Kant and the general freedom of action

The legal philosophy of Immanuel Kant is complex and often confusing. Nevertheless Kant developed one of the most important liberal theories in the history of legal philosophy. The basic idea is simple: The necessity to protect the general freedom of action is the starting point of his Doctrine of Law. The only condition for this protection is that this freedom has to be compatible with the freedom of everybody else. Accordingly, for Kant even allegedly trivial actions belong to the realm of the judicial protection of the universal law of right. The question, which is to be answered in this essay, is: Why? - For what reason, Kant thinks, that there is the necessity to protect the general freedom of action

Boundary element solutions for broad-band 3-D geo-electromagnetic problems accelerated by an adaptive multilevel fast multipole method

We have developed a generalized and stable surface integral formula for 3-D uniform inducing field and plane wave electromagnetic induction problems, which works reliably over a wide frequency range. Vector surface electric currents and magnetic currents, scalar surface electric charges and magnetic charges are treated as the variables. This surface integral formula is successfully applied to compute the electromagnetic responses of 3-D topography to low frequency magnetotelluric and high frequency radio-magnetotelluric fields. The standard boundary element method which is used to solve this surface integral formula quickly exceeds the memory capacity of modern computers for problems involving hundreds of thousands of unknowns. To make the surface integral formulation applicable and capable of dealing with large-scale 3-D geo-electromagnetic problems, we have developed a matrix-free adaptive multilevel fast multipole boundary element solver. By means of the fast multipole approach, the time-complexity of solving the final system of linear equations is reduced to O(m log m) and the memory cost is reduced to O(m), where m is the number of unknowns. The analytical solutions for a half-space model were used to verify our numerical solutions over the frequency range 0.001-300kHz. In addition, our numerical solution shows excellent agreement with a published numerical solution for an edge-based finite-element method on a trapezoidal hill model at a frequency of 2Hz. Then, a high frequency simulation for a similar trapezoidal hill model was used to study the effects of displacement currents in the radio-magnetotelluric frequency range. Finally, the newly developed algorithm was applied to study the effect of moderate topography and to evaluate the applicability of a 2-D RMT inversion code that assumes a flat air-Earth interface, on RMT field data collected at Smørgrav, southern Norway. This paper constitutes the first part of a hybrid boundary element-finite element approach to compute the electromagnetic field inside structures involving complex 3-D conductivity and permittivity distribution

A text-based measure for digital innovation - uncovering digital innovation and its impact on firm performance

Research has successfully conceptualized digital innovation (DI) to cope with its abstract and complex nature. However, scholars are lacking an adequate measure to support empirical understanding. We establish a new text-based measure for DI by applying an unsupervised machine learning algorithm to 10-K reports of S&P 500 firms. For the first time, our measure captures both DI creation activities and DI outcomes. It correlates strongly with patent-based DI activities of firms that have digital patents and also robustly captures DI activities of firms that do not have digital patents. 326 out of 721 firms in our sample have zero digital patents between 1997 and 2019. We use our novel measure to provide evidence of the positive relationship between DI and firm performance across industries. Our study makes an important methodological contribution to DI literature by establishing a novel measure that captures all facets of DI in mature firms

Synaptic MAGUK multimer formation is mediated by PDZ domains and promoted by ligand binding

To examine the scaffolding properties of PSD-95, we have taken advantage of established ligand/PDZ domain interactions and developed a cell-based assay for investigating protein complex formation. This assay enables quantitative analysis of PDZ domain-mediated protein clustering using bimolecular fluorescence complementation (BiFC). Two nonfluorescent halves of EYFP were fused to C-terminal PDZ ligand sequences to generate probes that sense for PDZ domain binding grooves of adjacent (interacting) molecules. When these probes are brought into proximity by the PDZ domains of a multiprotein scaffold, a functional fluorescent EYFP molecule can be detected. We have used this system to examine the properties of selected PSD-95 variants and thereby delineated regions of importance for PSD-95 complex formation. Further analysis led to the finding that PSD-95 multimerization is PDZ domain-mediated and promoted by ligand binding

