Miracle-dz/UniFAR-FTUs huggingface dataset:
Interactions between Diet, Lifestyle and IL10, IL1B, and PTGS2/COX-2 Gene Polymorphisms in Relation to Risk of Colorectal Cancer in a Prospective Danish Case-Cohort Study

Background & Aims Diet contributes to colorectal cancer development and may be potentially modified. We wanted to identify the biological mechanisms underlying colorectal carcinogenesis by assessment of diet-gene interactions. Methods The polymorphisms IL10 C-592A (rs1800872), C-rs3024505-T, IL1b C-3737T (rs4848306), G-1464C (rs1143623), T-31C (rs1143627) and PTGS2 (encoding COX-2) A-1195G (rs689466), G-765C (rs20417), and T8473C (rs5275) were assessed in relation to risk of colorectal cancer (CRC) and interaction with diet (red meat, fish, fibre, cereals, fruit and vegetables) and lifestyle (non-steroid-anti-inflammatory drug use and smoking status) was assessed in a nested case-cohort study of nine hundred and seventy CRC cases and 1789 randomly selected participants from a prospective study of 57,053 persons. Results IL1b C-3737T, G-1464C and PTGS2 T8473C variant genotypes were associated with risk of CRC compared to the homozygous wildtype genotype (IRR=0.81, 95%CI: 0.68-0.97, p=0.02, and IRR=1.22, 95%CI: 1.04-1.44, p=0.02, IRR=0.75, 95%CI: 0.57-0.99, p=0.04, respectively). Interactions were found between diet and IL10 rs3024505 (P-value for interaction (Pint); meat=0.04, fish=0.007, fibre=0.0008, vegetables=0.0005), C-592A (Pint; fibre=0.025), IL1b C-3737T (Pint; vegetables=0.030, NSAID use=0.040) and PTGS2 genotypes G-765C (Pint; meat=0.006, fibre=0.0003, fruit 0.004), and T8473C (Pint; meat 0.049, fruit=0.03) and A-1195G (Pint; meat 0.038, fibre 0.040, fruit=0.059, vegetables=0.025, and current smoking=0.046). Conclusions Genetically determined low COX-2 and high IL-1β activity were associated with increased risk of CRC in this northern Caucasian cohort. Furthermore, interactions were found between IL10, IL1b, and PTGS2 and diet and lifestyle factors in relation to CRC. The present study demonstrates that gene-environment interactions may identify genes and environmental factors involved in colorectal carcinogenesis.
Identification of the Ligands of Protein Interaction Domains through a Functional Approach*S

The identification of protein-protein interaction networks has often given important information about the functions of specific proteins and on the cross-talk among metabolic and regulatory pathways. The availability of entire genome sequences has rendered feasible the systematic screening of collections of proteins, often of unknown function, aimed to find the cognate ligands. Once identified by genetic and/or biochemical approaches, the interaction between two proteins should be validated in the physiologic environment. Herein we describe an experimental strategy to screen collections of protein-protein interaction domains to find and validate candidate interactors. The approach is based on the assumption that the overexpression in cultured cells of protein-protein interaction domains, isolated from the context of the whole protein, could titrate the endogenous ligand and, in turn, exert a dominant negative effect. The identification of the ligand could provide us with a tool to check the relevance of the interaction because the contemporary overexpression of the isolated domain and of its ligand could rescue the dominant negative phenotype. We explored this approach by analyzing the possible dominant negative effects on the cell cycle progression of a collection of phosphotyrosine binding (PTB) domains of human proteins. Of 47 PTB domains, we found that the overexpression of 10 of them significantly interfered with the cell cycle progression of NIH3T3 cells. Four of them were used as baits to identify the cognate interactors. Among these proteins, CARM1, interacting with the PTB domain of RabGAP1, and EF1α, interacting with RGS12, were able to rescue the block of the cell cycle induced by the isolated PTB domain of the partner protein, thus confirming in vivo the relevance of the interaction. These results suggest that the described approach can be used for the systematic screening of the ligands of various protein-protein interaction domains also by using different biological assays.
Sparse density estimation on multinomial manifold combining local component analysis

