153 research outputs found
Tutorial: From Topology to Hall Effects—Implications of Berry Phase Physics
No full textThe Berry phase is a fundamental concept in quantum mechanics with profound implications for understanding topological properties of quantum systems. This tutorial provides a comprehensive introduction to the Berry phase, beginning with the essential mathematical framework required to grasp its significance. We explore the intrinsic link between the emergence of a non-trivial Berry phase and the presence of topological characteristics in quantum systems, showing the connection between the Berry phase and the band structure as well as the phase's gauge-invariant nature during cyclic evolutions. The tutorial delves into various topological effects arising from the Berry phase, such as the quantum, anomalous, and spin Hall effects, which exemplify how these quantum phases manifest in observable phenomena. We then extend our discussion to cover the transport properties of topological insulators, elucidating their unique behaviour rooted in the Berry phase physics. This tutorial aims at equipping its readers with a robust understanding of the basic theory underlying the Berry phase and of its pivotal role in the realm of topological quantum phenomena
The death of drawing : architecture in the age of simulation /
No full text"The Death of Drawing explains how the shift from drawing by to hand to using building information models (BIM) is happening and the effect of this on how architects think and work. Author David Scheer helps you recognize that architectural drawings exist to represent construction and architectural simulations (BIM) exist to anticipate building performance. The values implicit in drawing - patience, care, attention to detail, knowledge of composition, appreciation of well-made things - which architects used to gain through years of drawing practice, don't apply to simulation, so Scheer discusses how losing this vital learning tool might affect your work and and the field of architecture. He also explains that simulation requires you to cast building information in the form of data, which means less of a distinction between designers and constructors, and, based on this, how your interactions with and relevance to clients and collaborators might impact your practice. Finally he reflects on this moment of profound transformation, to remember what drawing has meant to architecture so that you can anticipate what may follow"--Includes bibliographical references (pages 229-234) and index."The Death of Drawing explains how the shift from drawing by to hand to using building information models (BIM) is happening and the effect of this on how architects think and work. Author David Scheer helps you recognize that architectural drawings exist to represent construction and architectural simulations (BIM) exist to anticipate building performance. The values implicit in drawing - patience, care, attention to detail, knowledge of composition, appreciation of well-made things - which architects used to gain through years of drawing practice, don't apply to simulation, so Scheer discusses how losing this vital learning tool might affect your work and and the field of architecture. He also explains that simulation requires you to cast building information in the form of data, which means less of a distinction between designers and constructors, and, based on this, how your interactions with and relevance to clients and collaborators might impact your practice. Finally he reflects on this moment of profound transformation, to remember what drawing has meant to architecture so that you can anticipate what may follow"--Simulation and Representation -- Drawing and Architecture -- Building Information Modeling -- Performativity and Design -- Information Flow and Collaboration -- Computational Design -- Simulation and Design Thinking -- Architectures of Simulation
Helden am Himmel – Helden im Himmel. Sphärenwechsel zu den Sternen im griechischen Mythos.
No full textThe Catasterisms of Pseudo-Eratosthenes and the Astronomia, written by an author named Hyginus are the most important extant sources concerning ancient Greek star-myths. Analysing these texts this paper discusses questions about the reasons and circumstances that lead mythical heroes and heroines to changing the earthly sphere for the heavens in Greek myth. Which conse-quences did these changes inflict on the protagonists concerned? What did it mean to be put among the stars? The texts allowed their audience a wide range of possibilities “to think with”, including divine compassion, gratitude and eternal memory of great deeds as well as presenting warning examples for man-kind on earth. Since when these examples were told, is difficult to assess. The case of the Arkadian heroine Callisto shows how strata of mythical subjects (mythische Stoffe) changed over the centuries. The Homeric Odysseus was told of the ‘Bear’ as an important heavenly constellation, but it seems that it took some centuries before the heroine Callisto reached the sky and this bear finally got a personal name. Authors like Pseudo-Eratosthenes and Hyginus do not express the belief that such a changing of spheres included a happy afterlife or immortal feasting in the presence of the Olympic gods. Nevertheless their read-ers were at liberty to hope for it
A novel panel of mouse models to evaluate the role of human pregnane X receptor and constitutive androstane receptor in drug response
