Miracle-dz/UniFAR-FTUs huggingface dataset:
Myospreader improves gene editing in skeletal muscle by myonuclear propagation

Successful CRISPR/Cas9-based gene editing in skeletal muscle is dependent on efficient propagation of Cas9 to all myonuclei in the myofiber. However, nuclear-targeted gene therapy cargos are strongly restricted to their myonuclear domain of origin. By screening nuclear localization signals and nuclear export signals, we identify “Myospreader”, a combination of short peptide sequences that promotes myonuclear propagation. Appending Myospreader to Cas9 enhances protein stability and myonuclear propagation in myoblasts and myofibers. AAV-delivered Myospreader dCas9 better inhibits transcription of toxic RNA in a myotonic dystrophy mouse model. Furthermore, Myospreader Cas9 achieves higher rates of gene editing in CRISPR reporter and Duchenne muscular dystrophy mouse models. Myospreader reveals design principles relevant to all nuclear-targeted gene therapies and highlights the importance of the spatial dimension in therapeutic development.
Hypothesis Generation from Literature for Advancing Biological Mechanism Research: A Perspective

The number of biomedical literature being published has experienced significant growth, with a sharp increase in recent years. However, keeping pace with new knowledge in this complex and specialized field can be challenging. Hypothesis Generation is a literature-based discovery approach that utilizes existing literature to automatically generate implicit biomedical associations and provide reasonable predictions for future research. Despite its potential, current hypothesis generation methods face challenges when applied to research on biological mechanisms. In this perspective paper, we provide an overview of existing hypothesis generation approaches, and examine their limitations in the context of biological mechanism research. We propose practical solutions to overcome these challenges and highlight the potential of hypothesis generation in advancing our understanding of biological mechanisms.
On Parallel Repetition of PCPs

Parallel repetition refers to a set of valuable techniques used to reduce soundness error of probabilistic proofs while saving on certain efficiency measures. Parallel repetition has been studied for interactive proofs (IPs) and multi-prover interactive proofs (MIPs). In this paper we initiate the study of parallel repetition for probabilistically checkable proofs (PCPs). We show that, perhaps surprisingly, parallel repetition of a PCP can increase soundness error , in fact bringing the soundness error to one as the number of repetitions tends to infinity. This “failure” of parallel repetition is common: we find that it occurs for a wide class of natural PCPs for NP -complete languages. We explain this unexpected phenomenon by providing a characterization result: the parallel repetition of a PCP brings the soundness error to zero if and only if a certain “MIP projection” of the PCP has soundness error strictly less than one. We show that our characterization is tight via a suitable example. Moreover, for those cases where parallel repetition of a PCP does bring the soundness error to zero, the aforementioned connection to MIPs offers preliminary results on the rate of decay of the soundness error. Finally, we propose a simple variant of parallel repetition, called consistent parallel repetition (CPR), which has the same randomness complexity and query complexity as the plain variant of parallel repetition. We show that CPR brings the soundness error to zero for every PCP (with non-trivial soundness error). In fact, we show that CPR decreases the soundness error at an exponential rate in the repetition parameter.
Influence of Interplanetary magnetic field on Equatorial Electrojet-Observations from South India

The occurrence of equatorial Counter electrojet (CEJ) and Prompt penetration effects are studied at a newly established equatorial remote station, Vencode (VEN), Kanyakumari Dt, at the southern tip of India. The three month’s dataset (Nov, Dec-2010 and Jan-2011) of VEN along with permanent Hyderabad (HYB) Magnetic Observatory are used in the present study to assess the relationship between the CEJ and prompt penetration events with interplanetary parameters (IPP): Electric field (Ey) / southward component of magnetic field (Bz) and modeled penetration fields. The influence of short-term (~30-60 minutes) and long-term (~02-04 hours) fluctuations of the equatorial ionosphere on the horizontal (H) component of earth’s magnetic field at VEN are explained in terms of change in orientation of IPP. We found a strong correlation between the CEJ events with Bz orientation (north-south-north). Moderate correlation is found between the high frequency components of the derived Equatorial electric field (EEF) with Real time prompt penetration electric field model (PPEFM). The day-to-day variability in Equatorial electrojet (EEJ) strength associated with CEJ events highlight the role of equatorial ionosphere in the present study. Our results from VEN confirm the positive relation of about 70% between CEJ events with Bz polarity.
Towards an Extensible Framework for Understanding Spatial Narratives

