Miracle-dz/UniFAR-FTUs huggingface dataset:
TREM1 disrupts myeloid bioenergetics and cognitive function in aging and Alzheimer’s disease models

Human genetics implicate defective myeloid responses in the development of late onset, age-associated Alzheimer’s disease (AD). Aging is characterized by a decline in myeloid metabolism that triggers maladaptive, neurotoxic immune responses. TREM1 is an amplifier of pro-inflammatory myeloid responses, and here we find that Trem1 deficiency prevents age-dependent changes in myeloid metabolism, inflammation, and hippocampal memory function. Trem1 deficiency rescues age-associated declines in ribose-5P, a glycolytic intermediate and the precursor for purine, pyrimidine, and NAD+ biosynthesis. In vitro, Trem1 deficient microglia are resistant to bioenergetic changes induced by amyloid-ß42 oligomers (Aß42), suggesting that Aß42 stimulation disrupts homeostatic microglial metabolism and immune function via TREM1. In the 5XFAD model of amyloid accumulation, Trem1 haploinsufficiency prevents spatial memory loss, preserves homeostatic microglial morphology, and reduces neuritic dystrophy independent of amyloid accumulation or changes in the disease-associated microglial transcriptomic signature. In aging APPSwe mice, Trem1 deficiency restores synaptic mitochondrial function and cerebral glucose uptake and prevents hippocampal memory decline. In post-mortem human brain, microglial TREM1 expression increases with clinical and neuropathological severity. Thus, TREM1-mediated disruption of myeloid metabolism, both in the periphery and brain, promotes cognitive decline in aging and amyloid accumulation, two major risk factors for AD development.
NeuralPlayground: A Standardised Environment for Evaluating Models of Hippocampus and Entorhinal Cortex

Neural processes in the hippocampus and entorhinal cortex are thought to be crucial for spatial cognition. A growing variety of theoretical models have been proposed to capture the rich neural and behavioral phenomena associated with these circuits. However, systematic comparison of these theories, both against each other and against empirical data, remains challenging. To address this gap, we present NeuralPlayground, an open-source standardised software framework for comparisons between theory and experiment in the domain of spatial cognition. This Python software package offers a reproducible way to compare models against a centralised library of published experimental results, including neural recordings and animal behavior. The framework implements three Agents embodying different computational models; three Experiments comprising publicly available neural and behavioral datasets; a customisable 2-dimensional Arena (continuous and discrete) able to generate common and novel spatial layouts; and a Comparison tool that facilitates systematic comparisons between models and data. Each module can also be used separately, allowing standardised and flexible access to influential models and data sets. We hope NeuralPlayground, available on GitHub3, provides a starting point for a shared, standardized, open, and reproducible computational understanding of the role of the hippocampus and entorhinal cortex in spatial cognition.
Coseismic Slip Deficit of the 2017 Mw 6.5 Ormoc Earthquake That Occurred Along a Creeping Segment and Geothermal Field of the Philippine Fault

Coseismic surface deformation imaged through interferometric synthetic aperture radar (InSAR) measurements was used to estimate the fault geometry and slip distribution of the 2017 Mw 6.5 Ormoc earthquake along a creeping segment of the Philippine Fault on Leyte Island. Our best fitting faulting model suggests that the coseismic rupture occurred on a fault plane with high dip angle of 78.5° and strike angle of 325.8°, and the estimated maximum fault slip of 2.3 m is located at 6.5 km east‐northeast of the town of Kananga. The recognized insignificant slip in the Tongonan geothermal field zone implies that the plastic behavior caused by high geothermal gradient underneath the Tongonan geothermal field could prevent the coseismic failure in heated rock mass in this zone. The predicted Coulomb failure stress change shows that a significant positive Coulomb failure stress change occurred along the SE segment of central Philippine Fault with insignificant coseismic slip and infrequent aftershocks, which suggests an increasing risk for future seismic hazard.
Reconfigurable multi-component nanostructures built from DNA origami voxels

In cells, proteins rapidly self-assemble into sophisticated nanomachines. Bio-inspired self-assembly approaches, such as DNA origami, have achieved complex 3D nanostructures and devices. However, current synthetic systems are limited by lack of structural diversity, low yields in hierarchical assembly, and challenges in reconfiguration. Here, we develop a modular system of DNA origami ‘voxels’ with programmable 3D connections. We demonstrate multifunctional pools of up to 12 unique voxels that can assemble into many shapes, prototyping 50 structures. Multi-step assembly pathways with sequential reduction in conformational freedom were then explored to increase yield. Voxels were first assembled into flexible chains and then folded into rigid structures, increasing yield 100-fold. Furthermore, programmable switching of local connections between flexible and rigid states achieved rapid and reversible reconfiguration of global structures. We envision that foldable chains of DNA origami voxels can be integrated with scalable assembly methods to achieve new levels of complexity in reconfigurable nanomaterials.
Epidemiological inference at the threshold of data availability: an influenza A(H1N2)v spillover event in the United Kingdom

