Miracle-dz/UniFAR-FTUs huggingface dataset:
Coding for Deletion Channels with Multiple Traces

Motivated by the sequence reconstruction problem from traces in DNA-based storage, we consider the problem of designing codes for the deletion channel when multiple observations (or traces) are available to the decoder. We propose simple binary and non-binary codes based on Varshamov-Tenengolts (VT) codes. The proposed codes split the codeword in blocks and employ a VT code in each block. The availability of multiple traces helps the decoder to identify deletion-free copies of a block, and to avoid mis-synchronization while decoding. The encoding complexity of the proposed scheme is linear in the codeword length; the decoding complexity is linear in the codeword length, and quadratic in the number of deletions and the number of traces. The proposed scheme offers an explicit low-complexity technique for correcting deletions using multiple traces.
Language Brain Representation in Bilinguals With Different Age of Appropriation and Proficiency of the Second Language: A Meta-Analysis of Functional Imaging Studies

Language representation in the bilingual brain is the result of many factors, of which age of appropriation (AoA) and proficiency of the second language (L2) are probably the most studied. Many studies indeed compare early and late bilinguals, although it is not yet clear what the role of the so-called critical period in L2 appropriation is. In this study, we carried out coordinate-based meta-analyses to address this issue and to inspect the role of proficiency in addition to that of AoA. After the preliminary inspection of the early (also very early) and late bilinguals’ language networks, we explored the specific activations associated with each language and compared them within and between the groups. Results confirmed that the L2 language brain representation was wider than that associated with L1. This was observed regardless of AoA, although differences were more relevant in the late bilinguals’ group. In particular, L2 entailed a greater enrollment of the brain areas devoted to the executive functions, and this was also observed in proficient bilinguals. The early bilinguals displayed many activation clusters as well, which also included the areas involved in cognitive control. Interestingly, these regions activated even in L1 of both early and late bilingual groups, although less consistently. Overall, these findings suggest that bilinguals in general are constantly subjected to cognitive effort to monitor and regulate the language use, although early AoA and high proficiency are likely to reduce this.
Three Pairs of New Spirocyclic Alkaloid Enantiomers From the Marine-Derived Fungus Eurotium sp. SCSIO F452

Three pairs of new spirocyclic alkaloid enantiomers eurotinoids A–C (1–3), as well as a known biogenetically related racemate dihydrocryptoechinulin D (4) were isolated from a marine-derived fungus Eurotium sp. SCSIO F452. Their structures were determined by spectroscopic analyses and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 represent the first two “meta” products from a non-stereoselective [4 + 2] Diels-Alder cycloaddition presumably between an enone group of a diketopiperazine alkaloid and a diene group of a benzaldehyde derivative via a new head-to-tail coupling mode biosynthetically, while 3 and 4 were “ortho” products. Their enantiomers exhibited different antioxidative and cytotoxic activities. The modes of action were investigated by a preliminary molecular docking study.
Tau Phosphorylation Rates Measured by Mass Spectrometry Differ in the Intracellular Brain vs. Extracellular Cerebrospinal Fluid Compartments and Are Differentially Affected by Alzheimer’s Disease

