Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics and relative bioavailability of fixed-dose combination of clopidogrel and aspirin versus coadministration of individual formulations in healthy Korean men

Background Simultaneous prescription of clopidogrel and low-dose aspirin is recommended for the treatment of acute coronary syndrome because of improvements in efficacy and patient compliance. In this study, the pharmacokinetics of a fixed-dose combination (FDC) of clopidogrel and aspirin was compared with coadministration of individual formulations to clarify the equivalence of the FDC. Methods This was a randomized, open-label, two-period, two-treatment, crossover study in healthy Korean men aged 20–55 years. Subjects received two FDC capsules of clopidogrel/aspirin 75/100 mg (test) or two tablets of clopidogrel 75 mg and two capsules of aspirin 100 mg (reference) with a 14-day washout period. Plasma concentrations of clopidogrel, aspirin, and salicylic acid were measured using validated ultraperformance liquid chromatography–tandem mass spectrometry. Bioequivalence was assessed by analysis of variance and calculation of the 90% confidence intervals (CIs) of the ratios of the geometric means (GMRs) for AUClast and Cmax for clopidogrel and aspirin. Results Sixty healthy subjects were enrolled, and 53 completed the study. Clopidogrel, aspirin, and salicylic acid showed similar absorption profiles and no significant differences in Cmax, AUClast, and Tmax between FDC administration and coadministration of individual formulations. The GMRs (90% CI) for the Cmax and AUClast of clopidogrel were 1.08 (0.95, 1.23) and 0.93 (0.84, 1.03), respectively. The GMRs (90% CI) for the Cmax and AUClast of aspirin were 0.98 (0.84, 1.13) and 0.98 (0.93, 1.04), respectively. Both treatments were well tolerated in the study subjects. Conclusion The FDC of clopidogrel and aspirin was bioequivalent to coadministration of each individual formulation. The FDC capsule exhibited similar safety and tolerability profiles to the individual formulations. Therefore, clopidogrel/aspirin 75 mg/100 mg FDC capsules can be prescribed to improve patient compliance.
Learning and decisions in contextual multi-armed bandit tasks

Contextual Multi-Armed Bandit (CMAB) tasks are a novel framework to assess decision making in uncertain environments. In a CMAB task, participants are presented with multiple options (arms) which are characterized by a number of features (context) related to the reward associated with the arms. By choosing arms repeatedly and observing the reward, participants can learn about the relation between context and reward and improve their decision strategy. We present two studies on how people behave in CMAB tasks. Within a stationary environment, we find that participants are best described by Thompson Sampling-based Gaussian Process models. In a dynamic CMAB task we again find that participants are best described by probability matching of Gaussian Process expectations. Our findings imply that behavior previously referred to as "irrational" can actually be seen as a well-adapted strategy based on powerful inference algorithms.
What Do Transitive Inference and Class Inclusion Have in Common? Categorical (Co)Products and Cognitive Development

Transitive inference, class inclusion and a variety of other inferential abilities have strikingly similar developmental profiles—all are acquired around the age of five. Yet, little is known about the reasons for this correspondence. Category theory was invented as a formal means of establishing commonalities between various mathematical structures. We use category theory to show that transitive inference and class inclusion involve dual mathematical structures, called product and coproduct. Other inferential tasks with similar developmental profiles, including matrix completion, cardinality, dimensional changed card sorting, balance-scale (weight-distance integration), and Theory of Mind also involve these structures. By contrast, (co)products are not involved in the behaviours exhibited by younger children on these tasks, or simplified versions that are within their ability. These results point to a fundamental cognitive principle under development during childhood that is the capacity to compute (co)products in the categorical sense.
Does Internet and Computer "Addiction" Exist? Some Case Study Evidence

It has been alleged that social pathologies are beginning to surface in cyberspace (i.e., technological addictions). To date, there is very little empirical evidence that computing activities (i.e., internet use, hacking, programming) are addictive. Anecdotal evidence indicates that the typical "addict" is a teenager, usually male, with little or no social life, and little or no self-confidence. This article concentrates on five case studies of excessive computer usage. It is argued that of the five cases, only two of them describe "addicted" subjects. Addiction components criteria were used in the assessment. The excessive usage in the majority of cases was purely symptomatic and was highlighted how the subjects used the Internet/computer to counteract other deficiencies.
Remote Control of Smart Meters: Friend or Foe?

