Synthesen und absolute Konfigurationen von Piperidinolalkaloiden : Arbeiten zur Darstellung von Epothilon ; chirale [beta]-Hydroxycarbonsäureester als Intermediate in der Naturstoffsynthese

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The chemistry of sulfur and nitrogen species in a fog system A multiphase approach

Concentration and phase distribution of sulfur and nitrogen species during a particular fog episode in the Po Valley are experimentally described in this paper. Chemical measurements were carried out simultaneously at different heights within the fog layer, up to 50 m. Microphysical and meteorological parameters necessary for the description of the fog multiphase system were also concurrently measured as a function of height. The fog cycle (formation, evolution, dissipation) is described in terms of the total acidity of a unit volume of air containing gas species, interstitial aerosol particles and fog droplets. The fog system was not closed and input of acidic and basic components was observed during fog evolution. The driving force which determines the acidity of the fog multiphase atmospheric system was found to be the presence of NH 3 and its partitioning among the different phases. A strong decrease of fog water pH (from 5.6 down to 2.8) was observed during fog evolution and was attributed to a HNO 3 input to the system. These acidic and basic inputs are described in terms of a titration/back-titration process of the fog system. The SO 2 oxidation process in fog water was found to be of minor importance in determining the SO 4 = concentration within the fog system, due to both low SO 2 concentration and limited oxidant availability during the experiment. DOI: 10.1034/j.1600-0889.1992.t01-4-00005.

Physical activity monitoring in Alzheimer’s disease during sport interventions: a multi-methodological perspective

IntroductionAssessment methods for physical activity and fitness are of upmost importance due to the possible beneficial effect of physical conditioning on neurodegenerative diseases. The implementation of these methods can be challenging when examining elderly or cognitively impaired participants. In the presented study, we compared three different assessment methods for physical activity from the Dementia-MOVE trial, a 6-months intervention study on physical activity in Alzheimer’s disease. The aim was to determine the comparability of physical activity assessments in elderly participants with cognitive impairment due to Alzheimer’s disease.Material or methods38 participants (mean age 70 ± 7 years) with early-stage Alzheimer’s disease (mean MoCA 18.84 ± 4.87) were assessed with (1) fitness trackers for an average of 12 (± 6) days, (2) a written diary on daily activities and (3) a questionnaire on physical activity at three intervention timepoints. For comparison purposes, we present a transformation and harmonization method of the physical assessment output parameters: Metabolic equivalent of task (MET) scores, activity intensity minutes, calorie expenditure and moderate-to-vigorous physical activity (MVPA) scores were derived from all three modalities. The resulting parameters were compared for absolute differences, correlation, and their influence by possible mediating factors such as cognitive state and markers from cerebrospinal fluid.ResultsParticipants showed high acceptance and compliance to all three assessment methods. MET scores and MVPA from fitness trackers and diaries showed high overlap, whilst results from the questionnaire suggest that participants tended to overestimate their physical activity in the long-term retrospective assessment. All activity parameters were independent of the tested Alzheimer’s disease parameters, showing that not only fitness trackers, but also diaries can be successfully applied for physical activity assessment in a sample affected by early-stage Alzheimer’s disease.DiscussionOur results show that fitness trackers and physical activity diaries have the highest robustness, leading to a highly comparable estimation of physical activity in people with Alzheimer’s disease. As assessed parameters, it is recommendable to focus on MET, MVPA and on accelerometric sensor data such as step count, and less on activity calories and different activity intensities which are dependent on different variables and point to a lower reliability

Spacial Score – A Comprehensive Topological Indicator for Small Molecule Complexity

