Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative Analysis of Spontaneous and Mycobacterial Antigen‐Induced Secretion of Th1, Th2 and Pro‐Inflammatory Cytokines by Peripheral Blood Mononuclear Cells of Tuberculosis Patients

The cytokines produced by T helper (Th)1 cells (IFN‐γ, IL‐2 and TNF‐β) correlate with protection, whereas the cytokines released by Th2 cells (IL‐4, IL‐5) and the anti‐inflammatory cytokine IL‐10 correlate with pathogenesis of tuberculosis (TB). However, the pro‐inflammatory cytokines (IL‐1β, IL‐6, IL‐8, TNF‐α and IL‐12p70) are responsible for both protection and pathogenesis of TB. The aim of this work was to carry out a comparative analysis of cytokines present in early (day 2) and late (day 6) cultures of peripheral blood mononuclear cells (PBMCs) obtained from pulmonary tuberculosis patients. PBMCs were cultured in vitro in the absence and presence of exogenously added complex mycobacterial antigens and RD1 peptide pool. The supernatants were collected on day 2 and day 6 of culture and assayed for secreted cytokines using the flow cytomix assay. All of the cytokines, except for IL‐12p70, were spontaneously secreted by PBMCs of 27–100% TB patients, but only TNF‐α concentration was significantly higher on day 2 than day 6 (P < 0.05). Two days following antigenic stimulation, only IL‐1β, IL‐6, TNF‐α and IL‐10 were secreted in response to some mycobacterial antigens. However, 6 days later, all of the cytokines, except for IL‐2, IL‐4, IL‐5 and IL‐8, were secreted significantly in response to all complex antigens and RD1 peptides, compared with the non‐stimulated cultures (P < 0.05). In conclusion, the study shows that the longer in vitro stimulation time (6 days) was necessary for the optimal induction of IFN‐γ and TNF‐β, and practically convenient for the detection of IL‐10, IL‐1 β, TNF‐α and IL‐6.
Three new diarylbutane lignans from the resin of Bursera fagaroides

Three new diarylbutane lignans, named 9-acetyl-9′-pentadecanoil-dihydroclusin (1), 2,3-demethoxy-secoisolintetralin monoacetate (4) and dihydroclusin monoacetate (5), have been isolated from the resin of Bursera fagaroides, together with two known ones, 2,3-demethoxy-secoisolintetralin diacetate (2) and dihydroclusin diacetate (3). The complete structure assignments were obtained by means of 1H and 13C NMR spectra.
Assessment of Antioxidant Potential and Acute Toxicity Studies of Whole Plant Extract of Pergularia Daemia (Forsk)

Background: Pergularia daemia (Asclepiadacea) is a fetid- smelling perennial herb growing well along the river bang and road sides of India. Naturally the plant has powerful antioxidants including polyphenols, flavanoids, steroids and terpenoids. Objective: The aim of this study is to evaluate the in vitro antioxidant potential and to determine the median lethal dose (LD50) of crude ethyl acetate and methanol extracts of Pergularia daemia. The plant Pergularia daemia possess effective scavenging activity against 2, 2' azino bis (3 ethylbenzothiazoline 6 sulfonic acid (ABTS), nitric oxide and reducing power radicals at different concentrations (100, 200, 300, 400 & 500 µg/mL) of both extracts. Results: From the above in vitro assay we have exposed that the methanolic extract exert higher antioxidant activity at 400 µg/mL than ethyl acetate extract. Acute toxicity study revealed that the extracts showed no signs of toxicity upto a dose level of 2500 mg/kg b.wt. Conclusion: Thus our findings provide that both extracts of Pergularia daemia possess a strong antioxidant capacity and are relatively has high margin of safety.
HEALTH TECHNOLOGY ASSESSMENT AND PERSONALIZED MEDICINE: ARE ECONOMIC EVALUATION GUIDELINES SUFFICIENT TO SUPPORT DECISION MAKING?

