Einfluß der Segmentstruktur und der Vernetzung auf den Glasübergang Tg. Möglichkeiten der Vorausberechnung von Tg über die Kohäsionsenergie Ecoh

Linear polymers, particularly polyesters, and crosslinked epoxide systems were studied to determine the relationship between glass transition, T_g, and cohesive energy, E_coh, which was calculated from incremental values as described by Fedors. In the case of thermoplastics having no side chains and in the absence of pronounced intermolecular interactions, it was found that standardization of E_coh with reference to the number of structural elements capable of rather independent motions leads to a linear relationship between T_g, and E_coh from which T_g, can be predicted. Without modifying our equation to suit the polymer, the influence of substituents and side chains can as yet only be assessed when they form a small part of the total segment. In the case of crosslinked epoxide systems, addition of the contribution made by crosslinking to the value of T_g, for the uncured polymer calculated from E_coh results in a shift to higher T_g, values. In linear aliphatic polyamides and other polymers with analogous structure the formation of hydrogen bonds leads to an increase in T_g, comparable to the effect of chemical crosslinking. Reinforcing fillers also act as multifunctional crosslinks between the macromolecules and increase T_g. Just as E_coh can be used to calculate T_g, experimentally readily ascertainable T_g values can be used to calculate E_coh. This approach provides information on material properties like flexural strength at the yield point and torsional adhesive strength as well as on the effect of reinforcing fillers.     

The importance of dietary carbohydrates

Forty years ago carbohydrates (CHO) were regarded as a simple energy source whereas they are now recognized as important food components. The human diet contains a wide range of CHO, the vast majority of which are of plant origin. Modern techniques based on chemical classification of dietary CHO replaced the traditional "by difference" measurement. They provide a logical basis for grouping into categories of specific nutritional importance. The physiological effects of dietary CHO are highly dependent on the rate and extent of digestion and absorption in the small intestine and fermentation in the large intestine, interactions which promote human health. Current knowledge of the fate of dietary CHO means that the potentially undesirable properties of many modern foods could be altered by using processing techniques that yield foods with more intact plant cell wall structures. Such products would more closely resemble the foods in the pre-agriculture diet with respect to the rate of digestion and absorption of CHO in the small intestine. The potentially detrimental physiological consequences of eating sugars and starch that are rapidly digested and absorbed in the small intestine suggest that, as fibre, the form, as well as the amount of starch should be considered. Increasing consumer awareness of the relationship between diet and health has led to demands for more widespread nutrition labelling. The entry "carbohydrate" is required in most countries, and the value is usually obtained "by difference" and used in the calculation of energy content. However, the value provides no nutritional information per se. Food labels should provide values that aid consumers in selecting a healthy diet.     

Injection Moulding: Evaluation of Appropriate Melt Injection Points for the Gas Injection Technique

In gas assisted injection moulding the melt front advancement has a considerable effect on the gas penetration. The evaluation of an appropriate melt filling is an important step to avoid instabilities in the process sequence. Taking a sample moulded part a procedure is presented that enables the part designer to evaluate required melt and gas injection points according to the gas injection technique. Using finite element simulations, different calculations for the melt front advancement lead to the correct gate location.

Presentation of different degrees of filling for the optimised article geometry.     

The backward Monte Carlo method for semiconductor device simulation

A backward Monte Carlo method for the numerical solution of the semiconductor Boltzmann equation is presented. The method is particularly suited to simulate rare events. The general theory of the backward Monte Carlo method is described, and several estimators for the contact current are derived from that theory. The transition probabilities for the construction of the backward trajectories are chosen so as to satisfy the principle of detailed balance. This property guarantees stability of the numerical method and allows for a clear physical interpretation of the estimators. A symmetric sampling method which generates wave vectors always in pairs symmetric to the origin can be shown to yield zero current exactly as thermal equilibrium is approached. The properties of the different estimators are evaluated by simulation of an n-channel MOSFET. Quantities varying over many orders of magnitude can be resolved with ease. Such quantities are the drain current in the sub-threshold region, the high-energy tail of the carrier distribution function, and the so-called acceleration integral which varies over 30 orders in the example shown.     

