Miracle-dz/UniFAR-FTUs huggingface dataset:
Discovering Novel Alternaria solani Succinate Dehydrogenase Inhibitors by in Silico Modeling and Virtual Screening Strategies to Combat Early Blight

Alternaria blight is an important foliage disease caused by Alternaria solani. The enzyme Succinate dehydrogenase (SDH) is a potential drug target because of its role in tricarboxylic acid cycle. Hence targeting Alternaria solani SDH enzyme could be efficient tool to design novel fungicides against A. solani. We employed computational methodologies to design new SDH inhibitors using homology modeling; pharmacophore modeling and structure based virtual screening. The three dimensional SDH model showed good stereo-chemical and structural properties. Based on virtual screening results twelve commercially available compounds were purchased and tested in vitro and in vivo. The compounds were found to inhibit mycelial growth of A. solani. Moreover in vitro trials showed that inhibitory effects were enhanced with increase in concentrations. Similarly increased disease control was observed in pre-treated potato tubers. Hence the applied in silico strategy led us to identify novel fungicides.
Postcards from the mind: The relationship between speech, imagistic gesture and thought

In this paper, I compare three different assumptions about the relationship between speech, thought and gesture. These assumptions have profound consequences for theories about the representations and processing involved in gesture and speech production. I associate these assumptions with three simplified processing architectures. In the Window Architecture, gesture provides us with a ‘window into the mind’. In the Language Architecture, properties of language have an influence on gesture. In the Postcard Architecture, gesture and speech are planned by a single process to become one multimodal message. The popular Window Architecture is based on the assumption that gestures come, as it were, straight out of the mind. I argue that during the creation of overt imagistic gestures, many processes, especially those related to (a) recipient design, and (b) effects of language structure, cause an observable gesture to be very different from the original thought that it expresses. The Language Architecture and the Postcard Architecture differ from the Window Architecture in that they both incorporate a central component which plans gesture and speech together, however they differ from each other in the way they align gesture and speech. The Postcard Architecture assumes that the process creating a multimodal message involving both gesture and speech has access to the concepts that are available in speech, while the Language Architecture relies on interprocess communication to resolve potential conflicts between the content of gesture and speech.
Individual differences in cognitive control processes and their relationship to emotion regulation

Cognitive control and emotional control share many similarities, but the specific relationship between these processes is not well understood. This study explored the relationship between three types of cognitive control (working memory updating, response inhibition and set-shifting) and two emotional regulation strategies (expressive suppression and cognitive reappraisal). Corrugator electromyography, behaviour and self-reports of affect were measured as indices of emotion regulation. Results indicate that working memory updating predicted negative affect reduction during reappraisal and during expressive suppression. This study specifically shows that the working memory component of cognitive control is associated with negative affect reduction. Response inhibition and set-shifting were not specifically related to negative affect reduction, but these variables did predict aspects of emotional behaviour and regulation. These results suggest a general role for cognitive control in some aspects of emotion regulation as well as a specific modulatory role for working memory updating in the regulation of negative affect.
Valproate‐induced hyperammonemia

A patient with carbamyl phosphate synthetase deficiency had four episodes of hyperammonemia, up to 226 μM, associated with valproate (VPA) treatment. These were accompanied by vomiting, lethargy, and coma. A group of epileptic patients receiving VPA remained asymptomatic but had significantly higher mean plasma ammonium levels when compared to epileptic patients receiving other anticonvulsants: 33.6 ± 1.9 (SEM) versus 23.6 ± 1.5 μM. Thus, VPA caused symptomatic hyperammonemia in a patient with an impairment in urea synthesis and resulted in mildly elevated ammonium levels in epileptic patients. These data suggest that ammonium levels should be monitored in patients receiving VPA who exhibit signs of vomiting or lethargy.
Isocryptotanshinone Induced Apoptosis and Activated MAPK Signaling in Human Breast Cancer MCF-7 Cells

