Miracle-dz/UniFAR-FTUs huggingface dataset:
A Comprehensive Molecular Interaction Map for Rheumatoid Arthritis

Background Computational biology contributes to a variety of areas related to life sciences and, due to the growing impact of translational medicine - the scientific approach to medicine in tight relation with basic science -, it is becoming an important player in clinical-related areas. In this study, we use computation methods in order to improve our understanding of the complex interactions that occur between molecules related to Rheumatoid Arthritis (RA). Methodology Due to the complexity of the disease and the numerous molecular players involved, we devised a method to construct a systemic network of interactions of the processes ongoing in patients affected by RA. The network is based on high-throughput data, refined semi-automatically with carefully curated literature-based information. This global network has then been topologically analysed, as a whole and tissue-specifically, in order to translate the experimental molecular connections into topological motifs meaningful in the identification of tissue-specific markers and targets in the diagnosis, and possibly in the therapy, of RA. Significance We find that some nodes in the network that prove to be topologically important, in particular AKT2, IL6, MAPK1 and TP53, are also known to be associated with drugs used for the treatment of RA. Importantly, based on topological consideration, we are also able to suggest CRKL as a novel potentially relevant molecule for the diagnosis or treatment of RA. This type of finding proves the potential of in silico analyses able to produce highly refined hypotheses, based on vast experimental data, to be tested further and more efficiently. As research on RA is ongoing, the present map is in fieri, despite being -at the moment- a reflection of the state of the art. For this reason we make the network freely available in the standardised and easily exportable . xml CellDesigner format at ‘www.picb. ac.cn/ClinicalGenomicNTW/temp.html’ and ‘www.celldesigner. org’.
Compressive Sensing Based Interference Cancellation for Ultra Dense Network

In this work, we focus on ultra dense network (UDN) which is widely considered as a key component to increase the spectral efficiency for future mobile networks. For the reason that macro and small cells are operating on the same frequencies to increase spectral efficiency, interference from macro-cells and other small-cell users has an impact which can not be neglected. To cope with this challenge, we proposed a minimum mean square error (MMSE) based algorithm to eliminate interference to protect small cell users from macro and small cell interferences in compressive domain. Then Basis Pursuit De-Noising (BPDN) based algorithm is used to reconstruct the desired signal and lower noise. Simulations show that the proposed solution achieves better performance in recovered signal-to-noise ratio (SNR) and complexity reduction.
STING-dependent translation inhibition restricts RNA virus replication

Significance In mammalian cells, a protein called STING (stimulator of IFN genes) is typically viewed as a factor dedicated to defense strategies induced by DNA viruses. The antiviral activities of STING are linked to its ability to induce the expression of genes that combat viral replication cycles. In our study, we have discovered a transcription-independent function for STING in the restriction of viruses that contain RNA genomes. We found that cells lacking STING are sensitive to RNA virus infections and that during these infections, STING inhibits the translation machinery to prevent viral protein synthesis. This study therefore establishes that STING has dual functions in host defense, regulating antiviral gene expression or interfering with translation, to restrict replication of distinct classes of viruses. In mammalian cells, IFN responses that occur during RNA and DNA virus infections are activated by distinct signaling pathways. The RIG-I–like-receptors (RLRs) bind viral RNA and engage the adaptor MAVS (mitochondrial antiviral signaling) to promote IFN expression, whereas cGAS (cGMP–AMP synthase) binds viral DNA and activates an analogous pathway via the protein STING (stimulator of IFN genes). In this study, we confirm that STING is not necessary to induce IFN expression during RNA virus infection but also find that STING is required to restrict the replication of diverse RNA viruses. The antiviral activities of STING were not linked to its ability to regulate basal expression of IFN-stimulated genes, activate transcription, or autophagy. Using vesicular stomatitis virus as a model, we identified a requirement of STING to inhibit translation during infection and upon transfection of synthetic RLR ligands. This inhibition occurs at the level of translation initiation and restricts the production of viral and host proteins. The inability to restrict translation rendered STING-deficient cells 100 times more likely to support productive viral infections than wild-type counterparts. Genetic analysis linked RNA sensing by RLRs to STING-dependent translation inhibition, independent of MAVS. Thus, STING has dual functions in host defense, regulating protein synthesis to prevent RNA virus infection and regulating IFN expression to restrict DNA viruses.
A Standard System to Study Vertebrate Embryos