Background: Many jurisdictions delivering health care, including Canada, have developed guidance for conducting economic evaluation, often in the service of larger health technology assessment (HTA) and reimbursement processes. Like any health intervention, personalized medical (PM) interventions have costs and consequences that must be considered by reimbursement authorities with limited resources. However, current approaches to economic evaluation to support decision making have been largely developed from population-based approaches to therapy—that is, evaluating the costs and consequences of single interventions across single populations. This raises the issue as to whether these methods, as they are or more refined, are adequate to address more targeted approaches to therapy, or whether a new paradigm for assessing value in PM is required. Objectives: We describe specific issues relevant to the economic evaluation of diagnostics-based PM and assess whether current guidance for economic evaluation is sufficient to support decision making for PM interventions. Methods: Issues were identified through literature review and informal interviews with national and international experts (n = 10) in these analyses. This article elaborates on findings and discussion at a workshop held in Ottawa, Canada, in January 2012. Results: Specific issues related to better guiding economic evaluation of personalized medicine interventions include: how study questions are developed, populations are characterized, comparators are defined, effectiveness is evaluated, outcomes are valued and how resources are measured. Diagnostics-based PM also highlights the need for analyses outside of economic evaluation to support decision making. Conclusions: The consensus of this group of experts is that the economic evaluation of diagnostics-based PM may not require a new paradigm. However, greater complexity means that existing approaches and tools may require improvement to undertake these more analyses.
Glaucoma Medication Adherence among African Americans: Program Development

Purpose To elucidate barriers and facilitators related to glaucoma medication adherence among African Americans (AA) with glaucoma and to elicit input from a community-based participatory research team to guide the development of a culturally informed health promotion program for improving glaucoma medication adherence among AAs. Methods The nominal group technique (NGT), a highly structured focus group methodology, was implemented with 12 separate groups of AA patients with glaucoma (N = 89) to identify barriers and facilitators related to glaucoma medication usage. Participant rank-ordering votes were summed across groups and categorized into themes. Next, an individually and culturally targeted health promotion program promoting appropriate medication adherence was developed based on focus group results and input from a community-based participatory research team. Results The top five barriers included problems with forgetfulness, side effects, cost/affordability, eyedrop administration, and the eyedrop schedule. The most salient top five facilitators were fear or thoughts about the consequences of not taking eyedrops; use of memory aids, cues, or strategies; maintaining a regular routine or schedule for eyedrop administration; ability to afford eyedrops; and keeping eyedrops in the same area. The resulting health promotion program was based on a multicomponent empowerment framework that included glaucoma education, motivational interviewing, and problem-solving training to improve glaucoma medication adherence. Conclusions Barriers and facilitators related to glaucoma medication adherence among AAs are multifactorial. Based on the NGT themes and input from the community-based participatory research team, a culturally informed health promotion program was designed and holds great promise for improving medication adherence among this vulnerable population.
The elite and stochastic model for iPS cell generation: Multilineage‐differentiating stress enduring (Muse) cells are readily reprogrammable into iPS cells

Induced pluripotent stem (iPS) cells have attracted a great deal of attention, although the mechanism by which they are generated is still not fully understood. Currently, two theories, the stochastic and elite models, have been proposed. Some reports provide theoretical support for the stochastic model. Other reports, however, support the elite model. For example, some human fibroblasts, such as Multilineage‐differentiating stress enduring (Muse) cells, are reported to be pluripotent and a primary source of iPS cells. Thus, the mechanism of iPS cell generation continues to be debated. In this review, we discuss the properties of the original cell source, such as the components of the original populations and the potential of each population to become iPS cells, and further discuss the implications of the two theories for iPS cell research. © 2012 International Society for Advancement of Cytometry
Movies and emotional engagement: laughing matters in lecturing.

