Optimal Opinion Control: The Campaign Problem

Opinion dynamics is nowadays a very common field of research. In this article we formulate and then study a novel, namely strategic perspective on such dynamics: There are the usual normal agents that update their opinions, for instance according the well-known bounded confidence mechanism. But, additionally, there is at least one strategic agent. That agent uses opinions as freely selectable strategies to get control on the dynamics: The strategic agent of our benchmark problem tries, during a campaign of a certain length, to influence the ongoing dynamics among normal agents with strategically placed opinions (one per period) in such a way, that, by the end of the campaign, as much as possible normals end up with opinions in a certain interval of the opinion space. Structurally, such a problem is an optimal control problem. That type of problem is ubiquitous. Resorting to advanced and partly non-standard methods for computing optimal controls, we solve some instances of the campaign problem. But even for a very small number of normal agents, just one strategic agent, and a ten-period campaign length, the problem turns out to be extremely difficult. Explicitly we discuss moral and political concerns that immediately arise, if someone starts to analyze the possibilities of an optimal opinion control.Comment: 47 pages, 12 figures, and 11 table

Wie streitanfällig ist das österreichische Steuerrecht? Eine empirische Untersuchung der Urteile des österreichischen Verwaltungsgerichtshofs nach Bemessungsgrundlagen-, Zeit- und Tarifeffekten

In diesem Beitrag werden die Urteile des österreichischen Verwaltungsgerichtshofs (VwGH) zu Ertragsteuern nach Bemessungsgrundlagen-, Zeit- und Tarifeffekten untersucht. Mit einem Anteil von fast 80% machen die Bemessungsgrundlageneffekte den überwiegenden Teil steuerlicher Effekte aus. Trotz der Dominanz von Zeiteffekten in der betriebswirtschaftlichen Literatur entfallen auf diese nur 14% der Urteile. Mit 6% der Urteile sind die Tarifeffekte von untergeordneter Bedeutung. Betrachtet man die Streitanfälligkeit als Indiz für die Erhebungskosten einzelner steuerlicher Regelungen, so könnte Steuervereinfachung paradoxerweise durch detailliertere Steuergesetze erzielt werden. Da eine Abgrenzung zwischen Einkommenserzielung und Konsum in jedem Steuersystem nur mit begrenzter Trennschärfe möglich ist, ist eine gänzliche Vermeidung der Streitanfälligkeit nicht möglich. --Österreichisches Steuerrecht,Steuererhebungskosten,Steuervereinfachung,Zeiteffekte,Bemessungsgrundlageneffekte,Tarifeffekte

Glutathione-conjugating and membrane-remodeling activity of GDAP1 relies on amphipathic C-terminal domain

Mutations in the ganglioside-induced differentiation associated protein 1 (GDAP1) cause severe peripheral motor and sensory neuropathies called Charcot-Marie-Tooth disease. GDAP1 expression induces fission of mitochondria and peroxisomes by a currently elusive mechanism, while disease causing mutations in GDAP1 impede the protein’s role in mitochondrial dynamics. In silico analysis reveals sequence similarities of GDAP1 to glutathione S-transferases (GSTs). However, a proof of GST activity and its possible impact on membrane dynamics are lacking to date. Using recombinant protein, we demonstrate for the first time theta-class-like GST activity for GDAP1, and it’s activity being regulated by the C-terminal hydrophobic domain 1 (HD1) of GDAP1 in an autoinhibitory manner. Moreover, we show that the HD1 amphipathic pattern is required to induce membrane dynamics by GDAP1. As both, fission and GST activities of GDAP1, are critically dependent on HD1, we propose that GDAP1 undergoes a molecular switch, turning from a pro-fission active to an auto-inhibited inactive conformation.ISSN:2045-232

Recalling and Updating Research on Diamagnetic Cavities: Experiments, Theory, Simulations

In the decade from the mid 80's to the mid 90's there was considerable interest in the generation of diamagnetic cavities produced by the sub-Alfvenic expansion of heavy ions across a background magnetic field. Examples included the AMPTE and CRRES barium releases in the magnetotail and magnetosphere as well as laser experiments at various laboratories in the United States and the Soviet Union. In all of these experiments field-aligned striations and other small-scale structures were produced as the cavities formed. Local and non-local linear theory as well as full particle (PIC), hybrid, and Hall-MHD simulations (mostly 2-D) were developed and used to understand at least qualitatively the features of these experiments. Much of this review is a summary of this work, with the addition of some new 3-D PIC and Hall-MHD simulations that clarify old issues associated with the origin and evolution of cavities and their surface features. In the last part of this review we discuss recent extensions of the earlier efforts: new space observations of cavity-like structures as well as new laboratory experiments and calculations with greatly improved diagnostics of cavities formed by expansions of laser-produced ions at super-Alfvenic speeds both across and along the background magnetic field

