Miracle-dz/UniFAR-FTUs huggingface dataset:
Chikusetsu saponin IVa protects pancreatic β cell against intermittent high glucose-induced injury by activating Wnt/β-catenin/TCF7L2 pathway

Islet β cell mass reduction induced by glucose fluctuation is crucial for the development and progression of T2DM. Chikusetsu saponin IVa (CHS) had protective effects against DM and related injuries. Here we aimed to investigate the role of CHS in β cell injuries and its possible mechanism involved. Isolated rat islets, βTC3 cells and T2DM mice were used in this study. The results showed that CHS restored the secretion activity, promoted β cell survival by increasing β cell proliferation and decreasing apoptosis which induced by intermittent high glucose (IHG). In vivo, CHS protected β cell apoptosis to normalize blood glucose and improve insulin sensitivity in DM mice. Further studies showed that CHS activated Wnt3a signaling, inhibited HBP1, promoted β-catenin nuclear translocation, enhanced expressions of TCF7L2, GIPR and GLP-1R, inhibited p53, p27 and p21. The protective effect of CHS was remarkably suppressed by siRNAs against TCF7L2 or XAV-939 (a Wnt/β-catenin antagonist) in vitro and in β-catenin-/- mice. In conclusion, we identified a novel role of CHS in protecting β cell survival and regeneration by mechanisms involving the activation of Wnt3a/β-catenin/TCF7L2 signaling. Our results indicated the potential value of CHS as a possible intervention drug for T2DM.
The IDH-TAU-EGFR triad defines the neovascular landscape of diffuse gliomas

TAU is expressed in the less aggressive gliomas where it impairs the mesenchymal transdifferentiation of tumor cells and normalizes the vasculature. The positive side of TAU Gliomas, brain tumors originating in glial cells, are classified according to histologic as well as genetic features. Mutations in the IDH1/2 genes are associated with more favorable prognosis, whereas mutations in EGFR are characteristic of aggressive tumors. How these genes affect the microenvironment is not completely clear. Now, Gargini et al. show that TAU protein, classically associated with neurodegenerative disorders, is increased in less aggressive tumors. TAU inhibited the transition toward an aggressive phenotype by blocking EGFR activation. Mutated EGFR was no longer sensitive to TAU inhibition, possibly explaining the aggressive phenotype associated with EGFR mutations. The results suggest that TAU might play a main role in determining glioma aggressiveness. Gliomas that express the mutated isoforms of isocitrate dehydrogenase 1/2 (IDH1/2) have better prognosis than wild-type (wt) IDH1/2 gliomas. However, how these mutant (mut) proteins affect the tumor microenvironment is still a pending question. Here, we describe that the transcription of microtubule-associated protein TAU (MAPT), a gene that has been classically associated with neurodegenerative diseases, is epigenetically controlled by the balance between wt and mut IDH1/2 in mouse and human gliomas. In IDH1/2 mut tumors, we found high expression of TAU that decreased with tumor progression. Furthermore, MAPT was almost absent from tumors with epidermal growth factor receptor (EGFR) mutations, whereas its trancription negatively correlated with overall survival in gliomas carrying wt or amplified (amp) EGFR. We demonstrated that the overexpression of TAU, through the stabilization of microtubules, impaired the mesenchymal/pericyte-like transformation of glioma cells by blocking EGFR, nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) and the transcriptional coactivator with PDZ-binding motif (TAZ). Our data also showed that mut EGFR induced a constitutive activation of this pathway, which was no longer sensitive to TAU. By inhibiting the transdifferentiation capacity of EGFRamp/wt tumor cells, TAU protein inhibited angiogenesis and favored vascular normalization, decreasing glioma aggressiveness and increasing their sensitivity to chemotherapy.
A priori and a posteriori methods in comparative evolutionary studies of host–parasite associations

