Miracle-dz/UniFAR-FTUs huggingface dataset:
Developing Antagonists for the Met-HGF/SF Protein–Protein Interaction Using a Fragment-Based Approach

In many cancers, aberrant activation of the Met receptor tyrosine kinase leads to dissociation of cells from the primary tumor, causing metastasis. Accordingly, Met is a high-profile target for the development of cancer therapies, and progress has been made through development of small molecule kinase inhibitors and antibodies. However, both approaches pose significant challenges with respect to either target specificity (kinase inhibitors) or the cost involved in treating large patient cohorts (antibodies). Here, we use a fragment-based approach in order to target the protein–protein interaction (PPI) between the α-chain of hepatocyte growth factor/scatter factor (HGF/SF; the NK1 fragment) and its high-affinity binding site located on the Met Sema domain. Surface plasmon resonance was used for initial fragment library screening and hits were developed into larger compounds using substructure (similarity) searches. We identified compounds able to interfere with NK1 binding to Met, disrupt Met signaling, and inhibit tumorsphere generation and cell migration. Using molecular docking, we concluded that some of these compounds inhibit the PPI directly, whereas others act indirectly. Our results indicate that chemical fragments can efficiently target the HGF/SF-Met interface and may be used as building blocks for generating biologically active lead compounds. This strategy may have broad application for the development of a new class of Met inhibitors, namely receptor antagonists, and in general for the development of small molecule PPI inhibitors of key therapeutic targets when structural information is not available. Mol Cancer Ther; 15(1); 3–14. ©2015 AACR.
Global patterns and sources of dissolved organic matter export to the coastal zone: Results from a spatially explicit, global model

Here we describe, test, and apply a system of spatially explicit, global models for predicting river export of three dissolved organic matter (DOM) components: dissolved organic carbon (DOC), dissolved organic nitrogen (DON), and dissolved organic phosphorus (DOP). The DON and DOP models represent the first attempt to model DON and DOP export in a spatially explicit, global manner. DOC, DON, and DOP models explain 88%, 77%, and 91% of the variability in DOC, DON, and DOP yield (kg C, N, or P km−2 yr−1) from validation basins, respectively, and all models are relatively bias free. When applied globally, these models predict that 170 Tg C yr−1, 10 Tg N yr−1, and 0.6 Tg P yr−1 are exported by rivers to the coastal zone as DOC, DON, and DOP, respectively. Because predicted spatial patterns of export for DOC, DON, and DOP are all largely driven by water runoff, geographic distributions of high and low fluxes are fairly consistent across elements, with high fluxes of DOC, DON, and DOP generally predicted for high runoff systems and low fluxes predicted for arid systems. However, there are important regional differences in predicted rates of DOC, DON, and DOP export due to anthropogenic inputs of DON and DOP and wetland influence on DOC.
Investigation of Cross-Linked and Additive Containing Polymer Materials for Membranes with Improved Performance in Pervaporation and Gas Separation

Pervaporation and gas separation performances of polymer membranes can be improved by crosslinking or addition of metal-organic frameworks (MOFs). Crosslinked copolyimide membranes show higher plasticization resistance and no significant loss in selectivity compared to non-crosslinked membranes when exposed to mixtures of CO2/CH4 or toluene/cyclohexane. Covalently crosslinked membranes reveal better separation performances than ionically crosslinked systems. Covalent interlacing with 3-hydroxypropyldimethylmaleimide as photocrosslinker can be investigated in situ in solution as well as in films, using transient UV/Vis and FTIR spectroscopy. The photocrosslinking yield can be determined from the FTIR-spectra. It is restricted by the stiﬀness of the copolyimide backbone, which inhibits the photoreaction due to spatial separation of the crosslinker side chains. Mixed-matrix membranes (MMMs) with MOFs as additives (fillers) have increased permeabilities and often also selectivities compared to the pure polymer. Incorporation of MOFs into polysulfone and Matrimid® polymers for MMMs gives defect-free membranes with performances similar to the best polymer membranes for gas mixtures, such as O2/N2 H2/CH4, CO2/CH4, H2/CO2, CH4/N2 and CO2/N2 (preferentially permeating gas is named first). The MOF porosity, its particle size and content in the MMM are factors to influence the permeability and the separation performance of the membranes.
Prevalence and clinical implications of testosterone deficiency in men with end-stage renal disease.

