Critical review of models for H2-permeation through polymers with focus on the differential pressure method

To reduce loss of hydrogen in storage vessels with high energy-to-weight-ratio, new materials, especially polymers, have to be developed as barrier materials. Very established methods for characterization of barrier materials with permeation measurements are the time-lag and flow rate method along with the differential pressure method, which resembles the nature of hydrogen vessel systems very well. Long measurement durations are necessary to gain suitable measurement data for these evaluation methods, and often restrictive conditions have to be fullfilled. For these reasons, common models for hydrogen permeation through single-layer and multi-layer membranes, as well as models for hydrogen gas properties were collected and reviewed. Using current computer power together with these models can reduce measurement time for characterization of the barrier properties of materials, while additional information about the quality of the measurement results is obtained.     

Design and Characterization of a New pVII Combinatorial Phage Display Peptide Library for Protease Substrate Mining Using Factor VII Activating Protease (FSAP) as Model

We describe a novel, easy and efficient combinatorial phage display peptide substrate-mining method to map the substrate specificity of proteases. The peptide library is displayed on the pVII capsid of the M13 bacteriophage, which renders pIII necessary for infectivity and efficient retrieval, in an unmodified state. As capture module, the 3XFLAG was chosen due to its very high binding efficiency to anti-FLAG mAbs and its independency of any post-translational modification. This library was tested with Factor-VII activating protease (WT-FSAP) and its single-nucleotide polymorphism variant Marburg-I (MI)-FSAP. The WT-FSAP results confirmed the previously reported Arg/Lys centered FSAP cleavage site consensus as dominant, as well as reinforcing MI-FSAP as a loss-of-function mutant. Surprisingly, rare substrate clones devoid of basic amino acids were also identified. Indeed one of these peptides was cleaved as free peptide, thus suggesting a broader range of WT-FSAP substrates than previously anticipated.     

Stray current-induced corrosion in cathodic protection installations of steel-reinforced concrete structures: FEM study of the critical parameters

A wide range of parameters was investigated by numerical calculations concerning their impact on DC stray current corrosion of reinforced concrete (RC) structures. A simplified model geometry was used to extract the relevant parameters and their interaction in terms of stray current-affected structures. This study mainly focuses on RC structures that are fitted with cathodic protection installations. The findings reveal a complex interaction between the investigated parameters. The possible relevance of further parameters, which is not the subject of this study, was emphasised.     

Chemotherapy response of pancreatic cancer by diffusion-weighted imaging (DWI) and intravoxel incoherent motion DWI (IVIM-DWI) in an orthotopic mouse model

Magnetic Resonance Materials in Physics, Biology and Medicine - To investigate the value of using diffusion-weighted imaging (DWI) and intravoxel incoherent motion DWI (IVIM-DWI) to assess the...     

0.18μm铜金属双重镶嵌工艺中空间成像套刻精度分析

由于空间成像套刻(Overlay)技术的预算随集成电路(IC)设计规范的紧缩而吃紧,因此,Overlay测量技术准确度的重要意义也随之提高。通过对后开发(AfterDevelopDI)阶段和后蚀刻(AfterEtchFI)阶段的Overlay测量结果进行比较,研究了0.18μm设计规范下的铜金属双重镶嵌工艺过程中的Overlay准确度。在确保对同一个晶圆进行后开发(DI)阶段和后蚀刻(FI)阶段测试的条件下,我们对成品晶圆的5个工艺层进行了比较。此外,还利用CD-SEM(线宽-扫描电子显微镜)测量了某个工艺层(PolyGate)上的芯片内Overlay,并与采用分割线方法的光学Overlay测量结果进行了比较。发现对芯片内overlay的校准存在着严重的局限性,即在应用CD-SEM时缺乏合适的结构进行Overlay测量。我们还将继续为大家提供定量的比较结果,同时也会向大家推荐组合的CD-SEM测量结构,使其能够被应用到今后的光刻设计中。     

Extraction of heavy metals from soils using biodegradable chelating agents

Metal pollution of soils is widespread across the globe, and the clean up of these soils is a difficulttask. One possible remediation technique is ex-situ soil washing using chelating agents. Ethylenediaminetetraacetic acid (EDTA) is a very effective chelating agent for this purpose but has the disadvantage that it is quite persistent in the environment due to its low biodegradability. The aim of our work was to investigate the biodegradable chelating agents [S,S]-ethylenediaminedisuccinic acid (EDDS), iminodisuccinic acid (IDSA), methylglycine diacetic acid (MGDA), and nitrilotriacetic acid (NTA) as potential alternatives and compare them with EDTA for effectiveness. Kinetic experiments showed for all metals and soils that 24 h was the optimum extraction time. Longer times only gave minor additional benefits for heavy metal extraction but an unwanted increase in iron mobilization. For Cu at pH 7, the order of the extraction efficiency for equimolar ratios of chelating agent to metal was EDDS > NTA> IDSA > MGDA > EDTA and for Zn it was NTA > EDDS > EDTA >MGDA > IDSA. The comparatively low efficiency of EDTA resulted from competition between the heavy metals and co-extracted Ca. For Pb the order of extraction was EDTA > NTA >EDDS due to the much stronger complexation of Pb by EDTA compared to EDDS. At higher concentration of complexing agent, less difference between the agents was found and less pH dependence. There was an increase in heavy metal extraction with decreasing pH, but this was offset by an increase in Ca and Fe extraction. In sequential extractions EDDS extracted metals almost exclusively from the exchangeable, mobile, and Mn-oxide fractions. We conclude that the extraction with EDDS at pH 7 showed the best compromise between extraction efficiency for Cu, Zn, and Pb and loss of Ca and Fe from the soil.     

