Miracle-dz/UniFAR-FTUs huggingface dataset:
Interplay of actin nematodynamics and anisotropic tension controls endothelial mechanics

Blood vessels expand and contract actively, while continuously experiencing dynamic external stresses from the blood flow. The mechanical response of the vessel wall is that of a composite material: its mechanical properties depend on a diverse set of cellular mechanical components, which change dynamically as cells respond to external stress. Mapping the relationship between these underlying cellular processes and emergent tissue mechanics is an on-going challenge, in particular in endothelial cells. Here we use a microstretcher mimicking the native environment of blood vessels to assess both the mechanics and cellular dynamics of an endothelial tube in response to a physiological increase in luminal pressure. The characterization of the instantaneous monolayer elasticity reveals a strain-stiffening, actin-dependent and substrate-responsive behavior. In response to a maintained pressure increase, the tissue displays a fluid-like expansion, accompanied by the reorientation of cell shape and of actin fibers. This actin-driven reorientation depends on focal adhesions and adherens junctions, two key mechanosensors. We introduce a mechanical model coupling actin fiber nematodynamics with active and elastic tension generation by actin fibers in the endothelium, which recapitulates the response to pressure of endothelial tubes.
Demographic history and the efficacy of selection in the globally invasive mosquito Aedes aegypti

Aedes aegypti is the main vector species of yellow fever, dengue, zika and chikungunya. The species is originally from Africa but has experienced a spectacular expansion in its geographic range to a large swath of the world, the demographic effects of which have remained largely understudied. In this report, we examine whole-genome sequences from 6 countries in Africa, North America, and South America to investigate the demographic history of the spread of Ae. aegypti into the Americas its impact on genomic diversity. In the Americas, we observe patterns of strong population structure consistent with relatively low (but probably non-zero) levels of gene flow but occasional long-range dispersal and/or recolonization events. We also find evidence that the colonization of the Americas has resulted in introduction bottlenecks. However, while each sampling location shows evidence of a past population contraction and subsequent recovery, our results suggest that the bottlenecks in America have led to a reduction in genetic diversity of only ∼35% relative to African populations, and the American samples have retained high levels of genetic diversity (expected heterozygosity of ∼0.02 at synonymous sites) and have experienced only a minor reduction in the efficacy of selection. These results evoke the image of an invasive species that has expanded its range with remarkable genetic resilience in the face of strong eradication pressure.
Globally distributed bacteriophage genomes reveal mechanisms of tripartite phage-bacteria-coral interactions

Reef-building corals depend on an intricate community of microorganisms for functioning and resilience. Bacteriophages are the most abundant and diverse members of these communities, yet very little is known about their functions in the holobiont due to methodological limitations that have prevented the recovery of high-quality viral genomes and bacterial host assignment from coral samples. Here, we introduce a size-fractionation approach which increased bacterial and viral recovery in coral metagenomes by 9-fold and 3-fold, respectively, and enabled the assembly and binning of bacterial and viral genomes at relatively low sequencing coverage. We combined these viral genomes with those derived from 677 publicly available metagenomes, viromes, and bacterial isolates from stony corals to build a Global Coral Virome Database of over 20,000 viral genomes and genome fragments spanning four viral realms. The tailed bacteriophage families Kyanoviridae and Ackermannviridae were the most abundant, replacing the since-abolished groups Podoviridae and Siphoviridae. Prophage and CRISPR spacer linkages between these viruses and 626 bacterial metagenome-assembled genomes and bacterial isolates showed that most viruses infected Alphaproteobacteria, the most abundant class, and less abundant taxa like Halanaerobiia and Bacteroidia. A host-phage-gene network identified keystone viruses with the genomic capacity to eavesdrop and modulate bacterial quorum sensing, interfere with sulfur cycling, and direct molecular interactions with eukaryotic cells through the release of extracellular effectors. This study reveals the basis of bacteriophage roles in modulating ecological interactions not only among bacterial community members but also directly affecting tripartite interactions with the coral host and its endosymbiotic algae.
Human assembloid model of the ascending neural sensory pathway

