Miracle-dz/UniFAR-FTUs huggingface dataset:
Pro-fibrotic compounds induce stellate cell activation, ECM-remodelling and Nrf2 activation in a human 3D-multicellular model of liver fibrosis

Background & Aims Currently most liver fibrosis research is performed in vivo, since suitable alternative in vitro systems which are able to recapitulate the cellular events leading to liver fibrosis are lacking. Here we aimed at generating a system containing cells representing the three key players of liver fibrosis (hepatocyte, Kupffer cells and stellate cells) and assess their response to pro-fibrotic compounds such as TGF-β1, methotrexate (MTX) and thioacetamide (TAA). Methods Human cell lines representing hepatocytes (HepaRG), Kupffer cell (THP-1 macrophages) and stellate cells (hTERT-HSC) were co-cultured using the InSphero hanging drop technology to generate scaffold-free 3D microtissues, that were treated with pro-fibrotic compounds (TGF-β1, MTX, TAA) for up to 14 days. The response of the microtissues was evaluated by determining the expression of cytokines (TNF-α, TGF-β1 and IL6), the deposition and secretion of ECM proteins and induction of gene expression of fibrosis biomarkers (e.g. αSMA). Induction of Nrf2 and Keap1, as key player of defence mechanism, was also evaluated. Results We could demonstrate that the multicellular 3D microtissue cultures could be maintained in a non-activated status, based on the low expression levels of activation markers. Macrophages were activated by stimulation with LPS and hTERT-HSC showed activation by TGF-β1. In addition, MTX and TAA elicited a fibrotic phenotype, as assessed by gene-expression and protein-deposition of ECM proteins such as collagens and fibronectin. An involvement of the antioxidant pathway upon stimulation with pro-fibrotic compounds was also observed. Conclusion Here, for the first time, we demonstrate the in vitro recapitulation of key molecular and cellular events leading to liver fibrosis: hepatocellular injury, antioxidant defence response, activation of Kupffer cells and activation of HSC leading to deposition of ECM.
Perspectives on bilingual children's narratives elicited with the Multilingual Assessment Instrument for Narratives

This Special Issue is all about the stories of children: preschool- and school-age children; bilingual and monolingual children; children developing typically or identified as having a specific language impairment (SLI); and children speaking and experiencing one or more of the following languages: English, Finnish, German, Greek, Hebrew, Italian, Russian, Slovak, Swedish, and Turkish in minority or majority language contexts. The stories are fictional ones, about baby birds and baby goats, a cat and a dog: a cast of characters the reader will come to know well as they read the Introduction (Gagarina, Klop, Tsimpli, & Walters, 2016) and individual articles. They were collected using a new narrative assessment tool that is common to all the articles within the issue: the Language Impairment Testing in Multilingual Settings—Multilingual Assessment Instrument for Narratives (LITMUS-MAIN; Gagarina et al., 2012, 2015), described at some length by its developers in the Introduction to the Special Issue.
Experiments, policy, and theory in development economics: a response to Glenn Harrison’s ‘field experiments and methodological intolerance’

In ‘Field Experiments and Methodological Intolerance,’ Glenn Harrison develops a criticism of randomized field experiments and denounces ‘intolerance’ for lab experiments and a ‘disconnect from theory. ’ We argue that (i) lab experiments and RCTs are based on different methodological approaches and therefore fulfill different scientific objectives; (ii) key features of the RCT methodology make it highly relevant for policy-making, which accounts for a large part of its uptake; (iii) RCTs foster a convergence of interests between policy-makers and researchers around the study of economic mechanisms, which makes it possible to challenge and improve economic theory based on real-world facts; and (iv) hybrid forms of experimentation are being increasingly used and open promising avenues. In sum, economic research based on RCTs is more and more connected to theory and other forms of experiment, while also helping policy-makers tackle daunting problems of poverty and exclusion.
Escin Chemosensitizes Human Pancreatic Cancer Cells and Inhibits the Nuclear Factor-kappaB Signaling Pathway

