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Regulation of somatic hypermutation by higher-order chromatin structure
No full textThe generation of protective antibodies by somatic hypermutation (SHM) is essential for antibody maturation and adaptive immunity. SHM involves co-transcriptional mutagenesis of immunoglobulin variable (V) regions regulated by enhancers located hundreds of kilobases away. How 3D chromatin topology affects SHM is poorly understood. Here, we measure higher-order interactions on single alleles of the human immunoglobulin heavy-chain locus (IGH) using Tri-C. We find that SHM is underpinned by a multiway hub wherein the V region is proximal to all enhancers. Cohesin-mediated loop extrusion is dispensable for IGH transcription and hub architecture. Transcription and mutagenesis of IGH switch regions, which are necessary for antibody class-switch recombination, create new chromatin loops that can form without cohesin. However, these additional loops do not compromise hub integrity, V region transcription, or SHM. Thus, antibody maturation occurs within a multiway hub accommodating several gene-enhancer loops in which transcription and mutagenesis of different segments occur non-competitively
The impact of EEG preprocessing parameters on ultra-low-power seizure detection
No full textObjectiveClosed-loop neurostimulation is a promising treatment for drug-resistant focal epilepsy. A major challenge is fast and reliable seizure detection via electroencephalography (EEG). Although many approaches have been published, they often lack statistical power and practical utility. The use of various EEG preprocessing parameters and performance metrics hampers comparability. Additionally, the critical issue of energy consumption for an application in medical devices is rarely considered. Addressing these points, we present a systematic analysis of the impact of EEG preprocessing parameters on seizure detection performance and energy consumption, using one to four EEG channels.MethodsWe analyzed in 145 patients with focal epilepsy the impact of different sampling rates, window sizes, digital resolutions, and number of EEG channels on seizure detection performance and energy consumption. Focusing on clinically relevant, event-based metrics, we evaluated seizure detection performance of a state-of-the-art convolutional neural network (CNN) via the Seizure Community Open-Source Research Evaluation (SzCORE) framework. Statistical relevance of parameter changes was assessed using linear mixed-effects models. Energy consumption was analyzed using an ultra-low-power microcontroller.ResultsReducing the sampling rate from 256 to 64 Hz decreased sensitivity (p = .015) and false detections per hour (FD/h; p = .002). Larger windows reduced FD/h between 1 s and all other sizes (all p SignificanceThis study provides guidance on choosing EEG preprocessing parameters for innovative developments of closed-loop neurostimulation devices to further advance the treatment of drug-resistant focal epilepsy
Electricity market design for 100 % renewable energy in Germany – Challenges and solutions
No full textThe transition to a renewable energy system poses several challenges for electricity market design. This paper examines the structural changes required to accommodate a fully renewable-based electricity system in Germany, emphasising the integration of renewable energy sources, dispatchable power plants, and flexibility options regarding dispatch, investment, and localisation. We provide a broad overview of prospective measures to support such an energy system. We identify nine main challenges and seventeen solutions, conduct a strengths and weaknesses analysis for the solutions, identify the relevance of the challenges, and how well they can be addressed by the solutions. Renewable investment is analysed in greater depth since a steady increase of RES installations is central to the transformation, and as the share of renewables grows, additional challenges arise. Uncertainty surrounding future electricity prices remain significant, with current investments already reflecting an almost complete renewable system. Two pending regulatory decisions in particular contribute to these uncertainties: Bidding zone allocation and subsidies for hydrogen prices. The paper concludes that while current approaches tackle several market design challenges, further research is needed to enhance investment in renewables, flexibility options, and dispatchable resources
Adherence to an enhanced recovery protocol in colorectal surgery before and during a structured implementation - a prospective cohort study from nine German hospitals
No full textResolving inconsistent effects of tDCS on learning using a homeostatic structural plasticity model
No full textTranscranial direct current stimulation (tDCS) is increasingly used to modulate motor learning. Current polarity and intensity, electrode montage, and application before or during learning had mixed effects. Both Hebbian and homeostatic plasticity were proposed to account for the observed effects, but the explanatory power of these models is limited. In a previous modeling study, we showed that homeostatic structural plasticity (HSP) model can explain long-lasting after-effects of tDCS and transcranial magnetic stimulation (TMS). The interference between motor learning and tDCS, which are both based on HSP in our model, is a candidate mechanism to resolve complex and seemingly contradictory experimental observations
