混合动力汽车对功率模块稳定性的要求

汽车用功率半导体模块的的使用寿命取决于其工作环境和基于运行工况对其提出的稳定性要求。为了评估用于混合动力汽车（HEV）功率半导体模块所具备的热循环、功率循环能力,使用了汽车行驶工况循环曲线来计算模块的热可靠性要求。这种计算是基于模块损耗、热仿真模型和模块寿命模型。本文通过将功率模块连接至不同的冷却系统,探讨了主动／被动热应力条件下,诸如IGBT芯片焊接或绑定线连接等键合点。     

N-Hydroxysuccinimide-Modified Ethynylphosphonamidates Enable the Synthesis of Configurationally Defined Protein Conjugates

Herein, the application of N-hydroxysuccinimide-modified phosphonamidate building blocks for the incorporation of cysteine-selective ethynylphosphonamidates into lysine residues of proteins, followed by thiol addition with small molecules and proteins, is reported. It is demonstrated that the building blocks significantly lower undesired homo-crosslinking side products that can occur with commonly applied succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC) under physiological pH. The previously demonstrated stability of the phosphonamidate moiety additionally solves the problem of premature maleimide hydrolysis, which can hamper the efficiency of subsequent thiol addition. Furthermore, a method to separate the phosphonamidate enantiomers to be able to synthesize protein conjugates in a defined configuration has been developed. Finally, the building blocks are applied to the construction of functional antibody–drug conjugates, analogously to FDA-approved, SMCC-linked Kadcyla, and to the synthesis of a functional antibody–protein conjugate.     

Verwendung von Schottersäulen bei Setzungen und für Verflüssigung anfälligen Böden

The use of stone columns on settlement and liquefaction susceptible soils. The new Paradisus Coco Beach Resort in Rio Grande (Puerto Rico) is located on an old swamp area which has been filled with relatively clean to silty sands. The swampy deposits consist of organic silts, peat and loose fine to medium sand and silty sand. The project required the placement of 1.0 to 1.5 meters of additional fill together with the construction of light structures. The need for the fill triggers the development of settlements in the underlaying weak and compressible stratum. Furthermore, the susceptibility of the loose sand to liquefaction during an earthquake was considered. This paper describes the soil improvement by means of vibro‐replacement, the purpose of which was threefold: reduction in total and differential settlement, acceleration of settlements during the surcharge period and densification of the loose sand to reduce its liquefaction potential. The predesign is presented together with relevant construction details of the preliminary trial areas from which the final column diameter and grid spacing were derived. Instrumentation together with settlement observations during the surcharge period are presented as well and compared with the initial predictions. Finally an analysis of the results was done with the program DC‐Vibro (DC‐Software GmbH) for the verification of the results following the approach of Priebe.     

"Signaling in expository hypertexts compensates for deficits in reading skill": Correction to Naumann et al. (2007).

Reports an error in "Signaling in expository hypertexts compensates for deficits in reading skill" by Johannes Naumann, Tobias Richter, Jürgen Flender, Ursula Christmann and Norbert Groeben (Journal of Educational Psychology, 2007[Nov], Vol 99[4], 791-807). The URL published for the supplemental material was incorrect. The correct URL is provided in the erratum. (The following abstract of the original article appeared in record 2007-17712-008.) Expository hypertexts may contain specific types of signals such as navigable topical overviews and hyperlinks that map conceptual relationships between text contents. Two experiments with German university students (N = 130, 75% female, mean age 25 years) were conducted to test the hypothesis that hypertext-specific signals particularly support learners with badly routinized reading skills in organizing and integrating complex learning materials. The experiments were based on naturalistic texts and essay-writing tasks typical for exam preparation. Learning outcomes were measured by characteristics of participants' essays (amount of knowledge, knowledge focusing, knowledge integration). In both experiments, a hypertext with a high amount of signaling yielded better learning outcomes than did a linear text for readers with a low level of skill, whereas there were no differences for readers with a high level of skill (ΔR2 from .03 to .08 for the interaction). In Experiment 2, the same interaction pattern was found for hypertext with a high versus a low amount of hypertext-specific signals (ΔR2 from .04 to .10). Moreover, a lack of signals led to less efficient navigation behavior. These results demonstrate that hypertexts equipped with hypertext-specific signals may compensate for deficits in reading skill. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Protein Corona Mediated Stealth Properties of Biocompatible Carbohydrate-based Nanocarriers

Carbohydrates possess ideal properties for the synthesis of biocompatible nanocarriers. Therefore, hydroxyethyl starch was chosen as building material to produce biodegradable nanocarriers allowing the encapsulation of drugs. A mandatory feature for the successful application of nanocarriers in drug delivery is to avoid non-specific uptake into macrophages. Todays’ gold standard is poly(ethylene glycol) (PEG) attached onto the surface of nanocarriers. As alternatives, we synthesize completely carbohydrate-based nanocarriers by functionalizing the surface with different sugar derivatives (hydroxyethyl starch, dextran, or glucose) via copper-free click reaction. Studying the interaction of sugar-modified nanocarriers and plasma proteins indicates a strong enrichment of adsorbed ‘stealth’ proteins (clusterin) which are also identified on PEGylated nanocarriers. Cellular uptake studies proved that there is no unspecific interaction between carbohydrate- modified nanocarriers and phagocytic cells, herby underlining the stealth properties.     