Background. There is an urgent need to develop new treatment strategies and drugs for pancreatic cancer that is highly resistant to radio-chemotherapy. Aesculus hippocastanum (the horse chestnut) known in Chinese medicine as a plant with anti-inflammatory, antiedema, antianalgesic, and antipyretic activities. The main active compound of this plant is Escin (C54H84O23). Objective. To evaluate the effect of Escin alone and combined with chemotherapy on pancreatic cancer cell survival and to unravel mechanism(s) of Escin anticancer activity. Methods. Cell survival was measured by XTT colorimetric assay. Synergistic effect of combined therapy was determined by CalcuSyn software. Cell cycle and induction of apoptosis were evaluated by FACS analysis. Expression of NF-κB-related proteins (p65, IκBα, and p-IκBα) and cyclin D was evaluated by western blot analysis. Results. Escin decreased the survival of pancreatic cancer cells with IC50 = 10–20 M. Escin combined with gemcitabine showed only additive effect, while its combination with cisplatin resulted in a significant synergistic cytotoxic effect in Panc-1 cells. High concentrations of Escin induced apoptosis and decreased NF-κB-related proteins and cyclin D expression. Conclusions. Escin decreased pancreatic cancer cell survival, induced apoptosis, and downregulated NF-κB signaling pathway. Moreover, Escin sensitized pancreatic cancer cells to chemotherapy. Further translational research is required.
The Study of Crack Mechanism During Arc Brazing of Cooling Pipe to ITER Magnet Support System

It is suggested using arc brazing to attach the cooling pipe to the ITER magnet supports system due to the high bond strength as well as the good thermal conductivity. A microcrack, which is terrible for system safety, was found during the test. In this paper, the mechanism of the microcrack during arc brazing is investigated.
An asymptotic error bound for testing multiple quantum hypotheses

We consider the problem of detecting the true quantum state among $r$ possible ones, based of measurements performed on $n$ copies of a finite-dimensional quantum system. A special case is the problem of discriminating between $r$ probability measures on a finite sample space, using $n$ i.i. d. observations. In this classical setting, it is known that the averaged error probability decreases exponentially with exponent given by the worst case binary Chernoff bound between any possible pair of the $r$ probability measures. Define analogously the multiple quantum Chernoff bound, considering all possible pairs of states. Recently, it has been shown that this asymptotic error bound is attainable in the case of $r$ pure states, and that it is unimprovable in general. Here we extend the attainability result to a larger class of $r$-tuples of states which are possibly mixed, but pairwise linearly independent. We also construct a quantum detector which universally attains the multiple quantum Chernoff bound up to a factor 1/3.
Affective Predictors of Disrupted Reward-Seeking in Depression

Background: Anhedonia, or the diminished anticipation and pursuit of reward, is a core symptom of major depressive disorder (MDD). Trait behavioral activation (BA), as a proxy measure of anhedonia, and behavioral inhibition (BI) may moderate the relationship between MDD and reward-seeking. The present studies (Study 1 and Study 2) probed for reward learning deficits, potentially due to aberrant BA and/or BI, in individuals with active or remitted MDD compared to healthy controls (HC). Methods: Active MDD (in Study 1) and remitted MDD (in Study 2) participants completed the modified monetary incentive delay task (mMIDT), a behavioral reward-seeking measure whose response window parameters were individually titrated to theoretically elicit equivalent accuracy between groups. Participants completed the Behavioral Inhibition Scale and Behavioral Activation Reward-Responsiveness and Drive Scales. Results: Despite individual response speed titration, active MDD participants won significantly less money than HCs. Higher Reward-Responsiveness scores predicted a greater amount won, whereas Drive and BI did not predict performance. Remitted MDD participants did not differ from controls on mMIDT performance, and trait measures of BA or BI did not predict r-MDD performance. Discussion: These results suggest that diminished reward-responsiveness may contribute to decreased motivation and reward pursuit during active MDD, and that reward learning is intact in remission. Understanding individual reward processing deficits in MDD may inform personalized intervention for alleviating anhedonia and motivation deficits in select active MDD patients. Limitations include small sample sizes, different age ranges in the two studies, and collecting the data during fMRI in Study 1 but not Study 2.
Academic Civic Mindedness and Model Citizenship in the International Baccalaureate Diploma Programme

