Miracle-dz/UniFAR-FTUs huggingface dataset:
Altered expression of transcription factors IRF4 and IRF8 in peripheral blood B cells is associated with clinical severity and circulating plasma cells frequency in patients with myasthenia gravis

Abstract Previous studies have shown that interferon regulatory factor-4 (IRF4) and IRF8 play critical but distinct roles in the differentiation of B cells into plasma cells (PCs). In the present study, we aimed to measure the expression levels of IRF4 and IRF8 in B cells from patients with myasthenia gravis (MG) and to investigate whether the expression of IRF4 and IRF8 associates with pathogenesis of MG. A total of 35 anti-acetylcholine receptor (AChR) antibody (Ab)-positive patients with MG [20 generalized MG (GMG) and 15 ocular MG (OMG) and 25 healthy donors were recruited in this study. The quantitative myasthenia gravis score (QMGS) was used to evaluate the clinical severity. Real-time PCR and Western blot were used to measure the levels of IRF4 and IRF8 expressed in peripheral blood B cells. Peripheral blood CD138+ PCs were assayed by flow cytometry. Our data demonstrated that the mRNA/protein levels of IRF4 and IRF8 were significantly higher and lower, respectively, in patients with OMG/GMG groups compared with healthy controls. In addition, IRF4 expression was significantly higher and IRF8 expression was significantly lower in GMG group than in OMG group. Pearson’s correlation analysis revealed that IRF8 expression was negatively correlated with clinical severity, PCs frequency and anti-AChR Ab levels, while IRF4 expression and IRF4/IRF8 ratio was positively correlated with these parameters in two MG subgroups. Finally, glucocorticoid treatment can relieve the imbalance of IRF4/IRF8 in peripheral blood B cells, and this restoration is accompanied by reduced PCs frequency and clinical symptoms. These evidences suggest that IRF4 and IRF8 are important in the counter-balancing mechanisms controlling differentiation of PCs in MG. The disruption of the balanced IRF4/IFR8 ratio in B cells may play important roles in the pathogenesis of MG and offer a promising therapeutic target for the development of novel immunotherapy for MG patients.
Efficient Computation of Importance Based Communities in Web-Scale Networks Using a Single Machine

Finding decompositions of a graph into a family of communities is crucial to understanding its underlying structure. Algorithms for finding communities in networks often rely only on structural information and search for cohesive subsets of nodes. In practice however, we would like to find communities that are not only cohesive, but also influential or important. In order to capture such communities, Li, Qin, Yu, and Mao introduced a novel community model called "k-influential community" based on the concept of $k$-core, with numerical values representing "influence" assigned to the nodes. They formulate the problem of finding the top-r most important communities as finding r connected k-core subgraphs ordered by the lower-bound of their importance. In this paper, our goal is to scale-up the computation of top-r, k-core communities to web-scale graphs of tens of billions of edges. We feature several fast new algorithms for this problem. With our implementations, we show that we can efficiently handle massive networks using a single consumer-level machine within a reasonable amount of time.
A SAS ® Macro for Computing Pooled Likelihood Ratio Tests with Multiply Imputed Data

For multilevel analyses (e.g., linear mixed models), researchers are often interested in pooling, interpreting, and testing both fixed effects and random effects. PROC MIANALYZE has two shortcomings in this regard. First, it cannot easily pool variance estimates. Second, the significance tests of these estimates are Wald-type tests that are inappropriate for testing variance estimates. Likelihood ratio testing is a more flexible approach, as it can be used to compare models that differ in both fixed and random effects. The likelihood ratio test statistic requires a complex calculation that is not included in PROC MIANALYZE. This paper describes a SAS macro, MMI_ANALYZE, that fits two user-specified models in PROC MIXED, pools the estimates from those models (including variance components), and implements a pooled likelihood ratio test.
Comparative pharmacokinetics of diaveridine in pigs and chickens following single intravenous and oral administration