BACKGROUND Abnormally low serum testosterone levels were recently associated with an increased mortality risk in male dialysis patients. However, the prevalence of testosterone deficiency in end-stage renal disease (ESRD) is not well defined. We hereby explore the prevalence and correlates of clinical testosterone deficiency in a large cohort of ESRD male patients. METHODS Two hundred and sixty ESRD men [median age 59 (25th-75th percentile 48-67) years] were included. Testosterone concentration and testosterone deficiency (<10 nmol/L) were studied in relation to clinically evident cardiovascular disease and markers of inflammation at baseline as well as deaths registered during the following 36 months. RESULTS Testosterone deficiency was present in 44% of the patients, while 33% showed testosterone insufficiency (10-14 nmol/L), and only 23% had normal testosterone values (>14 nmol/L). Testosterone was strongly and inversely correlated to inflammatory markers (CRP, IL-6 and fibrinogen), even after correction for age and sex hormone-binding globulin. In a crude spline curve, low testosterone concentrations were associated with worse outcome. A clinical condition of testosterone deficiency was independently associated with cardiovascular co-morbidity [odds ratio (OR) 2.51; 95% confidence interval (CI) 1.32-4.76] and death (OR 2.00; 95% CI 1.01-3.97) in logistic regression analyses. CONCLUSIONS Testosterone deficiency is a common finding among male ESRD patients, and it is independently associated with inflammation, cardiovascular co-morbidity and outcome. Future studies are needed to determine the potential adverse effects of male hypogonadism in ESRD and the possibility of improving risk profile, quality of life, and ultimately outcome with testosterone supplementation in these patients.
Neuronal regulation of astrocyte morphology in vitro is mediated by GABAergic signaling

The addition of isolated neurons to monolayers of cultured astrocytes induced a morphological change in the astrocytes that came into contact with the added neuronal cell bodies or neurites. The change, which included an increase in the complexity of cell shape, took at least 3 days to become detectable and was enhanced in proportion to the number of attached neurons. Astrocytes that did not make contact with any neurons had a less complex contour, comparable to those in control cultures with no neurons added. Treatment of neuron‐astrocyte cocultures with a sodium channel blocker, tetrodotoxin, suppressed the neuron‐induced morphological changes in astrocytes. A GABAA‐receptor antagonist, bicuculline, mimicked the inhibitory effect of tetrodotoxin. In cultures without added neurons, morphological alteration of astrocytes was also observed when cultures were incubated for 1 or more days with exogenous GABA together with a GABA‐uptake inhibitor, 4,5,6,7‐tetrahydroisoxazolo[4,5‐c]pyridin‐3‐ol. The effect of exogenous GABA was mimicked by treatment with a GABAA‐receptor agonist, muscimol, and blocked by bicuculline treatment. These results suggest that GABA released from neurons with their activity serves as a signal from neurons to astrocytes that triggers the morphological change in astrocytes through the activation of GABAA receptors. GLIA 20:1‐9, 1997. © 1997 Wiley‐Liss, Inc.
‘Playing the Game called Writing’: Children’s Views and Voices

Abstract Teachers’ perceptions of their changing practice in the context of the National Literacy Strategy have been well documented in recent years. However, few studies have collected pupils’ views or voices. As part of a collaborative research and development project into the teaching and learning of writing, 390 primary pupils’ views were collected. A marked difference in attitude to writing and self-esteem as writers was found between Key Stages 1 and 2, as well as a degree of indifference and disengagement from in-school writing for some KS2 writers. A strong desire for choice and greater autonomy as writers was expressed and a preference for narrative emerged. This part of the research project ‘We’re Writers’ has underlined the importance of listening to pupils’ views about literacy, in order to create a more open dialogue about language and learning, and to negotiate the content of the curriculum in response to their perspectives.
Why Do Shadow Systems Exist after an ERP Implementation? Lessons from a Case Study

