Miracle-dz/UniFAR-FTUs huggingface dataset:
Chromatin priming elements direct tissue-specific gene activity prior to hematopoietic specification

Tissue-specific gene regulation during development involves the interplay between transcription factors and epigenetic regulators binding to enhancer and promoter elements. The pattern of active enhancers defines the cellular differentiation state. However, developmental gene activation involves a previous step called chromatin priming which is not fully understood. We recently developed a genome-wide functional assay that allowed us to functionally identify enhancer elements integrated in chromatin regulating each of five stages spanning the in vitro differentiation of embryonic stem cells to blood. We also measured global chromatin accessibility, histone modifications and transcription factor binding. The integration of these data identified and characterised cis-regulatory elements which become activated prior to the onset of gene expression, some of which are primed in a signalling-dependent fashion. Deletion of such a priming element leads to a delay in the upregulation of its associated gene in development. Our work uncovers the details of a complex network of regulatory interactions with the dynamics of early chromatin opening being at the heart of dynamic tissue-specific gene expression control. Summary blurb In this manuscript, we exploited a new dataset of functionally characterised enhancer elements active at five stages of differentiation from mouse embryonic stem cells to blood to determine the developmental stages at which these elements are being activated. We show that many enhancer elements are activated at the level of chromatin prior to the activation of their associated genes (priming), which can be associated with signalling events. Elimination of priming elements within a gene locus leads to a delay in cellular development.
Comparing peptide identifications by FAIMS versus quadrupole gas-phase fractionation

High-field asymmetric waveform ion mobility spectrometry (FAIMS) coupled to liquid chromatography-mass spectrometry (LC-MS) has been shown to increase peptide and protein detections compared to LC-MS/MS alone. However, FAIMS has not been compared to other methods of gas-phase fractionation, such as quadrupole gas-phase fractionation, which could increase our understanding of the mechanisms of improvement. The goal of this work was to assess whether FAIMS improves peptide identifications because 1) gas-phase fractionation enables the analysis of less abundant signals by excluding more abundant precursors from filling the ion trap, 2) the use of FAIMS reduces co-isolation of peptides during the MS/MS process resulting in a reduction of chimeric spectra, or 3) a combination of both. To investigate these hypotheses, pooled human brain tissue samples were measured in triplicate using FAIMS gas-phase fractionation, quadrupole gas-phase fractionation, or no gas-phase fractionation on two Thermo Eclipse Tribrid Mass Spectrometers. On both instruments, our data confirmed prior observations that FAIMS increased the number of peptides identified. We further demonstrated that the main benefit of FAIMS is due to the reduced co-isolation of persistent peptide precursor ions, which results in a decrease in chimeric spectra.
Myostatin is a major endocrine driver of follicle-stimulating hormone synthesis

Myostatin is a paracrine myokine that regulates muscle mass in a variety of species, including humans. Here, we report a functional role for myostatin as an endocrine hormone directly promoting pituitary follicle-stimulating hormone (FSH) synthesis and thereby ovarian function. Previously, this FSH-stimulating role was attributed to other members of the transforming growth factor β family, the activins. The results both challenge activin’s eponymous role in FSH synthesis and establish an endocrine axis between skeletal muscle and the pituitary gland. The data also suggest that efforts to antagonize myostatin to treat muscle wasting disorders may have unintended consequences on fertility. One-Sentence Summary Hormone synthesis and reproduction depend on crosstalk between skeletal muscle and the pituitary gland.
High-resolution imaging of presynaptic ER networks in Atlastin mutants

The endoplasmic reticulum (ER) is a continuous organelle that extends to the periphery of neurons and regulates many neuronal functions including neurite outgrowth, neurotransmission, and synaptic plasticity. Mutations in proteins that control ER shape are linked to the neurodegenerative disorder Hereditary Spastic Paraplegia (HSP). However, the ultrastructure and dynamics of the neuronal ER have been under-investigated, particularly at presynaptic terminals. Here we developed new super-resolution and live imaging methods in D. melanogaster larval motor neurons to investigate ER structure at presynaptic terminals from wild-type animals, and in null mutants of the HSP gene Atlastin. Previous studies indicated diffuse localization of an ER lumen marker at Atlastin mutant presynaptic terminals, which was attributed to ER fragmentation. By contrast, we found using an ER membrane marker that the ER in Atlastin mutants formed robust networks. Further, our high-resolution imaging results suggest that overexpression of luminal ER proteins in Atlastin mutants causes their progressive displacement to the cytosol at synapses, perhaps due to proteostatic stress and/or changes in ER membrane integrity. Remarkably, these luminal ER proteins remain correctly localized in cell bodies, axons, and other cell types such as body wall muscles, suggesting that ER tubules at synapses have unique structural and functional characteristics. This displacement phenotype has not been reported in numerous studies of Atlastin in non-neuronal cells, emphasizing the importance of conducting experiments in neurons when investigating the mechanisms leading to upper motor neuron dysfunction in HSP.
Comprehensive analysis of A-type lamin tail region for repairing the nuclear lamina

