Miracle-dz/UniFAR-FTUs huggingface dataset:
Sphingosine 1-phosphate and ceramide 1-phosphate: expanding roles in cell signaling

The phosphorylated sphingolipid metabolites sphingosine 1-phosphate (S1P) and ceramide 1-phosphate (C1P) have emerged as potent bioactive agents. Recent studies have begun to define new biological functions for these lipids. Generated by sphingosine kinases and ceramide kinase, they control numerous aspects of cell physiology, including cell survival and mammalian inflammatory responses. Interestingly, S1P is involved in cyclooxygenase-2 induction and C1P is required for the activation and translocation of cPLA2. This suggests that these two sphingolipid metabolites may act in concert to regulate production of eicosanoids, important inflammatory mediators. Whereas S1P functions mainly via G-protein-coupled receptors, C1P appears to bind directly to targets such as cPLA2 and protein phosphatase 1/2A. S1P probably also has intracellular targets, and in plants it appears to directly regulate the G protein α subunit GPA1.
The Role of Plant Nutrients in Disease Development with Emphasis on Citrus and Huanglongbing

Mineral nutrients are important for the growth and development of plants and microorganisms, and are important factors in plant–disease interactions. How each nutrient affects a plant’s response to disease is unique to each plant–disease complex, and in general, nutrient–pathogen interactions are not well understood. Plant nutrients may affect disease susceptibility through plant metabolic changes, thereby creating a more favorable environment for disease development. For example, calcium defi ciency can lead to membrane leakage of sugars, amino acids, and other low-molecular weight compounds that then become available for pathogen use. Many nutrient metals at elevated concentrations have broad antibacterial properties so pathogens that directly or indirectly reduce these plant nutrients may have an advantage. Relatively little is known about the changes in plant nutrition associated with huanglongbing (HLB) despite its leaf symptoms often being characterized as “nutrient defi ciency-like. ” Recent analyses comparing symptomatic (blotchy mottle) and asymptomatic leaves from HLB-infected trees and leaves from healthy trees have shown that HLB increased K while Mg, Ca, and B decreased. The micronutrients Zn and Mn, whose defi ciency symptoms are commonly seen on HLB-infected trees, were not actually defi cient in HLB-infected samples when the dry mass of the samples was corrected for the large amounts of starch accumulation caused by HLB. It remains to be seen whether remedial foliar applications of these or other nutrients can reduce the effects of HLB. Here we provide a brief review on plant nutrition and disease susceptibility, with an emphasis on K, Ca, Mg, and B, and discuss the changes in these nutrients associated with HLB infection in citrus.
Contesting Professionalism: Legal Aid and Nonlawyers in England and Wales

Professions are granted a form of cartel that enables them to charge more than would arise in a free market on the assumption that they provide better quality and are more trustworthy than free-market actors would be. The theoretical assumption that lawyers are more competent than nonlawyers has given rise to significant formal protections for professions in many jurisdictions. Two testable propositions arise from this theory: (1) lawyers cost more, but (2) they deliver higher quality. It is a testing of these twin propositions that is the subject of this article, with well-triangulated data and a deeper understanding of the theoretical differences between lawyers and nonlawyers.
Trans/forming teachers: new professional learning and transformative teacher professionalism

Abstract This article focuses upon the development of transformative teacher professionalism. It explores issues of teacher professional identity and the ways in which this is contributed to by teacher responsiveness to the changing and demanding educational environments in which they find themselves. It includes a review of significant literature within the field and suggests ways in which professional learning can support the development of a transformative teaching profession. Finally, it points to a number of conditions under which such a profession might emerge.
Reassessment of autoreactivity of the broadly neutralizing HIV antibodies 4E10 and 2F5 and retrospective analysis of clinical safety data

