Miracle-dz/UniFAR-FTUs huggingface dataset:
A Genome-wide Small Interfering RNA (siRNA) Screen Reveals Nuclear Factor-κB (NF-κB)-independent Regulators of NOD2-induced Interleukin-8 (IL-8) Secretion*

Background: Interleukin-8 (IL-8) is a potent proinflammatory cytokine. Results: We identify many regulators of IL-8 secretion induced by the pattern recognition receptor NOD2. Conclusion: Many diverse cellular processes, including protein ubiquitination and trafficking, specifically affect IL-8 secretion. Significance: The identified regulators, particularly those present in inflammatory disease loci, reveal molecular targets for therapeutic modulation of IL-8. NOD2 encodes an intracellular multidomain pattern recognition receptor that is the strongest known genetic risk factor in the pathogenesis of Crohn disease (CD), a chronic relapsing inflammatory disorder of the intestinal tract. NOD2 functions as a sensor for bacterial cell wall components and activates proinflammatory and antimicrobial signaling pathways. Here, using a genome-wide small interfering RNA (siRNA) screen, we identify numerous genes that regulate secretion of the proinflammatory cytokine IL-8 in response to NOD2 activation. Moreover, many of the identified IL-8 regulators are linked by protein-protein interactions, revealing subnetworks of highly connected IL-8 regulators implicated in processes such as vesicle formation, mRNA stability, and protein ubiquitination and trafficking. A TNFα counterscreen to induce IL-8 secretion in an NOD2-independent manner reveals that the majority of the identified regulators affect IL-8 secretion irrespective of the initiating stimuli. Using immortalized macrophages, we validate the ubiquitin protease, USP8, and the endosomal sorting protein, VPS28, as negative regulators of NOD2-induced cytokine secretion. Interestingly, several genes that affect NOD2-induced IL-8 secretion are present in loci associated with CD risk by genome-wide association studies, supporting a role for the NOD2/IL-8 pathway, and not just NOD2, in the pathogenesis of CD. Overall, this screen provides a valuable resource in the advancement of our understanding of the genes that regulate the secretion of IL-8.
The Role of Problem Classification in Online Meta-cognition

Agents operating in open environments must be able to adapt their processing to available resources, deadlines, their goal criteria, and their current problem solving contexts. This paper describes the role of meta-cognition in this process; in particular, we define a meta-cognition framework that uses Naive Bayesian classification of the agent's current context in order to represent the meta-level control problem as a Markov decision process.
GEOMETRIC APPROACHES TO ESTABLISH THE FUNDAMENTALS OF LORENTZ SPACES R 32 AND R 21

The aim of this paper is to investigate the orthogonality of vectors to each other and the Gram-Schmidt method in the Minkowski space R 3 2 . Hyperbolic cosine formulas are given for all triangle types in the Minkowski plane R 21 . Moreover, the Pedoe inequality is explained for each type of triangle with the help of hyperbolic cosine formulas. Thus, the Pedoe inequality allowed us to establish a connection between two similar triangles in the Minkowski plane. In the continuation of the study, the rotation matrix that provides both point and axis rotation in the Minkowski plane is obtained by using the Lorentz matrix multiplication. Also, it is stated to be an orthogonal matrix. More-over, the orthogonal projection formulas on the spacelike and timelike lines are given in the Minkowski plane. In addition, the distances of any point from the spacelike or timelike line are formulated.
The Development of Wormholes in Laboratory‐Scale Fractures: Perspectives From Three‐Dimensional Simulations

We investigate the development of wormholes in laboratory‐scale fractures using three‐dimensional numerical simulations. Well‐controlled initial conditions, involving a small perturbation near the inlet of an otherwise flat fracture aperture field, were used to make a systematic study of the effects of flow rate and reaction rate on the aperture evolution. We find at least two characteristic wormhole shapes, which can be grouped within a phase diagram in the space of Péclet and Damköhler numbers. We investigate how this phase diagram depends on fracture geometry, specifically the length (L) and width (W) in comparison to the initial aperture (h0). This information is used to determine an effective Damköhler number that leads to a Péclet and length‐independent phase boundary between wormholes and uniform dissolution. We relate these observations to experimental studies of wormhole formation in dissolving fractures.
Adapting to survive: addressing the global problem of Antimicrobial Resistance

