Miracle-dz/UniFAR-FTUs huggingface dataset:
A marmoset brain cell census reveals influence of developmental origin and functional class on neuronal identity

The mammalian brain is composed of many brain structures, each with its own ontogenetic and developmental history. Transcriptionally-based cell type taxonomies reveal cell type composition and similarity relationships within and across brain structures. We sampled over 2.4 million brain cells across 18 locations in the common marmoset, a New World monkey primed for genetic engineering, and used single-nucleus RNA sequencing to examine global gene expression patterns of cell types within and across brain structures. Our results indicate that there is generally a high degree of transcriptional similarity between GABAergic and glutamatergic neurons found in the same brain structure, and there are generally few shared molecular features between neurons that utilize the same neurotransmitter but reside in different brain structures. We also show that in many cases the transcriptional identities of cells are intrinsically retained from their birthplaces, even when they migrate beyond their cephalic compartments. Thus, the adult transcriptomic identity of most neuronal types appears to be shaped much more by their developmental identity than by their primary neurotransmitter signaling repertoire. Using quantitative mapping of single molecule FISH (smFISH) for markers for GABAergic interneurons, we found that the similar types (e.g. PVALB+ interneurons) have distinct biodistributions in the striatum and neocortex. Interneuron types follow medio-lateral gradients in striatum but form complex distributions across the neocortex that are not described by simple gradients. Lateral prefrontal areas in marmoset are distinguished by high relative proportions of VIP+ neurons. We further used cell-type-specific enhancer driven AAV-GFP to visualize the morphology of molecularly-resolved interneuron classes in neocortex and striatum, including the previously discovered novel primate-specific TAC3+ striatal interneurons. Our comprehensive analyses highlight how lineage and functional class contribute to the transcriptional identity and biodistribution of primate brain cell types. One-Sentence Summary Adult primate neurons are imprinted by their region of origin, more so than by their functional identity.
the near wake dynamics for a square prism Numerical and experimental investigation of

regions. two regions is obtained by analyzing the phase averaged streamlines for both workers for different bluff bodies. New inside into the vortex dynamics of the vortex shedding mechanism is similar to the models proposed by Perry and coand phase averaged velocity field is analyzed. It is found that the near wake numerically (LES) and experimentally (LDV) investigated. The time averaged The shear layer formation and the near wake regions of a square prism are
The Parameterized Complexity of Coordinated Motion Planning

In Coordinated Motion Planning (CMP), we are given a rectangular-grid on which $k$ robots occupy $k$ distinct starting gridpoints and need to reach $k$ distinct destination gridpoints. In each time step, any robot may move to a neighboring gridpoint or stay in its current gridpoint, provided that it does not collide with other robots. The goal is to compute a schedule for moving the $k$ robots to their destinations which minimizes a certain objective target - prominently the number of time steps in the schedule, i.e., the makespan, or the total length traveled by the robots. We refer to the problem arising from minimizing the former objective target as CMP-M and the latter as CMP-L. Both CMP-M and CMP-L are fundamental problems that were posed as the computational geometry challenge of SoCG 2021, and CMP also embodies the famous $(n^2-1)$-puzzle as a special case. In this paper, we settle the parameterized complexity of CMP-M and CMP-L with respect to their two most fundamental parameters: the number of robots, and the objective target. We develop a new approach to establish the fixed-parameter tractability of both problems under the former parameterization that relies on novel structural insights into optimal solutions to the problem. When parameterized by the objective target, we show that CMP-L remains fixed-parameter tractable while CMP-M becomes para-NP-hard. The latter result is noteworthy, not only because it improves the previously-known boundaries of intractability for the problem, but also because the underlying reduction allows us to establish - as a simpler case - the NP-hardness of the classical Vertex Disjoint and Edge Disjoint Paths problems with constant path-lengths on grids.
Line Intersection Searching Amid Unit Balls in 3-Space

