Multimerization of cRGD Peptides by Click Chemistry: Synthetic Strategies,Chemical Limitations,and Influence on Biological Properties

Integrin α_νβ₃ is overexpressed on endothelial cells of growing vessels as well as on several tumor types, and so integrin‐binding radiolabeled cyclic RGD pentapeptides have attracted increasing interest for in vivo imaging of α_νβ₃ integrin expression by positron emission tomography (PET). Of the cRGD derivatives available for imaging applications, systems comprising multiple cRGD moieties have recently been shown to exhibit highly favorable properties in relation to monomers. To assess the synthetic limits of the cRGD‐multimerization approach and thus the maximum multimer size achievable by using different efficient conjugation reactions, we prepared a variety of multimers that were further investigated in vitro with regard to their avidities to integrin α_νβ_3. The synthesized peptide multimers containing increasing numbers of cRGD moieties on PAMAM dendrimer scaffolds were prepared by different click chemistry coupling strategies. A cRGD hexadecimer was the largest construct that could be synthesized under optimized reaction conditions, thus identifying the current synthetic limitations for cRGD multimerization. The obtained multimeric systems were conjugated to a new DOTA‐based chelator developed for the derivatization of sterically demanding structures and successfully labeled with ⁶⁸Ga for a potential in vivo application. The evaluated multimers showed very high avidities—increasing with the number of cRGD moieties—in in vitro studies on immobilized α_νβ₃ integrin and U87MG cells, of up to 131‐ and 124‐fold, respectively, relative to the underivatized monomer.     

Novel Silicon-Boron-Carbon-Nitrogen Materials Thermally Stable up to 2200°C

Three novel Si-C-B-N ceramic compositions, namely Si_2.9B_1.0C₁₄N_2.9, Si_3.9B_1.0C₁₁N_3.2 and Si_5.3B_1.0C₁₉N_3.4, were synthesized using the polymer-to-ceramic transformation of the polyorganoborosilazanes [B(C₂H₄Si(Ph)NH)₃]_n, [B(C₂H₄Si(CH₃)NH)₂–(C₂H₄Si(CH₃)N(SiH₂Ph))]_n, and [B(C₂H₄Si(CH₃)–N(SiH₂Ph))₃]_n, where Ph is phenyl (C₆H₅), at 1050°C in argon. The Si-B-C-N ceramics exhibited significant stability with respect to composition and mass change in the temperature range between 1000° and 2200°C, including isothermal annealing of the samples at the final temperature for 30 min in argon. The mass loss rate at 2200°C was as low as 1.4 wt%·h⁻¹ for Si_5.3B_1.0C₁₉N_3.4, 1.7 wt%·h⁻¹ for Si_2.9B_1.0C₁₄N_2.9, and 2.4 wt%·h⁻¹ for Si_3.9B_1.0C₁₁N_3.2. The measured amount of mass loss rate was comparable to that of pure SiC materials. As crystalline phases, β-Si₃N₄ and β-SiC were found exclusively in the samples annealed at 2200°C at 0.1 MPa in argon. For thermodynamic reasons, β-Si₃N₄ should have decomposed into the elements silicon and nitrogen at that particular temperature and gas pressure. However, the presence of β-Si₃N₄ in our materials indicated that carbon and boron kinetically stabilized the Si₃N₄-based composition.     

Morphology of the transparent IPN‐like system PE: (BMA‐co‐S)

In the study of interpenetrating polymer networks (IPN)‐like systems consisting of polyethylene (PE) and butyl methacrylate (BMA)–styrene (S) copolymer PE/(BMA‐co‐S), the effect of the crosslinker on the morphology of IPN by using electron microscopy and atomic force microscopy (AFM) was investigated. The IPN‐like system PE/(BMA‐co‐S) represents a two‐phase system with finely dispersed domains of crosslinked PE matrix. The interphase between dispersed domains and PE matrix is inhomogeneous and is considered the most interpenetrated part of this IPN‐like system. The size of the domains decreases with the content of crosslinker used. The AFM micrographs allowed the observation of PE lamellae with lengths of about 25 nm. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 81: 2615–2620, 2001     

Phase behavior, morphology and interfacial structure in thermoset/thermoplastic elastomer blends of poly(propylene glycol)-type epoxy resin and polystyrene–b-polybutadiene

Thermoset/thermoplastic elastomer (TPE) blends of poly(propylene glycol) (PPG)-type epoxy resin (ER) and a diblock copolymer, polystyrene–b-polybutadiene (SB, with 30% styrene content), were prepared using 4,4′-diaminodiphenylmethane (DDM) as curing agent. The miscibility and thermal transition behavior of DDM-cured ER/SB blends were investigated by differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA). The existence of three separate glass transitions, which are independent of the blend composition, indicates that SB is immiscible with DDM-cured ER. Neither the PS block nor the PB block exhibits miscibility with the cured ER. There exist three phases in the blends: a PS microphase, an ER-rich phase and a PB microphase. The phase structure and morphology of the ER/SB blends were studied using both scanning and transmission electron microscopy (SEM and TEM); a variety of morphologies were observed, depending on the blend composition. For the blends with 5 and 10 wt% SB, SB domains with irregular shapes and broadly distributed sizes are dispersed in a continuous cured ER matrix. For the blends with 20–60 wt% SB, interpenetrating bicontinuous phase structures are observed. For the blends with 70 wt% and more SB, a dispersion of cured ER particles in the SB matrix is obtained. The TEM observation showed that the two phases in the blends exhibit a good interfacial adhesion. The interfacial layer between the ER and SB phases varies from 100 to 300 nm for the blend with 20 wt% SB content, SB micelles are formed surrounding the SB domains in the ER matrix. Small-angle X-ray scattering (SAXS) experiments reveal that the SB diblock polymer still exhibits a lamellar microphase structure within the SB phase and the long spacing of lamellae nearly does not change in the blends. The SB diblock copolymer is microphase separated in the macroscopically phase separated ER/SB blends.     

