Verankerung von Rhodium-Hydrierkatalysatoren an Alkylthiolat-beschichtete Goldkolloide

In this project, a new approach to heterogeneous catalysts based on selfassembled monolayers has been investigated. Catalytically active metal complexes, containing a linker with a thiol group, were attached to the surface of gold particles or colloids and were embedded in an environment of spacers. Gold as a solid support Gold surfaces have the advantage that they are inert and do not interact with the active metal center. Gold particles or colloids can be prepared with a variable diameter and surface area and catalyst immobilization takes place under mild conditions. Gold particles We have developed a general synthesis of a range of thiols, symmetrical and unsymmetrical disulfides (chapters 2.2 and 2.3). To determine the amount of metal complex attached to the gold surface, we attached p-nitrophenylester groups to the linkers, which are easily cleavable under certain conditions. With this system we were able to study the immobilization and loading under different conditions, e.g. solvent, time, concentration and gold core size (chapters 4.3, 4.4, 4.5 and 5.4). We have also immobilized a metal complex on the gold surface (without spacers) and used it in catalysis. The system was active, but the gold particles were too large (d = 1000 nm) and 5.40 g of gold had to be used for a reaction with 0.5 mmol substrate (chapter 4.8). Therefore, we decided to investigate the immobilization on gold colloids, which are approximately 1000 times smaller and therefore have a much larger surface area per gram of gold. Gold colloids A series of n-alkanethiolate-protected gold colloids with diameters between 2.3 - 3.5 ± 0.6 nm were prepared by the sodium borohydride reduction of AuCl4 - in the presence of an n-alkylthiol. Thermogravimetric analysis and XPS-measurements proved that the S-Au bond is stable up to 150 °C (chapters 5.5.5 and 5.5.7). Gold colloids were modified with a monolayer of apolar (methyl and adamantyl), polar (OH and NH2) or chiral (norephedrine derived) thiolates. The apolar and chiral colloids were purified by precipitation from toluene with ethanol. Rhodium(I)- complexes 49 and 74 were introduced according to the "place exchange" methodology described by Murray and co-workers. The resulting functionalized colloids were purified by precipitation from ethanol with hexane. Asymmetric Hydrogenation The catalytic activity and selectivity of the colloids 98 - 100 were similar to the corresponding homogeneous catalyst 49. At the end of the reaction, the modified colloids could be recovered by filtration after the addition of 2 eq. of cyclooctadiene. The activity and selectivity of the colloids 101 and 102 were lower than those of the corresponding homogeneous catalyst 49. STM-Investigations The exchange reaction was also carried out on (111) oriented Au surfaces by immersing a gold film in n-octanethiol solutions. The obtained films were investigated with STM under ambient conditions. The best conditions, giving a highly ordered upright standing arrangement of thiolates, were found in ethanol with a concentration of 10-1 M, a immobilization temperature of 55 °C and an incubation time of 8 h (chapter 6.9). STM studies showed that n-octanethiolates were exchanged by functionalized thiols, which contain a longer chain length than C8, and that the catalytic sites are distributed statistically (chapter 6.12). The exchange reaction with the rhodiumpyrphos- complex 49 showed much perturbation on the (111) gold surface during the measurements, probably due to the flexible head-group of the immobilized catalyst (chapter 6.13)

Wrong Patient, Wrong Drug: An Unfortunate Confluence of Events

Older adults, aged 65 years or older, represent 14.9% of U.S. population, and are projected to increase to 22% by 2050. It is estimated that almost half of hospitalized patients are older adults and is expected to increase as the population ages. Hospitalized older adults are most vulnerable to adverse events because of aging‐related conditions, physiological changes, and multiple comorbidities as well as fragmented care. The primary goal of health care providers is to improve patient safety and decrease adverse events. This chapter will use a complex clinical scenario with numerous potential overlapping risks to address the many active and latent factors that lead to patient safety‐related adverse events. Factors involved, as well as preventive strategies, will be discussed in detail

