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Phenotypic and Genetic Exploration of Novel Saccharomyces Yeast Hybrids with Enhanced Beer Brewing Characteristics
Non-domesticated Saccharomyces yeasts have promising brewing characteristics for beer diversification particularly when used in the generation of de novo interspecific hybrids. Here, non-cerevisiae Saccharomyces interspecific hybrids are explored in wort fermentations for exotic lagers and non-alcoholic beers with complex aroma profiles. Maltose and maltotriose utilization, typically associated with domesticated ale/lager brewing strains, were found in multiple Saccharomyces isolates using high-throughput screening. Saccharomyces mikatae successfully grew on maltotriose as the sole carbon source, a trait until recently unidentified for this species and only recently demonstrated in Saccharomyces jurei, another “wild” species of the clade. Remarkably, de novo hybrids between maltotriose-utilizing S. mikatae/S. jurei and the maltotriose-negative Saccharomyces eubayanus displayed heterosis on maltotriose outperforming both parents. The hybrids were only able to ferment maltose in lager brewing conditions; nevertheless, favorable fruity esters were produced. This study shows that novel hybrids can add to the diversity of lager brewing. Strains unable to grow on either sugar were identified, making them suitable candidates for brewing low-alcohol beers. Wort fermentations hinted the potential for low-alcohol brewing using novel maltose/maltotriose negative Saccharomyces hybrids producing low levels of off-flavors with one S. arboricola isolate highlighted for future studies. Interspecific Saccharomyces hybrids are sterile, hindering genetic analysis of traits of interest. One desired trait in lager brewing is cold-tolerance, with alternative hybrid combinations utilizing cold-tolerant yeasts possible. The cold-tolerance of Saccharomyces arboricola was investigated by successfully restoring fertility in Saccharomyces cerevisiae x S. arboricola hybrids and mapping quantitative trait loci (QTL) responsible in a multigeneration population with a focus on mitochondrial-nuclear interactions. QTL were successfully mapped in the S. cerevisiae genomes of the hybrids with the majority exclusive to specific mitotype. QTL in S. arboricola were not mapped due to lower diversity in the strains used. The method described here provides valuable lessons toward unraveling genetic determinants behind brewing traits in Saccharomyces hybrids
Comparing the long-term effects of health behaviours and health problems on depression among the elderly in Germany and Taiwan
Depression is rising both in Germany and Taiwan among all age groups but specially, also among elderly. In Taiwan, a larger proportion of users of antidepressants are over 65 years of age (NHI, 2020). In Germany, 24 % of people aged 65+ reporting depression symptoms in 2017 (OECD, 2019).
Data were extracted from the DEAS and the TLSA. Both of DEAS and TLSA were a countrywide representative survey. The scale used to measure depression in the two surveys was the CES-D. Data analysis included regression models, specifically logistic regression, and Generalized Estimating Equations. The McNemar test and Mantel-Haenszel test was applied to examine the consistency of the responses of the same group of subjects before and after the test.
The study found that in Germany, subjects with heart disease, cancer, and poor self-rated health (SRH) were more likely to suffer from depression. In Taiwan, subjects with diabetes, heart disease, stroke, cancer, and poor SRH were more likely to be depressed. Both countries showed that the drinking and exercise groups had a lower chance of developing depression. Widowhood increased the risk of developing depression, but there was no gender difference.
In addition to maintaining and improving physical health, exercise has been proven in this study to relieve psychological depression. Partnerships, on the other hand, provide social bonding and social support for middle-aged and older adults. Without a spouse, there is an association with more psychological health constraints like depression in older people living in Germany and Taiwan. Getting out and building relationships with friends and exercising together could be a good way to decrease the risk of depression among the elderly. According to attachment theory, having a stable relationship with some friends can also help the emotions of the elderly recover from the death of their spouse
The effects of climate change and climate variability on the distribution of Atlantic cod (Gadus morhua) in the Arctic
The Arctic is experiencing warming to a much higher degree compared to other regions on Earth. The annual mean surface temperature between 1971 and 2019 was three times higher than the global average (AMAP 2021). While previous warm episodes like the Early Arctic warming occurring from the 1920s to 1960s are known to be driven by natural processes like changes in the North Atlantic Oscillation (NAO), recent studies provide evidence that the ongoing Arctic warming process differs from the earlier phases and that it is caused by anthropogenically induced large-scale global warming. Consequences for the local marine ecosystem can be, among other things, a shift in species abundance and distribution from a polar towards a more boreal community. In this context, fish species like the Atlantic cod (Gadus morhua) are reported to have risen in abundance in the Arctic region over the last decades.
