Laser synthesis for strong field physics

The work of this thesis involves temporal and spatial synthesis of the laser beam for use in strong field applications, such as high harmonic generation. The results include simulations of the electron trajectories with a temporally synthesised electric field, particularly the sub cycle laser field. The synthesis is produced by mixing of single colour fields and varying the phase between the two pulses. This showed an extension of the high harmonic cutoff from the typical 3.17UP to 5.05UP, and is due to the longer time the electron spends in the continuum due to the subcycle temporal synthesis. A temporal synthesis of the pulse envelope was carried out using a birefringent plate and cube polariser. A pair of birefringent wedges at 45 degrees relative to the laser polarisation was used to vary the phase between the two generated pulses. The spectrum of the laser is shown to shift depending on the relative phase between the two pulses. Subsequent simulations of this effect is presented and compared to the experimental results of which there is agreement in the periodicity of the spectral shift and magnitude. High harmonic generation was also measured and studied to show the harmonic frequency shifting proportionally to the laser depending on the harmonic order. Spatial synthesis of the laser field was studied and also used for generation of high harmonics. A pair of concentric phase plates was used to generate a spatial flat top intensity profile in the focus of the laser beam. The flat top was found to extend plus/minus 1mm either side of the focus of 100 um. The beam waist at the focus increased from 45 um to 100 um during this synthesis, causing a drop in intensity such that harmonics were very hard to achieve.Open Acces

The Relevance of Organization Theory to the Field of Business and Information Systems Engineering

Information and communication systems (ICS) impact their organizational environment in significant ways; hence, the design, implementation, and use of ICS are inseparably linked to fundamental issues of organizational design and behavior. Current research in the field of business and information systems engineering (BISE), however, is primarily technology- or practice-oriented and concerned with the construction and validation of prototypes, whereas little attention is paid to theoretical insights into organizational phenomena and relationships. In this paper, we argue that paying more attention to organization theory would provide valuable guidance in addressing the close links between ICS on the one hand, and organizational systems on the other. To support our argument, we refer to selected theoretical perspectives and highlight their potential relevance to the BISE field

Alternative splicing affects the function and tissue-specific expression of the human constitutive androstane receptor

BACKGROUND: The constitutive androstane receptor (CAR) plays a key role in the control of drug metabolism and transport by mediating the phenobarbital-type induction of many phase I and II drug metabolizing enzymes and drug transporters. RESULTS: We identified transcripts generated by four different alternative splicing events in the human CAR gene. Two of the corresponding ligand binding domain isoforms demonstrated novel functional properties: First, CAR(SV3), which is encoded by a transcript containing an lengthened exon 7, differentially transactivated target gene promoters. Second, CAR(SV2), which results from the use of an alternative 3' splice site lengthening exon 8, showed ligand-dependent instead of constitutive interaction with coactivators. Furthermore, alternatively spliced transcripts demonstrated a tissue-specific expression pattern. In most tissues, only transcripts generated by alternative splicing within exon 9 were expressed. The encoded variant demonstrated a loss-of-function phenotype. Correct splicing of exon 8 to exon 9 is restricted to only a few tissues, among them liver and small intestine for which CAR function has been demonstrated, and is associated with the induction of CAR expression during differentiation of intestinal cells. CONCLUSION: Due to their specific activities, CAR variant proteins SV2 and SV3 may modulate the activity of reference CAR(SV1). Furthermore, we propose that transcriptional activation and regulation of splicing of exon 9 may be coupled to ensure appropriate tissue- and differentiation state-specific expression of transcripts encoding functional CAR protein. Altogether, alternative splicing seems to be of utmost importance for the regulation of CAR expression and function

Directed Evolution of a Cytochrome P450 Carbene Transferase for Selective Functionalization of Cyclic Compounds

Transfers of carbene moieties to heterocycles or cyclic alkenes to obtain C(sp^2)–H alkylation or cyclopropane products are valuable transformations for synthesis of pharmacophores and chemical building blocks. Through their readily tunable active-site geometries, hemoprotein “carbene transferases” could provide an alternative to traditional transition metal catalysts by enabling heterocycle functionalizations with high chemo-, regio-, and stereocontrol. However, carbene transferases accepting heterocyclic substrates are scarce; the few enzymes capable of heterocycle or cyclic internal alkene functionalization described to date are characterized by low turnovers or depend on artificially introduced, costly iridium–porphyrin cofactors. We addressed this challenge by evolving a cytochrome P450 for highly efficient carbene transfer to indoles, pyrroles, and cyclic alkenes. We first developed a spectrophotometric high-throughput screening assay based on 1-methylindole C3-alkylation that enabled rapid analysis of thousands of P450 variants and comprehensive directed evolution via random and targeted mutagenesis. This effort yielded a P450 variant with 11 amino acid substitutions and a large deletion of the non-catalytic P450 reductase domain, which chemoselectively C_3-alkylates indoles with up to 470 turnovers per minute and 18 000 total turnovers. We subsequently used this optimized alkylation variant for parallel evolution toward more challenging heterocycle carbene functionalizations, including C_2/C_3 regioselective pyrrole alkylation, enantioselective indole alkylation with ethyl 2-diazopropanoate, and cyclic internal alkene cyclopropanation. The resulting set of efficient biocatalysts showcases the tunability of hemoproteins for highly selective functionalization of cyclic targets and the power of directed evolution to enhance the scope of new-to-nature enzyme catalysts