Tau protein aggregation into neurofibrillary tangles in the central nervous system contributes to the etiology of certain neurodegenerative disorders, including Alzheimer’s disease (AD). Though the mechanism of tau destabilization is not fully understood yet, tau protein has been found to be hyperphosphorylated in tau aggregates. To investigate this further, we developed a highly sensitive and specific mass spectrometry (MS) method using parallel reaction monitoring (PRM) to identify tau phosphorylation sites. This method enables us to compare the abundance of phosphorylation sites in tau proteins in the brain and cerebrospinal fluid (CSF) in humans with and without AD. We detected 29 distinct phosphorylated tau (p-tau) sites in full-length tau from soluble human brain lysate and 12 sites on truncated tau in CSF, mainly in the mid-domain. Brain soluble tau phosphorylation sites are localized on three domains including a proline-rich mid-domain, the C-terminus, and a cluster on the N-terminal projection domain not previously characterized. Some phosphorylation sites increased in CSF, while others decreased compared to brain. Notably, phosphorylation on T205 and S208, recognized by AT8 antibody defining Braak stages of brain tau aggregation, were not detected in normal brain soluble tau but were found in the CSF. Comparison of the p-tau rates from the brain and the CSF indicated that the abundance of phosphorylated sites varied in a site-specific manner. CSF tau proteins from non-AD participants were significantly hyperphosphorylated on T111, T205, S208, T217 and T231. In AD CSF, hyperphosphorylation on these sites was exacerbated, and phosphorylation on T153 and T175 specifically were detected. This supports the hypothesis that tau hyperphosphorylation could be a physiological process amplified by AD pathology. Conversely, we found that S202 was hypophosphorylated in CSF and was not hyperphosphorylated in AD, demonstrating that p-tau isoforms could have different metabolisms depending on which sites are phosphorylated. These site-specific p-tau rates are independent of tau concentration and distinct of current CSF tau and p-tau assays measuring tau isoforms levels. Targeted MS multiplexing ability and high-throughput capacity lets us envision the use of these new p-tau measurements as promising biomarkers for AD diagnosis and tracking therapeutic responses.
Redundancy Among Parameters Describing the Input-Output Relation of Motor Evoked Potentials in Healthy Subjects and Stroke Patients

Background: Transcranial magnetic stimulation (TMS) is widely used to probe corticospinal excitability through Motor Evoked Potential (MEP) amplitude measurements. The input-output (I/O) curve is a sigmoid-shaped relation between the MEP amplitude at incremented TMS intensities. The aim of this study was to examine the relationships between seven parameters derived from the sigmoid function. Methods: Principal Component Analysis and Spearman's rank correlation matrices were used to determine if the seven I/O curve parameters capture similar or, conversely, different aspects of the corticospinal excitability in 24 healthy subjects and 40 stroke survivors with a hand motor impairment. Results: Maximum amplitude (MEPmax), peak slope, area under the I/O curve (AUC), and MEP amplitude recorded at 140% of the resting motor threshold showed strong linear relationships with each other (ρ > 0.72, p < 0.001). Results were found to be similar in healthy subjects and in both hemispheres of stroke patients. Our results did not support an added benefit of sampling entire I/O curves in both healthy subjects and stroke patients, with the exception of S50, the stimulus intensity needed to obtain half of MEPmax amplitude. Conclusions: This demonstrates that MEP elicited at a single stimulus intensity allows to capture the same characteristics of the corticospinal excitability as measured by the AUC, MEPmax and the peak slope, which may be of interest in both clinical and research settings. However, it is still necessary to plot I/O curves if an effect or a difference is expected at S50.
Survivability and molecular variation in Vibrio cholerae from epidemic sites in China

SUMMARY The survival behaviour of Vibrio cholerae in cholera epidemics, together with its attributes of virulence-associated genes and molecular fingerprints, are significant for managing cholera epidemics. Here, we selected five strains representative of V. cholerae O1 and O139 involved in cholera events, examined their survival capacity in large volumes of water sampled from epidemic sites of a 2005 cholera outbreak, and determined virulence-associated genes and molecular subtype changes of the surviving isolates recovered. The five strains exhibited different survival capacities varying from 17 to 38 days. The virulence-associated genes of the surviving isolates remained unchanged, while their pulsotypes underwent slight variation. In particular, one waterway-isolated strain maintained virulence-associated genes and evolved to share the same pulsotype as patient strains, highlighting its role in the cholera outbreak. The strong survival capacity and molecular attributes of V. cholerae might account for its persistence in environmental waters and the long duration of the cholera outbreak, allowing effective control measures.
Object-oriented Modeling of Heat and Humidity Budgets of Biosphere 2 Using Bond Graphs

Biosphere 2 is a closed ecosystem located near Tucson, Arizona, designed for studying the interactions between different biological species among each other and with their materially closed controlled environment, taking into account the limited resources that such an environment provides. Energy considerations play a central role in how these interactions play out. To this end, bond graph models were designed that enable the researcher to better understand the nature of these interactions, hopefully offering some insight into the much larger ecosystem of planet Earth
Metabolism and disposition of 2,2′,4,4′,5-pentabromodiphenyl ether (BDE99) following a single or repeated administration to rats or mice