Viruses which infect animals regularly spill over into the human population, but individual events may lead to anything from a single case to a novel pandemic. Rapidly gaining an understanding of a spillover event is critical to calibrating a public health response. We here propose a novel method, using likelihood free rejection sampling to evaluate the properties of an outbreak of swine-origin influenza A(H1N2)v in the United Kingdom, detected in November 2023. From the limited data available we generate historical estimates of the probability that the outbreak had died out in the days following the detection of the first case. Our method suggests that the outbreak could have been said to be over with 95% certainty between 19 and 29 days after the first case was detected, depending upon the probability of a case being detected. We further estimate the number of undetected cases conditional upon the outbreak still being live, the epidemiological parameter R0, and the date on which the spillover event itself occurred. Our method requires minimal data to be effective. While our calculations were performed after the event, the real-time application of our method has potential value for public health responses to cases of emerging viral infection.
Mechanisms underlying the loss of migratory behaviour in a long-lived bird

Human-induced environmental changes are shifting the migration patterns of birds worldwide. Species are adjusting migration timings, shortening and diversifying migratory routes, or even completely disrupting migration and transitioning towards residency. Whilst the ultimate causes driving changes in migratory patterns are well established, the underlying mechanisms by which migratory species adapt to environmental change remain unclear. Here, we studied the mechanisms driving the recent and rapid loss of migratory behaviour in Iberian white storks Ciconia ciconia, a long-lived and previously fully migratory species through the African-Eurasian flyway. We combined 25 years of census data, GPS-tracking data from 213 individuals (80 adults and 133 first-year juveniles) followed for multiple years, and whole-genome sequencing, to disentangle whether within- (phenotypic flexibility) or between- (developmental plasticity or microevolution, through selection) individual shifts in migratory behaviour over time can explain the observed population-level changes towards residency. Between 1995 and 2020, the proportion of individuals no longer migrating and remaining in Southern Europe year-round increased dramatically, from 18% to 68-83%. We demonstrate that this behavioural shift is likely explained by developmental plasticity. Within first-year birds, 98% crossed the Strait of Gibraltar towards their African wintering grounds, in Morocco or Sub-Saharan Africa. However, the majority shifted towards a non-migratory strategy as they aged - the proportion of migrants decreased to 67% and 33%, on their second and third year of life, respectively - suggesting that migratory behaviour is determined during ontogeny. Supporting these findings, only 19% of GPS-tracked adults migrated. Moreover, we did not find evidence of phenotypic flexibility, as adults were highly consistent in migratory behaviour over multiple years (only 3 individuals changed strategy between years, out of 113 yearly transitions), nor of selection acting on genetic variation, since genomes of migrants and residents are essentially undifferentiated. Our results suggest that through developmental plasticity, traits that are plastic during specific windows of development, become fixed during adulthood. Thus, inter-generational shifts in the frequency of migratory and non-migratory young individuals could drive population changes in migratory behaviour. This can provide a fast mechanism for long-lived migratory birds to respond to rapid human-driven environmental changes.
Nucleomorph phylogenomics suggests a deep and ancient origin of cryptophyte plastids within Rhodophyta

The evolutionary origin of red algae-derived complex plastids remains obscure. Cryptophyta, one of four eukaryotic lineages harboring these plastids, still contain nucleomorphs, highly reduced remnants of red algal nuclei. The genes present on nucleomorph genomes can be used for phylogenomic reconstruction in order to unravel the evolutionary origin of all red complex plastids and provide data independent from previously analyzed plastid-encoded datasets. Here, we leverage these genes in a first attempt at pinpointing the position of cryptophyte nucleomorphs within a comprehensive diversity of Rhodophyta, including new sequence representatives from seven deep-branching red algae. Our analyses place cryptophyte nucleomorphs as sister to the extremophilic subphylum Cyanidiophytina. This conflicts with published analyses based on plastidial genes that placed red complex plastids closer to the mesophilic Rhodophytina. Our results reject a nucleomorph origin within any known subgroup of Rhodophyta, instead suggesting a deep and possibly freshwater origin of complex red plastids.
Planning techniques and the action language golog (Planungstechniken und die Aktionssprache Golog)

