Miracle-dz/UniFAR-FTUs huggingface dataset:
Constructing irregular surfaces to enclose macromolecular complexes for mesoscale modeling using the discrete surface charge optimization (DISCO) algorithm

Salt‐mediated electrostatics interactions play an essential role in biomolecular structures and dynamics. Because macromolecular systems modeled at atomic resolution contain thousands of solute atoms, the electrostatic computations constitute an expensive part of the force and energy calculations. Implicit solvent models are one way to simplify the model and associated calculations, but they are generally used in combination with standard atomic models for the solute. To approximate electrostatics interactions in models on the polymer level (e.g., supercoiled DNA) that are simulated over long times (e.g., milliseconds) using Brownian dynamics, Beard and Schlick have developed the DiSCO (Discrete Surface Charge Optimization) algorithm. DiSCO represents a macromolecular complex by a few hundred discrete charges on a surface enclosing the system modeled by the Debye‐Hückel (screened Coulombic) approximation to the Poisson‐Boltzmann equation, and treats the salt solution as continuum solvation. DiSCO can represent the nucleosome core particle (>12,000 atoms), for example, by 353 discrete surface charges distributed on the surfaces of a large disk for the nucleosome core particle and a slender cylinder for the histone tail; the charges are optimized with respect to the Poisson‐Boltzmann solution for the electric field, yielding a ∼5.5% residual. Because regular surfaces enclosing macromolecules are not sufficiently general and may be suboptimal for certain systems, we develop a general method to construct irregular models tailored to the geometry of macromolecules. We also compare charge optimization based on both the electric field and electrostatic potential refinement. Results indicate that irregular surfaces can lead to a more accurate approximation (lower residuals), and the refinement in terms of the electric field is more robust. We also show that surface smoothing for irregular models is important, that the charge optimization (by the TNPACK minimizer) is efficient and does not depend on the initial assigned values, and that the residual is acceptable when the distance to the model surface is close to, or larger than, the Debye length. We illustrate applications of DiSCO's model‐building procedure to chromatin folding and supercoiled DNA bound to Hin and Fis proteins. DiSCO is generally applicable to other interesting macromolecular systems for which mesoscale models are appropriate, to yield a resolution between the all‐atom representative and the polymer level. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 2063–2074, 2003
Flavonoids Influence Monocytic GTPase Activity and Are Protective in Experimental Allergic Encephalitis

In the chronic disabling disease multiple sclerosis (MS), migration of monocytes across the blood-brain barrier is a crucial step in the formation of new lesions in the central nervous system (CNS). Infiltrating monocyte-derived macrophages secrete inflammatory mediators such as oxygen radicals, which contribute to axonal demyelination and damage, resulting in neurological deficits. Flavonoids are compounds occurring naturally in food, which scavenge oxygen radicals and have antiinflammatory properties. To investigate whether they might suppress clinical symptoms in MS, we treated rats sensitized for acute and chronic experimental allergic encephalomyelitis, an experimental model of MS, with flavonoids. We demonstrated that the flavonoid luteolin substantially suppressed clinical symptoms and prevented relapse when administered either before or after disease onset. Luteolin treatment resulted in reduced inflammation and axonal damage in the CNS by preventing monocyte migration across the brain endothelium. Luteolin influenced migration by modulating the activity of Rho GTPases, signal transducers involved in transendothelial migration. Oral administration of luteolin also significantly reduced clinical symptoms.
Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract

The cytokine interleukin (IL) 25 has been implicated in the initiation of type 2 immunity by driving the expression of type 2 cytokines such as IL-5 and IL-13, although its role in the regulation of immunity and infection-induced inflammation is unknown. Here, we identify a dual function for IL-25: first, in promoting type 2 cytokine-dependent immunity to gastrointestinal helminth infection and, second, in limiting proinflammatory cytokine production and chronic intestinal inflammation. Treatment of genetically susceptible mice with exogenous IL-25 promoted type 2 cytokine responses and immunity to Trichuris. IL-25 was constitutively expressed by CD4+ and CD8+ T cells in the gut of mouse strains that are resistant to Trichuris, and IL-25–deficient mice on a genetically resistant background failed to develop a type 2 immune response or eradicate infection. Furthermore, chronically infected IL-25−/− mice developed severe infection-induced intestinal inflammation associated with heightened expression of interferon-γ and IL-17, identifying a role for IL-25 in limiting pathologic inflammation at mucosal sites. Therefore, IL-25 is not only a critical mediator of type 2 immunity, but is also required for the regulation of inflammation in the gastrointestinal tract.
Coded aperture design for hyper-spectral image recovery via Matrix Completion

A spectral image is a 3-dimensional spatio-spectral set with a large amount of spectral information for each spatial location of a scene. Compressive Spectral Imaging techniques (CSI) permit to capture the 3D scene in 2-dimensional coded projections. The Coded Aperture Snapshot Spectral Imager (CASSI) is an optical architecture to sense a spectral image in a single projection by applying CSI. CSI increases the sensing speed and reduces the amount of collected data compared to traditional methods. The 3D scene is then recovered by solving an ℓ1-based optimization problem. However, this problem assumes that the scene is sparse in some known orthonormal basis. In contrast, a technique called Matrix Completion (MC) allows the recovery of a scene without such prior knowledge. The MC reconstruction algorithms rely on a low-rank structure of the scene. Moreover, the quality of the estimated scene from CASSI measurements depends on the coded aperture patterns used in the sensing process. Therefore, this paper proposes the design of an optimal coded aperture set for the MC methodology. The designed set is attained by maximizing the distance between the translucent elements in the coded aperture. Simulations show average improvement of around 5 dB when the designed set is used.
A role for primary cilia in aortic valve development and disease

Background: Bicuspid aortic valve (BAV) disease is the most common congenital heart defect, affecting 0.5–1.2% of the population and causing significant morbidity and mortality. Only a few genes have been identified in pedigrees, and no single gene model explains BAV inheritance, thus supporting a complex genetic network of interacting genes. However, patients with rare syndromic diseases that stem from alterations in the structure and function of primary cilia (“ciliopathies”) exhibit BAV as a frequent cardiovascular finding, suggesting primary cilia may factor broadly in disease etiology. Results: Our data are the first to demonstrate that primary cilia are expressed on aortic valve mesenchymal cells during embryonic development and are lost as these cells differentiate into collagen‐secreting fibroblastic‐like cells. The function of primary cilia was tested by genetically ablating the critical ciliogenic gene Ift88. Loss of Ift88 resulted in abrogation of primary cilia and increased fibrogenic extracellular matrix (ECM) production. Consequentially, stratification of ECM boundaries normally present in the aortic valve were lost and a highly penetrant BAV phenotype was evident at birth. Conclusions: Our data support cilia as a novel cellular mechanism for restraining ECM production during aortic valve development and broadly implicate these structures in the etiology of BAV disease in humans. Developmental Dynamics 246:625–634, 2017. © 2017 Wiley Periodicals, Inc.
Embolization or Simple Coverage to Exclude the Internal Iliac Artery During Endovascular Repair of Aortoiliac Aneurysms? Systematic Review and Meta-analysis of Comparative Studies