ABSTRACT This study uses interview and survey methods to describe the International Baccalaureate (IB) Diploma Programme's (DP) development of students' “academic civic mindedness” and “model citizenship” at four public schools in California. Results indicate that the DP pedagogy enables students to develop many of the skills that are necessary for civic advocacy and that the DP places a strong emphasis on students' knowledge of issues related to public policy. The DP develops students' citizenship through promoting their awareness of political and social issues and required active engagement with a local or global issue. Most IB students and teachers feel that the DP develops students' academic civic mindedness and model citizenship to a considerably greater extent than other curricular alternatives. Finally, teachers feel that the strongest limitation to their prioritization of students' citizenship development is their lack of clarity on how to frame the civic implications of what they teach.
Opposite Root Growth Phenotypes of hy5 versus hy5 hyh Mutants Correlate with Increased Constitutive Auxin Signaling

The Arabidopsis transcription factor HY5 controls light-induced gene expression downstream of photoreceptors and plays an important role in the switch of seedling shoots from dark-adapted to light-adapted development. In addition, HY5 has been implicated in plant hormone signaling, accounting for the accelerated root system growth phenotype of hy5 mutants. Mutants in the close HY5 homolog HYH resemble wild-type, despite the largely similar expression patterns and levels of HY5 and HYH, and the functional equivalence of the respective proteins. Moreover, the relative contribution of HYH to the overall activity of the gene pair is increased by an alternative HYH transcript, which encodes a stabilized protein. Consistent with the enhanced root system growth observed in hy5 loss-of-function mutants, constitutively overexpressed alternative HYH inhibits root system growth. Paradoxically, however, in double mutants carrying hy5 and hyh null alleles, the hy5 root growth phenotype is suppressed rather than enhanced. Even more surprisingly, compared to wild-type, root system growth is diminished in hy5 hyh double mutants. In addition, the double mutants display novel shoot phenotypes that are absent from either single mutant. These include cotyledon fusions and defective vasculature, which are typical for mutants in genes involved in the transcriptional response to the plant hormone auxin. Indeed, many auxin-responsive and auxin signaling genes are misexpressed in hy5 mutants, and at a higher number and magnitude in hy5 hyh mutants. Therefore, auxin-induced transcription is constitutively activated at different levels in the two mutant backgrounds. Our data support the hypothesis that the opposite root system phenotypes of hy5 single and hy5 hyh double mutants represent the morphological response to a quantitative gradient in the same molecular process, that is gradually increased constitutive auxin signaling. The data also suggest that HY5 and HYH are important negative regulators of auxin signaling amplitude in embryogenesis and seedling development.
Ten Things You Should Know About the Dynamic Conditional Correlation Representation

The purpose of the paper is to discuss ten things potential users should know about the limits of the Dynamic Conditional Correlation (DCC) representation for estimating and forecasting time-varying conditional correlations. The reasons given for caution about the use of DCC include the following: DCC represents the dynamic conditional covariances of the standardized residuals, and hence does not yield dynamic conditional correlations; DCC is stated rather than derived; DCC has no moments; DCC does not have testable regularity conditions; DCC yields inconsistent two step estimators; DCC has no asymptotic properties; DCC is not a special case of GARCC, which has testable regularity conditions and standard asymptotic properties; DCC is not dynamic empirically as the effect of news is typically extremely small; DCC cannot be distinguished empirically from diagonal BEKK in small systems; and DCC may be a useful filter or a diagnostic check, but it is not a model.
THE WELFARE EFFECTS OF SOCIAL SECURITY IN A MODEL WITH AGGREGATE AND IDIOSYNCRATIC RISK

