any clear reason why such elements should not have similar behaviour. Diffusion experiments carried out with Sr2+, Cs+ and Eu(III) on all of the clayrocks gave mixed results and tend to show that coupled diffusion-sorption migration is much more complex than expected, leading generally to greater mobility than that predicted by coupling a batch-determined K-d and Ficks law based on the diffusion behaviour of HTO. If the K-d measured on equivalent dispersed systems holds as was shown to be the case for Sr, Cs (and probably Co) for Opalinus Clay, these results indicate that these cations have a D-e value higher than HTO (up to a factor of 10 for Cs+). Results are as yet very limited for very moderate to strongly sorbing species (e.g. Co(II), Eu(III), Cu(II)) because of their very slow transfer characteristics. (C) 2011 Elsevier Ltd. All rights reserved.

Ranibizumab versus verteporfin for neovascular age-related macular degeneration

BACKGROUND: We compared ranibizumab--a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A--with photodynamic therapy with verteporfin in the treatment of predominantly classic neovascular age-related macular degeneration. METHODS: During the first year of this 2-year, multicenter, double-blind study, we randomly assigned patients in a 1:1:1 ratio to receive monthly intravitreal injections of ranibizumab (0.3 mg or 0.5 mg) plus sham verteporfin therapy or monthly sham injections plus active verteporfin therapy. The primary end point was the proportion of patients losing fewer than 15 letters from baseline visual acuity at 12 months. RESULTS: Of the 423 patients enrolled, 94.3% of those given 0.3 mg of ranibizumab and 96.4% of those given 0.5 mg lost fewer than 15 letters, as compared with 64.3% of those in the verteporfin group (P<0.001 for each comparison). Visual acuity improved by 15 letters or more in 35.7% of the 0.3-mg group and 40.3% of the 0.5-mg group, as compared with 5.6% of the verteporfin group (P<0.001 for each comparison). Mean visual acuity increased by 8.5 letters in the 0.3-mg group and 11.3 letters in the 0.5-mg group, as compared with a decrease of 9.5 letters in the verteporfin group (P<0.001 for each comparison). Among 140 patients treated with 0.5 mg of ranibizumab, presumed endophthalmitis occurred in 2 patients (1.4%) and serious uveitis in 1 (0.7%). CONCLUSIONS: Ranibizumab was superior to verteporfin as intravitreal treatment of predominantly classic neovascular age-related macular degeneration, with low rates of serious ocular adverse events. Treatment improved visual acuity on average at 1 year. (ClinicalTrials.gov number, NCT00061594 [ClinicalTrials.gov].).

[The SPI implant system: clinical experience and one-year results]

The new Swiss implant system SPI became available three years ago and is used in combination with fixed and removable prosthetic reconstructions. In a pilot study the clinical procedures were evaluated and data of prosthetic complications of maintenance service were collected. 25 patients participated in the study with a total of 79 SPI implants during the time period from 2003-2004. 37 implants were located in the maxilla and 42 implants in the mandible. Two implants failed during the healing period, but no loaded implant was lost. Thus, the survival rate was 97.5% (77/79). 44 implants supported a fixed prosthesis, including nine single crowns and 33 implants were used in combination with removable partial denture. Four implants were used with ball anchor retention, 29 with bar support. The ELEMENT implant with the low implant shoulder allows very good esthetics. Prosthetic complications and maintenance service during the first year of function was comparable with other implant systems. Since the design of the abutment screws, healing caps and screwdriver was changed, the system has become easier in its application.

Molecular characterisation of BSR4, a novel bradyzoite-specific gene from Neospora caninum

Here we present the identification and cloning of the NcBSR4 gene, the putative Neospora caninum orthologue to the Toxoplasma gondii TgBSR4 gene. To isolate NcBSR4, genome walking PCR was performed on N. caninum genomic DNA using the expressed sequence tag NcEST3c28h02.y1 sequence, which shares a 44% identity with the TgBSR4 gene, as a framework. Nucleotide sequencing of amplified DNA fragments revealed a single uninterrupted 1227 bp open reading frame that encodes a protein of 408 amino acids with 66% similarity to the TgBSR4 antigen. A putative 39-residue signal peptide was found at the NH2-terminus, followed by a hydrophilic region. At the COOH-terminus, a potential site for a glycosylphosphatidylinositol anchor was identified at amino acid 379. A polyclonal serum against recombinant NcBSR4 protein was raised in rabbits, and immunolabelling demonstrated stage-specific expression of the NcBSR4 antigen in N. caninum bradyzoites produced in vitro and in vivo. Furthermore, RT-PCR analysis showed a slight increase of NcBSR4 transcripts in bradyzoites generated during in vitro tachyzoite-to-bradyzoite stage-conversion, suggesting that this gene is specifically expressed at the bradyzoite stage and that its transcription relies on the switch to this stage.

