Publication Server of Constructor University Library
Not a member yet
858 research outputs found
Sort by
Site-selective intermolecular mono aldolization of prochiral diketone substrates
No full textOrganocatalysis is a relatively new field that focuses on using sub-stoichiometric quantities of small organic molecules to furnish advanced building blocks of medicinal value. In comparison to enzymes and metal catalaysis, organocatalysis at times offer competitive solutions regarding enantioselectivity, diastereoselectivity and yield. Amine based organocatalysts are the most studied organocatalysts and are used for a number of asymmetric organic reactions, typical are Michael and aldol reactions. Over the last 16 years a large variety of acyclic and cyclic ketone substrates, were reported for asymmetric aldol reactions but so far very limited examples are available for diketone substrates in aldol chemistry. Site-selective aldolization of non-hindered diketone substrates using organocatalysts represents a significant chemical challenge. In order to pursue this challenge I synthesized different 4-substituted cyclohexanone to test this concept. The outcome of a site-selective diketone reaction is that one of the two diketone carbonyl moieties is selectively targeted. During this research with 4-substituted cyclohexanones this means that I was able to functionalize the cyclohexanone carbonyl moiety selectively over the ketone carbonyl moiety. This thesis focuses on my progress towards simultaneous site-, chemo-, regio-, diastereo-, and enantiolselective aldol reactions of these diketones
Permeation of peptides and antibiotics across the major outer membrane channel of Campylobacter jejuni
No full textIn this thesis, we investigated two different subjects: Firstly, we studied the permeation of peptides and a fluoroquinolone antibiotic namely, ciprofloxacin across the major channel of Campylobacter jejuni (C. jejuni). Secondly, we studied the gating properties of another complex porin from Pseudomonas aeruginosa (P. aeruginosa). In-vitro single channel measurements were utilized to understand the permeation of peptide and antibiotics. However, in addition to electrophysiology, molecular simulations were also performed to better understand the gating properties of the porin from P. aeruginosa. With respect to the transport properties of porin, in the second chapter, we studied the translocation of short cationic peptides across the major outer membrane protein (MOMP) channel from C. jejuni. Basic single channel properties such as ion-conductance and selectivity were reported. Furthermore, to understand the transport properties, short cationic peptides were used. Voltage dependent transport properties of peptides through MOMP was reported.In Chapter 2.2, we studied the translocation of ciprofloxacin across the MOMP channel. Interestingly, we studied the single channel properties of two different variants of MOMP namely the MOMP purified from C. jejuni (nMOMP) and the heterologously expressed in E. coli (rMOMP). The channel was further tested with the divalent cation, Ca2+. The presence of Ca2+, has influenced the binding kinetics across the MOMP channel of Campylobacter.In the third chapter (Annexe, Manuscript in preparation) we made a detailed study in the gating properties of OccK5 porin of P. aeruginosa. The gating transitions were analysed in all environmental conditions such as pH and ion-concentration. In addition, we report a single point mutation (Gln) can drastically modulate the gating scheme of the channel
Radical Optimization of Expanded Bed Chromatography by the Implementation of an Interaction Energy Predictive Framework
No full textExpanded Bed Adsorption (EBA) is an ingenious approach to reducing the steps required in primary purification while simultaneously allowing the processing of fermentation broths with extremely high cell densities. Most of the downsides of the first generation EBA have been negated with optimized flow distribution as well as the development of new chromatographic materials of sufficient weight to ensure an adequately fluidized and stable bed. This technology has become one of the most promising ways into the future of downstream processing. Nevertheless, a major problem yet to be solved for EBA are the unfavorable biomass-adsorbent interactions as well as the cell aggregation phenomenon, i.e. adhesive interactions between the adsorbent and crude biomass, which are the major cause of poor process performance, low product recovery, and in the worst case, bed collapse.
The research work reported in this Ph.D. thesis is aimed to develop a predictive framework for optimized EBA process conditions, for which we have coined the term IntEP (Interaction Energy Predictor). This framework employs classical colloid theory, namely extended Derjaguin, Landau, Verwey and Overbeek (xDLVO) theory, to determine (within specified operation windows) best-case scenarios of mobile phase composition that will result in the maximization of repulsive interactions between biomass and adsorbent.