The traditional electrical grid is transitioning into the smart grid. New equipment is being installed to simplify the process of monitoring and managing the grid, making the system more transparent to use but also introducing new security problems. Smart meters are replacing the traditional electrical utility meters, offering new functionalities such as remote reading, automatic error reporting, and the possibility for remote shutoff. This last feature is studied in this paper through two scenarios where the effects are outlined, both on a theoretical level and through a simulation. In the first scenario, the frequency property of the grid is the target to possibly cause a blackout. In the second scenario, the voltage is driven out of bounds by the adversary.
Large-Scale Screening of a Targeted Enterococcus faecalis Mutant Library Identifies Envelope Fitness Factors

Spread of antibiotic resistance among bacteria responsible for nosocomial and community-acquired infections urges for novel therapeutic or prophylactic targets and for innovative pathogen-specific antibacterial compounds. Major challenges are posed by opportunistic pathogens belonging to the low GC% Gram-positive bacteria. Among those, Enterococcus faecalis is a leading cause of hospital-acquired infections associated with life-threatening issues and increased hospital costs. To better understand the molecular properties of enterococci that may be required for virulence, and that may explain the emergence of these bacteria in nosocomial infections, we performed the first large-scale functional analysis of E. faecalis V583, the first vancomycin-resistant isolate from a human bloodstream infection. E. faecalis V583 is within the high-risk clonal complex 2 group, which comprises mostly isolates derived from hospital infections worldwide. We conducted broad-range screenings of candidate genes likely involved in host adaptation (e.g., colonization and/or virulence). For this purpose, a library was constructed of targeted insertion mutations in 177 genes encoding putative surface or stress-response factors. Individual mutants were subsequently tested for their i) resistance to oxidative stress, ii) antibiotic resistance, iii) resistance to opsonophagocytosis, iv) adherence to the human colon carcinoma Caco-2 epithelial cells and v) virulence in a surrogate insect model. Our results identified a number of factors that are involved in the interaction between enterococci and their host environments. Their predicted functions highlight the importance of cell envelope glycopolymers in E. faecalis host adaptation. This study provides a valuable genetic database for understanding the steps leading E. faecalis to opportunistic virulence.
Enzyme Immobilization: An Overview on Nanoparticles as ImmobilizationMatrix

Immobilization process is to optimize the operational performance of an enzyme for industrial applications. So far different matrices have been described in the literature to improve the performance of the immobilized enzymes. With the advent of nanotechnology, the nanomaterials because of their unique physico-chemical properties constitute novel and interesting matrices for enzyme immobilization. The nanomaterials possess ideal characteristics to equilibrate principal factors which determine biocatalysts efficiency, including specific surface area, mass transfer resistance and effective enzyme loading. This review presents the current scenario and techniques in enzyme immobilization. An overview of the main methods used to combine proteins/enzymes with nanoparticles is given in the study. The advantages and disadvantages of nanoparticles as immobilization matrix are also discussed.
Use of Waste Plastic in Concrete Mixture as Aggregate Replacement

One of the environmental issues in most regions of Iran is the large number of bottles made from poly-ethylene terephthalate (PET) deposited in domestic wastes and landfills. Due to the high volume of these bottles, more than 1 million m3 landfill spaces are needed for disposal every year. The purpose of this experimental study was to investigate the possibility of using PET waste in asphalt concrete mixes as aggregate replacement (Plastiphalt) to reduce the environmental effects of PET disposal. Concrete is the most widely used man made construction material in the w and its second only to water as the most utilized substance in the planet. Seeking aggregates for concrete and to dispose of the waste from various commodities is the present concern. Today sustainability has got top priority in construction industry. In the present study the recycled plastics were used to prepare the coarse aggregates thereby providing a sustainable option to deal with the plastic waste There are many recycling plants across the world, but as plastics are recycled they lose their strength with the number of recycling. So these plastics will end up as earth fill. In this circumstance instead of recycling it repeatedly, if it is utilized to prepare aggregates for concrete, it will be a boon to the construction industry. Most of the failures in concrete structures occur due to the failure of concrete by crushing of aggregates. Plastic aggregate which have low crushing values will not be crushed as easily as the stone aggregates. These aggregates are also lighter in weight compared to stone aggregates. Since a complete substitution for Conventional Aggregate was not found feasible, a partial substitution with various percentage of plastic aggregate was done. Both volumetric and grade substitution was employed in this investigation.
Generating security event correlation rules through k-means clustering

Current implementations of intrusion detection systems (IDSs) have two drawbacks: 1) they normally generate far too many false positives, overloading human operators to such an extent that they can not respond effectively to the real alerts; 2) depending on the proportion of genuine attacks within the total network traffic, an IDS may never be effective. One approach to overcoming these obstacles is to correlate information from a wide variety of networks sensors, not just IDSs, in order to obtain a more complete picture on which to base decisions as to whether alerted events represent malicious activity or not. The challenge in such an analysis is the generation of the correlation rules that are to be used. At present, creating these rules is a time consuming manual task that requires expert knowledge. This work describes how data mining, specifically the k-means clustering technique, can be employed to assist in the semi-automatic generation of such correlation rules.
Shape-Controlled Synthesis and Surface Plasmonic Properties of Metallic Nanostructures

