Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural and Functional Profiling of Environmental Ligands for Estrogen Receptors

Background: Individuals are exposed daily to environmental pollutants that may act as endocrine-disrupting chemicals (EDCs), causing a range of developmental, reproductive, metabolic, or neoplastic diseases. With their mostly hydrophobic pocket that serves as a docking site for endogenous and exogenous ligands, nuclear receptors (NRs) can be primary targets of small molecule environmental contaminants. However, most of these compounds are chemically unrelated to natural hormones, so their binding modes and associated hormonal activities are hardly predictable. Objectives: We conducted a correlative analysis of structural and functional data to gain insight into the mechanisms by which 12 members of representative families of pollutants bind to and activate the estrogen receptors ERα and ERβ. Methods: We used a battery of biochemical, structural, biophysical, and cell-based approaches to characterize the interaction between ERs and their environmental ligands. Results: Our study revealed that the chemically diverse compounds bound to ERs via varied sets of protein–ligand interactions, reflecting their differential activities, binding affinities, and specificities. We observed xenoestrogens binding to both ERs—with affinities ranging from subnanomolar to micromolar values—and acting in a subtype-dependent fashion as full agonists or partial agonists/antagonists by using different combinations of the activation functions 1 and 2 of ERα and ERβ. Conclusions: The precise characterization of the interactions between major environmental pollutants and two of their primary biological targets provides rational guidelines for the design of safer chemicals, and will increase the accuracy and usefulness of structure-based computational methods, allowing for activity prediction of chemicals in risk assessment. Citation: Delfosse V, Grimaldi M, Cavaillès V, Balaguer P, Bourguet W. 2014. Structural and functional profiling of environmental ligands for estrogen receptors. Environ Health Perspect 122:1306–1313; http://dx.doi. org/10.1289/ehp.1408453
Genomic insights into the evolutionary origin of Myxozoa within Cnidaria

Significance Myxozoans are a diverse group of microscopic parasites that infect invertebrate and vertebrate hosts. The assertion that myxozoans are highly reduced cnidarians is supported by the presence of polar capsules, which resemble cnidarian stinging structures called “nematocysts. ” Our study characterizes the genomes and transcriptomes of two distantly related myxozoan species, Kudoa iwatai and Myxobolus cerebralis, and another cnidarian parasite, Polypodium hydriforme. Phylogenomic analyses that use a broad sampling of myxozoan taxa confirm the position of myxozoans within Cnidaria with P. hydriforme as the sister taxon to Myxozoa. Analyses of myxozoan genomes indicate that the transition to the highly reduced body plan was accompanied by massive reduction in genome size, including depletion of genes considered hallmarks of animal multicellularity. The Myxozoa comprise over 2,000 species of microscopic obligate parasites that use both invertebrate and vertebrate hosts as part of their life cycle. Although the evolutionary origin of myxozoans has been elusive, a close relationship with cnidarians, a group that includes corals, sea anemones, jellyfish, and hydroids, is supported by some phylogenetic studies and the observation that the distinctive myxozoan structure, the polar capsule, is remarkably similar to the stinging structures (nematocysts) in cnidarians. To gain insight into the extreme evolutionary transition from a free-living cnidarian to a microscopic endoparasite, we analyzed genomic and transcriptomic assemblies from two distantly related myxozoan species, Kudoa iwatai and Myxobolus cerebralis, and compared these to the transcriptome and genome of the less reduced cnidarian parasite, Polypodium hydriforme. A phylogenomic analysis, using for the first time to our knowledge, a taxonomic sampling that represents the breadth of myxozoan diversity, including four newly generated myxozoan assemblies, confirms that myxozoans are cnidarians and are a sister taxon to P. hydriforme. Estimations of genome size reveal that myxozoans have one of the smallest reported animal genomes. Gene enrichment analyses show depletion of expressed genes in categories related to development, cell differentiation, and cell–cell communication. In addition, a search for candidate genes indicates that myxozoans lack key elements of signaling pathways and transcriptional factors important for multicellular development. Our results suggest that the degeneration of the myxozoan body plan from a free-living cnidarian to a microscopic parasitic cnidarian was accompanied by extreme reduction in genome size and gene content.
Numerical Simulation and Experimental Studies for High Gas Velocity Electrostatic Precipitator

