Data driven consistency (working title)

We are motivated by applications that need rich model classes to represent them. Examples of rich model classes include distributions over large, countably infinite supports, slow mixing Markov processes, etc. But such rich classes may be too complex to admit estimators that converge to the truth with convergence rates that can be uniformly bounded over the entire model class as the sample size increases (uniform consistency). However, these rich classes may still allow for estimators with pointwise guarantees whose performance can be bounded in a model dependent way. The pointwise angle of course has the drawback that the estimator performance is a function of the very unknown model that is being estimated, and is therefore unknown. Therefore, even if the estimator is consistent, how well it is doing may not be clear no matter what the sample size is. Departing from the dichotomy of uniform and pointwise consistency, a new analysis framework is explored by characterizing rich model classes that may only admit pointwise guarantees, yet all the information about the model needed to guage estimator accuracy can be inferred from the sample at hand. To retain focus, we analyze the universal compression problem in this data driven pointwise consistency framework.Comment: Working paper. Please email authors for the current versio

Limiting shapes of confined lipid vesicles

We theoretically study the shapes of lipid vesicles confined to a spherical cavity, elaborating a framework based on the so-called limiting shapes constructed from geometrically simple structural elements such as double-membrane walls and edges. Partly inspired by numerical results, the proposed non-compartmentalized and compartmentalized limiting shapes are arranged in the bilayer-couple phase diagram which is then compared to its free-vesicle counterpart. We also compute the area-difference-elasticity phase diagram of the limiting shapes and we use it to interpret shape transitions experimentally observed in vesicles confined within another vesicle. The limiting-shape framework may be generalized to theoretically investigate the structure of certain cell organelles such as the mitochondrion

Climate change and climate change velocity analysis across Germany

Although there are great concerns to what extent current and future climate change impacts biodiversity across different spatial and temporal scales, we still lack a clear information on different climate change metrics across fine spatial scales. Here we present an analysis of climate change and climate change velocity at a local scale (1 × 1 km) across Germany. We focus on seasonal climate variability and velocity and investigate changes in three time periods (1901–2015, 1901–1950 and 1951–2015) using a novel statistical approach. Our results on climate variability showed the highest trends for the 1951–2015 time period. The strongest (positive/negative) and spatially the most dispersed trends were found for Summer maximum temperature and Summer minimum temperatures. For precipitation the strongest positive trends were most pronounced in the summer (1951–2015) and winter (1901–2015). Results for climate change velocity showed that almost 90% of temperature velocities were in the range of 0.5 to 3 km/year, whereas all climate velocities for precipitation were within the range of −3.5 to 4.5 km/year. The key results amplify the need for more local and regional scale studies to better understand species individualistic responses to recent climate change and allow for more accurate future projections and conservation strategies

QuizMap: Open social student modeling and adaptive navigation support with TreeMaps

In this paper, we present a novel approach to integrate social adaptive navigation support for self-assessment questions with an open student model using QuizMap, a TreeMap-based interface. By exposing student model in contrast to student peers and the whole class, QuizMap attempts to provide social guidance and increase student performance. The paper explains the nature of the QuizMap approach and its implementation in the context of self-assessment questions for Java programming. It also presents the design of a semester-long classroom study that we ran to evaluate QuizMap and reports the evaluation results. © 2011 Springer-Verlag Berlin Heidelberg

Local genetic context shapes the function of a gene regulatory network

Gene expression levels are influenced by multiple coexisting molecular mechanisms. Some of these interactions such as those of transcription factors and promoters have been studied extensively. However, predicting phenotypes of gene regulatory networks (GRNs) remains a major challenge. Here, we use a well-defined synthetic GRN to study in Escherichia coli how network phenotypes depend on local genetic context, i.e. the genetic neighborhood of a transcription factor and its relative position. We show that one GRN with fixed topology can display not only quantitatively but also qualitatively different phenotypes, depending solely on the local genetic context of its components. Transcriptional read-through is the main molecular mechanism that places one transcriptional unit (TU) within two separate regulons without the need for complex regulatory sequences. We propose that relative order of individual TUs, with its potential for combinatorial complexity, plays an important role in shaping phenotypes of GRNs

LFRic: meeting the challenges of scalability and performance portability in weather and climate models

This paper describes LFRic: the new weather and climate modelling system being developed by the UK Met Office to replace the existing Unified Model in preparation for exascale computing in the 2020s. LFRic uses the GungHo dynamical core and runs on a semi-structured cubed-sphere mesh. The design of the supporting infrastructure follows object-oriented principles to facilitate modularity and the use of external libraries where possible. In particular, a `separation of concerns' between the science code and parallel code is imposed to promote performance portability. An application called PSyclone, developed at the STFC Hartree centre, can generate the parallel code enabling deployment of a single source science code onto different machine architectures. This paper provides an overview of the scientific requirement, the design of the software infrastructure, and examples of PSyclone usage. Preliminary performance results show strong scaling and an indication that hybrid MPI/OpenMP performs better than pure MPI

Simulations of idealised 3D atmospheric flows on terrestrial planets using LFRic-Atmosphere

We demonstrate that LFRic-Atmosphere, a model built using the Met Office's GungHo dynamical core, is able to reproduce idealised large-scale atmospheric circulation patterns specified by several widely-used benchmark recipes. This is motivated by the rapid rate of exoplanet discovery and the ever-growing need for numerical modelling and characterisation of their atmospheres. Here we present LFRic-Atmosphere's results for the idealised tests imitating circulation regimes commonly used in the exoplanet modelling community. The benchmarks include three analytic forcing cases: the standard Held-Suarez test, the Menou-Rauscher Earth-like test, and the Merlis-Schneider Tidally Locked Earth test. Qualitatively, LFRic-Atmosphere agrees well with other numerical models and shows excellent conservation properties in terms of total mass, angular momentum and kinetic energy. We then use LFRic-Atmosphere with a more realistic representation of physical processes (radiation, subgrid-scale mixing, convection, clouds) by configuring it for the four TRAPPIST-1 Habitable Atmosphere Intercomparison (THAI) scenarios. This is the first application of LFRic-Atmosphere to a possible climate of a confirmed terrestrial exoplanet. LFRic-Atmosphere reproduces the THAI scenarios within the spread of the existing models across a range of key climatic variables. Our work shows that LFRic-Atmosphere performs well in the seven benchmark tests for terrestrial atmospheres, justifying its use in future exoplanet climate studies.Comment: 34 pages, 9(12) figures; Submitted to Geoscientific Model Development; Comments are welcome (see Discussion tab on the journal's website: https://egusphere.copernicus.org/preprints/2023/egusphere-2023-647

G-CSF Prevents the Progression of Structural Disintegration of White Matter Tracts in Amyotrophic Lateral Sclerosis: A Pilot Trial

Background: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible.Methods: Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 mu g/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS), a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days). The total number of adverse events (AE) and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI), brain volumetry, and voxel-based morphometry.Results: Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA) encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF.Conclusions: Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of clinical data showed no significant effect, DTI measurements suggest that the widespread and progressive microstructural neural damage in ALS can be modulated by G-CSF treatment. These findings may carry significant implications for further clinical trials on ALS using growth factors