Comparative pharmacokinetic profiles of diaveridine following single intravenous and oral dose of 10 mg/kg body weight in healthy pigs and chickens were investigated, respectively. Concentrations of diaveridine in plasma samples were determined using a validated high-performance liquid chromatography-ultraviolet (HPLC-UV) method. The concentration-time data were subjected to noncompartmental kinetic analysis by WinNonlin program. The corresponding pharmacokinetic parameters in pigs or chickens after single intravenous administration were as follows, respectively: t1/2β (elimination half-life) 0.74 ± 0.28 and 3.44 ± 1.07 h; Vd (apparent volume of distribution) 2.70 ± 0.99 and 3.86 ± 0.92 L/kg; ClB (body clearance) 2.59 ± 0.62 and 0.80 ± 0.14 L/h/kg; and AUC0-∞ (area under the blood concentration vs. time curve) 4.11 ± 1.13 and 12.87 ± 2.60 μg∙h/mL. The corresponding pharmacokinetic parameters in pigs or chickens after oral administration were as follows, respectively: t1/2β 1.78 ± 0.41 and 2.91 ± 0.57 h; Cmax (maximum concentration) 0.43 ± 0.24 and 1.45 ± 0.57 μg/mL; Tmax (time to reach Cmax ) 1.04 ± 0.67 and 3.25 ± 0.71 h; and AUC0-∞ 1.33 ± 0.55 and 9.28 ± 2.69 μg∙h/mL. The oral bioavailability (F) of diaveridine in pigs or chickens was determined to be 34.6% and 72.2%, respectively. There were significant differences between the pharmacokinetics profiles in these two species.
Formation of Ultra-High-Density Ferromagnetic Column Arrays Beyond 1 Tera/inch2 Using Porous Alumina Template

The formation of ultra-high-density ferromagnetic column arrays beyond 1 Tera/inch2 was investigatedusing porous alumina films formed on Si substrate. It was empirically known that a pitch of nanohole array shrunk with a reduction of anodic voltage. We carried out anodic oxidation of sputtered Al film at the anodic voltage below 10V, and found that the density of the nanohole arraysincreased significantly with a reduction of the anodic voltage.and reached 1.5 Tera/inch2 when the anodic voltage was 5.0 V. We also succeeded in the electro-plating of Co column array in these fine holes.The Co column arrays formed by electroplating in the nanoholes were polycrystalline. and showed perpendicular magnetic anisotropy when their aspect ratio was larger than 3. The coercive field of Co columns tended to increase with a reduction of the hole diameter, which was confirmed by micromagnetic simulation based on the LLG equations. These results strongly suggest that ferromagnetic nano column arrays buried in porous alumina film on substrate have a high potential for application to a future ultra-high density magnetic recording media.
Multi-Example Search in Rich Information Graphs

In rich information spaces, it is often hard for users to formally specify the characteristics of the desired answers, either due to the complexity of the schema or of the query language, or even because they do not know exactly what they are looking for. Exemplar queries constitute a query paradigm that overcomes those problems, by allowing users to provide examples of the elements of interest in place of the query specification. In this paper, we propose a general approach where the user-provided example can comprise several partial specification fragments, where each fragment describes only one part of the desired result. We provide a formal definition of the problem, which generalizes existing formulations for both the relational and the graph model. We then describe exact algorithms for its solution for the case of information graphs, as well as top-k algorithms. Experiments on large real datasets demonstrate the effectiveness and efficiency of the proposed approach.
Modeling and Computer Simulation of Block Copolymer/Nanoparticle Composites