Antimicrobial resistance (AMR) is a significant, emerging threat to global public health. In this article, we describe the scale of the threat and why it is such a global concern. We also outline actions that have been identified to address this threat, which includes focusing on the education of healthcare workers and clinicians, as well as members of the public. We describe how medical curricula currently offer opportunities for improving educational interventions that are focused on better prescribing and antimicrobial stewardship. Finally, we argue that by itself, this is not sufficient. Medical students also require a robust understanding of key microbiological principles to underpin and consolidate their prescribing skills when it comes to antibiotics and this need to be consolidated throughout the duration of all medical curricula and beyond. Integrating the medical sciences to create a clinical behaviour change is key to combating (AMR).
Grid Block Design Based on Monte Carlo Simulated Dosimetry, the Linear Quadratic and Hug–Kellerer Radiobiological Models

Purpose: The clinical efficacy of Grid therapy has been examined by several investigators. In this project, the hole diameter and hole spacing in Grid blocks were examined to determine the optimum parameters that give a therapeutic advantage. Methods: The evaluations were performed using Monte Carlo (MC) simulation and commonly used radiobiological models. The Geant4 MC code was used to simulate the dose distributions for 25 different Grid blocks with different hole diameters and center-to-center spacing. The therapeutic parameters of these blocks, namely, the therapeutic ratio (TR) and geometrical sparing factor (GSF) were calculated using two different radiobiological models, including the linear quadratic and Hug–Kellerer models. In addition, the ratio of the open to blocked area (ROTBA) is also used as a geometrical parameter for each block design. Comparisons of the TR, GSF, and ROTBA for all of the blocks were used to derive the parameters for an optimum Grid block with the maximum TR, minimum GSF, and optimal ROTBA. A sample of the optimum Grid block was fabricated at our institution. Dosimetric characteristics of this Grid block were measured using an ionization chamber in water phantom, Gafchromic film, and thermoluminescent dosimeters in Solid WaterTM phantom materials. Results: The results of these investigations indicated that Grid blocks with hole diameters between 1.00 and 1.25 cm and spacing of 1.7 or 1.8 cm have optimal therapeutic parameters (TR > 1.3 and GSF~0.90). The measured dosimetric characteristics of the optimum Grid blocks including dose profiles, percentage depth dose, dose output factor (cGy/MU), and valley-to-peak ratio were in good agreement (±5%) with the simulated data. Conclusion: In summary, using MC-based dosimetry, two radiobiological models, and previously published clinical data, we have introduced a method to design a Grid block with optimum therapeutic response. The simulated data were reproduced by experimental data.
Optimisation cycle : a concept for optimal software development

The current state of traditional software development is surveyed and essential problems are investigated on the basis of system theoretical considerations. The concept of optimisation cycle is proposed as a solution. The relation of several different kinds of local optimisation cycles to the specifications, the communications, and the optimisation barrier is integrated into a concept of participatory software development.
Correlated Event-by-Event Fluctuations of Flow Harmonics in Pb-Pb Collisions at root S-NN=2.76

We report the measurements of correlations between event-by-event fluctuations of amplitudes of anisotropic flow harmonics in nucleus-nucleus collisions, obtained for the first time using a new analysis method based on multiparticle cumulants in mixed harmonics. This novel method is robust against systematic biases originating from nonflow effects and by construction any dependence on symmetry planes is eliminated. We demonstrate that correlations of flow harmonics exhibit a better sensitivity to medium properties than the individual flow harmonics. The new measurements are performed in Pb-Pb collisions at the center-of-mass energy per nucleon pair of ﬃﬃﬃﬃﬃﬃﬃﬃ s NN p ¼ 2 . 76 TeV by the ALICE experiment at the Large Hadron Collider. The centrality dependence of correlation between event-by-event fluctuations of the elliptic v 2 and quadrangular v 4 flow harmonics, as well as of anticorrelation between v 2 and triangular v 3 flow harmonics are presented. The results cover two different regimes of the initial state configurations: geometry dominated (in midcentral collisions) and fluctuation dominated (in the most central collisions). Comparisons are made to predictions from Monte Carlo Glauber, viscous hydrodynamics, AMPT , and HIJING models. Together with the existing measurements of the individual flow harmonics the presented results provide further constraints on the initial conditions and the transport properties of the system produced in heavy-ion collisions.
High-throughput discovery of novel developmental phenotypes openly available. Please share how this access benefits you. Your story matters