The high gas velocity electrostatic precipitator (HGVESP) is simulated by computational fluid dynamics (CFD) technology. The SIMPLE algorithm is used to calculate and the geometry model is divided by pre-processing software ICEM. The relationship of gas velocity, dust particle size and voltage is examined by FLUENT. The results suggest that with the improvement of applied voltage and dust particle size, collection efficiency increases. The results show that HGVESP with transverse plates can not only have a high efficiency, but also increase treatment capacity, which achieve miniaturization. Then the correctness of the model is verified by experiments.
Uptake in supraclavicular area fat ("USA-Fat"): description on 18F-FDG PET/CT.

UNLABELLED The supraclavicular region is a common site for lymph node metastases. A commonly reported type of nonmalignant (18)F-FDG uptake on PET imaging in the supraclavicular region is "muscle uptake" purportedly due to muscle contraction in tense patients during the (18)F-FDG uptake phase. PET/CT offers the unique opportunity to correlate PET findings with CT anatomy in the supraclavicular region. METHODS Images from the first 359 consecutive clinical whole-body studies (in 347 patients) using (18)F-FDG and a PET/CT scanner (with CT attenuation correction and ordered-subsets expectation maximization [OSEM] reconstruction) were retrospectively reviewed. The supraclavicular region was evaluated for the presence of abnormal uptake on PET images, and the corresponding CT findings were assessed. Three distinct patterns of abnormal (18)F-FDG uptake were noted: pattern A (uptake localizing to supraclavicular area fat [USA-fat], i.e., without corresponding lymph node or muscle uptake on CT), pattern B (uptake localizing to muscle on CT), and pattern C (uptake localizing to lymph nodes or soft-tissue masses on CT). RESULTS Forty-nine patients (14.1%) (32 female, 17 male; mean age, 51.4 +/- 15.6 y; age range, 12-77 y) showed abnormal (18)F-FDG uptake in the supraclavicular region. Twenty patients (5.8%) had muscle uptake (group B); 15 (4.3%) had definite abnormal lymph nodes (group C). However, 14 patients (4.0%) had USA-fat (group A) and foci of very low Hounsfield units on CT. These foci were also present on (68)Ge attenuation-corrected images (when obtained) and non-attenuation-corrected images. Uptake in USA-fat was typically bilateral and symmetric, intense, more often multifocal than linear, and located in fat on PET/CT. Age was not significantly different for group C versus the 2 other groups. Intensity; mean standardized uptake value, lean (SUV(L MEAN)); or maximum standardized uptake value, lean (SUV(L MAX)), did not allow differentiation between patterns A and C (P > 0.05). Standardized uptake values (SUV(L MAX), 3.1; SUV(L MEAN), 2.1) were significantly lower in group B than in the 2 other groups (P < 0.005). CONCLUSION So-called muscle uptake in the supraclavicular region may be caused in a significant proportion of cases by an unrelated process we call the USA-fat finding, with (18)F-FDG uptake in tissues of low-Hounsfield (fat) density. This finding most likely reflects an underlying nonpathologic process that we hypothesize to be in foci of brown fat. This intense supraclavicular uptake should be recognized and should not be misinterpreted as a malignant metastatic process or as muscle uptake.
Improved non-malleable extractors, non-malleable codes and independent source extractors

