Miracle-dz/UniFAR-FTUs huggingface dataset:
Allosteric modulators of NR2B‐containing NMDA receptors: molecular mechanisms and therapeutic potential

N‐methyl‐D‐aspartate receptors (NMDARs) are ion channels gated by glutamate, the major excitatory neurotransmitter in the mammalian central nervous system (CNS). They are widespread in the CNS and are involved in numerous physiological and pathological processes including synaptic plasticity, chronic pain and psychosis. Aberrant NMDAR activity also plays an important role in the neuronal loss associated with ischaemic insults and major degenerative disorders including Parkinson's and Alzheimer's disease. Agents that target and alter NMDAR function may, thus, have therapeutic benefit. Interestingly, NMDARs are endowed with multiple extracellular regulatory sites that recognize ions or small molecule ligands, some of which are likely to regulate receptor function in vivo. These allosteric sites, which differ from agonist‐binding and channel‐permeation sites, provide means to modulate, either positively or negatively, NMDAR activity. The present review focuses on allosteric modulation of NMDARs containing the NR2B subunit. Indeed, the NR2B subunit confers a particularly rich pharmacology with distinct recognition sites for exogenous and endogenous allosteric ligands. Moreover, NR2B‐containing receptors, compared with other NMDAR subtypes, appear to contribute preferentially to pathological processes linked to overexcitation of glutamatergic pathways. The actions of extracellular H+, Mg2+, Zn2+, of polyamines and neurosteroids, and of the synthetic compounds ifenprodil and derivatives (‘prodils’) are presented. Particular emphasis is put upon the structural determinants and molecular mechanisms that underlie the effects exerted by these agents. A better understanding of how NR2B‐containing NMDARs (and NMDARs in general) operate and how they can be modulated should help define new strategies to counteract the deleterious effects of dysregulated NMDAR activity.
Fighting for space in supervision: fantasies, fairytales, fictions and fallacies

In higher education the supervision of graduate research students is an uncertain practice. When given the opportunity, supervisors and students ask what it means and how it should be done. In this paper, the author interprets the uncertain state of supervision affairs as an effect of many competing and contradictory social discourses that offer us more ways of making sense of supervision than in the past. Each discourse figures its Loyal Supervisor and Student, its ‘Proper’ Supervision, in particular ways. These are the multiple and contradictory fantasies, fairytales, fictions and fallacies of the title. First each discourse is described and then a close reading is given of some extracts of data from the author's research with Master's students and their supervisors to illustrate various discourses at work. Finally, there is discussion of which discourses are the most powerful at the present time and some implications, both dangers and fruitful possibilities, of the author's interpretation are suggested.
Trackmenot: Resisting Surveillance in Web Search

TrackMeNot (TMN) is a Firefox browser extension designed to achieve privacy in web search by obfuscating users' queries within a stream of programatically-generated decoys. Since August 2006, when the initial version of TMN was made publicly available, free of charge, there have been over 350,000 downloads. TMN protects web users against data-profiling by simulating HTTP search requests to search engines with queries extracted from the web. In an attempt to mimic users' search behavior this basic functionality is augmented with several technical mechanisms: dynamic query-lists, real-time search awareness, live header maps, burst-mode queries, and cookie-anonymization. We describe each of these mechanisms, evaluate its strengths and weaknesses, and demonstrate how the consideration of values directly informed design and implementation. In the discussion section we conceptualize TMN within a broader class of software systems serving ethical, political and expressive ends. Finally we address why web search privacy is particularly important and why TMN’s approach, for the present moment, is both legitimate and necessary.
Increased Expression of the Glucocorticoid Receptor β in Infants With RSV Bronchiolitis

