Miracle-dz/UniFAR-FTUs huggingface dataset:
The Gastrointestinal Tract Is a Major Source of Echinocandin Drug Resistance in a Murine Model of Candida glabrata Colonization and Systemic Dissemination

ABSTRACT Candida species are a part of the human microbiome and can cause systemic infection upon immune suppression. Candida glabrata infections are increasing and have greater rates of antifungal resistance than other species. Here, we present a C. glabrata gastrointestinal (GI) colonization model to explore whether colonized yeast exposed to caspofungin, an echinocandin antifungal, develop characteristic resistance mutations and, upon immunosuppression, breakthrough causing systemic infection. Daily therapeutic dosing (5 mg/kg of body weight) of caspofungin resulted in no reduction in fecal burdens, organ breakthrough rates similar to control groups, and resistance rates (0 to 10%) similar to those reported clinically. Treatment with 20 mg/kg caspofungin initially reduced burdens, but a rebound following 5 to 9 days of treatment was accompanied by high levels of resistance (FKS1/FKS2 mutants). Although breakthrough rates decreased in this group, the same FKS mutants were recovered from organs. In an attempt to negate drug tolerance that is critical for resistance development, we cotreated mice with daily caspofungin and the chitin synthase inhibitor nikkomycin Z. The largest reduction (3 log) in GI burdens was obtained within 3 to 5 days of 20 mg/kg caspofungin plus nikkomycin treatment. Yet, echinocandin resistance, characterized by a novel Fks1-L630R substitution, was identified following 5 to 7 days of treatment. Therapeutic caspofungin plus nikkomycin treatment left GI burdens unchanged but significantly reduced organ breakthrough rates (20%; P < 0.05). Single-dose pharmacokinetics demonstrated low levels of drug penetration into the GI lumen posttreatment with caspofungin. Overall, we show that C. glabrata echinocandin resistance can arise within the GI tract and that resistant mutants can readily disseminate upon immunosuppression.
Brave New Schools: Challenging Cultural Illiteracy Through Global Learning Networks

Notes on the Contributors Introduction: D.Punter PART ONE: THEORY: REGIONS OF THE GOTHIC The Gothic Production of the Unconscious F.Botting Ceremonial Gothic D.Puntert The Nurture of the Gothic, or, How Can a Text be Both Popular and Subversive? W.Veeder PART TWO: HEARTLANDS: THE BRITISH NINETEENTH CENTURY Lost Cities: London's Apocalypse A.Warwick Hell is a City: Symbolic Systems and Epistemological Scepticism in The City of Dreadful Night D.Seed 'A Pestilence Which Walketh in Darkness': Diagnosing the Victorian Vampire R.Mighall PART THREE: AMERICA: STATES OF INSTABILITY American Gothic Landscapes: The New World to Vietnam J.Idiart & J.Schulz Gothic Numbers in the New Republic: The Federalist No. 10 and its Spectral Factions H.F. Thompson Spectres of Abjection: The Queer Subject of James's 'The Jolly Corner' E.Savoy PART FOUR: EUROPE: DIMENSIONS OF THE BODY The Gothic and 'Otherings' of Ascendant Culture: The Original Phantom of the Opera J.Hogle Heiner Muller's Medea: Towards a Paradigm for the Contemporary Gothic Anatomy B.Turner PART FIVE: (RE)VERSIONS Deaths in Venice: Daphne du Maurier's 'Don't Look Now' A.Horner & S.Zlosnik Dr McGrath's Disease: Radical Pathology in Patrick McGrath's Neo-Gothicism C.Ferguson Index
Careful calculation or a leap of faith? A field study of the translation of CBCA ratings to final credibility judgements

This field experiment investigated the influence of Criteria-Based Content Analysis (CBCA) ratings on ultimate decision accuracy regarding the credibility of children's statements of sexual abuse. Following a selection procedure, based on case facts independent of statement quality, 21 truthful accounts and 10 fabricated accounts of 6- to 17-year olds were analysed. Two experts rated the presence of the CBCA criteria and made overall credibility judgements for each statement. Rater one achieved an overall hit rate of 84% (95% for truthful statements and 60% for fabricated statements) and rater two a hit rate of 81% (81% for both truthful and fabricated statements) but the raters did not always agree. The CBCA criteria appeared more often in the truthful statements compared to the fabricated statements. Additional factors that influenced raters' credibility judgements, besides CBCA scores, are discussed.
A Study of Hypnotically Induced Complexes by Means of the Luria Technique