Spatial narratives help us to organize experiences and give them meaning. Previous approaches to understanding geographies in textual sources focus on geoparsing to automatically identify place names and allocate them to coordinates. Those are highly quantitative, and are limited to named places with coordinates, and have little concept of time. Narratives of journeys indicate that human experiences of geography are often subjective and more suited to qualitative representation. Geography is not limited to named places but incorporates the vague, imprecise, and ambiguous, e.g "the camp", or "the hills in the distance", and relative locations such as "near to", "on the left", "north of" or "a few hours' journey from". Places are organized worlds of meaning, characterized by experience, emotion, and memory as well as by geography. In this paper, we discuss our approach to gaining more insight from textual data beyond the toponyms and introduce an extensible framework for extracting, analyzing, and visualizing spatial elements that define the 'locale' as well as the 'sense of place' referenced in text using two test corpora --the Corpus of the Lake District Writing and Holocaust Survivors' Testimonies.
The Plat Sjambok Anorthosite and its tonalitic country rocks: Mesoproterozoic pre-tectonic intrusions in the Kaaien Terrane, Namaqua–Natal Province, southern Africa

The Plat Sjambok Anorthosite crops out near Prieska Copper Mines in the Namaqua–Natal Province of southern Africa. It is a massif-type anorthosite, previously regarded as a late-tectonic intrusion and part of the ca. 1100 Ma bimodal Keimoes Suite. Our new ion probe U–Pb zircon data show that the Plat Sjambok massif intruded at 1259 ± 5 Ma, before the 1220 Ma Namaqua collision events and is thus approximately 150 million years older than the Keimoes Suite. Despite the proximity to Prieska Mines, the anorthosite is located in the Kaaien Terrane close to the Brakbos Fault, which is the boundary with the Areachap Terrane in which Prieska Mines is situated. We dated the Nelspoortjie Tonalite, the main country rock of the Plat Sjambok Anorthosite, by laser ablation ICPMS at 1273 ± 13 Ma. Both intrusions thus originated concurrently with the 1286–1241 Ma volcanic rocks of the Areachap Group, which developed in a subduction-related arc setting, prior to its collision with the Kaaien Terrane and Kaapvaal Craton. Metamorphic zircon rims in the Plat Sjambok Anorthosite give an age of 1122 ± 7 Ma, a time that corresponds to a quiet period in the Areachap Terrane. We propose a tectonic model in which formation of the Nelspoortjie Tonalite and Plat Sjambok Anorthosite was driven by intrusions from the mantle into a back-arc related tensional environment within the Kaaien Terrane, possibly situated above an Archaean crustal tongue. This led to heating in a thickened crustal setting in which the tonalite originated as a partial melt of amphibolite. The anorthosite then formed as a mixture of mantle-derived gabbro and Archaean crustal rocks, which explains the 2100–2600 Ma zircon–Hf crustal residence ages and the Sm–Nd trend towards an old crustal source. The anorthosite and its country rocks were only juxtaposed with the Prieska Copper Mining District by late-tectonic uplift and transpressional movements on the Brakbos Fault towards the end of the Namaqua tectogenesis.
Addressing climate change and migration in Asia and the Pacific

Addressing climate change and migration in Asia and the Pacific. Asian Development Bank, March 2012, 94 p. http://beta.adb. org/sites/default/files/pub/2012/addressing-climate-change-migration.pdf Description (source and copyright © ADB) : Climate change will increase the frequency of extreme weather events, making more geographic places inhospitable to human habitation and secure livelihoods. This report presents a detailed picture of the potential impacts of climate change on migration in As.
Integrating Sparklis and ViziQuer for Enhanced SPARQL Querying and Visualization