OBJECTIVES: The majority of studies on glucocorticoid treatment in respiratory syncytial virus (RSV) bronchiolitis concluded that there are no beneficial effects. We hypothesized that RSV-infected patients may have an increased glucocorticoid receptor (GR) β expression, the isoform that is unable to bind cortisol and exert an antiinflammatory action. METHODS: By using real-time polymerase chain reaction, we studied the expression of α and β GR in the peripheral blood mononuclear cells obtained from 49 RSV-infected infants (<1 year of age) with severe (n = 29) and mild to moderate (n = 20) illness. In plasma, we analyzed the level of cortisol by radioimmunoassay and inflammatory cytokines interleukin (IL)-10, IL-6, tumor necrosis factor-α, IL-1β, IL-8, IL-12p70, IL-2, IL-4, IL-5, interferon-γ, and IL-17 by cytometric beads assay. Statistical analysis was performed by nonparametric analysis of variance. RESULTS: We found a significant increase of β GR expression in patients with severe illness compared with those with mild disease (P < .001) and with a group of healthy controls (P < .01). The α:β GR ratio decreased significantly in infants with severe disease compared with those with mild illness (P < .01) and with normal controls (P < .001). The expression of β GR was positively correlated with the clinical score of severity (r = .54; P < .0001). CONCLUSIONS: The decrease of the α:β GR ratio by an increase of β receptors expression is related to illness severity and may partly explain the insensitivity to corticoid treatment in RSV-infected infants. The increased expression of β GR could be a marker of disease severity.
Councillors' Notions of Democracy, and their Role Perception and Behaviour in the Changing Context of Local Democracy

Abstract This article starts with an analysis of responses by councillors which can be related either to a representative or to a broader participatory understanding of democracy. This general pattern appears, with slight variations, in all the countries included in the study on councillors in municipal assemblies. The findings on the understanding of democracy will be linked to the formal horizontal power relations between councillors, the mayor and the leading bureaucrats of the municipal administration, as determined by different local government systems. This is done to test whether or not the appearance of councillors with a particular understanding of democracy is determined by different institutional conditions which offer councillors options to perform a specific role according to their understanding of democracy. Also considered is the question of whether councillors' understanding of democracy is linked to personal characteristics. As argued in the introduction to this special issue, particular options offered to councillors by a council's formal competences may neither attract nor repel actors with a specific understanding of democracy to become councillors. Instead, notions of democracy as expressions of a person's basic beliefs and subjective norms can be related to that individual's personal character. Finally, councillors' role perceptions, role behaviour and attitudes towards reforms at the local level are identified and analysed to see whether or not councillors' notions of democracy can be related to their role perceptions, role behaviour and attitudes towards reforms as dependent variables.
Grade retention: decision-making and effects on learning as well as social and emotional development

This article presents a summary of results from a Swiss nationwide empirical study of the determinants of grade retention, its effects on learning, and its social and emotional consequences. Results show that the decision for grade retention does not rest only on the pupil's actual academic performance but also on the teacher's attitudes and evaluations. With regard to improvement in learning, the study yields contrasting short- and medium-term results: They are positive in the case of same-grade comparisons and negative when same-age comparisons are applied. However, globally, the effectiveness of grade retention is rather unsatisfactory, particularly when one considers its long-term consequences, although there is no evidence of negative social or emotional consequences. It is nevertheless suggested that grade retention should be avoided at the primary school level.
Characteristic polynomial method for verification and test of combinational circuits

In a recent paper, Jain et al. [1992] probabilistically establish the equivalence of two given Boolean functions. They assign randomly selected integers to input variables and compute integer-valued transform functions. If the evaluations give the same value, the Boolean functions are shown to be identical with some probability of error, The error probability is reduced as the domain from which the integers are obtained is enlarged. Also, for a fixed domain, the probability of error can be reduced by taking multiple samples for inputs. In this paper, we assign randomly selected real numbers to input variables and show that when the characteristic polynomials of two Boolean functions give the same value, then the functions are identical with probability 1. It can be shown that when the inputs are sampled from the real domain [0,1], and are interpreted as probabilities of logic 1, then the corresponding value of the characteristic polynomial gives the probability of output logic 1 for the Boolean function.
Transcriptional regulation of neurofilament expression by protein kinase A