Purpose: To compare results of simple coverage vs preemptive embolization to exclude the internal iliac artery (IIA) during endovascular repair of aortoiliac aneurysms. Methods: A systematic review of the literature was conducted by searching MEDLINE, CENTRAL, and OpenGray databases until March 2016. Primary outcome measures were safety and efficacy of the 2 strategies. Safety was determined by 30-day mortality and the minor and major complication rates. Efficacy was determined by absence of endoleak from the target IIA. Secondary outcomes of any endoleak, reintervention, operative time, fluoroscopy time, blood loss, contrast volume, and length of hospitalization were also examined. The random effects model was used to calculate combined overall effect sizes of pooled data. Data are presented as the odds ratio (OR) or mean difference (MD) with 95% confidence interval (CI). Forest plots and inconsistency (I2) statistics were used to evaluate the heterogeneity of the included studies. Results: Eight observational studies were included in the analysis. Overall, 284 and 255 subjects underwent IIA coverage or embolization, respectively. IIA coverage resulted in a significantly lower major complication rate (6% vs 29%; OR 2.97, 95% CI 1.46 to 6.04, p=0.003; I2=0%) and shorter hospitalization (MD 0.48 days, 95% CI 0.08 to 0.89, p=0.02; I2=0%), while differences in all other outcomes were not statistically significant. Conclusion: In the presence of limited data, available evidence suggests that simple coverage of the IIA may result in significantly fewer major complications compared to preemptive embolization; at the same time, the rates of endoleaks and/or reinterventions are similar between groups.
Minor Changes in the Hemagglutinin of Influenza A(H1N1)2009 Virus Alter Its Antigenic Properties

Background The influenza A(H1N1)2009 virus has been the dominant type of influenza A virus in Finland during the 2009–2010 and 2010–2011 epidemic seasons. We analyzed the antigenic characteristics of several influenza A(H1N1)2009 viruses isolated during the two influenza seasons by analyzing the amino acid sequences of the hemagglutinin (HA), modeling the amino acid changes in the HA structure and measuring antibody responses induced by natural infection or influenza vaccination. Methods/Results Based on the HA sequences of influenza A(H1N1)2009 viruses we selected 13 different strains for antigenic characterization. The analysis included the vaccine virus, A/California/07/2009 and multiple California-like isolates from 2009–2010 and 2010–2011 epidemic seasons. These viruses had two to five amino acid changes in their HA1 molecule. The mutation(s) were located in antigenic sites Sa, Ca1, Ca2 and Cb region. Analysis of the antibody levels by hemagglutination inhibition test (HI) indicated that vaccinated individuals and people who had experienced a natural influenza A(H1N1)2009 virus infection showed good immune responses against the vaccine virus and most of the wild-type viruses. However, one to two amino acid changes in the antigenic site Sa dramatically affected the ability of antibodies to recognize these viruses. In contrast, the tested viruses were indistinguishable in regard to antibody recognition by the sera from elderly individuals who had been exposed to the Spanish influenza or its descendant viruses during the early 20th century. Conclusions According to our results, one to two amino acid changes (N125D and/or N156K) in the major antigenic sites of the hemagglutinin of influenza A(H1N1)2009 virus may lead to significant reduction in the ability of patient and vaccine sera to recognize A(H1N1)2009 viruses.
Optimal Market Participation of Distributed Load Resources Under Distribution Network Operational Limits and Renewable Generation Uncertainties

Distributed load resources are encouraged nowadays to actively participate in the energy market. As a part of the distribution system, they affect the power flow pattern of the network and interact with intermittent renewable generation in the distribution system. In this regard, one fundamental challenge, not yet addressed, is to derive an optimal market participation model, under the demand bidding paradigm, that systemically accounts for the operational limits of a physical distribution grid considering uncertainty associated with both the electricity market, and distribution network system. Accordingly, this paper addresses the optimal demand biding under uncertain market and distribution system data and network operational limits. Assuming a price-taker distribution utility with renewable energy, inflexible and deferrable loads and a two-settlement market model, we develop a two-stage robust stochastic bidding formulation solved using a decomposition algorithm. We derive optimal bid curves that minimize energy procurement cost and fully comply with the operational standards of the distribution network. Moreover, novel indexes are proposed to help the utility evaluate the operational performance of its network with regard to deferrable loads and renewable resources. Finally, we illustrate the advantage of the proposed model from a set of numerical experiments on an example system and the 33-bus system.
Scene selection and the use of NASA's global orthorectified Landsat dataset for land cover and land use change monitoring