Chemical Approach to Biological Safety: Molecular‐Level Control of an Integrated Zinc Finger Nuclease

Application of artificial nucleases (ANs) in genome editing is still hindered by their cytotoxicity related to off‐target cleavages. This problem can be targeted by regulation of the nuclease domain. Here, we provide an experimental survey of computationally designed integrated zinc finger nucleases, constructed by linking the inactivated catalytic centre and the allosteric activator sequence of the colicin E7 nuclease domain to the two opposite termini of a zinc finger array. DNA specificity and metal binding were confirmed by electrophoretic mobility shift assays, synchrotron radiation circular dichroism spectroscopy, and nano‐electrospray ionisation mass spectrometry. In situ intramolecular activation of the nuclease domain was observed, resulting in specific cleavage of DNA with moderate activity. This study represents a new approach to AN design through integrated nucleases consisting of three (regulator, DNA‐binding, and nuclease) units, rather than simple chimera. The optimisation of such ANs could lead to safe gene editing enzymes.     

DNA Primer Extension with Cyclopropenylated 7‐Deaza‐2′‐deoxyadenosine and Efficient Bioorthogonal Labeling in Vitro and in Living Cells

A deoxyadenosine triphosphate (dATP) analogue for DNA labeling was synthesized with the 1‐methylcyclopropene (1MCP) group at the 7‐position of 7‐deaza‐2′‐deoxyadenosine and applied for primer extension experiments. The real‐time kinetic data reveals that this 1MCP‐modified dATP analogue is incorporated into DNA much faster than that of the similarly 1MCP‐modified deoxyuridine triphosphate (dUTP) analogue. The postsynthetic fluorescent labeling of these oligonucleotides works efficiently according to PAGE analysis, and can be applied for immobilization of a functional antibody on a surface. Site‐specific labeling at two different positions in DNA was achieved and the bioorthogonality of the postsynthetic fluorescent labeling was demonstrated in living HeLa cells.     

Synthetic Indolactam V Analogues as Inhibitors of PAR2‐Induced Calcium Mobilization in Triple‐Negative Breast Cancer Cells

Human proteinase‐activated receptor 2 (PAR2), a transmembrane G‐protein‐coupled receptor (GPCR), is an attractive target for a novel anticancer therapy, as it plays a critical role in cell migration and invasion. Selective PAR2 inhibitors therefore have potential as anti‐metastatic drugs. Knowing that the natural product teleocidin A2 is able to inhibit PAR2 in tumor cells, the goal of the present study was to elaborate structure–activity relationships and to identify potent PAR2 inhibitors with lower activity against the adverse target, protein kinase C (PKC). For this purpose, an efficient gram‐scale total synthesis of indolactam V (i.e., the parent structure of all teleocidins) was developed, and a library of derivatives was prepared. Some compounds were indeed found to exhibit high potency as PAR2 inhibitors at low nanomolar concentrations with improved selectivity (relative to teleocidin A2). The pseudopeptidic fragment bridging the C3 and C4 positions of the indole core proved to be essential for target binding, whereas activity and target selectivity depends on the substituents at N1 or C7. This study revealed novel derivatives that show high efficacy in PAR2 antagonism combined with increased selectivity.     

Synthesis,Characterization, and Initial Biological Evaluation of [99mTc]Tc‐Tricarbonyl‐labeled DPA‐α‐MSH Peptide Derivatives for Potential Melanoma Imaging

α‐Melanocyte stimulating hormone (α‐MSH) derivatives target the melanocortin‐1 receptor (MC1R) specifically and selectively. In this study, the α‐MSH‐derived peptide NAP‐NS1 (Nle‐Asp‐His‐d ‐Phe‐Arg‐Trp‐Gly‐NH₂) with and without linkers was conjugated with 5‐(bis(pyridin‐2‐ylmethyl)amino)pentanoic acid (DPA‐COOH) and labeled with [^99mTc]Tc‐tricarbonyl by two methods. With the one‐pot method the labeling was faster than with the two‐pot method, while obtaining similarly high yields. Negligible trans‐chelation and high stability in physiological solutions was determined for the [^99mTc]Tc‐tricarbonyl–peptide conjugates. Coupling an ethylene glycol (EG)‐based linker increased the hydrophilicity. The peptide derivatives displayed high binding affinity in murine B16F10 melanoma cells as well as in human MeWo and TXM13 melanoma cell homogenates. Preliminary in vivo studies with one of the [^99mTc]Tc‐tricarbonyl–peptide conjugates showed good stability in blood and both renal and hepatobiliary excretion. Biodistribution was performed on healthy rats to gain initial insight into the potential relevance of the ^99mTc‐labeled peptides for in vivo imaging.