Let B be a set of n unit balls in R 3 . We present a linear-size data structure for storing B that can determine in O ∗ ( n 1 / 2 ) time whether a query line intersects any ball of B and report all k such balls in additional O ( k ) time. The data structure can be constructed in O ( n log n ) time. (The O ∗ ( · ) notation hides subpolynomial factors, e.g., of the form O ( n ε ), for arbitrarily small ε > 0, and their coefficients which depend on ε . ) We also consider the dual problem: Let L be a set of n lines in R 3 . We preprocess L , in O ∗ ( n 2 ) time, into a data structure of size O ∗ ( n 2 ) that can determine in O ∗ (1) time whether a query unit ball intersects any line of L , or report all k such lines in additional O ( k ) time. 2012 ACM Subject Classification Theory of computation; Theory of computation → Computational geometry
Slice, Simplify and Stitch: Topology-Preserving Simplification Scheme for Massive Voxel Data

We focus on efficient computations of topological descriptors for voxel data. This type of data includes 2D greyscale images, 3D medical scans, but also higher-dimensional scalar fields arising from physical simulations. In recent years we have seen an increase in applications of topological methods for such data. However, computational issues remain an obstacle. We therefore propose a streaming scheme which simplifies large 3-dimensional voxel data – while provably retaining its persistent homology. We combine this scheme with an efficient boundary matrix reduction implementation, obtaining an end-to-end tool for persistent homology of large data. Computational experiments show its state-of-the-art performance. In particular, we are now able to robustly handle complex datasets with several billions voxels on a regular laptop. A software implementation called Cubicle is available as open-source: https://bitbucket.org/ hubwag/cubicle .
Non-consciously processed physical activity for survival versus consciously deliberated exercise for health

Humans evolved to become dependent on physical activity for their survival, but they have not evolved to exercise today. Because survival in modern society is heavily reliant on conscious thinking, most people (54%) have evolved away from physical activity and become occasional exercisers. This transition from non-conscious to conscious processing prevents people from capitalizing on evolution’s wisdom for survival and wellbeing as they consciously deliberate on the utility of health practices to achieve certain outcomes (e.g., weight loss). Unlike in early times, people today have a choice of not engaging in physical activity and yet surviving. As a result, they struggle with the question whether the gains from exercising are greater than losses from not doing it, weighing positive gains and losses against negative gains and losses. Such conscious deliberations, however, can easily be overridden by solving cognitive dissonance (e.g., “exercise is good for my health” vs. “I don’t exercise”) through conscious rationalizations and non-conscious dismissal. Today’s exercise problem can only be solved by individually acquiring the mindset of early times of evolution when the initiation of physical activity was largely a matter of non-conscious thoughts and feelings.
Temporal–spatial dynamics of typical ecosystem services in the Chaobai River basin in the Beijing-Tianjin-Hebei urban megaregion

Human demand for ecosystem services dominates ecosystem changes and impacts the temporal–spatial patterns of ecosystem services and their trade- offs. In the process of urbanization, the supply service, regulation service, and cultural service of the ecosystem are difficult to improve in synergy in the city and its surrounding areas, which is tough for urban construction and development. This study took the Chaobai River basin located in the Beijing-Tianjin-Hebei urban megaregion in northern China as the research area. The temporal and spatial changes from 2000 to 2015 of three typical ecosystem services in the study area, including food production, water conservation, and recreation, were evaluated and analyzed through modeling. The ecosystem service hotspots, service-gain areas, and service-loss areas were identified based on spatial analysis. The dynamic change mechanism of ecosystem services was explored from the perspective of land use change and hotspot analysis. The results showed that (1) recreation and food production services showed an increasing trend, while water conservation showed a fluctuating increasing trend. (2) The service-gain area was significantly larger than the service-loss area. (3) The main land use change form in the study area during the study period was the regional conversion of cultivated land to forest land and construction land, which led to the increase in water conservation services and the reduction of food production services in the corresponding patches. However, this conversion did not affect the overall improvement of the three ecosystem services in the study area. (4) Ecosystem service hotspots have gradually changed from being single-service dominant to two co-leading services. The area of food production-recreation hotspots continued to increase, indicating synergy between them. The area of water conservation-recreation hotspots continued to decrease, indicating trade-offs between them. Different types of ecosystem services improve in synergy in the Beijing-Tianjin-Hebei urban megaregion in the process of urbanization through the improvement of agricultural technology and productivity and the promotion of leisure and sightseeing agriculture. This provides an example for other cities.
A novel ACE2 decoy for both neutralization of SARS-CoV-2 variants and killing of infected cells