Background:The broadly neutralizing recombinant human HIV-1 antibodies 4E10, 2F5 and Igh1b12 are reported to have autoreactive potential, which is significant for HIV-1 vaccine development and passive immunotherapy using these antibodies. Objective:To investigate the clinical relevance of these findings in subjects receiving passive immunotherapy with these antibodies. Methods:Four types of investigations were performed: (1) Investigation of clotting parameters in an ongoing clinical study with 4E10, 2F5 and 2G12. (2) Mixing experiments of pooled plasma with the same antibodies. (3) Retrospective analysis of serum from patients who received passive immunotherapy with 4E10, 2F5 and 2G12 either alone or in combination. (4) Assessment of clinical safety data obtained after 418 infusions with these antibodies. Results:Standard clinical assays confirmed that 4E10 showed low-level cross-reactivity with cardiolipin, while previously reported cardiolipin cross-reactivity for 2F5 could not be confirmed. High serum titers of 4E10 induced mild prolongation of the activated partial thromboplastin time, which resolved with the wash out of 4E10. Neither 2F5 nor 2G12 affected coagulation. Repeated high-dose infusions of the monoclonal antibody combination were well tolerated with no incidence for thrombotic complications after 418 infusions in 39 subjects. Conclusions:Monoclonal antibody 4E10 but not 2F5 or 2G12 showed autoreactive binding specificities. Infusion of 4E10 resulted in transient low anticardiolipin titers. Although an increased thromboembolic risk cannot definitely be excluded, this risk appears to be low and likely depend on underlying disorders.
Pressor Factors and Responsiveness in Hypertension Accompanying Diabetes Mellitus

Hypertension accompanying diabetes mellitus may involve abnormalities in at least two major blood pressure-regulating systems: the body sodium-fluid volume state and cardiovascular reactivity. In metabolically stable nonazotemie diabetes, exchangeable sodium is increased by 10% on average, regardless of age, insulin dependence or nondependence, or the presence or absence of diabetic retinopathy or clinical nephropathy (proteinuria > 0.3 g/24 hr). Possible contributing mechanisms include renal sodium retention and an extravascular shift of fluid and sodium; intracellu-lar accumulation is not excluded. Circulatory volume is normal or low and the total exchangeable sodium/blood volume ratio increased. In hypertensive diabetes, the latter abnormality is particularly pronounced; systolic pressure tended to correlate with exchangeable sodium (r = 0.47, p < 0.001) and diastolic pressure with the plasma sodium/potassium ratio (r = 0.25, p < 0.05). Plasma aldosterone, renin, epinephrine, and norepinephrine levels are generally normal or sometimes low in metabolically stable nonazotemie diabetic patients with normal or high blood pressure; the plasma clearance of norepinephrine also appears to be unaltered. The cardiovascular pressor responsiveness to norepi-nephrine is often exaggerated relative to concomitant plasma concentrations, regardless of age, type of antidiabetic treatment, or presence or absence of diabetic retinopathy, peripheral neuropathy, or high blood pressure. Pressor responsiveness to angiotensin II also may sometimes be increased relative to plasma renin levels. Sodium retention and diabetic vasculopathy of resistance vessels could be impor-tant complementary mechanisms of hyperreactivity. In diabetes with mild hypertension, diuretic treatment restored exchangeable sodium, norepinephrine pressor responsiveness, and blood pressure toward normal. Thus sodium retention and cardiovascular hyperreactivity tend to occur even at the normotensive, nonazotemie stage of diabetes and may concomitantly predispose for the frequent development of hypertension in thediabetic population.
Gaming and Territorial Negotiations in Family Life

This article examines territorial negotiations concerning gaming, drawing on video recordings of gaming practices in middle-class families. It explores how private vs public gaming space was co-construed by children and parents in front of the screen as well as through conversations about games. Game equipment was generally located in public places in the homes, which can be understood in terms of parents’ surveillance of their children, on the one hand, and actual parental involvement, on the other. Gaming space emerged in the interplay between game location, technology and practices, which blurred any fixed boundaries between public and private, place and space, as well as traditional age hierarchies.
Cultural bias in the SON-R test: comparative study of Brazilian and dutch children