RN46A cells, a conditionally immortalized neuronal cell line derived from E12 rat medullary raphe nucleus, upregulate low Mr (68 kDa, neurofilament [NF]‐L) and medium Mr (160 kDa, NF‐M) neurofilament protein expression upon activation of protein kinase A (PKA). To examine possible transcriptional regulation of neurofilament protein expression by PKA, two cell lines were used; RN46A cells and CαEV6 cells, a cell line derived from RN46A cells that stably expresses the catalytic subunit of PKA under the control of the metallothionein promoter. Treatment of RN46A cells with dbcAMP resulted in an increase in the steady‐state levels of both NF‐L and NF‐M, but not high Mr (200 kDa, NF‐H) neurofilament mRNA. These increases were both time and dose dependent and were sensitive to treatment with the protein synthesis inhibitor cycloheximide. In CαEV6 cells, activation of PKA by 80 μM ZnSO4 upregulated the expression of Cα mRNA with maximal levels reached 8 hr post‐treatment and maintained at 24 hr. Reporter gene assays in CαEV6 cells following transfection with increasing lengths of the NF‐L promoter demonstrated that both a putative Sp1‐like and a cAMP response (CRE), but not a NGFI‐A, element were likely involved in PKA‐dependent activation of the NF‐L promoter. Electrophoretic mobility shift assays confirmed these results but showed that the nuclear proteins induced by PKA which bound to the NF‐L promoter Sp1‐like sequence were not Sp1. Collectively, these data suggest that constitutively expressed Sp1 may be involved in basal NF‐L promoter activity, and newly synthesized, PKA‐dependent nuclear proteins may synergistically activate the rat NF‐L promoter. J. Neurosci. Res. 47:242–252, 1997. © 1997 Wiley‐Liss, Inc.
Universal Health Insurance and Equity in Primary Care and Specialist Office Visits: A Population-Based Study

PURPOSE Universal coverage of physician services should serve to reduce socioeconomic disparities in care, but the degree to which a reduction occurs is unclear. We examined equity in use of physician services in Ontario, Canada, after controlling for health status using both self-reported and diagnosis-based measures. METHODS Ontario respondents to the 2000–2001 Canadian Community Health Survey (CCHS) were linked with physician claim files in 2002–2003 and 2003–2004. Educational attainment and income were based on self-report. The CCHS was used for self-reported health status and Johns Hopkins Adjusted Clinical Groups was used for diagnosis-based health status. RESULTS After adjustment, higher education was not associated with at least 1 primary care visit (odds ratio [OR] = 1.05; 95% confidence interval [CI], 0.87–1.24), but it was inversely associated with frequent visits (OR = 0.77; 95% CI, 0.65–0.88). Higher education was directly associated with at least 1 specialist visit (OR = 1.20; 95% CI, 1.07–1.34), with frequent specialist visits (OR = 1.21; 95% CI, 1.03–1.39), and with bypassing primary care to reach specialists (OR = 1.23, 95% CI 1.02–1.44). The largest inequities by education were found for dermatology and ophthalmology. Income was not independently associated with inequities in physician contact or frequency of visits. CONCLUSIONS After adjusting for health status, we found equity in contact with primary care for educational attainment but inequity in specialist contact, frequent visits, and bypassing primary care. In this setting, universal health insurance appears to be successful in achieving income equity in physician visits. This strategy alone does not eliminate education-related gradients in specialist care.
Network models of the diffusion of innovations