A new sparse kernel density estimator is introduced based on the minimum integrated square error criterion combining local component analysis for the finite mixture model. We start with a Parzen window estimator which has the Gaussian kernels with a common covariance matrix, the local component analysis is initially applied to find the covariance matrix using expectation maximization algorithm. Since the constraint on the mixing coefficients of a finite mixture model is on the multinomial manifold, we then use the well-known Riemannian trust-region algorithm to find the set of sparse mixing coefficients. The first and second order Riemannian geometry of the multinomial manifold are utilized in the Riemannian trust-region algorithm. Numerical examples are employed to demonstrate that the proposed approach is effective in constructing sparse kernel density estimators with competitive accuracy to existing kernel density estimators.
Sequence‐based methods for detecting and evaluating the human gut mycobiome

We surveyed the fungal microbiota in 16 faecal samples from healthy humans with a vegetarian diet. Fungi were identified using molecular cloning, 454 pyrosequencing and a Luminex analyte‐specific reagent (ASR) assay, all targeting the ITS region of the rRNA genes. Fungi were detected in each faecal sample and at least 46 distinct fungal operational taxonomic units (OTUs) were detected, from two phyla — Ascomycota and Basidiomycota. Fusarium was the most abundant genus, followed by Malassezia, Penicillium, Aspergillus and Candida. Commonly detected fungi such as Aspergillus and Penicillium, as well as known dietary fungi Agaricus bisporus and Ophiocordyceps sinensis, are presumed to be transient, allochthonous members due to their abundance in the environment or dietary associations. No single method identified the full diversity of fungi in all samples; pyrosequencing detected more distinct OTUs than the other methods, but failed to detect OTUs in some samples that were detected by cloning and/or ASR assays. ASRs were limited by the commercially available assays, but the potential to design new, optimized assays, coupled with speed and cost, makes the ASR method worthy of further study.
Trehalose diester glycolipids are superior to the monoesters in binding to Mincle, activation of macrophages in vitro and adjuvant activity in vivo

The T-cell adjuvanticity of mycobacterial cord factor trehalose 6,6'-dimycolate (TDM) is well established. The identification of the C-type lectin Mincle on innate immune cells as the receptor for TDM and its synthetic analogue trehalose 6,6'-dibehenate (TDB) has raised interest in development of synthetic Mincle ligands as novel adjuvants. Trehalose mono- (TMXs) and diesters (TDXs) with symmetrically shortened acyl chains [denoted by X: arachidate (A), stearate (S), palmitate (P), and myristate (M)] were tested. Upon stimulation of murine macrophages, G-CSF secretion and NO production were strongly augmented by all TDXs tested, in a wide concentration range. In contrast, the TMXs triggered macrophage activation only at high concentrations. Macrophage activation by all TDXs required Mincle, but was independent of MyD88. The superior capacity of TDXs for activating macrophages was paralleled by direct binding of TDXs, but not of TMXs, to a Mincle-Fc fusion protein. Insertion of a short polyethylene glycol between the sugar and acyl chain in TDS reduced Mincle-binding and macrophage activation. Immunization of mice with cationic liposomes containing the analogues demonstrated the superior adjuvant activity of trehalose diesters. Overall, immune activation in vitro and in vivo by trehalose esters of simple fatty acids requires two acyl chains of length and involves Mincle.
Surveillance investigations after high-dose therapy with stem cell rescue for recurrent follicular lymphoma have no impact on management