Purpose Isocryptotanshinone (ICTS) is a natural bioactive product that is isolated from the roots of the widely used medical herb Salvia miltiorrhiza. However, few reports exist on the mechanisms underlying the therapeutic effects of ICTS. Here, we report that ICTS has anticancer activity and describe the mechanism underlying this effect. Methods The antiproliferative effect of ICTS was determined using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and clonogenic assays. The effect of ICTS on the cell cycle was measured using flow cytometry. Apoptosis was determined by Hoechst 33342 staining, DNA fragmentation assays, and Western blotting for apoptotic proteins. Finally, the effect of ICTS on mitogen-activated protein kinases (MAPKs) was determined by Western blotting. Results ICTS significantly inhibited proliferation of MCF-7 and MDA-MB-231 human breast cancer cells, HepG2 human liver cancer cells, and A549 human lung cancer cells in vitro. Among the tested cell lines, MCF-7 cells showed the highest sensitivity to ICTS. ICTS significantly inhibited colony formation by MCF-7 cells. Furthermore, exposure of MCF-7 cells to ICTS induced cell cycle arrest at the G1 phase and decreased mitochondrial membrane potential. Hoechst 33342 staining and Western blot analysis for apoptotic proteins suggested that ICTS induced apoptosis in MCF-7 cells. In addition, ICTS activated MAPK signaling in MCF-7 cells by inducing time- and concentration-dependent phosphorylation of JNK, ERK, and p38 MAPK. Conclusion Our results suggest that ICTS inhibited MCF-7 cell proliferation by inducing apoptosis and activating MAPK signaling pathways.
Efficient Higher-Order CRFs for Morphological Tagging

Training higher-order conditional random fields is prohibitive for huge tag sets. We present an approximated conditional random field using coarse-to-fine decoding and early updating. We show that our implementation yields fast and accurate morphological taggers across six languages with different morphological properties and that across languages higher-order models give significant improvements over 1-order models.
Key Ideas in Educational Research

Foreword Preface Introduction A-Z of terms Subject index Author index. Complete list of headwords: abduction access action research agency alignment anti-racism assessment biography / autobiography case study categorisation causation childhood research closed and open systems coding comparative research content analysis conversation analysis correlational research critical discourse analysis critical incidents critical realism critical theory culture data display data reduction deconstruction deduction design determinism diaries discourse dissemination distribution documentary analysis downward conflation emotionalism empiricism empowerment epistemology / ontology ethics ethnography ethnomethodology evaluation evidence-based practice experiment fallacies fallibility feminist research focus groups gender generalisation grounded theory hermeneutics historical research ideal speech situation induction interpretativism interview life history linguistic discourse analysis literature review longitudinal observation studies mathematical modelling media method methodology mixed methods narrative naturalistic observation nomothetic statements objectivity observation paradigm phenomenology plagiarism positivism postmodernism power prediction publishing qualitative research quantitative research questionnaire realism reductionism refereeing reflexivity referencing systems regression analysis relativism relevance reliability replication representativeness research assessment exercise research community respondent validation retroduction sampling social constructionism statistics strategy structuralism / post-structuralism structure subjectivity survey symbolic interactionism systematic observation telephone interviews tests textuality transferability triangulation validity value-added values variable analysis virtual research writing writing for academic purposes writing as representation. Author index Subject index.
Stimulation of CTP:Phosphocholine Cytidylyltransferase by Free Cholesterol Loading of Macrophages Involves Signaling through Protein Dephosphorylation (*)