Editor’s Note: In this column, teachers who are currently using literary and artistic materials as part of their curricula will briefly summarize specific works, delineate their purposes and goals in using these media, describe their audience and teaching strategies, discuss their methods of evaluation, and speculate about the impact of these teaching tools on learners (and teachers). Submissions should be three to five double-spaced pages with a minimum of references. Send your submissions to me at University of California, Irvine, Department of Family Medicine, 101 City Drive South, Building 200, Room 512, Route 81, Orange, CA 92868-3298. 949-824-3748. Fax: 714-456-7984. jfshapir@uci.edu.
A Dynamic Collective Choice Model with an Advertiser

This paper studies a dynamic collective choice model in the presence of an advertiser, where a large number of consumers are choosing between two alternatives. Their choices are influenced by the group’s aggregate choice and an advertising effect. The latter is produced by an advertiser making investments to convince as many consumers as possible to choose a specific alternative. In schools, for example, teenagers’ decisions to smoke are considerably affected by their peers’ decisions, as well as the ministry of health campaigns against smoking. We model the problem as a Stackelberg dynamic game, where the advertiser makes its investment decision first, and then the consumers choose one of the alternatives. On the methodological side, we use the theory of mean field games to solve the game for a continuum of consumers. This allows us to describe the consumers’ individual and aggregate behaviors, and the advertiser’s optimal investment strategies. When the consumers have sufficiently diverse a priori opinions toward the alternatives, we show that a unique Nash equilibrium exists between them, which predicts the distribution of choices over the alternatives, and the advertiser can always make optimal investments. For a certain uniform distribution of a priori opinions, we give an explicit form of the advertiser’s optimal investment strategy and of the consumers’ optimal choices.
Validation of the German version of the Ford Insomnia Response to Stress Test

The purpose of this study was to assess the psychometric properties of a German version of the Ford Insomnia Response to Stress Test with groups with and without sleep problems. Three studies were analysed. Data set 1 was based on an initial screening for a sleep training program (n = 393), data set 2 was based on a study to test the test–retest reliability of the Ford Insomnia Response to Stress Test (n = 284) and data set 3 was based on a study to examine the influence of competitive sport on sleep (n = 37). Data sets 1 and 2 were used to test internal consistency, factor structure, convergent validity, discriminant validity and test–retest reliability of the Ford Insomnia Response to Stress Test. Content validity was tested using data set 3. Cronbach's alpha of the Ford Insomnia Response to Stress Test was good (α = 0.80) and test–retest reliability was satisfactory (r = 0.72). Overall, the one‐factor model showed the best fit. Furthermore, significant positive correlations between the Ford Insomnia Response to Stress Test and impaired sleep quality, depression and stress reactivity were in line with the expectations regarding the convergent validity. Subjects with sleep problems had significantly higher scores in the Ford Insomnia Response to Stress Test than subjects without sleep problems (P < 0.01). Competitive athletes with higher scores in the Ford Insomnia Response to Stress Test had significantly lower sleep quality (P = 0.01), demonstrating that vulnerability for stress‐induced sleep disturbances accompanies poorer sleep quality in stressful episodes. The findings show that the German version of the Ford Insomnia Response to Stress Test is a reliable and valid questionnaire to assess the vulnerability to stress‐induced sleep disturbances.
Relational Markov Networks

One of the key challenges for statistical relational learning is the design of a representation language that allows flexible modeling of complex relational interactions. Many of the formalisms presented in this book are based on the directed graphical models (probabilistic relational models, probabilistic entity-relationship models, Bayesian logic programs). In this chapter, we present a probabilistic modeling framework that builds on undirected graphical models (also known as Markov random fields or Markov networks). Undirected models address two limitations of the previous approach. First, undirected models do not impose the acyclicity constraint that hinders representation of many important relational dependencies in directed models. Second, undirected models are well suited for discriminative training, where we optimize the conditional likelihood of the labels given the features, which generally improves classification accuracy. We show how to train these models effectively, and how to use approximate probabilistic inference over the learned model for collective classification and link prediction. We provide experimental results on hypertext and social network domains, showing that accuracy can be significantly improved by modeling relational dependencies.1
Detection of Stress Proteins as Biomarkers of Oxidative Stress