The Gup1 homologue of Trypanosoma brucei is a GPI glycosylphosphatidylinositol remodelase

Glycosylphosphatidylinositol (GPI) lipids of Trypanosoma brucei undergo lipid remodelling, whereby longer fatty acids on the glycerol are replaced by myristate (C14:0). A similar process occurs on GPI proteins of Saccharomyces cerevisiae where Per1p first deacylates, Gup1p subsequently reacylates the anchor lipid, thus replacing a shorter fatty acid by C26:0. Heterologous expression of the GUP1 homologue of T. brucei in gup1Delta yeast cells partially normalizes the gup1Delta phenotype and restores the transfer of labelled fatty acids from Coenzyme A to lyso-GPI proteins in a newly developed microsomal assay. In this assay, the Gup1p from T. brucei (tbGup1p) strongly prefers C14:0 and C12:0 over C16:0 and C18:0, whereas yeast Gup1p strongly prefers C16:0 and C18:0. This acyl specificity of tbGup1p closely matches the reported specificity of the reacylation of free lyso-GPI lipids in microsomes of T. brucei. Depletion of tbGup1p in trypanosomes by RNAi drastically reduces the rate of myristate incorporation into the sn-2 position of lyso-GPI lipids. Thus, tbGup1p is involved in the addition of myristate to sn-2 during GPI remodelling in T. brucei and can account for the fatty acid specificity of this process. tbGup1p can act on GPI proteins as well as on GPI lipids.

[HbA1c revisited (again and again ...)]

The "International Federation of Clinical Chemistry" (IFCC) has developed a new international reference measurement system as anchor for worldwide standardization of HbA1c determinations. The use of IFCC-referenced methods results in "true" HbA1c-values that are 1 - 2% lower compared to traditional methods. This leads to potential risks of clinical misjudgement. For the evaluation of glycaemic control it is, therefore, important to know the method used, its normal range as well as possibilities of mathematical conversion of results. To reduce the risk of wrong interpretation of results the Swiss Society of Endocrinology and Diabetes recommends that reports of HbA1c clearly indicate whether the values are "IFCC-" or "DCCT-traceable". "IFCC"-results should best be reported in mmol/mol. In addition, the normal range has to be indicated properly.

Intracellular localization of the BCL-2 family member BOK and functional implications

The pro-apoptotic BCL-2 family member BOK is widely expressed and resembles the multi-BH domain proteins BAX and BAK based on its amino acid sequence. The genomic region encoding BOK was reported to be frequently deleted in human cancer and it has therefore been hypothesized that BOK functions as a tumor suppressor. However, little is known about the molecular functions of BOK. We show that enforced expression of BOK activates the intrinsic (mitochondrial) apoptotic pathway in BAX/BAK-proficient cells but fails to kill cells lacking both BAX and BAK or sensitize them to cytotoxic insults. Interestingly, major portions of endogenous BOK are localized to and partially inserted into the membranes of the Golgi apparatus as well as the endoplasmic reticulum (ER) and associated membranes. The C-terminal transmembrane domain of BOK thereby constitutes a 'tail-anchor' specific for targeting to the Golgi and ER. Overexpression of full-length BOK causes early fragmentation of ER and Golgi compartments. A role for BOK on the Golgi apparatus and the ER is supported by an abnormal response of Bok-deficient cells to the Golgi/ER stressor brefeldin A. Based on these results, we propose that major functions of BOK are exerted at the Golgi and ER membranes and that BOK induces apoptosis in a manner dependent on BAX and BAK.

Single-Molecule Conductance of Functionalized Oligoynes: Length Dependence and Junction Evolution

We report a combined experimental and theoretical investigation of the length dependence and anchor group dependence of the electrical conductance of a series of oligoyne molecular wires in single-molecule junctions with gold contacts. Experimentally, we focus on the synthesis and properties of diaryloligoynes with n = 1, 2, and 4 triple bonds and the anchor dihydrobenzo[b]thiophene (BT). For comparison, we also explored the aurophilic anchor group cyano (CN), amino (NH2), thiol (SH), and 4-pyridyl (PY). Scanning tunneling microscopy break junction (STM-BJ) and mechanically controllable break junction (MCBJ) techniques are employed to investigate single-molecule conductance characteristics. The BT moiety is superior as compared to traditional anchoring groups investigated so far. BT-terminated oligoynes display a 100% probability of junction formation and possess conductance values which are the highest of the oligoynes studied and, moreover, are higher than other conjugated molecular wires of similar length. Density functional theory (DFT)-based calculations are reported for oligoynes with n = 1−4 triple bonds. Complete conductance traces and conductance distributions are computed for each family of molecules. The sliding of the anchor groups leads to oscillations in both the electrical conductance and the binding energies of the studied molecular wires. In agreement with experimental results, BT-terminated oligoynes are predicted to have a high electrical conductance. The experimental attenuation constants βH range between 1.7 nm−1 (CN) and 3.2 nm−1 (SH) and show the following trend: βH(CN) < βH(NH2) < βH(BT) < βH(PY) ≈ βH(SH). DFT-based calculations yield lower values, which range between 0.4 nm−1 (CN) and 2.2 nm−1 (PY).