Resume Pour tester la methode de Luria d'associer les reponses volontaires et verbales dans le but de decouvrir des conflits affectifs, on a repete l'une de ses experiences. On a fait l'essai de produire des complexes chez douze sujets pendant l'hypnose et on les a examines avant, pendant, et apres la production du complexe. On a etudie les reponses verbales, volontaires, involontaires et respiratoires, et les temps de reaction verbale. Il y a eu des temoignages que neuf sujets ont accepte le complexe comme quelque chose qu'ils ont fait et qu'il a produit une reaction chez eux. Chez six d'entre les neuf quelque aspect moteur de la technique a revele la presence du conflit. Dans l'etat hypnotique ces sujets ont tendu a donner des reponses verbales relatives au conflit avec relativement peu de desordres moteurs, mais dans l'etat de reveil l'importance relative des desordres moteurs est devenue plus grande. On suggere l'hypothese qu'il peut etre des “niveaux de decharge” de sorte que, si l'excitation creee p.
Genetic and environmental influences on anorexia nervosa syndromes in a population–based twin sample

Background. Genetic and environmental influences on broadly-defined anorexia nervosa (AN) syndrome were examined in a population-based twin sample. Methods. AN syndrome was assessed in 672 female 17 year-old twins using structured interviews and a self-report questionnaire. Results. Twenty-six probands with AN syndrome were identified. Biometrical model-fitting analyses indicated that genetic and non-shared environmental factors accounted for 74 % and 26 % of the variance in AN syndrome, respectively. Conclusions. Findings support previous research indicating significant genetic and non-shared environmental influences on AN syndromes.
Minimally Manipulated Bone Marrow Concentrate Compared with Microfracture Treatment of Full-Thickness Chondral Defects: A One-Year Study in an Equine Model

Background: Microfracture is commonly performed for cartilage repair but usually results in fibrocartilage. Microfracture augmented by autologous bone marrow concentrate (BMC) was previously shown to yield structurally superior cartilage repairs in an equine model compared with microfracture alone. The current study was performed to test the hypothesis that autologous BMC without concomitant microfracture improves cartilage repair compared with microfracture alone. Methods: Autologous sternal bone marrow aspirate (BMA) was concentrated using a commercial system. Cells from BMC were evaluated for chondrogenic potential in vitro and in vivo. Bilateral full-thickness chondral defects (15-mm diameter) were created on the midlateral trochlear ridge in 8 horses. Paired defects were randomly assigned to treatment with BMC without concomitant microfracture, or to microfracture alone. The repairs were evaluated at 1 year by in vitro assessment, arthroscopy, morphological magnetic resonance imaging (MRI), quantitative T2-weighted and ultrashort echo time enhanced T2* (UTE-T2*) MRI mapping, and histological assessment. Results: Culture-expanded but not freshly isolated cells from BMA and BMC underwent cartilage differentiation in vitro. In vivo, cartilage repairs in both groups were fibrous to fibrocartilaginous at 1 year of follow-up, with no differences observed between BMC and microfracture by arthroscopy, T2 and UTE-T2* MRI values, and histological assessment (p > 0.05). Morphological MRI showed subchondral bone changes not observed by arthroscopy and improved overall outcomes for the BMC repairs (p = 0.03). Differences in repair tissue UTE-T2* texture features were observed between the treatment groups (p < 0.05). Conclusions: When BMC was applied directly to critical-sized, full-thickness chondral defects in an equine model, the cartilage repair results were similar to those of microfracture. Our data suggest that, given the few mesenchymal stem cells in minimally manipulated BMC, other mechanisms such as paracrine, anti-inflammatory, or immunomodulatory effects may have been responsible for tissue regeneration in a previous study in which BMC was applied to microfractured repairs. While our conclusions are limited by small numbers, the better MRI outcomes for the BMC repairs may have been related to reduced surgical trauma to the subchondral bone. Clinical Relevance: MRI provides important information on chondral defect subsurface repair organization and subchondral bone structure that is not well assessed by arthroscopy.
Effects of emotionally contagious films on changes in hemisphere-specific cognitive performance.