Viral factors in influenza pandemic risk assessment

The threat of an influenza A virus pandemic stems from continual virus spillovers from reservoir species, a tiny fraction of which spark sustained transmission in humans. To date, no pandemic emergence of a new influenza strain has been preceded by detection of a closely related precursor in an animal or human. Nonetheless, influenza surveillance efforts are expanding, prompting a need for tools to assess the pandemic risk posed by a detected virus. The goal would be to use genetic sequence and/or biological assays of viral traits to identify those non-human influenza viruses with the greatest risk of evolving into pandemic threats, and/or to understand drivers of such evolution, to prioritize pandemic prevention or response measures. We describe such efforts, identify progress and ongoing challenges, and discuss three specific traits of influenza viruses (hemagglutinin receptor binding specificity, hemagglutinin pH of activation, and polymerase complex efficiency) that contribute to pandemic risk

SECTM1 Produced by Tumor Cells Attracts Human Monocytes via CD7-Mediated Activation of the PI3K Pathway

Tumor-associated macrophages (TAMs) have essential roles in tumor progression and metastasis. Tumor cells recruit myeloid progenitors and monocytes to the tumor site, where they differentiate into TAMs; however, this process is not well studied in humans. Here we show that human CD7, a T-cell and NK cell receptor, is highly expressed by monocytes and macrophages. Expression of CD7 decreases in M-CSF-differentiated macrophages and in melanoma-conditioned medium–induced macrophages (MCMI/Mφ) in comparison to monocytes. A ligand for CD7, SECTM1 (secreted and transmembrane protein 1), is highly expressed in many tumors, including melanoma cells. We show that SECTM1 binds to CD7 and significantly increases monocyte migration by activation of the PI3K (phosphatidylinositol 3′-kinase) pathway. In human melanoma tissues, tumor-infiltrating macrophages expressing CD7 are present. These melanomas, with CD7-positive inflammatory cell infiltrations, frequently highly express SECTM1, including an N-terminal, soluble form, which can be detected in the sera of metastatic melanoma patients but not in normal sera. Taken together, our data demonstrate that CD7 is present on monocytes and tumor macrophages and that its ligand, SECTM1, is frequently expressed in corresponding melanoma tissues, possibly acting as a chemoattractant for monocytes to modulate the melanoma microenvironment

Viral to metazoan marine plankton nucleotide sequences from the Tara Oceans expedition

A unique collection of oceanic samples was gathered by the Tara Oceans expeditions (2009-2013), targeting plankton organisms ranging from viruses to metazoans, and providing rich environmental context measurements. Thanks to recent advances in the field of genomics, extensive sequencing has been performed for a deep genomic analysis of this huge collection of samples. A strategy based on different approaches, such as metabarcoding, metagenomics, single-cell genomics and metatranscriptomics, has been chosen for analysis of size-fractionated plankton communities. Here, we provide detailed procedures applied for genomic data generation, from nucleic acids extraction to sequence production, and we describe registries of genomics datasets available at the European Nucleotide Archive (ENA, www.ebi.ac.uk/ena). The association of these metadata to the experimental procedures applied for their generation will help the scientific community to access these data and facilitate their analysis. This paper complements other efforts to provide a full description of experiments and open science resources generated from the Tara Oceans project, further extending their value for the study of the world's planktonic ecosystems

The European Reference Genome Atlas: piloting a decentralised approach to equitable biodiversity genomics.

ABSTRACT: A global genome database of all of Earth’s species diversity could be a treasure trove of scientific discoveries. However, regardless of the major advances in genome sequencing technologies, only a tiny fraction of species have genomic information available. To contribute to a more complete planetary genomic database, scientists and institutions across the world have united under the Earth BioGenome Project (EBP), which plans to sequence and assemble high-quality reference genomes for all ∼1.5 million recognized eukaryotic species through a stepwise phased approach. As the initiative transitions into Phase II, where 150,000 species are to be sequenced in just four years, worldwide participation in the project will be fundamental to success. As the European node of the EBP, the European Reference Genome Atlas (ERGA) seeks to implement a new decentralised, accessible, equitable and inclusive model for producing high-quality reference genomes, which will inform EBP as it scales. To embark on this mission, ERGA launched a Pilot Project to establish a network across Europe to develop and test the first infrastructure of its kind for the coordinated and distributed reference genome production on 98 European eukaryotic species from sample providers across 33 European countries. Here we outline the process and challenges faced during the development of a pilot infrastructure for the production of reference genome resources, and explore the effectiveness of this approach in terms of high-quality reference genome production, considering also equity and inclusion. The outcomes and lessons learned during this pilot provide a solid foundation for ERGA while offering key learnings to other transnational and national genomic resource projects.info:eu-repo/semantics/publishedVersio