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"Neubert, Peter"
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Applied homogeneous catalysis
Adopting a didactic approach at an advanced, masters level, 'Applied Homogeneous Catalysis' provides an array of questions and answers, and features numerous industrial case studies and examples.
Book
The development of viola instruction at the Paris Conservatoire during the nineteenth century and the evolution of an idiomatic style of writing for the viola as seen through the music of the viola concours, 1896–1918
The viola in the nineteenth century was an instrument without a dearly defined pedagogical history, mainly due to the lack of a performance tradition that was independent of that of the violin. During the eighteenth century the physical dimensions of the instrument hardly differed from those of the violin, thus viola literature merely reflected the instrument's range (being a fifth below that of the violin) without offering a technical approach substantially different from that of its higher cousin. Fortunately this situation began to change in the nineteenth century as composers embarked on a quest for a true viola timbre—neither the instruments nor the players capable of realizing their vision had yet appeared, but suddenly more rewarding parts were being written for the viola in almost every contemporary genre. Soon enough luthiers were inspired by this literature to build larger violas which could produce this sought-after tone color, and since these instruments' physical dimensions differed significantly from those of the violin, methods of instruction in the “new” viola technique were required in order to be able to give voice to the timbre that these instruments possessed. The end of the eighteenth century also witnessed the birth of the Paris Conservatoire, an academy of musical instruction that would grow into the preeminent institution of its kind in nineteenth-century Europe. This first viola class was taught by Théophile Laforge, who had graduated from the Paris Conservatoire as a violin student. As the class progressed through his twenty-four-year tenure, however, the music that the students performed took on a more identifiably “violistic” character. Composers who wrote works specifically to be performed on the annual viola competitions held at the Conservatoire at the end of each academic year helped to define an evolving idiomatic approach to writing for the viola. From this vantage point the Paris Conservatoire's first viola class can also be seen to mirror the way in which the viola asserted its individuality vis-à-vis the violin, building a body of repertoire and developing its own traditions of performance and instruction. (Abstract shortened by UMI.)
Dissertation
A comparison of vector symbolic architectures
Vector Symbolic Architectures combine a high-dimensional vector space with a set of carefully designed operators in order to perform symbolic computations with large numerical vectors. Major goals are the exploitation of their representational power and ability to deal with fuzziness and ambiguity. Over the past years, several VSA implementations have been proposed. The available implementations differ in the underlying vector space and the particular implementations of the VSA operators. This paper provides an overview of eleven available VSA implementations and discusses their commonalities and differences in the underlying vector space and operators. We create a taxonomy of available binding operations and show an important ramification for non self-inverse binding operations using an example from analogical reasoning. A main contribution is the experimental comparison of the available implementations in order to evaluate (1) the capacity of bundles, (2) the approximation quality of non-exact unbinding operations, (3) the influence of combining binding and bundling operations on the query answering performance, and (4) the performance on two example applications: visual place- and language-recognition. We expect this comparison and systematization to be relevant for development of VSAs, and to support the selection of an appropriate VSA for a particular task. The implementations are available.
Journal Article
Enhancing Product Quality in High-Variant Manufacturing: Combining Physics-Based Simulations and Data Science for Target Variable Estimation in an IoT- and Machine Learning-Driven Context
Due to growing demands for quality, sustainability, and digitalization, data science and artificial intelligence are gaining importance across industries. The extensive product range in many sectors often poses considerable challenges. For example, machine learning (ML) models may struggle with limited data per production variant. The present paper proposes a methodology that integrates the fields of data science and physical simulations. The results from finite element method (FEM) simulations are utilized to transform the process data in such a manner that it can be compared across processes for different production variants and employed for machine learning (ML) methods and statistical analyses. The method is illustrated using an example of aluminum production. A key advantage of this approach is that it can effectively model even production variants with very low quantities. The following discussion will present how this method can be used to enhance production processes, specifically to identify parameters that directly influence product quality, which would not be evident using alternative approaches. Furthermore, the work explores the potential for precisely controlling these parameters using ML models and discusses some major challenges.
