Mechanisms of IVIG Efficacy in Chronic Inflammatory Demyelinating Polyneuropathy

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common treatable acquired chronic polyneuropathy. Corticosteroids, plasmapheresis and intravenous immunoglobulins (IVIG) have been shown to be effective in randomized controlled clinical trials and IVIG is widely used as a first-line initial and maintenance treatment for CIDP. Studies in animal models of autoimmune diseases indicated that the inhibitory Fc-gamma receptor FcγRIIB, expressed on myeloid cells and B cells, is required for the anti-inflammatory activity of IVIG. Summary: We found that untreated patients with CIDP, compared to demographically matched healthy controls, show lower FcγRIIB expression levels on naïve B cells and fail to upregulate or to maintain upregulation of FcγRIIB as B cells progress from the naive to the memory compartment. Furthermore, FcγRIIB protein expression is upregulated on B cells and monocytes following clinically effective IVIG therapy suggesting that impaired expression of the inhibitory FcγR in CIDP can, at least partially, be restored by IVIG treatment. In B cells, FcγRIIB transduces an inhibitory signal upon colligation with the B cell receptor, thereby preventing B cells with low affinity or self-reactive receptors from entering the germinal center and becoming IgG positive plasma cells. Our data suggest that this late B cell differentiation checkpoint is impaired in CIDP. Modulating FcγRIIB function might be a promising approach to efficiently limit antibody-mediated immunopathology in CID

VANTED: A system for advanced data analysis and visualization in the context of biological networks

BACKGROUND: Recent advances with high-throughput methods in life-science research have increased the need for automatized data analysis and visual exploration techniques. Sophisticated bioinformatics tools are essential to deduct biologically meaningful interpretations from the large amount of experimental data, and help to understand biological processes. RESULTS: We present VANTED, a tool for the visualization and analysis of networks with related experimental data. Data from large-scale biochemical experiments is uploaded into the software via a Microsoft Excel-based form. Then it can be mapped on a network that is either drawn with the tool itself, downloaded from the KEGG Pathway database, or imported using standard network exchange formats. Transcript, enzyme, and metabolite data can be presented in the context of their underlying networks, e. g. metabolic pathways or classification hierarchies. Visualization and navigation methods support the visual exploration of the data-enriched networks. Statistical methods allow analysis and comparison of multiple data sets such as different developmental stages or genetically different lines. Correlation networks can be automatically generated from the data and substances can be clustered according to similar behavior over time. As examples, metabolite profiling and enzyme activity data sets have been visualized in different metabolic maps, correlation networks have been generated and similar time patterns detected. Some relationships between different metabolites were discovered which are in close accordance with the literature. CONCLUSION: VANTED greatly helps researchers in the analysis and interpretation of biochemical data, and thus is a useful tool for modern biological research. VANTED as a Java Web Start Application including a user guide and example data sets is available free of charge at

Polar boundary layer bromine explosion and ozone depletion events in the chemistry-climate model EMAC v2.52: Implementation and evaluation of AirSnow algorithm

Ozone depletion events (ODEs) in the polar boundary layer have been observed frequently during springtime. They are related to events of boundary layer enhancement of bromine. Consequently, increased amounts of boundary layer volume mixing ratio (VMR) and vertical column densities (VCDs) of BrO have been observed by in situ observation, ground-based as well as airborne remote sensing, and from satellites. These so-called bromine explosion (BE) events have been discussed serving as a source of tropospheric BrO at high latitudes, which has been underestimated in global models so far. We have implemented a treatment of bromine release and recycling on sea-ice- and snow-covered surfaces in the global chemistry–climate model EMAC (ECHAM/MESSy Atmospheric Chemistry) based on the scheme of Toyota et al. (2011). In this scheme, dry deposition fluxes of HBr, HOBr, and BrNO3 over ice- and snow-covered surfaces are recycled into Br2 fluxes. In addition, dry deposition of O3, dependent on temperature and sunlight, triggers a Br2 release from surfaces associated with first-year sea ice. Many aspects of observed bromine enhancements and associated episodes of near-complete depletion of boundary layer ozone, both in the Arctic and in the Antarctic, are reproduced by this relatively simple approach. We present first results from our global model studies extending over a full annual cycle, including comparisons with Global Ozone Monitoring Experiment (GOME) satellite BrO VCDs and surface ozone observations

Brominated VSLS and their influence on ozone under a changing climate

Very short-lived substances (VSLS) contribute as source gases significantly to the tropospheric and stratospheric bromine loading. At present, an estimated 25 % of stratospheric bromine is of oceanic origin. In this study, we investigate how climate change may impact the ocean–atmosphere flux of brominated VSLS, their atmospheric transport, and chemical transformations and evaluate how these changes will affect stratospheric ozone over the 21st century. Under the assumption of fixed ocean water concentrations and RCP6.0 scenario, we find an increase of the ocean–atmosphere flux of brominated VSLS of about 8–10 % by the end of the 21st century compared to present day. A decrease in the tropospheric mixing ratios of VSLS and an increase in the lower stratosphere are attributed to changes in atmospheric chemistry and transport. Our model simulations reveal that this increase is counteracted by a corresponding reduction of inorganic bromine. Therefore the total amount of bromine from VSLS in the stratosphere will not be changed by an increase in upwelling. Part of the increase of VSLS in the tropical lower stratosphere results from an increase in the corresponding tropopause height. As the depletion of stratospheric ozone due to bromine depends also on the availability of chlorine, we find the impact of bromine on stratospheric ozone at the end of the 21st century reduced compared to present day. Thus, these studies highlight the different factors influencing the role of brominated VSLS in a future climate