Molecular dynamics computer simulation is used to explore the phase behavior and structural properties of block copolymers and block copolymer nanocomposites. Block copolymers microphase separate into ordered structures with domains on a nanometer length scale, which can then be used as a template for nanoparticles. This research provides insight into the fundamental physics that govern phase behavior and properties of these materials. We first focus on the case of neat diblock copolymers. We performed discontinuous molecular dynamics simulation to study the phase behavior of diblock copolymers modeled as chains of tangent hard spheres with square shoulder repulsions between unlike species as a function of chain length, volume fraction (f) and interaction strength (χ). The location of the order-disorder transition for a symmetric copolymer is close to the predictions of Fredrickson and Helfand. Our simulation results for packing fractions of 0.35, 0.40 and 0.45 and chain lengths 10 and 20 are summarized in phase diagrams which display disordered, lamellae, perforated lamellae, cylindrical and BCC spherical phases in the χN vs. f plane. These phase diagrams are consistent with phase diagrams from other simulation studies. Contrary to theoretical predictions we observe the perforated lamellar phase near regions of predicted gyroid stability, and the spherical phase only in the systems with high packing fraction and long chain length. These discrepancies may be due to the short chain lengths considered, as they are less evident in the 20-bead chains than the 10-bead chains. We examine the structural spacing of the microphases and the variation of that spacing with χN. We also examine the internal energy and entropy and their variation with χN. Our results are consistent with self-consistent field theory results for the strong segregation limit. We then extend our simulations to study the phase behavior and properties of diblock copolymer/nanoparticle composites. The nanoparticles are modeled as hard spheres with a square shoulder repulsion with one of the copolymer blocks. The resulting phase diagrams are presented for composites containing nanoparticles of various sizes and interaction strengths, and include lamellae, perforated lamellae, cylinders and disordered phases. Composites containing large nanoparticles also exhibit two-phase coexistence between different copolymer phases, or between a copolymer phase and a nanoparticle phase, depending upon the nanoparticle interaction strength. We also present concentration profiles perpendicular to the lamellar interface for nanoparticles of different sizes and interaction strengths. Neutral nanoparticles concentrate at the interface between copolymer domains while interacting nanoparticles concentrate within the favorable domain. The larger nanoparticles are more easily localized, but have less impact on the copolymer concentration profiles. The lamellar spacing increases with nanoparticle volume fraction for interacting nanoparticles,…
Rheem : Enabling Multi-Platform Task Execution – A Shortcut to Freedom –

Many emerging applications, from domains such as healthcare and oil & gas, require several data processing systems for complex analytics. This demo paper showcasesRheem, a framework that provides multi-platform task execution for such applications. It features a three-layer data processing abstraction and a new query optimization approach for multi-platform settings. We will demonstrate the strengths of Rheem by using real-world scenarios from three di↵erent applications, namely, machine learning, data cleaning, and data fusion.
Second-generation p-values: Improved rigor, reproducibility, & transparency in statistical analyses

Verifying that a statistically significant result is scientifically meaningful is not only good scientific practice, it is a natural way to control the Type I error rate. Here we introduce a novel extension of the p-value—a second-generation p-value (pδ)–that formally accounts for scientific relevance and leverages this natural Type I Error control. The approach relies on a pre-specified interval null hypothesis that represents the collection of effect sizes that are scientifically uninteresting or are practically null. The second-generation p-value is the proportion of data-supported hypotheses that are also null hypotheses. As such, second-generation p-values indicate when the data are compatible with null hypotheses (pδ = 1), or with alternative hypotheses (pδ = 0), or when the data are inconclusive (0 < pδ < 1). Moreover, second-generation p-values provide a proper scientific adjustment for multiple comparisons and reduce false discovery rates. This is an advance for environments rich in data, where traditional p-value adjustments are needlessly punitive. Second-generation p-values promote transparency, rigor and reproducibility of scientific results by a priori specifying which candidate hypotheses are practically meaningful and by providing a more reliable statistical summary of when the data are compatible with alternative or null hypotheses.
The nature of the electron acceptor (MnIV/NO3) triggers the differential expression of genes associated with stress and ammonium limitation responses in Shewanella algae C6G3

Shewanella algae C6G3 can dissimilatively reduce nitrate into ammonium and manganese oxide (MnIV) into MnII. It has the unusual ability to anaerobically produce nitrite from ammonium in the presence of MnIV. To gain insight into their metabolic capabilities, global mRNA expression patterns were investigated by RNA-seq and qRT-PCR in cells growing with lactate and ammonium as carbon and nitrogen sources, and with either MnIV or nitrate as electron acceptors. Genes exhibiting higher expression levels in the presence of MnIV belonged to functional categories of carbohydrate, coenzyme, lipid metabolisms and inorganic ion transport. The comparative transcriptomic pattern between MnIV and NO3 revealed that the strain presented an ammonium limitation status with MnIV, despite the presence of a non-limiting concentration of ammonium under both culture conditions. In addition, in the presence of MnIV, ntrB/nrtC regulators, ammonium channel, nitrogen regulatory protein P-II, glutamine synthetase and asparagine synthetase glutamine-dependent genes were over-represented. Under the nitrate condition, the expression of genes involved in the synthesis of several amino acids was increased. Finally, the expression level of genes associated with the general stress response was also amplified in both conditions and among them, katE, a putative catalase/peroxidase present on several Shewanella genomes, was highly expressed with a median value relatively higher in the MnIV condition.
Cashew gum microencapsulation protects the aroma of coffee extracts

