Miracle-dz/UniFAR-FTUs huggingface dataset:
Graspot: A graph attention network for spatial transcriptomics data integration with optimal transport

Spatial transcriptomics (ST) technologies enable the measurement of mRNA expression while simultaneously capturing spot locations. By integrating ST data, the 3D structure of a tissue can be reconstructed, yielding a comprehensive understanding of the tissue’s intricacies. Nevertheless, a computational challenge persists: how to remove batch effects while preserving genuine biological structure variations across ST data. To address this, we introduce Graspot, a graph attention network designed for spatial transcriptomics data integration with unbalanced optimal transport. Graspot adeptly harnesses both gene expression and spatial information to align common structures across multiple ST datasets. It embeds multiple ST datasets into a unified latent space, facilitating the partial alignment of spots from different slices. Demonstrating superior performance compared to existing methods on four real spatial transcriptomics datasets, Graspot excels in ST data integration, including tasks that require partial alignment. In particular, Graspot unveils subtle tumor microenvironment structures of breast cancer, and accurately aligns the spatio-temporal transcriptomics data to reconstruct human heart developmental processes. The code for Graspot is available at https://github.com/zhan009/Graspot.
Transposon mutagenesis screen in Klebsiella pneumoniae identifies genetic determinants required for growth in human urine and serum

Klebsiella pneumoniae is a global public health concern due to the rising myriad of hypervirulent and multi-drug resistant clones both alarmingly associated with high mortality. The molecular microbial genetics underpinning these recalcitrant K. pneumoniae infections is unclear, coupled with the emergence of lineages resistant to nearly all present day clinically important antimicrobials. In this study, we performed a genome-wide screen in K. pneumoniae ECL8, a member of the endemic K2-ST375 pathotype most often reported in Asia, to define genes essential for growth in a nutrient-rich laboratory medium (Luria-Bertani medium), human urine and serum. Through transposon directed insertion-site sequencing (TraDIS), a total of 427 genes were identified as essential for growth on LB agar, whereas transposon insertions in 11 and 144 genes decreased fitness for growth in either urine or serum, respectively. These studies provide further knowledge on the genetics of this pathogen but also provide a strong impetus for discovering new antimicrobial targets to improve current therapeutic options for K. pneumoniae infections.
Featural and spatial interference with functionally active and passive items in working memory

We hypothesised that functionally active and passive states in working memory might be related to different neural mechanisms. Memoranda in active states might be maintained by persistent neural firing, whereas memoranda in passive states might be maintained through short-term synaptic plasticity. We reasoned that this might make these items differentially susceptible to interference during maintenance, and that passive items in particular might be more robust. To test this hypothesis, we gave our participants a working memory task in which one item was prioritised (active) by always probing it first, while the other item was deprioritised (passive) by always probing it second. In three experiments, we presented an interfering task during memory maintenance, in which the stimuli matched either the feature dimension of the memory items (colour or orientation), their spatial location, or both. We found that both active and passive memory items were affected by interference, to a similar extent, with overall performance being closely matched. However, we observed a qualitative difference in the nature of their representations. Specifically, featural interference seemed to produce reduced precision for active items, whereas it resulted in higher guess rates for passive items. The existence of this qualitative difference suggests that functionally active and passive working memory states may indeed map onto different neural mechanisms, even though on average they seem to be equally robust to interference.
Large-scale multi-omics analyses identified root-microbiome associations underlying plant nitrogen nutrition