The action language Golog allows specifying the behavior of autonomous systems with very flexible programs that leave certain aspects open to be resolved by the system. Such open aspects are often planning tasks, where the system needs to find a suitable course of actions to reach a given goal. The first part of this thesis aims to make highly efficient planning systems available to the Golog system as sub-solvers for such tasks. The main barrier is that both systems use different formalisms to represent their knowledge about the world and that the basic action theories underlying Golog are much more expressive than the PDDL fragment most commonly used by planning systems. We therefore identify a maximal fragment of basic action theories that can be translated to PDDL. An empirical evaluation shows that Golog systems can impressively benefit from the integration of a planning system. The second part of the thesis concentrates on the internals of the planning systems. The dominant approach in automated planning is heuristic search. For optimal planning, this usually means using the A∗ algorithm with some admissible heuristic. Well-known theoretical analyses suggest that such heuristic search algorithms can obtain better than exponential scaling behavior, provided that the heuristics are accurate enough. We show that for a number of common planning benchmark domains, including ones that admit optimal solution in polynomial time, general search algorithms such as A∗ must necessarily explore an exponential number of search nodes even under the optimistic assumption of almost perfect heuristic estimators, whose heuristic error is bounded by a small additive constant. We therefore argue that other enhancements are necessary to further improve the scaling behavior of optimal heuristic planners. These results do not carry over to satisficing planning, where the system does not need to prove the optimality of the solution. One possibility to better guide the search is to develop new, stronger estimators. Alternatively, we can use multiple existing heuristics concurrently to exploit their complementary strengths. We empirically examine several ways of using multiple heuristics in a satisficing best-first search algorithm to compare their performance in terms of coverage, plan quality and runtime.
Automated detection and quantification of single RNAs at cellular resolution in zebrafish embryos

Analysis of differential gene expression is crucial for the study of cell fate and behavior during embryonic development. However, automated methods for the sensitive detection and quantification of RNAs at cellular resolution in embryos are lacking. With the advent of single-molecule fluorescence in situ hybridization (smFISH), gene expression can be analyzed at single-molecule resolution. However, the limited availability of protocols for smFISH in embryos and the lack of efficient image analysis pipelines have hampered quantification at the (sub)cellular level in complex samples such as tissues and embryos. Here, we present a protocol for smFISH on zebrafish embryo sections in combination with an image analysis pipeline for automated transcript detection and cell segmentation. We use this strategy to quantify gene expression differences between different cell types and identify differences in subcellular transcript localization between genes. The combination of our smFISH protocol and custom-made, freely available, analysis pipeline will enable researchers to fully exploit the benefits of quantitative transcript analysis at cellular and subcellular resolution in tissues and embryos.
A new radiodontan oral cone with a unique combination of anatomical features from the early Cambrian Guanshan Lagerstätte, eastern Yunnan, South China

Abstract. The radiodontans, including anomalocaridids and their allies, are enigmatic stem-group euarthropods and are the most ancient apex giant predators known from the fossil record. Most studies on their feeding behaviors have emphasized their diverse and abundant raptorial frontal appendages, while the oral cone surrounding the mouth opening in these animals has attracted less attention. At present, three oral cone morphotypes are known, from Anomalocaris Whiteaves, 1892, Peytoia Walcott, 1911, and Hurdia Walcott, 1912, respectively. In this paper, we report on a novel form of radiodontan oral cone from the Guanshan Lagerstätte (Cambrian Series 2, Stage 4) in the Wulongqing Formation, eastern Yunnan, South China. This oral cone is unique in combining features seen in Peytoia/Hurdia and Anomalocaris. It possesses a Peytoia/Hurdia-type ‘tetraradial’ configuration comprising a 32-plate outer ring that consists of four perpendicularly arranged large plates and 28 small plates, in addition to furrowed folds and scale-like nodes on plate surfaces otherwise seen only in Anomalocaris. As an intermediate morphotype, the Guanshan oral cone improves our understanding of the occurrence and morphological disparity of radiodontan oral cones, illuminates future investigations on potentially variable radiodontan feeding mechanisms, and reveals possible evolutionary transformations of these peculiar feeding structures. The resolution of current radiodontan phylogeny would be potentially improved by new knowledge on other body parts apart from frontal appendages in future studies.
An introduction to the classification of the physiognomic landscape types: methodology and results of testing in the area of Kazimierz Landscape Park (Poland)