Staged embryonic series are important as reference for different kinds of biological studies. I summarise problems that occur when using ‘staging tables’ of ‘model organisms’. Investigations of developmental processes in a broad scope of taxa are becoming commonplace. Beginning in the 1990s, methods were developed to quantify and analyse developmental events in a phylogenetic framework. The algorithms associated with these methods are still under development, mainly due to difficulties of using non-independent characters. Nevertheless, the principle of comparing clearly defined newly occurring morphological features in development (events) in quantifying analyses was a key innovation for comparative embryonic research. Up to date no standard was set for how to define such events in a comparative approach. As a case study I compared the external development of 23 land vertebrate species with a focus on turtles, mainly based on reference staging tables. I excluded all the characters that are only identical for a particular species or general features that were only analysed in a few species. Based on these comparisons I defined 104 developmental characters that are common either for all vertebrates (61 characters), gnathostomes (26), tetrapods (3), amniotes (7), or only for sauropsids (7). Characters concern the neural tube, somite, ear, eye, limb, maxillary and mandibular process, pharyngeal arch, eyelid or carapace development. I present an illustrated guide listing all the defined events. This guide can be used for describing developmental series of any vertebrate species or for documenting specimen variability of a particular species. The guide incorporates drawings and photographs as well as consideration of species identifying developmental features such as colouration. The simple character-code of the guide is extendable to further characters pertaining to external and internal morphological, physiological, genetic or molecular development, and also for other vertebrate groups not examined here, such as Chondrichthyes or Actinopterygii. An online database to type in developmental events for different stages and species could be a basis for further studies in comparative embryology. By documenting developmental events with the standard code, sequence heterochrony studies (i.e. Parsimov) and studies on variability can use this broad comparative data set.
Identifying Discourse Boundaries in Group Discussions using a Multimodal Embedding Space

In group discussion, it is not always easy for the participants to effectively control the discussion to make it fruitful. With the goal of contributing to facilitating group discussions, this study proposes a method of segmenting a discussion. Predicted discussion boundaries may be useful for tracking the discussion topics, analyzing the discussion structure, and determining a timing for intervention. We created a multimodal embedding space using an autoencoder, and represented each multimodal utterance data in the embedding space. Then, a simple unsupervised approach was used to detect the discussion boundary. In a preliminary analysis, we found that the proposed method can generate discussion segments that are comprehensible for analyzing a discourse structure. But, the performance in the discourse segmentation task should be improved as future work. Author
Assumption versus evidence: the case of digoxin in atrial fibrillation and heart failure