This study examines the utility of NASA's circa 1990 and circa 2000 global orthorectified Landsat dataset for land cover and land use change mapping and monitoring across Africa. This is achieved by comparing the temporal and spatial variation of NDVI, measured independently by the NOAA‐AVHRR at the time of Landsat scene acquisition, against the seasonal mean for each Landsat scene extent. Decadal sequences of drift‐corrected NOAA‐AVHRR imagery were used to calculate NDVI means and standard deviations for the periods covered by the scenes composing the c.1990 and c.2000 Landsat datasets. The specific NOAA‐AVHRR NDVI values at the acquisition date of each individual Landsat scene were also calculated and the differences, both from the mean and scaled by standard deviation, were mapped for the Landsat scene footprints in the c.1990 and c.2000 datasets. The resulting maps show the temporal position of each Landsat scene within the seasonal NDVI cycle, and provide a valuable guide to assist in quantifying uncertainty and interpreting land cover and land use changes inferred from these Landsat data.
Recombinant outer membrane vesicles carrying Chlamydia muridarum HtrA induce antibodies that neutralize chlamydial infection in vitro

Background Outer membrane vesicles (OMVs) are spheroid particles released by all Gram-negative bacteria as a result of the budding out of the outer membrane. Since they carry many of the bacterial surface-associated proteins and feature a potent built-in adjuvanticity, OMVs are being utilized as vaccines, some of which commercially available. Recently, methods for manipulating the protein content of OMVs have been proposed, thus making OMVs a promising platform for recombinant, multivalent vaccines development. Methods Chlamydia muridarum DO serine protease HtrA, an antigen which stimulates strong humoral and cellular responses in mice and humans, was expressed in Escherichia coli fused to the OmpA leader sequence to deliver it to the OMV compartment. Purified OMVs carrying HtrA (CM rHtrA-OMV) were analyzed for their capacity to induce antibodies capable of neutralizing Chlamydia infection of LLC-MK2 cells in vitro. Results CM rHtrA-OMV immunization in mice induced antibodies that neutralize Chlamydial invasion as judged by an in vitro infectivity assay. This was remarkably different from what observed with an enzymatically functional recombinant HtrA expressed in, and purified from the E. coli cytoplasm (CM rHtrA). The difference in functionality between anti-CM rHtrA and anti-CM rHtrA-OMV antibodies was associated to a different pattern of protein epitopes recognition. The epitope recognition profile of anti-CM HtrA-OMV antibodies was similar to that induced in mice during Chlamydial infection. Conclusions When expressed in OMVs HtrA appears to assume a conformation similar to the native one and this results in the elicitation of functional immune responses. These data further support the potentiality of OMVs as vaccine platform.
Discriminative and participant-rated effects of methylphenidate in children diagnosed with attention deficit hyperactivity disorder (ADHD).

Despite the demonstrated beneficial effects of methylphenidate and d-amphetamine for the treatment of attention-deficit hyperactivity disorder (ADHD), the discriminative and subjective effects of these compounds in children are not well understood. This study was designed to characterize such effects in children diagnosed with ADHD. In a series of 3 experiments, 17 children were examined to determine whether methylphenidate (n = 12) and d-amphetamine (n = 5) could be reliably discriminated at doses typically used in clinical practice. Under some conditions (e.g., when they were instructed to attend to the drug effects or when a wide range of doses was used), children discriminated methylphenidate (5.0-30.0 mg) from placebo. Children tested under a range of doses of d-amphetamine (2.5-20.0 mg) were unable to discriminate this drug from placebo reliably. Neither methylphenidate nor d-amphetamine produced reliable participant-rated effects.
A fast and reliable algorithm for video noise estimation based on spatio-temporal sobel gradients

