Miracle-dz/UniFAR-FTUs huggingface dataset:
Autism-Associated Variant in the SLC6A3 Gene Alters the Oral Microbiome and Metabolism in a Murine Model

Background: Altered dopamine (DA) signaling has been associated with autism spectrum disorder (ASD), a neurodevelopmental condition estimated to impact 1 in 54 children in the United States. There is growing evidence for alterations in both gastrointestinal function and oral microbiome composition in ASD. Recent work suggests that rare variants of the SLC6A3 gene encoding the DA transporter (DAT) identified in individuals with ASD result in structural and functional changes to the DAT. One such recently identified de novo mutation is a threonine to methionine substitution at position 356 of the DAT (DAT T356M). The DAT T356M variant is associated with ASD-like phenotypes in mice homozygous for the mutation (DAT T356M+/+), including social deficits, hyperactivity, and impaired DA signaling. Here, we determine the impact of this altered DA signaling as it relates to altered oral microbiota, and metabolic and gastrointestinal dysfunction. Methods: In the DAT T356M+/+ mouse, we determine the oral microbiota composition, metabolic function, and gastrointestinal (GI) function. We examined oral microbiota by 16S RNA sequencing. We measured metabolic function by examining glucose tolerance and we probed gastrointestinal parameters by measuring fecal dimensions and weight. Results: In the DAT T356M+/+ mouse, we evaluate how altered DA signaling relates to metabolic dysfunction and altered oral microbiota. We demonstrate that male DAT T356M+/+ mice weigh less (Wild type (WT) = 26.48 ± 0.6405 g, DAT T356M+/+ = 24.14 ± 0.4083 g) and have decreased body fat (WT = 14.89 ± 0.6206%, DAT T356M+/+ = 12.72 ± 0.4160%). These mice display improved glucose handling (WT = 32.60 ± 0.3298 kcal/g, DAT T356M+/+ = 36.97 ± 0.4910 kcal/g), and an altered oral microbiota. We found a significant decrease in Fusobacterium abundance. The abundance of Fusobacterium was associated with improved glucose handling and decreased body fat. Conclusions: Our findings provide new insights into how DAT dysfunction may alter gastrointestinal function, composition of the oral microbiota, and metabolism. Our data suggest that impaired DA signaling in ASD is associated with a number of metabolic and gastrointestinal changes which are common in individuals with ASD.
Promoting the Performance of Li–CO2 Batteries via Constructing Three-Dimensional Interconnected K+ Doped MnO2 Nanowires Networks

Nowadays, Li–CO2 batteries have attracted enormous interests due to their high energy density for integrated energy storage and conversion devices, superiorities of capturing and converting CO2. Nevertheless, the actual application of Li–CO2 batteries is hindered attributed to excessive overpotential and poor lifespan. In the past decades, catalysts have been employed in the Li–CO2 batteries and been demonstrated to reduce the decomposition potential of the as-formed Li2CO3 during charge process with high efficiency. However, as a representative of promising catalysts, the high costs of noble metals limit the further development, which gives rise to the exploration of catalysts with high efficiency and low cost. In this work, we prepared a K+ doped MnO2 nanowires networks with three-dimensional interconnections (3D KMO NWs) catalyst through a simple hydrothermal method. The interconnected 3D nanowires network catalysts could accelerate the Li ions diffusion, CO2 transfer and the decomposition of discharge products Li2CO3. It is found that high content of K+ doping can promote the diffusion of ions, electrons and CO2 in the MnO2 air cathode, and promote the octahedral effect of MnO6, stabilize the structure of MnO2 hosts, and improve the catalytic activity of CO2. Therefore, it shows a high total discharge capacity of 9,043 mAh g−1, a low overpotential of 1.25 V, and a longer cycle performance.
Balloon-Assisted Coils Embolization for Ophthalmic Segment Aneurysms of the Internal Carotid Artery