The metabolism and disposition of 14C-labelled 2,2′,4,4′,5-pentabromodiphenyl ether (BDE99) were studied in F344 rats and B6C3F1 mice. Approximately 85% of a 1 µmol kg−1 oral dose was absorbed by male rats and mice. Within 24 h following oral doses ranging from 0.1 to 1000 µmol kg−1 to rats, 39–47% of the dose was excreted in the faeces (including 16% unabsorbed), up to 2% was excreted in the urine, and 34–38% remained in the tissues, mostly in adipose tissue. Mice excreted more in the urine and less in the faeces than rats. Tissue accumulation was observed following repeated dosing to rats. Two dihydrohydroxy-S-glutathionyl and two S-glutathionyl conjugates of BDE99, 2,4,5-tribromophenol glucuronide, two mono-hydroxylated BDE99 glucuronides, and three mono-hydroxylated tetrabromodiphenyl ether glucuronides were identified in male rat bile. 2,4,5-Tribromophenol and its glucuronide and sulfate conjugates, were identified in male rat urine. 2,4,5-Tribromophenol, one mono-hydroxylated tetrabromodiphenyl ether, and two mono-hydroxylated BDE99 were characterized in male rat faeces. BDE99 undergoes more extensive metabolism than does BDE47. Half of the absorbed oral dose in male rats was excreted in 10 days mostly as metabolites derived from arene oxide intermediates.
Bariatric Surgery Modulates Urinary Levels of MicroRNAs Involved in the Regulation of Renal Function

Background: Obesity and diabetes cause chronic kidney disease with a common pathophysiology that is characterized by the accumulation of collagen in the extracellular matrix. Recent evidence has implicated the epithelial-to-mesenchymal transition (EMT) as a key step in this pathology with regulation by microRNAs. Weight loss leads to improvements in renal function; therefore, this study hypothesized that bariatric-surgery aided weight loss would lead to changes in urinary microRNAs involved in the regulation of renal function. Materials and methods: Twenty-four bariatric patients undergoing Roux-en-Y gastric bypass and sleeve gastrectomy donated urine pre-operatively and at 2–6 months and 1–2 years post-operatively. Urine samples were also obtained from 10 healthy weight and 7 morbidly obese non-surgical controls. Expression levels of kidney microRNAs were assessed in urine and the function of microRNAs was assessed through the in vitro transfection of HK-2 cells, a kidney proximal tubule cell line. Results: Levels of miR 192, miR 200a, and miR 200b were upregulated in urine following bariatric surgery. This increase was consistent across surgical type and diabetes status and was maintained and enhanced with time. Bariatric surgery alters urinary miR 192 expression from levels seen in morbidly obese patients to levels seen in healthy weight control patients. In mechanistic studies, the transfection of miR 192 in HK-2 cells increased miR 200a expression and decreased ZEB2, a key transcriptional promoter of kidney fibrosis. Conclusions: Bariatric surgery increased miR 192 and miR 200 urinary levels, key anti-fibrotic microRNAs that could contribute to a renal-protective mechanism and may be of value as urinary biomarkers following surgery. These findings suggest that urinary microRNAs may represent potential novel biomarkers for obesity-associated renal function.
Dyslipidemia Part 2

Dyslipidemia is one of the major modifiable risk factors associated with atherosclerotic cardiovascular disease. Appropriate modification of lipid profiles reduces the progression of atherosclerosis in vessel walls across all vascular beds. The management of dyslipidemia has evolved over the last several decades, especially since the discovery of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, also known as statins. Statin use in atherosclerotic heart disease is well described in observational and prospective placebo-controlled studies, citing both lipid-lowering and pleiotropic effects. However, the effect of statins and other lipid-lowering agents on noncoronary arterial beds (the aorta, arteries to the extremities, renal, and carotid arteries) is less understood. This article is part 2 of a 2-part review, with part 1 having focused on lipid metabolism and the downstream effects of lipids on the development of atherosclerosis. The current review (part 2) will discuss trials, retrospective reviews, and observational cohort studies regarding the use of statins and/or other lipid-lowering drugs for primary and secondary prevention of peripheral noncoronary atherosclerotic disease.
Unravelling the Scientific Debate on How to Address Wolf-Dog Hybridization in Europe

