Synthesis of Long-Chain β-Lactones and Their Antibacterial Activities against Pathogenic Mycobacteria

In the quest for new antibacterial agents, a series of novel long- and medium-chain mono- and disubstituted β-lactones was developed. Their activity against three pathogenic mycobacteria—M. abscessus, M. marinum, and M. tuberculosis—was assessed by the resazurin microtiter assay (REMA). Among the 16 β-lactones synthesized, only 3-hexadecyloxetan-2-one (VM005) exhibited promising activity against M. abscessus, whereas most of the β-lactones showed interesting activities against M. marinum, similar to that of the classical antibiotic, isoniazid. Regarding M. tuberculosis, six compounds were found to be active against this mycobacterium, with β-lactone VM008 [trans-(Z)-3-(hexadec-7-en-1-yl)-4-propyloxetan-2-one] being the best growth inhibitor. The promising antibacterial activities of the best compounds in this series suggest that these molecules may serve as leads for the development of much more efficient antimycobacterial agents.     

Nonhydrolyzable Heptose Bis- and Monophosphate Analogues Modulate Pro-inflammatory TIFA-NF-κB Signaling

d -Glycero-d -manno-heptose-1β,7-bisphosphate (HBP) and d -glycero-d -manno-heptose-1β-phosphate (H1P) are bacterial metabolites that were recently shown to stimulate inflammatory responses in host cells through the activation of the TIFA-dependent NF-κB pathway. To better understand structure-based activity in relation to this process, a family of nonhydrolyzable phosphonate analogues of HBP and H1P was synthesized. The inflammation modulation by which these molecules induce the TIFA-NF-κB signal axis was evaluated in vivo at a low-nanomolar concentration (6 nM) and compared to that of the natural metabolites. Our data showed that three phosphonate analogues had similar stimulatory activity to HBP, whereas two phosphonates antagonized HBP-induced TIFA-NF-κB signaling. These results open new horizons for the design of pro-inflammatory and innate immune modulators that could be used as vaccine adjuvant.     

Matrix Transformation in Boron Containing High-Temperature Co–Re–Cr Alloys

An addition of boron largely increases the ductility in polycrystalline high-temperature Co–Re alloys. Therefore, the effect of boron on the alloy structural characteristics is of high importance for the stability of the matrix at operational temperatures. Volume fractions of ε (hexagonal close-packed—hcp), γ (face-centered cubic—fcc) and σ (Cr₂Re₃ type) phases were measured at ambient and high temperatures (up to 1500 °C) for a boron-containing Co–17Re–23Cr alloy using neutron diffraction. The matrix phase undergoes an allotropic transformation from ε to γ structure at high temperatures, similar to pure cobalt and to the previously investigated, more complex Co–17Re–23Cr–1.2Ta–2.6C alloy. It was determined in this study that the transformation temperature depends on the boron content (0–1000 wt. ppm). Nevertheless, the transformation temperature did not change monotonically with the increase in the boron content but reached a minimum at approximately 200 ppm of boron. A probable reason is the interplay between the amount of boron in the matrix and the amount of σ phase, which binds hcp-stabilizing elements (Cr and Re). Moreover, borides were identified in alloys with high boron content.     

Vehicle detection by means of stereo vision-based obstacles features extraction and monocular pattern analysis.

This paper presents a stereo vision system for the detection and distance computation of a preceding vehicle. It is divided in two major steps. Initially, a stereo vision-based algorithm is used to extract relevant three-dimensional (3-D) features in the scene, these features are investigated further in order to select the ones that belong to vertical objects only and not to the road or background. These 3-D vertical features are then used as a starting point for preceding vehicle detection; by using a symmetry operator, a match against a simplified model of a rear vehicle's shape is performed using a monocular vision-based approach that allows the identification of a preceding vehicle. In addition, using the 3-D information previously extracted, an accurate distance computation is performed.     

Kommunikationsoberfläche Membran‐ Vorbild für moderne Nanoanalytik

A central event in the life of a cellular system is the interaction between the exterior and the interior compartments. Biochemical signals arrive at the cellular surface, bind to their membrane bound receptor followed by a conformational change triggering the release of an internal chemical or electrical signal.This basic principle is followed by all our perceptive abilities like sense of smell or taste, but also by different signal transduction pathways involved in nerve conductivity, vision, sense of touch or hearing. To follow and mimic this principle of parallel registration is one of the aims of modern nanobiotechnology. If we are able to specifically biofunctionalize small arrays of a solid surface, which could be an electrode or a semiconductor, this approach will enable us to build up devices called “biochips” or “biosensors” that allow the determination of bioactive molecules with high specificity at lowest concentrations. Potential pharmacological active substrates might be screened as well as new receptors may be determined. Applications in genomics as well as proteomics are realistic. The major prerequisite for such a broad spectrum of applications is the fabrication of receptive surfaces. Biomolecules have to be surface‐adsorbed in a highly reproducible, oriented and well organised fashion, a task which in biology is taken by the cellular membranes as external or internal receptive surfaces. The physical principles like hydrogen bonds, electrostatic or hydrophobic interactions that lead to such an organized surface are well known. To synthesize molecular building blocks and to position them onto an otherwise unspecific surface is one of the challenges of nanobiotechnology combining biological knowledge and chemical skills with biophysical techniques that allow to handle or analyze even single molecules.     

Intra- and inter-laboratory reproducibility of estrogen and progesterone receptor enzyme immunoassay in breast cancer cytosol samples--a Swedish multicenter study. Swedish Society of Cancer Study Group

Estrogen and progesterone receptor analysis results were compared within and between six laboratories in Sweden using frozen breast cancer cytosol samples, and the same technique (enzyme immunoassay, Abbott Laboratories). The concordance in receptor status (positive vs. negative) was excellent (98.4% (571/580)). The discordant results were attributable to values near cut-off (n = 4) or outliers (n = 5), the latter probably being due to analytical errors. One laboratory reported significantly higher ER concentrations than the others; thus caution should be observed when comparing absolute values from different centers. For PgR there were similar differences between the laboratories. However, the intra- and inter-laboratory differences were small compared with the overall variability in ER and PgR content between different samples in a large database. The range of the median intra-laboratory coefficient of variation was 11-23% for ER and 12-19% for PgR, indicating that there is room for improvement in the quality of assay performance.