In this paper we give improved constructions of several central objects in the literature of randomness extraction and tamper-resilient cryptography. Our main results are: (1) An explicit seeded non-malleable extractor with error ε and seed length d=O(logn)+O(log(1/ε)loglog(1/ε)), that supports min-entropy k=Ω(d) and outputs Ω(k) bits. Combined with the protocol by Dodis and Wichs, this gives a two round privacy amplification protocol with optimal entropy loss in the presence of an active adversary, for all security parameters up to Ω(k/logk), where k is the min-entropy of the shared weak random source. Previously, the best known seeded non-malleable extractors require seed length and min-entropy O(logn)+log(1/ε)2O√loglog(1/ε), and only give two round privacy amplification protocols with optimal entropy loss for security parameter up to k/2O(√logk). (2) An explicit non-malleable two-source extractor for min entropy k ≥ (1 - Υ)n, some constant Υ>0, that outputs Ω(k) bits with error 2-Ω(n/logn). We further show that we can efficiently uniformly sample from the pre-image of any output of the extractor. Combined with the connection found by Cheraghchi and Guruswami this gives a non-malleable code in the two-split-state model with relative rate Ω(1/logn). This exponentially improves previous constructions, all of which only achieve rate n-Ω(1). (3) Combined with the techniques by Ben-Aroya et. al, our non-malleable extractors give a two-source extractor for min-entropy O(logn loglogn), which also implies a K-Ramsey graph on N vertices with K=(logN)O(logloglogN). Previously the best known two-source extractor by Ben-Aroya et. al requires min-entropy logn 2O(√logn), which gives a Ramsey graph with K=(logN)2O(√logloglogN). We further show a way to reduce the problem of constructing seeded non-malleable extractors to the problem of constructing non-malleable independent source extractors. Using the non-malleable 10-source extractor with optimal error by Chattopadhyay and Zuckerman, we give a 10-source extractor for min-entropy O(logn). Previously the best known extractor for such min-entropy by Cohen and Schulman requires O(loglogn) sources. Independent of our work, Cohen obtained similar results to (1) and the two-source extractor, except the dependence on ε is log(1/ε)poly loglog(1/ε) and the two-source extractor requires min-entropy logn poly loglogn.
Measuring interaction: An empirical comparison of three OLS regression models

The capacity to correctly assess the existence of interaction is a high-value modeling capability among researchers of information systems (IS), especially those focusing on behavioural paradigm studies. Interaction is a notable aspect for the major theoretical frameworks of the IS field, particularly the adoption theories. Allowing for crossover effects in the Theory of Planned Behaviour resulted in improvements in model prediction (Taylor & Todd, 1995b). This study presents the trimmed model, which does not permit crossover effect relations among variables. In complex models, as mentioned by Pedhazur (1997), one variable may affect another variable indirectly through multiple paths. According to him, it stands to reason that indirect effects, through certain paths, may be more meaningful and/or stronger than others. The findings of this quantitative study lead one to conclude that crossover effect models are more capable of showing the interaction among models’ variables, as well as explaining the highest percentage of variation for a single dependent variable, in comparison to the full and trimmed
Mining new protein-protein interactions

One of the most reliable approaches for determining a function of a given functionally unknown protein is to see if it is interacting with another protein with a known function. This problem of combining protein class information to data on protein-protein interactions to systematically predict unknown protein-protein interactions is solved by a probabilistic model-based approach. In general, a probabilistic model for clustering is a latent-variable model in which a latent variable takes values, each of which corresponds to a cluster. This paper extends such typical latent-variable model to a model having two (lower- and upper-level) latent variables hierarchically. This hierarchical probabilistic structure is a key feature of this model. It should be noted that this hierarchical dependency is reasonable since it cannot be observed which pair of protein classes is useful for predicting protein-protein interactions, although what protein pairs are interacting with each other can be observed. This structure allows to systematically deal with a set of protein classes as a latent variable of observable protein-protein interactions. Results show that the approach presented in this paper for capturing guilt-by-association interactions successfully outperformed existing methods and support vector machines, being statistically significant in predicting new protein-protein interactions. Thus, predicting protein-protein interactions should be conducted by unsupervised learning approach, and then the performance of hierarchical aspect model (HAM) should be compared with those of other unsupervised methods.
Ouabain Enhances ADPKD Cell Apoptosis via the Intrinsic Pathway