A robust estimator for the tail index of Pareto-type distributions

In extreme value statistics, the extreme value index is a well-known parameter to measure the tail heaviness of a distribution. Pareto-type distributions, with strictly positive extreme value index (or tail index) are considered. The most prominent extreme value methods are constructed on efficient maximum likelihood estimators based on specific parametric models which are fitted to excesses over large thresholds. Maximum likelihood estimators however are often not very robust, which makes them sensitive to few particular observations. Even in extreme value statistics, where the most extreme data usually receive most attention, this can constitute a serious problem. The problem is illustrated on a real data set from geopedology, in which a few abnormal soil measurements highly influence the estimates of the tail index. In order to overcome this problem, a robust estimator of the tail index is proposed, by combining a refinement of the Pareto approximation for the conditional distribution of relative excesses over a large threshold with an integrated squared error approach on partial density component estimation. It is shown that the influence function of this newly proposed estimator is bounded and through several simulations it is illustrated that it performs reasonably well at contaminated as well as uncontaminated data.     

Probing 2H-Indazoles as Templates for SGK1, Tie2, and SRC Kinase Inhibitors

The broader and systematic application of a novel scaffold is often hampered by the unavailability of a short and reliable synthetic access. We investigated a new strategy for the design and synthesis of an array of N2-substituted aza-2H-indazole derivatives as potential kinase inhibitors. Guided by a rational ligand alignment approach to qualify the so-far underrepresented aza-2H-indazole scaffold, indazoles were connected at the N2 position with a phenyl spacer and an arylsulfonamide or amide linkage. Initial profiling against a panel of 30 kinases confirmed the in silico predicted selectivity bias. A synthesized focused library of 52 different aza-2H-indazole derivatives showed good initial selective inhibition against SGK1, Tie2, and SRC kinases, with the best representatives having IC₅₀ values in the range of 500 nm . In a comparative computational study, these data were analyzed and rationalized in light of docking studies.     

The cystine knot of a squash-type protease inhibitor as a structural scaffold for Escherichia coli cell surface display of conformationally constrained peptides

The Ecballium elaterium trypsin inhibitor II (EETI-II), a memberof the squash family of protease inhibitors, is composed of28 amino acid residues and is a potent inhibitor of trypsin.Its compact structure is defined by a triple-stranded antiparallelß-sheet, which is held together by three intramoleculardisulfide bonds forming a cystine knot. In order to explorethe potential of the EETI-II peptide to serve as a structuralscaffold for the presentation of randomized oligopeptides, weconstructed two EETI-II derivatives, where the six-residue inhibitorloop was replaced by a 13-residue epitope of Sendai virus L-proteinand by a 17-residue epitope from human bone Gla-protein. EETI-IIand derived variants were produced via fusion to maltose bindingprotein MalE. By secretion of the fusion into the periplasmicspace, fully oxidized and correctly folded EETI-II was obtainedin high yield. EETI-II and derived variants could be presentedon the Escherichia coli outer membrane by fusion to truncatedLpp'–OmpA', which comprises the first nine residues ofmature lipoprotein plus the membrane spanning ß-strandfrom residues 46–66 of OmpA protein. Gene expression wasunder control of the strong and tightly regulated tetA promoter/operator.Cell viability was found to be drastically reduced by high levelexpression of Lpp'–OmpA'–EETI-II fusion protein.To restore cell viability, net accumulation of fusion proteinin the outer membrane was reduced to a tolerable level by introductionof an amber codon at position 9 of the lpp' sequence and utilizingan amber suppressor strain as expression host. Cells expressingEETI-II variants containing an epitope were shown to be surfacelabeled with the respective monoclonal antibody by indirectimmunofluorescence corroborating the cell surface exposure ofthe epitope sequences embedded in the EETI-II cystine knot scaffold.Cells displaying a particular epitope sequence could be enriched10⁷-fold by combining magnetic cell sorting with fluorescence-activatedcell sorting. These results demonstrate that E.coli cell surfacedisplay of conformationally constrained peptides tethered tothe EETI-II cystine knot scaffold has the potential to becomean effective technique for the rapid isolation of small peptidemolecules from combinatorial libraries that bind with high affinityto acceptor molecules.