Peptidyl Vinyl Ketone Irreversible Inhibitors of Rhodesain: Modifications of the P2 Fragment

In this paper, we report the design, synthesis and biological investigation of a series of peptidyl vinyl ketones obtained by modifying the P2 fragment of previously reported highly potent inhibitors of rhodesain, the main cysteine protease of Trypanosoma brucei rhodesiense. Investigation of the structure–activity relationship led us to identify new rhodesain inhibitors endowed with an improved selectivity profile (a selectivity index of up to 22 000 towards the target enzyme), and/or an improved antitrypanosomal activity in the sub-micromolar range.     

Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.     

Industrie 4.0

Industry 4.0 – Challenges for constructions of vacuum systems Vacuum systems are finding their way into branches and belonging modern process chains which were hardly in contact with UHV technology in the past. Besides an automatic operation and a flawless processing of parts, vacuum systems and their peripheral devices have to feature options for data output and analysis for subsequent processing in e.g. MES to come up with Industry 4.0 requirements. Subcomponents in vacuum technology partly comply with these requirements in a insufficient way because of their unchanged demands over the last decades. This makes integration into an automatic system more difficult. Despite of that, Industry 4.0 compliant vacuum systems are already producible when there's access to high-level experiences in vacuum and automation technology. This is shown by the examples of residual gas analysis and cleanliness measurement systems and the vacuum bake out oven. A cooperation of vacuum system manufacturers and manufacturers of components is necessary in the future to be able to produce automated vacuum systems in a more efficient way.     

Beneficial and harmful explanatory machine learning

Machine Learning - Given the recent successes of Deep Learning in AI there has been increased interest in the role and need for explanations in machine learned theories. A distinct notion in this...     

Vibrational Spectroscopic Investigation of Blood Plasma and Serum by Drop Coating Deposition for Clinical Application

In recent decades, vibrational spectroscopic methods such as Raman and FT-IR spectroscopy are widely applied to investigate plasma and serum samples. These methods are combined with drop coating deposition techniques to pre-concentrate the biomolecules in the dried droplet to improve the detected vibrational signal. However, most often encountered challenge is the inhomogeneous redistribution of biomolecules due to the coffee-ring effect. In this study, the variation in biomolecule distribution within the dried-sample droplet has been investigated using Raman and FT-IR spectroscopy and fluorescence lifetime imaging method. The plasma-sample from healthy donors were investigated to show the spectral differences between the inner and outer-ring region of the dried-sample droplet. Further, the preferred location of deposition of the most abundant protein albumin in the blood during the drying process of the plasma has been illustrated by using deuterated albumin. Subsequently, two patients with different cardiac-related diseases were investigated exemplarily to illustrate the variation in the pattern of plasma and serum biomolecule distribution during the drying process and its impact on patient-stratification. The study shows that a uniform sampling position of the droplet, both at the inner and the outer ring, is necessary for thorough clinical characterization of the patient’s plasma and serum sample using vibrational spectroscopy.     

Hydrothermal Carbonization of Biomass: Major Organic Components of the Aqueous Phase

Process waters obtained from hydrothermal carbonization (HTC) of wheat straw, a biogas digestate derived thereof, and four woody biomass feedstocks were quantified regarding the total organic carbon (TOC) and selected organic compounds. HTC runs revealed that TOC loads were largely unaffected by process severity or type of feedstock whereas the C₂–C₆ fatty acids, determined by GC, displayed clear effects of temperature and feedstock. HPLC demonstrated simultaneously the initial increase and subsequent consumption of cellulose‐derived furfural and 5‐hydroxymethylfurfural as well as the increase of the lignin‐derived 2‐methoxyphenol. 2‐Methylbenzofuran, an example for a substance potentially harmful to aquatic biota, was observed in high concentration in the HTC liquor from wheat straw‐based feedstocks.     

Zuverlässige Prozesse durch Vakuumkomponenten mit definierten Ausgasraten

Reliable processes by use of vacuum components with specified outgassing rates Contamination of vacuum components cannot be avoided in the manufacturing process. In order to significantly reduce particulate and organic impurities, a multi-stage cleaning process and proof of cleanliness are essential. In order to guarantee a reproducible quality of the cleanliness of vacuum components, uniform standards for defined outgassing rates are necessary. The development of Vacom Purity Classes serves the generally accessible specification of components and characterises their vacuum and cleanroom suitability. Vacom Vacuum Classes guarantee the suitability of vacuum components for use in UHV/XHV. In this article, the importance of cleaning of vacuum chambers and components is examined as well as the need to establish a uniform method for the quantitative measurement of the outgassing rate is highlighted. The systematic division into Vacom Purity and Vacuum Classes provides the basis for a cross-industry standard for the defined quality of vacuum processes.