Despite development of new and innovative medical therapies, still millions of patients with chronic heart failure (HF) with reduced ejection fraction and/or atrial fibrillation (AF) are treated with cardiac glycosides (overall 122 millions of patients defined daily dose prescriptions 2013 in Germany). 1 Randomized evidence for efficacy of this treatment strategy is, however, sparse. For HF with reduced ejection fraction (HFrEF), the only randomized controlled outcome trial (RCT) of reasonable size is the DIG trial.2 Although the DIG Trial could not demonstrate a benefit on total mortality in the overall trial population, hospitalization for worsening of HF was significantly reduced. Moreover, subgroup analysis suggested a benefit on total mortality in patients with low plasma levels of digoxin.3,4 Randomized controlled outcome trials prospectively investigating the impact of digoxin on mortality and morbidity in patients with AF are not available. In the very recent past, quite a number of cohort studies, post hoc analyses of RCTs (initiated to investigate other treatments), and meta-analyses,5–11 which are all liable to prescription bias as randomization was not targeting digoxin therapy,12 retrospectively investigated whether digoxin treatment would eventually increase mortality in AF. These analyses surely are invaluable sources to generate important hypotheses to be investigated in prospective RCTs, which are costly, time consuming, and in need of high resources. However, it is very important to interpret their results with caution, and potential sources of bias require careful assessment and discussion. The AFFIRM study originally investigated survival outcome of patients with AF randomized to treatment for either rate (defined as therapy with beta blocker, calcium-channel blocker, digoxin, and combinations of these drugs) or rhythm control (antiarrhythmic drug use upon discretion of the treating physician). 13 Rhythm control did not offer advantages over rate control. In a first post hoc analysis of …
How to deal with multi-source data for tree detection based on deep learning

In the field of remote sensing, it is very common to use data from several sensors in order to make classification or segmentation. Most of the standard Remote Sensing analysis use machine learning methods based on image descriptions as HOG or SIFT and a classifier as SVM. In recent years neural networks have emerged as a key tool regarding the detection of objects. Due to the heterogeneity of information (optical, infrared, LiDAR), the combination of multi-source data is still an open issue in the Remote Sensing field. In this paper, we focus on managing data from multiple sources for the task of localization of urban trees in multi-source (optical, infrared, DSM) aerial images and we evaluate the different effects of preprocessing on the input data of a CNN.
Mice Deficient in Nuclear Factor (NF)-κB/p52 Present with Defects in Humoral Responses, Germinal Center Reactions, and Splenic Microarchitecture

p52 is a subunit of nuclear factor (NF)-κB transcription factors, most closely related to p50. Previously, we have shown that p52, but not p50 homodimers can form transactivating complexes when associated with Bcl-3, an unusual member of the IκB family. To determine nonredundant physiologic roles of p52, we generated mice deficient in p52. Null mutant mice were impaired in their ability to generate antibodies to T-dependent antigens, consistent with an absence of B cell follicles and follicular dendritic cell networks in secondary lymphoid organs, and an inability to form germinal centers. Furthermore, the splenic marginal zone was disrupted. These phenotypes are largely overlapping with those observed in Bcl-3 knockout animals, but distinct from those of p50 knockouts, supporting the notion of a physiologically relevant complex of p52 homodimers and Bcl-3. Adoptive transfer experiments further suggest that such a complex may be critical in accessory cell functions during antigen-specific immune reactions. Possible roles of p52 and Bcl-3 are discussed that may underlie the oncogenic potential of these proteins, as evidenced by recurrent chromosomal translocations of their genes in lymphoid tumors.
Lifetime Reliability Optimization for Embedded Systems : A System-Level Approach

This paper presents an automatic reliability-aware system-level design methodology to tolerate hardware defects caused by manufacturing tolerances as well as destructive agents and aging processes at the places of activity of the system components. This is achieved by (1) integrating the capability of a redundant placement of software tasks in an automatic design process to cope with the hardware defects, (2) providing an automatic lifetime reliability analysis to trade off the arising costs in favor of the achieved reliability increase, and (3) proposing a software architecture for the runtime phase. Real-life case studies from the automotive domain illustrate the effectiveness of the proposed techniques. Keywords— Embedded Systems, Lifetime Reliability, Dependability, Analysis, Optimization, Design Space Exploration, System-Level
Cardiorespiratory noise correction improves the ASL signal