Transvenous lead extraction in children with bidirectional rotational dissection sheaths

Objectives: Due to the limited longevity of endovascular leads, children require thoughtful lifetime lead management strategies including conservation of access vessel patency. Consequently, there is an increasing interest in transvenous lead extraction (TLE) in children, however, data on TLE and the use of powered mechanical dissection sheaths is limited. Methods: We performed a retrospective cohort study analyzing all children <18 years that underwent TLE in our institution from 2015 to 2022. Procedural complexity, results and complications were defined as recommended by recent consensus statements. Results: Twenty-eight children [median age 12.8 (interquartile range 11.3-14.6) years] were included. Forty-one leads were extracted [median dwell time 85 (interquartile range 52-102) months]. Extractions of 31 leads (76%) in 22 patients (79%) were complex, requiring advanced extraction tools including powered bidirectional rotational dissection sheaths in 14 children. There were no major complications. Complete procedural success was achieved in 18 (64%) and clinical success in 27 patients (96%), respectively. Procedural success and complexity varied between lead types. The Medtronic SelectSecure (TM) lead was associated with increased odds of extraction by simple traction (p = 0.006) and complete procedural success (p < 0.001) while the Boston Scientific Fineline (TM) II lead family had increased odds of partial procedural failure (p = 0.017). Conclusions: TLE with the use of mechanical powered rotational dissection sheaths is feasible and safe in pediatric patients. In light of rare complications and excellent overall clinical success, TLE should be considered an important cornerstone in lifetime lead management in children. Particular lead types might be more challenging and less successful to extract

FluxMap: A VANTED add-on for the visual exploration of flux distributions in biological networks

<p>Abstract</p> <p>Background</p> <p>The quantification of metabolic fluxes is gaining increasing importance in the analysis of the metabolic behavior of biological systems such as organisms, tissues or cells. Various methodologies (wetlab or drylab) result in sets of fluxes which require an appropriate visualization for interpretation by scientists. The visualization of flux distributions is a necessary prerequisite for intuitive flux data exploration in the context of metabolic networks.</p> <p>Results</p> <p>We present FluxMap, a tool for the advanced visualization and exploration of flux data in the context of metabolic networks. The template-based flux data import assigns flux values and optional quality parameters (e. g. the confidence interval) to biochemical reactions. It supports the discrimination between mass and substance fluxes, such as C- or N-fluxes. After import, flux data mapping and network-based visualization allow the interactive exploration of the dataset. Various visualization options enable the user to adapt layout and network representation according to individual purposes.</p> <p>Conclusions</p> <p>The Vanted add-on FluxMap comprises a comprehensive set of functionalities for visualization and advanced visual exploration of flux distributions in biological networks. It is available as a Java open source tool from http://www.vanted.org/fluxmap.</p

Factorization and the Soft Overlap Contribution to Heavy-to-Light Form Factors

Using the formalism of soft-collinear effective theory, a complete separation of short- and long-distance contributions to heavy-to-light transition form factors at large recoil is performed. The universal functions $\zeta_M(E)$ parameterizing the ``soft overlap'' contribution to the form factors are defined in terms of matrix elements in the effective theory. Endpoint configurations corresponding to kinematic situations where one of the valence partons in the external mesons carries very small momentum are accounted for in terms of operators involving soft-collinear messenger fields. They contribute at leading order in $\Lambda_{\rm QCD}/E$ and spoil factorization. An analysis of operator mixing and renormalization-group evolution in the effective theory reveals that the intermediate scale $\sqrt{E\Lambda}$ is without significance to the soft functions $\zeta_M(E)$, and that the soft overlap contribution does not receive a significant perturbative (Sudakov) suppression.Comment: 30 pages, 6 figures. Erratum adde

Specifications of Standards in Systems and Synthetic Biology: Status and Developments in 2016

Standards are essential to the advancement of science and technology. In systems and synthetic biology, numerous standards and associated tools have been developed over the last 16 years. This special issue of the Journal of Integrative Bioinformatics aims to support the exchange, distribution and archiving of these standards, as well as to provide centralised and easily citable access to them

A Game-based Approach to Understand Human Factors in Supply Chains and Quality Management

Abstract Quality management is an important function for viable production networks. In order to qualify decision makers to understand the fundamental principles of quality management in production networks, a game-based simulation and learning environment is developed, which can furthermore be used to understand how human factors influence the quality of decisions in complex production networks. Previous studies have shown that underlying factors must exist, which predict the players&apos; performance. It is currently unexplored, which factors are contributing to high performance. To deeper investigate which human factors are critical for supply chain success and to further refine the quality management game a series of studies were examined. As expected, expertise had a great impact on performance, however contrary to the expectations cognitive skills had none. The refined decision dashboard, with seamlessly integrated self-adapting visualizations on key performance indicators, had a significant positive impact on game performance. The studies suggest that the developed game is a valuable contribution for the qualification of quality managers, as the quality of decision increased