Approximately one third of all mammalian genes are essential for life. Phenotypes resulting from mouse knockouts of these genes have provided tremendous insight into gene function and congenital disorders. As part of the International Mouse Phenotyping Consortium effort to generate and phenotypically characterize 5000 knockout mouse lines, we have identified 410 lethal genes during the production of the first 1751 unique gene knockouts. Using a standardised phenotyping platform that incorporates high-resolution 3D imaging, we identified novel phenotypes at multiple time points for previously uncharacterized genes and additional phenotypes for genes with previously reported mutant phenotypes. Unexpectedly, our analysis reveals that incomplete penetrance and variable expressivity are common even on a defined genetic background. In addition, we show that human disease genes are enriched for essential genes identified in our screen, thus providing a novel dataset that facilitates prioritization and validation of mutations identified in clinical sequencing efforts.
Flooding attacks to internet threat monitors (ITM): Modeling and counter measures using botnet and honeypots

The Internet Threat Monitoring (ITM),is a globally scoped Internet monitoring system whose goal is to measure, detect, characterize, and track threats such as distribute denial of service(DDoS) attacks and worms. To block the monitoring system in the internet the attackers are targeted the ITM system. In this paper we address flooding attack against ITM system in which the attacker attempt to exhaust the network and ITM's resources, such as network bandwidth, computing power, or operating system data structures by sending the malicious traffic. We propose an information-theoretic frame work that models the flooding attacks using Botnet on ITM. Based on this model we generalize the flooding attacks and propose an effective attack detection using Honeypots.
A Multilingual Webcam Eye-Tracking-While-Reading Dataset

We create W EB QA M G AZE , a multilingual low-cost eye-tracking-while-reading dataset, designed to support the development of fair and transparent NLP models. W E - B QA M G AZE includes webcam eye-tracking data from 332 participants naturally reading English, Spanish and German texts. Each participant performs two reading tasks composed of ﬁve texts, a normal reading and an information-seeking task. After preprocessing the data, we ﬁnd that ﬁxations on relevant spans seem to indicate correctness when answering the comprehension questions. Additionally, we perform a comparative analysis of the data collected to high-quality eye-tracking data. The results show a moderate correlation between the features obtained with the webcam-ET compared to those of a commercial ET device. We believe this data can advance webcam-based reading studies and open a way to cheaper and more accessible data collection. W EB QA M G AZE is useful to learn about the cognitive processes behind question answering (QA) and to apply these insights to computational models of language understanding.
Improved hemodynamic function during hypoxia with Carbicarb, a new agent for the management of acidosis.

Carbicarb is a mixture of Na2CO3/NaHCO3 that buffers similarly to NaHCO3, but without net generation of CO2. We studied the effects of carbicarb in an animal preparation of hypoxic lactic acidosis (HLA). HLA was induced by ventilating dogs with an hypoxic gas mixture (8% O2/92% N2). Dogs with HLA (n = 28) were then treated with 2.5 meq/kg of either NaHCO3 or carbicarb over 1 hr. Measurements were made, after 1 hr of hypoxia and 1 hr of therapy, of: cardiac hemodynamics, blood gases, liver intracellular pH (pHi), oxygen consumption, and regional lactate production. After therapy, the arterial pH rose with carbicarb (7.22 to 7.27, p less than .01), and fell with NaHCO3 (7.18 to 7.13, p less than .01). Mixed venous PCO2 did not change with carbicarb but increased with NaHCO3 (p less than .05). Arterial lactates stabilized with carbicarb but rose with NaHCO3 (by 3.1 mmol/liter, p less than .005). Lactate use by muscle, gut, and liver all improved with carbicarb and decreased with NaHCO3. The liver pHi (normal = 6.99, hypoxia = 6.80) improved with carbicarb (to 6.92), but decreased further with NaHCO3 (to 6.40). Muscle O2 consumption rose with carbicarb, whereas it decreased with NaHCO3. Arterial pressure fell less with carbicarb (-12 vs -46 mm Hg, p less than .006) and the cardiac output was stable with carbicarb but decreased with NaHCO3 (from 143 to 98 ml/kg/min, p less than .004). Stroke volume also improved with carbicarb but there was no change in pulmonary capillary wedge pressure, suggesting that carbicarb had a beneficial effect on myocardial contractility. (ABSTRACT TRUNCATED AT 250 WORDS)
A comparative study of physiological and subjective effects of heroin and morphine administered intravenously in postaddicts.