One of the main promises of an ERP implementation is the ‘full integration of a business’. Reports of shadow systems in post ERP implementations suggest that this is not always the case. Using an exploratory single case study method with grounded theory coding techniques this study investigates why shadow systems exist after an ERP implementation. This paper provides a theoretical framework which reveals that the causal factors found in the categories of technology, organization, business procedures and people all contribute to the phenomenon of shadow systems in an ERP context.
Teaching for Human Well-being: Curricular Implications for the Capability Approach

Amartya Sen and Martha Nussbaum state clearly that education is a foundational capacity intrinsically important for human well-being and an enabling capacity for people to live lives they have reason to value. This article explores the resonance the capability approach (CA) has for the authors who, as veteran educators, have drawn their core professional values from democratic, critical, and feminist approaches to pedagogy. The CA provides a critical, generative lens for guiding and assessing curriculum development and pedagogical practices. To aid in their critical reflection and dialogue, the authors developed a heuristic to explore the following question: given contemporary educational challenges, what does the CA have to offer educators who have embraced libratory pedagogical principles? The authors conclude that the CA to education can be a powerful antidote to disturbing and dehumanizing past conditions, present realities, and current trends in education.
Is ect safe in patients with cerebrovascular disease?

A 70‐year‐old man with a history of peripheral vascular disease was treated initially with antidepressants, then bilateral electroconvulsive therapy (ECT) for a depressive illness. Apart from an episode of delirium following ECT he recovered fully. Four years later he relapsed. Low‐dose antidepressants caused disorientation and oversedation, as did ECT. Shortly afterwards he developed a multi‐infarct state with Parkinsonian symptoms, transient schaemic attacks (TIAs) and cerebrovascular attacks (CVAs). His cognitive deficits implicated pathology in the frontal and subcortical areas of the brain. Postmortem examination confirmed widespread atherosclerotic disease, also cerebrovascular disease. The haemodynamic and cerebral effects of ECT are condidered in the context of vascular disease. It is postulated that ECT given to such patients might cause permanent impairment of cognitive function through ischaemia of an already compromised cerebral circulation. Suggestions are outlined regarding a policy for a more comprehensive assessment of patients with atherosclerotic disease. Deficiencies of ECT procedures are highlighted.
Shoulder Joint Position Sense Improves With External Load

Joint position sense (JPS) is important in the maintenance of optimal movement coordination of limb segments in functional activities. Researchers have shown that the sensitivity of musculotendinous mechanoreceptors increases as muscle activation levels increase. In the present study, when 25 participants tried to replicate the same presented position, both vector and elevation angle repositioning errors decreased linearly as the external load increased up to 40% above unloaded shoulder torque. However, external load had no effect on plane repositioning error. The results indicated that JPS increased under conditions of increasing external load but only in the direction of the applied load. That finding indicates that JPS acuity improves as muscle activation levels increase.
O modelo ideológico de letramento e a concepção de escrita como trabalho: um paralelo

By studying the peculiarities of the ideological model of literacy, we can note that it has similarities with what the writing conception as work proposes. This way, this paper has as objective to present the common points between these two visions, in order to show that the idealized literacy can be applied in classes through the complex work that can be done with the writing. In this context, we present the literacy notion as a social practice, the writing conceptions and the parallel between the theories, so that we can fulfill our expectations. The ideological model of literacy points practices which cover different contexts where a person can be and, in the case of writing, it can be applied in classes through the writing conception as work, since it considers the discursive practices, developed in effective communicative situations, where purpose, interlocutor and discursive genre are elements that compose them.
A META-ANALYSIS OF THE RELATIONSHIP BETWEEN ANXIETY TOWARD MATHEMATICS AND ACHIEVEMENT IN MATHEMATICS