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to millions of infections and deaths worldwide. As this virus evolves rapidly, there is a high need for treatment options that can win the race against new emerging variants of concern. Here, we describe a novel immunotherapeutic drug based on the SARS-CoV-2 entry receptor ACE2 and provide experimental evidence that it cannot only be used for (i) neutralization of SARS-CoV-2 in vitro and in SARS-CoV-2-infected animal models but also for (ii) clearance of virus-infected cells. For the latter purpose, we equipped the ACE2 decoy with an epitope tag. Thereby, we converted it to an adapter molecule, which we successfully applied in the modular platforms UniMAB and UniCAR for retargeting of either unmodified or universal chimeric antigen receptor-modified immune effector cells. Our results pave the way for a clinical application of this novel ACE2 decoy, which will clearly improve COVID-19 treatment.
Leveraging technology in public-private partnerships: a model to address public health inequities

Long-standing inequities in healthcare access and outcomes exist for underserved populations. Public-private partnerships (PPPs) are where the government and a private entity jointly invest in the provision of public services. Using examples from the Health Equity Consortium (HEC), we describe how technology was used to facilitate collaborations between public and private entities to address health misinformation, reduce vaccine hesitancy, and increase access to primary care services across various underserved communities during the COVID-19 pandemic. We call out four enablers of effective collaboration within the HEC-led PPP model, including: 1. Establishing trust in the population to be served 2. Enabling bidirectional flow of data and information 3. Mutual value creation and 4. Applying analytics and AI to help solve complex problems. Continued evaluation and improvements to the HEC-led PPP model are needed to address post-COVID-19 sustainability.
Associations between underlying diseases with COVID-19 and its symptoms among adults: a cross-sectional study

Background Specific underlying diseases were reported to be associated with severe COVID-19 outcomes, but little is known about their combined associations. The study was aimed to assess the relations of number of and specific underlying diseases to COVID-19, severe symptoms, loss of smell, and loss of taste. Methods A total of 28,204 adult participants in the National Health Interview Survey 2021 were included. Underlying diseases (including cardiovascular diseases, cancer, endocrine diseases, respiratory diseases, neuropsychiatric diseases, liver and kidney diseases, fatigue syndrome, and sensory impairments), the history of COVID-19, and its symptoms were self-reported by structured questionnaires. Multivariable logistic regression models were used to assess the combined relation of total number of underlying diseases to COVID-19 and its symptoms, while mutually adjusted logistic models were used to examine their independent associations. Results Among the 28,204 participants (mean ± standard deviation: 48.2 ± 18.5 years), each additional underlying disease was related to 33, 20, 37, and 39% higher odds of COVID-19 (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.29–1.37), severe symptoms (OR: 1.20, 95% CI: 1.12–1.29), loss of smell (OR: 1.37, 95% CI: 1.29–1.46), and loss of taste (OR: 1.39, 95% CI: 1.31–1.49). In addition, independent associations of sensory impairments with COVID-19 (OR: 3.73, 95% CI: 3.44–4.05), severe symptoms (OR: 1.37, 95% CI: 1.13–1.67), loss of smell (OR: 8.17, 95% CI: 6.86–9.76), and loss of taste (OR: 6.13, 95% CI: 5.19–7.25), cardiovascular diseases with COVID-19 (OR: 1.13, 95% CI: 1.03–1.24), neuropsychiatric diseases with severe symptoms (OR: 1.41, 95% CI: 1.15–1.74), and endocrine diseases with loss of taste (OR: 1.28, 95% CI: 1.05–1.56) were observed. Conclusion A larger number of underlying diseases were related to higher odds of COVID-19, severe symptoms, loss of smell, and loss of taste in a dose–response manner. Specific underlying diseases might be individually associated with COVID-19 and its symptoms.
Identification of candidate genes for soybean seed coat-related traits using QTL mapping and GWAS