Free cholesterol-loaded macrophages in atheromata synthesize excess phosphatidylcholine (PC), which may be an important adaptive response to the excess free cholesterol (FC) load. We have recently shown that FC loading of macrophages leads to 2-4-fold increases in PC mass and biosynthesis and to the post-translational activation of the membrane-bound form of CTP:phosphocholine cytidylyltransferase (CT), a key enzyme in PC biosynthesis. Herein, we explore further the mechanism of CT activation in FC-loaded macrophages. First, enrichment of membranes from control macrophages with FC in vitro did not increase CT activity, and PC biosynthesis in vivo is up-regulated by FC loading even when CT and FC appear to be mostly in different intracellular sites. These data imply that FC activates membrane-bound CT by a signaling mechanism. That the proposed signaling mechanism involves structural changes in the CT protein was suggested by data showing that two different antibodies against synthetic CT peptides showed increased recognition of membrane-bound CT from FC-loaded cells despite no increase in CT protein. Since CT is phosphorylated, two-dimensional maps of peptides from P-labeled control and FC-loaded macrophages were compared: six peptide spots from membrane-bound CT, but none from soluble CT, were dephosphorylated in the FC-loaded cells. Furthermore, incubation of FC-loaded macrophages with the phosphatase inhibitor, calyculin A, blocked increases in both PC biosynthesis and antipeptide-antibody recognition of CT. Last, treatment of membranes from control macrophages with phage protein phosphatase in vitro increased both CT activity (2-fold) and antipeptide-antibody recognition of CT; soluble CT activity and antibody recognition were not substantially affected by phosphatase treatment. In summary, FC loading of macrophages leads to the partial dephosphorylation of membrane-bound CT, and possibly other cellular proteins, which appears to be important in CT activation. This novel regulatory action of FC may allow macrophages to adapt to FC loading in atheromata.
Democracy Disfigured: Opinion, Truth, and the People

In "Democracy Disfigured, "Nadia Urbinati diagnoses the ills that beset the body politic in an age of hyper-partisanship and media monopolies and offers a spirited defense of the messy compromises and contentious outcomes that define democracy.Urbinati identifies three types of democratic disfiguration: the unpolitical, the populist, and the plebiscitarian. Each undermines a crucial division that a well-functioning democracy must preserve: the wall separating the free forum of public opinion from the governmental institutions that enact the will of the people. Unpolitical democracy delegitimizes political opinion in favor of expertise. Populist democracy radically polarizes the public forum in which opinion is debated. And plebiscitary democracy overvalues the aesthetic and nonrational aspects of opinion. For Urbinati, democracy entails a permanent struggle to make visible the issues that citizens deem central to their lives. Opinion is thus a form of action as important as the mechanisms that organize votes and mobilize decisions.Urbinati focuses less on the overt enemies of democracy than on those who pose as its friends: technocrats wedded to procedure, demagogues who make glib appeals to "the people," and media operatives who, given their preference, would turn governance into a spectator sport and citizens into fans of opposing teams.
Urinary Clara cell protein and alpha 1-microglobulin – biomarkers of changes in kidney and airway function

Validated biomarkers are useful tools for screening large populations. The benefit of screening may be improved risk assessment or early indications of adverse effects before detection or onset of symptoms. Screening is valuable in studies of environmental exposures and their effects on human health, for example after exposure to air pollution and toxic metals in our daily environment. The overall aim of this thesis was to optimize sampling of urinary Clara cell 16 kDa protein (CC16) and alpha 1-microglobulin (A1M) and test them as biomarkers of changes in kidney and airway function. For optimized sampling of urinary CC16 and A1M, timed or creatinine-corrected first morning samples are preferable. This is the time of day when the variation in excretion due to influence of urine flow and daily activities is low. For all urinary CC16 sampling, men should discard the first 100 ml to wash out post-renal excretion of CC16 before collection. Urinary and serum CC16 were tested as biomarkers of changes in the permeability of the respiratory epithelium. This was examined after exposure to wood smoke for 4 hours and compared with a session of filtered clean air for 4 hours. Exposure to wood smoke significantly increased serum CC16 after 20 hours and there was tendency towards increased urinary CC16. Both urinary CC16 and A1M are sensitive to changes in tubular function and were analysed together with another tubular biomarker, retinol-binding protein (RBP), in the urine of small children with urinary tract infection (UTI). Clara cell 16 kDa protein was significantly higher in children with upper UTI compared with children with lower UTI. Also, the association between decreased uptake of dimercaptosuccinic acid (DMSA) and increased excretion of CC16 was strong. There was no difference in A1M excretion between upper and lower UTI. In patients with community-acquired pneumonia (CAP), urinary CC16 was increased compared with the control group. By contrast, serum CC16 was decreased in patients with CAP. The increase in urinary CC16 was probably due to fever-related proteinuria since urinary A1M and RBP were also increased. The decrease in serum CC16 could be explained by increased renal excretion. Also, asthma, chronic obstructive pulmonary disease (COPD) and smoking (known to decrease serum CC16) were common among patients with CAP. In conclusion, this thesis demonstrates that both CC16 and A1M are useful biomarkers of tubular renal function. There is also a possibility to use urinary CC16 as an airway biomarker in screening studies of air pollution under the right conditions, using optimal sampling methods.
Comparison of effect sizes associated with biomarkers reported in highly cited individual articles and in subsequent meta-analyses.