Cardiorespiratory fluctuations such as changes in heart rate or respiration volume influence the temporal dynamics of cerebral blood flow (CBF) measurements during arterial spin labeling (ASL) fMRI. This “physiological noise” can confound estimates of resting state network activity, and it may lower the signal‐to‐noise ratio of ASL during task‐related experiments. In this study we examined several methods for minimizing the contributions of both synchronized and non‐synchronized physiological noise in ASL measures of CBF, by combining the RETROICOR approach with different linear deconvolution models. We evaluated the amount of variance in CBF that could be explained by each method during physiological rest, in both resting state and task performance conditions. To further demonstrate the feasibility of this approach, we induced low‐frequency cardiorespiratory deviations via peripheral adrenergic stimulation with isoproterenol, and determined how these fluctuations influenced CBF, before and after applying noise correction. By suppressing physiological noise, we observed substantial improvements in the signal‐to‐noise ratio at the individual and group activation levels. Our results suggest that variations in cardiac and respiratory parameters can account for a large proportion of the variance in resting and task‐based CBF, and indicate that regressing out these non‐neuronal signal variations improves the intrinsically low signal‐to‐noise ratio of ASL. This approach may help to better identify and control physiologically driven activations in ASL resting state and task‐based analyses.
Camellia sinensis Prevents Perinatal Nicotine-Induced Neurobehavioral Alterations, Tissue Injury, and Oxidative Stress in Male and Female Mice Newborns

Nicotine exposure during pregnancy induces oxidative stress and leads to behavioral alterations in early childhood and young adulthood. The current study aimed to investigate the possible protective effects of green tea (Camellia sinensis) against perinatal nicotine-induced behavioral alterations and oxidative stress in mice newborns. Pregnant mice received 50 mg/kg C. sinensis on gestational day 1 (PD1) to postnatal day 15 (D15) and were subcutaneously injected with 0.25 mg/kg nicotine from PD12 to D15. Nicotine-exposed newborns showed significant delay in eye opening and hair appearance and declined body weight at birth and at D21. Nicotine induced neuromotor alterations in both male and female newborns evidenced by the suppressed righting, rotating, and cliff avoidance reflexes. Nicotine-exposed newborns exhibited declined memory, learning, and equilibrium capabilities, as well as marked anxiety behavior. C. sinensis significantly improved the physical development, neuromotor maturation, and behavioral performance in nicotine-exposed male and female newborns. In addition, C. sinensis prevented nicotine-induced tissue injury and lipid peroxidation and enhanced antioxidant defenses in the cerebellum and medulla oblongata of male and female newborns. In conclusion, this study shows that C. sinensis confers protective effects against perinatal nicotine-induced neurobehavioral alterations, tissue injury, and oxidative stress in mice newborns.
Identifying Cis-Regulatory Sequences by Word Profile Similarity

Background Recognizing regulatory sequences in genomes is a continuing challenge, despite a wealth of available genomic data and a growing number of experimentally validated examples. Methodology/Principal Findings We discuss here a simple approach to search for regulatory sequences based on the compositional similarity of genomic regions and known cis-regulatory sequences. This method, which is not limited to searching for predefined motifs, recovers sequences known to be under similar regulatory control. The words shared by the recovered sequences often correspond to known binding sites. Furthermore, we show that although local word profile clustering is predictive for the regulatory sequences involved in blastoderm segmentation, local dissimilarity is a more universal feature of known regulatory sequences in Drosophila. Conclusions/Significance Our method leverages sequence motifs within a known regulatory sequence to identify co-regulated sequences without explicitly defining binding sites. We also show that regulatory sequences can be distinguished from surrounding sequences by local sequence dissimilarity, a novel feature in identifying regulatory sequences across a genome. Source code for WPH-finder is available for download at http://rana.lbl. gov/downloads/wph.tar. gz.
Identification of novel hyper- or hypomethylated CpG sites and genes associated with atherosclerotic plaque using an epigenome-wide association study