urbisphere - ASSURE: Bristol: Across-Scale processeS in URban Environments on our way to coupling dynamic cities and climate
No full textWorsening local and global environmental conditions from climate change affect most of the world’s urban population. To develop sustainable, resilient and healthy environments in the face of these challenge requires support from improved modelling crossing neighbourhood-influenced scales of next-generation weather (0.1–1 km) and climate (2-10 km) forecast models need to resolve. Hence, there is a pressing need is to establish which processes should be parametrised and which resolved, to capture urban heterogeneity adequately in space and time. Two crosscutting challenges are associated with heterogeneity of the arrangement of urban obstacles (i.e. urban form) and anthropogenic activities (i.e. urban function).To address Street (100 m) to Neighbourhood (1 km), to City (10 km), to Region (100 km) scales,. we combine field observations and interviews (RWO), high-resolution numerical simulations (LES, ABM, NWP) and wind tunnel (WT) experiments to advance theoretical understanding and inform development of new parametrisations for larger-scale urban meteorological models. Field work and modelling focus on Bristol, as its physical scale and urban geography allow whole-city approaches, whilst including a range of complex terrain features.. The Bristol project is a continuation of year-long urbisphere field campaigns in Berlin, and Paris, and is complemented by other urbisphere medium-sized city campaigns in complex-terrain in Freiburg (Germany) and Heraklion (Greece).In this talk, we provide an overview of the WT, LES and NWP modelling and RWO observations published and undertaken so far, in this ongoing project
Tall-tower urban eddy covariance flux ratios of CO2, CO, and NOx in three European cities
No full textIn-situ measurements of CO2 emissions play a critical role in quantifying cities’ contributions to regional and global emissions and are a key tool in the validation of city emission inventories and models. Cities are also complex environments containing a multitude of anthropogenic CO2 emission sources such as traffic, residential heating, and industrial production. Correct sectoral attribution of urban GHG emissions is necessary to monitor emission reduction efforts, compare against emission inventories, and separate anthropogenic from biogenic emissions.As part of the ICOS-Cities (PAUL - Pilot Application in Urban Landscapes) project, tall-tower urban eddy covariance (EC) systems were installed in a small city (Zurich, Switzerland), a moderate-sized city (Munich, Germany) and a large city (Paris, France). Use of a high-frequency multi-species gas analyser (MGA-7, MIRO Analytical, Switzerland) together with an ultrasonic anemometer (CSAT3, Campbell Scientific, USA), enabled simultaneous flux measurements of CO2, and co-emitted species CO and NOx. EC measurements provide gas fluxes which integrate all emission sources and sinks within the measurement footprint. By examining the ratio of these gas fluxes in combination with a spatially-resolved emission inventory within the EC footprint, one may validate or improve the emission inventory.We present six months of EC flux ratios of CO2/CO, CO2/NOx, and NOx/CO from each of the three cities covering both growth and dormant seasons, comparing diurnal and seasonal trends in the fluxes and flux ratios, as well as direct comparison against bottom-up emission inventory ratios for each species pair. We further demonstrate that a linear-mixing model is able to generally decompose CO2 fluxes into major sectors and anthropogenic vs biogenic emissions and discuss its performance and limitations
Holmium laser enucleation of the prostate and strictures: long-term outcomes, stricture characteristics, and risk factors
No full textHigh-resolution stereolithography of amorphous, dense and mechanically stable bioactive glass
No full textBioactive glasses (BG) are used for various applications in bone regeneration due to their ability to promote new bone formation. Porous scaffolds made of BG are of particular interest as they allow fast tissue ingrowth and replacement with new bone. The microstructure of these scaffolds influences several aspects of the bioactivity and mechanical properties. Therefore, controlling the geometry is highly desirable. Stereolithography (SL) is able to structure BG composites with high resolution and full design freedom. However, the SL of BG is predominantly performed with glass compositions that crystallize during sintering, leading to a reduction in bioactivity and hindering densification. In addition, features smaller than 200 µm have not been printed, limiting the potential application of the fabricated structures. Here, the high-resolution SL of the BG 13 93 is demonstrated. Crystallization is avoided, and full density and mechanical stability are achieved. Different porous scaffolds, including replication of human bone, are fabricated with a minimum feature size of 77 µm. The mechanical stability of these scaffolds is comparable to human bone. This work enables the 3D printing of complex scaffolds with previously unachieved precision and geometric control, which can be utilized to optimize the performance of BG