Efficient multi-level hp-finite elements in arbitrary dimensions

We present an efficient algorithmic framework for constructing multi-level hp-bases that uses a data-oriented approach that easily extends to any number of dimensions and provides a natural framework for performance-optimized implementations. We only operate on the bounding faces of finite elements without considering their lower-dimensional topological features and demonstrate the potential of the presented methods using a newly written open-source library. First, we analyze a Fichera corner and show that the framework does not increase runtime and memory consumption when compared against the classical p-version of the finite element method. Then, we compute a transient example with dynamic refinement and derefinement, where we also obtain the expected convergence rates and excellent performance in computing time and memory usage

PEDIATRIC TULAREMIA– A CASE SERIES FROM A SINGLE CENTER IN SWITZERLAND

Background The incidence of tularemia has recently increased throughout Europe. Pediatric tularemia typically presents with ulceroglandular or glandular disease and requires antimicrobial therapy not used in the empirical management of childhood acute lymphadenitis. We describe the clinical presentation and course in a case series comprising 20 patients. Methods Retrospective analysis of a single-center case series of microbiologically confirmed tularemia in patients below 16 years of age diagnosed between 2010 and 2021. Results Nineteen patients (95%) presented with ulceroglandular (n = 14) or glandular disease (n = 5), respectively. A characteristic entry site lesion (eschar) was present in 14 (74%). Fever was present at illness onset in 15 patients (75%) and disappeared in all patients before targeted therapy was initiated. The diagnosis was confirmed by serology in 18 patients (90%). While immunochromatography (ICT) was positive as early as on day 7, a microagglutination test (MAT) titer 1:≥160 was found no earlier than on day 13. Sixteen patients (80%) were initially treated with an antimicrobial agent ineffective against F. tularensis. The median delay (range) from illness onset to initiation of targeted therapy was 12 days (range, 6-40). Surgical incision and drainage was ultimately performed in 12 patients (60%). Conclusion Pediatric tularemia in Switzerland usually presents with early, self-limiting fever, and a characteristic entry site lesion with regional lymphadenopathy draining the scalp or legs. Particularly in association with a tick exposure history, this presentation may allow early first-line therapy with an agent specifically targeting F. tularensis, potentially obviating the need for surgical therapy

Crustal structure of the Niuafo’ou Microplate and Fonualei Rift and Spreading Center in the northeastern Lau Basin, Southwestern Pacific

Key points: First insights into the crustal structure of the northeastern Lau Basin, along a 290 km transect at 17°20’S. Crust in southern Fonualei Rift and Spreading Center was created by extension of arc crust and variable amount of magmatism. Magmatic underplating is present in some parts of the southern Niuafo’ou Microplate The northeastern Lau Basin is one of the fastest opening and magmatically most active back‐arc regions on Earth. Although the current pattern of plate boundaries and motions in this complex mosaic of microplates is reasonably understood, the internal structure and evolution of the back‐arc crust are not. We present new geophysical data from a 290 km long east‐west oriented transect crossing the Niuafo’ou Microplate (back‐arc), the Fonualei Rift and Spreading Centre (FRSC) and the Tofua Volcanic Arc at 17°20’S. Our P‐wave tomography model and density modelling suggests that past crustal accretion inside the southern FRSC was accommodated by a combination of arc crustal extension and magmatic activity. The absence of magnetic reversals inside the FRSC supports this and suggests that focused seafloor spreading has until now not contributed to crustal accretion. The back‐arc crust constituting the southern Niuafo’ou Microplate reveals a heterogeneous structure comprising several crustal blocks. Some regions of the back‐arc show a crustal structure similar to typical oceanic crust, suggesting they originate from seafloor spreading. Other crustal blocks resemble a structure that is similar to volcanic arc crust or a ‘hydrous’ type of oceanic crust that has been created at a spreading center influenced by slab‐derived water at distances < 50 km to the arc. Throughout the back‐arc region we observe a high‐velocity (Vp 7.2‐7.5 km s‐1) lower crust, which is an indication for magmatic underplating, which is likely sustained by elevated upper mantle temperatures in this region

Laser beam shape optimization: Exploring alternative profiles to Gaussian-shaped laser beams in powder bed fusion of metals