DNA methylation is an important epigenetic modification that has been implicated in the pathogenesis of atherosclerosis. Although previous studies have identified various CpG sites and genes whose methylation is associated with atherosclerosis in populations with European or Mexican ancestry, the genome-wide pattern of DNA methylation in the atherosclerotic human aorta is yet to be elucidated in Japanese individuals. In the present study, a genome-wide analysis of DNA methylation at ~853,000 CpG sites was performed using 128 postmortem aortic intima specimens obtained from 64 Japanese patients. To avoid the effects of interindividual variation, intraindividual paired comparisons were performed between atheromatous plaque lesions and corresponding plaque-free tissue for each patient. Bisulfite-modified genomic DNA was analyzed using a specific microarray for DNA methylation. DNA methylation at each CpG site was calculated as the β value, where β = (intensity of the methylated allele)/(intensity of the methylated allele + intensity of the unmethylated allele + 100). Bonferroni's correction for statistical significance of association was applied to compensate for multiple comparisons. The methylation of 2,679 CpG sites differed significantly (P<5.86×10−8) between atheromatous plaque lesions and the corresponding plaque-free intima, with 2,272 and 407 CpG sites in atheromatous plaques being hyper- or hypomethylated, respectively. A total of 5 hypermethylated CpG sites in atheromatous plaques were demonstrated to have a difference in β value of >0.15 (plaque lesion-plaque-free intima) and 11 had a β ratio of >1.50 (plaque/plaque-free intima). A further 15 and 17 hypomethylated CpG sites in atheromatous plaques were observed to have a difference in β value of <−0.15 or a β ratio of <0.67, respectively. According to these limits, a total of 16 novel genes that were significantly hyper- or hypomethylated in atheromatous plaque lesions compared with the plaque-free intima were identified in the present study. The results of the present study suggest that the methylation of these genes may contribute to the pathogenesis of atherosclerosis in the Japanese population.
Simulation and Prediction of the Adaptive Immune Response to Influenza A Virus Infection

ABSTRACT The cellular immune response to primary influenza virus infection is complex, involving multiple cell types and anatomical compartments, and is difficult to measure directly. Here we develop a two-compartment model that quantifies the interplay between viral replication and adaptive immunity. The fidelity of the model is demonstrated by accurately confirming the role of CD4 help for antibody persistence and the consequences of immune depletion experiments. The model predicts that drugs to limit viral infection and/or production must be administered within 2 days of infection, with a benefit of combination therapy when administered early, and cytotoxic CD8 T cells in the lung are as effective for viral clearance as neutralizing antibodies when present at the time of challenge. The model can be used to investigate explicit biological scenarios and generate experimentally testable hypotheses. For example, when the adaptive response depends on cellular immune cell priming, regulation of antigen presentation has greater influence on the kinetics of viral clearance than the efficiency of virus neutralization or cellular cytotoxicity. These findings suggest that the modulation of antigen presentation or the number of lung resident cytotoxic cells and the combination drug intervention are strategies to combat highly virulent influenza viruses. We further compared alternative model structures, for example, B-cell activation directly by the virus versus that through professional antigen-presenting cells or dendritic cell licensing of CD8 T cells.
Characterization of silicon-substituted hydroxyapatite powders synthesized by a wet precipitation method

The preparation of nano sized silicated hydroxyapatite Ca10(PO4)6-x(SiO4)x(OH)2-x (Si-HA) with three different silicon concentrations were investigated using a wet precipitation method. The effects of the Si substitution on crystallite size, lattice parameters and fraction of crystalline phase of the powders were discussed. The crystalline phase, chemical composition,and crystallite size of hydroxyapatite and silicon substituted hydroxyapatites were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), inductively coupled plasma and transmission electron microscopy. The crystallite size and fraction of crystalline phase decreases with increase in silicon content and particle morphology spheroidal for pure hydroxyapatite changes to elongated ellipsoidalcrystals while silicon substitution increases. FTIR analysis reveals, the silicon incorporation to hydroxyapatite lattice occurs via substitution of silicate groups for phosphate groups. Substitution of phosphate group by silicate in the Si-HA structure results an increase in the lattice parameters in both a-axis and c-axis of the unit cell.