The microbiome determines the performance and fitness of the host plant. Nevertheless, the causal interaction between host genetic variation, gene regulation and the impact of the microbiome on the host phenotype remain unknown. Here we generated 1,341 paired root transcriptome, rhizosphere microbiome and root ionome samples and performed a multi-omics analyses of the host-microbe association at the root-soil interface using 175 rapeseeds (Brassica napus L.) resequenced ecotypes at two field environments. We observed the highest statistically explained variance for root nitrogen uptake among natural ionomic variation by overall transcriptome-wide gene expression and microbial abundance variation. Moreover, we identified significant genome-wide associations for 203 highly heritable amplicon sequence variants (ASVs) at multiple genetic loci regulated by eQTL hotspots associated with nitrogen metabolism components. These associations involved a central bacterial genus (Sphingopyxis), which plays a dominant role on gene regulatory effect on its variation regulated by eQTL hotspots. In addition, we performed high-throughput bacterial cultivation from rapeseed roots and subjected Sphingopyxis to whole genome sequencing. Finally, targeted metabolite profiling and confocal imaging assays demonstrated a host-microbiome regulatory effect on Sphingopyxis established by lateral root development and plant nitrogen nutrition. In summary, our integrative approach reveals the genetic basis of host-microbiome trait associations in the transcriptional, nutritional and environmental domains and suggests that the microbiome might have causal effects on root development with implications towards the breeding of nutrient-efficient crops.
Geometry and cell wall mechanics guide early pollen tube growth in Arabidopsis thaliana

In Arabidopsis thaliana, successful fertilization relies on the precise guidance of the pollen tube tip as it navigates through the female pistil tissues to deliver non-motile sperm cells to ovules. While prior studies have unveiled the role of the pistil in directing pollen tubes to ovules, growth guidance mechanisms within the stigmatic epidermis during the initial phase of the pollen tube’s journey remains elusive. A recent analysis comparing wild-type (WT) pollen tube paths in WT and ktn1-5 stigmatic cells revealed a tight connection between directed pollen tube growth and the mechanical properties of the invaded stigmatic cell. Building upon these observations, we constructed here a mathematical model to explore the mechanisms guiding early pollen tube growth through the papilla cell wall (CW). We found that in ktn1-5, the pollen tube moves freely on the curved papilla surface, following geodesics, while the WT papilla exerts directional guidance on the pollen tube. An order of magnitude analysis of the mechanical forces involved in pollen tube growth in papillae suggests a guidance mechanism, where the elongated papilla geometry and the CW elasticity combine to efficiently direct pollen tube growth towards the papilla base.
Local muscle pressure stimulates the principal receptors for proprioception

Proprioception plays a vital role in motor coordination and self-perception. Muscle spindles are considered the principal receptors for proprioception and are believed to encode stretch and signal limb position and velocity. Here, we applied percutaneous pressure on a small area of extensor muscles at the forearm while simultaneously recording spindle afferent responses, skeletal muscle activity and hand kinematics. Three target levels of press force were applied periodically on the spindle-bearing muscle when the hand was immobile (‘isometric’ condition) and when the participant’s hand moved rhythmically about the wrist in the flexion-extension plane (‘sinusoidal’ condition). We show that local muscle pressure is an ‘adequate’ stimulus for human spindles in isometric conditions, and that pressure enhances spindle afferent responses during stretch, as hypothesized to occur due to compression of the spindle capsule. Our findings redefine basic muscle feedback and urge a reconsideration of its role in sensorimotor function and various neuromuscular pathologies. HIGHLIGHTS Local muscle pressure is an adequate stimulus for spindles in isometric conditions Local pressure enhances spindle afferent responses during muscle stretch Spindles are better at encoding pressure in isometric conditions than kinematics during stretch
Spotiflow: accurate and efficient spot detection for imaging-based spatial transcriptomics with stereographic flow regression