Brooks parsimony analysis (BPA) and reconciliation methods in studies of host–parasite associations differ fundamentally, despite using the same null hypothesis. Reconciliation methods may eliminate or modify input data to maximize fit of single parasite clades to a null hypothesis of cospeciation, by invoking different a priori assumptions, including a known host phylogeny. By examining the degree of phylogenetic congruence among multiple parasite clades, using hosts as analogs of taxa but not presuming a host phylogeny or any degree of cospeciation a priori, BPA modifies the null hypothesis of cospeciation if necessary to maintain the integrity of the input data. Two exemplars illustrate critical empirical differences between reconciliation methods and BPA: (1) reconciliation methods rather than BPA may select the incorrect general host cladogram for a set of data from different clades of parasites, (2) BPA rather than reconciliation methods provides the most parsimonious interpretation of all available data, and (3) secondary BPA, proposed in 1990, when applied to data sets in which host‐switching produces hosts with reticulate histories, provides the most parsimonious and biologically realistic interpretations of general host cladograms. The extent to which these general host cladograms, based on cospeciation among different parasite clades inhabiting the same hosts, correspond to host phylogeny can be tested, a posteriori, by comparison with a host phylogeny generated from nonparasite data. These observations lead to the conclusion that BPA and reconciliation methods are designed to implement different research programs based on different epistemologies. BPA is an a posteriori method that is designed to assess the host context of parasite speciation events, whereas reconciliation methods are a priori methods that are designed to fit parasite phylogenies to a host phylogeny. Host‐switching events are essential for explaining complex histories of host–parasite associations. BPA assumes coevolutionary complexity (historical contingency), relying on parsimony as an a posteriori explanatory tool to summarize complex results, whereas reconciliation methods, which embody formalized assumptions of maximum cospeciation, are based on a priori conceptual parsimony. Modifications of basic reconciliation methods, embodied in TreeMap 1.0 and TreeMap 2.02, represent the addition of weighting schemes in which the researcher specifies allowed departures from cospeciation a priori, with the result that TreeMap results more closely agree with BPA results than do reconciled tree analysis results.
Determinants of place of delivery : A comparison between an urban and a rural community in Nigeria

Child-birth is a risk producing event that requires timely and adequate medical intervention for women who experience obstetric complications. The provision of a health worker with midwifery skills at every birth, plus access to emergency hospital obstetric care, is the option to mitigate this risk. However, in sub Saharan Africa, most births take place outside health facilities and without skilled attendants. This study aimed to determine and compare the factors which influence the choice of place of delivery among women in an urban and a rural community in Sokoto. It was a cross-sectional comparative study of 600 randomly selected women of reproductive age, in Sokoto South and Gwadabawa Local Government Areas of Sokoto State, Nigeria using semi-structured interviewer administered questionnaires. The proportion of women who delivered in health facilities was 65.0 and 4.7% in the urban and rural groups, respectively; whereas the proportion that had skilled attendants at delivery was 70 and 4.3% in the urban and rural groups, respectively. Lack of consent from husband, no privacy in health facilities, distance to the health facility and non-availability of delivery wards were the reasons for home deliveries in the rural study group, while the emergency nature of labour was the reason in the urban group. Women residing in rural areas need health promotion interventions in order to meet the International Conference on Population and Development + target of achieving 90% births attended by skilled attendants by 2015.
Pioglitazone Attenuates Reoxygenation Injury in Renal Tubular NRK-52E Cells Exposed to High Glucose via Inhibiting Oxidative Stress and Endoplasmic Reticulum Stress