The present study, including 83 Brazilian and 51 Dutch children, evaluated the presence of cultural bias in items of the SON-R 5½-17 that make use of concrete objects and situations. Two procedures were followed to detect item bias. The first consisted of asking the children, immediately after an incorrect answer, whether they recognized the pictures. The second procedure compared item difficulties of the Brazilian children with those of the Dutch children belonging to the standardization sample of the SON-R 5½-17. Fourteen items were detected with bias: ten of these favored the Dutch group and four the Brazilian group. The cultural disadvantage for Brazilian children is rather small, taking the large amount of investigated items into account. This study indicated which items of the SON-R 5½-17 should be improved, not only for reasons of cultural bias, but also because children, irrespective of their cultural background, encountered problems with the recognition of several pictures.
Planning Through Consensus Building: A New View of the Comprehensive Planning Ideal

Abstract Thirty years ago, Alan Altshuler, in a devastating critique that has never been effectively answered, challenged the legitimacy of comprehensive planning and of planners' expertise. He called on the field to reinforce its theoretical arsenal. This article takes up his challenge, contending that not only have practices now arisen that make comprehensive planning possible, but also political and social theory has evolved to provide its intellectual grounding. The article argues that consensus building with stakeholders offers a model for planning that responds to each of Altshuler's critiques. Consensus building is shown to be founded on assumptions about the nature of knowledge, about the organization of interests, and about the nature of the public interest that differ from those Altshuler applied. Evidence is taken from eight in-depth case studies of consensus building over growth and environmental issues in California, and from a study of the New Jersey state planning process. The article concl.
Dendritic cells pulsed with viral oncolysates potently stimulate autologous T cells from cancer patients.

We demonstrated before that primary operated breast cancer patients contain in their bone marrow (BM) cancer reactive memory T cells (MTC) which have to be re-activated to become tumor infiltrating effector cells. The aim of this study was to optimize an ex vivo stimulation protocol for MTC based on autologous dendritic cells (DC). As source of tumor antigens we used lysates from unmodified tumor cells or from tumor cells infected with Newcastle Disease Virus (NDV) which contain IFN-alpha inducing viral dsRNA as one danger signal. DC from breast cancer patients were pulsed with lysates from the MCF-7 breast cancer line (Tu-L) or from NDV infected MCF-7 cells (TuN-L, viral oncolysates) and compared for stimulatory capacity in an ELISPOT response of autologous BM derived MTC. To analyze potential further danger signals derived from NDV infection, we employed MALDI mass spectrometry, Western blots, FACS cytometry and ELISA tests. DC pulsed with viral oncolysates showed increased expression of co-stimulatory molecules in comparison to Tu-L pulsed DC and induced significantly higher ELISPOT MTC responses. Supernatants from co-cultures of MTC and TuN-L pulsed DC contained increased titers of IFN-alpha and IL-15. NDV infection of tumor cells resulted in a number of differences in protein expression including a heat-shock protein (HSP27) which became phosphorylated. The results suggest that a DC preparation pulsed with viral oncolysate includes danger signals (e.g. dsRNA, cytokines, HSP molecules) and is superior for MTC stimulation to a DC preparation pulsed with lysate from non-infected tumor cells.
The PINK1 phenotype can be indistinguishable from idiopathic Parkinson disease

Mutations in the PINK1 gene cause autosomal recessive parkinsonism characterized by early onset and a variable phenotypic presentation. A patient homozygous for the Ala168Pro mutation has been fully characterized clinically. Apart from onset at age 39 years and the excellent and sustained response to levodopa, all clinical and laboratory features, including SPECT and assessment of autonomic function, were indistinguishable from typical idiopathic Parkinson disease.
Tensions in policy and practice: influences on play in Abu Dhabi's New School Model KG framework

This article reports on three salient socio-cultural and systemic factors that are influential in play in Abu Dhabi Education Council's (ADEC's) kindergarten (KG) framework from the teacher perspective. Anecdotal evidence suggests that during ADEC's progressive educational reform, emphasis has reverted to academic performance outcomes rather than whole child learning through play. Tensions may then occur surrounding the nature and extent of play practices for early learning. Following semi-structured interviews with 60 KG teachers, three salient factors emerged. These are illustrated in this article and discussed in light of the international literature on play. Tensions in policy and practice highlighted in this article are: a focus on academic performance outcomes; children's readiness to engage in play and parent perspectives on play. The article then discusses what these tensions may mean for the future of play in ADEC KGs situated within a period of educational reform.
The “Batty” Politic: Toward an Aesthetic of the Black Female Body