The identification of spot-like structures in large and noisy microscopy images is an important task in many life science techniques, and it is essential to their quantitative performance. For example, imaging-based spatial transcriptomics (iST) methods rely critically on the accurate detection of millions of transcripts in low signal-to-noise ratio (SNR) images. While recent developments in computer vision have revolutionized many bioimage tasks, currently adopted spot detection approaches for iST still rely on classical signal processing methods that are fragile and require manually tuning. In this work we introduce Spotiflow, a deep-learning method that casts the spot-detection problem as a multiscale stereographic flow regression problem that yields subpixel-accurate localizations. Spotiflow is robust to different noise conditions and generalizes across different chemistries while being up to an order-of-magnitude more time and memory efficient than commonly used methods. We show the efficacy of Spotiflow by comprehensive quantitative comparisons against other methods on a variety of datasets and demonstrate the impact of its increased accuracy on the biological conclusions drawn from iST and live imaging experiments. Spotiflow is available as an easy-to-use Python library as well as a napari plugin at http://www.github. com/weigertlab/spotiflow.
YraN is a helicase-associated nuclease fostering extended recombination events by natural transformation

Natural transformation is a widespread molecular pathway of horizontal gene transfer involving the uptake and recombination of exogenous DNA. Exogenous DNA follows a pathway involving genes sequentially required for its capture, internalization, protection, and recombination with the chromosome. Most of these genes were identified through the isolation of transformation-defective mutants and/or based on their expression preceding natural transformation. Yet, genes required for key steps of the pathway remain elusive. We sought to identify any missing component by comparing Tn-seq data obtained in two distantly-related transformable diderm species, the human pathogen Legionella pneumophila and the cyanobacterium Synechococcus elongatus. We identified yraN, a widespread and highly conserved gene of unknown function required for natural transformation. We provide evidence that YraN is a nuclease associated with the ComM helicase, which cooperate to process the D-loop formed by the invasion of the transforming DNA in the chromosomal DNA strands. We propose a model in which cleavage of the displaced strand by YraN can promote the recombination of transforming DNA, leading to extended recombination events. The identification of this YraN/ComM nuclease/helicase system supports the hypothesis that bacteria possess a conserved pathway for the transport and recombination of exogenous DNA. Significance Many bacteria use a dedicated pathway to internalize and integrate extracellular DNA into their chromosome. This allows them to naturally acquire genes, or gene variants, that can confer them new traits, hence the term of natural transformation. Although reported nearly a century ago by Frederick Griffith, several aspects of the mechanism of natural transformation remain elusive. Specifically, it is not clear whether or not all the conserved molecular players of the pathway have been identified. We queried two distinct bacterial species for any gene that would be required for natural transformation. We confirmed all core players of the pathway, but also uncovered a highly conserved one, YraN. We provide evidence that YraN is an endonuclease, which in association with the ComM helicase, promotes the efficient integration of the extracellular DNA in the bacterial chromosome.
Transdifferentiation of Human Dental Pulp Mesenchymal Stem Cells into Spiral Ganglion-like Neurons

Spiral ganglion neurons (SGN) carry auditory information from sensory hair cells (HCs) to the brain. These auditory neurons, which are the target neurons of cochlear implants, degenerate following sensorineural hearing loss (SNHL). Prosthetic devices such as cochlear implants function by bypassing lost HCs and stimulating the residual SGNs, allowing restoration of hearing in deaf patients. Emerging cell-replacement therapies for SNHL include replacing damaged SGNs using stem cell-derived otic neuronal progenitors (ONPs). However, the availability of renewable, accessible, and patient-matched sources of human stem cells constitutes a major prerequisite towards cell replacement for auditory nerve recovery. Human dental pulp stem cells (hDPSCs) extracted from human wisdom teeth are self-renewing stem cells that originate from the neural crest during development. In this study, we developed a stepwise in vitro guidance procedure to differentiate hDPSCs into ONPs and then to SGNs. The procedure relies on the modulation of BMP and TGF-β pathways for neurosphere formation as a first step, then a differentiation step based on two culture paradigms exploiting major signaling pathways (Wnt, Shh, RA) and neurotrophic factors involved in early otic neurogenesis. Gene and protein expression analyses revealed efficient induction of a comprehensive panel of known ONP and SGN-like cell markers over the course of in vitro differentiation. The use of atomic force microscopy revealed that hDPSC-derived SGN-like cells exhibit similar nanomechanical properties compared to their in vivo SGN counterparts. Furthermore, neurites extended between hDPSC-derived ONPs and rat SGN explants 4-6 days after co-culturing, suggesting the formation of neuronal contacts. These data indicate that the in vitro differentiated cells closely replicate the phenotypic and nanomechanical characteristics of human SGNs, advancing our culture differentiation system to the level to be used in next-generation cochlear implants and/or inner ear cell-based strategies for SNHL.
Content may be King, but (Peering) Location matters: A Progress Report on the Evolution of Content Delivery in the Internet