Renal ischemia-reperfusion injury is a major cause of acute kidney injury. In the present study, we investigated the effects of pioglitazone on hypoxia/reoxygenation (H/R) injury in rat renal tubular epithelial cells (RTECs) under normal- (NG) or high-glucose (HG) culture conditions via evaluating oxidative stress and endoplasmic reticulum stress (ERS). The RTECs (NRK-52E cells) were divided into six groups as follows: NG group, HG group, NG + H/R group, HG + H/R group, NG + Pio + H/R group, and HG + Pio + H/R group, among which cells in H/R groups were subjected to 4 h of hypoxia followed by 12 h of reoxygenation. After that, the cells were evaluated using the Cell Counting Kit-8 assay for the determination of their viability and flow cytometry assay for the detection of apoptosis. The levels of superoxide dismutase (SOD), glutathione reductase (GSH), catalase (CAT), and malondialdehyde (MDA) were determined via colorimetric chemical assays. In addition, the expression of ERS-associated proteins, i.e. ATF4, ATF6, GRP78, and CHOP, was determined via western blotting. A HG environment could reduce the viability and increase the apoptotic rate of NRK-52E cells with increased MDA levels and decreased SOD, CAT, and GSH levels, and upregulate the expression of ERS-associated proteins, i.e. ATF4, ATF6, and GRP78. H/R injury could further aggravate changes in the above indicators, but pioglitazone could significantly reverse such changes and alleviate cell injury. Thus, Pioglitazone exhibits a cytoprotective effect on RTECs against H/R injury under NG or HG culture conditions by inhibiting oxidative stress and ERS.
Lipid Transfer Proteins and Membrane Contact Sites in Human Cancer

Lipid-transfer proteins (LTPs) were initially discovered as cytosolic factors that facilitate lipid transport between membrane bilayers in vitro. Since then, many LTPs have been isolated from bacteria, plants, yeast, and mammals, and extensively studied in cell-free systems and intact cells. A major advance in the LTP field was associated with the discovery of intracellular membrane contact sites (MCSs), small cytosolic gaps between the endoplasmic reticulum (ER) and other cellular membranes, which accelerate lipid transfer by LTPs. As LTPs modulate the distribution of lipids within cellular membranes, and many lipid species function as second messengers in key signaling pathways that control cell survival, proliferation, and migration, LTPs have been implicated in cancer-associated signal transduction cascades. Increasing evidence suggests that LTPs play an important role in cancer progression and metastasis. This review describes how different LTPs as well as MCSs can contribute to cell transformation and malignant phenotype, and discusses how “aberrant” MCSs are associated with tumorigenesis in human.
Using Clustering Methods in Multinomial Logit Model for Departure Time Choice

Travellers have to make some decisions for each trip, and one of them is the choice of departure time. Discrete choice models have been employed as an approach to departure time modelling by many researchers. In this method, preparing choice set is a primary challenge which involves the definition of some departure periods to be selected by the traveller. In this research, choice sets were formed by applying the clustering methods on departure times. Afterwards, we developed Multinomial Logit (MNL) models on different choice sets and compared the models. The data used throughout this research belonged to Mashhad City. Research results indicated that Ward’s hierarchical clustering method is improper for time discretization; furthermore, the K-means clustering method is more efficient than the expectation maximization and K-medoids methods in the time discretization for MNL modelling. The developed model (based on K-means clustering method) accurately predicts departure time for 58% of persons within the test group, which reflects the effectiveness of the resulting model compared to the 36% which is obtained without the model.
CREDIBILITY AND POPULISM: A BAYESIAN APPROACH TO THE GOULART ADMINISTRATIONS IN BRAZIL

The Goulart Administrations (1961-1964), which include a parliamentary and a presidential period, are considered typical examples of populism in Brazil. The literature usually defines their economic policies as “hesitating”, “irrational” or “ambiguous”. We use a model of credibility to argue that there is a pattern in the way economic policies were conducted. The credibility of the economic policies is defined to be the subjective probability that the government is following a monetary rule. The Administrations began with measures to fight inflation. As time passes, though, as a result of the costs associated with the policies, they abandoned the austerity, their credibility decreased and the attempts toward stabilization failed. Then, we may imply that: a) there is a logic and a coherence in the economic policies implemented which cannot therefore be considered irrational or erratic; b) orthodoxy is present both in the speech and in the actual implementation of the policies, especially in the first phase of each of the conjunctures, what prevents us to see the populist phenomenon only as an option for growth, totally disregarding stability; c) despite being present, this option for inflation fight was not maintained along either of the analysed periods; d) never was the transition between the option for stability and the one for growth abrupt, what does not support theses that mention a "shift" that would have occurred at a point in time that could serve as a landmark separating the two opposing economic policies; e) the prodevelopment rhetoric was present in the two phases of the analysed conjuncture, but only in the end of each one the option for growth was set as a priority, putting stability in the background; and f) finally, the prodevelopment speech took a quite critical tone, associating to nationalistic pledges, usually blaming foreign capital and international organizations for the deepening of the crisis, in a radical tone not seen in the first stages.
Characterization of a Novel Moderately Thermophilic Solvent-Tolerant Esterase Isolated From a Compost Metagenome Library