CLCN4-Related Neurodevelopmental Disorder

Clinical characteristics CLCN4-related neurodevelopmental disorder (CLCN4-NDD), an X-linked disorder, is characterized in the 36 males reported to date by developmental delay or intellectual disability, behavioral/mental health issues (e.g., autism spectrum disorder, anxiety, hyperactivity, and bipolar disorder), epilepsy, and gastrointestinal dysfunction. The five heterozygous females with a de novo CLCN4 variant reported to date had findings very similar to those of affected males. Twenty-two of 25 heterozygous females identified in family studies following identification of an affected male were unaffected or had only mild specific learning difficulties and/or mental health concerns, whereas three were more severely affected. Diagnosis/testing The diagnosis of CLCN4-NDD is established in a male proband with suggestive findings and a hemizygous pathogenic variant in CLCN4 identified by molecular genetic testing. The diagnosis of CLCN4-NDD is usually established in a female proband with suggestive findings and a heterozygous pathogenic variant in CLCN4 identified by molecular genetic testing; however, the phenotype in females with a pathogenic variant can range from asymptomatic to severe. Management Treatment of manifestations: Treatment is supportive and often includes multidisciplinary specialists in neurology, pediatrics, mental health, physiatry, occupational and physical therapy, gastroenterology, feeding therapy, ophthalmology, audiology, and medical genetics. Surveillance: Routine monitoring of neurologic findings (response to anti-seizure medications; emergence of new findings), development and educational progress, psychiatric/behavioral issues (response to medications; emergence of new findings), mobility and self-help skills, growth and gastrointestinal manifestations, ophthalmologic findings, hearing, and family support systems. Genetic counseling CLCN4-NDD is inherited in an X-linked manner. The father of an affected male will not have the disorder nor will he be hemizygous for the CLCN4 pathogenic variant. If the mother of a proband has a CLCN4 pathogenic variant, the chance of transmitting it in each pregnancy is 50%: males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be heterozygotes and may be unaffected or have clinical findings ranging from mild learning difficulties and mental health concerns to severe manifestations. If the proband represents a simplex case and if the CLCN4 pathogenic variant cannot be detected in the leukocyte DNA of the mother, the risk to sibs is presumed to be low but greater than that of the general population. Once the CLCN4 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible

Transdifferente Positionalitäten als Manifestationen biografischer Grenzerfahrungen

'Im Rahmen des Beitrages wird das Konzept der transdifferenten Positionalität vorgestellt und in den Diskussionszusammenhang 'Identitäten im Zwischenraum' gestellt. Transdifferente Positionalitäten nehmen biographische Grenzgänger ein, welche die Erfahrung kultureller Mehrfachzugehörigkeit machen. Sie sind eine ambivalente Erfahrung, insofern sie einerseits erlitten werden, andererseits aber neue Möglichkeiten eröffnen. Im Unterschied zu Breinig und Lösch wird das Konzept der transdifferenten Positionalität jedoch nicht auf kulturelle Grenzgänger beschränkt, sondern lässt sich auch auf Transsexuelle, transplantierte Menschen, Menschen mit Nahtoderfahrungen sowie allgemein Erfahrungen an der Grenze von Vernunft und Unvernunft anwenden, wie literarische Beispiele belegen. Als größte Errungenschaft des Konzeptes wird dabei angesehen, dass es eine präzisere Fassung von Identitäten im Zwischenraum erlaubt.' (Autorenreferat)'In this article the author presents the concept of transdifferent positioning and integrate it in the discussion of 'in-between-identities'. Especially biographical border crossers with experiences of multiple cultural belongings develop a transdifferent positioning. Transdifferent experiences are ambivalent in nature, because on the one hand they make people suffer, but on the other hand they open up new possibilities of living. In contrast to the founders of the term transdifference, Breinig and Lösch, the author does not limit the concept to experiences of multiple cultural belonging, but extend it to experiences of transsexuality, transplantation, near-death experiences and experiences at the edge of rationality. All these experiences are illustrated by literary examples. As a result, it can be stated that the concept of transdifference contributes to an improved understanding of 'in-between-identities'.' (author's abstract)

A Teoria Kantiana da Ponderação

  Este artigo procura mostrar que a discussão de Kant sobre os deveres morais imperfeitos contém um esboço de uma teoria da ponderação de normas conflitantes. Particularmente interessante são as semelhanças com a mais importante teoria da ponderação do século XX, a teoria jurídica da ponderação de Robert Alexy. Ambas as teorias se baseiam na distinção teórico-normativa entre regras e princípios, ou seja, a distinção entre deveres perfeitos e imperfeitos. Colisões entre princípios, ou seja, colisões entre deveres imperfeitos, ocorrem na dimensão do peso. Tanto Alexy quanto Kant desenvolvem uma lei de ponderação segundo a qual é possível determinar, através da ponderação, em casos específicos, uma relação de precedência entre as normas conflitantes