Differences in Fabry Cardiomyopathy Between Female and Male Patients Consequences for Diagnostic Assessment

ObjectivesWe hypothesized that Fabry cardiomyopathy in female patients might differ substantially from that in male patients and sought to prove this hypothesis in a large cohort consisting of 104 patients with Fabry disease.BackgroundFabry cardiomyopathy in male patients is characterized by left ventricular (LV) hypertrophy, impaired myocardial function, and subsequent progressive myocardial fibrosis. In contrast, the occurrence of these 3 cardiomyopathic hallmarks in female patients remains unknown.MethodsIn 104 patients (58 females, age 42 ± 16 years; 46 males, age 42 ± 13 years) with genetically proven Fabry disease, LV hypertrophy, regional myocardial deformation and myocardial fibrosis were assessed by standard echocardiography, strain rate imaging, and cardiac magnetic resonance (CMR) imaging–guided late enhancement (LE).ResultsIn men, end-diastolic left ventricular wall thickness (LVWT) ranged from 6 to 19.5 mm (LV mass CMR 55 to 200 g/m2), and LE was never seen with LVWT <12 mm (LV mass <99 g/m2). In contrast in female patients, LVWT ranged from 5 to 15.5 mm, LV mass ranged from 39 to 146 g/m2, and LE was already detectable with an LVWT of 9 mm (LV mass 56 g/m2). When LV mass was examined in CMR, LE was detected in 23% of the female patients without hypertrophy (n = 9), whereas LE was never seen in male patients with normal LV mass. LE was always associated with low systolic strain rate, but the severity of impairment was independent of LVWT in female patients (lateral strain rate in patients with LV hypertrophy with LE −0.7 ± 0.2 s−1; patients without LV hypertrophy with LE −0.8 ± 0.2 s−1; p = 0.45).ConclusionsIn contrast to male patients, the loss of myocardial function and the development of fibrosis do not necessarily require myocardial hypertrophy in female patients with Fabry disease. Thus, in contrast to actual recommendations, initial cardiac staging and monitoring should be based on LV hypertrophy and on replacement fibrosis in female patients with Fabry disease

Pathogen-based precision medicine for drug-resistant tuberculosis

The implementation of next generation sequencing techniques, such as whole genome sequencing (WGS), in tuberculosis (TB) research has enabled timely, cost-effective, and comprehensive insights into the genetic repertoire of the human pathogens of the Mycobacterium tuberculosis complex (MTBC). WGS data allow for detailed epidemiological analysis based on genomic distance of the MTBC strains under investigation, e.g. for tracing outbreaks; it can accelerate diagnostics by predicting drug resistance from a mutation catalogue (figure 1). Indeed, specific mutations even permit predictions on the possible clinical treatment course and outcome

Perspectives for systems biology in the management of tuberculosis

Standardised management of tuberculosis may soon be replaced by individualised, precision medicine-guided therapies informed with knowledge provided by the field of systems biology. Systems biology is a rapidly expanding field of computational and mathematical analysis and modelling of complex biological systems that can provide insights into mechanisms underlying tuberculosis, identify novel biomarkers, and help to optimise prevention, diagnosis and treatment of disease. These advances are critically important in the context of the evolving epidemic of drug-resistant tuberculosis. Here, we review the available evidence on the role of systems biology approaches - human and mycobacterial genomics and transcriptomics, proteomics, lipidomics/metabolomics, immunophenotyping, systems pharmacology and gut microbiomes - in the management of tuberculosis including prediction of risk for disease progression, severity of mycobacterial virulence and drug resistance, adverse events, comorbidities, response to therapy and treatment outcomes. Application of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach demonstrated that at present most of the studies provide "very low" certainty of evidence for answering clinically relevant questions. Further studies in large prospective cohorts of patients, including randomised clinical trials, are necessary to assess the applicability of the findings in tuberculosis prevention and more efficient clinical management of patients.Publisher PDFPeer reviewe