Suzuki–Miyaura Cross‐Coupling under Solvent‐Free Conditions

A solvent‐free reaction protocol for Suzuki–Miyaura cross‐couplings was developed. (Hetero)aryl bromides and chlorides are coupled with pinacol arylboronates in high yields. The reaction is catalyzed by conventional bis(triphenylphosphine)palladium(II) chloride [(PPh₃)₂PdCl₂] and/or palladium(II) acetate/SPhos [Pd(OAc)₂/SPhos] under air.

     

Quality Considerations for the Evaluation of Thermal Spray Coatings

Revealing the true structural and mechanical properties is of utmost importance for the optimized use of thermal sprayed coatings. Only the true properties can be expected to correlate to the spray parameters. During the recent decade, the gas turbine industry has experienced a focus on the laboratory procedures being the weakest link in a frozen and robust process. This article will show several results indicating that the laboratory procedures are more essential to the evaluation results than the spray parameters themselves. With new and robust laboratory techniques, the true properties of thermal spray coatings are revealed, causing a major problem with respect to the quality standards developed 30-40 years ago. In many cases, these old specifications need updates, which is a difficult task from a cost, time, and quality perspective for OEM’s. Coatings that have been successfully used for almost half a century no longer conform to the specification they were optimized to, because of these new appropriate laboratory techniques and procedures. What is actually meant when stating the following? (1) The coating has 5% porosity; (2) No cracks are allowed; (3) Tensile bond is 50 Mpa; (4) Hardness is 1000 HV; and (5) Coating thickness is 100 μm. This article also initiates a discussion on the measurement inaccuracies, for testing of thermally sprayed coatings, with respect to the commonly used general international standards (such as QS9000, ISO17025, AS9003, and ISO10012), as well as with respect to recommendations from the Six Sigma methodology.     

Complete Reaction Phenotyping of Propranolol and 4-Hydroxypropranolol with the 19 Enzymes of the Human UGT1 and UGT2 Families

Propranolol is a competitive non-selective beta-receptor antagonist that is available on the market as a racemic mixture. In the present study, glucuronidation of propranolol and its equipotent phase I metabolite 4-hydroxypropranolol by all 19 members of the human UGT1 and UGT2 families was monitored. UGT1A7, UGT1A9, UGT1A10 and UGT2A1 were found to glucuronidate propranolol, with UGT1A7, UGT1A9 and UGT2A1 mainly acting on (S)-propranolol, while UGT1A10 displays the opposite stereoselectivity. UGT1A7, UGT1A9 and UGT2A1 were also found to glucuronidate 4-hydroxypropranolol. In contrast to propranolol, 4-hydroxypropranolol was found to be glucuronidated by UGT1A8 but not by UGT1A10. Additional biotransformations with 4-methoxypropanolol demonstrated different regioselectivities of these UGTs with respect to the aliphatic and aromatic hydroxy groups of the substrate. Modeling and molecular docking studies were performed to explain the stereoselective glucuronidation of the substrates under study.     

Harmicens,Novel Harmine and Ferrocene Hybrids: Design,Synthesis and Biological Activity

Cancer and malaria are both global health threats. Due to the increase in the resistance to the known drugs, research on new active substances is a priority. Here, we present the design, synthesis, and evaluation of the biological activity of harmicens, hybrids composed of covalently bound harmine/β-carboline and ferrocene scaffolds. Structural diversity was achieved by varying the type and length of the linker between the β-carboline ring and ferrocene, as well as its position on the β-carboline ring. Triazole-type harmicens were prepared using Cu(I)-catalyzed azide-alkyne cycloaddition, while the synthesis of amide-type harmicens was carried out by applying a standard coupling reaction. The results of in vitro biological assays showed that the harmicens exerted moderate antiplasmodial activity against the erythrocytic stage of P. falciparum (IC₅₀ in submicromolar and low micromolar range) and significant and selective antiproliferative activity against the MCF-7 and HCT116 cell lines (IC₅₀ in the single-digit micromolar range, SI > 5.9). Cell localization experiments showed different localizations of nonselective harmicene 36 and HCT116-selective compound 28, which clearly entered the nucleus. A cell cycle analysis revealed that selective harmicene 28 had already induced G1 cell cycle arrest after 24 h, followed by G2/M arrest with a concomitant drastic reduction in the percentage of cells in the S phase, whereas the effect of nonselective compound 36 on the cell cycle was much less pronounced, which agreed with their different localizations within the cell.     

Behavioral Phenotyping of Bbs6 and Bbs8 Knockout Mice Reveals Major Alterations in Communication and Anxiety

The primary cilium is an organelle with a central role in cellular signal perception. Mutations in genes that encode cilia-associated proteins result in a collection of human syndromes collectively termed ciliopathies. Of these, the Bardet-Biedl syndrome (BBS) is considered one of the archetypical ciliopathies, as patients exhibit virtually all respective clinical phenotypes, such as pathological changes of the retina or the kidney. However, the behavioral phenotype associated with ciliary dysfunction has received little attention thus far. Here, we extensively characterized the behavior of two rodent models of BBS, Bbs6/Mkks, and Bbs8/Ttc8 knockout mice concerning social behavior, anxiety, and cognitive abilities. While learning tasks remained unaffected due to the genotype, we observed diminished social behavior and altered communication. Additionally, Bbs knockout mice displayed reduced anxiety. This was not due to altered adrenal gland function or corticosterone serum levels. However, hypothalamic expression of Lsamp, the limbic system associated protein, and Adam10, a protease acting on Lsamp, were reduced. This was accompanied by changes in characteristics of adult hypothalamic neurosphere cultures. In conclusion, we provide evidence that behavioral changes in Bbs knockout mice are mainly found in social and anxiety traits and might be based on an altered architecture of the hypothalamus.     