Progression of autosomal dominant polycystic kidney disease (ADPKD) is highly influenced by factors circulating in blood. We have shown that the hormone ouabain enhances several characteristics of the ADPKD cystic phenotype, including the rate of cell proliferation, fluid secretion and the capacity of the cells to form cysts. In this work, we found that physiological levels of ouabain (3 nM) also promote programmed cell death of renal epithelial cells obtained from kidney cysts of patients with ADPKD (ADPKD cells). This was determined by Alexa Fluor 488 labeled-Annexin-V staining and TUNEL assay, both biochemical markers of apoptosis. Ouabain-induced apoptosis also takes place when ADPKD cell growth is blocked; suggesting that the effect is not secondary to the stimulatory actions of ouabain on cell proliferation. Ouabain alters the expression of BCL family of proteins, reducing BCL-2 and increasing BAX expression levels, anti- and pro-apoptotic mediators respectively. In addition, ouabain caused the release of cytochrome c from mitochondria. Moreover, ouabain activates caspase-3, a key “executioner” caspase in the cell apoptotic pathway, but did not affect caspase-8. This suggests that ouabain triggers ADPKD cell apoptosis by stimulating the intrinsic, but not the extrinsic pathway of programmed cell death. The apoptotic effects of ouabain are specific for ADPKD cells and do not occur in normal human kidney cells (NHK cells). Taken together with our previous observations, these results show that ouabain causes an imbalance in cell growth/death, to favor growth of the cystic cells. This event, characteristic of ADPKD, further suggests the importance of ouabain as a circulating factor that promotes ADPKD progression.
Cytokinesis in tobacco BY-2 and root tip cells: a new model of cell plate formation in higher plants

Cell plate formation in tobacco root tips and synchronized dividing suspension cultured tobacco BY-2 cells was examined using cryofixation and immunocytochemical methods. Due to the much improved preservation of the cells, many new structural intermediates have been resolved, which has led to a new model of cell plate formation in higher plants. Our electron micrographs demonstrate that cell plate formation consists of the following stages: (1) the arrival of Golgi-derived vesicles in the equatorial plane, (2) the formation of thin (20 +/- 6 nm) tubes that grow out of individual vesicles and fuse with others giving rise to a continuous, interwoven, tubulo-vesicular network, (3) the consolidation of the tubulo-vesicular network into an interwoven smooth tubular network rich in callose and then into a fenestrated plate-like structure, (4) the formation of hundreds of finger-like projections at the margins of the cell plate that fuse with the parent cell membrane, and (5) cell plate maturation that includes closing of the plate fenestrae and cellulose synthesis. Although this is a temporal chain of events, a developing cell plate may be simultaneously involved in all of these stages because cell plate formation starts in the cell center and then progresses centrifugally towards the cell periphery. The "leading edge" of the expanding cell plate is associated with the phragmoplast microtubule domain that becomes concentrically displaced during this process. Thus, cell plate formation can be summarized into two phases: first the formation of a membrane network in association with the phragmoplast microtubule domain; second, cell wall assembly within this network after displacement of the microtubules. The phragmoplast microtubules end in a filamentous matrix that encompasses the delicate tubulo-vesicular networks but not the tubular networks and fenestrated plates. Clathrin-coated buds/vesicles and multivesicular bodies are also typical features of the network stages of cell plate formation, suggesting that excess membrane material may be recycled in a selective manner. Immunolabeling data indicate that callose is the predominant lumenal component of forming cell plates and that it forms a coat-like structure on the membrane surface. We postulate that callose both helps to mechanically stabilize the early delicate membrane networks of forming cell plates, and to create a spreading force that widens the tubules and converts them into plate-like structures. Cellulose is first detected in the late smooth tubular network stage and its appearance seems to coincide with the flattening and stiffening of the cell plate.
Boosting Trees for Anti-Spam Email Filtering

This paper describes a set of comparative experiments for the problem of automatically filtering unwanted electronic mail messages. Several variants of the AdaBoost algorithm with confidence-rated predictions [Schapire & Singer, 99] have been applied, which differ in the complexity of the base learners considered. Two main conclusions can be drawn from our experiments: a) The boosting-based methods clearly outperform the baseline learning algorithms (Naive Bayes and Induction of Decision Trees) on the PU1 corpus, achieving very high levels of the F1 measure; b) Increasing the complexity of the base learners allows to obtain better ``high-precision'' classifiers, which is a very important issue when misclassification costs are considered.
The third fibronectin type III repeat is required for L1 to serve as an optimal substratum for neurite extension