No full textThe pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are closely related orphan nuclear hormone receptors that play a critical role as xenobiotic sensors in mammals. Both receptors regulate the expression of genes involved in the biotransformation of chemicals in a ligand-dependent manner. As the ligand specificity of PXR and CAR have diverged between species, the prediction of in vivo PXR and CAR interactions with a drug are difficult to extrapolate from animals to humans. We report the development of what we believe are novel PXR- and CAR-humanized mice, generated using a knockin strategy, and Pxr- and Car-KO mice as well as a panel of mice including all possible combinations of these genetic alterations. The expression of human CAR and PXR was in the predicted tissues at physiological levels, and splice variants of both human receptors were expressed. The panel of mice will allow the dissection of the crosstalk between PXR and CAR in the response to different drugs. To demonstrate the utility of this panel of mice, we used the mice to show that the in vivo induction of Cyp3a11 and Cyp2b10 by phenobarbital was only mediated by CAR, although this compound is described as a PXR and CAR activator in vitro. This panel of mouse models is a useful tool to evaluate the roles of CAR and PXR in drug bioavailability, toxicity, and efficacy in humans.</p
Continuation of chronic antiplatelet therapy is not associated with increased need for transfusions: a cohort study in critically ill septic patients
No full textFuchs C, Scheer CS, Wauschkuhn S, et al. Continuation of chronic antiplatelet therapy is not associated with increased need for transfusions: a cohort study in critically ill septic patients. BMC Anesthesiology . 2024;24(1): 146.BACKGROUND: The decision to maintain or halt antiplatelet medication in septic patients admitted to intensive care units presents a clinical dilemma. This is due to the necessity to balance the benefits of preventing thromboembolic incidents and leveraging anti-inflammatory properties against the increased risk of bleeding.; METHODS: This study involves a secondary analysis of data from a prospective cohort study focusing on patients diagnosed with severe sepsis or septic shock. We evaluated the outcomes of 203 patients, examining mortality rates and the requirement for transfusion. The cohort was divided into two groups: those whose antiplatelet therapy was sustained (n=114) and those in whom it was discontinued (n=89). To account for potential biases such as indication for antiplatelet therapy, propensity score matching was employed.; RESULTS: Therapy continuation did not significantly alter transfusion requirements (discontinued vs. continued in matched samples: red blood cell concentrates 51.7% vs. 68.3%, p=0.09; platelet concentrates 21.7% vs. 18.3%, p=0.82; fresh frozen plasma concentrates 38.3% vs. 33.3%, p=0.7). 90-day survival was higher within the continued group (30.0% vs. 70.0%; p0.05).; CONCLUSIONS: The findings suggest that continuing antiplatelet therapy in septic patients admitted to intensive care units could be associated with a significant survival benefit without substantially increasing the need for transfusion. These results highlight the importance of a nuanced approach to managing antiplatelet medication in the context of severe sepsis and septic shock. © 2024. The Author(s)
Development and implementation of a genome-wide CRISPR/Cas9 screen for identification of cellular factors affecting recombinant adeno-associated virus (rAAV) production
No full textAdvances in the development of gene therapy pharmaceuticals offer a great opportunity to treat or potentially cure previously untreatable diseases. Recombinant adeno-associated viral vectors (rAAV) are emerging as the most promising gene delivery tools for in vivo gene therapies, as demonstrated by numerous recent approvals of rAAV-based therapeutics. Despite advantages such as low immunogenicity and the ability for long-term episomal expression, the limited scalability of existing rAAV production systems is a persistent challenge. To address this problem, we have developed a screening method to identify cellular genes that either supports or repress rAAV production in a fully stable, plasmid- and helper virus-free rAAV suspension packaging cell line. We created an innovative genome-wide Lenti-AAV-CRISPR plasmid screening library (pLAC library) containing 68,563 unique sgRNAs. After packaging this library into lentiviral particles, we transduced a human stable AAV packaging cell line, adapted for the constitutive expression of Cas9. The rAAVs produced by the transduced packaging cells were then analysed by next generation sequencing. This revealed a large number of over- or underrepresented sgRNAs, indicating that inactivation of the corresponding cellular genes had a positive or negative impact on rAAV production. To validate the screening method initially, genes with a putative positive impact on rAAV production were selected and inactivated in individual rAAV packaging cell lines. Subsequently, an AAV transfer vector was integrated into the cells by lentiviral transduction to generate stable rAAV production cell lines, which allowed the investigation of the potential target genes in a fully stable and inducible production system. In a second project, we have screened the AAV producer cells to identify novel integration sites for targeted and reusable integration of transgene cassettes enabling strong and stable overexpression. Such integration sites