This dissertation focuses on the effects of climate change and climate variability on the population structure and spatial distribution of Atlantic cod in the fjords of Svalbard. A combination of different methods was used and included fishing campaigns in several locations on the coast of Svalbard, genetic studies on the ecotype composition of the catches, otolith studies on subpopulation structure, and year-round in situ camera observations on the occurrence of juvenile cod in the shallow waters of the Kongsfjorden ecosystem.
Based on the combined use of observation, otolith shape, and genetic tools, a local ecotype, the “Svalbard coastal cod (SCC)” could be identified as a potential permanent resident in Svalbard fjords. Eggs or larvae of Atlantic cod could not be identified in the catches, nevertheless, eggs of long rough dab have been found during the ichthyoplanktonic surveys indicating spawning in the area. Both, Atlantic cod, and the long rough dab share a similar lifestyle and demonstrate the recent invasion of boreal species into the Arctic marine ecosystem
From Bench to Bedside: Development of a MAPPs assay-based personalized healthcare tool to evaluate the clinical immunogenicity of therapeutic antibodies
Despite success, the use of therapeutic monoclonal antibodies (mAbs) in clinical settings has been complicated by the ability of the patient’s immune system to provoke an unwanted humoral immune response against the drug, generally through the formation of anti-drug antibodies (ADAs) – termed immunogenicity. ADA onset may compromise clinical efficacy and impact safety in patients. A fundamental area of immunogenicity research is investigating mAb-derived peptides processed by dendritic cells (DCs) and presented through major histocompatibility complex (MHC) class II receptors. These mAb-derived peptides, representing potential T cell engaging epitopes, orchestrate the immunogenicity cascade by directly influencing T cell activation leading to ADA production. The MHC-II-associated peptide proteomics (MAPPs) assay is a Roche-invented methodology to identify and quantify such potential T cell epitopes. As an integrated approach during preclinical drug development, MAPPs is used alongside other in vitro, in silico, and in vivo tools to address the risk of immunogenicity. This PhD work aims to extend the applications of MAPPs for the development of a tool for personalized healthcare (PHC) in the clinic with the purpose of identifying patients with a potential risk of immunogenicity prior to treatment in order to devise an ideal treatment plan (main aim 1). Moreover, since most MAPPs studies are currently restricted to HLA-DR as the dominant MHC-II genotype due to lack of satisfactory MHC-II receptor-precipitating reagents available, an immunoprecipitation strategy using the MAPPs assay alongside the advanced epitope–prediction algorithm NetMHCIIpan was developed to accommodate MHC-II pan receptors for improved predictability of potential T cell epitopes (main aim 2). Taken together, these reformed uses of the MAPPs assay will lead to an invaluable clinical tool for immunogenicity risk assessments that support personalized healthcare
Study of E. coli outer membrane proteins to understand and combat antibiotic resistance
Antibiotic resistance poses severe threats on mankind and ruins the greatest of medical advancements. At the economic level, it not only causes loss of productivity but also creates huge burden on healthcare expenses. Regarding antibiotic resistance Gram-negative bacteria especially the ESCAPE pathogens are in the limelight as they are responsible for the highest mortality rates. Their multidrug resistance results from a combination of factors including modification of antibiotic uptake pathway as well as decreased intracellular concentration of drugs. Reduced intracellular drug retention is a result of drug elimination and is mostly driven by RND-family of efflux pumps. AcrAB-TolC is a prototype of this family in E. coli. TolC being the outer membrane component of this efflux machinery is readily available for reconstitution on synthetic lipid bilayers and thus allows substrate interactions to be studied at a single channel level. In the present study, biophysical approach to identify small chemical molecules as TolC inhibitors is described. In order to observe their interaction with TolC at a single molecule level, traditional electrophysiology technique has been used and method’s resolution is extended using principles of protein engineering as well as novel data analysis considering also the ion current fluctuations. At the same time, porin dependent translocation of a therapeutically important class of antibiotics is studied and novel uptake pathways are reported. Although, not directly beneficial to clinical development, outcomes of these studies will help to open new ways for further research and I hope this thesis will be useful despite having many open-ended questions
Synthesis, Structural Characterization and Catalytic Studies of Peroxo-Containing Heteropolyanions