The interaction of light with free electrons in a gold or silver nanostructure can give rise to collective excitations commonly known as surface plasmons. Plasmons provide a powerful means of confining light to metal/dielectric interfaces, which in turn can generate intense local electromagnetic fields and significantly amplify the signal derived from analytical techniques that rely on light, such as Raman scattering. With plasmons, photonic signals can be manipulated on the nanoscale, enabling integration with electronics (which is now moving into the nano regime). However, to benefit from their interesting plasmonic properties, metal structures of controlled shape (and size) must be fabricated on the nanoscale. This issue of MRS Bulletin examines how gold and silver nanostructures can be prepared with controllable shapes to tailor their surface plasmon resonances and highlights some of the unique applications that result, including enhancement of electromagnetic fields, optical imaging, light transmission, colorimetric sensing, and nanoscale waveguiding.
The challenges of overcoming antibiotic resistance: Plant extracts as potential sources of antimicrobial and resistance modifying agents

The problem of antibiotic resistance, which has limited the use of cheap and old antibiotics, has necessitated the need for a continued search for new antimicrobial compounds. Understanding the mechanisms of resistance is important in the development of strategies to solving the problem. Active efflux of drugs, alteration of target sites and enzymatic degradations are the strategies by which pathogenic bacteria acquire or develop intrinsic resistance to antibiotics. Multi-drug resistance (MDR) pumps, capable of recognizing and expelling a variety of structurally unrelated compounds from the bacterial cell and conferring resistance to a wide range of antibiotics have since been characterized in many gram positive and gram negative pathogens like Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and, more recently, in mycobacteria. The ability of some chemical compounds (called MDR inhibitors or resistance modifying agents) to modify the resistance phenotype in bacteria by working synergistically with antibiotics in vitro has since been observed. The search for such compounds which can be combined with antibiotics in the treatment of drug resistant infections may be an alternative to overcoming the problem of resistance in bacteria. Crude extracts of medicinal plants stand out as veritable sources of potential resistance modifying agents and the African biosphere promises to be a potential source of such compounds owing to its rich plant species diversity.
Managing severe burn injuries: challenges and solutions in complex and chronic wound care

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MicroRNA-16 inhibits the proliferation, migration and invasion of glioma cells by targeting Sal-like protein 4.

MicroRNAs (miRNAs or miRs), a class of non-coding RNAs 18-25 nucleotides in length, act as key regulators in the development and malignant progression of various human cancers by modulating the expression of their target genes. Recently, miR‑16 has been demonstrated to be play a role in glioma. However, the regulatory mechanisms of miR‑16 in glioma growth and metastasis remain largely unclear. In the present study, qRT-PCR revealed that miR‑16 was significantly downregulated in 23 glioma tissue specimens compared to 7 normal brain tissue specimens. Moreover, its levels were markedly lower in the glioma samples at stages T2-T4 compared to those at stage T1. The overexpression of miR-16 significantly suppressed the proliferation, migration and invasion of U251 and U87 glioma cells. Luciferase reporter assay identified Sal-like protein 4 (SALL4) as a target gene of miR‑16, and its protein levels were found to be decreased in miR‑16-overexpressing U251 and U87 cells. Furthermore, the overexpression of SALL4 significantly reversed the suppressive effects of miR‑16 on the proliferation, migration and invasion of U251 and U87 cells, suggesting that miR‑16 playsa tumor suppressor role in glioma by inhibiting cell proliferation and invasion through the targeting of SALL4. Finally, we found that SALL4 was significantly upregulated in glioma tissues compared to normal brain tissues, and its levels were markedly higher in the glioma tissues at stages T2-T4 compared to those at stage T1. In addition, the expression levels of SALL4 inversely correlated with the miR‑16 levels in glioma tissues, suggesting that the downregulation of miR‑16 contributes to the upregulation of SALL4 in glioma. On the whole, the findings of this study indicate a role for the miR‑16/SALL4 axis in glioma. Our data may also provide a potential therapeutic target for the treatment of glioma.
Chapter 1 Iterated Local Search : A Concise Review ∗

Iterated local search is a metaheuristic that embeds an improvement heuristic within an iterative process generating a chain of solutions. Often, the improvement method is some kind of local search algorithm and, hence, the name of the metaheuristic. The iterative process in iterated local search consists in a perturbation of the current solution, leading to some intermediate solution that is used as a new starting solution for the improvement method. An additional acceptance criterion decides which of the solutions to keep for continuing this process. This simple idea has led to some very powerful algorithms that have been successfully used to tackle hard combinatorial optimization problems. In this article, we review the main ideas of iterated local search, exemplify its application to combinatorial problems, discuss historical aspects of the development of the method and give an overview of some successful applications.
Effects of Shield1 on the viral replication of varicella-zoster virus containing FKBP-tagged ORF4 and 48

