Miracle-dz/UniFAR-FTUs huggingface dataset:
Electromyography Classification during Reach-to-Grasp Motion using Manifold Learning

Electromyography (EMG) is a simple, non-invasive, and cost-effective technology for sensing muscle activity. However, EMG is also noisy, complex, and high-dimensional. It has nevertheless been widely used in a host of human-machine-interface applications (electrical wheelchairs, virtual computer mice, prosthesis, robotic fingers, etc.) and in particular to measure reaching and grasping motions of the human hand. Here, we developd a more automated pipeline to predict object weight in a reach-and-grasp task from an open dataset relying only on EMG data. In that we shifted the focus from manual feature-engineering to automated feature-extraction by using raw (filtered) EMG signals and thus letting the algorithms select the features. We further compared intrinsic EMG features, derived from several dimensionality-reduction methods, and then ran some classification algorithms on these low-dimensional representations. We found that the Laplacian Eigenmap algorithm generally outperformed other dimensionality-reduction methods. What is more, optimal classification accuracy was achieved using a combination of Laplacian Eigenmaps (simple-minded) and k-Nearest Neighbors (88% for 3-way classification). Our results, using EMG alone, are comparable to others in the literature that used EMG and EEG together. They also demonstrate the usefulness of dimensionality reduction when classifying movement based on EMG signals and more generally the usefulness of EMG for movement classification.
CRISPR-Cas9-mediated editing of myb28 impairs glucoraphanin accumulation of Brassica oleracea in the field

We sought to quantify the role of MYB28 in the regulation of aliphatic glucosinolate biosynthesis and associated sulphur metabolism in field-grown B. oleracea with the use of CRISPR-Cas9-mediated gene editing technology. We describe the first characterised myb28 knockout mutant in B. oleracea, and the first UK field trial of CRISPR-Cas9-mediated gene edited plants under the European Court of Justice interpretation of the 2001/18 EU GMO directive. We report that knocking-out myb28 results in downregulation of aliphatic glucosinolate biosynthesis genes and reduction in accumulation of the methionine-derived glucosinolate, glucoraphanin, in leaves and florets of field-grown myb28 mutant broccoli plants. There were no significant changes to the accumulation of sulphate, S-methyl cysteine sulfoxide and indole glucosinolate in leaf and floret tissues.
On the Organization of the Locomotor CPG: Insights From Split-Belt Locomotion and Mathematical Modeling

Rhythmic limb movements during locomotion are controlled by a central pattern generator (CPG) circuits located in the spinal cord. It is considered that these circuits are composed of individual rhythm generators (RGs) for each limb interacting with each other through multiple commissural and long propriospinal circuits. The organization and operation of each RG are not fully understood, and different competing theories exist about interactions between its flexor and extensor components, as well as about left-right commissural interactions between the RGs. The central idea of circuit organization proposed in this study is that with an increase of excitatory input to each RGs (or an increase in locomotor speed) the rhythmogenic mechanism within the RGs changes from “flexor-driven” rhythmicity to a “classical half-center” mechanism. We test this hypothesis using our experimental data on changes in duration of stance and swing phases in the intact and spinal cats walking on the ground or tied-belt treadmills (symmetric conditions) or split-belt treadmills with different left and right belt speeds (asymmetric conditions). We compare these experimental data with the results of mathematical modeling, in which simulated CPG circuits operate in similar symmetric and asymmetric conditions with matching or differing control drives to the left and right RGs. The obtained results support the proposed concept of state-dependent changes in RG operation and specific commissural interactions between the RGs. The performed simulations and mathematical analysis of model operation under different conditions provide new insights into CPG network organization and limb coordination during locomotion. Key Point Summary Limb movements during locomotion are controlled by neural circuits located within the spinal cord. These circuits include rhythm generators (RGs) controlling each limb interacting through multiple commissural pathways. The organization and operation of spinal RGs are not fully understood, and different competing concepts exists. We suggest that the operation of RGs is state-dependent, so that with an increase of external excitation the rhythmogenesis changes from “flexor-driven” oscillations to a “classical half-center” mechanism. A mathematical model of spinal circuits representing bilaterally-interacting RGs has been developed based on the above suggestion and used to interpret experimental data from intact and spinal cats walking on the ground or tied-belt treadmills (symmetric conditions) as well as on split-belt treadmills with different left and right belt speeds (asymmetric conditions). The performed simulations and mathematical analysis of the model under different conditions provide new insights into operation of spinal circuits and limb coordination during locomotion.
Making data-driven hypotheses for gene functions by integrating dependency, expression, and literature data