Seed coat color is a typical morphological trait that can be used to reveal the evolution of soybean. The study of seed coat color-related traits in soybeans is of great significance for both evolutionary theory and breeding practices. In this study, 180 F10 recombinant inbred lines (RILs) derived from the cross between the yellow-seed coat cultivar Jidou12 (ZDD23040, JD12) and the wild black-seed coat accession Y9 (ZYD02739) were used as materials. Three methods, single-marker analysis (SMA), interval mapping (IM), and inclusive composite interval mapping (ICIM), were used to identify quantitative trait loci (QTLs) controlling seed coat color and seed hilum color. Simultaneously, two genome-wide association study (GWAS) models, the generalized linear model (GLM) and mixed linear model (MLM), were used to jointly identify seed coat color and seed hilum color QTLs in 250 natural populations. By integrating the results from QTL mapping and GWAS analysis, we identified two stable QTLs (qSCC02 and qSCC08) associated with seed coat color and one stable QTL (qSHC08) related to seed hilum color. By combining the results of linkage analysis and association analysis, two stable QTLs (qSCC02, qSCC08) for seed coat color and one stable QTL (qSHC08) for seed hilum color were identified. Upon further investigation using Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we validated the previous findings that two candidate genes (CHS3C and CHS4A) reside within the qSCC08 region and identified a new QTL, qSCC02. There were a total of 28 candidate genes in the interval, among which Glyma.02G024600, Glyma.02G024700, and Glyma.02G024800 were mapped to the glutathione metabolic pathway, which is related to the transport or accumulation of anthocyanin. We considered the three genes as potential candidate genes for soybean seed coat-related traits. The QTLs and candidate genes detected in this study provide a foundation for further understanding the genetic mechanisms underlying soybean seed coat color and seed hilum color and are of significant value in marker-assisted breeding.
Clinical and bi-genomic DNA findings of patients suspected to have mitochondrial diseases

Background: Mitochondrial diseases are the most common group of inherited metabolic disorders, causing difficulties in definite diagnosis due to clinical and genetic heterogeneity. Clinical components are predominantly associated with pathogenic variants shown in nuclear or mitochondrial genomes that affect vital respiratory chain function. The development of high-throughput sequencing technologies has accelerated the elucidation of the genetic etiology of many genetic diseases that previously remained undiagnosed. Methods: Thirty affected patients from 24 unrelated families with clinical, radiological, biochemical, and histopathological evaluations considered for mitochondrial diseases were investigated. DNA isolated from the peripheral blood samples of probands was sequenced for nuclear exome and mitochondrial DNA (mtDNA) analyses. MtDNA sequencing was also performed from the muscle biopsy material in one patient. For segregation, Sanger sequencing is performed for pathogenic alterations in five other affected family members and healthy parents. Results: Exome sequencing revealed 14 different pathogenic variants in nine genes encoding mitochondrial function peptides (AARS2, EARS2, ECHS1, FBXL4, MICOS13, NDUFAF6, OXCT1, POLG, and TK2) in 12 patients from nine families and four variants in genes encoding important for muscle structure (CAPN3, DYSF, and TCAP) in six patients from four families. Three probands carried pathogenic mtDNA variations in two genes (MT-ATP6 and MT-TL1). Nine variants in five genes are reported for the first time with disease association: (AARS2: c.277C>T/p.(R93*), c.845C>G/p.(S282C); EARS2: c.319C>T/p.(R107C), c.1283delC/p.(P428Lfs*); ECHS1: c.161G>A/p.(R54His); c.202G>A/p.(E68Lys); NDUFAF6: c.479delA/p.(N162Ifs*27); and OXCT1: c.1370C>T/p.(T457I), c.1173-139G>T/p.(? ). Conclusion: Bi-genomic DNA sequencing clarified genetic etiology in 67% (16/24) of the families. Diagnostic utility by mtDNA sequencing in 13% (3/24) and exome sequencing in 54% (13/24) of the families prioritized searching for nuclear genome pathologies for the first-tier test. Weakness and muscle wasting observed in 17% (4/24) of the families underlined that limb-girdle muscular dystrophy, similar to mitochondrial myopathy, is an essential point for differential diagnosis. The correct diagnosis is crucial for comprehensive genetic counseling of families. Also, it contributes to making treatment-helpful referrals, such as ensuring early access to medication for patients with mutations in the TK2 gene.
Inter-rater agreement for the annotation of neurologic signs and symptoms in electronic health records