Planung und Bau einer Autobahnbrücke über den Teltowkanal in Berlin

Design and construction of the motorway bridge over the Teltowkanal in Berlin. In Berlin, the construction of the Autobahn 113 is currently underway. The Autobahn 113 will link Berlin's ring road and the planned new international airport with the orbital autobahn and is one of the city's largest transport infrastructure projects. The new autobahn also crosses the navigable Teltow canal. The main characteristics are the complicated geometry and the unusual structural framework. The twin span bridge is a trough bridge of composite steel structure and supports the entire cross section of the autobahn. The floor plates are exchangeable sections to provide sufficient room for a temporary traffic lane during maintenance work.     

Disperse Amphiphilic Submicron Particles as Non‐Covalent Supports for Cationic Homogeneous Catalysts

A simple method for the effective immobilization of homogeneous catalysts on polystyrene colloids via non‐covalent binding is demonstrated. Stable latices with sufficiently high loading of accessible borate anions are prepared via emulsion polymerization. Incorporation of cationic rhodium complexes, supported via their borate counter‐anion is efficient, and these supported homogeneous catalysts maintain constant catalytic activity for CC hydrogenation during several recycles, with very low metal leaching.     

Influencing factors of horizontal leaders' role identity in projects: A sequential mixed method approach

Horizontal leadership is temporary and often short-term compared with vertical leadership. Therefore, the role identity of horizontal leaders' is more difficult to be legitimated. In this study, we investigated how different factors interact and work in concert to influence horizontal leaders' role identity (hereafter, HLs' role identity). A sequential mixed method approach was chosen to conduct this research. Twenty-four interviews were analysed, and we identified eleven influencing factors associated with HLs' role identity. Subsequently, a sample of 150 questionnaires was analysed by using fuzzy-set qualitative comparative analysis (fsQCA) to ascertain the collective effect of different influencing factors on HLs' strong and weak role identities. The results showed that high job complexity, intrinsic rewards, self-efficacy and personal expectations were the necessary conditions for HLs' strong role identity. The lack of expectations of other team members was the only necessary condition that resulted in HLs' weak role identity. Based on the 13 configurations of HLs' strong and weak role identities that were obtained from this research, we formed an HLs' role identity model. It was found that the expectations of other project team members together with empowerment by project managers are the most common and effective ways to establish HLs' strong role identity. Through a comparison, experienced and less experienced team members take different paths towards a strong or weak role identity. The theoretical and managerial implications are discussed.     

Resources and nutrients oriented greywater treatment for non-potable reuses

This paper evaluated the performance and suitability of a resources and nutrients oriented decentralized greywater treatment system which uses a submerged spiral wound module. This greywater treatment system is aimed at treating and recovering the resources present in the wastewater. The study revealed that the UF membrane filtration system was able to maintain a permeate flux between 6 and 10 L/m2/h. TOC can be reduced from the influent value of 161 to 28.6 mg/L in the permeate, meaning an average elimination rate of 83.4%. In addition, soluble nutrients such as ammonia and phosphorus can pass through the UF membrane and remain in the permeate. The total nitrogen and total phosphorus in the permeate were 16.7 and 6.7 mg/L respectively. The permeate was low in turbidity (below 1 NTU) and free of suspended solids and E. coli and had an excellent physical appearance. The permeate can be used in gardening and agriculture for irrigation and soil fertilization or alternatively for toilet flushing after disinfection. The retentate generated in this system can be treated with blackwater and kitchen waste in an anaerobic digester at a later stage for producing biogas or compost.     

Effects of Wall Vessel Rotation on the Growth of Larval Zebrafish Inner Ear Otoliths

Stimulus dependence is a general feature of developing sensory systems. It has been shown earlier that the growth of otoliths of late-stage Cichlid fish (Oreochromis mossambicus) and Zebrafish (Danio rerio) was slowed down by hypergravity, whereas microgravity during spaceflight yielded an opposite effect, i.e., larger than 1 g otoliths, in Swordtail (Xiphophorus helleri) late-stage embryos. Using ground-based techniques to apply simulated weightlessness, long-term clinorotation (exposure on a fast-rotating clinostat with one axis of rotation for 7 days) led to larger than 1 g otoliths in late-stage Cichlid fish, which is fully in line with the results obtained on Swordtails from spaceflight. Hitherto, early-staged fish have not yet been subjected to (simulated or real) long-term (i.e., more than 3 or 4 days) weightlessness to investigate otolith growth. The present study was carried out in order to fill this gap. Therefore, we subjected Zebrafish at a somite-stage to Wall Vessel Rotation (WVR; a method regarded to provide simulated weightlessness), when the anlage of the inner ear already is present (10 h post fertilisation, hpf). Siblings were maintained under WVR for 3, 6, 9 and 12 days. Further short-term experiments (3 days) were carried out on 10 hpf animals as well as on very early larvae (1 K cell stage, 3 hpf) at two different rotation speeds. WVR (both rotation speeds) had no effect on otolith biogenesis in both stages as all otoliths were present after the experiments. In comparison with 1 g controls, WVR had significantly increased otolith growth (normalised by fish length) after 3 and 6 days of exposure, but significant differences of otolith growth between experimental animals and controls were not found after 9 and 12 days. In conclusion, WVR (at least within a time-span of exposure of up to 6 days) brings, comparable to the situation in real microgravity, a kind of feedback mechanism into action, resulting in larger otoliths. Later, possible effects of WVR might be overruled by normal allometric growth since the action of the feedback mechanism may be discontinued in the course of an adaptation.