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.     

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.     

Lithium Phosphonate Functionalized Polymer Coating for High-Energy Li[Ni0.8Co0.1Mn0.1]O2 with Superior Performance at Ambient and Elevated Temperatures

High-energy Ni-rich lithium transition metal oxides such as Li[Ni_0.8Co_0.1Mn_0.1]O₂ (NCM₈₁₁) are appealing positive electrode materials for next-generation lithium batteries. However, the high sensitivity toward moist air during storage and the high reactivity with common organic electrolytes, especially at elevated temperatures, are hindering their commercial use. Herein, an effective strategy is reported to overcome these issues by coating the NCM₈₁₁ particles with a lithium phosphonate functionalized poly(aryl ether sulfone). The application of this coating allows for a substantial reduction of lithium-based surface impurities (e.g., LiOH, Li₂CO₃) and, generally, the suppression of detrimental side reactions upon both storage and cycling. As a result, the coated NCM₈₁₁-based cathodes reveal superior Coulombic efficiency and cycling stability at ambient and, particularly, at elevated temperatures up to 60 ° C (a temperature at which the non-coated NCM₈₁₁ electrodes rapidly fail) owing to the formation of a stable cathode electrolyte interphase with enhanced Li⁺ transport kinetics and the well-retained layered crystal structure. These results render the herein presented coating strategy generally applicable for high-performance lithium battery cathodes.     

Dynamic force microscopy imaging of native membranes

We employed magnetic ACmode atomic force microscopy (MACmode AFM) as a novel dynamic force microscopy method to image surfaces of biological membranes in their native environments. The lateral resolution achieved under optimized imaging conditions was in the nanometer range, even when the sample was only weakly attached to the support. Purple membranes (PM) from Halobacterium salinarum were used as a test standard for topographical imaging. The hexagonal arrangement of the bacteriorhodopsin trimers on the cytoplasmic side of PM was resolved with 1.5nm lateral accuracy, a resolution similar to images obtained in contact and tapping-mode AFM. Human rhinovirus 2 (HRV2) particles were attached to mica surfaces via nonspecific interactions. The capsid structure and 2nm sized protein loops of HRV2 were routinely obtained without any displacement of the virus. Globular and filamentous structures on living and fixed endothelial cells were observed with a resolution of 5-20nm. These examples show that MACmode AFM is a favorable method in studying the topography of soft and weakly attached biological samples with high resolution under physiological conditions.     

Irradiation effects on AlGaN HFET devices and GaN layers

AlGaN/GaN heterostructure field effect transistors (HFETs) were irradiated with protons as well as carbon, oxygen, iron and krypton ions of high (68 and 120 MeV) and low (2 MeV) energy with fluences in the range from 1 × 10⁷ to 1 × 10¹³ cm^?2. High energy irradiation with protons, carbon and oxygen produced no degradation in devices while krypton irradiation at the fluence of 1 × 10¹⁰ cm^?2 resulted in a small reduction of 2% in the transconductance. Similarly, for GaN samples irradiated with protons, carbon and oxygen at high energy no changes were seen by XRD, PL and Hall effect, while changes in lattice constant and a reduction in PL intensity were observed after irradiation with high energy krypton. Low energy irradiation with carbon and oxygen at a fluence of 5 × 10¹⁰ cm^?2 results in small change in the device performance while remarkable changes in device characteristics are seen at a fluence of 1 × 10¹² cm^?2 for carbon, oxygen, iron and krypton irradiation. Similarly changes are also observed by XRD, PL and Hall effect for the thick GaN layer irradiated at the fluence of 1 × 10¹² cm^?2. The device results and GaN layer properties are strongly correlated.     

Three-dimensional nonwoven scaffolds from a novel biodegradable poly(ester amide) for tissue engineering applications

Biodegradable polyesters are established biomaterials in medicine due to their chemical characteristics and options for material processing. A main problem, however, is the release of acid degradation products during biodegradation with severe local pH-drops and inflammatory reactions. Polyesteramides, in contrast, show a less prominent pH-drop during degradation. In this study, we developed a simple, reproducible synthesis of the poly(ester amide) (PEA) type C starting from ε-caprolactame, 1,4-butanediol, and adipic acid in a one-batch two-step reaction and conducted the manufacturing of PEA-derived 3D textile scaffolds applicable for tissue engineering purposes. The thermal and mechanical properties of PEA-type C were analysed and the structural conformity of different batches was confirmed by NMR spectroscopy and size exclusion chromatography. The polymer was formed into nonwovens by textile manufacturing. Cytotoxicity tests and X-ray photoelectron spectroscopy (XPS) were used to analyze the effect of scaffold extraction before cell seeding. The manufactured carriers were seeded with human preadipocytes and examined for cellular proliferation and differentiation. The production of PEA type C successfully occurred via simultaneous ring-opening polymerization of ε-caprolactame and polycondensation with 1,4-butanediol and adipic acid at 250 °C under high-vacuum. Soxhlet extraction allowed optimal cleaning of nonwoven scaffolds. Extracted PEA-derived matrices were capable of allowing good adherence, proliferation, and differentiation of preadipocytes. These results are encouraging and guidance towards an optimally prepared nonwoven carrier applicable for clinical use. K. Hemmrich and J. Salber have contributed equally.