A novel esterase, EstCS1, was isolated from a compost metagenomics library. The EstCS1 protein, which consists of 309 amino acid residues with an anticipated molecular mass of 34 kDa, showed high amino acid sequence identities to predicted esterases and alpha/beta hydrolases (59%) from some cultured bacteria and to predicted lipases/esterases from uncultured bacteria. The phylogenetic analysis suggested that the EstCS1 belongs to the hormone-sensitive lipase family of lipolytic enzyme classification and contains a catalytic triad including Ser155–Asp255–His285. The Ser155 residue of the catalytic triad in the EstCS1 was located in the consensus active-site motif, GXSXG. Besides, a conserved HGGG motif placed in an oxyanion hole of the hormone-sensitive lipase family was discovered, too. The EstCS1 demonstrated the highest activity toward p-nitrophenyl propionate (C3) and caproate (C6) and was normally stable up to 60°C with optimal activity at 50°C. In addition, an optimal activity was observed at pH 8, and the EstCS1 possessed its stability within the pH range between 5 and 10. Interestingly, EstCS1 had an outstanding stability in up to 30% (v/v) organic solvents and activity over 50% in the presence of 50% (v/v) acetone, ethanol, dimethyl sulfoxide (DMSO), and N,N-dimethylformamide. The EstCS1 hydrolyzed sterically hindered tertiary alcohol esters of t-butyl acetate and linalyl acetate. Considering the properties, such as the moderate thermostability, stability against organic solvents, and activity toward esters of tertiary alcohols, the EstCS1 will be worthwhile to be used for organic synthesis and related industrial applications.
Cobordism invariance of topological edge-following states

We prove that a spectral gap-filling phenomenon occurs whenever a Hamiltonian operator encounters a coarse index obstruction upon compression to a domain with boundary. Furthermore, the gap-filling spectra contribute to quantised current channels, which follow and are localised at the possibly complicated boundary. This index obstruction is shown to be insensitive to deformations of the domain boundary, so the phenomenon is generic for magnetic Laplacians modelling quantum Hall systems and Chern topological insulators. A key construction is a quasi-equivariant version of Roe's algebra of locally compact finite propagation operators.
Learning Distributional Programs for Relational Autocompletion

Relational autocompletion is the problem of automatically filling out some missing values in multi-relational data. We tackle this problem within the probabilistic logic programming framework of Distributional Clauses (DCs), which supports both discrete and continuous probability distributions. Within this framework, we introduce DiceML – an approach to learn both the structure and the parameters of DC programs from relational data (with possibly missing data). To realize this, DiceML integrates statistical modeling and DCs with rule learning. The distinguishing features of DiceML are that it (1) tackles autocompletion in relational data, (2) learns DCs extended with statistical models, (3) deals with both discrete and continuous distributions, (4) can exploit background knowledge, and (5) uses an expectation–maximization-based (EM) algorithm to cope with missing data. The empirical results show the promise of the approach, even when there is missing data.
Deep Learning for Lung Cancer Nodules Detection and Classification in CT Scans

Detecting malignant lung nodules from computed tomography (CT) scans is a hard and time-consuming task for radiologists. To alleviate this burden, computer-aided diagnosis (CAD) systems have been proposed. In recent years, deep learning approaches have shown impressive results outperforming classical methods in various fields. Nowadays, researchers are trying different deep learning techniques to increase the performance of CAD systems in lung cancer screening with computed tomography. In this work, we review recent state-of-the-art deep learning algorithms and architectures proposed as CAD systems for lung cancer detection. They are divided into two categories—(1) Nodule detection systems, which from the original CT scan detect candidate nodules; and (2) False positive reduction systems, which from a set of given candidate nodules classify them into benign or malignant tumors. The main characteristics of the different techniques are presented, and their performance is analyzed. The CT lung datasets available for research are also introduced. Comparison between the different techniques is presented and discussed.
Interdisciplinary and Multilevel Approach to Organic and Sustainable Agriculture Education at North Carolina State University