Part 1 Introduction: Diffusion of Innovations and Network Analysis Diffusion Versus Collective Behaviour Datasets Analysed Contagion. Part 2 Prior Research on Thresholds and the Critical Mass: Epidemiology Geography Markets and Economics Collective Behaviour Interactive Communication Technologies Public Opinion Decay Processes Subgroups. Part 3 Relational Diffusion Networks: Opinion Leadership Group Membership Personal Network Density Personal Network Exposure. Part 4 Structural Diffusion Networks: The Strength of Weak Ties Centrality Positional Equivalence Structural Equivalence Relational vs. Structural. Part 5 Threshold Models of Diffusion: Threshold Models Network Thresholds Personal Network Exposure Threshold Lags Structural Network Thresholds. Part 6 Critical Mass Models of Diffusion: Inflection Points Structural Measures of the Critical Mass Finding Critical Mass Testing Critical Mass Definitions. Part 7 Empirical Analyses of Threshold Models: Micro- and Macrolevels of Analysis Adopted Categories A Threshold/Critical Mass (T/CM) Model. Part 8 Other Network Models and Methods: Other Threshold Models Corrected Thresholds Event History Analysis Complementarity Dyads. Part 9 Conclusions and Discussions: Applications Contrasting Network Thresholds with the Classic Diffusion Model Conclusions Limitations Future Research.
Uses and Misuses of Student Opinion Surveys in Eight Australian Universities

Student opinion surveys (SOSs) are commonly used in universities to measure student perceptions of teaching performance. Ostensibly their prime purpose is to improve teaching quality. This paper critically examines SOSs in eight Australian universities where survey design and analysis were examined and compared with literature recommendations. We find that current SOSs are neither designed nor structured according to sound questionnaire technique and that, as part of a teaching evaluation system, they are seriously flawed. Deficiencies include: their use as the sole measure of teaching effectiveness, the tendency for universities to rely on unmoderated student opinion without tempering the results with contextual factors, and a lack of testing for reliability and validity that renders the data of unknown precision. We argue that, at present, SOSs expose teachers to unreliable, invalid opinions that influence teacher career advancement and job security.
Tracking Visitor Engagement in the Blogosphere for Leveraging Rankings

Current blog search engines use rankings, such as BIImpact or B2Rank, focusing on the link structure and thereat criteria externally extracted for blogs. A good, but due to the unavailability, not often used criteria is the visitor engagement. This metric can leverage the quality of a ranking extremely. For this reason, we propose to gather visitor information from log authors by providing a new blog plug in. This plug in on the one hand tracks the visitor information and on the other hand provides important analysis information for the blog author. Finally, this leads into a win-win situation for both, the blog search engine and the blogger. The benefit of this plug in is to provide analytics based on the blog where the plug in is installed as well as analytics based on the whole community of bloggers. With this information a blogger is able to gain significant knowledge advantage.
Structure and Function of Cultured Endometrial Epithelial Cells

Uterine endometrial epithelial cells undergo profound changes in structure and function in preparation for blastocyst implantation. The dynamics of this process for human endometrium can be studied only in cell culture. Primary cell cultures started from tissue removed at varying times during the cycle retain some aspects of differentiation as manifest in regulated protein synthesis. Differentiation of endometrial, epithelial cell lines will occur when culture conditions are varied. Domes, gland-like structures, polarized sheets and spheroids can be produced. Studying the process of differentiation in vitro should provide information about differentiation in vivo, particularly about how changing protein synthesis accompanies changing cell structure. Endometrial epithelial cells in culture can also be manipulated to allow study of steroid agonism and antagonism, cancer, menses and regeneration and endometriosis.
Inkjet-printed GSM900 band RF power harvester on paper-based substrates

In this article the outcomes of an experimental investigation on the inkjet-printed power harvester for GSM900 band are presented. In this survey, a passive one-stage discrete rectifier and a planar antenna are fabricated on cardboard using inkjet-printing technology. For the rectifier a voltage doubler structure and for the antenna a broadband planar monopole antenna are utilized. Then, the functionality of the whole module is proven by measuring the output voltage in the real environment. The measurement results demonstrate appropriate absorbed voltage level for feeding a low power circuit by the presented power harvester. By the exploitation of the proposed idea, the fabrication of low-cost environmentally-friendly battery-less wireless modules is feasible.
Prevalence of typical atrial flutter with reentry circuit posterior to the superior vena cava: use of entrainment at the atrial roof.