Identifying the key functions of human genes is a major biomedical research goal. While some genes are well-studied, most human genes we know little about. New tools in data science -- a combination of computer programming, math & statistics, and topical expertise -- combined with the rapid adoption of open science and data sharing allow scientists to access publicly available datasets and interrogate these data before performing any experiments. We present here a new research tool called data-driven hypothesis (DDH) for predicting pathways and functions for thousands of genes across the human genome. Importantly, this method integrates gene essentiality, gene expression, and literature mining to identify candidate molecular functions or pathways of known and unknown genes. Beyond single gene queries, DDH can uniquely handle queries of defined gene ontology pathways or custom gene lists containing multiple genes. The DDH project holds tremendous promise to generate hypotheses, data, and knowledge in order to provide a deep understanding of the dynamic properties of mammalian genes. We present this tool via an intuitive online interface, which will provide the scientific community a platform to query and prioritize experimental hypotheses to test in the lab.
Genome-Scale CRISPR Screening reveals novel factors regulating Wnt-dependent regeneration of mouse gastric organoids

An ability to safely harness the powerful regenerative potential of adult stem cells for clinical applications is critically dependent on a comprehensive understanding of the underlying mechanisms regulating their activity. Epithelial organoid cultures accurately recapitulate many features of in vivo stem cell-driven epithelial regeneration, providing an excellent ex vivo platform for interrogation of key regulatory mechanisms. Here, we employed a Genome-Scale CRISPR Knock-Out (GeCKO) screening assay using mouse gastric epithelial organoids to identify novel modulators of Wnt-driven stem cell-dependent epithelial regeneration in the gastric mucosa. In addition to known Wnt pathway regulators such as Apc, we found that knock-out (KO) of Alk, Bclaf3 or Prkra supports the Wnt independent self-renewal of gastric epithelial cells ex vivo. In adult mice, expression of these factors is predominantly restricted to non Lgr5-expressing stem cell zones above the gland base, implicating a critical role for these factors in suppressing Wnt-dependent self-renewal of gastric epithelia. Furthermore, using comprehensive RNA-sequencing analysis, we found that these factors influence epithelial regeneration by regulating Wnt signalling, apoptosis and expression of Reg family genes which could contribute to the epithelial regeneration through JAK/STAT3 pathway.
Targeted intragenic demethylation initiates chromatin rewiring for gene activation

Aberrant DNA methylation in the region surrounding the transcription start site is a hallmark of gene silencing in cancer. Currently approved demethylating agents lack specificity and exhibit high toxicity. Herein we show, using the p16 gene as an example, that targeted demethylation of the promoter-exon 1-intron 1 (PrExI) region initiates an epigenetic wave of local chromatin remodeling and distal long-range interactions, culminating in gene-locus specific activation. Through development of CRISPR-DiR (DNMT1-interacting RNA), in which ad hoc edited guides block methyltransferase activity in a locus-specific fashion, we demonstrate that demethylation is coupled to epigenetic and topological changes. These results suggest the existence of a specialized “demethylation firing center (DFC)” which can be switched on by an adaptable and selective RNA-mediated approach for locus-specific transcriptional activation. One Sentence Summary Locus demethylation via CRISPR-DiR reshapes chromatin structure and specifically reactivates its cognate gene.
VAE-SNE: a deep generative model for simultaneous dimensionality reduction and clustering