There is an increasing demand for education in organic and sustainable agriculture from undergraduates, graduate students and extension agents. In this paper, we discuss highlights and evaluations of a multilevel approach to education currently being developed at North Carolina State University (NCSU) that integrates interdisciplinary training in organic and sustainable agriculture and the related discipline of agroecology through a variety of programs for undergraduate students, graduate students, and extension agents. These educational programs are possible because of a committed interdisciplinary faculty team and the Center for Environmental Farming Systems, a facility dedicated to sustainable and organic agriculture research, education, and outreach. Undergraduate programs include an inquiry-based sustainable agriculture summer internship program, a sustainable agriculture apprenticeship program, and an interdisciplinary agroecology minor that includes two newly developed courses in agroecology and a web-based agroecology course. Research projects and a diversity of courses focusing on aspects of sustainable and organic agriculture are available at NCSU for graduate students and a PhD sustainable agriculture minor is under development. A series of workshops on organic systems training offered as a graduatelevel course at NCSU for extension agents is also described. Connecting experiential training to a strong interdisciplinary academic curriculum in organic and sustainable agriculture was a primary objective and a common element across all programs. We believe the NCSU educational approach and programs described here may offer insights for other land grant universities considering developing multilevel sustainable agriculture educational programs.
Food terrorism: do we care?

According to the New Zealand Security Intelligence Service (NZSIS), terrorist elements exist and are active in New Zealand (Smith, 2003). This paper focused on the lack of pre and post-employment security vetting, security concerns around contract manufacturing of food products and exporting finished food products to security sensitive countries. There appeared to be a laissez-faire attitude towards security and this was evident in their processes. This relaxed attitude can be explained using Hofstede’s uncertainty avoidance category (Hofstede, 1984; Peter, 2011; Peter, Losekoot and Poulston, 2013; Adams, 2013a). This exploratory study seeks to raise awareness of the issues outlined and thereby increase efforts to enhance food security in New Zealand.
Low-frequency conductivity in many-body localized systems

We argue that the a.c. conductivity $\sigma(\omega)$ in the many-body localized phase is a power law of frequency $\omega$ at low frequency: specifically, $\sigma(\omega) \sim \omega^\alpha$ with the exponent $\alpha$ approaching 1 at the phase transition to the thermal phase, and asymptoting to 2 deep in the localized phase. We identify two separate mechanisms giving rise to this power law: deep in the localized phase, the conductivity is dominated by rare resonant pairs of configurations; close to the transition, the dominant contributions are rare regions that are locally critical or in the thermal phase. We present numerical evidence supporting these claims, and discuss how these power laws can also be seen through polarization-decay measurements in ultracold atomic systems.
Factorial Structure and Measurement Invariance of the Acceptance and Action Questionnaire-Stigma (AAQ-S) in Spain

The objective of the present study was to validate and adapt the Acceptance and Action Questionnaire-Stigma (AAQ-S) to the Spanish context. Method: The study included the participation of 1212 subjects, with an average age of 17.12 years old. Results: The confirmatory factorial analysis revealed a number of adequate fit indices for the new version of the scale χ2/df = 3.24; Comparative Fit Index = 0.96; Incremental Fit Index = 0.96; Root Mean Square Error of Approximation = 0.060; Standardized Root Mean Square Residual = 0.035, in which the factorial structures displayed gender invariance. The two factors comprise the scale both exhibited high internal consistency (+0.90) and temporal stability. Conclusion: The Spanish version of the AAQ-S proved to be a robust and adequate psychometric instrument. In this sense, future lines of research focused on determining the role of psychological flexibility in stigma and the processes of change at the base of interventions could benefit substantially from the use of AAQ-S.