The ascending somatosensory pathways convey crucial information about pain, touch, itch, and body part movement from peripheral organs to the central nervous system. Despite a significant need for effective therapeutics modulating pain and other somatosensory modalities, clinical translation remains challenging, which is likely related to species-specific features and the lack of in vitro models to directly probe and manipulate this polysynaptic pathway. Here, we established human ascending somatosensory assembloids (hASA)– a four-part assembloid completely generated from human pluripotent stem cells that integrates somatosensory, spinal, diencephalic, and cortical organoids to model the human ascending spinothalamic pathway. Transcriptomic profiling confirmed the presence of key cell types in this circuit. Rabies tracing and calcium imaging showed that sensory neurons connected with dorsal spinal cord projection neurons, which ascending axons further connected to thalamic neurons. Following noxious chemical stimulation, single neuron calcium imaging of intact hASA demonstrated coordinated response, while four-part concomitant extracellular recordings and calcium imaging revealed synchronized activity across the assembloid. Loss of the sodium channel SCN9A, which causes pain insensitivity in humans, disrupted synchrony across the four-part hASA. Taken together, these experiments demonstrate the ability to functionally assemble the essential components of the human sensory pathway. These findings could both accelerate our understanding of human sensory circuits and facilitate therapeutic development.
Pre-trained molecular representations enable antimicrobial discovery

The rise in antimicrobial resistance poses a worldwide threat, reducing the efficacy of common antibiotics. Yet, determining the antimicrobial activity of new chemical compounds through experimental methods is still a time-consuming and costly endeavor. Compound-centric deep learning models hold the promise to speed up the search and prioritization process. Here, we introduce a lightweight computational strategy for antimicrobial discovery that builds on MolE (Molecular representation through redundancy reduced Embedding). MolE is a non-contrastive self-supervised Graph Neural Network framework that leverages unlabeled chemical structures to learn task-independent molecular representations. By combining a pre-trained MolE representation with experimentally validated compound-bacteria activity data, we build an antimicrobial prediction model that re-discovers recently reported growth-inhibitory compounds that are structurally distinct from current antibiotics. Using the model as a compound prioritization strategy, we identify and experimentally confirm three human-targeted drugs as growth-inhibitors of Staphylococcus aureus, highlighting MolE’s potential to accelerate the discovery of new antibiotics.
Local FK506 delivery induces osteogenesis in in vivo rat bone defect and rabbit spine fusion models

Bone grafting procedures are commonly used for the repair, regeneration, and fusion of bones in in a wide range of orthopaedic surgeries, including large bone defects and spine fusion procedures. Autografts are the clinical gold standard, though recombinant human bone morphogenetic proteins (rhBMPs) are often used, particularly in difficult clinical situations. However, treatment with rhBMPs can have off-target effects and significantly increase surgical costs, adding to patients’ already high economic and mental burden. Recent studies have identified that FDA-approved immunosuppressant drug, FK506 (Tacrolimus), can also activate the BMP pathway by binding to its inhibitors. This study tested the hypothesis that FK506, as a standalone treatment, could induce osteogenic differentiation of human mesenchymal stromal cells (hMSCs), as well as functional bone formation in a rat segmental bone defect model and rabbit spinal fusion model. FK506 potentiated the effect of low dose BMP-2 to enhance osteogenic differentiation and mineralization of hMSCs in vitro. Standalone treatment with FK506 delivered on a collagen sponge, produced consistent bone bridging of a rat critically-sized femoral defect with functional mechanical properties comparable to naïve bone. In a rabbit single level posterolateral spine fusion model, treatment with FK506 delivered on a collagen sponge successfully fused the L5-L6 vertebrae at rates comparable to rhBMP-2 treatment. These data demonstrate the ability of FK506 to induce bone formation in human cells and two challenging in vivo models, and indicate FK506 can be utilized either as a standalone treatment or in conjunction with rhBMP to treat a variety of spine disorders. Graphical Abstract
The histone chaperone CAF-1 maintains the stability of the ribosomal RNA gene cluster by suppressing end resection of replication-associated DNA double-strand breaks