The extraction of patient signs and symptoms recorded as free text in electronic health records is critical for precision medicine. Once extracted, signs and symptoms can be made computable by mapping to signs and symptoms in an ontology. Extracting signs and symptoms from free text is tedious and time-consuming. Prior studies have suggested that inter-rater agreement for clinical concept extraction is low. We have examined inter-rater agreement for annotating neurologic concepts in clinical notes from electronic health records. After training on the annotation process, the annotation tool, and the supporting neuro-ontology, three raters annotated 15 clinical notes in three rounds. Inter-rater agreement between the three annotators was high for text span and category label. A machine annotator based on a convolutional neural network had a high level of agreement with the human annotators but one that was lower than human inter-rater agreement. We conclude that high levels of agreement between human annotators are possible with appropriate training and annotation tools. Furthermore, more training examples combined with improvements in neural networks and natural language processing should make machine annotators capable of high throughput automated clinical concept extraction with high levels of agreement with human annotators.
Changes in Medicago truncatula seed proteome along the rehydration–dehydration cycle highlight new players in the genotoxic stress response

Introduction Several molecular aspects underlying the seed response to priming and the resulting vigor profile are still poorly understood. Mechanisms involved in genome maintenance deserve attention since the balance between stimulation of germination and DNA damage accumulation versus active repair is a key determinant for designing successful seed priming protocols. Methods Changes in the Medicago truncatula seed proteome were investigated in this study, using discovery mass spectrometry and label-free quantification, along the rehydration-dehydration cycle of a standard vigorization treatment (hydropriming plus dry-back), and during post-priming imbibition. Resuts and discussion From 2056 to 2190 proteins were detected in each pairwise comparison, among which six were differentially accumulated and 36 were detected only in one condition. The following proteins were selected for further investigation: MtDRP2B (DYNAMIN-RELATED PROTEIN), MtTRXm4 (THIOREDOXIN m4), and MtASPG1 (ASPARTIC PROTEASE IN GUARD CELL 1) showing changes in seeds under dehydration stress; MtITPA (INOSINE TRIPHOSPHATE PYROPHOSPHORYLASE), MtABA2 (ABSCISIC ACID DEFICIENT 2), MtRS2Z32 (SERINE/ARGININE-RICH SPLICING FACTOR RS2Z32), and MtAQR (RNA HELICASE AQUARIUS) that were differentially regulated during post-priming imbibition. Changes in the corresponding transcript levels were assessed by qRT-PCR. In animal cells, ITPA hydrolyses 2’-deoxyinosine triphosphate and other inosine nucleotides, preventing genotoxic damage. A proof of concept was performed by imbibing primed and control M. truncatula seeds in presence/absence of 20 mM 2’-deoxyinosine (dI). Results from comet assay highlighted the ability of primed seeds to cope with dI-induced genotoxic damage. The seed repair response was assessed by monitoring the expression profiles of MtAAG (ALKYL-ADENINE DNA GLYCOSILASE) and MtEndoV (ENDONUCLEASE V) genes that participate in the repair of the mismatched I:T pair in BER (base excision repair) and AER (alternative excision repair) pathways, respectively.
Loss of TDP-43 causes ectopic endothelial sprouting and migration defects through increased fibronectin, vcam 1 and integrin α4/β1

Aggregation of the Tar DNA-binding protein of 43 kDa (TDP-43) is a pathological hallmark of amyotrophic lateral sclerosis and frontotemporal dementia and likely contributes to disease by loss of nuclear function. Analysis of TDP-43 function in knockout zebrafish identified an endothelial directional migration and hypersprouting phenotype during development prior lethality. In human umbilical vein cells (HUVEC) the loss of TDP-43 leads to hyperbranching. We identified elevated expression of FIBRONECTIN 1 (FN1), the VASCULAR CELL ADHESION MOLECULE 1 (VCAM1), as well as their receptor INTEGRIN α4β1 (ITGA4B1) in HUVEC cells. Importantly, reducing the levels of ITGA4, FN1, and VCAM1 homologues in the TDP-43 loss-of-function zebrafish rescues the angiogenic defects indicating the conservation of human and zebrafish TDP-43 function during angiogenesis. Our study identifies a novel pathway regulated by TDP-43 important for angiogenesis during development.