4‐Biphenylalanine‐ and 3‐Phenyltyrosine‐Derived Hydroxamic Acids as Inhibitors of the JumonjiC‐Domain‐Containing Histone Demethylase KDM4A

Overexpression of the histone lysine demethylase KDM4A, which regulates H3K9 and H3K36 methylation states, has been related to the pathology of several human cancers. We found that a previously reported hydroxamate‐based histone deacetylase (HDAC) inhibitor (SW55) was also able to weakly inhibit this demethylase with an IC₅₀ value of 25.4 μm . Herein we report the synthesis and biochemical evaluations, with two orthogonal in vitro assays, of a series of derivatives of this lead structure. With extensive chemical modifications on the lead structure, also by exploiting the versatility of the radical arylation with aryldiazonium salts, we were able to increase the potency of the derivatives against KDM4A to the low‐micromolar range and, more importantly, to obtain demethylase selectivity with respect to HDACs. Cell‐permeable derivatives clearly showed a demethylase‐inhibition‐dependent antiproliferative effect against HL‐60 human promyelocytic leukemia cells.     

Sanierung eines PCE-Schadens in einem makroskopisch oxischen Grundwasserleiter durch Stimulation anaerober dehalogenierender Bakterien

Grundwasser - Eine erfolgreiche biologische In-situ-Sanierung von PCE-kontaminierten Grundwasserleitern erfordert hinreichend reduzierende Bedingungen sowie die Anwesenheit von molekularem...     

Chemical Attraction of Gall Midge Pollinators (Cecidomyiidae: Cecidomyiinae) to Anthurium acutangulum (Araceae)

Flowering plants often use chemical signals to attract their pollinators, and compounds that elicit attraction are known for several groups of pollinators. For other pollinators such as gall midges, however, compounds responsible for their attraction to flowers are largely unknown. Here, we describe the pollination biology of Anthurium acutangulum, a Neotropical aroid species found to be attractive to gall midges. We collected and analyzed its floral scent by dynamic headspace collections and gas chromatography coupled to mass spectrometry, and identified compounds responsible for pollinator attraction. The inflorescences were almost exclusively visited by gall midges (females; Cecidomyiidae: Cecidomyiinae) and released a strong scent reminiscent of freshly cut cucumber, mainly (5S,7S)-trans-conophthorin, (E2,Z6)-2,6-nonadienal, and cis-conophthorin. Behavioral assays with the two most abundant compounds identified (E2,Z6)-2,6-nonadienal as being highly attractive to the female gall midge pollinators, whereas (5S,7S)-trans-conophthorin was not attractive. Overall, we introduce a new specialized gall midge pollination system and identify the chemical mediating communication between the pollinators and their host plants.

     

Multicriteria optimization as enabler for Sustainable Ceramic Matrix Composites

Over the past 40 years, development of Ceramic Matrix Composites (CMCs) has focused mainly on the improvement of material performance and optimization of cost-efficient production routes. Recently, more fields of application have opened up for CMCs, in which environmental impacts are relevant. These impacts have barely been investigated so far but receive growing interest due to increasing awareness of the environmental consequences. Our innovative approach frames material properties in relation to environmental impacts (e.g., global warming potential in CO₂ emission) by varying process parameters to balance optimum performance against environmental considerations. First, the process of wet filament winding has been investigated up to the Carbon Fiber Reinforced Plastic (CFRP) state by changing both the curing and tempering temperatures. During the production of CFRP plates, mass and energy flows were tracked in each step. Three point-bending and interlaminar shear tests have been performed on the resulting samples to identify basic mechanical properties. The environmental impacts are determined by a cradle-to-gate Life Cycle Assessment (LCA), using the software SimaPro. The resulting tradeoffs between mechanical properties and environmental impacts show nonlinear behavior, thus revealing optimum points above which improved mechanical properties are associated with significantly higher CO₂ emissions.     

Efficient Engineering and Production Concepts for Products in Regulated Environments – Dream or Nightmare?

Manufacturing of chemical‐pharmaceutical products is moving increasingly fast on a global scale. Therefore, developing and starting up production facilities fast, with high quality, and at reasonable costs has become extremely challenging. Engineering concepts like modularization, standardization and simultaneous/parallel engineering are discussed as methods for speeding up process design and filing for regulatory approval. Transfer from batch to continuous operation mode of production is pointed out as the key‐issue in such strategies.     