Scientific datasets are growing rapidly in scale and complexity. Consequently, the task of understanding these data to answer scientific questions increasingly requires the use of compression algorithms that reduce dimensionality by combining correlated features and cluster similar observations to summarize large datasets. Here we introduce a method for both dimension reduction and clustering called VAE-SNE (variational autoencoder stochastic neighbor embedding). Our model combines elements from deep learning, probabilistic inference, and manifold learning to produce interpretable compressed representations while also readily scaling to tens-of-millions of observations. Unlike existing methods, VAE-SNE simultaneously compresses high-dimensional data and automatically learns a distribution of clusters within the data — without the need to manually select the number of clusters. This naturally creates a multi-scale representation, which makes it straightforward to generate coarse-grained descriptions for large subsets of related observations and select specific regions of interest for further analysis. VAE-SNE can also quickly and easily embed new samples, detect outliers, and can be optimized with small batches of data, which makes it possible to compress datasets that are otherwise too large to fit into memory. We evaluate VAE-SNE as a general purpose method for dimensionality reduction by applying it to multiple real-world datasets and by comparing its performance with existing methods for dimensionality reduction. We find that VAE-SNE produces high-quality compressed representations with results that are on par with existing nonlinear dimensionality reduction algorithms. As a practical example, we demonstrate how the cluster distribution learned by VAE-SNE can be used for unsupervised action recognition to detect and classify repeated motifs of stereotyped behavior in high-dimensional timeseries data. Finally, we also introduce variants of VAE-SNE for embedding data in polar (spherical) coordinates and for embedding image data from raw pixels. VAE-SNE is a robust, feature-rich, and scalable method with broad applicability to a range of datasets in the life sciences and beyond.
Evaluating a harvest control rule to improve the sustainability of Japanese fisheries

Fisheries management in Japan is currently at a turning point. MSY based reference points have historically been rejected because of impacts on the fishing industry that would result from their adoption. We propose and evaluate a new harvest control rule (HCR) that uses the biological reference points based on sustainable yield from the stochastic hockey-stick stock recruitment relationship. Management strategy evaluation simulations conditioned on data from Japanese stocks demonstrate that the new HCR avoided recruitment overfishing while providing stable and near maximum catch. The new HCR outperformed Japan’s traditional HCR in terms of conservation, and it outperformed an alternative HCR which is widely used around the world in terms of initial catch reduction and future catch variation. For forecasting and hindcasting simulations, the new HCR showed considerable improvements over traditional HCRs in terms of biomass and catch. This new management procedure can improve the current and future status of many overfished stocks in Japan as well as increase economic efficiency and better protect ecosystems.
Brain transcriptome analysis reveals subtle effects on mitochondrial function and iron homeostasis of mutations in the SORL1 gene implicated in early onset familial Alzheimer’s disease

To prevent or delay the onset of Alzheimer’s disease (AD), we must understand its molecular basis. The great majority of AD cases arise sporadically with a late onset after 65 years of age (LOAD). However, rare familial cases of AD can occur due to dominant mutations in a small number of genes that cause an early onset prior to 65 years of age (EOfAD). As EOfAD and LOAD share similar pathologies and disease progression, analysis of EOfAD genetic models may give insight into both subtypes of AD. Sortilin-related receptor 1 ( SORL1 ) is genetically associated with both EOfAD and LOAD and provides a unique opportunity to investigate the relationships between both forms of AD. Currently, the role of SORL1 mutations in AD pathogenesis is unclear. To understand the molecular consequences of SORL1 mutation , we performed targeted mutagenesis of the orthologous gene in zebrafish. We generated an EOfAD-like mutation, V1482Afs, and a putatively null mutation, to investigate whether EOfAD-like mutations in sorl1 display haploinsufficiency by acting through loss-of-function mechanisms. We performed mRNA-sequencing on whole brains, comparing wild type fish with their siblings heterozygous for EOfAD-like or putatively loss-of-function mutations in sorl1 , or transheterozygous for these mutations. Differential gene expression analysis identified a small number of differentially expressed genes due to the sorl1 genotypes. We also performed enrichment analysis on all detectable genes to obtain a more complete view on changes to gene expression by performing three methods of gene set enrichment analysis, then calculated an overall significance value using the harmonic mean p-value. This identified subtle effects on expression of genes involved in energy production, mRNA translation and mTORC1 signalling in both the EOfAD-like and null mutant brains, implying that these effects are due to sorl1 haploinsufficiency. Surprisingly, we also observed changes to expression of genes occurring only in the EOfAD-mutation carrier brains, suggesting gain-of-function effects. Transheterozygosity for the EOfAD-like and null mutations (i.e. lacking wild type sorl1 ), caused apparent effects on iron homeostasis and other transcriptome changes distinct from the single-mutation heterozygous fish. Our results provide insight into the possible early brain molecular effects of an EOfAD mutation in human SORL1 . Differential effects of heterozygosity and complete loss of normal SORL1 expression are revealed .
Feeding ecology of the southern lanternshark (Etmopterus baxteri) and the brown lanternshark (E. unicolor) off southeastern Australia