Microencapsulation of materials rich in volatile compounds by spray drying presents the challenge of removing water by vapourization without loss of odour and/or flavour components. Crioconcentrated coffee extracts rich in odour components were used as a substrate core to evaluate microencapsulation with cashew gum from Anacardium occidentale L. In Brazil, cashew gum is a low cost alternative to the traditional Arabic gum. A suspension containing coffee extract and the wall material was dissolved in water and then passed through a spray dryer. Core microcapsules were microwave-assisted extracted (MAE) and the aroma protection of the microcapsules produced was evaluated using gas chromatography and mass spectroscopy (GC/MS). The external morphology and size distribution of the microcapsules were obtained by scanning electron microscopy (SEM) and light scattering techniques, respectively. When comparing Arabic and cashew gum microencapsulation of coffee extracts both wall materials were observed to have similar aroma protection, external morphology and size distribution. Sensory analysis was employed to examine flavour protection and consumer preference with microencapsulation. These biochemical, sensory and structural data suggest that low cost cashew gum is a well suited alternative for odour microencapsulation to the more costly Arabic gum currently used in Brazil.
Genotyping Candida albicans from Candida Leukoplakia and Non-Candida Leukoplakia Shows No Enrichment of Multilocus Sequence Typing Clades but Enrichment of ABC Genotype C in Candida Leukoplakia

Oral leukoplakias are histopathologically-diagnosed as Candida leukoplakia or non-Candida leukoplakia by the presence or absence of hyphae in the superficial epithelium. Candida leukoplakia lesions have significantly increased malignant potential. Candida albicans is the most prevalent fungal species associated with oral leukoplakia and may contribute to malignant transformation of Candida leukoplakia. To date, no detailed population analysis of C. albicans isolates from oral leukoplakia patients has been undertaken. This study investigated whether specific C. albicans genotypes were associated with Candida leukoplakia and non-Candida leukoplakia in a cohort of Irish patients. Patients with histopathologically-defined Candida leukoplakia (n = 31) or non-Candida leukoplakia (n = 47) were screened for Candida species by culture of oral rinse and lesional swab samples. Selected C. albicans isolates from Candida leukoplakia patients (n = 25), non-Candida leukoplakia patients (n = 19) and oral carriage isolates from age and sex matched healthy subjects without leukoplakia (n = 34) were subjected to multilocus sequence typing (MLST) and ABC genotyping. MLST revealed that the clade distribution of C. albicans from both Candida leukoplakia and non-Candida leukoplakia lesions overlapped with the corresponding clade distributions of oral carriage isolates and global reference isolates from the MLST database indicating no enrichment of leukoplakia-associated clones. Oral leukoplakia isolates were significantly enriched with ABC genotype C (12/44, 27.3%), particularly Candida leukoplakia isolates (9/25, 36%), relative to oral carriage isolates (3/34, 8.8%). Genotype C oral leukoplakia isolates were distributed in MLST clades 1,3,4,5,8,9 and 15, whereas genotype C oral carriage isolates were distributed in MLST clades 4 and 11.
Magnetic graphene@PANI@porous TiO2 ternary composites for high-performance electromagnetic wave absorption