In this meta-analysis I examined 26 studies on the relationship between anxiety toward mathematics and achievement in mathematics among elementary and secondary students. The common population correlation for the relationship is significant (-.27). A series of general linear models indicated that the relationship is consistent across gender groups, grade-level groups, ethnic groups, instruments measuring anxiety, and years of publication. The relationship, however, differs significantly among instruments measuring achievement as well as among types of publication. Researchers using standardized achievement tests tend to report a relationship of significantly smaller magnitude than researchers using mathematics teachers' grades and researcher-made achievement tests. Published studies tend to indicate a significantly smaller magnitude of the relationship than unpublished studies. There are no significant interaction effects among key variables such as gender, grade, and ethnicity.
Virtual Government–Citizen Relations

Public administration theory and practice suggest that e-government, citizen participation, and government–citizen collaboration are contributing to a movement toward New Public Service—as opposed to Old Public Administration and New Public Management. We explore this by focusing on the relationship between the Washington, D.C., police and local residents via online discussion groups. We ask, How do police interact with citizens virtually? How are these interactions structured? and Are they informational, transactional, or collaborative? Using descriptive data and thread analysis, and drawing distinctions between districts, we conclude that the bulk of activity is informational, a fair amount of activity is transactional, and less activity is collaborative. Thus, the relationship most closely approximates Old Public Administration, rather than New Public Management or New Public Service. The evidence offers some cause for hope for the future of police–community relations in virtual space and ideas for future research.
Induction in vivo and in vitro of terminal deoxynucleotidyl transferase by thymosin in bone marrow cells from athymic mice

Terminal deoxynucleotidyl transferase (TdT) expression in bovine serum albumin (BSA) gradient-fractionated bone marrow cells was examined in NIH Swiss nu/nu and thymectomized C57BL/6 mice. In nude mice, TdT levels were approximately 10% of those of thymus-bearing littermates. In C57BL/6 mice, thymectomy caused a time-dependent loss of TdT activity in bone marrow cells. To determine whether or not not the apparent thymic requirement for TdT expression in bone marrow was mediated by thymic hormones, we examined the effects of thymosin fraction 5. Treatment of either NIH Swiss nu/nu or thymectomized C57BL/6 mice with thymosin fraction 5 restored the levels of TdT activity in BSA gradient-fractionated bone marrow cells to normal. Moreover, treatment of BSA gradient-fractionated bone marrow cells from NIH Swiss nu/nu or thymectomized C57BL/6 mice in tissue culture with thymosin fraction 5 induced TdT expression. In tissue culture, TdT induction was optimal with 25 ng/ml of thymosin fraction 5, it occurred within 6 h, and it was completely inhibited by actinomycin D. The effect was specific in that neither control nor spleen fraction 5- treated cells were induced to express TdT. These data demonstrate that TdT expression in bone marrow cells is under the direct control of thymic polypeptide hormones.
The Ulp1 SUMO isopeptidase

Protein modification by the ubiquitin-like SUMO protein contributes to many cellular regulatory mechanisms. In Saccharomyces cerevisiae, both sumoylating and desumoylating activities are essential for viability. Of its two known desumoylating enzymes, Ubl-specific protease (Ulp)1 and Ulp2/Smt4, Ulp1 is specifically required for cell cycle progression. A ∼200-residue segment, the Ulp domain (UD), is conserved among Ulps and includes a core cysteine protease domain that is even more widespread. Here we demonstrate that the Ulp1 UD by itself can support wild-type growth rates and in vitro can cleave SUMO from substrates. However, in cells expressing only the UD of Ulp1, many SUMO conjugates accumulate to high levels, indicating that the nonessential Ulp1 NH2-terminal domain is important for activity against a substantial fraction of sumoylated targets. The NH2-terminal domain also includes sequences necessary and sufficient to concentrate Ulp1 at nuclear envelope sites. Remarkably, NH2-terminally deleted Ulp1 variants are able, unlike full-length Ulp1, to suppress defects of cells lacking the divergent Ulp2 isopeptidase. Thus, the NH2-terminal regulatory domain of Ulp1 restricts Ulp1 activity toward certain sumoylated proteins while enabling the cleavage of others. These data define key functional elements of Ulp1 and strongly suggest that subcellular localization is a physiologically significant constraint on SUMO isopeptidase specificity.
Collective psychological ownership within the work and organizational context: Construct introduction and elaboration