Little is known about the ecological interactions between bycatch species and orange roughy (Hoplostethus atlanticus) within exploited slope and seamount communities off Tasmania. The diet of Etmopterus baxteri and E. unicolor, two important bycatch species of these fisheries, is described using four indices [percentage frequency of occurrence, percentage by number, percentage by weight, and percentage by the index of relative importance (%IRI)] calculated for broad prey categories, individual prey taxa, and functional prey groups. The identifiable diet of E. unicolor was dominated by benthic cephalopods (96%IRI), whereas benthic teleost prey, notably orange roughy (43%IRI), dominated the diet of E. baxteri. Similar trophic mechanisms appear to support aggregations of orange roughy and Etmopterus spp. off Tasmania; they feed on demersal species and mesopelagic or vertically migrating nekton advected laterally onto the mid-slope. The importance of teleost prey in the diet of E. baxteri apparently increases with shark length, whereas crustaceans become less important, which is a similar diet shift to that of orange roughy. Etmopterus baxteri is both a potential competitor and predator of orange roughy in these ecosystems. Fishery managers need to understand and consider the complex trophic interactions between orange roughy, sharks, and other exploited species in managing recently reopened deep-water fisheries off southeastern Australia.
The Step-Wise C-Truncation and Transport of ESyt3 to Lipid Droplets Reveals a Mother Primordial Cisterna

Extended synaptotagmins (E-Syts) are endoplasmic reticulum (ER) proteins consisting of an SMP domain and multiple C2 domains that bind phospholipids and Ca2+. E-Syts create contact junctions between the ER and plasma membrane to facilitate lipid exchange. During adipocyte differentiation, the proteasome-based removal of the C2C domain results in targeting of E-Syt3 to the primordial cisterna, a previously undescribed giant annular organelle that mothers the LDs. Further cleavage causes the E-Syt3 relocation to the surface of LDs. Fragmentation of the primordial cisterna and LD budding into its lumen are early events in the biogenesis of LDs in the 3T3-L1 adipocyte. Electron tomography-based 3D reconstruction of the fragmented primordial cisterna revealed patches of a tightly packed E-Syt3-rich network of varicose tubules in close contact with young LDs. Esyt3 binds avidly phosphatidylethanolamine through its SMP domain, a main component of the LD membrane that fosters LD biogenesis. Repression of E-Syt3 effectively inhibits LD biogenesis and growth.
Piezo1 potentially mediates inflammation in balloon-inflated rat brain and its bidirectional mechanosensitivity

