Directed Chaotic Transport in Hamiltonian Ratchets

We present a comprehensive account of directed transport in one-dimensional Hamiltonian systems with spatial and temporal periodicity. They can be considered as Hamiltonian ratchets in the sense that ensembles of particles can show directed ballistic transport in the absence of an average force. We discuss general conditions for such directed transport, like a mixed classical phase space, and elucidate a sum rule that relates the contributions of different phase-space components to transport with each other. We show that regular ratchet transport can be directed against an external potential gradient while chaotic ballistic transport is restricted to unbiased systems. For quantized Hamiltonian ratchets we study transport in terms of the evolution of wave packets and derive a semiclassical expression for the distribution of level velocities which encode the quantum transport in the Floquet band spectra. We discuss the role of dynamical tunneling between transporting islands and the chaotic sea and the breakdown of transport in quantum ratchets with broken spatial periodicity.Comment: 22 page

What are the Drivers of Tax Complexity for Multinational Corporations? Evidence from 108 Countries

All over the world, firms and governments are increasingly concerned about the rise in tax complexity. To manage it and develop effective simplification measures, detailed information on the current drivers of complexity is required. However, research on this topic is scarce. This is surprising as the latest developments - for example, triggered by the BEPS project - give rise to the conjecture that complexity drivers may have changed, thus questioning the findings of prior studies. In this paper, we shed light on this issue and provide a global picture of the current drivers of tax complexity that multinational corporations face based on a survey of 221 highly experienced tax practitioners from 108 countries. Our results show that prior complexity drivers of the tax code are still relevant, with details and changes of tax regulations being the two most influential complexity drivers. We also find evidence for new relevant complexity drivers emerging from different areas of the tax framework, such as inconsistent decisions among tax officers (tax audits) or retroactively applied tax law amendments (tax enactment). Based on the responses of the practitioners, we develop a concept of tax complexity that distinguishes two pillars, tax code and tax framework complexity, and illustrates the various aspects that should be considered when assessing the complexity of a country's tax system.Series: WU International Taxation Research Paper Serie

The Tax Complexity Index – A Survey-Based Country Measure of Tax Code and Framework Complexity

This paper introduces the Tax Complexity Index (TCI). The TCI comprehensively measures the complexity of countries’ corporate income tax systems faced by multinational corporations. It builds on surveys of highly experienced tax consultants of the largest international tax services networks. The TCI is composed of a tax code subindex covering tax regulations and a tax framework subindex covering tax processes and features. For a sample of 100 countries, we find that tax complexity varies considerably across countries, and tax code and framework complexity also vary within countries. Among others, tax complexity is strongly driven by the complexity of transfer pricing regulations in the tax code and tax audits in the tax framework. When analyzing the associations with other country characteristics, we identify different patterns. For example, we find a positive association of GDP with tax code complexity and a negative association with tax framework complexity, suggesting that highly economically developed countries tend to have more complex tax codes and less complex frameworks. Overall, the tax complexity measures can serve as valuable proxies in future research and supportive tools for a variety of firm decisions and national and international tax policy discussions.Series: WU International Taxation Research Paper Serie

Emberger Syndrome – A Family History Over 3 Generations

# Introduction Haploinsufficiency of _GATA2_ leads to impaired genesis and function of hematopoietic stem and progenitor cells, resulting in impairment of all subsequent blood cell lineages. Germline mutations in _GATA2_ are transmitted by autosomal-dominant inheritance. Leading clinical symptoms of _GATA2_ deficiency syndromes are immunodeficiency, infections (mainly nontuberculous mycobacteria and human papillomavirus), predisposition to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), pulmonary alveolar proteinosis (PAP) and primary lymphedema. _GATA2_ mutations underlie not only Emberger syndrome (primary lymphedema and MDS), but also other syndromes like monocytopenia and mycobacterial infections syndrome (MonoMAC), dendritic cell/monocytopenia/natural killer (NK)-cell/B-cell lymphoid deficiency (DCML) and familial MDS/AML syndrome. We report the history of a Swiss family with Emberger syndrome extending over three generations. In addition, a review of the literature on _GATA2_ deficiencies is provided. # Methods Based on a general practitioner's observation of father and son sharing similar declined blood values and lymphedema, we examined the whole family for the presence of _GATA2_ mutation and a possible genotype-phenotype correlation. Publications on _GATA2_ deficiencies were researched on the PubMed database. # Results Six family members were diagnosed with _GATA2_ mutation, demonstrating individually variable penetrance and diversity of leading symptoms. # Conclusion Careful investigation of personal and family history, as well as meticulous examination, led to suspicion of the rare diagnosis of familial Emberger syndrome. Early diagnosis is mandatory for appropriate disease management

Experimentally induced incomplete burst fractures - a novel technique for calf and human specimens

Background: Fracture morphology is crucial for the clinical decision-making process preceding spinal fracture treatment. The presented experimental approach was designed in order to ensure reproducibility of induced fracture morphology. Results: The presented method resulted in fracture morphology, found in clinical classification systems like the Magerl classification. In the calf spine samples, 70% displayed incomplete burst fractures corresponding to type A3.1 and A3.2 fractures. In all human samples, superior incomplete burst fractures (Magerl A3.1) were identified by an independent radiologist and spine surgeon. Conclusions: The presented set up enables the first experimental means to reliably model and study distinct incomplete burst fracture patterns in an in vitro setting. Thus, we envisage this protocol to facilitate further studies on spine fracture treatment of incomplete burst fractures