Since the commercialization of the Internet, content and related applications, including video streaming, news, advertisements, and social interaction have moved online. It is broadly recognized that the rise of all of these different types of content (static and dynamic, and increasingly multimedia) has been one of the main forces behind the phenomenal growth of the Internet, and its emergence as essential infrastructure for how individuals across the globe gain access to the content sources they want. To accelerate the delivery of diverse content in the Internet and to provide commercial-grade performance for video delivery and the Web, content delivery networks (CDNs) were introduced. This paper describes the current CDN ecosystem and the forces that have driven its evolution. We outline the different CDN architectures and consider their relative strengths and weaknesses. Our analysis highlights the role of location, the growing complexity of the CDN ecosystem, and its relationship to and the implications for interconnection markets.
Success probability of the L0-regularized box-constrained Babai point and column permutation strategies

We consider the success probability of the L 0 -regularized box-constrained Babai point, which is a suboptimal solution to the L 0 -regularized box-constrained integer least squares problem and can be used for MIMO detection. First, we derive formulas for the success probability of both L 0 -regularized and unregularized box-constrained Babai points. Then we investigate the properties of the L 0 -regularized box-constrained Babai point, including the optimality of the regularization parameter, the monotonicity of its success probability, and the monotonicity of the ratio of the two success probabilities. A bound on the success probability of the L 0 -regularized Babai point is derived. After that, we analyze the effect of the LLL-P permutation strategy on the success probability of the L 0 -regularized Babai point. Then we propose some success probability based column permutation strategies to increase the success probability of the L 0 -regularized box-constrained Babai point. Finally, we present numerical tests to conﬁrm our theoretical results and to show the advantage of the L 0 regularization and the effectiveness of the proposed column permutation algorithms compared to existing strategies.
Trends, fads, and futures: computers in learning in tertiary education, 1983-2002

ASCILITE, the Australasian Society for Computers in Learning in Tertiary Education, is a professional society focusing on computers in learning in tertiary education that has been sponsoring conferences for its membership since 1986. Prior to this, three earlier conferences formed the genesis of ASCILITE. Over that period there have been significant changes in pedagogy and technology but few attempts, if any, have been made to analyse the ways in which conference proceedings have reflected these changes and shifts. The purpose of this research paper is to review the ASCILITE proceedings and provide an analysis of “trends, fads and futures” to reflect on past initiatives, propose potential directions and assist the society identify strategic directions. In addition, the analysis will provide a basis from which further research can be justified in terms of better understanding “computers in learning in tertiary education”.
Board 399: The Freshman Year Innovator Experience (FYIE): Bridging the URM Gap in STEM

The project focuses on increasing “effective STEM education and broadening participation” in underrepresented minority (URM) STEM students at the University of Texas Rio Grande Valley (UTRGV) to successfully face academic and professional challenges, recently exacerbated by the COVID-19 pandemic. The Freshman Year Innovator Experience proposes the development of self-transformation skills in freshman mechanical engineering students to successfully face academic and professional challenges exacerbated by the COVID-19 pandemic while working on two parallel projects of technical design innovation and academic career pathways. The authors will present the work in progress and preliminary results from a pilot implementation of the Freshman Year Innovator Experience. This project is funded by NSF award 2225247
In Vitro Antibacterial Activity of Ceftobiprole and Comparator Compounds against Nation-Wide Bloodstream Isolates and Different Sequence Types of MRSA