CONTEXT Many biomarkers are proposed in highly cited studies as determinants of disease risk, prognosis, or response to treatment, but few eventually transform clinical practice. OBJECTIVE To examine whether the magnitude of the effect sizes of biomarkers proposed in highly cited studies is accurate or overestimated. DATA SOURCES We searched ISI Web of Science and MEDLINE until December 2010. STUDY SELECTION We included biomarker studies that had a relative risk presented in their abstract. Eligible articles were those that had received more than 400 citations in the ISI Web of Science and that had been published in any of 24 highly cited biomedical journals. We also searched MEDLINE for subsequent meta-analyses on the same associations (same biomarker and same outcome). DATA EXTRACTION In the highly cited studies, data extraction was focused on the disease/outcome, biomarker under study, and first reported relative risk in the abstract. From each meta-analysis, we extracted the overall relative risk and the relative risk in the largest study. Data extraction was performed independently by 2 investigators. RESULTS We evaluated 35 highly cited associations. For 30 of the 35 (86%), the highly cited studies had a stronger effect estimate than the largest study; for 3 the largest study was also the highly cited study; and only twice was the effect size estimate stronger in the largest than in the highly cited study. For 29 of the 35 (83%) highly cited studies, the corresponding meta-analysis found a smaller effect estimate. Only 15 of the associations were nominally statistically significant based on the largest studies, and of those only 7 had a relative risk point estimate greater than 1.37. CONCLUSION Highly cited biomarker studies often report larger effect estimates for postulated associations than are reported in subsequent meta-analyses evaluating the same associations.
Limbic system‐associated membrane protein (LAMP) in primate amygdala and hippocampus

The distribution of the limbic system‐associated membrane protein in the amygdaloid complex and hippocampal formation of cynomolgus monkeys (Macaca fascicularis) was studied with immunohistochemical procedures. A highly complex and heterogeneous staining pattern is encountered in the macaque amygdala. The basal, lateral, and accessory basal nuclei display the most intense immunostaining with local heterogeneities. The lateral division of the central nucleus also stains intensely, whereas the medial division of the central nucleus and the medial nucleus are more weakly stained. The dorsal division of the bed nucleus‐amygdala continuum (extended amygdala) is strongly immunoreactive. The hippocampus displays the strongest immunoreactivity encountered so far in the primate brain. The intensity of the immunostaining is highest in the cornu Ammonis (Ammon's horn; CA1‐CA3 fields) and gradually decreases toward the dentate gyrus or the subicular area. In the hippocampus proper, the stratum radiatum, the pyramidal layer, the stratum oriens, and the alveus all display intense immunoreactivity. The immunostaining is much less prominent in the dentate gyrus, whose granule cell layer is completely devoid of labeling. In the subicular area, there is a lateromedial decreasing gradient in immunostaining intensity, the subiculum being moderately stained and the parasubiculum weakly stained. These results reveal that the limbic system‐associated membrane protein labels structures that form the core of the limbic system in primates. Within each of these structures, however, the labeling is highly heterogeneous and appears to be confined to specific functional domains. © 1996 Wiley‐Liss, Inc.
Feminism and globalisation: the promise of Beijing and neoliberal capitalism in Africa