Successful Induction of Specific Immunological Tolerance by Combined Kidney and Hematopoietic Stem Cell Transplantation in HLA-Identical Siblings

Induction of immunological tolerance has been the holy grail of transplantation immunology for decades. The only successful approach to achieve it in patients has been a combined kidney and hematopoietic stem cell transplantation from an HLA-matched or -mismatched living donor. Here, we report the first three patients in Europe included in a clinical trial aiming at the induction of tolerance by mixed lymphohematopoietic chimerism after kidney transplantation. Two female and one male patient were transplanted with a kidney and peripherally mobilized hematopoietic stem cells from their HLA-identical sibling donor. The protocol followed previous studies at Stanford University: kidney transplantation was performed on day 0 including induction with anti-thymocyte globulin followed by conditioning with 10x 1.2 Gy total lymphoid irradiation and the transfusion of CD34+ cells together with a body weight-adjusted dose of donor T cells on day 11. Immunosuppression consisted of cyclosporine A and steroids for 10 days, cyclosporine A and mycophenolate mofetil for 1 month, and then cyclosporine A monotherapy with tapering over 9-20 months. The 3 patients have been off immunosuppression for 4 years, 19 months and 8 months, respectively. No rejection or graft-versus-host disease occurred. Hematological donor chimerism was stable in the first, but slowly declining in the other two patients. A molecular microscope analysis in patient 2 revealed the genetic profile of a normal kidney. No relevant infections were observed, and the quality of life in all three patients is excellent. During the SARS-CoV-2 pandemic, all three patients were vaccinated with the mRNA vaccine BNT162b2 (Comirnaty®), and they showed excellent humoral and in 2 out 3 patients also cellular SARS-CoV-2-specific immunity. Thus, combined kidney and hematopoietic stem cell transplantation is a feasible and successful approach to induce specific immunological tolerance in the setting of HLA-matched sibling living kidney donation while maintaining immune responsiveness to an mRNA vaccine (ClinicalTrials.gov: NCT00365846). Keywords: COVID - 19; chimerism; hematopoietic stem cell transplantation (HSCT); immunocompetence; kidney transplantation; toleranc

Balancing intestinal and systemic inflammation through cell type-specific expression of the aryl hydrocarbon receptor repressor

As a sensor of polyaromatic chemicals the aryl hydrocarbon receptor (AhR) exerts an important role in immune regulation besides its requirement for xenobiotic metabolism. Transcriptional activation of AhR target genes is counterregulated by the AhR repressor (AhRR) but the exact function of the AhRR in vivo is currently unknown. We here show that the AhRR is predominantly expressed in immune cells of the skin and intestine, different from other AhR target genes. Whereas AhRR antagonizes the anti-inflammatory function of the AhR in the context of systemic endotoxin shock, AhR and AhRR act in concert to dampen intestinal inflammation. Specifically, AhRR contributes to the maintenance of colonic intraepithelial lymphocytes and prevents excessive IL- 1β production and Th17/Tc17 differentiation. In contrast, the AhRR enhances IFN-γ-production by effector T cells in the inflamed gut. Our findings highlight the physiologic importance of cell-type specific balancing of AhR/AhRR expression in response to microbial, nutritional and other environmental stimuli

Performance of the New FlashCam-based Camera in the 28\,m Telescope of H.E.S.S

In October 2019, the central 28 m telescope of the H.E.S.S. experiment has been upgraded with a new camera. The camera is based on the FlashCam design which has been developed in view of a possible future implementation in the Medium-Sized Telescopes of the Cherenkov Telescope Array (CTA), with emphasis on cost and performance optimization and on reliability. The fully digital design of the trigger and readout system makes it possible to operate the camera at high event rates and to precisely adjust and understand the trigger system. The novel design of the front-end electronics achieves a dynamic range of over 3,000 photoelectrons with only one electronics readout circuit per pixel. Here we report on the performance parameters of the camera obtained during the first year of operation in the field, including operational stability and optimization of calibration algorithms.Comment: Proceedings of the 37th International Cosmic Ray Conference (ICRC 2021

Distinct, IgG1-driven antibody response landscapes demarcate individuals with broadly HIV-1 neutralizing activity

Understanding pathways that promote HIV-1 broadly neutralizing antibody (bnAb) induction is crucial to advance bnAb-based vaccines. We recently demarcated host, viral, and disease parameters associated with bnAb development in a large HIV-1 cohort screen. By establishing comprehensive antibody signatures based on IgG1, IgG2, and IgG3 activity to 13 HIV-1 antigens in 4,281 individuals in the same cohort, we now show that the same four parameters that are significantly linked with neutralization breadth, namely viral load, infection length, viral diversity, and ethnicity, also strongly influence HIV-1-binding antibody responses. However, the effects proved selective, shaping binding antibody responses in an antigen and IgG subclass-dependent manner. IgG response landscapes in bnAb inducers indicated a differentially regulated, IgG1-driven HIV-1 antigen response, and IgG1 binding of the BG505 SOSIP trimer proved the best predictor of HIV-1 neutralization breadth in plasma. Our findings emphasize the need to unravel immune modulators that underlie the differentially regulated IgG response in bnAb inducers to guide vaccine development