In the framework of models on the lateralized involvement of the cortical hemispheres in affect and psychopathology, the authors examined whether cognitive processes associated with the left and the right prefrontal cortex varied as a function of valence, motivational direction, or intensity of induced mood. Affective states (cheerfulness, anxiety, sadness, anger, and neutral mood) were experimentally induced by short "emotionally contagious films. " Findings confirmed that the newly developed films were suitable to effectively elicit the expected affective states and to differentially change the dimensions of interest. Changes in verbal versus figural fluency performance were examined as a function of positive versus negative valence, approach versus withdrawal motivation, and low versus high emotional arousal. Level of interest was evaluated as a control. Both the tendency to withdraw and emotional arousal seemed to produce relative advantages for cognitive processes that are more strongly represented in the right than left prefrontal cortex. Findings suggest that changes in cognitive performance might be best explained by an additive combination of motivational direction and arousal.
The many facets of transformative learning theory and practice

The theme of this issue is 'Transformative learning in action: insights from practice'. Selected chapters are indexed from TD/TNC 64.142 to TD/TNC 64.144. Transformative learning can be rational or extrarational. It can be a personal story or a social change. Transformative learning takes place in classrooms, in private struggles, and in self-directed groups. In this chapter, the author reflects on these perspectives to discuss the nature of transformative learning and how the process is being practised.
Changes in articular synovial lining volume measured by magnetic resonance in a randomized, double-blind, controlled trial of intra-articular samarium-153 particulate hydroxyapatite for chronic knee synovitis.

OBJECTIVE Magnetic resonance techniques have recently been investigated as tools with which to monitor inflammatory joint disease. Our aim was to use a contrast-enhanced T1-weighted protocol to monitor the short-term changes in knee synovial lining volume in a double-blind, randomized, controlled trial of intra-articular samarium-153 particulate hydroxyapatite (Sm-153 PHYP). METHODS Twenty-four out-patients with chronic knee synovitis, from a cohort who had been recruited to a long-term clinical efficacy trial, were recruited for this study. Patients received either intra-articular Sm-153 PHYP combined with 40 mg triamcinolone hexacetonide or 40 mg intra-articular triamcinolone hexacetonide alone. Synovial lining volumes were calculated from three-dimensional T1-weighted contrast-enhanced images made before and after contrast enhancement with thresholding and pixel counting, immediately before and 3 months after treatment. RESULTS Paired pre- and post-treatment magnetic resonance data were obtained for 18/24 (75%) patients. There was no significant difference in mean pre-treatment synovial volume between the two treatment groups (139 vs 127 ml). A mean reduction in synovial lining volume was detected in the Sm-153 PHYP/steroid-treated group (139 to 110 ml, P = 0.07) and in the steroid-treated group (127 to 58 ml, P < 0.001). The reduction was significantly greater in the steroid-treated group (-61% vs -23%, P < 0.05). CONCLUSIONS Short-term changes in articular synovial lining in response to intra-articular treatment for chronic synovitis may be monitored by magnetic resonance imaging. After 3 months, a greater mean reduction in synovial lining volume had occurred in response to intra-articular steroid alone compared to combined Sm-153 PHYP/steroid injection.
Relationship between second grade oral reading fluency and third grade reading

Oral reading fluency is a critical feature and outcome of early literacy instruction and it has amassed great attention as a powerful predictor of success at all levels of schooling. We examined relationships between second grade oral reading fluency scores and third grade end-of-grade reading achievement scores for students (N = 9562) in a large school district in the United States. Stakeholder interviews were also conducted. In our model, oral reading fluency and reading comprehension scores were moderately correlated; oral reading fluency was the strongest predictor of subsequent achievement, followed by ethnicity; growth on oral reading fluency was not strongly associated with end-of-grade performance; and greater than 90% of students classified as ‘at risk’ on benchmark assessments performed poorly on third grade assessments. Stakeholders believed that oral reading fluency testing was not necessary above selected levels of proficiency. We discuss implications of our findings for future research and practice.
Identity Formation Re-revisited: A Rejoinder to Waterman on Developmental and Cross-Cultural Issues.

