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Existing curricula for entrepreneurship education do not necessarily represent the best way of teaching. How could entrepreneurship curricula be improved? To answer this question, we aim to identify and rank desirable teaching objectives, teaching contents, teaching methods, and assessment methods for higher entrepreneurship education. To this end, we employ an international real-time Delphi study with an expert panel consisting of entrepreneurship education instructors and researchers. The study reveals 17 favorable objectives, 17 items of content, 25 teaching methods, and 15 assessment methods, which are ranked according to their desirability and the group consensus. We contribute to entrepreneurship curriculum research by adding a normative perspective.
‘Modern talking’
(2024)
Despite growing interest, we lack a clear understanding of how the arguably ambiguous phenomenon of agile is perceived in government practice. This study aims to alleviate this puzzle by investigating how managers and employees in German public sector organisations make sense of agile as a spreading management fashion in the form of narratives. This is important because narratives function as innovation carriers that ultimately influence the manifestations of the concept in organisations. Based on a multi-case study of 31 interviews and 24 responses to a qualitative online survey conducted in 2021 and 2022, we provide insights into what public sector managers, employees and consultants understand (and, more importantly, do not understand) as agile and how they weave it into their existing reality of bureaucratic organisations. We uncover three meta-narratives of agile government, which we label ‘renew’, ‘complement’ and ‘integrate’. In particular, the meta-narratives differ in their positioning of how agile interacts with the characteristics of bureaucratic organisations. Importantly, we also show that agile as a management fad serves as a projection surface for what actors want from a modern and digital organisation. Thus, the vocabulary of agile government within the narratives is inherently linked to other diffusing phenomena such as new work or digitalisation.
During the last decades, therapeutical proteins have risen to great significance in the pharmaceutical industry. As non-human proteins that are introduced into the human body cause a distinct immune system reaction that triggers their rapid clearance, most newly approved protein pharmaceuticals are shielded by modification with synthetic polymers to significantly improve their blood circulation time. All such clinically approved protein-polymer conjugates contain polyethylene glycol (PEG) and its conjugation is denoted as PEGylation. However, many patients develop anti-PEG antibodies which cause a rapid clearance of PEGylated molecules upon repeated administration. Therefore, the search for alternative polymers that can replace PEG in therapeutic applications has become important. In addition, although the blood circulation time is significantly prolonged, the therapeutic activity of some conjugates is decreased compared to the unmodified protein. The reason is that these conjugates are formed by the traditional conjugation method that addresses the protein's lysine side chains. As proteins have many solvent exposed lysines, this results in a somewhat uncontrolled attachment of polymer chains, leading to a mixture of regioisomers, with some of them eventually affecting the therapeutic performance.
This thesis investigates a novel method for ligating macromolecules in a site-specific manner, using enzymatic catalysis. Sortase A is used as the enzyme: It is a well-studied transpeptidase which is able to catalyze the intermolecular ligation of two peptides. This process is commonly referred to as sortase-mediated ligation (SML). SML constitutes an equilibrium reaction, which limits product yield. Two previously reported methods to overcome this major limitation were tested with polymers without using an excessive amount of one reactant.
Specific C- or N-terminal peptide sequences (recognition sequence and nucleophile) as part of the protein are required for SML. The complementary peptide was located at the polymer chain end. Grafting-to was used to avoid damaging the protein during polymerization. To be able to investigate all possible combinations (protein-recognition sequence and nucleophile-protein as well as polymer-recognition sequence and nucleophile-polymer) all necessary building blocks were synthesized. Polymerization via reversible deactivation radical polymerization (RDRP) was used to achieve a narrow molecular weight distribution of the polymers, which is required for therapeutic use.
The synthesis of the polymeric building blocks was started by synthesizing the peptide via automated solid-phase peptide synthesis (SPPS) to avoid post-polymerization attachment and to enable easy adaptation of changes in the peptide sequence. To account for the different functionalities (free N- or C-terminus) required for SML, different linker molecules between resin and peptide were used.
To facilitate purification, the chain transfer agent (CTA) for reversible addition-fragmentation chain-transfer (RAFT) polymerization was coupled to the resin-immobilized recognition sequence peptide. The acrylamide and acrylate-based monomers used in this thesis were chosen for their potential to replace PEG.