could be used, for example, to overexpress cellular genes which could have a potentially beneficial effect on rAAV production. Stable integration of transgenes into host cells is a widely used strategy for cell line development. Typically, this is accomplished through random transgene integration, requiring an elaborate and time-consuming screening process to identify clones with long-term stability and high expression levels. In contrast, utilizing a well-characterized chromosomal locus allows a much faster and reliable generation of such clones. Using CRISPR/Cas9-mediated homologous recombination of a reporter cassette, we identified a genomic region immediately downstream of the highly conserved ACTB locus encoding for actin beta. To assess the relative expression strength compared to other loci, additional clones with single copy integrations were generated in a non-targeted screening approach employing a random expression cassette integration. Analysis of different clones revealed relatively high expression of single copy transgene insertions into the ACTB locus, demonstrating stability over multiple passages. Subsequent single copy insertion of a C1 esterase inhibitor expression cassette into this site resulted in strong expression. In conclusion, the results pave the way for the development of an optimized, fully scalable rAAV production cell line. The targets investigated so far show great potential for the targeted optimization of rAAV productivity. In addition, the over- or under- represented sgRNAs identified in the screening provide further promising targets that still need to be investigated. With the identification of the region downstream of the ACTB locus, we have also created the basis for the targeted integration of transgenes such as genes with a positive influence on rAAV production, to optimize cellular production systems. Moreover, both the screening method and the described locus offer potential applications for other cell lines and viruses, which makes the development interesting beyond the AAV field
Review of \u3ci\u3eGovernor Lady: The Life and Times of Nellie Tayloe Ross\u3c/i\u3e By Teva J. Scheer
No full textNellie Tayloe Ross, governor of Wyoming from January 5, 1925-January 3, 1927, was sworn into office fifteen days before Miriam Ferguson in Texas, a precedence that earned the former a lasting legacy as the nation\u27s first woman governor. The novelty of her status and her elegant charm won Ross the attention of her contemporaries. A series of autobiographical essays titled Governor Lady, published in 1927 by Good Housekeeping, fed the interests of an admiring public. A more recent tribute is Teva Scheer\u27s Governor Lady: The Life of Times of Nellie Tayloe Ross. How should history evaluate the nation\u27s first woman governor? asks the author. For despite Ross\u27s later accomplishments as an organizer for the national Democratic Party and director of the U.S. Mint, it is as Wyoming\u27s governor that she is most remembered. Scheer\u27s evaluation, reflecting extensive research, is an affirmative one that recognizes Ross\u27s historical significance and argues her continuing importance.
Even as Ross extolled the virtues of hearth and home, after her husband\u27s death in 1924 she would seldom devote her own energies there. Ross\u27s story involves copious context, ranging from late nineteenth-century farming conditions to early twentieth-century monetary policy, from the nuances of Wyoming state politics through the years to postsuffrage feminism. Ross is described as a kindergarten teacher in Omaha and wife in Cheyenne, as gubernatorial candidate in the West and Chautauqua speaker in the East, as a political outsider among former suffragists and a Washington, D.C., insider during a succession of administrations. Explaining these shifts involves introducing a swelling cast of characters and conditions as much as portraying the woman herself.
Scheer describes Ross as the Missouri-born child of former slave owners, accounting for her Southern manners and perhaps some racist comments revealed in Ross\u27s later correspondence. She connects Ross with the typical middle-class American woman of her era, in contrast to her college-educated contemporaries who also distinguished themselves as female firsts in the public sector
Die GAL4/UAS-Methode zur gezielten Genexpression: eine kritische Betrachtung ihrer funktionellen Anwendung beim Zebrafisch, Danio rerio
No full textDetermining groundwater velocity with DTS at the Máximakanaal and in the Horstermeerpolder
No full textA suggested approach for determining groundwater flow in unconsolidated aquifers is tested. Performing a heat pulse response test by using a heat- and fibre-optic cable should result in a vertical profile of groundwater velocities. These cables are installed by using direct push ensuring the direct contact between cable and aquifer. The suggested approach is tested with two case studies. The first case study near the Máximakanaal was meant to determine if the canal is leaking. This experiment failed during the installation which was discovered after analyzing the results. The mistakes that were made during this case study have been analyzed and are discussed. The second case study was not performed by the author of this thesis. Nonetheless, the measurements of this case study enabled the completion of retrieving groundwater velocities from distributed temperature sensing and reviewing the approach
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