Brain injury after intracerebral hemorrhage is extremely complicated, and the exact mechanism remains puzzling. Piezo1, a novel mammalian mechanosensitive ion channel, has been identified to play important roles in several pathologic and physiologic procedures that involve cellular mechanotransduction. However, the role of Piezo1 in hematoma compression after intracerebral hemorrhage is still unclear. In the present study, we established a balloon-inflated rat brain model mimicking the pure mechanical compression of a hematoma and detected balloon compression in the basal ganglia region of the brain, resulting in abnormal behaviors and a significant increase in the expression of Piezo1 and proinflammatory cytokines. These effects were reversed by GsMTx4, an antagonist of Piezo1. Additionally, the balloon deflation time affected behavioral function and the levels of Piezo1 and proinflammatory cytokines. These results establish the first in vivo evidence for the role of Piezo1 in blood-brain neuroinflammation after hematoma compression. Piezo1 may therefore be a potential therapeutic target for the treatment of intracerebral hemorrhage.
Compensating Misalignment Using Dynamic Random-Effect Control System: A Case of High-Mixed Wafer Fabrication

It is vital to have an exclusive modification in semiconductor production process because of meeting differentiated customer demands in dynamic and competitive global minuscule semiconductor technology market and the highly complex fabrication process. In this paper, we propose a control system based on the dynamic mixed-effect least-square support vector regression (LS-SVR) control system for overlay error compensation with stochastic metrology delay to minimize the misalignment of the patterning process. Moreover, for the stability of the control system in the presence of metrology delay and to deal with nonlinearity among the overlay factors, the novel Lyapunov-based kernel function is merged with the LS-SVR controller. The proposed controller’s operation has been validated and implemented by a major semiconductor manufacturer in Taiwan. The experiments are verified that mixed-effect LS-SVR controller has the higher validity and higher efficiency in comparison with the exponentially weighted moving average (EWMA) and threaded EWMA controllers which had been previously implemented at the company or applied in similar studies. Note to Practitioners—Due to high production complexity in semiconductor manufacturing process, a meticulous and intelligent process control is needed to achieve higher throughput and customer satisfaction. Monitoring a complex system is challenging because the process components and variables operate autonomously and interoperate with other manufacturing segments. This paper proposes a novel run-to-run (R2R) control system to compensate the overlay error during the photolithography process that efficiently deals with the high-mixed manufacturing environment and metrology delay.
uBin – a manual refining tool for metagenomic bins designed for educational purposes

Resolving bacterial and archaeal genomes from metagenomes has revolutionized our understanding of Earth’s biomes, yet producing high quality genomes from assembled fragments has been an ever-standing problem. While automated binning software and their combination produce prokaryotic bins in high-throughput, their manual refinement has been slow and sometimes difficult. Here, we present uBin, a GUI-based, standalone bin refiner that runs on all major operating platforms and was specifically designed for educational purposes. When applied to the public CAMI dataset, refinement of bins was able to improve 78.9% of bins by decreasing their contamination. We also applied the bin refiner as a standalone binner to public metagenomes from the International Space Station and demonstrate the recovery of near-complete genomes, whose replication indices indicate active proliferation of microbes in Earth’s lower orbit. uBin is an easy to install software for bin refinement, binning of simple metagenomes and communication of metagenomic results to other scientists and in classrooms. The software is open source and available under https://github.com/ProbstLab/uBin.
Perceptual responses to microstimulation frequency are spatially organized in human somatosensory cortex

Microstimulation in the somatosensory cortex can evoke artificial tactile percepts and can be incorporated into bidirectional brain-computer interfaces (BCIs) to restore function after injury or disease. However, little is known about how stimulation parameters themselves affect perception. Here, we stimulated through microelectrode arrays implanted in the somatosensory cortex of a human participant with a cervical spinal cord injury and varied the stimulus amplitude, duration, and frequency. Increasing the amplitude and duration increased the perceived intensity on all tested electrodes. Surprisingly, we found that increasing the frequency evoked more intense percepts on some electrodes but evoked less intense percepts on most electrodes. Electrodes divided into three groups which evoked distinct perceptual qualities that depended on the stimulus frequency and were spatially organized in cortex. These results contribute to our growing understanding of the structure and function of the somatosensory cortex and will facilitate principled development of stimulation strategies for bidirectional BCIs.