Objective: To explore the role of balloon-assisted coils technique for ophthalmic segment aneurysms (OSAS). Methods: Clinical data of 30 patients with OSAS were reviewed between December 2017 and December 2018. OSAS were defined as arising from the internal carotid artery (ICA), reaching from the distal dural ring to the origin of the posterior communicating artery. OSAS were classified into four types based on the angiographic findings. The balloon-assisted coils technique was used for the embolization of aneurysms. The duration of balloon inflation cycles, as well as difficulty and complications during the embolization procedure, were recorded. The immediate angiographic results were evaluated according to the Raymond scale. Clinical results were evaluated based on the MRS score. Follow-ups were performed at 18 months post-embolization by DSA or MRA at our institution. Results: Thirty-two aneurysms in 30 patients were detected by digital subtraction angiography (DSA), which included 30 unruptured and two ruptured cases. The patients with ruptured aneurysms were grade II status according to the Hunt-Hess scale. Three cases were type A, nine cases were type B, 17 cases were type C, and three cases were type D. According to aneurysm size, there were 19 cases of small, 11 cases of medium, two cases of large aneurysm. Thirty-two aneurysms were successfully embolized in 30 patients by balloon-assisted coils technique. The ophthalmic artery could be protected by an engorged balloon in the procedure, especially for type A aneurysms. Considering that type D aneurysm arises from the side-wall of the artery and near to tortuous ICA siphon, the balloon catheter was inflated to stabilize the microcatheter allowing for overinflation when necessary. The average duration of balloon dilatation was 4 min, and the average time was 2.5 times. Raymond class was one in 28 aneurysms and two in four aneurysms according to the immediate post-embolization angiographic results. All the patients achieved good clinical effects, except for one patient who presented with brain ischemia resulting in dizziness and contralateral limb weakness for 10 h due to prolonged temporary clamping of the responsible ICA. The follow-up angiography results were satisfactory at 18 months post-embolization. Conclusion: OSAS endovascular treatment with balloon-assisted coils has different advantages in a different classification. The technique is safe, effective, and relatively inexpensive, especially for small and medium OSAS.
Opportunities to Apply Precision Livestock Management on Rangelands

Precision livestock management has become a new field of study as the result of recent advancements in real-time global positioning system (GPS) tracking, accelerometer and other sensor technologies. Real-time tracking and accelerometer monitoring has the potential to remotely detect livestock disease, animal well-being and grazing distribution issues and notify ranchers and graziers so that they can respond as soon as possible. On-going research has shown that accelerometers can remotely monitor livestock behavior and detect activity changes that are associated with disease and parturition. GPS tracking can also detect parturition by monitoring the distance between a ewe and the remainder of the flock. Tracking also has the potential to detect water system failures. Combinations of GPS tracking and accelerometer monitoring may be more accurate than either device used by itself. Real-time GPS tracking can identify when livestock congregate in environmental sensitive areas which may allow managers the chance to respond before resource degradation occurs. Identification of genetic markers associated with terrain use, decreased cost of GPS tracking and novel tracking data processing should facilitate development of tools needed for genetic selection for cattle grazing distribution. Precision livestock management has potential to improve welfare of livestock grazing rangelands and forested lands, reduce labor costs and improve ranch profitability and improve the condition and sustainability of riparian areas and other environmental sensitive areas on grazing lands around the world.
A Metabolic Landscape for Maintaining Retina Integrity and Function

Neurons have high metabolic demands that are almost exclusively met by glucose supplied from the bloodstream. Glucose is utilized in complex metabolic interactions between neurons and glia cells, described by the astrocyte-neuron lactate shuttle (ANLS) hypothesis. The neural retina faces similar energy demands to the rest of the brain, with additional high anabolic needs to support continuous renewal of photoreceptor outer segments. This demand is met by a fascinating variation of the ANLS in which photoreceptors are the central part of a metabolic landscape, using glucose and supplying surrounding cells with metabolic intermediates. In this review we summarize recent evidence on how neurons, in particular photoreceptors, meet their energy and biosynthetic requirements by comprising a metabolic landscape of interdependent cells.
Immunological Consequences of In Utero Exposure to Foreign Antigens