In eukaryotes, chromatin assembly is coupled to DNA replication by the histone chaperone chromatin assembly factor-1 (CAF-1). Here, we demonstrate that CAF-1 maintains the stability of the ribosomal RNA gene (rDNA) cluster in budding yeast. Absence of CAF-1 led to homologous recombination (HR)-mediated rDNA copy number changes as well as the production of extrachromosomal rDNA circles in response to Fob1-dependent replication fork arrest at the replication fork barrier (RFB) site in the rDNA. CAF-1-mediated rDNA stabilization depends on its interaction with Proliferating Cell Nuclear Antigen. The absence of CAF-1 affected neither DNA replication fork arrest at the RFB nor subsequent DNA double-strand breaks (DSBs) but led to an increased frequency of DSB end resection, which initiates HR. Absence of CAF-1 caused the derepression of transcription of noncoding RNA from the regulatory promoter E-pro located near the RFB, which contributed to enhanced DSB end resection. Moreover, its absence led to the generation of longer Okazaki fragments, which is indicative of lower nucleosome density in the rDNA. Taken together, our findings suggest that CAF-1-mediated chromatin assembly facilitates silencing of transcription from E-pro and proper nucleosome deposition behind replication forks, leading to the restriction of DSB end resection and subsequent rearrangement-prone DSB repair.
Transcranial Functional Ultrasound Imaging Detects Focused Ultrasound Neuromodulation Induced Hemodynamic Changes in Mouse and Nonhuman Primate Brains In Vivo

Focused ultrasound (FUS) is an emerging noinvasive technique for neuromodulation in the central nervous system (CNS). To evaluate the effects of FUS-induced neuromodulation, many studies used behavioral changes, functional magnetic resonance imaging (fMRI) or electroencephalography (EEG). However, behavioral readouts are often not easily mapped to specific brain activity, EEG has low spatial resolution limited to the surface of the brain and fMRI requires a large importable scanner that limits additional readouts and manipulations. In this context, functional ultrasound imaging (fUSI) holds promise to directly monitor the effects of FUS neuromodulation with high spatiotemporal resolution in a large field of view, with a comparatively simple and flexible setup. fUSI uses ultrafast Power Doppler Imaging (PDI) to measure changes in cerebral blood volume, which correlates well with neuronal activity and local field potentials. We designed a setup that aligns a FUS transducer with a linear array to allow immediate subsequent monitoring of the hemodynamic response with fUSI during and after FUS neuromodulation. We established a positive correlation between FUS pressure and the size of the activated area, as well as changes in cerebral blood volume (CBV) and found that unilateral sonications produce bilateral hemodynamic changes with ipsilateral accentuation in mice. We further demonstrated the ability to perform fully noninvasive, transcranial FUS-fUSI in nonhuman primates for the first time by using a lower-frequency transducer configuration.
Synergizing Theory and Practice of Automated Algorithm Design for Optimization (Dagstuhl Seminar 23332)

This report documents the program and the outcomes of Dagstuhl Seminar 23332, which focused on automated algorithm design (AAD) for optimization. AAD aims to propose good algorithms and/or parameters thereof for optimization problems in an automated fashion, instead of forcing this decision on the user. As such, AAD is applicable in a variety of domains. The seminar brought together a diverse, international set of researchers from AAD and closely related fields. Especially, we invited people from both the empirical and the theoretical domain. A main goal of the seminar was to enable vivid discussions between these two groups in order to synergize the knowledge from either domain, thus advancing the area of AAD as a whole, and to reduce the gap between theory and practice. Over the course of the seminar, a good mix of breakout sessions and talks took place, which were very well received and which we detail in this report. Efforts to synergize theory and practice bore some fruit, and other important aspects of AAD were highlighted and discussed. Overall, the seminar was a huge success.
Communication Cost of Joins over Federated Data