The present study aimed to explore the effects of a stabilizing ligand, Shield-1, on the replication of recombinant varicella-zoster virus (VZV) containing FK506 binding protein (FKPB) tags in essential open reading frames (ORF) 4 and 48. A specific galactokinase (galK) selection method was conducted, following the addition of galK labels to VZV ORF4 and 48, using a SW102 VZV bacterial artificial chromosome (BAC) system. Subsequently, recombinant VZV containing FKPB tags in ORF4 and 48 was constructed by counterselection and homologous recombination. Recombinant viral plasmids containing FKPB-tagged VZV ORF4 and 48 were extracted and transfected into human acute retinal pigment epithelial ARPE-19 cells. The results demonstrated that the FKPB-tagged viral protein was rapidly degraded by proteases in recombinant virus-infected ARPE-19 cells. In addition, the recombinant VZVORF4-FKBP-ORF48-FKBP virus could not grow if a synthetic ligand of FKBP, Shield1, was not added to the ARPE-19 cell culture medium; however, the degradation of FKPB-tagged viral protein was prevented if Shield1 was added to the ARPE-19 cell culture medium, thereby allowing viral replication in ARPE-19 cells. These results indicated that Shield1 may regulate replication of recombinant VZVORF4-FKBP-ORF48-FKBP following transfection into human epithelial cells.
Object Recognition in Picasso’s Abstract Art

The visual arts have for hundreds of years presented viewers with images that have been more or less representational of the external world. In fact, many of these images have been such convincing representations of the world that they can fool the viewer into thinking that the representation is in fact reality or a photograph, and not paint on a canvas. Examples of such trompe I’oeil (fool the eye) paintings are some of the works of Jan Vermeer, or Fra Andrea Pozzo's painting on the ceiling of the Church of Sant' Ignazio in Rome (Rock, 1984). There are certain limitations on being fooled, however. For example, spectators must view the painting from the same angle from which the artist viewed it. Characteristics of paintings that would destroy the illusion, such as brush strokes, must also be concealed (Rock, 1984). It is not just in trompe I'oeil paintings that viewers experience a percep­ tion of what is represented in the picture. In viewing representational art, the spectator perceives both the scene depicted and the markings and brushstrokes that are characteristics of the surface of the painting. The philosopher Michael Polanyi refers to the latter as our "subsidiary awareness" and the former as our "focal awareness. " (Rock, 1984) Moreover, objects are recognizably specific objects in many styles of painting. With trompe I'oeil paintings, the same visual processes, including those dealing with object recognition, would seem to operate as with objects in the real world. What about paintings that are not strictly representational? Everyone knows that paintings that are not exceptionally well-painted and are not entirely convincing representa­ tions still convey a sense that certain objects are represented. What about other styles of paintings? If objects are recognizable in paintings that are not exact representations of the world, then objects should also be recognizable (to some degree) in art that is more abstract. How readily an object in a painting is recognized should depend on how closely it resembles the actual object. This pattern should break down at some point, when the object is abstracted beyond recognition. The great twentieth-century artist Pablo Picasso (1881-1973) is still thought of as notorious by many for his very free abstractions and the distortions of objects in his work. Despite this notoriety, most people have little difficulty in recognizing specific objects in many of his paintings, drawings and sculptures. The enormous stylistic variety of Picasso's abstract work can provide an excellent basis for examining exactly how
Application of Multiple-imputation-particle-filter for Parameter Estimation of Visual Binary Stars with Incomplete Observations

In visual binary stars, mass estimation can be accomplished through the study of their orbital parameters –Kepler’s Third Law establishes a strict mathematical relation between orbital period, orbit size (semi-major axis) and the system total mass. Although, in theory, few observations on the plane of the sky may be enough to obtain a decent estimate for binary star orbits, astronomers must frequently deal with the problem of partial measurements (i.e.; observations having one component missing, either in (X; Y ) or (rho, theta) representation), which are often discarded. This article presents a particlefilter-based method to perform the estimation and uncertainty characterization of these orbital parameters in the context ofpartial measurements. The proposed method uses a multiple imputation strategy to cope with the problem of missing data. The algorithm is tested on synthetic data of relative position of binary stars. The following cases are studied: i) fully available data (ground truth); ii) incomplete observations are discarded; iii) multiple imputation approach is used. In comparison to a situation where partial observations are ignored,a significant reduction in the empirical estimation variance is observed when using multiple imputation schemes; with no numerically significant decrease on estimate accuracy.