Immunologic tolerance refers to a state of immune nonreactivity specific to particular antigens as an important issue in the field of transplantation and the management of autoimmune diseases. Tolerance conceptually originated from Owen’s observation of blood cell sharing in twin calves. Owen’s conceptual framework subsequently constituted the backbone of Medawar’s “actively acquired tolerance” as the major tenet of modern immunology. Based upon this knowledge, the delivery of genetically distinct hematopoietic stem cells into pre-immune fetuses represented a novel and unique approach to their engraftment without the requirement of myeloablation or immunosuppression. It might also make fetal recipients commit donor alloantigens to memory of their patterns as “self” so as to create a state of donor-specific tolerance. Over the years, the effort made experimentally or clinically toward in utero marrow transplantation could not reliably yield sufficient hematopoietic chimerism for curing candidate diseases as anticipated, nor did allogeneic graft tolerance universally develop as envisaged by Medawar following in utero exposure to various forms of alloantigens from exosomes, lymphocytes or marrow cells. Enduring graft tolerance was only conditional on a state of significant hematopoietic chimerism conferred by marrow inocula. Notably, fetal exposure to ovalbumin, oncoprotein and microbial antigens did not elicit immune tolerance, but instead triggered an event of sensitization to the antigens inoculated. These fetal immunogenic events might be clinically relevant to prenatal imprinting of atopy, immune surveillance against developmental tumorigenesis, and prenatal immunization against infectious diseases. Briefly, the immunological consequences of fetal exposure to foreign antigens could be tolerogenic or immunogenic, relying upon the type or nature of antigens introduced. Thus, the classical school of “actively acquired tolerance” might oversimplify the interactions between developing fetal immune system and antigens. Such interactions might rely upon fetal macrophages, which showed up earlier than lymphocytes and were competent to phagocytose foreign antigens so as to bridge toward antigen-specific adaptive immunity later on in life. Thus, innate fetal macrophages may be the potential basis for exploring how the immunological outcome of fetal exposure to foreign antigens is determined to improve the likelihood and reliability of manipulating fetal immune system toward tolerization or immunization to antigens.
Permeability studies of lipid vesicles by Fluorescence Correlation Spectroscopy and Monte Carlo simulations

Unmodified phospholipid membranes show a pronounced increase in the transmembrane permeability in the gel-fluid phase transition regime. Fluorescence correlation spectroscopy was used to determine the characteristic time it takes for the fluorescence dye rhodamine 6G chloride to escape from large unilamellar vesicles composed of dipalmitoylphosphatidylcholine. The observed selfdiffusion rates of the fluorophores could be changed by more than six orders of magnitude by inducing a phase transition in the membranes by adjusting the temperature or adding a general anaesthetic to the phospholipid membranes. The results are compared to numerical simulations based on the Monte Carlo method. In the numerical model the pore formation processes are similarly found to be closely coupled to the area fluctuations of the membrane, which are also strongest at the transition point. Acknowledgements First of all, I wish to thank my supervisor Thomas Heimburg. He has been a great source of inspiration, and without his help this project would not have been possible. I also wish to thank the members of the NBI Membrane Biophysics Group for their patience and willingness to help, and in particular Konrad Kaufmann for an excellent discussion about the history of the field. I would also like to show my gratitude to the people on the Kb-floor at the Niels Bohr Institute for keeping me entertained and sane during the writing of this thesis. Lastly, I wish to thank Lars Holm Ogendal for providing the Dynamic Light Scattering data as well as thoughtful discussion and good genes. A note on figures All of the figures in this thesis were made using • IGOR Pro (www.wavemetrics.com) • CorelDRAW X3 (www.corel.com) • PyMOL (pymol.sourceforge.net) • POVray (www.povray.org) Unless explicitly noted otherwise, all figures were made by Andreas Blicher. Some figures have been adapted from other sources, meaning that the data was extracted from the original figure and then replotted.
Bacterial Hsp90 Facilitates the Degradation of Aggregation-Prone Hsp70–Hsp40 Substrates