A two-step strategy combining in situ polymerization and a hydrothermal process has been developed for coupling polyaniline (PANI) with porous TiO2 anchored on magnetic graphene. The microstructure and morphology of magnetic graphene@PANI@porous TiO2 were characterized by FETEM, FESEM, XRD, XPS and VSM in detail. The results indicated that magnetic graphene@PANI was completely covered by porous TiO2 with random orientations and the saturation magnetization value of the composite was 19.2 emu g−1. PANI was used to decrease the absorber thickness, while the porous TiO2 with a large surface area was designed to enhance the interaction between the electromagnetic (EM) wave and the absorber through multiple reflections, thus enhancing EM wave absorption properties. As an EM wave absorber, the maximum reflection loss of the composite was up to −45.4 dB due to the better normalized characteristic impedance (close to 1) at a thickness of only 1.5 mm and the absorption bandwidths exceeding −10 dB were 11.5 GHz when the thickness ranged from 1 to 3.5 mm. The excellent EM wave absorption performance was ascribed to the combined contribution from the enhanced dielectric relaxation processes, the unique porous nanostructures, the quarter-wave length matching model and the well-matched normalized characteristic impedance. Consequently, it is believed that the composite could be used as an excellent EM wave absorption material and the two-step strategy offered an effective way to design a high-performance EM wave absorber with a relatively thin thickness.
Perfusion bioreactors for bone tissue engineering: A combined experimental and computational approach

Bone tissue engineering aims to overcome the drawbacks of current bone regeneration techniques in orthopaedics. Bioreactors are widely used in the field of bone tissue engineering, as they help support efficient nutrition of cultured cells with the possible combination of applying mechanical stimuli. Beneficial influencing parameters of in-vitro cultures are difficult to find and are mostly determined by trial and error, which is associated with significant time and money spent. Mathematical simulations can support the finding of optimal parameters. Simulations have evolved over the last 20 years from simple analytical models to complex and detailed computational models. They allow researchers to simulate the mechanical as well as the biological environment experienced by cells seeded on scaffolds in a bioreactor. Based on the simulation results, it is possible to give recommendations about specific parameters for bone bioreactor cultures, such as scaffold geometries, scaffold mechanical properties, the level of applied mechanical loading or nutrient concentrations. This article reviews the evolution in simulating various aspects of dynamic bone culture in bioreactors and reveals future research directions.
Crystal Structure of Pim1 Kinase in Complex with a Pyrido[4,3-D]Pyrimidine Derivative Suggests a Unique Binding Mode

Human Pim1 kinase is a serine/threonine protein kinase that plays important biological roles in cell survival, apoptosis, proliferation, and differentiation. Moreover, Pim1 is up-regulated in various hematopoietic malignancies and solid tumors. Thus, Pim1 is an attractive target for cancer therapeutics, and there has been growing interest in developing small molecule inhibitors for Pim1. Here, we describe the crystal structure of Pim1 in complex with a newly developed pyrido[4,3-d]pyrimidine-derivative inhibitor (SKI-O-068). Our inhibitor exhibits a half maximum inhibitory concentration (IC50) of 123 (±14) nM and has an unusual binding mode in complex with Pim1 kinase. The interactions between SKI-O-068 and the Pim1 active site pocket residue are different from those of other scaffold inhibitor-bound structures. The binding mode analysis suggests that the SKI-O-068 inhibitor can be improved by introducing functional groups that facilitate direct interaction with Lys67, which aid in the design of an optimized inhibitor.
Challenges and impossibilities of ‘standing alongside’ in an intolerable context: Learning from refugees and volunteers in the Calais camp

This article describes the experience of setting up a psychosocial and therapeutic support project in the French Calais refugee camp, by a group of family therapists and clinical psychologists from the United Kingdom. This came about in response to reports of a humanitarian crisis unfolding on our doorstep, with the British government’s lack of support for the growing numbers of refugees gathering along the UK border with France. The project involved working alongside other agencies in the camp to provide psychosocial and resilience-based therapeutic support to unaccompanied young people, women, children and their families and also to many volunteers in the camp. The process of setting up the work is described, as well as the challenges and dilemmas of offering an intervention in extremely unsafe and insanitary conditions, where for most the experience of trauma was ongoing. The project was informed by systemic–narrative practice and community/liberation psychology, which incorporate the political and social context. A narrative framework offered a way of drawing on people’s strengths and resources, rooted in their cultural and social histories and helping them connect with preferred identities, which we found to be essential in the context of ongoing crisis.