I assess representations of black women's derrieres, which are often depicted as grotesque, despite attempts by some black women artists to create a black feminist aesthetic that recognizes the black female body as beautiful and desirable. Utilizing a black feminist disability theory, I revisit the history of the Hottentot Venus, which contributed to the shaping of this representational trope, and I identify a recurring struggle among these artists to recover the “unmirrored” black female body.
Excitation of GABAergic Neurons in the Bed Nucleus of the Stria Terminalis Triggers Immediate Transition from Non-Rapid Eye Movement Sleep to Wakefulness in Mice

Emotionally salient situations usually trigger arousal along with autonomic and neuroendocrine reactions. To determine whether the extended amygdala plays a role in sleep–wakefulness regulation, we examined the effects of optogenetic and pharmacogenetic excitation of GABAergic neurons in the bed nucleus of the stria terminalis (GABABNST neurons). Acute optogenetic excitation of these cells during nonrapid eye movement (NREM) sleep resulted in an immediate state transition to wakefulness, whereas stimulation during REM sleep showed no effect on sleep–wakefulness states in male mice. An anterograde tracing study suggested GABABNST neurons send axonal projections to several brain regions implicated in arousal, including the preoptic area, lateral hypothalamus, periaqueductal gray, deep mesencephalic nucleus, and parabrachial nucleus. A dual orexin receptor antagonist, DORA-22, did not affect the optogenetic transition from NREM sleep to wakefulness. Chemogenetic excitation of GABABNST neurons evoked a sustained wakefulness state, but this arousal effect was markedly attenuated by DORA-22. These observations suggest that GABABNST neurons play an important role in transition from NREM sleep to wakefulness without the function of orexin neurons, but prolonged excitation of these cells mobilizes the orexin system to sustain wakefulness. SIGNIFICANCE STATEMENT We examined the role of the bed nucleus of the stria terminalis (BNST) in the regulation of wakefulness. Optogenetic excitation of GABAergic neurons in the BNST (GABABNST neurons) during nonrapid eye movement (NREM) sleep in mice resulted in immediate transition to a wakefulness state without function of orexins. Prolonged excitation of GABABNST neurons by a chemogenetic method evoked a longer-lasting, sustained wakefulness state, which was abolished by preadministration of a dual orexin receptor antagonist, DORA-22. This study revealed a role of the BNST GABAergic system in sleep–wakefulness control, especially in shifting animals' behavioral states from NREM sleep to wakefulness, and provides an important insight into the pathophysiology of insomnia and the role of orexin in arousal regulation.
Rethinking Social Divisions: Some Notes towards a Theoretical Framework

This paper attempts to provide a framework for theorising the social divisions of gender, ethnicity and class in terms of parameters of differentiation and inequality which lie at the heart of ‘the social’. The paper argues that there are common parameters to the social divisions of gender, ethnicity, ‘race’ (and class) in terms of categories of difference and positionality. The paper explores the distinctive ontological spaces or domains of gender and ethnos and argues that their study must be undertaken in local and specific contexts paying attention to their articulation. The articulation of the different social processes at the experiential, inter-subjective, organisational and representational levels produces specific social outcomes. Finally, a schematic outline of some of these articulations is presented.
In Vitro and In Vivo Evaluation of 89Zr-DS-8273a as a Theranostic for Anti-Death Receptor 5 Therapy