Polyoxometalates (POMs) are discrete, anionic metal-oxo clusters comprising early d-block metal ions in high oxidation states. Due to the large compositional and structural variety, POMs exhibit many interesting physicochemical properties including catalysis.POMs containing peroxo-groups are of special interest in hydrogen peroxide-assisted oxidation catalysis. In this thesis, the focus is on the synthesis of novel peroxo-containing POMs, the solid-state and solution characterization, and a study of their H2O2-based biphasic homogenous as well as heterogenous oxidation catalysis. Chapter 1 is an introduction of POMs and peroxo-POMs, whereas in Chapter 2 the motivation for the planned work is lined out. In Chapter 3, the experimental details are described, as well as the instruments used for the structural characterization and catalytic studies. In Chapter 4 some novel peroxo-Zr/Hf-containing Wells-Dawson anions are reported, which were studied for various H2O2-mediated oxidation reactions, using homogenous and supported conditions. A comparative study was also carried out on structurally-related peroxo-Zr/Hf Keggin anions. In Chapter 5 several novel peroxo-Ce-containing POMs of the Wells-Dawson type were isolated and structurally characterized in solution and in the solid state, followed by a comparative catalytic study using homogenous and supported conditions for the biphasic alcohol oxidation as well as alkene epoxidation. Chapter 6 describes the synthesis and characterization of a peroxo-Ce-containing POM of the Keggin type with the highest nuclearity amongst all peroxo-cerium POMs reported to date. Finally, Chapter 8 describes the synthesis and structural characterization of two dimethylarsinate-containing molybdenum-oxo clusters, a large, anionic mixed-valence wheel and a small neutral species. The novel compounds were mainly characterized in the solid state by FTIR,TGA, elemental analysis and XPS, and in solution by NMR and UV-Vis spectroscopy
The Potential of Fungal Biomass as Industrial Catalyst: Modification of Lipids
This study investigated the potential of fungal biomass as industrial catalyst through developing an alternative catalyst for biodiesel production using fungal biomasses for whole-cell catalysis. The research explored various fungal isolates and identified the most potent isolates. The transesterification catalytic capability of the selected isolates was improved through random genetic mutagenesis and optimization of the cultivation conditions of the chosen mutants.
Aspergillus flavus and Rhizopus stolonifer two fungal species belong to two different phyla (Ascomycota and Zygomycota) revealed the capability of their biomasses to catalyze the transesterification reaction efficiently up to 95.5 %, in relatively short reaction time (24 h.). The biomass produced was also capable of catalyzing the transesterification reaction using different acyl-acceptors. A. flavus and R. stolonifer biomasses proved the probability of using biomasses cocktails to catalyze transesterification reaction. In addition, the fungal biomass investigated exhibited considerable ability to catalyze the hydrolysis of triglycerides, which means an opportunity of producing multifunctional catalytic fungal biomass. A. flavus showed a potential to be implemented in biorefinery processes that include wastewater treatment by microalgae as part of a circular economy approach, where A. flavus biomass produced in a biorefinery approach was effectively capable of catalyzing the modification of lipids
Leading the Transition from Analog to Digital within Personal Service Firms
Given the profound changes in the demand for new innovative ways of developing and delivering services, the so-called “personal services” are responding to the digital challenge by using different approaches and at varying speed. Personal services are those services that can be found in sectors such as education, retail, hospitality (hotels, restaurants), craftmanship, art and entertainment. These are services that have been for so long designed around the idea that they only require “high-touch” personal encounters. However, due to the fact that the world today is becoming more digitalized and is heading towards what is known as a “digital revolution”, firms from this sector must look for new and alternative ways on how to adapt their business models, organizational structures, and service offerings, especially by taking advantage of the use and application of digital technologies. Thus, leading these firms to avoid what could be a long-term business collapse.
Despite the fact that it is true that certain companies within this industry such as Airbnb, VR-All-Art, or HelloFresh have managed to disrupt traditional business paradigms, even leading to building billion-dollar businesses, the reality is that personal services represent one of the few service sectors struggling the most to achieve the transition from analog to digital and thus, primarily rely on traditional and analog business models. Guidance regarding the path towards becoming digital is lacking.