A method for increasing the accuracy of “on-workpiece” machining with small industrial robots for composite repair

Composites offer outstanding mechanical properties in combination with a low density. To profit from the full potential of these materials there are still some challenges to meet. Efficient, reproducible, and material appropriate repair is one of them. It requires accurate machining on damaged structures to generate an optimal surface for the following bonded repair. In case of large scale structures, machining has to be done on-workpiece because those structures are not removable. This application requires a flexible, low-weight and cost-efficient machine, but also a system that considers the elasticities of on-work-piece machining setups. Small industrial robots offer high availability and flexibility, low investment costs, and a low weight in combination with a suitable workspace. The general disadvantage of these machines is a low stiffness in addition to the existing elasticities. However, in this application only moderate process forces occur. Furthermore, high system elasticity is expected any way, due to the detachable fixation and the workpiece. Accordingly, in this paper an online, low frequency method for the compensation of tool deviations is proposed to enhance the performance of small robots as on-workpiece milling machines. For a high industrial acceptance, a simple robot model for compensation is chosen, thus the measurement effort is minimal and the method can be integrated into a state of the art robot controller without external hardware. Additionally, a concept for an extended method for deviation compensation is presented which also considers the changing elasticity of fixation and workpiece.     

Technical note: Effects of attachment of hind teats before cleaning and attachment of front teats on milking characteristics in automatic milking systems

Milking characteristics differ between the 4 quarters of a dairy cow udder. In particular, milking time is mostly prolonged in hind quarters compared with front quarters because of the usually higher amount of stored milk. The standard milking routine (STDMR) in both conventional and automatic milking systems (AMS) consists of teat preparation of all 4 quarters, followed by attachment of the 4 teat cups, regardless of the distribution of milk between quarters. In the current study, an alternative teat preparation and milking routine (ALTMR) in AMS was tested, which consisted of cleaning and starting the milking of hind teats before cleaning and attachment of front teats. The hypothesis was based on the fact that hind quarters have usually a longer milking time than front quarters. Starting the milking of hind quarters while the front teats are being cleaned may reduce the difference in the end of milking between front and hind quarters and thus reduce total milking time. Both routines were tested on 5 Swedish dairy farms equipped with AMS in a 4-wk experiment in which treatments were alternated weekly. Total milk yield did not differ between treatments. Machine-on time (MOT) was longer in ALTMR than in STDMR because the difference in milking time between hind and front quarters was less than the time needed to prepare the front teats. However, the longer MOT in ALTMR was compensated by a shorter total preparation time, including the attachment of the first teat cup, as only the hind teats (instead of all 4 teats) were cleaned before milking was started. This resulted in a similar total milking time from start of cleaning of the first quarter until the end of milking of the last quarter in both treatments. Because of the prolonged MOT, average milk flow rate was lower in ALTMR than STDMR. Peak flow rate was higher in ALTMR than STDMR, but only in teat cups 1 (first attached, hind quarter) and 3 (third attached, front quarter), whereas main milk flow was higher in ALTMR than STDMR in both front quarters. In conclusion, splitting teat cleaning and the start of milking between hind and front quarters does not prolong total milking time, including teat cleaning. The partially positive effect on peak and main milk flow indicates that the ALTMR is a suitable milking routine in AMS. In herds with a greater difference of milk stored in hind compared with front quarters, a reduced total milking time can be expected for ALTMR.     

Identification of chemical markers for the sensory shelf-life of saveloy

The aroma composition, the microbial composition and the sensory profile were measured in sliced saveloy samples packed in modified atmosphere (MA). The main objective was to identify aroma compounds with potential as chemical markers to identify the sensory changes of saveloy. The 60 aroma compounds isolated from the saveloy samples by dynamic headspace extraction and measured by Gas Chromatography Mass Spectrometry (GC-MS) were used to model the sensory attributes sour&old odour and meaty odour using partial least squares regression (PLS). 2- and 3-methylbutanal, 2- and 3-methylbutanol, acetoin and diacetyl were found to have the highest impact on both sour&old odour and meaty odour of the samples. The results show that these four aroma compounds have high potential as chemical markers for the sensory shelf-life of sliced and MA-packed saveloy.