Laser-based powder bed fusion of metals (PBF-LB/M) commonly utilizes Gaussian-shaped laser beams characterized by a high intensity at the center. However, this type of profile leads to localized high temperatures and temperature gradients. When the laser power is increased beyond a certain threshold, the temperature inside the melt pool can reach the boiling point, causing excessive metal evaporation, hydrodynamic instabilities, and undesired effects such as keyholing. On the other hand, ring-shaped laser beams generate a more uniform temperature distribution but tend to produce shallower, wider, and shorter melt pools with reduced resolution compared to the Gaussian profiles. The deep, narrow, and elongated melt pools generated by the Gaussian shapes still have advantages for increased precision in the PBF-LB/M processes. This contribution uses numerical optimization to generate a new laser beam shape that also leads to a deep, narrow, and elongated melt pool, similar to a Gaussian-shaped beam, while maintaining a lower and more uniform temperature distribution inside the melt pool. The resulting optimized laser profile lowers the maximum laser intensity by 40 % without decreasing the total laser power compared to the Gaussian profile. The more uniform distribution of temperature with a peak value of just above 3 000 ◦C indicates a conduction dominated process with less hydrodynamic and minimal evaporative effects. This is expected to reduce the associated defects and improve the process stabilityMechanical Engineerin

Explanation as a Social Practice: Toward a Conceptual Framework for the Social Design of AI Systems

none20siThe recent surge of interest in explainability in artificial intelligence (XAI) is propelled by not only technological advancements in machine learning, but also by regulatory initiatives to foster transparency in algorithmic decision making. In this article, we revise the current concept of explainability and identify three limitations: passive explainee, narrow view on the social process, and undifferentiated assessment of understanding. In order to overcome these limitations, we present explanation as a social practice in which explainer and explainee co-construct understanding on the microlevel. We view the co-construction on a microlevel as embedded into a macrolevel, yielding expectations concerning, e.g., social roles or partner models: Typically, the role of the explainer is to provide an explanation and to adapt it to the current level of understanding of the explainee; the explainee, in turn, is expected to provide cues that guide the explainer. Building on explanations being a social practice, we present a conceptual framework that aims to guide future research in XAI. The framework relies on the key concepts of monitoring and scaffolding to capture the development of interaction. We relate our conceptual framework and our new perspective on explaining to transparency and autonomy as objectives considered for XAInoneKatharina J. Rohlfing; Philipp Cimiano; Ingrid Scharlau; Tobias Matzner; Heike M. Buhl; Hendrik Buschmeier; Elena Esposito; Angela Grimminger; Barbara Hammer; Reinhold Häb-Umbach; Ilona Horwath; Eyke Hüllermeier; Friederike Kern; Stefan Kopp; Kirsten Thommes; Axel-Cyrille Ngonga Ngomo; Carsten Schulte; Henning Wachsmuth; Petra Wagner; Britta WredeKatharina J. Rohlfing; Philipp Cimiano; Ingrid Scharlau; Tobias Matzner; Heike M. Buhl; Hendrik Buschmeier; Elena Esposito; Angela Grimminger; Barbara Hammer; Reinhold Häb-Umbach; Ilona Horwath; Eyke Hüllermeier; Friederike Kern; Stefan Kopp; Kirsten Thommes; Axel-Cyrille Ngonga Ngomo; Carsten Schulte; Henning Wachsmuth; Petra Wagner; Britta Wred

Experimental warming differentially affects vegetative and reproductive phenology of tundra plants

Rapid climate warming is altering Arctic and alpine tundra ecosystem structure and function, including shifts in plant phenology. While the advancement of green up and flowering are well-documented, it remains unclear whether all phenophases, particularly those later in the season, will shift in unison or respond divergently to warming. Here, we present the largest synthesis to our knowledge of experimental warming effects on tundra plant phenology from the International Tundra Experiment. We examine the effect of warming on a suite of season-wide plant phenophases. Results challenge the expectation that all phenophases will advance in unison to warming. Instead, we find that experimental warming caused: (1) larger phenological shifts in reproductive versus vegetative phenophases and (2) advanced reproductive phenophases and green up but delayed leaf senescence which translated to a lengthening of the growing season by approximately 3%. Patterns were consistent across sites, plant species and over time. The advancement of reproductive seasons and lengthening of growing seasons may have significant consequences for trophic interactions and ecosystem function across the tundra.publishedVersio

Haematopoietic stem cells in perisinusoidal niches are protected from ageing.

With ageing, intrinsic haematopoietic stem cell (HSC) activity decreases, resulting in impaired tissue homeostasis, reduced engraftment following transplantation and increased susceptibility to diseases. However, whether ageing also affects the HSC niche, and thereby impairs its capacity to support HSC function, is still widely debated. Here, by using in-vivo long-term label-retention assays we demonstrate that aged label-retaining HSCs, which are, in old mice, the most quiescent HSC subpopulation with the highest regenerative capacity and cellular polarity, reside predominantly in perisinusoidal niches. Furthermore, we demonstrate that sinusoidal niches are uniquely preserved in shape, morphology and number on ageing. Finally, we show that myeloablative chemotherapy can selectively disrupt aged sinusoidal niches in the long term, which is linked to the lack of recovery of endothelial Jag2 at sinusoids. Overall, our data characterize the functional alterations of the aged HSC niche and unveil that perisinusoidal niches are uniquely preserved and thereby protect HSCs from ageing