In eukaryotes, the 90-kDa heat shock proteins (Hsp90s) are profusely studied chaperones that, together with 70-kDa heat shock proteins (Hsp70s), control protein homeostasis. In bacteria, however, the function of Hsp90 (HtpG) and its collaboration with Hsp70 (DnaK) remains poorly characterized. To uncover physiological processes that depend on HtpG and DnaK, we performed comparative quantitative proteomic analyses of insoluble and total protein fractions from unstressed wild-type (WT) Escherichia coli and from knockout mutants ΔdnaKdnaJ (ΔKJ), ΔhtpG (ΔG), and ΔdnaKdnaJΔhtpG (ΔKJG). Whereas the ΔG mutant showed no detectable proteomic differences with wild-type, ΔKJ expressed more chaperones, proteases and ribosomes and expressed dramatically less metabolic and respiratory enzymes. Unexpectedly, we found that the triple mutant ΔKJG showed higher levels of metabolic and respiratory enzymes than ΔKJ, suggesting that bacterial Hsp90 mediates the degradation of aggregation-prone Hsp70–Hsp40 substrates. Further in vivo experiments suggest that such Hsp90-mediated degradation possibly occurs through the HslUV protease.
Numerosities and Other Magnitudes in the Brains: A Comparative View

The ability to represent, discriminate, and perform arithmetic operations on discrete quantities (numerosities) has been documented in a variety of species of different taxonomic groups, both vertebrates and invertebrates. We do not know, however, to what extent similarity in behavioral data corresponds to basic similarity in underlying neural mechanisms. Here, we review evidence for magnitude representation, both discrete (countable) and continuous, following the sensory input path from primary sensory systems to associative pallial territories in the vertebrate brains. We also speculate on possible underlying mechanisms in invertebrate brains and on the role played by modeling with artificial neural networks. This may provide a general overview on the nervous system involvement in approximating quantity in different animal species, and a general theoretical framework to future comparative studies on the neurobiology of number cognition.
Engineering Tunneling Selector to Achieve High Non-linearity for 1S1R Integration

Memristor devices have been extensively studied as one of the most promising technologies for next-generation non-volatile memory. However, for the memristor devices to have a real technological impact, they must be densely packed in a large crossbar array (CBA) exceeding Gigabytes in size. Devising a selector device that is CMOS compatible, 3D stackable, and has a high non-linearity (NL) and great endurance is a crucial enabling ingredient to reach this goal. Tunneling based selectors are very promising in these aspects, but the mediocre NL value limits their applications in large passive crossbar arrays. In this work, we demonstrated a trilayer tunneling selector based on the Ge/Pt/TaN1+x/Ta2O5/TaN1+x/Pd layers that could achieve a NL of 3 × 105, which is the highest NL achieved using a tunnel selector so far. The record-high tunneling NL is partially attributed to the bottom electrode's ultra-smoothness (BE) induced by a Ge/Pt layer. We further demonstrated the feasibility of 1S1R (1-selector 1-resistor) integration by vertically integrating a Pd/Ta2O5/Ru based memristor on top of the proposed selector.
Comprehensive RNA-Seq Analysis of Potential Therapeutic Targets of Gan–Dou–Fu–Mu Decoction for Treatment of Wilson Disease Using a Toxic Milk Mouse Model

Background: Gan–Dou–Fu–Mu decoction (GDFMD) improves liver fibrosis in experimental and clinical studies including those on toxic mouse model of Wilson disease (Model). However, the mechanisms underlying the effect of GDFMD have not been characterized. Herein, we deciphered the potential therapeutic targets of GDFMD using transcriptome analysis. Methods: We constructed a tx-j Wilson disease (WD) mouse model, and assessed the effect of GDFMD on the liver of model mice by hematoxylin and eosin, Masson, and immunohistochemical staining. Subsequently, we identified differentially expressed genes (DEGs) that were upregulated in the Model (Model vs. control) and those that were downregulated upon GDFMD treatment (compared to the Model) using RNA-sequencing (RNA-Seq). Biological functions and signaling pathways in which the DEGs were involved were determined by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses. A protein–protein interaction (PPI) network was constructed using the STRING database, and the modules were identified using MCODE plugin with the Cytoscape software. Several genes identified in the RNA-Seq analysis were validated by real-time quantitative PCR. Results: Total of 2124 DEGs were screened through the Model vs. control and Model vs. GDFMD comparisons, and dozens of GO and KEGG pathway terms modulated by GDFMD were identified. Dozens of pathways involved in metabolism (including metabolic processes for organic acids, carboxylic acids, monocarboxylic acids, lipids, fatty acids, cellular lipids, steroids, alcohols, eicosanoids, long-chain fatty acids), immune and inflammatory response (such as complement and coagulation cascades, cytokine–cytokine receptor interaction, inflammatory mediator regulation of TRP channels, antigen processing and presentation, T-cell receptor signaling pathway), liver fibrosis (such as ECM-receptor interactions), and cell death (PI3K-Akt signaling pathway, apoptosis, TGF-beta signaling pathway, etc.) were identified as potential targets of GDFMD in the Model. Some hub genes and four modules were identified in the PPI network. The results of real-time quantitative PCR analysis were consistent with those of RNA-Seq analysis. Conclusions: We performed gene expression profiling of GDFMD-treated WD model mice using RNA-Seq analysis and found the genes, pathways, and processes effected by the treatment. Our study provides a theoretical basis to prevent liver fibrosis resulting from WD using GDFMD.
Learning Temporal Point Processes with Intermittent Observations