The nuclear lamina (NL) lines the inner nuclear membrane (INM) of the nuclear envelope (NE) to maintain nuclear structure in metazoan cells. The major NL components, the nuclear lamins contribute to the protection against NE rupture induced by mechanical stress. Lamin C (LC) but not lamin A (LA) is rapidly diffused from the nucleoplasm to sites of NE rupture induced by laser microirradiation in immortalized mouse embryonic fibroblasts (MEFs). However, the molecular mechanism for differentiating LA from LC with respect to the localization/accumulation at the rupture sites still remains unknown. In this study, we reveal by immunofluorescence, live-cell imaging and fluorescence correlation spectroscopy (FCS) that the CaaX motif, the second cleavage site and the LA-characteristic segment (LACS) regulate the localization of LA to the rupture sites. Our data suggest that Hutchinson–Gilford Progeria syndrome (HGPS) might exhibit the delay in localizing LA to the rupture sites through this mechanism.
Molecular evolution of male reproduction across species with highly divergent sperm morphology in diverse murine rodents

Sperm competition can drive rapid evolution of male reproductive traits, but it remains unclear how variation in sperm competition intensity shapes phenotypic and molecular diversity across clades. Old World mice and rats (subfamily Murinae) comprise a rapid radiation and exhibit incredible diversity in sperm morphology and production. We combined phenotype and sequence data to model the evolution of reproductive traits and genes across 78 murine species. We identified several shifts towards smaller relative testes mass, a trait reflective of reduced sperm competition. Several sperm traits were associated with relative testes mass, suggesting that mating system evolution likely selects for convergent traits related to sperm competitive ability. Molecular evolutionary rates of spermatogenesis proteins also correlated with relative testes mass, but in an unexpected direction. We predicted that sperm competition would result in rapid divergence among species with large relative testes mass, but instead found that many spermatogenesis genes evolve more rapidly in species with smaller relative testes mass due to relaxed purifying selection. While some reproductive genes evolved under positive selection, relaxed selection played a greater role underlying rapid evolution in small testes species. Our work demonstrates that sexual selection can impose strong purifying selection shaping the evolution of male reproduction.
Flexible and abstract neural representations of abstract structural knowledge

Humans’ ability for generalisation is outstanding. Our previous research has demonstrated that humans can generalise over tasks that share the same statistical rules (structural form) that govern the relational structure between states within a task. Studies suggest that the brain represents non-spatial tasks’ structure similarly to the representation of spatial tasks and have highlighted the entorhinal cortex (EC) as a possible neural substrate for this structural generalisation. EC spatial representation generalises across environment’s size and shape. However, in non-spatial domains this was only shown across tasks with the exact same underlying graphs. Here we show with fMRI that EC representations generalise across complex non-spatial tasks that share a hexagonal grid structural form but differ in their size and sensory stimuli, i.e. their only shared feature is the rule governing their statistical structure.
Improved Chemical Text Mining of Patents with Infinite Dictionaries and Automatic Spelling Correction

The text mining of patents of pharmaceutical interest poses a number of unique challenges not encountered in other fields of text mining. Unlike fields, such as bioinformatics, where the number of terms of interest is enumerable and essentially static, systematic chemical nomenclature can describe an infinite number of molecules. Hence, the dictionary- and ontology-based techniques that are commonly used for gene names, diseases, species, etc., have limited utility when searching for novel therapeutic compounds in patents. Additionally, the length and the composition of IUPAC-like names make them more susceptible to typographic problems: OCR failures, human spelling errors, and hyphenation and line breaking issues. This work describes a novel technique, called CaffeineFix, designed to efficiently identify chemical names in free text, even in the presence of typographical errors. Corrected chemical names are generated as input for name-to-structure software. This forms a preprocessing pass, independent of the name-to-structure software used, and is shown to greatly improve the results of chemical text mining in our study.
Online Threats Detection in Hausa Language