This paper introduces a multimodal SPARQL query system that combines the capabilities of Sparklis and ViziQuer, two powerful tools for SPARQL query building and visualization. Sparklis offers a faceted user interface for constructing SPARQL queries, while ViziQuer provides a rich visual interface for constructing and visualizing SPARQL queries. By integrating the two applications, the system facilitates the automatic visualization of SPARQL queries constructed in Sparklis within the ViziQuer visual environment.
Developmental Trajectory of Cerebral Lateralization

The pattern of lateralization in the developing brain partly reveals the maturation of the brain and provides a reliable reference for researchers to assess whether the brain is developing normally. Functions associated with distinct patterns of brain lateralization related to functions such as language and visuospatial ability have attracted the attention of researchers for a long time, while the trajectories of developmental lateralization patterns in various brain regions across the brain is still poorly understood. In this study, we divided the resting-state functional magnetic resonance imaging (rs-fMRI) data of subjects aged 8-21 years from Lifespan Human Connectome Project Development (HCP-D) into different groups according to their age and used the support vector machine (SVM) to investigate the distinguishability of the lateralization patterns in different age groups by classification accuracy. We found that the changing rate of lateralization patterns slows down with age and the onset age of maturation of lateralization patterns varies across brain regions.
Dynamic Analysis of Emotional Causal Brain Network Based on Directed Transfer Function: 1

Emotions are composed of cognitive and logical responses in various situations, which are derived from changes in physiology, cognition, and behavior. Accurate and automatic emotion recognition can promote the development of man-machine interface. Objective measurement and prediction of emotions have made great progress. We need to study models to predict emotional states more accurately. EEG signals provide a non-invasive and non-radioactive solution for emotions. In the research of complex network, emotion research based on causal network is still in the development stage, and there are few researches on emotion recognition induced by directional information transfer. This study involves the causal brain network constructed by directed transfer function. The network connection modes and complex networks characteristics under different emotional states are analyzed. CCS CONCEPTS • Hardware∼Emerging technologies∼Biology-related information processing∼Neural systems•Mathematics of computing∼Discrete mathematics∼Graph theory•Hardware∼Emerging technologies∼Biology-related information processing
Coherence Factor Based Beamformer with Plane Wave Compounding

In recent years, plane wave ultrasound has received significant research interest due to its high frame rate capabilities. The image quality of plane wave ultrasound imaging is largely influenced by beamformer performance. Coherent plane wave compounding has been developed as a method to enhance image quality through the coherent summation of data from various transmission angles. Additionally, coherence factor-based beamformers have been developed to improve image contrast. In this study, we investigated the impact of compounding on three types of coherence-based beamformers using ultrasound simulations and phantom experiments. The results demonstrated that coherence factor beamformers, generalized coherence beamformers, and phase coherence beamformers achieve higher image quality in terms of lateral resolution, contrast ratio and generalized contrast to noise ratio as the number of compounding angles increases. These results suggest that plane wave compounding can enhance the image quality of coherence-based beamformers.
Algebraic properties of the maps χn

The Boolean map χ n : F n 2 → F n 2 , x (cid:55)→ y deﬁned by y i = x i + ( x i +1 + 1) x i +2 (where i ∈ Z /n Z ) is used in various permutations that are part of cryptographic schemes, e.g., Keccak -f (the SHA-3-permutation), ASCON (the winner of the NIST Lightweight competition), Xoodoo, Rasta and Subterranean (2.0). In this paper, we study various algebraic properties of this map. We consider χ n (through vectorial isomorphism) as a univariate polynomial. We show that it is a power function if and only if n = 1 , 3. We furthermore compute bounds on the sparsity and degree of these univariate polynomials, and the number of diﬀer-ent univariate representations. Secondly, we compute the number of monomials of given degree in the inverse of χ n (if it exists). This number coincides with binomial coeﬃcients. Lastly, we consider χ n as a polynomial map, to study whether the same rule ( y i = x i + ( x i +1 + 1) x i +2 ) gives a bijection on ﬁeld extensions of F 2 . We show that this is not the case for extensions whose degree is divisible by two or three. Based on these results, we conjecture that this rule does not give a bijection on any extension ﬁeld of F 2 .
Numerical Analysis Of Infiltration In A Drained Beach