Vergleichende und funktionelle Studien zur Evolution der dorsoventralen Musterbildung bei Insekten

Im Gegensatz zur Etablierung der dorsoventralen Achse des Drosophila Embryos, ist die Spezifizierung dieser Körperachse in Kurzkeiminsekten bislang größtenteils unverstanden. Da die meisten Segmente von einer posterioren Wachstumszone in einer zellulären Umgebung hervorgebracht werden, stellt sich die Frage, ob maternale Faktoren Einfluss auf die dorsoventrale Musterbildung solcher Segmente haben können. Der Nf-kB ähnliche Faktor Tribolium Dorsal erfüllt, wie Drosophila Dorsal, essentielle Funktionen in der generellen Polarisierung der dorsoventralen Achse des Tribolium Embryos. Während wichtige Zielgene wie twist und sog zwischen Drosophila und Tribolium Dorsal offensichtlich konserviert sind, scheint die Regulierung anderer möglicher Zielgene durch TcDorsal indirekt zu verlaufen. Die Funktion von TcDorsal wird ebenfalls zur Spezifizierung des dorsoventralen Musters der posterioren Segmente benötigt, die erst nach Beendigung der Expression von Dorsal erzeugt werden. Tribolium und Anopheles zeigen Anzeichen für eine Initiierung der Erzeugung der embryonalen Achsen bereits während der Oogenese. Dies ist umso erstaunlicher, als der Aufbau der Ovarien in Coleopteren von dem der Ovarien in Dipteren abweicht. In dieser Arbeit konnte gezeigt werden, dass die asymmetrische Positionierung des Oozytenkerns und eine nachfolgende, asymmetrische Expression von Homologen des Drosophila Gens pipe im Follikelepithel konservierte Merkmale darstellen, die entscheidende maternale Beiträge zur Festlegung der ventralen Seite des zukünftigen Embryos liefern können. Das isolierte Tccactus Gen besitzt ein Expressionsmuster, das eine Rolle in der Verfeinerung des Dorsal Gradienten oder in der Übertragung der maternalen polarisierenden Information an zygotische Gene nahe legt. Obwohl maternale RNA im frühen Tribolium Embryo nicht nachweisbar ist, könnte die beobachtete maternale Expression der Tccactus mRNA in Ovarien eine Quelle zur Erzeugung von maternalem Cactus Protein sein, dass im frühen Embryo eine Rolle als genereller cytoplasmatischer Inhibitor für TcDorsal erfüllen könnte. Somit erscheinen entscheidende Prozesse der Achsenbildung zwischen Kurz- und Langkeiminsekten konserviert. Die beobachteten Unterschiede zwischen beiden Insektengruppen in Bezug zur Bedeutung des maternalen Toll/Dorsal Signalweges im Vergleich zu zygotischen Genen für die Achenfestlegung könnten hierbei in speziellen Anpassungen an den jeweiligen Modus der Embryogenese begründet sein

Two-dimensional probabilistic inversion of plane-wave electromagnetic data: methodology, model constraints and joint inversion with electrical resistivity data

Probabilistic inversion methods based on Markov chain Monte Carlo (MCMC) simulation are well suited to quantify parameter and model uncertainty of nonlinear inverse problems. Yet, application of such methods to CPU-intensive forward models can be a daunting task, particularly if the parameter space is high dimensional. Here, we present a 2-D pixel-based MCMC inversion of plane-wave electromagnetic (EM) data. Using synthetic data, we investigate how model parameter uncertainty depends on model structure constraints using different norms of the likelihood function and the model constraints, and study the added benefits of joint inversion of EM and electrical resistivity tomography (ERT) data. Our results demonstrate that model structure constraints are necessary to stabilize the MCMC inversion results of a highly discretized model. These constraints decrease model parameter uncertainty and facilitate model interpretation. A drawback is that these constraints may lead to posterior distributions that do not fully include the true underlying model, because some of its features exhibit a low sensitivity to the EM data, and hence are difficult to resolve. This problem can be partly mitigated if the plane-wave EM data is augmented with ERT observations. The hierarchical Bayesian inverse formulation introduced and used herein is able to successfully recover the probabilistic properties of the measurement data errors and a model regularization weight. Application of the proposed inversion methodology to field data from an aquifer demonstrates that the posterior mean model realization is very similar to that derived from a deterministic inversion with similar model constraint