One of the widely used technological inventions is the Internet which gives rise to online social media platforms such as Twitter and Facebook to proliferate. These platforms are quite instrumental as a means for socialisation and information exchange among diverse users. The use of online social media to spread information can be both beneficial and harmful. From the positive side, the information can be useful in the areas of security, economy and climate change. Motivated by the growing number of online users and widespread availability of contents with the potential of causing harm, this study examines how online contents with threatening themes are being expressed in Hausa language. We collected the first collection of Hausa datasets with threatening contents from Twitter and develop a classification system to help in curtailing security risks by informing decisions on tackling insecurity and related challenges. We employ and train four machine learning algorithms: Random Forest (RF), XGBoost, Decision Tree (DT) and Naive Bayes, to classify the annotated dataset. The result of the classifications shows an accuracy score of 72% for XGBoost, 71% for RF, 67% for DT and Naive Bayes having the lowest of 57%.
Nalaquq ("it is found"): a knowledge co-production framework for environmental sensing and communication in Indigenous arctic communities

In 2007, the Yup’ik village of Quinhagak contacted archaeologists after locals found precontact artifacts on a nearby beach. This collaboration led to the subsequent excavation of Nunalleq, an important ancestral site threatened by climate change. Since then, an international research team has partnered with Yup’ik leadership in Quinhagak to address the larger impact of climate change. In turn, this article introduces Nalaquq—our framework for combining custom sensor networks with traditional knowledge to study ellavut (trans. “Our land and weather”). Doing so provides a guide for communication scholars interested in working alongside Indigenous circumpolar communities to visualize and communicate climate science.
Towards Human-Centered Explainable AI: A Survey of User Studies for Model Explanations

Explainable AI (XAI) is widely viewed as a sine qua non for ever-expanding AI research. A better understanding of the needs of XAI users, as well as human-centered evaluations of explainable models are both a necessity and a challenge. In this paper, we explore how human-computer interaction (HCI) and AI researchers conduct user studies in XAI applications based on a systematic literature review. After identifying and thoroughly analyzing 97 core papers with human-based XAI evaluations over the past five years, we categorize them along the measured characteristics of explanatory methods, namely trust, understanding, usability, and human-AI collaboration performance. Our research shows that XAI is spreading more rapidly in certain application domains, such as recommender systems than in others, but that user evaluations are still rather sparse and incorporate hardly any insights from cognitive or social sciences. Based on a comprehensive discussion of best practices, i.e., common models, design choices, and measures in user studies, we propose practical guidelines on designing and conducting user studies for XAI researchers and practitioners. Lastly, this survey also highlights several open research directions, particularly linking psychological science and human-centered XAI.
A Topic Lifecycle Trend Prediction Algorithm on Facebook

Recently, social media has been widely used for people to discuss public opinions and share their views. Internet public opinions have attracted a lot of attention from the government, enterprises and the general public. How to properly analyze, utilize and guide these online opinions is an extremely important issue that the world is currently faced with, and the prediction of topic lifecycle trends is the key to solving this problem. This paper proposes a topic lifecycle trend prediction algorithm based on Facebook data. The algorithm takes into account the similarity between new topics and historical topics in terms of lifecycle curves and the similarity in terms of text content, finds a curve that can best represent the future lifecycle trend of new topics, and then effectively predicts the trend of new topics. It is helpful and meaningful to use this method in the early warnings and predictions of online public opinions and hot topics.
Aerodynamics of wind erosion.

HE dynamic action of fluids on the land surface takes many forms. While all of them are in somc mcasure geological processes, they may assume economic importancc through, or to, the activiticr of man. The problems may be the accelerated downslope movement of soil by surface runoff or rainfall impact on cultivated lands. It mny consist of the bcating of wind-formed wavcs eroding the materials along a highly dcvclopcd shore line. Again, it may be the distribution of drifting snow affccting thc snowmelt from mountainous areas or the distribution of moisturc in rairic rcgions. It may bc the rolling of sediment along the be& of streams and rivers. Finally. exposed soils may be moved bodily by the action of the wind. Basically, a11 of these phenomena prcscnt related rcsearch problems: namely, (a ) the detcrminatnoo of thc incidcncc and nature of a fluid force near the interfaces of fluid and solid media, and (b) the determination of the propertics of thc matcrial in question to resist thc fluid forcc. Mcthods of control must stri& l a ) to modifv the forcc on the material susccptiblc to movcmcnt or transpo;tation by thc fluid or (b) to mbdify the material either to increase or to decrease its detachability. As carly as 1711. Frcc(J)* published a bibliography of aeolian geography. It contains 2,475 references having to do with phcnomcna rclatcd to wind and soil formation, transportation, detachment, ctc. It is interesting to note that approxi. mately 75 per ccnt of thc articles listed arc of forcign origin. Again, in 1741. Malina(l1) published a rcvicw paper. cntitlcd "Rcccnt Dcvclopmcnt in the Dynamics of Wind Erosion. " This pa er contains 19 references and is an exccllcnt summary of deve P ooments to that date.
SWEETNESS AND LIGHT: CHEMICAL EVIDENCE OF BEESWAX AND TALLOW CANDLES AT FOUNTAINS ABBEY, NORTH YORKSHIRE