Background: DS-8273a, an anti-human death receptor 5 (DR5) agonistic antibody, has cytotoxic activity against human cancer cells and induces apoptosis after specific binding to DR5. DS-8273a is currently being used in clinical Phase I trials. This study evaluated the molecular imaging of DR5 expression in vivo in mouse tumor models using SPECT/CT and PET/MRI, as a tool for drug development and trial design. Methods: DS-8273a was radiolabeled with indium-111 and zirconium-89. Radiochemical purity, immunoreactivity, antigen binding affinity and serum stability were assessed in vitro. In vivo biodistribution and pharmacokinetic studies were performed, including SPECT/CT and PET/MR imaging. A dose-escalation study using a PET/MR imaging quantitative analysis was also performed to determine DR5 receptor saturability in a mouse model. Results: 111In-CHX-A″-DTPA-DS-8273a and 89Zr-Df-Bz-NCS-DS-8273a showed high immunoreactivity (100%), high serum stability, and bound to DR5 expressing cells with high affinity (Ka, 1.02-1.22 × 1010 M-1). The number of antibodies bound per cell was 32,000. In vivo biodistribution studies showed high and specific uptake of 111In-CHX-A″-DTPA-DS-8273a and 89Zr-Df-Bz-NCS-DS-8273a in DR5 expressing COLO205 xenografts, with no specific uptake in normal tissues or in DR5-negative CT26 xenografts. DR5 receptor saturation was observed in vivo by biodistribution studies and quantitative PET/MRI analysis. Conclusion: 89Zr-Df-Bz-NCS-DS-8273a is a potential novel PET imaging reagent for human bioimaging trials, and can be used for effective dose assessment and patient response evaluation in clinical trials.
The Digital Construction of Technology: Rethinking the History of Computers in Society

In recent decades, the history of computing has moved beyond its traditional focus on machines towards a broader study of people, processes, and practices. The study of software in particular has opened up new avenues for exploring questions about gender, labor history, organizational politics, users and use-practices, expertise, and professional identity as they relate to the changing role of computers in society. Beginning with a creative re-imagining of Bruno Latour’s classic study of laboratory life in the context of modern computational biology and bio-informatics, the author argues that the ubiquitous presence of the computer in the material practices of the laboratory reflects a larger shift in the epistemological foundations of science from experiment to simulation. He suggests that by focusing on digitization, rather than computerization, historians can better understand the range of technological and conceptual innovations that have dramatically transformed the work of scientists and engineers in almost every discipline.
Web-Based Learning Environments Guided by Principles of Good Teaching Practice

In this article, we describe the preparation and execution of a statistics course, an undergraduate econometrics course, and a microeconomic theory course, each of which uses Internet technology as an integral part of the delivery of the course. We address the pedagogical and technical issues that must be resolved to achieve each of Chickering and Gamson's (1987) seven principles for good teaching practice using this medium. Pedagogical issues are paramount if the goal is to achieve the best teaching practice. Of equivalent importance, however, is choosing a technology that will support the chosen pedagogical strategy and work well over the World Wide Web. We make extensive use of the Web through an on-line syllabus-a series of Web pages that
Serum neuron-specific enolase, carnosinase, and their ratio in acute stroke. An enzymatic test for predicting outcome?

BACKGROUND AND PURPOSE Few admission variables adequately predict neuronal damage and prognosis in individual patients after stroke. Therefore, there is a need for a reliable non-invasive surrogate measure of clinical outcome. METHODS We have developed a surrogate measure of stroke outcome using the ratio of serum neuron-specific enolase (NSE) to human serum carnosinase (HSC) in 124 patients with acute ischemic or hemorrhagic stroke and 61 matched control subjects. Serum NSE is known to rise and HSC to fall after neuronal injury such as cerebral ischemia. RESULTS Serum NSE levels were significantly higher and HSC levels lower in the patient group. The NSE/HSC ratio was elevated in patients with stroke: median (semiquartile) hemorrhages, 0.072 (0.033); infarcts, 0.039 (0.026); and control subjects, 0.019 (0.014), P = . 0001. Patients with a primary intracerebral hemorrhage had nonsignificantly higher ratios than those with an infarct (P = .082). The NSE/HSC ratio was significantly associated with 90-day outcome measured in two out of three disability and handicap scales: modified Barthel Index (rs = -.34, P = .001), modified Rankin Scale (rs = .30, P = .002), and Lindley Score (rs = .19, P = .057). Patients who died or were institutionalized had higher ratios than those who were discharged home: 0.069 (0.043) versus 0.038 (0.024), P = . 011. Correlations between the NSE/HSC ratio and outcome were comparable to those between patient age or consciousness level on admission and clinical outcome. CONCLUSIONS We believe that measurement of NSE, HSC, or their ratio may be useful in the assessment of patients with acute stroke with respect to diagnosis and prediction of clinical outcome.