We study the problem of querying different data sources, which we assume out of our control and that are made available by standard web communication protocols. In this scenario, the time spent communicating data often dominates the time spent processing local queries in each server. Thus, our focus is on algorithms that minimize the communication between the query processing server and the federated servers containing data. However, any federated query can always be answered with linear communication, simply by requesting all the data to the federated sources. Further, one can show that certain queries do require this amount of communication. But sending all the data is definitely not a relevant algorithm from a practical point of view. This worst-case analysis is, therefore, not useful for our needs. There is a growing body of work in terms of designing strategies that minimize communication in query federation, but these strategies are commonly based in heuristics, and we currently miss a formal analysis providing guidelines for the design of such strategies. We focus on the communication complexity of federated joins when the problem is parameterized by a measure commonly referred to as the certificate of the instance: a framework that has been used before in the context of set intersection and local query processing. We show how to process any conjunctive query in time given by the certificate of instances. Our algorithm is an adaptation of Minesweeper, one of the algorithms devised for local query processing, into our federating setting. When certificates are of the size of the instance, this amount to sending the entire database, but our strategy provides drastic reductions in the communication needed for queries and instances with small certificates. We also show matching communication lower bounds for cases where the certificate is smaller than the size of active domain of the instances.
Low Complexity Hybrid Precoding Design for Sub-Connected Massive MIMO Systems

Hybrid analog and digital precoding architectures facilitate the practical implementation of millimeter wave (mmW) massive multiple-input multiple-output (mmWmMIMO) systems by reducing the number of employed radio frequency chains. The spectral efficiency (SE) optimization problems of these systems are non-convex and NP-hard due to the joint optimization between the analog and digital precoding and the constant modulus constraints required by the analog phase shifters. To address this problem, we propose a decoupled two-stage design where in the first stage, a closed approximation of the effective channel is proposed, hence the SE maximization problem is recast as a effective channel gain maximization problem, then the analog precoding matrices are determined, which are taken into account in the second stage to design the digital precoding matrix to maximize the system’s SE. Simulation results are provided and validate the effectiveness of our proposed hybrid precoding schemes.
Coupled Output Synchronization for Leader-Follower Vehicle Platooning

A novel framework in multi-agent system networks is introduced and analyzed in this article, namely coupled output synchronization over directed graph topologies. Under assumptions of a rooted spanning tree, we design a distributed control law for synchronization of Laplacian coupled outputs of double integrator dynamics. The analysis of the closed-loop systems communicating over digraphs is carried out via Lyapunov methods. The vehicle platooning problem is demonstrated as a direct application of our results on coupled output synchronization. The control is distributed and independent of the knowledge of eigenvalues of the graph Laplacian. Simulations verify the performance of the controller with and without disturbance.
Flocking Control Algorithm of Multiple Agents Based on Layered Pinning Control Theory

This paper starts from the concept of multi-Agent pinning control algorithm applied to UAV flocking control. Layered pinning control algorithm is proposed to optimize the tracking results for the problem of target tracking loss that may occur when the UAV clusters are large and there is external interference. According to the idea of breadth-first search, the speed and position feedback of its parent node is added to the control input of ordinary agents, and the speed matching term of the control input is improved by proposing a speed correction factor, which determines the degree of being affected by the neighborhood by judging the state of each other, so as to realize layer-by-layer transfer feedback and strengthen the tracking ability of the child nodes, which enables the whole network to avoid splitting and reach flocking. The simulation results show that the algorithm can strengthen the tracking ability of the agent and can track the target faster than the traditional pinning flocking control algorithm, which is suitable for large-scale UAV cluster flocking control.
Designs of Finite Resolution IRS-aided MIMO Multiuser Communications Based on SZFDPC