Journal Article
molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule
IRE1 couples endoplasmic reticulum unfolded protein load to RNA cleavage events that culminate in the sequence-specific splicing of the Xbp1 mRNA and in the regulated degradation of diverse membrane-bound mRNAs. We report on the identification of a small molecule inhibitor that attains its selectivity by forming an unusually stable Schiff base with lysine 907 in the IRE1 endonuclease domain, explained by solvent inaccessibility of the imine bond in the enzyme-inhibitor complex. The inhibitor (abbreviated 4μ8C) blocks substrate access to the active site of IRE1 and selectively inactivates both Xbp1 splicing and IRE1-mediated mRNA degradation. Surprisingly, inhibition of IRE1 endonuclease activity does not sensitize cells to the consequences of acute endoplasmic reticulum stress, but rather interferes with the expansion of secretory capacity. Thus, the chemical reactivity and sterics of a unique residue in the endonuclease active site of IRE1 can be exploited by selective inhibitors to interfere with protein secretion in pathological settings.
Journal Article
Targeting cyclin-dependent kinases for the treatment of pulmonary arterial hypertension
Pulmonary arterial hypertension (PAH) is a devastating disease with poor prognosis and limited therapeutic options. We screened for pathways that may be responsible for the abnormal phenotype of pulmonary arterial smooth muscle cells (PASMCs), a major contributor of PAH pathobiology, and identified cyclin-dependent kinases (CDKs) as overactivated kinases in specimens derived from patients with idiopathic PAH. This increased CDK activity is confirmed at the level of mRNA and protein expression in human and experimental PAH, respectively. Specific CDK inhibition by dinaciclib and palbociclib decreases PASMC proliferation via cell cycle arrest and interference with the downstream CDK-Rb (retinoblastoma protein)-E2F signaling pathway. In two experimental models of PAH (i.e., monocrotaline and Su5416/hypoxia treated rats) palbociclib reverses the elevated right ventricular systolic pressure, reduces right heart hypertrophy, restores the cardiac index, and reduces pulmonary vascular remodeling. These results demonstrate that inhibition of CDKs by palbociclib may be a therapeutic strategy in PAH.
Cells of the pulmonary vasculature show a hyperproliferative phenotype in pulmonary arterial hypertension (PAH), thus contributing to the disease pathogenesis. Here the authors show that cyclin-dependent kinases are overactivated in PAH, and that their pharmacological inhibition attenuates the disease in two independent rodent models
Journal Article
Phosphorylation-driven epichaperome assembly is a regulator of cellular adaptability and proliferation
The intricate network of protein-chaperone interactions is crucial for maintaining cellular function. Recent discoveries have unveiled the existence of specialized chaperone assemblies, known as epichaperomes, which serve as scaffolding platforms that orchestrate the reconfiguration of protein-protein interaction networks, thereby enhancing cellular adaptability and proliferation. This study explores the structural and regulatory aspects of epichaperomes, with a particular focus on the role of post-translational modifications (PTMs) in their formation and function. A key finding is the identification of specific PTMs on HSP90, particularly at residues Ser226 and Ser255 within an intrinsically disordered region, as critical determinants of epichaperome assembly. Our data demonstrate that phosphorylation of these serine residues enhances HSP90’s interactions with other chaperones and co-chaperones, creating a microenvironment conducive to epichaperome formation. Moreover, we establish a direct link between epichaperome function and cellular physiology, particularly in contexts where robust proliferation and adaptive behavior are essential, such as in cancer and pluripotent stem cell maintenance. These findings not only provide mechanistic insights but also hold promise for the development of novel therapeutic strategies targeting chaperone assemblies in diseases characterized by epichaperome dysregulation, thereby bridging the gap between fundamental research and precision medicine.
Epichaperomes are chaperone assemblies that reorganize protein networks under stress. Here, authors reveal how HSP90 phosphorylation drives epichaperome formation, linking this process to cancer cell behaviors and pluripotent stem cell functions.