This article is a Rejoinder to Waterman's (1999) Commentary on our longitudinal study of identity development (Meeus, Iedema, Helsen, & Vollebergh, 1999). In this rejoinder we consider six points: the similarities and differences between American and Dutch research with respect to (a) the direction of identity development, (b) the relative stability of the statuses, and (c) gender differences; we then discuss (d) the American research on age differences in the frequency of specific patterns of identity status change, (e) the superiority of log-linear analysis compared with cross-table analysis, and (f) age differences with respect to trajectories and mechanisms of identity development. The most important substantive conclusions are that identity development is systematically found to be progressive and may be described with the trajectory diffusion → closure/moratorium → achieving commitment, and that age differences are found with respect to the trajectories but not with respect to the mechanisms of identity development.
Linguistic markets in Rwanda: language use in advertisements and on signs

Abstract Rwanda has experienced major changes during the last decade due to the genocide in 1994. After the civil war, in addition to establishing political and economical stability, peace and reconciliation, the government was faced with the return of refugees from neighbouring, mostly English-speaking, countries. The new socio-demographic conditions resulted in a change in the official language policy from Rwanda–French bilingualism to Rwanda–French–English trilingualism. During the post-genocide period, therefore, English has been introduced into official domains and has contributed towards a new linguistic situation in Rwanda. This paper investigates how these recent changes are reflected in newspaper advertisements (10 issues of state-owned Imvaho Nshya), 914 shop signs and 221 billboards in Kigali and Butare. The basic assumption of the analysis is that the languages in Rwanda are currently in a competitive position on the linguistic market, affecting not only the use of the national and official language, Rwanda, but also the position of the non African official languages. This competition is an ongoing process, which will necessitate further studies from a macro-sociolinguistic perspective in order to establish the roles and usages of the three official languages of Rwanda.
‘Your mum and dad can't teach you!’: constraints on agency among rural learners of English in the developing world

Abstract Learning outcomes are always the product of the interaction between individual learner agency and social structures. Recently concern has been expressed about unequal access to English, recognised as an important resource for social advancement, for rural populations in developing countries. This paper explores this issue by focusing on one element of learner agency (motivation) in a small group of young adolescent learners in rural Indonesia, who were sampled from a previous quantitative study. Through interviews with the learners and their parents, the study strives to understand the nature of their agency and the way it is shaped by contextual constraints and affordances. Results suggest that the learners do develop Ideal L2 selves though these tend towards fantasy, that they do exert effort to learn English, but this is not systematic or well-resourced, and that their parents are very aware of the limited support they can offer their children. While these constraints may help explain the rural learners' slow progress in English, the paper argues that spreading mobile technologies offer hope for improved outcomes in the future.
Deep LAC: Deep localization, alignment and classification for fine-grained recognition

We propose a fine-grained recognition system that incorporates part localization, alignment, and classification in one deep neural network. This is a nontrivial process, as the input to the classification module should be functions that enable back-propagation in constructing the solver. Our major contribution is to propose a valve linkage function (VLF) for back-propagation chaining and form our deep localization, alignment and classification (LAC) system. The VLF can adaptively compromise the errors of classification and alignment when training the LAC model. It in turn helps update localization. The performance on fine-grained object data bears out the effectiveness of our LAC system.
Complex balanced translocation t(1;5;7)(p32.1;q14.3;p21.3) and two microdeletions del(1)(p31.1p31.1) and del(7)(p14.1p14.1) in a patient with features of Greig cephalopolysyndactyly and mental retardation