Following that, surface-initiated (SI) ATRP and RAFT polymerization were attempted, but failed. As a result, the newly developed method of xanthate-supported photo-iniferter (XPI) RAFT polymerization in solution was used successfully to obtain a library of various peptide-polymer conjugates with different chain lengths and narrow molar mass distributions.
After peptide side chain deprotection, these constructs were used first to ligate two polymers via SML, which was successful but revealed a limit in polymer chain length (max. 100 repeat units). When utilizing equimolar amounts of reactants, the use of Ni2+ ions in combination with a histidine after the recognition sequence to remove the cleaved peptide from the equilibrium maximized product formation with conversions of up to 70 %.
Finally, a model protein and a nanobody with promising properties for therapeutical use were biotechnologically modified to contain the peptide sequences required for SML. Using the model protein for C- or N-terminal SML with various polymers did not result in protein-polymer conjugates. The reason is most likely the lack of accessibility of the protein termini to the enzyme. Using the nanobody for C-terminal SML, on the other hand, was successful. However, a similar polymer chain length limit was observed as in polymer-polymer SML. Furthermore, in case of the synthesis of protein-polymer conjugates, it was more effective to shift the SML equilibrium by using an excess of polymer than by employing the Ni2+ ion strategy.
Overall, the experimental data from this work provides a good foundation for future research in this promising field; however, more research is required to fully understand the potential and limitations of using SML for protein-polymer synthesis. In future, the method explored in this dissertation could prove to be a very versatile pathway to obtain therapeutic protein-polymer conjugates that exhibit high activities and long blood circulation times.
Coastal areas are highly diverse, ecologically rich, regions of key socio-economic activity, and are particularly sensitive to sea-level change. Over most of the 20th century, global mean sea level has risen mainly due to warming and subsequent expansion of the upper ocean layers as well as the melting of glaciers and ice caps. Over the last three decades, increased mass loss of the Greenland and Antarctic ice sheets has also started to contribute significantly to contemporary sea-level rise. The future mass loss of the two ice sheets, which combined represent a sea-level rise potential of similar to 65 m, constitutes the main source of uncertainty in long-term (centennial to millennial) sea-level rise projections. Improved knowledge of the magnitude and rate of future sea-level change is therefore of utmost importance. Moreover, sea level does not change uniformly across the globe and can differ greatly at both regional and local scales. The most appropriate and feasible sea level mitigation and adaptation measures in coastal regions strongly depend on local land use and associated risk aversion. Here, we advocate that addressing the problem of future sea-level rise and its impacts requires (i) bringing together a transdisciplinary scientific community, from climate and cryospheric scientists to coastal impact specialists, and (ii) interacting closely and iteratively with users and local stakeholders to co-design and co-build coastal climate services, including addressing the high-end risks.
An accurate estimation of crop yield under climate change scenarios is essential to quantify our ability to feed a growing population and develop agronomic adaptations to meet future food demand. A coordinated evaluation of yield simulations from process-based eco-physiological models for climate change impact assessment is still missing for soybean, the most widely grown grain legume and the main source of protein in our food chain. In this first soybean multi-model study, we used ten prominent models capable of simulating soybean yield under varying temperature and atmospheric CO2 concentration [CO2] to quantify the uncertainty in soybean yield simulations in response to these factors. Models were first parametrized with high quality measured data from five contrasting environments. We found considerable variability among models in simulated yield responses to increasing temperature and [CO2]. For example, under a + 3 degrees C temperature rise in our coolest location in Argentina, some models simulated that yield would reduce as much as 24%, while others simulated yield increases up to 29%. In our warmest location in Brazil, the models simulated a yield reduction ranging from a 38% decrease under + 3 degrees C temperature rise to no effect on yield. Similarly, when increasing [CO2] from 360 to 540 ppm, the models simulated a yield increase that ranged from 6% to 31%. Model calibration did not reduce variability across models but had an unexpected effect on modifying yield responses to temperature for some of the models. The high uncertainty in model responses indicates the limited applicability of individual models for climate change food projections. However, the ensemble mean of simulations across models was an effective tool to reduce the high uncertainty in soybean yield simulations associated with individual models and their parametrization. Ensemble mean yield responses to temperature and [CO2] were similar to those reported from the literature. Our study is the first demonstration of the benefits achieved from using an ensemble of grain legume models for climate change food projections, and highlights that further soybean model development with experiments under elevated [CO2] and temperature is needed to reduce the uncertainty from the individual models.