Using a variety of subjective and objective measures, the relative potency of heroin to morphine administered intravenously to postaddicts found 1.80 to 2.66 mg of morphine sulfate equal to 1 mg of heroin. In addition, it was found that postaddicts could identify heroin and morphine as such with a high degree of accuracy when these agents were administered intravenously either on an acute or chronic basis. Though postaddicts showed no preference for one or the other of these drugs when administered on a single injection basis, five out of eight expressed a preference for heroin in the short-term addiction study. However, on the basis of postaddicts9 reports on "the most important effects of morphine and heroin," no constellation of effects could be discerned that explained the preference for heroin. Equipotent doses of these drugs had quite comparable action time courses when administered intravenously, and on this basis there was no marked difference in their ability to produce feelings of "euphoria," ambition, nervousness, relaxation, drowsiness, or sleepiness. Although the heroin abstinence syndrome was of shorter duration than that of morphine, the peak intensity was quite comparable for the two drugs. Data acquired during short-term addiction studies did not support the statement that tolerance develops more rapidly to heroin than to morphine. These findings have been discussed in relation to the physicochemical properties of heroin and morphine and the metabolism of heroin.
Chemical and molecular mechanisms of antioxidants: experimental approaches and model systems

• Introduction • Free radical scavenging ‐ Scavenging superoxide and other ROS ‐ Scavenging hydroxyl radical and other ROS ‐ Stable radical scavenging • Metal ion (Fe2+, Fe3+, Cu2+ and Cu+) chelating • Inhibition of free radical generating enzymes • Activation of internal antioxidant enzymes • Prevention of lipid peroxidation • Prevention of DNA damage • Prevention of protein modification • Conclusions
Development of a new software and test setup for analyzing hVOR in very young children by vHIT.

INTRODUCTION Earlier work revealed that vHIT examination is often difficult to perform on very young children. In particular, the calibration of the system can be difficult, as active cooperation of the patient is required. Additionally, the patient must be able to follow the examiner's instructions, which is challenging for very young children. Therefore, the aim of the present study was to develop and validate a new, software-based approach enabling vHIT testing of young children and infants. METHODS AND MATERIALS Six patients (3 boys and 3 girls) aged 5-36 months were included in a prospective, monocentric study between January 2015 and August 2015.The newly developed intuitive software enabled calibration of the eye position signal with the subjects fixating on animated animal graphics which were projected on a screen. Testing ten healthy adults validated this new calibration and measurement method. After calibration, a vHIT goggle (EyeSeeCam ©) was used to perform head impulses in the horizontal plane while the patient was watching a movie sitting on their parent's lap or in a baby chair. At least 15 impulses to each side were obtained and the occurrence of refixation saccades was analyzed. All tests were performed by one of two experienced examiners. RESULTS The new calibration method and modified test setup provided reproducible results for all patients tested. An increased incidence of artifacts was not observed. In 2 patients, more than one test was needed. None of the included children showed catch-up overt or catch-up covert saccades. There was no gain reduction of more than two standard deviations as compared to the normative results published in the literature on vHIT examinations of children. CONCLUSION The proposed protocol allows vHIT testing in very young children and infants (aged 5 months to 3 years). The study emphasizes that vHIT is an easy and sensitive screening tool to evaluate vestibular function in children and should be used as the gold standard in pediatric vestibular assessment.
Student dropout in primary and secondary education in the Republic of Serbia