Bloodstream infections by bacteria, especially multidrug-resistant bacteria, remain a worldwide public health concern. We evaluated the antibacterial activity of ceftobiprole and comparable drugs against different bloodstream isolates and different sequence types of methicillin-resistant Staphylococcus aureus (MRSA) in China. We found that MRSA, methicillin-susceptible Staphylococcus aureus (MSSA), and methicillin-susceptible coagulase-negative Staphylococcus (MSCNS) displayed ceftobiprole sensitivity rates of >95%, which are similar to the rates for linezolid, daptomycin, and vancomycin. Of the tested MRCNS strains, 90.4% were sensitive to ceftobiprole. The sensitivities of ST59, ST398, and ST22 MRSA to ceftobiprole were higher than that of ST239. Ceftobiprole’s MIC50/90 value against Enterococcus faecalis was 0.25/2 mg/L, whereas Enterococcus faecium was completely resistant to this drug. Ceftobiprole exhibited no activity against ESBL-positive Enterobacterales, with resistance rates between 78.6% and 100%. For ESBL-negative Enterobacterales, excluding Klebsiella oxytoca, the sensitivity to ceftobiprole was comparable to that of ceftazidime, ceftriaxone, and cefepime. The MIC50/90 value of ceftobiprole against Pseudomonas aeruginosa was 2/16 mg/L, and for Acinetobacter baumannii, it was 32/>32 mg/L. Thus, ceftobiprole shows excellent antimicrobial activity against ESBL-negative Enterobacterales and Pseudomonas aeruginosa (comparable to that of ceftazidime, ceftriaxone, and cefepime); however, it is not effective against ESBL-positive Enterobacterales and Acinetobacter baumannii. These results provide important information to clinicians.
An Analysis of the Relationship Between School Climate and the Implementation of Middle School Practices

AbstractThis study was designed to examine the relationship between the level of implementation of recommended middle school practices and school climate in Oklahoma middle schools. The Middle School Practices Index was sent to all middle school principals in the state. MSPI scores were used to identify one group of schools with high levels of implementation of recommended middle school practices and another group with low levels of implementation. Faculty from these two groups of schools were surveyed using the NASSP School Climate Survey. An analysis was performed to identify relationships between the implementation of middle school practices and school climate. Perceptions of school climate by teachers were in the high implementation schools were higher on 7 of the 10 school climate indicators. Two of those differences were found to be significant at the . 05 level. A correlational analysis found 19 significant relationships between middle school practices and school climate indicators. Based upon this .
Dynamic response of rocking masonry elements to long period strong ground motion

Damage and collapse in masonry structures often take place locally. Due to the dynamic action, the damage mechanisms develop as loss of equilibrium of rigid blocks capable of sliding and rotating. Actually the rocking mechanisms of masonry elements, typically non-linear, show high displacement capacity until collapse, high fundamental period of vibration in the non-linear range that can further increase because of the nearly non-tensile strength of masonry. Recent works (e.g. Resemini et al. 2006) propose an approach based on the Equilibrium Limit Analyses (kinematic theorem), in order to describe these out-of-plane mechanisms. Nevertheless, the chaotic dynamic response of these rocking elements needs further studies. The rocking behaviour and its relation to different input and structural parameters are investigated by means of non-linear numerical simulations, with special attention to the long period range. Using a non-linear dynamic model, several step-by-step dynamic analyses on the equivalent SDOF systems are performed. In these analyses, the ground motion characterization is a crucial topic: from a selection of digital recorded accelerograms (Paolucci et al. 2008, Cauzzi and Faccioli, 2008), long period strong ground motions representative of different conditions (magnitude, focal distance, etc.) are used as input for the structural analyses, both dynamic and simplified (proposing a method based on overdamped response spectra). The aim is to verify the applicability of response spectra parameters to simplified procedures for the structural verification of damage mechanisms in masonry structures. Moreover, the influence on the response of ground motion characteristics (PGA, PGV, PGD, Housner intensity, etc.) is analysed.