CT and MRI Imaging of Theranostic Bimodal Fe3O4@Au NanoParticles in Tumor Bearing Mice

Gold-containing nanoparticles are proven to be an effective radiosensitizer in the radiotherapy of tumors. Reliable imaging of nanoparticles in a tumor and surrounding normal tissues is crucial both for diagnostics and for nanoparticle application as radiosensitizers. The Fe₃O₄ core was introduced into gold nanoparticles to form a core/shell structure suitable for MRI imaging. The aim of this study was to assess the in vivo bimodal CT and MRI enhancement ability of novel core/shell Fe₃O₄@Au theranostic nanoparticles. Core/shell Fe₃O₄@Au nanoparticles were synthesized and coated with PEG and glucose. C57Bl/6 mice bearing Ca755 mammary adenocarcinoma tumors received intravenous injections of the nanoparticles. CT and MRI were performed at several timepoints between 5 and 102 min, and on day 17 post-injection. Core/shell Fe₃O₄@Au nanoparticles provided significant enhancement of the tumor and tumor blood vessels. Nanoparticles also accumulated in the liver and spleen and were retained in these organs for 17 days. Mice did not show any signs of toxicity over the study duration. These results indicate that theranostic bimodal Fe₃O₄@Au nanoparticles are non-toxic and serve as effective contrast agents both for CT and MRI diagnostics. These nanoparticles have potential for future biomedical applications in cancer diagnostics and beyond.     

GMES4Mining: GMES-based Geoservices for Mining to Support Prospection and Exploration and the Integrated Monitoring for Environmental Protection and Operational Security

The GMES4Mining R&D project started in summer 2011 with the purpose of supporting management in all phases of a mining cycle. In most states of the European Union, the mines are in phases of operation or reclamation, but in other countries there is an interest in prospecting and exploring new areas for mining. In order to support the implementation of legal responsibilities, GMES4Mining investigates the potential of innovative remote sensing technologies for mining monitoring, prospection and exploration. In an early phase of this GMES4Mining project, a detailed query on the users’ requirements on remote sensing was performed. Currently, spaceborne radar data and ground measurements are tested for an early detection of slope slides in operational mines, slope stability in dumps, surface ground movements and subsidence. Satellite- and air-borne optical remote sensors are meant to monitor changes in ground water depth, directly through the estimation of soil moisture or indirectly by mapping changes in vegetation, both in the exploitation and the reclamation phases. For the scope of the GMES4Mining project two study sites were selected in the northern part of the German Ruhrgebiet. An important scope of the project is to report the quality of data and methods. Moreover, the results of the research will be integrated in a spatial data infrastructure (SDI) and disseminated via a web portal. This paper gives an introduction to the project and its different parts.     

Evolving priority scheduling heuristics with genetic programming

This paper investigates the use of genetic programming in automated synthesis of scheduling heuristics for an arbitrary performance measure. Genetic programming is used to evolve the priority function, which determines the priority values of certain system elements (jobs, machines). The priority function is used within an appropriate meta-algorithm for a given environment, which forms the priority scheduling heuristic. The evolved solutions are compared with existing scheduling heuristics and found to perform similarly to or better than existing algorithms. We intend to show that this approach is particularly useful for combinations of scheduling environments and performance measures for which no adequate scheduling algorithms exist.     

Authentication study of volatile flavour compounds composition in Slavonian traditional dry fermented salami “kulen”

Volatiles from famous Slavonian salami “kulen” were isolated by nitrogen purge and steam distillation (NPSD) and analysed, for the first time, by gas chromatography and mass spectrometry (GC and GC–MS). In all, 119 organic compounds were identified that originated from lipid oxidation, amino acid degradation, smoke treatment and added spices with different distribution among NPSD traps. NPSD method enabled comprehensive profiling with almost exclusive distribution of several major compounds in particular trap with little or no interference from abundant lipid constituents in the samples. The major identified flavour important compounds were methylphenols, methoxyphenols, organosulphur compounds (diallyl sulphide, diallyl disulphide, methylallyl disulphide, diallyl trisulphide and methional) and several derivatives of 2-cyclopenten-1-one such as ethyl cyclotene. Non-important flavour constituents such as high-molecular fatty acids, alcohols and aldehydes were also present among abundant compounds. General trends for possible discrimination of “kulen” volatiles profile among other European salami volatiles were noticed (lower amount of terpenes and higher percentages of diallyl sulphide, methoxyphenols, methylphenols and 2-cyclopenten-1-one derivatives).