The beach drainage system (BDS) is a ‘soft’ engineering solution for coastal protection and management. It artificially increases beach permeability by inducing the groundwater table lowering and, consequently, it favours the infiltration of sea water inside the beach. The new hydrodynamic condition would produce a reduction of the offshore sediment transport and the settlement of the suspended load. The present work focuses on a numerical simulation of infiltration processes in drained conditions by using the HYDRUS-2D code. The groundwater flow through a partially saturated porous media is described by using the well-known Richard’s equation. Numerical results are then compared with experimental ones obtained during an intensive experimental program performed at the Grosser Wellen–Kanal in Hannover on a BDS prototype. Moreover, different beach permeabilities (ranging from silt to coarse sand) and different drain altimetric positions are numerically simulated. These analyses allow to draw some first considerations about BDS design criteria. In particular, a ‘limit drain depth’, strictly related to beach permeability, is defined as the maximum depth that produces the maximum water table lowering and, as a consequence, the best system efficacy in drying the porous medium.
Hyperbolic Chamfer Distance for Point Cloud Completion

Chamfer distance (CD) is a standard metric to measure the shape dissimilarity between point clouds in point cloud completion, as well as a loss function for (deep) learning. However, it is well known that CD is vulnerable to outliers, leading to the drift towards suboptimal models. In contrast to the literature where most works address such issues in Euclidean space, we propose an extremely simple yet powerful metric for point cloud completion, namely Hyperbolic Chamfer Distance (HyperCD), that computes CD in hyperbolic space. In backpropagation, HyperCD consistently assigns higher weights to the matched point pairs with smaller Euclidean distances. In this way, good point matches are likely to be preserved while bad matches can be updated gradually, leading to better completion results. We demonstrate state-of-the-art performance on the benchmark datasets, i.e. PCN, ShapeNet-55, and ShapeNet34, and show from visualization that HyperCD can significantly improve the surface smoothness. Code is available at: https://github.com/Zhang-VISLab.
Evolución de las precipitaciones en la cuenca del Ebro: caracterización espacial y análisis de tendencias

In this work a spatial-time characterisation of the rainfall evolution in the Ebro river basin is carried out. A database for a network of 29 rainfall stations throughout the basin with monthly rainfall information for the period 1916-2000 has been built. The annual and seasonal series were subjected to a homogenisation process. A cluster analysis complemented with a trend analysis of the annual rainfall for each station allows us to classify the basin in eight different areas. Finally, a time series describing rainfall evolution in each defined region has been built and analysed for its trend behaviour.
Phosphorus Chemistry at the Roots of Bioenergetics: Ligand Permutation as the Molecular Basis of the Mechanism of ATP Synthesis/Hydrolysis by FOF1-ATP Synthase