Journal Article
Free amino acid contents of selected Ethiopian plant and fungi species: a search for alternative natural free amino acid sources for cosmeceutical applications
Free amino acids (FAAs), the major constituents of the natural moisturizing factor (NMF), are very important for maintaining the moisture balance of human skin and their deficiency results in dry skin conditions. There is a great interest in the identification and use of nature-based sources of these molecules for such cosmeceutical applications. The objective of the present study was, therefore, to investigate the FAA contents of selected Ethiopian plant and fungi species; and select the best sources so as to use them for the stated purpose. About 59 different plant species and oyster mushroom were included in the study and the concentrations of 27 FAAs were analyzed. Each sample was collected, lyophilized, extracted using aqueous solvent, derivatized with Fluorenylmethoxycarbonyl chloride (Fmoc-Cl) prior to solid-phase extraction and quantified using Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometric (LC-ESI–MS/MS) system. All the 27 FAAs were detected in most of the samples. The dominant FAAs that are part of the NMF were found at sufficiently high concentration in the mushroom and some of the plants. This indicates that FAAs that could be included in the preparations for the management of dry skin condition can be obtained from a single natural resource and the use of these resources for the specified purpose have both economic and therapeutic advantage in addition to fulfilling customer needs.
Journal Article
Comparison of Individual Sensors in the Electronic Nose for Stress Detection in Forest Stands
Forests are increasingly exposed to natural disturbances, including drought, wildfires, pest outbreaks, and windthrow events. Due to prolonged droughts in the last years in Europe, European forest stands significantly lost vitality, and their health condition deteriorated, leading to high mortality rates, especially, but not limited to, Norway spruce. This phenomenon is growing, and new regions are being affected; thus, it is necessary to identify stress in the early stages when actions can be taken to protect the forest and living trees. Current detection methods are based on field walks by forest workers or deploying remote sensing methods for coverage of the larger territory. These methods are based on changes in spectral reflectance that can detect attacks only at an advanced stage after the significant changes in the canopy. An innovative approach appears to be a method based on odor mapping, specifically detecting chemical substances which are present in the forest stands and indicate triggering of constitutive defense of stressed trees. The bark beetle attacking a tree, for example, produces a several times higher amount of defense-related volatile organic compounds. At the same time, the bark beetle has an aggregation pheromone to attract conspecifics to overcome the tree defense by mass attack. These substances can be detected using conventional chemical methods (solid-phase microextraction fibers and cartridges), and it is proven that they are detectable by dogs. The disadvantage of classic chemical analysis methods is the long sampling time in the forest, and at the same time, the results must be analyzed in the laboratory using a gas chromatograph. A potential alternative novel device appears to be an electronic nose, which is designed to detect chemical substances online (for example, dangerous gas leaks or measure concentrations above landfills, volcanic activity, etc.). We tested the possibility of early-stage stress detection in the forest stands using an electronic nose Sniffer4D and compared the individual sensors in it for detecting the presence of attacked and dead trees. Our results indicate the promising applicability of the electronic nose for stress mapping in the forest ecosystem, and more data collection could prove this approach.
Journal Article
An ethogram analysis of cutaneous thermal pain sensitivity and oxycodone reward-related behaviors in rats
Inter-relationships between pain sensitivity, drug reward, and drug misuse are of considerable interest given that many analgesics exhibit misuse potential. Here we studied rats as they underwent a series of pain- and reward-related tests: cutaneous thermal reflex pain, induction and extinction of conditioned place preference to oxycodone (0.56 mg/kg), and finally the impact of neuropathic pain on reflex pain and reinstatement of conditioned place preference. Oxycodone induced a significant conditioned place preference that extinguished throughout repeated testing. Correlations identified of particular interest included an association between reflex pain and oxycodone-induced behavioral sensitization, and between rates of behavioral sensitization and extinction of conditioned place preference. Multidimensional scaling analysis followed by k-clustering identified three clusters: (1) reflex pain, rate of behavioral sensitization and rate of extinction of conditioned place preference (2) basal locomotion, locomotor habituation, acute oxycodone-stimulated locomotion and rate of change in reflex pain during repeated testing, and (3) magnitude of conditioned place preference. Nerve constriction injury markedly enhanced reflex pain but did not reinstate conditioned place preference. These results suggest that high rates of behavioral sensitization predicts faster rates of extinction of oxycodone seeking/reward, and suggest that cutaneous thermal reflex pain may be predictive of both.
Journal Article