Balancing on a slackline: 8-year-olds vs. adults

Children are less stable than adults during static upright stance. We investigated whether the same holds true for a task that was novel for both children and adults and highly dynamic: single-legged stance on a slackline. We compared 8-year-olds with young adults and assessed the following outcome measures: time on the slackline, stability on the slack-line (calculated from slackline reaction force), gaze movement, head-in-space rotation and translation, trunk-in-space rotation, and head-on-trunk rotation. Eight-year-olds fell off the slackline quicker and were generally less stable on the slackline than adults. Eight-year-olds also showed more head-in-space rotation and translation, and more gaze variability around a visual anchor point they were instructed to fixate. Trunk-in-space and head-on-trunk rotations did not differ between groups. The results imply that the lower postural stability of 8-year-olds compared to adults – as found in simple upright stance – holds true for dynamic, novel tasks in which adults lack the advantage of more practice. They also suggest that the lack of head and gaze stability constitutes an important limiting factor in children’s ability to master such tasks

Novel prototype sewing device, EndoSew ® , for minimally invasive surgery: an extracorporeal ileal conduit construction pilot study in 10 patients

What's known on the subject? and What does the study add? The EndoSew® prototype was first tested in a porcine model several years ago. The investigators found it both simple to master and reliable, its greatest advantage being a 2.4-fold time saving compared with straight laparoscopic suturing. In addition to that publication, there is a single case report describing the performance of an open EndoSew® suture to close parts (16 cm) of an ileal neobladder. The time for suturing the 16 cm ileum was 25 min, which is in line with our experience. The knowledge on this subject is limited to these two publications. We report on the first consecutive series of ileal conduits performed in humans using the novel prototype sewing device EndoSew®. The study shows that the beginning and the end of the suture process represent the critical procedural steps. It also shows that, overall, the prototype sewing machine has the potential to facilitate the intracorporeal suturing required in reconstructive urology for construction of urinary diversions. Objective To evaluate the feasibility and safety of the novel prototype sewing device EndoSew® in placing an extracorporeal resorbable running suture for ileal conduits. Patients and Methods We conducted a prospective single-centre pilot study of 10 consecutive patients undergoing ileal conduit, in whom the proximal end of the ileal conduit was closed extracorporeally using an EndoSew® running suture. The primary endpoint was the safety of the device and the feasibility of the sewing procedure which was defined as a complete watertight running suture line accomplished by EndoSew® only. Watertightness was assessed using methylene blue intraoperatively and by loopography on postoperative days 7 and 14. Secondary endpoints were the time requirements and complications ≤30 days after surgery. Results A complete EndoSew® running suture was feasible in nine patients; the suture had to be abandoned in one patient because of mechanical failure. In three patients, two additional single freehand stitches were needed to anchor the thread and to seal tiny leaks. Consequently, all suture lines in 6/10 patients were watertight with EndoSew® suturing alone and in 10/10 patients after additional freehand stitches. The median (range) sewing time was 5.5 (3–10) min and the median (range) suture length was 4.5 (2–5.5) cm. There were no suture-related complications. Conclusions The EndoSew® procedure is both feasible and safe. After additional freehand stitches in four patients all sutures were watertight. With further technical refinements, EndoSew® has the potential to facilitate the intracorporeal construction of urinary diversions.

Traverse: Energie. Erzeugung, Verbreitung und Nutzung im 19. und 20. Jahrhundert

Energie ist eine der wichtigsten Ressourcen der Gegenwart. Wir nutzen sie täglich zum Heizen, Kochen, Beleuchten, Fortbewegen, Arbeiten. Neben der Endlichkeit der fossilen Energieträger rückten in den letzten Jahren auch die mit den Energieregimen verbundenen Risiken (wieder) vermehrt ins Bewusstsein. Gerade deshalb erlebte besonders die Energiegeschichte zum 20. Jahrhundert jüngst einen Aufschwung. Die einzelnen Beiträge zeichnen dabei nicht nur den ungestillten Energiehunger während des Wirtschaftsbooms nach dem Zweiten Weltkrieg nach, sondern gehen auch den Wurzeln des heutigen Energieregimes im 19. Jahrhundert nach. Thematisiert werden die wichtigsten Triebkräfte der Innovationen in der Wasserkraft, die Entwicklungslinien der Energieverwendung und des Energieverbrauchs im Verkehr und in der Landwirtschaft sowie die Auswirkungen eines mehrtägigen Stromausfalls auf die Gesellschaft.