Anthropogenic hybridization is widely perceived as a threat to the conservation of biodiversity. Nevertheless, to date, relevant policy and management interventions are unresolved and highly convoluted. While this is due to the inherent complexity of the issue, we hereby hypothesize that a lack of agreement concerning management goals and approaches, within the scientific community, may explain the lack of social awareness on this phenomenon, and the absence of effective pressure on decision-makers. By focusing on wolf x dog hybridization in Europe, we hereby (a) assess the state of the art of issues on wolf x dog hybridization within the scientific community, (b) assess the conceptual bases for different viewpoints, and (c) provide a conceptual framework aiming at reducing the disagreements. We adopted the Delphi technique, involving a three-round iterative survey addressed to a selected sample of experts who published at Web of Science listed journals, in the last 10 years on wolf x dog hybridization and related topics. Consensus was reached that admixed individuals should always be defined according to their genetic profile, and that a reference threshold for admixture (i.e., q-value in assignment tests) should be formally adopted for their identification. To mitigate hybridization, experts agreed on adopting preventive, proactive and, when concerning small and recovering wolf populations, reactive interventions. Overall, experts' consensus waned as the issues addressed became increasingly practical, including the adoption of lethal removal. We suggest three non-mutually exclusive explanations for this trend: (i) value-laden viewpoints increasingly emerge when addressing practical issues, and are particularly diverging between experts with different disciplinary backgrounds (e.g., ecologists, geneticists); (ii) some experts prefer avoiding the risk of potentially giving carte blanche to wolf opponents to (illegally) remove wolves, based on the wolf x dog hybridization issue; (iii) room for subjective interpretation and opinions result from the paucity of data on the effectiveness of different management interventions. These results have management implications and reveal gaps in the knowledge on a wide spectrum of issues related not only to the management of anthropogenic hybridization, but also to the role of ethical values and real-world management concerns in the scientific debate.
Uncertainty Quantification Using Periodic Random Variables

Many studies in uncertainty quantification have been carried out under the assumption of an input random field in which a countable number of independent random variables are each uniformly distributed on an interval, with these random variables entering linearly in the input random field (the so-called affine model). In this paper we consider an alternative model of the random field, in which the random variables have the same uniform distribution on an interval, but the random variables enter the input field as periodic functions. The field is constructed in such a way as to have the same mean and covariance function as the affine random field. Higher moments differ from the affine case, but in general the periodic model seems no less desirable. The new model of the random field is used to compute expected values of a quantity of interest arising from an elliptic PDE with random coefficients. The periodicity is shown to yield a higher order cubature convergence rate of $\mathcal{O}(n^{-1/p})$ independently of the dimension when used in conjunction with rank-1 lattice cubature rules constructed using suitably chosen smoothness-driven product and order dependent weights, where $n$ is the number of lattice points and $p$ is the summability exponent of the fluctuations in the series expansion of the random coefficient. We present numerical examples that assess the performance of our method.
CgGCS, Encoding a Glucosylceramide Synthase, Is Required for Growth, Conidiation and Pathogenicity in Colletotrichum gloeosporioides

Fungal glucosylceramide plays important role in cell division, hyphal formation and growth, spore germination and the modulation of virulence and has recently been considered as target for small molecule inhibitors. In this study, we characterized CgGCS, a protein encoding a glucosylceramide synthase (GCS) in Colletotrichum gloeosporioides. Disruption of CgGCS resulted in a severe reduction of mycelial growth and defects in conidiogenesis. Sphingolipid profile analysis revealed large decreases in glucosylceramide production in the mutant strains. Pathogenicity assays indicated that the ability of the ΔCgGCS mutants to invade both tomato and mango hosts was almost lost. In addition, the expression levels of many genes, especially those related to metabolism, were shown to be affected by the mutation of CgGCS via transcriptome analysis. Overall, our results demonstrate that C. gloeosporioides glucosylceramide is an important regulatory factor in fungal growth, conidiation, and pathogenesis in hosts.
A Novel Type of Neuron Within the Dorsal Striatum