To fill out this gap, this Ph.D. thesis aims to introduce a maturity model as a strategic and systematic instrument that help personal service firms to assess their current developmental digitalization stage and show trajectories for improvements to guide the transition from an analog towards a stage of “digital maturity” in a holistic and well-structured manner
Synthesis, Structure and Catalysis of Polyoxo-Noble-Metalates (Pt, Au, Pd) and Noble Metal (Pt, Rh)-Containing Polyoxometalates
This thesis is divided into six chapters. Chapter I generally introduces the historical background, structural aspects, properties, and applications of POMs, the state of the art of polyoxo-noble-metalates, noble-metal-containing POMs and arsenic compound, as well as the motivation to perform this work. Chapter II includes the information of applied analytical techniques and synthetic procedures for the used POM and organorhodium(III) precursors. Chapter III is devoted to polyoxoplatinate, polyoxopalladate and mixed polyoxo-noble-metalates, and 7 novel polyoxo-noble-metalates have been obtained with the following highlights: (i) The first PtIV-containing discrete polyoxoplatinate(II) Pt7 and polyoxopalladate(II) PtPd6 have been prepared and characterized in the solid-state, in solution, and in the gas phase; (ii) The first discrete mixed platinum(IV)-gold(III) oxoanion Pt2Au3 was structurally characterized in the solid state by single-crystal XRD and TGA, and in solution by multinuclear NMR and ESI-MS studies. Chapter IV presents 3 novel Platinum(II/III)-containing isopolytungstates. The polyoxoanion Pt3W11 consists of three {W3O13} and one {W2O10} fragments connected by three Pt(II) atoms forming linear {Pt3O12} triad. The polyoxoanion PtII2W5 and PtIII2W5 both consists of one lacunary Lindqvist fragments {W5O18}6− coordinated by two Pt(II) in square planar coordination and two Pt(III) with direct Pt–Pt bonding, respectively. Chapter V describes the synthesis of three all-inorganic platinum arenate(III) compound. The first two full inorganic discrete platinum arsenate(III) clusters: PtAs6 and Pt4As8, have been synthesized in aqua media. In Pt4As8, Each Pt atom is coordinated by two O atoms and two As atoms involved in direct As-Pt bonding. And a platinum arsenate(III) heteropolytungstate Pt2As6W4 has been synthesized in aqua media and characterized by 195Pt NMR.Chapter VI deals with the synthesis and characterization of two RhCp*-containing heteropolytungstates
Synthesis and Reactivity of 2-Diazo-1,1,3,3,3-Pentafluoropropyl Phosphonate
Diazo compounds are remarkable versatile building blocks and increasingly important molecules in organic synthesis. Even though the field of diazo chemistry was discovered more than hundred years ago it is still a subject of great research interest. Besides, the field of organofluorine chemistry has grown immensely in recent years, and fluorochemicals have permeated into nearly every aspect of our daily lives.
Hence, the aim of this work was the synthesis of a bench-stable 2-diazo-1,1,3,3,3-pentafluoropropyl phosphonate, the first fluorinated diazo compound bearing trifluoromethyl and difluoromethyl phosphonate moiety, along with a demonstration of its synthetic applications in a series of chemical reactions. After the successful synthesis, the novel diazo compound was incorporated in cyclopropanation reaction of aromatic and aliphatic terminal alkenes using CuI as a catalyst. Consequently, sixteen new cyclopropanes were synthesized in good to very good yields and under mild reaction conditions. Furthermore, a new pathway for synthesizing fluorinated β-alkoxy vinyl phosphonates via O-H insertion reaction using Rh2(OAc)4 as a catalyst is presented in this thesis. The insertion reaction of benzyl and aliphatic alcohols using the diazo compound were carried out under mild conditions and nineteen new fluorinated β-alkoxy vinyl phosphonates were synthesized in good to very good yields. The following reaction was a catalyst- and solvent-free 1,3-dipolar cycloaddition of alkynes and alkene with the diazo compound. This green approach provided an efficient route for direct synthesis of fluorinated pyrazoles and pyrazoline in moderate to excellent yields. Lastly, a Cu(II) catalysed [2,3]-sigmatropic rearrangement reaction of propargyl and allyl sulfides with the diazo compound produced products bearing difluoromethylphosphonate and trifluoromethyl groups