AIMS Upper turn-around of the reentry circuit in typical atrial flutter (AF) is classically described to be located in front of the superior vena cava (SVC), but circuits posterior to the SVC as well as lower loop reentry (LLR) involving only the lower part of the right atrium have been described. However, true prevalence of such AF circuits remains unknown. METHODS AND RESULTS Fifty consecutive patients (46 men, 68 +/- 9 years old) undergoing radiofrequency (RF) ablation of typical counter-clockwise AF were prospectively investigated. Prior to RF deliverance, AF was entrained by pacing 10 ms shorter than the AF cycle length (AFCL). Post-pacing interval (PPI) at the cavotricuspid isthmus (CTI) and at the atrial roof (AR)-between SVC and the high tricuspid annulus-were determined. AR was considered to be part of the AF circuit when local PPI-AFCL was < or =20 or 30 ms or, in case of long PPI at the CTI isthmus, if difference between AR-PPI and CT-PPI was < or =10 ms. In 47 patients, CTI-PPI-AFCL was < or =30 ms (94%). Among them, AR-PPI-AFCL was >30 ms in 12 cases (25%). In the remaining three patients, AR-PPI-AFCL did not exceed CTI-PPI-AFCL by more than 10 ms. In 42 patients, CTI-PPI-AFCL was < or =20 ms (84%). Among them, AR-PPI-AFCL was >20 ms in 16 cases (39%). In the remaining eight patients, AR-PPI-AFCL was more than 10 ms longer than CTI-PPI-AFCL in only one instance. Taken together, AR PPI was >20 or >30 ms longer than AFCL or >10 ms longer than CTI PPI when prolonged in 17 (34%) and 12 patients (24%), respectively. CONCLUSION In around a quarter to one-third of patients referred for RF ablation of typical AF, the atrial roof is not part of the circuit, thus they may present a 'posterior' variant of the typical counter-clockwise AF reentry circuit.
Le pilotage des forces de vente: État de l'art et modèle conceptuel

Cet article a pour but de placer les recherches récentes sur les systèmes de contrôle des forces de vente dans une perspective plus large. Il propose un modèle conceptuel du contrôle des commerciaux qui ne se limite plus à la distinction entre contrôles basés sur les résultats ou sur les comportements des vendeurs, mais qui propose également d'autres dimensions qui pourraient expliquer pourquoi les directeurs commerciaux choisissent des éléments particuliers de contrôle à l'intérieur même d'une catégorie donnée.
QUANTITATIVE STUDIES ON THE MIXED LYMPHOCYTE INTERACTION IN RATS

The proliferative interaction of cultured rat lymphocytes of immunogenetically disparate origin—the mixed lymphocyte interaction—was employed as an experimental model to examine the initial stages of the immune response mechanism. Using mixed cultures of cells derived from parental strain and F1 hybrid rats, in which only the parental lymphocytes respond, the following observations were made on the magnitude and kinetics of the reaction. After initiation of the cultures, there was a latent period of approximately 40 hours during which time no mitotic activity was detected. This inactive phase was followed by a period of proliferation in which previously nondividing cells entered the mitotic cycle for the first time. Activity in the cultures, as detected by incorporation of radioactive thymidine and measured by radioautography or scintillation spectrometry, increased exponentially with a doubling time (T2) of 9–10 hr. In this exponential proliferative phase, lasting approximately 100 hr, the dividing cells underwent a series of rapid sequential divisions with a generation time (Tc) of 8 hr, and few, if any, dropped out of the mitotic cycle. In addition to the cells which first entered mitosis at the beginning of the proliferative phase and then proceeded through multiple divisions, significant numbers of new, previously nondividing cells continued to enter the mitotic cycle during the entire exponential growth phase. The total number of these newly responsive, first division cells throughout the total culture period amounted to 1–3% of the original parental cell inoculum. This is a surprisingly large proportion of peripheral blood lymphocytes with demonstrable reactivity to a particular antigen system, if it is assumed that these first division cells in vitro are functionally related to the hypothetical antigen-sensitive cells which proliferate and differentiate into immunological effector cells. At present there is no entirely satisfactory explanation for this large number of reactive cells in the mixed lymphocyte interaction.