Although cosmic-ray neutron sensing (CRNS) is probably the most promising noninvasive proximal soil moisture measurement technique at the field scale, its application for hydrological simulations remains underexplored in the literature so far. This study assessed the use of CRNS to inversely calibrate soil hydraulic parameters at the intermediate field scale to simulate the groundwater recharge rates at a daily timescale. The study was conducted for two contrasting hydrological years at the Guaraira experimental basin, Brazil, a 5.84-km(2), a tropical wet and rather flat landscape covered by secondary Atlantic forest. As a consequence of the low altitude and proximity to the equator low neutron count rates could be expected, reducing the precision of CRNS while constituting unexplored and challenging conditions for CRNS applications. Inverse calibration for groundwater recharge rates was used based on CRNS or point-scale soil moisture data. The CRNS-derived retention curve and saturated hydraulic conductivity were consistent with the literature and locally performed slug tests. Simulated groundwater recharge rates ranged from 60 to 470 mm yr(-1), corresponding to 5 and 29% of rainfall, and correlated well with estimates based on water table fluctuations. In contrast, the estimated results based on inversive point-scale datasets were not in alignment with measured water table fluctuations. The better performance of CRNS-based estimations of field-scale hydrological variables, especially groundwater recharge, demonstrated its clear advantages over traditional invasive point-scale techniques. Finally, the study proved the ability of CRNS as practicable in low altitude, tropical wet areas, thus encouraging its adoption for water resources monitoring and management.
This article analyses incremental institutional change and subsequent organizational and performance outcomes of the digital transformation from a comparative perspective. Through 31 expert interviews, the authors compare two digitalized public services in Germany. Two digitalization approaches are identified. The voluntary, decentralized bottom-up approach involves layering of new rules, limited organizational restructuring, and performance deficits. Conversely, the compulsory, top-down approach with centralized control facilitates displacement of existing rules and far-reaching organizational change; in this study, it is also associated with improved performance.
Mathematical modelling and statistical inference provide a framework to evaluate different non-pharmaceutical and pharmaceutical interventions for the control of epidemics that has been widely used during the COVID-19 pandemic. In this paper, lessons learned from this and previous epidemics are used to highlight the challenges for future pandemic control. We consider the availability and use of data, as well as the need for correct parameterisation and calibration for different model frameworks. We discuss challenges that arise in describing and distinguishing between different interventions, within different modelling structures, and allowing both within and between host dynamics. We also highlight challenges in modelling the health economic and political aspects of interventions. Given the diversity of these challenges, a broad variety of interdisciplinary expertise is needed to address them, combining mathematical knowledge with biological and social insights, and including health economics and communication skills. Addressing these challenges for the future requires strong cross disciplinary collaboration together with close communication between scientists and policy makers.
Geodetic studies of crustal deformation using Global Navigation Satellite System (GNSS, earlier commonly referred to as Global Positioning System, GPS) measurements at CSIR-NGRI started in 1995 with the installation of a permanent GNSS station at CSIR-NGRI Hyderabad which later became an International GNSS Service (IGS) site. The CSIR-NGRI started expanding its GNSS networks after 2003 with more focussed studies through installation in the NE India, Himalayan arc, Andaman subduction zone, stable and failed rift regions of India plate. In each instance, these measurements helped in unravelling the geodynamics of the region and seismic hazard assessment, e.g., the discovery of a plate boundary fault in the Indo-Burmese wedge, rate and mode of strain accumulation and its spatial variation in the Garhwal-Kumaun and Kashmir region of the Himalayan arc, the influence of non-tectonic deformation on tectonic deformation in the Himalayan arc, nature of crustal deformation through earthquake cycle in the Andaman Sumatra subduction zone, and localised deformation in the intraplate region and across the paleo rift regions. Besides these, GNSS measurements initiated in the Antarctica region have helped in understanding the plate motion and influence of seasonal variations on deformation. Another important by-product of the GNSS observations is the capabilities of these observations in understanding the ionospheric variations due to earthquake processes and also due to solar eclipse. We summarize these outcomes in this article.