The fraction of sp3 hybridised carbons (Fsp3) and the fraction of stereogenic carbons (FCstereo) are two widely employed scores of molecular complexity with a strong link to biologically relevant features such as frequency, potency and selectivity of protein binding. However, due to their simplistic nature, they do not comprehensively express molecular topology and they often do not match the chemical intuition of complexity. We propose the spacial score (SPS) as an empirical scoring system that builds upon the principle underlying Fsp3 and FCstereo and expresses the spacial complexity of a compound in a uniform manner and on a highly granular scale for convenient ranking of and comparison between molecules. The size-normalised SPS (nSPS) can differentiate distributions of natural products and synthetic compounds and is applicable in the analysis of biological activity data. Analysis of the ChEMBL database revealed general trends of increasing selectivity and potency with increasing nSPS. Notably, SPS can also be used advantageously in planning and analysis of synthesis programs for direct comparison of chemical transformations and intermediates in reaction sequences, for instance in natural product total syntheses

Pseudo-Natural Products Occur Frequently in Biologically Relevant Compounds

A new methodology for classifying fragment combinations and characterizing pseudo-natural products (PNPs) is described. The source code is based on open-source tools and is organized as a Python package. Tasks can be executed individually or within the context of scalable, robust workflows. First, structures are standardized and duplicate entries are filtered out. Then, molecules are probed for the presence of predefined fragments. For molecules with more than one match, fragment combinations are classified. The algorithm considers the pair-wise relative position of fragments within the molecule (fused atoms, linkers, intermediary rings), resulting in 18 different possible fragment combination categories. Finally, all combinations for a given molecule are assembled into a fragment combination graph, with fragments as nodes and combination types as edges. This workflow was applied to characterize PNPs in the ChEMBL database via comparison of fragment combination graphs with Natural Product (NP) references, represented by the Dictionary of Natural Products. The Murcko fragments extracted from 2,000 structures previously described were used to define NP-fragments. The results indicate that ca. 23% of the biologically relevant compounds listed in ChEMBL comply to the PNP definition, and that, therefore, PNPs occur frequently among known biologically relevant small molecules. The majority (>95%) of PNPs contains two to four fragments, mainly (>95%) distributed in five different combination types. These findings may provide guidance for the design of new PNPs

A WR3-Band 2-bit Phase Shifter Based on Active SPDT Switches

The design and performance of a compact WR3-band 2-bit phase shifter manufactured in a 35-nm InGaAs technology are described. To compensate the loss of the phase shifting networks, active single-pole double-throw switches are embedded. The 180° and 90° phase shifting networks are based on a broadside-coupled 1:1 magnetic transformer and a hybrid edge-coupled tandem coupler, respectively. Measurements show a maximum gain of 0.22 dB with a 3-dB bandwidth of 44 GHz ranging from 235 to 279 GHz. Root-mean-square gain and phase errors are below 0.18 dB and 2.8°, respectively

Scaffold Remodelling of Diazaspirotricycles Enables Synthesis of Diverse sp3-Rich Compounds With Distinct Phenotypic Effects

A ‘top down’ scaffold remodelling approach to library synthesis was applied to spirotricyclic ureas prepared by a complexity-generating oxidative dearomatisation. Eighteen structurally-distinct, sp3-rich scaffolds were accessed from the parent tricycle through ring addition, cleavage and expansion strategies. Biological screening of a small compound library based on these scaffolds using the cell-painting assay demonstrated distinctive phenotypic responses engendered by different library members, illustrating the functional as well as structural diversity of the compounds

A compound-target pairs dataset: differences between drugs, clinical candidates and other bioactive compounds

Providing a better understanding of what makes a compound a successful drug candidate is crucial for reducing the high attrition rates in drug discovery. Analyses of the differences between active compounds, clinical candidates and drugs require high-quality datasets. However, most datasets of drug discovery programs are not openly available. This work introduces a dataset of compound-target pairs extracted from the open-source bioactivity database ChEMBL (release 32). Compound-target pairs in the dataset either have at least one measured activity or are part of the manually curated set of known interactions in ChEMBL. Known interactions between drugs or clinical candidates and targets are specifically annotated to facilitate analyses on differences between drugs, clinical candidates, and other active compounds. In total, the dataset comprises 614,594 compound-target pairs, 5,109 (3,932) of which are known interactions between drugs (clinical candidates) and targets. The extraction is performed in an automated manner and fully reproducible. We are providing not only the datasets but also the code to rerun the analyses with other ChEMBL releases