The striatum is predominantly composed of medium spiny projection neurons, with the remaining neurons consisting of several types of interneurons. Among the interneurons are a group of cells that express tyrosine hydroxylase (TH). Although the intrinsic electrical properties of these TH-expressing interneurons have been characterized, there is no agreement on the number of TH-expressing cell types and their electrical properties. Here, we have used transgenic mice in which YFP-tagged channelrhodopsin-2 (ChR2) was expressed in potential TH-expressing cells in a Cre-dependent manner. We found that the YFP+ neurons in the striatum were heterogeneous in their intrinsic electrical properties; unbiased clustering indicated that there are three main neuronal subtypes. One population of neurons had aspiny dendrites with high-frequency action potential (AP) firing and plateau potentials, resembling the TH interneurons (THIN) described previously. A second, very small population of labeled neurons resembled medium-sized spiny neurons (MSN). The third population of neurons had dendrites with an intermediate density of spines, showed substantial AP adaptation and generated prolonged spikes. This type of striatal neuron has not been previously identified in the adult mouse and we have named it the Frequency-Adapting Neuron with Spines (FANS). Because of their distinctive properties, FANS may play a unique role in striatal information processing.
KGAT: Knowledge Graph Attention Network for Recommendation

To provide more accurate, diverse, and explainable recommendation, it is compulsory to go beyond modeling user-item interactions and take side information into account. Traditional methods like factorization machine (FM) cast it as a supervised learning problem, which assumes each interaction as an independent instance with side information encoded. Due to the overlook of the relations among instances or items (e.g., the director of a movie is also an actor of another movie), these methods are insufficient to distill the collaborative signal from the collective behaviors of users. In this work, we investigate the utility of knowledge graph (KG), which breaks down the independent interaction assumption by linking items with their attributes. We argue that in such a hybrid structure of KG and user-item graph, high-order relations --- which connect two items with one or multiple linked attributes --- are an essential factor for successful recommendation. We propose a new method named Knowledge Graph Attention Network (KGAT) which explicitly models the high-order connectivities in KG in an end-to-end fashion. It recursively propagates the embeddings from a node's neighbors (which can be users, items, or attributes) to refine the node's embedding, and employs an attention mechanism to discriminate the importance of the neighbors. Our KGAT is conceptually advantageous to existing KG-based recommendation methods, which either exploit high-order relations by extracting paths or implicitly modeling them with regularization. Empirical results on three public benchmarks show that KGAT significantly outperforms state-of-the-art methods like Neural FM and RippleNet. Further studies verify the efficacy of embedding propagation for high-order relation modeling and the interpretability benefits brought by the attention mechanism. We release the codes and datasets at https://github.com/xiangwang1223/knowledge_graph_attention_network.
Phosphorylation of Glutamine Synthetase on Threonine 301 Contributes to Its Inactivation During Epilepsy

The astrocyte-specific enzyme glutamine synthetase (GS), which catalyzes the amidation of glutamate to glutamine, plays an essential role in supporting neurotransmission and in limiting NH4+ toxicity. Accordingly, deficits in GS activity contribute to epilepsy and neurodegeneration. Despite its central role in brain physiology, the mechanisms that regulate GS activity are poorly defined. Here, we demonstrate that GS is directly phosphorylated on threonine residue 301 (T301) within the enzyme’s active site by cAMP-dependent protein kinase (PKA). Phosphorylation of T301 leads to a dramatic decrease in glutamine synthesis. Enhanced T301 phosphorylation was evident in a mouse model of epilepsy, which may contribute to the decreased GS activity seen during this trauma. Thus, our results highlight a novel molecular mechanism that determines GS activity under both normal and pathological conditions.