Student dropout from school is a serious problem in educational systems all over the world. This paper will provide an overview of the various dropout definitions and their consequences for measuring and monitoring. Since a diversity of factors (individual, familial, school and systematic) is connected with student attrition in foreign research, the attempt has been made to systematise their results and provide data regarding similar Serbian studies. Considering the fact that there are no systematic analyses of students’ dropout rate in Serbia, the existing data from primary and secondary schools from a variety of statistical sources will be presented. We conclude that one way to reduce dropout in Serbia is to further develop research interest in the topic, as well as the strategies for monitoring, prevention and intervention.
Occurrence of urease-positive Vibrio parahaemolyticus in Kanagawa, Japan, with specific reference to presence of thermostable direct hemolysin (TDH) and the TDH-related-hemolysin genes

A total of 132 strains of V. parahaemolyticus isolated from patients and from the suspected causal food items of past food poisoning cases occurring in Kanagawa Prefecture, Japan, were examined for the ability to hydrolyze urea, with specific reference to the presence of the thermostable direct hemolysin gene (tdh) and the gene for thermostable direct hemolysin-related hemolysin (trh). Ten strains belonging to five different O-antigen serotypes were positive for urea hydrolysis (UH+), and four of these strains did not carry tdh. A total of 106 strains carried tdh, but less than 6% of them were UH+, whereas all trh-carrying strains were UH+. The evidence suggests that urea hydrolysis is not a reliable marker for identifying tdh-carrying V. parahaemolyticus strains in Japan (the Pacific Northeast) but may be a marker for trh-carrying strains.
Edinburgh Research Explorer Circulating 25-hydroxyvitamin D and survival outcomes of colorectal cancer: evidence from population-based prospective cohorts and Mendelian randomisation

BACKGROUND: To investigate the association between circulating 25-hydroxyvitamin D (25-OHD) and colorectal cancer (CRC) survival outcomes. METHODS: We conducted analyses among the Study of Colorectal Cancer in Scotland (SOCCS) and the UK Biobank (UKBB). Both cancer-speci ﬁ c survival (CSS) and overall survival (OS) outcomes were examined. The 25-OHD levels were categorised into three groups, and multi-variable Cox-proportional hazard models were applied to estimate hazard ratios (HRs). We performed individual-level Mendelian randomisation (MR) through the generated polygenic risk scores (PRS) of 25-OHD and summary-level MR using the inverse-variance weighted (IVW) method. RESULTS: We observed signi ﬁ cantly poorer CSS (HR = 0.65,95%CI = 0.55 – 0.76, P = 1.03 × 10 − 7 ) and OS (HR = 0.66,95% CI = 0.58 – 0.75, P = 8.15 × 10 − 11 ) in patients with the lowest compared to those with the highest 25-OHD after adjusting for covariates. These associations remained across patients with varied tumour sites and stages. However, we found no signi ﬁ cant association between 25-OHD PRS and either CSS (HR = 0.98,95%CI = 0.80 – 1.19, P = 0.83) or OS (HR = 1.07,95% CI = 0.91 – 1.25, P = 0.42). Furthermore, we found no evidence for causal effects by conducting summary-level MR analysis for either CSS (IVW:HR = 1.04,95%CI = 0.85 – 1.28, P = 0.70) or OS (IVW:HR = 1.10,95%CI = 0.93 – 1.31, P = 0.25). CONCLUSION: This study supports the observed association between lower circulating 25-OHD and poorer survival outcomes for CRC patients. Whilst the genotype-speci ﬁ c association between better outcomes and higher 25-OHD is intriguing, we found no support for causality using MR approaches.
Video Resizing for Mobile Device

This paper proposes a video retargeting method. The method makes multimedia more suitable for ubiquitous video access, including comfortable watching, interesting region detection and safety transmitting. Because of the rapid progress of electronic commercial product, video service needs to adapt different device. There are some challenges: First at all, the resolution, aspect ratio and size of display are different from the original video. Secondly, people do not have interesting on the whole movie. Based on face recognition, adaptive showing region function has been implemented. Some demonstrations are also presented.