ABSTRACT The publication of the European Landscape Convention (2000) had a stimulating effect on the development of both new systems of landscape classification and new methods of their evaluation and mapping. As an example, a new classification of physiognomic landscape types was developed in Poland in 2014. The objectives of the paper are to (1) popularize, on the international scale, the classification of physiognomic landscape types in a new, improved version, (2) present the original method of physiognomic landscape types mapping with the use of the system of basic landscape units, and (3) present the results of testing of the method in the area of the Kazimierz Landscape Park, Poland. In the area of the Kazimierz Landscape Park, 491 basic landscape units were delimited, within which, on the basis of the leading traits of land relief and cover forms, the physiognomic landscape types were identified. Maps of this type can be important tools in implementing the recommendations of the European Landscape Convention. The total number of physiognomic landscape types identified within a specific area can be one of the key indicators of landscape diversity.
conDENSE: Conditional Density Estimation for Time Series Anomaly Detection

In recent years deep learning methods, based on reconstruction errors, have facilitated huge improvements in unsupervised anomaly detection. These methods make the limiting assumption that the greater the distance between an observation and a prediction the lower the likelihood of that observation. In this paper we propose conDENSE, a novel anomaly detection algorithm, which does not use reconstruction errors but rather uses conditional density estimation in masked autoregressive flows. By directly estimating the likelihood of data, our model moves beyond approximating expected behaviour with a single point estimate, as is the case in reconstruction error models. We show how conditioning on a dense representation of the current trajectory, extracted from a variational autoencoder with a gated recurrent unit (GRU VAE), produces a model that is suitable for periodic datasets, while also improving performance on non-periodic datasets. Experiments on 31 time-series, including real-world anomaly detection benchmark datasets and synthetically generated data, show that the model can outperform state-of-the-art deep learning methods.
A Novel Gesture-Based Language for Underwater Human–Robot Interaction

The underwater environment is characterized by hazardous conditions that make it difficult to manage and monitor even the simplest human operation. The introduction of a robot companion with the task of supporting and monitoring the divers during their activities and operations underwater can help to solve some of the problems that usually arise in this scenario. In this context, a proper communication between the diver and the robot is imperative for the success of the dive. However, the underwater environment poses a set of technical challenges which are not readily surmountable thus limiting the spectrum from which possibilities can be chosen. This paper presents the design and development of a gesture-based communication language which has been employed for the entire duration of the European project CADDY (Cognitive Autonomous Diving Buddy). This language, the Caddian, was built upon consolidated and standardized underwater gestures that are commonly used in recreational and professional diving. Its use and integration during field tests with a remotely operated underwater vehicle (ROV) is also shown.
From intracrystalline distortion to plate motion: Unifying structural, kinematic, and textural analysis in heterogeneous shear zones through crystallographic orientation-dispersion methods

We present results from integrated field, microstructural, and textural analysis of the Burlington mylonite zone (BMZ) in eastern Massachusetts (northeastern USA) to establish a unified microkinematic framework for vorticity analysis in heterogeneous shear zones. Specifically, we develop a methodology for the structural analysis of polyphase lithologies that defines the vorticity-normal surface based on lattice-scale rotation axes calculated from electron backscatter diffraction data using orientation statistics. In doing so, we objectively identify a suitable reference frame for rigid grain methods of vorticity analysis that can be used in concert with field and microstructural methods of strain analysis and textural studies to constrain fieldto platescale kinematics and deformation geometries without assumptions that may bias tectonic interpretations, such as relationships between kinematic axes and fabric-forming elements or the nature of the deforming zone (e.g., monoclinic versus triclinic shear zones). Rocks within the BMZ comprise a heterogeneous mix of quartzo feldspathic ± hornblende-bearing mylonitic gneisses and quartzites. Vorticity axes inferred from lattice rotations lie within the plane of mylonitic foliation perpendicular to lineation—a pattern consistent with monoclinic deformation geometries involving simple shear and/or wrench-dominated transpression. The mean kinematic vorticity number (Wm) is calculated using rigid grain net analysis and ranges from 0.25 to 0.55, indicating dominant general shear. Using the calculated vorticity values and the dominant geographic fabric orientation, we constrain the angle of paleotectonic convergence between the Nashoba and Avalon terranes to ~56°–75° with the convergence vector trending ~142°–160° and plunging ~3°–10°. Application of the quartz recrystallized grain size piezometer suggests differential stresses in the BMZ mylonites ranging from ~44 to 92 MPa; patterns of quartz crystallographic preferred orientation are consistent with deformation at greenschistto amphibolite-facies conditions. We conclude that crustal strain localization in the BMZ involved a combination of pure and simple shear in a sinistral reverse transpressional shear zone that was active at or near the brittle-ductile transition under relatively high stress conditions. Moreover, we demonstrate the utility of combined crystallographic and rigid grain methods of vorticity analy sis for deducing deformation geometries, kinematics, and tectonic histories in polyphase shear zones.