RAFT-derived polymer-drug conjugates: poly(hydroxypropyl methacrylamide) (HPMA)-7-ethyl-10-hydroxycamptothecin (SN-38) conjugates

A series of well‐defined polymer–drug conjugates were prepared in order to modify the physical properties of a known cytotoxic drug, 7‐ethyl‐10‐hydroxycamptothecin (SN‐38), the active metabolite of irinotecan (CPT‐11). Reversible addition–fragmentation chain transfer (RAFT) polymerisation was used to covalently and site‐specifically append a defined N‐(2‐hydroxypropyl)methacrylamide (HPMA) polymer to SN‐38 using a graft‐from process. These poly‐HPMA–SN‐38 conjugates displayed excellent aqueous solubility and stability, whilst retaining the cytotoxic activity of the parent SN‐38. In vitro co‐culture assays containing both cancer and noncancer cell lines demonstrated the specificity of RAFT‐derived poly‐HPMA–SN‐38 conjugates for cancerous cells. The concept of post‐optimisation modification of small‐molecule drugs through a graft‐from polymer conjugation method is introduced.     

Rheology and colloidal structure of silver nanoparticles dispersed in diethylene glycol

Rheological behavior of agglomerated silver nanoparticles (~ 40 nm) suspended in diethylene glycol over a wide range of volumetric solids concentrations (? = 0.11–4.38%) was studied. The nanoparticle suspensions generally exhibited a yield pseudoplastic behavior. Bingham plastic, Herschel–Bulkley and Casson models were used to evaluate the shear stress-shear rate dependency. Analyzing the effect of silver concentrations on the yield stress and viscosity of the suspensions followed an exponential form, revealing an increase in the degree of interparticle interactions with increasing solid concentrations. Fractal dimension (D_f) was estimated from the suspension yield stress and ? dependence, and was determined as D_f = 1.51–1.62 for the flocculated nanoparticle suspensions. This suggested that the suspension structure was probably dominated by the diffusion-limited cluster–cluster aggregation (DLCA) due mostly to the strong attractions involved in the interparticle potentials. Maximum solids concentration of the suspensions was determined to be ?_m = 11%.     

Design of a General‐Purpose European Compound Screening Library for EU‐OPENSCREEN

This work describes a collaborative effort to define and apply a protocol for the rational selection of a general‐purpose screening library, to be used by the screening platforms affiliated with the EU‐OPENSCREEN initiative. It is designed as a standard source of compounds for primary screening against novel biological targets, at the request of research partners. Given the general nature of the potential applications of this compound collection, the focus of the selection strategy lies on ensuring chemical stability, absence of reactive compounds, screening‐compliant physicochemical properties, loose compliance to drug‐likeness criteria (as drug design is a major, but not exclusive application), and maximal diversity/coverage of chemical space, aimed at providing hits for a wide spectrum of drugable targets. Finally, practical availability/cost issues cannot be avoided. The main goal of this publication is to inform potential future users of this library about its conception, sources, and characteristics. The outline of the selection procedure, notably of the filtering rules designed by a large committee of European medicinal chemists and chemoinformaticians, may be of general methodological interest for the screening/medicinal chemistry community. The selection task of 200K molecules out of a pre‐filtered set of 1.4M candidates was shared by five independent European research groups, each picking a subset of 40K compounds according to their own in‐house methodology and expertise. An in‐depth analysis of chemical space coverage of the library serves not only to characterize the collection, but also to compare the various chemoinformatics‐driven selection procedures of maximal diversity sets. Compound selections contributed by various participating groups were mapped onto general‐purpose self‐organizing maps (SOMs) built on the basis of marketed drugs and bioactive reference molecules. In this way, the occupancy of chemical space by the EU‐OPENSCREEN library could be directly compared with distributions of known bioactives of various classes. This mapping highlights the relevance of the selection and shows how the consensus reached by merging the five different 40K selections contributes to achieve this relevance. The approach also allows one to readily identify subsets of target‐ or target‐class‐oriented compounds from the EU‐OPENSCREEN library to suit the needs of the diverse range of potential users. The final EU‐OPENSCREEN library, assembled by merging five independent selections of 40K compounds from various expert groups, represents an excellent example of a Europe‐wide collaborative effort toward the common objective of building best‐in‐class European open screening platforms.     

Discovery of a Short‐Chain Dehydrogenase from Catharanthus roseus that Produces a New Monoterpene Indole Alkaloid

Plant monoterpene indole alkaloids, a large class of natural products, derive from the biosynthetic intermediate strictosidine aglycone. Strictosidine aglycone, which can exist as a variety of isomers, can be reduced to form numerous different structures. We have discovered a short‐chain alcohol dehydrogenase (SDR) from plant producers of monoterpene indole alkaloids (Catharanthus roseus and Rauvolfia serpentina) that reduce strictosidine aglycone and produce an alkaloid that does not correspond to any previously reported compound. Here we report the structural characterization of this product, which we have named vitrosamine, as well as the crystal structure of the SDR. This discovery highlights the structural versatility of the strictosidine aglycone biosynthetic intermediate and expands the range of enzymatic reactions that SDRs can catalyse. This discovery further highlights how a sequence‐based gene mining discovery approach in plants can reveal cryptic chemistry that would not be uncovered by classical natural product chemistry approaches.