Heat shock or stress proteins are constitutively expressed redox‐sensitive proteins, the synthesis of which is induced in almost all organisms exposed to a range of stressors, including oxidative stress, heat shock, free radicals, UV radiation, and heavy metals. This unit details three methods, with supporting protocols, for their measurement in peripheral blood mononuclear cells, plasma, and serum. These are [35S]methionine protein labeling, immunoblotting, and ELISA.
Fast Duplicated Documents Detection using Multi-level Prefix-filter

Duplicate document detection is the problem of finding all document-pairs rapidly whose similarities are equal to or greater than a given threshold. There is a method proposed recently called prefix-filter that finds document-pairs whose similarities never reach the threshold based on the number of uncommon terms (words/characters) in a document-pair and removes them before similarity calculation. However, prefix-filter cannot decrease the number of similarity calculations sufficiently because it leaves many document-pairs whose similarities are less than the threshold. In this paper, we propose multi-level prefix-filter, which reduces the number of similarity calculations more efficiently and maintains the advantage of prefix-filter (no detection loss, no extra parameter) by applying multiple different prefix-filters.
Rod‐shaped iron oxide nanoparticles are more toxic than sphere‐shaped nanoparticles to murine macrophage cells

Variable sizes of nanoparticles, ranging from nano to micro scale, are of toxicological interest. In the present study, the authors hypothesized that, in addition to the size, the shape of iron oxide (Fe2O3) nanoparticles is a major factor that contributes to particle cytotoxicity. Cytotoxicity to mouse macrophage cells (RAW 264.7) was investigated using 3 different particles: micro‐sized Fe2O3 (M‐Fe2O3), nano‐sized Fe2O3 (N‐Fe2O3), and rod‐shaped Fe2O3 (R‐Fe2O3). Whereas M‐Fe2O3 and N‐Fe2O3 were located in the vacuole as aggregates, R‐Fe2O3 was often spread throughout the cytoplasm. The extent of cytotoxicity measured by the water soluble tetrazolium (WST‐1) assay was in the order R‐Fe2O3 ≈ N‐Fe2O3 > M‐Fe2O3, whereas the extent revealed by the lactate dehydrogenase assay was in the order R‐Fe2O3 >> N‐Fe2O3 ≈ M‐Fe2O3. In addition, the degree of tumor necrosis factor–α and reactive oxygen species (ROS) production was in the order of R‐Fe2O3 > N‐Fe2O3 > M‐Fe2O3. In addition, a much higher extent of necrosis was associated with the presence of R‐Fe2O3. These results suggest that the higher degree of necrosis due to R‐Fe2O3 is correlated with both the higher degree of membrane damage and ROS production by R‐Fe2O3 compared with the results of the other Fe2O3 particles. These results also showed that the degree of cytotoxicity of nanoparticles should be evaluated based on shape as well as size, because changes in shape and size are accompanied by alterations in surface area, which relate closely to cytotoxicity. Environ Toxicol Chem 2014;33:2759–2766. © 2014 SETAC
Stroke Prevention

PREVIEW The short-term risk of stroke after transient ischemic attack (TIA) is about 10% to 20% in the first 3 months, with much of the risk front-loaded in the first week. Unfortunately, little is known about the best therapies for hyperacute stroke prevention after TIA. A recent trial referred to by the acronym MATCH (for Management of Atherothrombosis With Clopidogrel in High-risk Patients With Recent Transient Ischemic Attack or Ischemic Stroke) provides hypothesis-generating data to suggest that double antiplatelet therapy in the short term may be appropriate. Here, the authors discuss treatment considerations, outlining the current knowledge and stressing the need for formal randomized trials to definitively establish the effectiveness of preventive therapies after minor stroke or TIA.
Walking Pattern Generation for a Biped Walking Robot Using Convolution Sum