Background The impact of active surveillance, comprising annual computed tomography scanning and bone marrow biopsies, in the follow-up of patients after high-dose therapy with autologous stem cell rescue for recurrent follicular lymphoma was analyzed. Design and Methods Seventy-one of 99 patients who received high-dose therapy commenced the surveillance program. Response duration, time to next treatment and overall survival were compared according to whether disease progression had been diagnosed on the basis of surveillance investigations or on clinical grounds. Results After a median follow-up of 16 years, progression was documented by surveillance in 16 patients and clinically in 18, the median response duration being 2.4 and 2.3 years, respectively (P=NS). Ten patients with a relapse detected clinically started treatment immediately, contrasting with one patient whose relapse was detected by surveillance investigations. Five patients with relapses detected by surveillance investigations have not required treatment after a median follow-up of 18 years, whereas all but two patients with a relapse detected clinically have been treated. The median time to next treatment was 7 years for patients with a relapse identified by surveillance investigations and 4 years for those whose relapse was manifested clinically (P=0.03). Overall survival was not significantly different between the two groups. Conclusions Surveillance investigations, consisting of annual computed tomography scanning and bone marrow biopsies, have no impact on the management of patients with recurrent follicular lymphoma and do not improve the outcome of these patients.
Refinement through restraint: bringing down the cost of verification

We present a framework aimed at significantly reducing the cost of verifying certain classes of systems software, such as file systems. Our framework allows for equational reasoning about systems code written in our new language, Cogent. Cogent is a restricted, polymorphic, higher-order, and purely functional language with linear types and without the need for a trusted runtime or garbage collector. Linear types allow us to assign two semantics to the language: one imperative, suitable for efficient C code generation; and one functional, suitable for equational reasoning and verification. As Cogent is a restricted language, it is designed to easily interoperate with existing C functions and to connect to existing C verification frameworks. Our framework is based on certifying compilation: For a well-typed Cogent program, our compiler produces C code, a high-level shallow embedding of its semantics in Isabelle/HOL, and a proof that the C code correctly refines this embedding. Thus one can reason about the full semantics of real-world systems code productively and equationally, while retaining the interoperability and leanness of C. The compiler certificate is a series of language-level proofs and per-program translation validation phases, combined into one coherent top-level theorem in Isabelle/HOL.
Resistance Training: (Re)shaping Extreme Forms of Workplace Health Promotion

As the number of workplace health initiatives grows, so does the variety of programming. This study examines a fitness apparel company’s attempts to promote a fitness culture through a particular brand of “extreme” fitness known as CrossFit. CrossFit is an intense fitness regimen that has generated controversy with a cult-like reputation. We looked at the evangelical promotion of CrossFit as a new corporate wellness initiative. Based on interviews and participant observations, we used a critical-interpretive lens to understand employee reactions to the extreme wellness initiative. The evangelical introduction of this program by management led to high rates of participation, influencing employee perceptions of health, fitness, and identity. Yet, we also found that employee resistance emerged, which helped to mark the limits of this managerial intervention in workplace fitness. Ultimately, the study advocates for more co-construction of workplace wellness initiatives.
Soil models and vehicle system dynamics

Abstract : The mechanical behavior of soils may be approximated using different models that depend on particular soil characteristics and simplifying assumptions. For this reason, researchers have proposed and expounded upon a large number of constitutive models and approaches that describe various aspects of soil behavior. However, there are few material models capable of predicting the behavior of soils for engineering applications and are at the same time appropriate for implementation into finite element (FE) and multibody system (MBS) algorithms. This paper presents a survey of some of the commonly used continuum-based soil models. The aim is to provide a summary of continuum-based soil models and examine their suitability for integration with the large-displacement FE absolute nodal coordinate formulation (ANCF) and MBS algorithms. Special emphasis is placed on the formulation of soils used in conjunction with vehicle dynamics models. The implementation of these soil models in MBS algorithms used in the analysis of complex vehicle systems is also discussed. Because semi-empirical terramechanics soil models are currently the most widely used to study vehicle/soil interaction, a review of classical terramechanics models is presented in order to be able to explain the modes of displacements that are not captured by these simpler models. Other methods such as the particle-based and mesh-free models are also briefly reviewed. A Cam-Clay soil model is used in this paper to explain how such continuum-mechanics based soil models can be implemented in FE/MBS algorithms.
Curriculum design for person-centredness: mindfulness training within a bachelor course in nursing