The construct collective psychological ownership is introduced. Reflecting the psychology of “us” and “ours,” collective psychological ownership emerges through interactive dynamics whereby individuals come to a single and shared mind-set as it relates to a sense of ownership for a particular object. After providing a conceptual definition for the construct, we turn our attention to a detailed elaboration of the construct, offering comments on its genesis, emergent context, underlying motives, and a discussion of what can and cannot be owned. We also provide a discussion of the dynamics associated with its formation, highlighting the paths down which groups travel that influence the emergence of this psychological state. Next, we turn our attention to the emergence of collective psychological ownership within the organizational and teamwork context paying particular attention to the role of work environment structure. We conclude with a discussion of a set of work-related attitudinal, motivational, behavioral, and stress-related outcomes that stem from this psychological state. Copyright © 2009 John Wiley & Sons, Ltd.
Regulation of G protein-coupled receptor kinases and arrestins during receptor desensitization.

With at least 1000 family members encoded by mammalian genomes, the G protein-coupled receptors (GPCRs) represent the most diverse group of signaling proteins known ([Bockaert and Pin, 1999][1]). GPCRs are involved in the regulation of a wide variety of physiological processes including, but not
Race disparities between black and white women in the incidence, treatment, and prognosis of endometrial cancer.

BACKGROUND Uterine cancer is the most common gynecologic malignancy in the United States, with an estimated 40,100 new cases and 7,470 deaths occurring in 2008. Although the incidence of endometrial cancer is lower among black women compared with white women, the proportion of cancer-related deaths among blacks is higher and has continued to rise over the past two decades. METHODS The authors conducted a survey of recent literature published in the English language and have used these articles as the basis for this review. RESULTS The etiology for the racial disparity among black women with endometrial cancer is multifactorial and may be the result of barriers that impede access to care, an increased incidence of comorbidities among black women, inequalities in surgical care, adjuvant chemotherapy and radiation treatment, and underlying biological differences associated with more aggressive tumors that often develop in black women. CONCLUSIONS Black women with endometrial cancer have a poorer prognosis compared with white women. Factors that contribute to this racial disparity include later diagnosis, treatment disparities, comorbid conditions, and genetic differences in tumors. An improved understanding of the causative factors associated with racial disparities in endometrial cancer outcome is needed to facilitate efforts aimed at correcting this important health care problem and providing individualized care to those at highest risk for poor outcome.
Identifying Cancer Specific Functionally Relevant miRNAs from Gene Expression and miRNA-to-Gene Networks Using Regularized Regression

Identifying microRNA signatures for the different types and subtypes of cancer can result in improved detection, characterization and understanding of cancer and move us towards more personalized treatment strategies. However, using microRNA's differential expression (tumour versus normal) to determine these signatures may lead to inaccurate predictions and low interpretability because of the noisy nature of miRNA expression data. We present a method for the selection of biologically active microRNAs using gene expression data and microRNA-to-gene interaction network. Our method is based on a linear regression with an elastic net regularization. Our simulations show that, with our method, the active miRNAs can be detected with high accuracy and our approach is robust to high levels of noise and missing information. Furthermore, our results on real datasets for glioblastoma and prostate cancer are confirmed by microRNA expression measurements. Our method leads to the selection of potentially functionally important microRNAs. The associations of some of our identified miRNAs with cancer mechanisms are already confirmed in other studies (hypoxia related hsa-mir-210 and apoptosis-related hsa-mir-296-5p). We have also identified additional miRNAs that were not previously studied in the context of cancer but are coherently predicted as active by our method and may warrant further investigation. The code is available in Matlab and R and can be downloaded on http://www.cs. toronto.edu/goldenberg/Anna_Goldenberg/Current_Research. html.