A fast and reliable spatio-temporal algorithm for estimating additive white Gaussian noise (AWGN) in video sequences is proposed. The input video is divided into right cuboids. Estimations are made on three independent domains (spatial, temporal-horizontal, and temporal-vertical). Inside each domain, homogeneous blocks are first identified based on Sobel gradients with an adaptive and self-determined threshold. The selected blocks are then filtered by a Laplacian operator. The average of the filtering convolutions provides the estimated noise variance for each domain. The arithmetic average of these three estimated variances is computed to be the final estimated noise variance. Experimental results show that the proposed algorithm achieves better performance and maintains low complexity for a variety of video sequences over a large range of noise variances.
Intravital Imaging of a Massive Lymphocyte Response in the Cortical Dura of Mice after Peripheral Infection by Trypanosomes

Peripheral infection by Trypanosoma brucei, the protozoan responsible for sleeping sickness, activates lymphocytes, and, at later stages, causes meningoencephalitis. We have videoed the cortical meninges and superficial parenchyma of C56BL/6 reporter mice infected with T.b. brucei. By use of a two-photon microscope to image through the thinned skull, the integrity of the tissues was maintained. We observed a 47-fold increase in CD2+ T cells in the meninges by 12 days post infection (dpi). CD11c+ dendritic cells also increased, and extravascular trypanosomes, made visible either by expression of a fluorescent protein, or by intravenous injection of furamidine, appeared. The likelihood that invasion will spread from the meninges to the parenchyma will depend strongly on whether the trypanosomes are below the arachnoid membrane, or above it, in the dura. Making use of optical signals from the skull bone, blood vessels and dural cells, we conclude that up to 40 dpi, the extravascular trypanosomes were essentially confined to the dura, as were the great majority of the T cells. Inhibition of T cell activation by intraperitoneal injection of abatacept reduced the numbers of meningeal T cells at 12 dpi and their mean speed fell from 11.64 ± 0.34 μm/min (mean ± SEM) to 5.2 ± 1.2 μm/min (p = 0.007). The T cells occasionally made contact lasting tens of minutes with dendritic cells, indicative of antigen presentation. The population and motility of the trypanosomes tended to decline after about 30 dpi. We suggest that the lymphocyte infiltration of the meninges may later contribute to encephalitis, but have no evidence that the dural trypanosomes invade the parenchyma.
Arabic Topic Detection using automatic text summarisation

With the exponential growth of the online available Arabic documents, classifying and processing large Arabic corpora has became a challenging task. The presence of noisy information embedded in these documents has made it even more difficult to get accurate results when applying a Topic Detection (TD) process. To address this problem, a proper features selection approach is needed to enhance the topic detection accuracy. In this paper, we explore the impact of using automatic summarisation technique along with a feature-selection process to enhance Arabic Topic Detection. In our work we show that using automatic summarisation reduces noisy information and results in a significant enhancement to the topic detection process and therefore increases the performance of our TD system. This was achieved by the ability of our summariser system in reducing documents size to speed up the detection process.
Join Query Optimization Techniques for Complex Event Processing Applications

Complex event processing (CEP) is a prominent technology used in many modern applications for monitoring and tracking events of interest in massive data streams. CEP engines inspect real-time information flows and attempt to detect combinations of occurrences matching predefined patterns. This is done by combining basic data items, also called "primitive events", according to a pattern detection plan, in a manner similar to the execution of multi-join queries in traditional data management systems. Despite this similarity, little work has been done on utilizing existing join optimization methods to improve the performance of CEP-based systems. In this paper, we provide the first theoretical and experimental study of the relationship between these two research areas. We formally prove that the CEP Plan Generation problem is equivalent to the Join Query Plan Generation problem for a restricted class of patterns and can be reduced to it for a considerably wider range of classes. This result implies the NP-completeness of the CEP Plan Generation problem. We further show how join query optimization techniques developed over the last decades can be adapted and utilized to provide practically efficient solutions for complex event detection. Our experiments demonstrate the superiority of these techniques over existing strategies for CEP optimization in terms of throughput, latency, and memory consumption.