abstract This article discusses the impact of neoliberal capitalism on women and reviews the promises of Beijing against the realities of women's lives in Africa. The focus is on South Africa post-1994, the impact of Growth Employment and Redistribution, and the neoliberal discourses contained in the New Partnership for Africa's Development. Against this contemporary analysis, the article calls for radical structural changes, a move towards social democracy, and for consciousness-raising among both men and women so that they understand the dynamics of power imbalances and how structural factors impact their lives. Given the devastatingly poor and marginalised positions of the majority of women, and the current lack of labour absorption capacity, the article advocates for comprehensive social security in the form of a basic income grant to positively impact the lives of women in South Africa.
STIMPY mediates cytokinin signaling during shoot meristem establishment in Arabidopsis seedlings

The establishment of the primary meristems through proliferation after germination is essential for plant post-embryonic development. Cytokinins have long been considered a key regulator of plant cell division. Here we show that cytokinins are essential for early seedling development of Arabidopsis. Loss of cytokinin perception leads to a complete failure of meristem establishment and growth arrest after germination. We also present evidence that cytokinin signaling is involved in activation of the homeobox gene STIMPY (STIP or WOX9) expression in meristematic tissues, which is essential for maintaining the meristematic fate. Cytokinin-independent STIP expression is able to partially compensate for the shoot apical meristem growth defects in mutants that cannot sense cytokinin. These findings identify a new branch of the cytokinin signaling network, linking cytokinin to the process of meristem and seedling establishment.
Constructing and Reconstructing Childhood: Contemporary Issues in the Sociological Study of Childhood

A new paradigm for the sociology of childhood? Provenance, promise and problems, Alan Prout and Allison James constructions and reconstructions of British childhood - an interpretive survey, 1800 to the present, Harry Hendrick psychology and the cultural construction of children's needs, Martin Woodhead a voice for children in statistical and social accounting - a plea for children's right to be heard, Jens Qvortrup it's a small world - Disneyland, the family and the multiple representations of American childhood, Pauline Hunt and Ronald Frankenberg negotiating childhood - changing constructions of age for Norwegian children, Anne Solberg street children - deconstructing a construct, Benno Glauser who are you kidding? children, power and the struggle against sexual abuse, Jenny Kitzinger childhood and the policy makers - a comparative perspective on the globalization of childhood, Jo Boyden re-presenting childhood - time and transition in the study of childhood, Allison James and Alan Prout.
Object Localization Does Not Imply Awareness of Object Category at the Break of Continuous Flash Suppression

In continuous flash suppression (CFS), a dynamic noise masker, presented to one eye, suppresses conscious perception of a test stimulus, presented to the other eye, until the suppressed stimulus comes to awareness after few seconds. But what do we see breaking the dominance of the masker in the transition period? We addressed this question with a dual-task in which observers indicated (i) whether the test object was left or right of the fixation mark (localization) and (ii) whether it was a face or a house (categorization). As done recently Stein et al. (2011a), we used two experimental varieties to rule out confounds with decisional strategy. In the terminated mode, stimulus and masker were presented for distinct durations, and the observers were asked to give both judgments at the end of the trial. In the self-paced mode, presentation lasted until the observers responded. In the self-paced mode, b-CFS durations for object categorization were about half a second longer than for object localization. In the terminated mode, correct categorization rates were consistently lower than correct detection rates, measured at five duration intervals ranging up to 2 s. In both experiments we observed an upright face advantage compared to inverted faces and houses, as concurrently reported in b-CFS studies. Our findings reveal that more time is necessary to enable observers judging the nature of the object, compared to judging that there is “something other” than the noise which can be localized, but not recognized. This suggests gradual transitions in the first break of CFS. Further, the results imply that suppression is such that no cues to object identity are conveyed in potential “leaks” of CFS (Gelbard-Sagiv et al., 2016).