Background: In the academic year 2013/14 the Faculty of Nursing of Fontys University of Applied Sciences agreed on a new first-year course in person-centred nursing, based on the framework of person-centred nursing by McCormack and McCance (2006; 2010). This programme’s components included a group project and presentation, problem-based learning sessions, interactive skills training and mindfulness training. The 400 first-year students received four weeks of intensive training in mindfulness with eight biweekly meetings lasting one-and-a-half hours each. Aims and objectives: This article provides an evaluation of this intensive four-week pilot training for the first cohort of 201 students, with the aim of assessing whether the use of mindfulness is suitable to cultivate relevant nursing ‘prerequisites’ for person-centred nursing. Conclusions: A strength of the present study was that it was a ‘real life study’ within the curriculum of first-year nursing students. The screening of the self-reflection reports revealed that the mindfulness training had positive effects on self-reflection, self-insight and self-care. The interviews with the mindfulness trainers and the focus group raised a number of issues and ideas for future development and implementation of the mindfulness training. Implications for practice: The value of this study lies in its contribution to linking the development of the person-centred attributes of the nurse and the skill of mindfulness. Moreover, issues are identified relating to the qualifications of those providing mindfulness training, whether mindfulness is best intoduced in the first year or later years, and group pressure among students.
Gravitational waves in general relativity XIV. Bondi expansions and the ‘polyhomogeneity’ of ℐ

The structure of polyhomogeneous space-times (i.e. space-times with metrics which admit an expansion in terms of r-j logi r) constructed by a Bondi-Sachs type method is analysed. The occurrence of some log terms in an asymptotic expansion of the metric is related to the non-vanishing of the Weyl tensor at ℐ. The validity in this more general context of various results from the standard treatment of ℐ, including the Bondi mass loss formula, the peeling-off of the Riemann tensor and the Newman-Penrose constants of motion, is considered.
Developmental Acquisition of a Rapid Calcium-Regulated Vesicle Supply Allows Sustained High Rates of Exocytosis in Auditory Hair Cells

Auditory hair cells (HCs) have the remarkable property to indefinitely sustain high rates of synaptic vesicle release during ongoing sound stimulation. The mechanisms of vesicle supply that allow such indefatigable exocytosis at the ribbon active zone remain largely unknown. To address this issue, we characterized the kinetics of vesicle recruitment and release in developing chick auditory HCs. Experiments were done using the intact chick basilar papilla from E10 (embryonic day 10) to P2 (two days post-hatch) by monitoring changes in membrane capacitance and Ca2+ currents during various voltage stimulations. Compared to immature pre-hearing HCs (E10-E12), mature post-hearing HCs (E18-P2) can steadily mobilize a larger readily releasable pool (RRP) of vesicles with faster kinetics and higher Ca2+ efficiency. As assessed by varying the inter-pulse interval of a 100 ms paired-pulse depolarization protocol, the kinetics of RRP replenishment were found much faster in mature HCs. Unlike mature HCs, exocytosis in immature HCs showed large depression during repetitive stimulations. Remarkably, when the intracellular concentration of EGTA was raised from 0.5 to 2 mM, the paired-pulse depression level remained unchanged in immature HCs but was drastically increased in mature HCs, indicating that the Ca2+ sensitivity of the vesicle replenishment process increases during maturation. Concomitantly, the immunoreactivity of the calcium sensor otoferlin and the number of ribbons at the HC plasma membrane largely increased, reaching a maximum level at E18-P2. Our results suggest that the efficient Ca2+-dependent vesicle release and supply in mature HCs essentially rely on the concomitant engagement of synaptic ribbons and otoferlin at the plasma membrane.
Verbal Self‐Monitoring in the Second Language