Marked temporal point processes (MTPP) have emerged as a powerful framework to model the underlying generative mechanism of asynchronous events localized in continuous time. Most existing models and inference methods in MTPP framework consider only the complete observation scenario i.e. the event sequence being modeled is completely observed with no missing events – an ideal setting barely encountered in practice. A recent line of work which considers missing events uses supervised learning techniques which require a missing or observed label for each event. In this work, we provide a novel unsupervised model and inference method for MTPPs in presence of missing events. We first model the generative processes of observed events and missing events using two MTPPs, where the missing events are represented as latent random variables. Then we devise an unsupervised training method that jointly learns both the MTPPs by means of variational inference. Experiments with real datasets show that our modeling and inference frameworks can effectively impute the missing data among the observed events, which in turn enhances its predictive prowess.
Communication Efficient Primal-Dual Algorithm for Nonconvex Nonsmooth Distributed Optimization

Decentralized optimization frequently appears in large scale machine learning problems. However, few works have been focused on solving the decentralized optimization problems under the difficult nonconvex nonsmooth setting. In this paper, we propose a distributed primal-dual algorithm to solve this type of problems in a decentralized manner and the proposed algorithm can achieve an O(1/ ) iteration complexity to attain an -solution, which is the well-known lower iteration complexity bound for nonconvex optimization. Furthermore, to reduce communication overhead, we also modify our algorithm by compressing the vectors exchanged between nodes. The iteration complexity of the algorithm with compression is still O(1/ ). To our knowledge, it is the first algorithm achieving this rate under a nonconvex, nonsmooth decentralized setting with compression. Besides, we apply the proposed algorithm to solve nonconvex linear regression problem and train a deep learning model, both of which demonstrate the efficacy of the proposed algorithms.
One-Sketch-for-All: Non-linear Random Features from Compressed Linear Measurements

RFF (random Fourier features) is a popular technique for approximating the commonly used Gaussian kernel. Due to the crucial tuning parameter γ in the Gaussian kernel, the design of effective quantization schemes for RFF appears to be challenging. Intuitively one would expect that a different quantizer is needed for a different γ value (and we need to store a different set of quantized data for each γ). Interestingly, the recent work (Li and Li, 2021) showed that only one Lloyd-Max (LM) quantizer is needed by showing that the marginal distribution of RFF is free of the tuning parameter γ. On the other hand, Li and Li (2021) still required to store a different set of quantized data for each γ value. In this paper, we adopt the “one-sketch-forall” paradigm for quantizing RFFs. Basically, we only store one set of quantized linear sketches after applying random projections on the original data. From the same set of quantized data, we construct RFFs to approximate Gaussian kernels for any tuning parameter γ. Compared with Li and Li (2021), our proposed “one-sketch-for-all” scheme would inevitably lose some accuracy as one should expect. Nevertheless, our proposed method still performs noticeably better than other quantization algorithms such as stochastic rounding. We provide statistical analysis on properties of the proposed quantization method, and conduct experiments to empirically illustrate its effectiveness. Proceedings of the 24 International Conference on Artificial Intelligence and Statistics (AISTATS) 2021, San Diego, California, USA. PMLR: Volume 130. Copyright 2021 by the author(s).