This paper describes a novel walking pattern generation method for a biped humanoid robot using a convolution sum. For a biped walking model, a single mass inverted pendulum model is generally used and the zero moment point (ZMP) equation is described by a decoupled linear differential equation. As a walking pattern generation method for the robot model, a novel method using a convolution sum is proposed in this paper. From the viewpoint of the linear system response, walking pattern generation can be regarded as a convolution of an arbitrary reference ZMP and the walking pattern for an impulse reference ZMP. For the calculation of convolution, the walking pattern for an impulse reference ZMP is first derived from the analytic walking pattern for a step reference ZMP. The convolution sum is then derived in two recursive forms, which can be applied online and offline, respectively. The proposed algorithm requires low computation power, since the walking pattern equation is composed of a recursive form. As the algorithm is expressed in analytic form, it is not necessary to solve optimization problems or calculate the fast Fourier transform, contrary to previous approaches. A computer simulation of walking demonstrates that the proposed algorithm yields excellent accuracy compared to the preview control method — one of the most highly regarded walking pattern generation methods. In addition, the application on the multi-point mass model is shown with the computer simulation. © Koninklijke Brill NV, Leiden, 2011
Vitamin D and the epigenome

Epigenetic mechanisms play a crucial role in regulating gene expression. The main mechanisms involve methylation of DNA and covalent modifications of histones by methylation, acetylation, phosphorylation, or ubiquitination. The complex interplay of different epigenetic mechanisms is mediated by enzymes acting in the nucleus. Modifications in DNA methylation are performed mainly by DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) proteins, while a plethora of enzymes, such as histone acetyltransferases (HATs), histone deacetylases (HDACs), histone methyltransferases (HMTs), and histone demethylases (HDMs) regulate covalent histone modifications. In many diseases, such as cancer, the epigenetic regulatory system is often disturbed. Vitamin D interacts with the epigenome on multiple levels. Firstly, critical genes in the vitamin D signaling system, such as those coding for vitamin D receptor (VDR) and the enzymes 25-hydroxylase (CYP2R1), 1α-hydroxylase (CYP27B1), and 24-hydroxylase (CYP24A1) have large CpG islands in their promoter regions and therefore can be silenced by DNA methylation. Secondly, VDR protein physically interacts with coactivator and corepressor proteins, which in turn are in contact with chromatin modifiers, such as HATs, HDACs, HMTs, and with chromatin remodelers. Thirdly, a number of genes encoding for chromatin modifiers and remodelers, such as HDMs of the Jumonji C (JmjC)-domain containing proteins and lysine-specific demethylase (LSD) families are primary targets of VDR and its ligands. Finally, there is evidence that certain VDR ligands have DNA demethylating effects. In this review we will discuss regulation of the vitamin D system by epigenetic modifications and how vitamin D contributes to the maintenance of the epigenome, and evaluate its impact in health and disease.
Nitrogen‐Doped Holey Graphitic Carbon from 2D Covalent Organic Polymers for Oxygen Reduction

Using covalent organic polymer pre-cursors, we have developed a new strategy for location control of N-dopant heteroatoms in the graphitic porous carbon, which otherwise is impossible to achieve with conventional N-doping techniques. The electrocatalytic activities of the N-doped holey graphene analogues are well correlated to the N-locations, showing possibility for tailoring the structure and property of N-doped carbon nanomaterials.
Optimizing indirect memory references with milk

Modern applications such as graph and data analytics, when operating on real world data, have working sets much larger than cache capacity and are bottlenecked by DRAM. To make matters worse, DRAM bandwidth is increasing much slower than per CPU core count, while DRAM latency has been virtually stagnant. Parallel applications that are bound by memory bandwidth fail to scale, while applications bound by memory latency draw a small fraction of much-needed bandwidth. While expert programmers may be able to tune important applications by hand through heroic effort, traditional compiler cache optimizations have not been sufficiently aggressive to overcome the growing DRAM gap. In this paper, we introduce milk - a C/C++ language extension that allows programmers to annotate memory-bound loops concisely. Using optimized intermediate data structures, random indirect memory references are transformed into batches of efficient sequential DRAM accesses. A simple semantic model enhances programmer productivity for efficient parallelization with OpenMP. We evaluate the Milk compiler on parallel implementations of traditional graph applications, demonstrating performance gains of up to 3×.