We report here on the composition of residues from a collection of metal candleholders from the 12th-century Cistercian Abbey of Fountains, one of Britain’s best-preserved monastic sites. Fountains Abbey and Studley Royal Estate, located in the valley of the River Skell near Ripon, is a World Heritage Site. The extensive collection of artefacts has been amassed, including all the objects discussed here, mainly from antiquarian excavations.87 Recent work has examined the collection of lead artefacts from Fountains Abbey.88 These investigations noted five artefacts, some thought to be candleholders, which contained small amounts of a white, flaky deposit presumed to be organic in origin. The discovery of these residues prompted investigation into other putative candleholders in the Fountains Abbey collection. Subsequently, three iron ‘cupped-stick’ candleholders were identified, typical of the late 14th century,89 containing similar deposits. The lead candleholders lack distinctive features, making typological dating problematic (Figs. 9–10; Tab. 1). However, the austere design probably dates from the 14th century or later.90 These artefact-dates do not necessarily date the residues. The latter could derive from post-Dissolution re-use of monastic objects, but this is unlikely to account for all the examples noted here. A total of nine samples from one iron and four lead candleholders were taken and prepared for analysis. The aim of the analytical programme was to identify the deposits in order to learn more about candle production and use at Fountains Abbey.
Morphology and microtextures of tephra particles

The purpose of this PhD thesis is to give insights into the dynamics of highly explosive eruptions and on both tephra dispersal and sedimentation, based on the characterization of the erupted material. A systematic and detailed morphological characterization of tephra particles from different eruptions and the calculation of their terminal fall velocity is carried out in order to give new insights in understanding the influence of the morphology of volcanic particles on the settling process. The May 2008 Chaiten eruption has been taken as a case study. The eruption has been studied based on the data collected in the field on January 2009 in order to describe its stratigraphy and to determine the main eruptive parameters (i.e., volume, column height, mass eruption rate). On May 6th the eruption reached its climax producing a tephra layer composed mainly of lithic lapilli and blocks (> 2 mm) and a 19 km high subplinian column. Textural analysis have been carried out on pumice samples produced in this phase and a fractal analysis of the associated ash have also been conducted in order to study the influence of the vescicularity on particle morphology and to get information about the dynamic processes that characterized the eruption.
Bias-Variance Tradeoffs for Designing Simultaneous Temporal Experiments

We study the analysis and design of simultaneous temporal experiments, where a set of interventions are applied concurrently in continuous time, and outcomes are measured on a sequence of events observed in time. As a motivating setting, suppose multiple data science teams are conducting experiments simultaneously and independently on a ride-hailing platform to test changes to marketplace algorithms such as pricing and matching, and estimating effects from observed event outcomes such as the rate at which ride requests are completed. The design problem involves partitioning a continuous space of time into intervals and assigning treatments at the interval level. Design and analysis must account for three factors: carryover effects from interventions at earlier times, correlation in event outcomes, and effects of interventions tested simultaneously. We provide simulations to build intuition and guidance for practitioners.
To improve their predictions, election forecasters should look to other disciplines like meteorology

The recent surge in public attention to election predictions has generated much discussion about how to improve forecasting model accuracy. Michael S. Lewis-Beck and Mary Stegmaier argue that advances in weather forecasting hold lessons for election forecasting. First, like weather models, election models should be based on sound theory. Second, more intensive data gathering, especially at the state level with repeated measurements over time, will capture the dynamics of the campaign and ultimately enhance the accuracy of predictions. Third, ensemble forecasting and applying expertise to adjust forecasts are other methods to consider for reducing forecast error.
Constrained Polynomial Likelihood

Starting from a distribution $z$, we develop a non-negative polynomial minimum-norm likelihood ratio $\xi$ such that $dp=\xi dz$ satisfies a certain type of shape restrictions. The coefficients of the polynomial are the unique solution of a mixed conic semi-definite program. The approach is widely applicable. For example, it can be used to incorporate expert opinion into a model, or as an objective function in machine learning algorithms.