Speakers monitor their own speech for errors. To do so, they may rely on perception of their own speech (external monitoring) but also on an internal speech representation (internal monitoring). While there are detailed accounts of monitoring in first language (L1) processing, it is not clear if and how monitoring is different in a second language (L2). Here, we ask whether L1 and L2 monitoring differ and, if so, where the differences lie. L1 and L2 might differ in the speed with which monitoring is performed but also in their monitoring foci. We discuss studies on bilingual language control and suggest that self-monitoring might function as a last-resort control process. We conclude with speculation on the role self-monitoring might play in L2 learning and suggestions for future research.
How do Tasks and Technology Fit? - Bringing order to the Open Innovation Chaos

Open innovation (OI) projects comprise various steps from the generation of ideas and their development to the market launch of a product (or service). Each step of the innovation process consists of tasks whose execution results in particular outputs. Following the paradigm shift towards OI, organizations increasingly allow external stakeholders to contribute during these steps by taking over certain tasks. Although the general benefit of OI is considered to be positively influential on innovativeness and competitiveness of a new product, the individual output of each task and, thus, the OI project varies tremendously. Research illustrates a broad range from projects with a focus on just initial idea generation to ones that result in complex strategies and marketable solutions. The question remains, which tasks or sub-tasks are involved in OI projects that lead to one particular output? To answer this question, the present study analyzes existing research on open innovation projects and summarizes the tasks that are performed. In addition to this process-oriented perspective, the technical side, i.e. the support of innovation tasks by ICT, lacks research. Recent developments, especially regarding social software, present new approaches to support these tasks. Hence, this paper uses its initial findings to develop profiles of fit between tasks and technology. By adapting the Task-Technology-Fit theory by Goodhue and Thompson (1995) this research helps organizations to select the most suitable application for a specific task.
Remembrance Day influence on national sentiments and hostility towards out-groups: evidence from a panel study in Israel

ABSTRACT While scholars have long emphasized the significant impact of national days on the masses, the actual impact of national days on people’s national sentiments have been ignored. This study set out to examine the ways in which exposure to Remembrance Day impacts national sentiments and hostility towards out-groups. Unlike previous cross-sectional-design studies, it adopted longitudinal design in order to explore the actual impact of exposure to Remembrance Day amongst Israeli Jews. While exposure to Remembrance Day increased the respondents’ sense of nationalism, neither their level of national identification and hostility towards out-groups nor the magnitude of the positive link between nationalism and hostility towards out-groups changed significantly. While national identification was unrelated to hostility prior to Remembrance Day, it became negatively related to it on Remembrance Day itself. The findings shed new light on the prevalent assumption regarding the impact national days have on public sentiment.
A Self-Organizing Connectionist Model of Bili ngual Processing

Current connectionist models of bili ngual language processing have been largely restricted to localist stationary models. To fully capture the dynamics of bili ngual processing, we present SOMBIP, a self-organizing model of bili ngual processing that has learning characteristics. SOMBIP consists of two interconnected selforganizing neural networks, coupled with a recurrent neural network that computes lexical co-occurrence constraints. Simulations with our model indicate that (1) the model can account for distinct patterns of the bili ngual lexicon without the use of language nodes or language tags, (2) it can develop meaningful lexical-semantic categories through self-organizing processes, and (3) it can account for a variety of priming and interference effects based on associative pathways between phonology and semantics in the lexicon, and (4) it can explain lexical representation in bili nguals with different levels of proficiency and working memory capacity. These capabiliti es of our model are due to its design characteristics in that (a) it combines localist and distributed properties of processing, (b) it combines representation and learning, and (c) it combines lexicon and sentences in bili ngual processing. Thus, SOMBIP serves as a new model of bili ngual processing and provides a new perspective on connectionist bili ngualism. It has the potential of explaining a wide variety of empirical and theoretical issues in bili ngual research.