The integration of phosphorus chemistry with the mechanism of ATP synthesis/hydrolysis requires dynamical information during ATP turnover and catalysis. Oxygen exchange reactions occurring at β-catalytic sites of the FOF1-ATP synthase/F1-ATPase imprint a unique record of molecular events during the catalytic cycle of ATP synthesis/hydrolysis. They have been shown to provide valuable time-resolved information on enzyme catalysis during ATP synthesis and ATP hydrolysis. The present work conducts new experiments on oxygen exchange catalyzed by submitochondrial particles designed to (i) measure the relative rates of Pi–ATP, Pi–HOH, and ATP–HOH isotope exchanges; (ii) probe the effect of ADP removal on the extent of inhibition of the exchanges, and (iii) test their uncoupler sensitivity/resistance. The objectives have been realized based on new experiments on submitochondrial particles, which show that both the Pi–HOH and ATP–HOH exchanges occur at a considerably higher rate relative to the Pi–ATP exchange, an observation that cannot be explained by previous mechanisms. A unifying explanation of the kinetic data that rationalizes these observations is given. The experimental results in (ii) show that ADP removal does not inhibit the intermediate Pi–HOH exchange when ATP and submitochondrial particles are incubated, and that the nucleotide requirement of the intermediate Pi–HOH exchange is adequately met by ATP, but not by ADP. These results contradicts the central postulate in Boyer’s binding change mechanism of reversible catalysis at a F1 catalytic site with Keq~1 that predicts an absolute requirement of ADP for the occurrence of the Pi–HOH exchange. The prominent intermediate Pi–HOH exchange occurring under hydrolytic conditions is shown to be best explained by Nath’s torsional mechanism of energy transduction and ATP synthesis/hydrolysis, which postulates an essentially irreversible cleavage of ATP by mitochondria/particles, independent from a reversible formation of ATP from ADP and Pi. The explanation within the torsional mechanism is also shown to rationalize the relative insensitivity of the intermediate Pi–HOH exchange to uncouplers observed in the experiments in (iii) compared to the Pi–ATP and ATP–HOH exchanges. This is shown to lead to new concepts and perspectives based on ligand displacement/substitution and ligand permutation for the elucidation of the oxygen exchange reactions within the framework of fundamental phosphorus chemistry. Fast mechanisms that realize the rotation/twist, tilt, permutation and switch of ligands, as well as inversion at the γ-phosphorus synchronously and simultaneously and in a concerted manner, have been proposed, and their stereochemical consequences have been analyzed. These considerations take us beyond the binding change mechanism of ATP synthesis/hydrolysis in bioenergetics.
Regulation of hippocampal mossy fiber-CA3 synapse function by a Bcl11b/C1ql2/Nrxn3(25b+) pathway

The transcription factor Bcl11b has been linked to neurodevelopmental and neuropsychiatric disorders associated with synaptic dysfunction. Bcl11b is highly expressed in dentate gyrus granule neurons and is required for the structural and functional integrity of mossy fiber-CA3 synapses. The underlying molecular mechanisms, however, remained unclear. We show that the synaptic organizer molecule C1ql2 is a direct functional target of Bcl11b that regulates synaptic vesicle recruitment and long-term potentiation at mossy fiber-CA3 synapses in vivo and in vitro. Furthermore, we demonstrate C1ql2 to exert its functions through direct interaction with a specific splice variant of neurexin-3, Nrxn3(25b+). Interruption of C1ql2-Nrxn3(25b+) interaction by expression of a non-binding C1ql2 mutant or by deletion of Nrxn3 in the dentate gyrus granule neurons recapitulates major parts of the Bcl11b as well as C1ql2 mutant phenotype. Together, this study identifies a novel C1ql2-Nrxn3(25b+)-dependent signaling pathway through which Bcl11b controls mossy fiber-CA3 synapse function. Thus, our findings contribute to the mechanistic understanding of neurodevelopmental disorders accompanied by synaptic dysfunction.
Labeling Neural Representations with Inverse Recognition

Deep Neural Networks (DNNs) demonstrate remarkable capabilities in learning complex hierarchical data representations, but the nature of these representations remains largely unknown. Existing global explainability methods, such as Network Dissection, face limitations such as reliance on segmentation masks, lack of statistical significance testing, and high computational demands. We propose Inverse Recognition (INVERT), a scalable approach for connecting learned representations with human-understandable concepts by leveraging their capacity to discriminate between these concepts. In contrast to prior work, INVERT is capable of handling diverse types of neurons, exhibits less computational complexity, and does not rely on the availability of segmentation masks. Moreover, INVERT provides an interpretable metric assessing the alignment between the representation and its corresponding explanation and delivering a measure of statistical significance. We demonstrate the applicability of INVERT in various scenarios, including the identification of representations affected by spurious correlations, and the interpretation of the hierarchical structure of decision-making within the models.