Based on IntEP-optimized conditions, lab-scale EBA experiments using MabDirect® Protein-A adsorbent beads to purify a proprietary mAb from high-density CHO cells feedstock performed. This experimental work leads to the conclusion that these optimized conditions not only improve process efficiency and hydrodynamics but also increase product recovery.
With IntEP, it is possible to circumvent the need for empirical determination of these optimal process conditions in EBA, thus leading to quicker method development and better purification
Molecular mechanism of peptide binding to major histocompatibility complex class I molecules in the cellular context
No full textPeptide fragments of all cellular proteins are constantly presented at the cell surface, in a complex with MHC (major histocompatibility complex) class I molecules, to cytotoxic T lymphocytes. The recognition of epitopes of viral or tumor origin induces the lysis of the presenting cell, and thus stops the spread of the infection. Not every peptide can bind to class I since each allotype has its own signature binding motif, manifested in the shape, chemical nature, and depth of the pockets of the binding groove into which side chains of the bound peptide protrude. The length of the bound peptide is usually 8-10 amino acids, since the ends of the binding groove are closed.
The structure of MHC class I molecules, and the mode of peptide binding at steady-state, are fairly well understood, whereas the dynamical and energy details of the peptide binding to class I are still a challenge. This is mainly because there is no available crystal or NMR structure of an empty class I molecule. Thus, in the absence of definitive experiments, understanding molecular details of the class I folding process and describing the differences between the peptide-bound and the peptide-free form of class I require a computational approach in addition to the biochemical and biophysical approaches.
Molecular dynamics (MD) simulation is a valuable computational approach. It applies the rules of classical mechanics to describe the details of folding and interactions at atomistic level. Enhanced sampling methods of MD estimate values of the energy barriers between the different conformational states of proteins.
In this work, I have used MD simulations to study the dynamics of class I in different peptide binding states. I have used several biophysical and biochemical assays to validate experimentally the theoretical assumptions. My data suggest a common model for empty class I molecules. In this model, the F pocket region has a prominent effect on the conformational and energy properties of the entire peptide binding site. When the peptide is absent, the F pocket region shows a high configurational entropy. This suggests partial unfolding of this region at longer time scales. The suggested model explains the dependence of a disease associated class I allotypes on the chaperone protein tapasin for binding peptides. Charge repulsion at the bottom of the F pocket region increases the flexibility of this region and destabilizes its conformation.
I have also investigated a mutant form of class I in which the two alpha helices that delineate the F pocket are linked by a disulfide bond that mimics the conformational and dynamic effects of the peptide. The data suggest a coupling between peptide and β2m binding to the F pocket region, which supports a folded conformation of class I.
The findings of this project demonstrate a method to describe the energy and conformational details of class I/peptide binding. The suggested model identifies parameters from theoretical simulations that can be used to predict the peptide binding behavior of novel or uncharacterized class I molecules. This work illustrates that MD simulations can be used and complemented by experimental approaches to describe the mechanism of ligand-receptor binding
Entangled? Linking governance systems for regional-scale coral reef management: Analysis of case studies in Brazil and Indonesia
No full textIncreasing anthropogenic impact on coastal and marine resources has led to extensive and sometimes irreversible damage of coral reef ecosystems. Decentralization and strengthening the role of local communities and non-governmental actors promises great advantages for governance, but marine ecosystems and resources are affected by drivers of change that lie outside the reach of small-scale approaches. This has caused strong drawbacks for their success. The multi-level governance approach thus incorporates the socio-economic, political and ecological interconnectedness to achieve sustainable outcomes at larger scales. It particularly highlights the need for integrating different levels of decision-making and emphasizes the need of continuous cross-level interaction to address uncertainty and dynamic change in coastal and marine Social-Ecological Systems.
This research examines marine governance in Brazil and Indonesia from a multi-level perspective to address the degradation of coral reef ecosystems and their associated flora and fauna. A policy analysis is conducted at the national level in Brazil and Indonesia to analyze the recent developments and examine the overall umbrella frameworks with regards to how effectively they enable the participation of resource users and balance between the needs of marine resource dependent local populations and conservation objectives. In light of the current developments in literature, this research then examines how governance actors are entangled across levels and scales for regional marine governance in two case study areas in Brazil and Indonesia. The results of the study contribute to improve understanding of how to link a growing number of actors across multiple jurisdictions and quasi-autonomous governance units and identify points of leverage to facilitate integrated multi-level marine governance
Characterization and modeling of nanostructured silicon thin-film optoelectronic devices
No full textDesign and fabrication at nanometer scale level have enabled development of novel optoelectronic devices. These devices take advantage of the optical phenomena that occur when light interacts with structures that are smaller than the wavelength of the incoming light. Depending on how these structures are employed, different functions can be achieved. When the thickness of devices is a fraction of the wavelength, they become transparent. On the other hand, optoelectronic devices become highly absorbing, when nanostructures are introduced at their interfaces. In this research, silicon thin-film optoelectronic devices with nanostructured layers and interfaces are studied.