The tundra phenology database: more than two decades of tundra phenology responses to climate change

Observations of changes in phenology have provided some of the strongest signals of the effects of climate change on terrestrial ecosystems. The International Tundra Experiment (ITEX), initiated in the early 1990s, established a common protocol to measure plant phenology in tundra study areas across the globe. Today, this valuable collection of phenology measurements depicts the responses of plants at the colder extremes of our planet to experimental and ambient changes in temperature over the past decades. The database contains 150 434 phenology observations of 278 plant species taken at 28 study areas for periods of 1\u201326 years. Here we describe the full data set to increase the visibility and use of these data in global analyses and to invite phenology data contributions from underrepresented tundra locations. Portions of this tundra phenology database have been used in three recent syntheses, some data sets are expanded, others are from entirely new study areas, and the entirety of these data are now available at the Polar Data Catalogue (https://doi.org/10.21963/13215)

Monitoring integrity and localization of modified single-stranded RNA oligonucleotides using ultrasensitive fluorescence methods

Short single-stranded oligonucleotides represent a class of promising therapeutics with diverse application areas. Antisense oligonucleotides, for example, can interfere with various processes involved in mRNA processing through complementary base pairing. Also RNA interference can be regulated by antagomirs, single-stranded siRNA and single-stranded microRNA mimics. The increased susceptibility to nucleolytic degradation of unpaired RNAs can be counteracted by chemical modification of the sugar phosphate backbone. In order to understand the dynamics of such single-stranded RNAs, we investigated their fate after exposure to cellular environment by several fluorescence spectroscopy techniques. First, we elucidated the degradation of four differently modified, dual-dye labeled short RNA oligonucleotides in HeLa cell extracts by fluorescence correlation spectroscopy, fluorescence cross-correlation spectroscopy and Forster resonance energy transfer. We observed that the integrity of the oligonucleotide sequence correlates with the extent of chemical modifications. Furthermore, the data showed that nucleolytic degradation can only be distinguished from unspecific effects like aggregation, association with cellular proteins, or intramolecular dynamics when considering multiple measurement and analysis approaches. We also investigated the localization and integrity of the four modified oligonucleotides in cultured HeLa cells using fluorescence lifetime imaging microscopy. No intracellular accumulation could be observed for unmodified oligonucleotides, while completely stabilized oligonucleotides showed strong accumulation within HeLa cells with no changes in fluorescence lifetime over 24 h. The integrity and accumulation of partly modified oligonucleotides was in accordance with their extent of modification. In highly fluorescent cells, the oligonucleotides were transported to the nucleus. The lifetime of the RNA in the cells could be explained by a balance between release of the oligonucleotides from endosomes, degradation by RNases and subsequent depletion from the cells

Regulation of miR-146a by RelA/NFkB and p53 in STHdhQ111/HdhQ111 Cells, a Cell Model of Huntington's Disease

Huntington's disease (HD) is caused by the expansion of N-terminal polymorphic poly Q stretch of the protein huntingtin (HTT). Deregulated microRNAs and loss of function of transcription factors recruited to mutant HTT aggregates could cause characteristic transcriptional deregulation associated with HD. We observed earlier that expressions of miR-125b, miR-146a and miR-150 are decreased in STHdhQ111/HdhQ111 cells, a model for HD in comparison to those of wild type STHdhQ7/HdhQ7 cells. In the present manuscript, we show by luciferase reporter assays and real time PCR that decreased miR-146a expression in STHdhQ111/HdhQ111 cells is due to decreased expression and activity of p65 subunit of NFkB (RelA/NFkB). By reporter luciferase assay, RT-PCR and western blot analysis, we also show that both miR-150 and miR-125b target p53. This partially explains the up regulation of p53 observed in HD. Elevated p53 interacts with RelA/NFkB, reduces its expression and activity and decreases the expression of miR-146a, while knocking down p53 increases RelA/NFkB and miR-146a expressions. We also demonstrate that expression of p53 is increased and levels of RelA/NFkB, miR-146a, miR-150 and miR-125b are decreased in striatum of R6/2 mice, a mouse model of HD and in cell models of HD. In a cell model, this effect could be reversed by exogenous expression of chaperone like proteins HYPK and Hsp70. We conclude that (i) miR-125b and miR-150 target p53, which in turn regulates RelA/NFkB and miR-146a expressions; (ii) reduced miR-125b and miR-150 expressions, increased p53 level and decreased RelA/NFkB and miR-146a expressions originate from mutant HTT (iii) p53 directly or indirectly regulates the expression of miR-146a. Our observation of interplay between transcription factors and miRNAs using HD cell model provides an important platform upon which further work is to be done to establish if such regulation plays any role in HD pathogenesis