We study the welfare effects of social security in an overlapping generations general equilibrium model with aggregate and idiosyncratic risk. Prior research on social security has only considered either aggregate or idiosyncratic risk. We show analytically that the aggregate and idiosyncratic risks interact due to the life-cycle structure of the economy. This interaction increases the welfare gains of a marginal introduction of an unfunded social security system. Adding a second interaction by making the variance of the idiosyncratic risk countercyclical further increases the welfare gains. In our quantitative experiment, raising the contribution rate from zero to two percent leads to long-run welfare gains of 3.5% of life-time consumption on average, even though the economy experiences substantial crowding out of capital. Approximately one third of these gains can be attributed to the interactions between idiosyncratic and aggregate risk. JEL classification: C68; E27; E62; G12; H55
Hamiltonicity of random graphs produced by 2‐processes

Suppose that a random graph begins with n isolated vertices and evolves by edges being added at random, conditional upon all vertex degrees being at most 2. The final graph is usually 2‐regular, but is not uniformly distributed. Some properties of this final graph are already known, but the asymptotic probability of being a Hamilton cycle was not known. We answer this question along with some related questions about cycles arising in the process. © 2006 Wiley Periodicals, Inc. Random Struct. Alg. , 2007
Intracerebroventricular Transplantation of Embryonic Neuronal Tissue from Inflammatory Resistant into Inflammatory Susceptible Rats Suppresses Specific Components of Inflammation

To more directly define the role of central nervous system factors in susceptibility to peripheral inflammatory disease, we examined the effect of intracerebroventricular transplantation of neuronal tissue from inflammatory resistant into inflammatory susceptible rats on subcutaneous carrageenan-induced inflammation (a measure of innate immunity), and on the relative percentage of naive and memory T helper cells in peripheral blood (a measure of the anamnestic immune response). Female inflammatory disease susceptible Lewis (LEW/N) rats transplanted with hypothalamic tissue from inflammatory resistant Fischer (F344/N) rats exhibited > 85% decrease in carrageenan inflammation compared to naive LEW/N rats, LEW/N rats transplanted with F344/N spinal cord, or sham-operated animals. LEW/N rats transplanted with LEW/N hypothalamic tissue exhibited > 50% decrease in carrageenan inflammation. In contrast, intracerebroventricular transplantation of neuronal tissue did not affect the characteristically twofold higher percentage of naive versus memory T helper cells in LEW/N rats, suggesting that the central nervous system (CNS) and hypothalamus play a greater role in the innate inflammatory response than in the acquired immune processes. Grafted tissue survived well and did not show extensive gliosis or inflammation. Compared to naive LEW/N rats, LEW/N rats transplanted with F344/N or LEW/N hypothalamic tissue expressed significantly greater hypothalamic corticotropin releasing hormone mRNA. LEW/N rats transplanted with F344/N hypothalamic tissue also showed significant increases in plasma corticosterone responses to lipopolysaccharide. These data indicate that intracerebroventricular transplantation of fetal hypothalamic tissue from inflammatory resistant into inflammatory susceptible rats suppresses peripheral inflammation partially through hypothalamic factors. These findings have implications for understanding the contribution of specific neuronal tissue in regulation of components of the immune/inflammatory response and in susceptibility to inflammatory disease. Furthermore, this model could be used in the development of potential new treatments for inflammatory/autoimmune diseases aimed specifically at sites within the CNS.
Sequencing and Comparative Genome Analysis of Two Pathogenic Streptococcus gallolyticus Subspecies: Genome Plasticity, Adaptation and Virulence