As a means of defining functionally important regions of the L1 neuronal cell adhesion molecule, neurite outgrowth from cerebellar neurons was compared on monolayers of L1‐negative B28 glioma cells, B28 cells transfected with wild‐type human L1, and B28 cells transfected with variant forms of L1. Neurite outgrowth on L1‐positive B28 cells is greatly enhanced over that seen on parental B28 cells. Neurite outgrowth on B28 cells expressing L1 variants that lack either the first or the fifth fibronectin type III repeat is comparable to that seen on monolayers expressing wild‐type L1. In contrast, B28 cells expressing L1 without the third fibronectin type III repeat do not support neurite outgrowth above the background level seen on parental B28 cells. This suggests that the third fibronectin type III repeat plays a key role in the ability of L1 to promote neurite extension. This is consistent with reports that the third fibronectin type III repeat mediates L1 homomultimerization and integrin binding and that plasmin cleavage within this domain interferes with L1 function by abolishing these molecular interactions. J. Neurosci. Res. 61:33–43, 2000. © 2000 Wiley‐Liss, Inc.
Maximum likelihood estimation of a multi‐dimensional log‐concave density

Summary. Let X1,…,Xn be independent and identically distributed random vectors with a (Lebesgue) density f. We first prove that, with probability 1, there is a unique log‐concave maximum likelihood estimator of f. The use of this estimator is attractive because, unlike kernel density estimation, the method is fully automatic, with no smoothing parameters to choose. Although the existence proof is non‐constructive, we can reformulate the issue of computing in terms of a non‐differentiable convex optimization problem, and thus combine techniques of computational geometry with Shor's r‐algorithm to produce a sequence that converges to . An R version of the algorithm is available in the package LogConcDEAD—log‐concave density estimation in arbitrary dimensions. We demonstrate that the estimator has attractive theoretical properties both when the true density is log‐concave and when this model is misspecified. For the moderate or large sample sizes in our simulations, is shown to have smaller mean integrated squared error compared with kernel‐based methods, even when we allow the use of a theoretical, optimal fixed bandwidth for the kernel estimator that would not be available in practice. We also present a real data clustering example, which shows that our methodology can be used in conjunction with the expectation–maximization algorithm to fit finite mixtures of log‐concave densities.
Acute myocardial infarction: association with time since stopping smoking in Italy

Study objective - The study aimed to investigate the relationship between years since stopping smoking and the risk of acute myocardial infarction. Design - This was a hospital based, mul-ticentre, case-control study conducted in Italy between September 1988 and June 1989 within the framework of the GISSI-2 clinical trial. Setting - Over 80 coronary care units in various Italian regions participated. Subjects - A total of 916 incident cases of acute myocardial infarction, below age 75 years, and with no history of ischaemic heart disease, and 1106 control subjects admitted to the same hospitals for acute, non-neoplastic, cardiovascular or cerebrovascular conditions that were not known or suspected to be related to cigarette smoking took part in the study.
Silicon-based system in packaging for light emitting diodes

Silicon-based packaging for light emitting diodes (LEDs) is the tendency of packaging for improving high-power LED performance. In this paper, a simple and high efficient wafer level packaging (WLP) based on silicon with TSV is proposed. Monte-Carlo ray-trace method is implemented to analyze the effect of the size of silicone lens on light extraction efficiency (LEE). The results show that LEE of hemisphere lens is higher than that of spherical segment lens. LEE increases with radius increasing and becomes stable when radius is above 1.2 mm due to the absorption of silicon for small part of light reflected back. Temperature distribution is uniform because of high thermal conductivity of copper and silicon; however, the mismatch of CTE between them causes high thermal stress which is alleviated in TSV when it partly filled with copper from analysis by three-dimensional finite element method. Six-axis micro-tester experiment shows the nominal shear strength of the silicone lens formed on a bare silicon with four TSVs improved 10% compared with that without TSVs. Wafer level packaging for LEDs is proposed. LEDs are encapsulated with silicon substrate with four TSVs filled with copper and other four TSVs filled with silicone. The processes of silicon substrate based on MEMS technology are used. TSV is filled with copper partly by two-step electroplating in order to avoid thinning of the substrate for blind vias. The phosphor conformal coating is implemented using capillary micro-channel, which can improve the angular color uniformity and consistency of WLP. The array of silicone lens using the mould method shows high coherence and few defects.