An ultra thin-film transparent photodetector is used to experimentally realize standing wave and transparent Fabry-Perot spectrometer. Optical models for these devices are developed using an analytical approach to solve Maxwell's equations. Excellent agreement between experimental and calculated results is demonstrated. The linear setup of these spectrometers,
allows for the realization of spectral imaging cameras where the spectrum of the light source is obtained by the Fourier transform of the detector signal.
The performances of silicon thin-film solar cells deposited on randomly textured substrates are investigated experimentally and by optical simulations. The investigation has been focused on the back contact losses. A comparison of experimental results and optical simulations reveals that the back contact losses are influenced by plasmonic resonances only when the nanofeatures are present at the interface between a metal reflector and solar cell. The plasmonic losses can be reduced by introducing a transparent conductive oxide buffer layer or by removing the nanofeatures. The optimization of the back contact leads to improved performances of silicon thin-film solar cells
Art and Neuroscience : The Historical Emergence and Conceptual Context of Neuro-Art
No full textThis study has developed on the premise that neuroscience has a significant impact on contemporary art, and on the observation that, from the dialogue with neuroscience, a new artistic tendency has been emerging. The aim of this research was therefore to investigate the roots, the emergence, and development of what I generically call neuro art. The main objective of the research was to initiate the history of neuro art.
This history of neuro art investigates, for the first time, the relationship between neuroscience and contemporary practice of the visual arts by identifying and examining those artworks that rely on knowledge of the brain and the nervous system. The study begins with a broad analysis of the role neuroscience plays in contemporary culture. The analysis situates neuro art within the larger context of cultural interactions with neuroscience, defines neuro art, and frames the history of neuro art in relation with two other disciplines: neuroaesthetics and neuroarthistory.
The core of the research addresses in detail the history of art objects about the brain and the nervous system. Setting the scene, the thesis first describes the earlier manifestations of neuro art and identifies its conceptual and historical roots. It further addresses the exhibitions of neuro art and it evaluates their role in the overall history of this phenomenon. The last, and most consistent part of this research is a detailed thematic analysis of the actual works of neuro art.
The thesis concludes by providing explicit answers to the questions that have guided this research, and by confronting its initial assumptions with actual findings about neuro art
Cluster Location: Is this the Place to be? An Investigation on the Influence of Cluster Affiliation on Firm Performance and Human Resources
No full textA Narrative Review on the Influence of Cluster Location on Firm Performance
A wide body of theoretical literature states that industry clusters can offer numerous benefits for resident companies. Advantages of cluster locations, such as access to multifaceted business partners and complementary resources, are believed to be the bedrock of added performance which clustered firms are suspected to acquire. Nonetheless, empirical results regarding the effect of cluster location on a firm’s success are diverse as well as fragmented, and even as of today a comprehensive summary of empirical findings is missing. In light of this, the purpose of this study is to review the findings of previous research on the general influence of cluster affiliation on firm performance, and to map the empirical evidence about underlying mechanisms influencing this relationship. Recommendations for managers and politicians are derived, and gaps for future research are identified.
The Influence of Cluster Affiliation on Firm’s Labor Supply and Labor Turnover
Theoretical cluster literature often emphasizes the specialized local labor pool as a potentially major source of competitive advantage for resident firms. Yet, empirical studies evaluating these assumed benefits are still scarce and fragmented. This study draws on an extended version of the resource-based view, exploring the influence of cluster location on company labor supply and labor turnover using a holistic approach. Survey data from the German ICT and wind energy industries were analyzed using partial least squares path modeling. Two cluster measurements were applied: a geographically narrow one for very local clusters, and a geographically wider one for broad clusters. The results reveal that firms in very local clusters benefit from a superior quality of applicants. With respect to labor turnover, cluster companies generally show a higher degree of desired labor turnover (desired from a company perspective). Furthermore, firms in broad cluster regions suffer from more non-desired labor turnover.