Complex chromosome rearrangements (CCRs) are rare structural abnormalities that involve at least two chromosomes and more than two breakpoints and are often associated with developmental delay, mental retardation, and congenital anomalies. We report on a de novo, apparently balanced translocation t(1;5;7)(p32.1;q14.3;p21.3) involving three chromosomes in a 7‐year‐old boy with severe psychomotor retardation, neonatal muscular hypertonia, congenital heart defect, polysyndactyly of hands and feet, and dysmorphic features resembling Greig cephalopolysyndactyly syndrome. Analysis of the chromosome breakpoints using fluorescence in situ hybridization (FISH) with locus‐specific BAC clones and long‐range PCR products did not identify chromosome imbalance at any of the interrogated regions. High‐resolution comparative genomic hybridization (HR‐CGH) and array CGH (aCGH) revealed two additional cryptic de novo deletions, del(1)(p31.1p31.1) and del(7)(p14.1p14.1), respectively, that are not associated with the translocation breakpoints. FISH and polymorphic marker analyses showed that the deletion on derivative chromosome 1 is between 4.2 and 6.1 Mb, and the deletion on derivative chromosome 7 is approximately 5.1 Mb, and that both are paternal in origin. The deletion on chromosome 7p encompasses the GLI3 gene that is causative for the Greig cephalopolysyndactyly, Pallister–Hall and some cases of Acrocallosal syndromes. We discuss the potential mechanisms of formation of the described CCR. © 2007 Wiley‐Liss, Inc.
Abrupt Strategy Change Underlies Gradual Performance Change: Bayesian Hierarchical Models of Component and Aggregate Strategy Use

While researchers have often sought to understand the learning curve in terms of multiple component processes, few studies have measured and mathematically modeled these processes on a complex task. In particular, there remains a need to reconcile how abrupt changes in strategy use can co-occur with gradual changes in task completion time. Thus, the current study aimed to assess the degree to which strategy change was abrupt or gradual, and whether strategy aggregation could partially explain gradual performance change. It also aimed to show how Bayesian methods could be used to model the effect of practice on strategy use. To achieve these aims, 162 participants completed 15 blocks of practice on a complex computer-based task—the Wynton-Anglim booking (WAB) task. The task allowed for multiple component strategies (i.e., memory retrieval, information reduction, and insight) that could also be aggregated to a global measure of strategy use. Bayesian hierarchical models were used to compare abrupt and gradual functions of component and aggregate strategy use. Task completion time was well-modeled by a power function, and global strategy use explained substantial variance in performance. Change in component strategy use tended to be abrupt, whereas change in global strategy use was gradual and well-modeled by a power function. Thus, differential timing of component strategy shifts leads to gradual changes in overall strategy efficiency, and this provides one reason for why smooth learning curves can co-occur with abrupt changes in strategy use.
Binding of curcumin near the GBT440 binding site at the alpha cleft in the sickle cell hemoglobin model [Pdb ID: 1NEJ]

Introduction: In sickle cell anemia, deoxygenated HbS molecules polymerize into long fibers in deep tissues during hypoxia, leading to erythrocyte sickling and capillary and vessel blockage. We are searching for new ligands, such as gbt440, that can inhibit HbS polymerization. Methods and Materials: We obtained the molecular model of hemoglobin [PDB ID: 1NEJ] from the Protein Data Bank and the molecular models of GBT440 and curcumin from the PubChem database. The physicochemical properties were investigated using SwissADME software, followed by docking to identify protein-ligand binding sites and determine their affinity. Finally, molecular dynamics simulations were conducted to assess the stability of the protein-ligand complex in the alpha-cleft of the hemoglobin tetramer model [PDB ID: 1NEJ]. Results and Discussion: The docking results revealed that curcumin exhibited a higher binding affinity than GBT440 to the nearby binding site of gbt440 in the alpha-cleft of the hemoglobin model. The hydrogen bonding and electrostatic interactions of the 1NEJ-GBT440 complex differed from those of the 1NEJ-curcumin complex. The results of the molecular dynamics simulation showed no significant difference in the flexibility of hemoglobin among the different ligand-hemoglobin complexes. Conclusion: The binding of curcumin to hemoglobin in the alpha cleft may inhibit the transition of hemoglobin to the tense state and stabilize the hemoglobin tetramer model [PDB ID: 1NEJ] in the R2 state. However, further investigation in the laboratory is necessary to confirm this