Streptococcus gallolyticus infections in humans are often associated with bacteremia, infective endocarditis and colon cancers. The disease manifestations are different depending on the subspecies of S. gallolyticus causing the infection. Here, we present the complete genomes of S. gallolyticus ATCC 43143 (biotype I) and S. pasteurianus ATCC 43144 (biotype II.2). The genomic differences between the two biotypes were characterized with comparative genomic analyses. The chromosome of ATCC 43143 and ATCC 43144 are 2,36 and 2,10 Mb in length and encode 2246 and 1869 CDS respectively. The organization and genomic contents of both genomes were most similar to the recently published S. gallolyticus UCN34, where 2073 (92%) and 1607 (86%) of the ATCC 43143 and ATCC 43144 CDS were conserved in UCN34 respectively. There are around 600 CDS conserved in all Streptococcus genomes, indicating the Streptococcus genus has a small core-genome (constitute around 30% of total CDS) and substantial evolutionary plasticity. We identified eight and five regions of genome plasticity in ATCC 43143 and ATCC 43144 respectively. Within these regions, several proteins were recognized to contribute to the fitness and virulence of each of the two subspecies. We have also predicted putative cell-surface associated proteins that could play a role in adherence to host tissues, leading to persistent infections causing sub-acute and chronic diseases in humans. This study showed evidence that the S. gallolyticus still possesses genes making it suitable in a rumen environment, whereas the ability for S. pasteurianus to live in rumen is reduced. The genome heterogeneity and genetic diversity among the two biotypes, especially membrane and lipoproteins, most likely contribute to the differences in the pathogenesis of the two S. gallolyticus biotypes and the type of disease an infected patient eventually develops.
The Relationship between Age and Willingness to Communicate in an Iranian EFL Context

The present study attempts to investigate the relationship between Iranian EFL Learners’ age and their willingness to communicate (WTC). To this end, 30 upper intermediate learners (19 females and 11 males) were randomly selected from an English language Institute in Shiraz, Iran. The participants were asked to fill out the WTC questionnaire developed by MacIntyre et al. (2001). In order to explore whether age has any influence on the WTC performance, four age groups were defined. Before running the ANOVA test, the homogeneity of variance test was conducted. The results revealed that there is not a meaningful relationship between age and WTC of the participants. These results can have beneficial implications for teaching methodology and syllabus design.
Is Computer Assisted Language Learning (CALL) efficient for grammar learning? An experimental study in French as a second language

any studies have attempted to assess the impact of Computer Assisted Language Learning (CALL) on learning. These studies focus either on the achievement of linguistic skills such as speaking, listening, writing and reading (Garrett 1998) or on motivation (Skinner & Austin, 1999, Rico Garcia & Arias, 2000). Concerning grammar teaching, while some studies find a significant advantage of these techniques, others find no significant difference between CALL and other teaching methods. For instance, a positive impact of CALL has been found by Nutta (1998) investigating the effect of computer-based
Song Function and the Evolution of Female Preferences: Why Birds Sing, Why Brains Matter

Abstract: Analyzing the function of song and its evolution as a communication signal provides an essential backdrop for understanding the physiological and neural mechanisms responsible for song learning, perception, and production. The reverse also is true—understanding the mechanisms underlying song learning provides insight into how song has evolved as a communication signal. Song has two primary functions: to repel other males from a defended space and to attract females and stimulate their courtship. The developmental stress hypothesis we present here builds on studies of the development of the song system to suggest how learned features of song, including complexity and local dialect structure, can serve as indicators of male quality useful to females in mate choice. The link between song and male quality depends on the fact that brain structures underlying song learning largely develop during the first few months post‐hatching and that during this same period, songbirds are likely to be subject to nutritional and other developmental stresses. Individuals faring well in the face of stress are able to invest more resources to brain development and are expected to be correspondingly better at song learning. Learned features of song thus become reliable indicators of male quality, with reliability maintained by the developmental costs of song. Data from both field and laboratory studies are now beginning to provide broad support for the developmental stress hypothesis, illustrating the utility of connecting mechanistic and evolutionary analyses of song learning.
Hostages of Each Other: The Transformation of Nuclear Safety Since Three Mile Island.

Preface 1: Introduction Pt. 1: Discovering Institutions 2: Lessons of Three Mile Island 3: Nuclear Regulatory Commission 4: Institute of Nuclear Power Operations Pt. 2: Communitarian Regulation 5: Industrial Morality 6: Communal Pressure Pt. 3: Institutionalizing Responsibility 7: Learning from Experience 8: The Professionalism Project 9: Conclusion Appendix: Nuclear Industry Safety Performance Indicators Notes Index