A novel design of MIMO downlink communications that is assisted by modern intelligent reflecting surfaces (IRS) is proposed in this paper. The new design employs successive zero-forcing dirty paper coding at base station and allows multiple receive antennas to be used at users, making it much more realistic than existing works, which are applicable only to cases of single receive antenna. Furthermore, the new design requires IRS elements with only finite phase resolution and is much more practical for implementation. Simulation results show that the proposed design can significantly improve the performance of IRS-aided downlink communications. In particular, for the classical scenario of single receive antenna at users, our design, using only a QPSK phases for IRS elements, increases by more than 200-540% the energy efficiency of several existing works that assume IRS elements with infinite resolution for phases.
Identification and characterization of autohthonus olive varieties in Istria (Croatia)

Different olive varieties are cultivated on the entire Istrian peninsula. With the aim of solving naming confusion, inventarization and identification of autochthonous olive varieties in Istrian County was performed. The investigation was carried out in the framework of the current long-term research project focused on preserving and valorization of indigenous olive varieties. Morphological description of 64 olive trees was performed during the last three years and data were used for cluster analysis. Samples were clustered in 6 potential variety groups with at least 14 different varieties. Further researches comprising morphological and genetic analyses will provide a deeper insight into biological resources so far not discovered.
COMPOSITION OF WEED SPECTRUM IN WHEAT FIELDS OF DISTRICT MUZAFFAR-GARH PUNJAB PAKISTAN

Weed flora was explored in wheat fields of District Muzaffar-Garh (Pakistan) during 201617. Studies were accomplished in eight different locations of the district using quadrat method. Weed spectrum varied spatially in most of these towns. The flora comprised 3 monocot and 7 dicot families. Thirteen dicot weed species belonging to 7 families and seven monocot species from three monocot families were identified in the study area. Family Fabaceae from the dicots and Poaceae among the monocots emerged as the largest families each comprising of five weed species. The next dominant family was Chenopodiaceae having 2 species while rest of the families were represented by a single species each. IVCI exhibited that at Kochak Baloch Cyprus-Spergula-Cheopodium community prevailed, while at Chak 54 L a different community Medicago-Melilotus-Rumex has been the predominant. At Fateh Pur site witnessed the superiority of Chenopodium-Lathyrus-Cyperus community, whereas at Saggray Wala Anagallis-Sonchus-Cynodon dominated. Pattal Munda and Rang Pur had overwhelming stands of Chenopodium, Melilotus Rumex community. While Chowk Sarwar Shaheed and Abbasi Chowk were infested with Avena-Poa-Rumex and AngallisRumex-Chenopodium communities, respectively. IVCI identified four most important weeds in the Distict Muzaffar Garh, Punjab Pakistan in descending order in wheat fields are Rumex dentatus (64), Chenopodium album (59.5), Anagallis arvensis (58.4) and Melilotus alba (48.6). In order to harvest the optimum yield of wheat proper management of these and other weeds is recommended.
Most discriminative stimuli for functional cell type clustering

Identifying cell types and understanding their functional properties is crucial for unraveling the mechanisms underlying perception and cognition. In the retina, functional types can be identified by carefully selected stimuli, but this requires expert domain knowledge and biases the procedure towards previously known cell types. In the visual cortex, it is still unknown what functional types exist and how to identify them. Thus, for unbiased identification of the functional cell types in retina and visual cortex, new approaches are needed. Here we propose an optimization-based clustering approach using deep predictive models to obtain functional clusters of neurons using Most Discriminative Stimuli (MDS). Our approach alternates between stimulus optimization with cluster reassignment akin to an expectation-maximization algorithm. The algorithm recovers functional clusters in mouse retina, marmoset retina and macaque visual area V4. This demonstrates that our approach can successfully find discriminative stimuli across species, stages of the visual system and recording techniques. The resulting most discriminative stimuli can be used to assign functional cell types fast and on the fly, without the need to train complex predictive models or show a large natural scene dataset, paving the way for experiments that were previously limited by experimental time. Crucially, MDS are interpretable: they visualize the distinctive stimulus patterns that most unambiguously identify a specific type of neuron.