Exploiting and engineering hemoproteins for abiological carbene and nitrene transfer reactions

The surge in reports of heme-dependent proteins as catalysts for abiotic, synthetically valuable carbene and nitrene transfer reactions dramatically illustrates the evolvability of the protein world and our nascent ability to exploit that for new enzyme chemistry. We highlight the latest additions to the hemoprotein-catalyzed reaction repertoire (including carbene Si–H and C–H insertions, Doyle–Kirmse reactions, aldehyde olefinations, azide-to-aldehyde conversions, and intermolecular nitrene C–H insertion) and show how different hemoprotein scaffolds offer varied reactivity and selectivity. Preparative-scale syntheses of pharmaceutically relevant compounds accomplished with these new catalysts are beginning to demonstrate their biotechnological relevance. Insights into the determinants of enzyme lifetime and product yield are providing generalizable cues for engineering heme-dependent proteins to further broaden the scope and utility of these non-natural activities

Family witnessed resuscitation - experience and attitudes of German intensive care nurses.

To explore German intensive care nurses' experiences and attitudes toward family witnessed resuscitation (FWR). The subject of FWR has fuelled much controversy among health professionals. Typically studies involving European critical and cardiac nurses' under-represent the perspective of individual countries. Arguably research exploring the experiences and attitudes of nurses by country may expand understanding and embrace cultural values. Descriptive survey. Three hundred and ninety-four German intensive care nurses attending a conference were invited to complete a 36-item questionnaire on their experiences and attitudes towards FWR. Participants were also invited to share, in writing, other thoughts relevant to the study. Data was analysed using descriptive statistics. A total of 166 (42.1%) questionnaires were returned completed. Seventy participants had experiences with family members being present and for 46 (65.7%) these were negative. Participants (68%) did not agree that family members should have the option to be with loved ones during resuscitation. Over half (56.0%) were concerned that family presence may adversely influence staff performance during resuscitation procedures. There was a lack of certainty about the outcomes of the practice, although 61% agreed that family presence could facilitate better understanding among relatives. Qualitative responses where characterized by four broad themes relating to individualized decision-making, supporting families, threats of violence and family involvement. German intensive care nurses have guarded attitudes towards FWR because of their experiences and concerns for the well-being of relatives and staff. Introducing this topic within nursing curricula, as part of resuscitation training and by wider professional debate will help challenge and resolve practitioner concerns and objections. Health professionals have anxieties about possible consequences of FWR, strategies involving education and simulation training may improve attitudes

Noise in an intensive care unit

Patients and staff in hospitals are exposed to a complex sound environment with rather high noise levels. In intensive care units, the main noise sources are hospital staff on duty and medical equipment, which generates both operating noise and acoustic alarms. Although noise in most cases is produced during activities for the purpose of saving life, noise can induce significant changes in the depth and quality of sleep and negatively affect health in general. Results of a survey of hospital staff are presented as well as measurements in two German hospital wards: a standard two-bed room and a special Intermediate Care Unit (IMC-Unit), each in a different Intensive Care Unit (ICU). Sound pressure data were collected over a 48 hour period and converted into different levels (LAFeq, LAFmax, LAFmin, LAF 5%), as well as a rating level LAr, which is used to take tonality and impulsiveness into account. An analysis of the survey and the measured data, together with a comparison of thresholds of national and international regulations and standards describe the acoustic situation and its likely noise effects on staff and patients

Assessment of low-frequency aeroacoustic emissions of a wind turbine under rapidly changing wind conditions based on an aero-servo-elastic CFD simulation

A meteorologically challenging situation that represents a demanding control task (rotational speed, pitch and yaw) for a wind turbine is presented and its implementation in a simulation is described. A high-fidelity numerical process chain, consisting of the computational fluid dynamics (CFD) solver FLOWer, the multi-body system (MBS) software SIMPACK and the Ffowcs Williams-Hawkings code ACCO, is used. With it, the aerodynamic, servoelastic and aeroacoustic (<20 Hz) behaviour of a generic wind turbine during a meteorological event with strong and rapid changes in wind speed and direction is investigated. A precursor simulation with the meteorological model system PALM is deployed to generate realistic inflow data. The simulated strong controller response of the wind turbine and the resulting aeroelastic behaviour are analysed. Finally, the low-frequency sound emissions are evaluated and the influence of the different operating and flow parameters during the variable inflow is assessed. It is observed that the wind speed and, linked to it, the rotational speed as well as the turbulence intensity are the main influencing factors for the emitted low-frequency sound power of the wind turbine. Yawed inflow, on the other hand, has little effect unless it changes the operational mode to load reduction, resulting in a swap of the main emitter from the blades to the tower