The Influence of Cluster Affiliation on Firm’s Human Resources
Clusters are often highly valued as areas where firms are advantageously located. In theoretical cluster literature, the specialized local labor pool of these regions is a characteristic which is emphasized to be a key benefit for resident companies. However, so far only a small fraction of empirical knowledge is available on the topic of firms’ human resources in clusters. Drawing upon an extended version of the resource-based view theory, this study comprehensively investigates the influence of cluster locations on firms’ skilled human resources. Survey data were analyzed from 72 companies specializing in the information and communication technology and wind energy sectors located in Germany. The cluster measurement is based on the number of same-industry firms within specific radius distances surrounding the investigated firms. One radius distance was geographically smaller, being that for narrow clusters (15-minutes travel distance by car), the second was geographically wider for broad clusters (50-minutes travel distance by car). The two key results via a partial least squares path model analysis indicate that firms located in narrow clusters enjoy higher degrees of external social capital of their skilled employees, whereas firms situated in broad clusters have to cope with shorter skilled employee tenures
Leadership in a Changing Business World. A Multilevel Perspective on Connecting Employees to Organizational Goals
No full textIn a dynamic business world, supervisors need to link employees to the organization. Yet, we know little about how leadership operates at different levels or boundary conditions for supervisors' effectiveness. I address these questions considering the alignment between the supervisor and the organizational context.
Chapter 2 explores the role of supervisors' psycho-social and career mentoring for organizational career management. I distinguish individual-level differentiated mentoring (i.e., deviation of individual perception from the average team perception) and group-level mentoring (i.e., average perception of all team members). Differentiated psycho-social mentoring enhances promotability via career motivation, and job satisfaction mediates the favorable effects of both differentiated mentoring functions on intentions to stay. In contrast to dyadically focused psycho-social mentoring, group-level career mentoring, which is aligned with more general organizational aspects, has contextual effects on both outcomes.
In Chapter 3, I find that nationality diversity is only positively related to diversity climate and team performance in interdependent teams when supervisors' cultural intelligence is high. However, the relationship is nonsignificant when the team is diverse in terms of age or gender, or when close cooperate is not needed. Thus, in order to be effective, supervisors' characteristics need to be aligned with the specific work group needs.
Chapter 4 explores the role of alignment between supervisor and the organization, represented by supervisors' cynicism about change. Supervisors' contingent reward leadership only attenuates employees' cynicism about change and enhances performance when supervisors' cynicism is low.
In sum, I shed light on the complex mechanism through which supervisors act as organizational sense-makers. By considering the implications of alignment, organizations can capitalize on supervisors' potential to manage contemporary careers, diversity, and change
Spatial variability of light regimes under Arctic sea ice
No full textLight transmission through Arctic sea ice is an important process for the energy partitioning in the climate system. Thus understanding its spatial variability is important for a precise determination and prediction of energy fluxes across the atmosphere-ice-ocean interface. In this thesis the variables driving this variability – such as melt pond cover and ice thickness – as well as the length scales of this variability are investigated together with experimental and theoretical analysis of the geometry of optical properties of the ice cover. The work is based on optical measurements conducted during under ice surveys with remotely operated vehicles employing an interdisciplinary sensor package. It is found that the spatial scale of the light field variability under sea ice is driven by variations in ice albedo on scales of hundred meters and by ice thickness variability on larger scales. Also, the geometry of the light-field under sea ice is strongly influenced by the lateral inhomogeneity of the sea ice cover, further complicating the interpretation of standard ocean optics measurements. This thesis shows, that due to the lamellar crystal structure of sea ice, light propagation within is dependent on the direction of photon travel. The operations of under ice remotely operated vehicles also enabled an interdisciplinary study, showing that the spatial distribution of algal aggregates underneath sea ice is not governed by typical habitat properties such as light availability or temperature, but by a hydrodynamic interaction of the buoyant algal aggregates with the ice bottom topography. These results were applied in a new light parameterization allowing for the calculation of Arctic wide in and under ice primary production and will lead to a better ability to assess the impact of the spatial inhomogeneity in sea ice on the large scale energy budget of the melting Arctic sea ice