1,790 research outputs found
The Point of Political Belief
An intuitive and widely accepted view is that (a) beliefs aim at truth, (b) many citizens have stable and meaningful political beliefs, and (c) citizens choose to support political candidates or parties on the basis of their political beliefs. We argue that all three claims are false. First, we argue that political beliefs often differ from ordinary world-modelling beliefs because they do not aim at truth. Second, we draw on empirical evidence from political science and psychology to argue that most people lack stable and meaningful political beliefs. Third, we claim that the true psychological basis for voting behavior is not an individualâs political beliefs but rather group identity. Along the way, we reflect on what this means for normative democratic theory
Bridging recommendation and adaptation:generic adaptation framework - twittomender compliance study
In this paper we consider Recommender System (RS) modeling in terms of Adaptive Hypermedia Systems (AHS) and investigate AHS and RS functionality compliance in terms of common features, functionality, building blocks and composition of the system. We bring up complementary aspects of adaptation, personalization and recommendation in a context of a generic framework which provides properties of information fusion and heterogeneity and could serve as a reference model. We show major recommendation functionality in terms of the reference structure and recommendation process by presenting a conceptual generic âadaptation-recommendationâ sequence chart which overlays and combines properties of adaptation and recommendations taking advantages of both. In fact we show that RS if implemented on the web can be considered as AHS, in this wise a generic framework should be capable of describing virtually any RS. In the case study we scrutinize the Twittomender3 RS. We decompose the system in building blocks, outline and highlight its properties along with the advantages and possible enhancements. We conclude by summarizing framework advantages and AH recommendation compliant features as well as lessons learned from this study
Oesophageal atresia is correctable and survivable in infants less than 1Â kg
INTRODUCTION: Management of oesophageal atresia (OA) and trachea-oesophageal fistula (TOF) in babies of low birth weight is challenging especially when associated with other anomalies. Birth weight of <1500Â g has previously formed part of a classification system designed to predict outcome, alongside the cardiac status of the patient. Improvements in neonatal care have led to increasing numbers of premature low birth weight infants surviving. The aim of this study was to look at the experience of our institution in the extremely low birth weight (ELBW) patients. METHODS: A retrospective review of our institutions OA database was performed from 1993 to June 2015. Patients of birth weight less than 1000Â g were included. A review of our OA/TOF clinical database and notes review established the following; gestation, birth weight, associated anomalies, operative procedures, morbidity and mortality. RESULTS: Of 349 patients with OA across the 22-year period, 9 ELBW patients were identified (<1000Â g). Six males and three females. Gestational age ranged from 23 to 34Â weeks and median birth weight was 815Â g ranging from 630 to 950Â g. Overall survival was 56Â % (5/9). There were double the numbers of ELBW OA/TOF patients seen in the second half of the study period presumably the result of improving neonatal care. Seven patients had type C OA with TOF and underwent emergency TOF ligation, two had concomitant oesophageal repair. One of these patients died from NEC; the other survived. Of the five who had isolated TOF ligation three died-two from cardiac disease and one from prematurity. Both type A patients survived and after initial gastrostomy placement one had a primary delayed repair, the other a gastric transposition. All three babies under 800Â g died-one from cardiac disease the others from conditions indicative of their prematurity-necrotising enterocolitis and intraventricular haemorrhage. CONCLUSIONS: 50Â % survival is achievable in OA/TOF under 1Â kg and the Spitz classification is still applicable in this group as a whole. However, none of the current classification systems are applicable in infants <800Â g who in our study all had poor outcomes. We suggest these should be considered as separate group when predicting outcomes
miRNAs are essential for survival and differentiation of newborn neurons but not for expansion of neural progenitors during early neurogenesis in the mouse embryonic neocortex
Neurogenesis during the development of the mammalian cerebral cortex involves a switch of neural stem and progenitor cells from proliferation to differentiation. To explore the possible role of microRNAs (miRNAs) in this process, we conditionally ablated Dicer in the developing mouse neocortex using Emx1-Cre, which is specifically expressed in the dorsal telencephalon as early as embryonic day (E) 9.5. Dicer ablation in neuroepithelial cells, which are the primary neural stem and progenitor cells, and in the neurons derived from them, was evident from E10.5 onwards, as ascertained by the depletion of the normally abundant miRNAs miR-9 and miR-124. Dicer ablation resulted in massive hypotrophy of the postnatal cortex and death of the mice shortly after weaning. Analysis of the cytoarchitecture of the Dicer-ablated cortex revealed a marked reduction in radial thickness starting at E13.5, and defective cortical layering postnatally. Whereas the former was due to neuronal apoptosis starting at E12.5, which was the earliest detectable phenotype, the latter reflected dramatic impairment of neuronal differentiation. Remarkably, the primary target cells of Dicer ablation, the neuroepithelial cells, and the neurogenic progenitors derived from them, were unaffected by miRNA depletion with regard to cell cycle progression, cell division, differentiation and viability during the early stage of neurogenesis, and only underwent apoptosis starting at E14.5. Our results support the emerging concept that progenitors are less dependent on miRNAs than their differentiated progeny, and raise interesting perspectives as to the expansion of somatic stem cells
Candidate LBV stars in galaxy NGC 7793 found via HST photometry + MUSE spectroscopy
Only about 19 Galactic and 25 extragalactic bonafide luminous blue variables (LBVs) are known to date. This incomplete census prevents our understanding of this crucial phase of massive star evolution which leads to the formation of heavy binary black holes via the classical channel. With large samples of LBVs one could better determine the duration and maximum stellar luminosity which characterize this phase. We search for candidate LBVs (cLBVs) in a new galaxy, NGC 7793. For this purpose, we combine high spatial resolution images from two Hubble Space Telescope (HST) programs with optical spectroscopy from the Multi Unit Spectroscopic Explorer (MUSE). By combining PSF-fitting photometry measured on F547M, F657N, and F814W images, with restrictions on point-like appearance (at HST resolution) and Hâα luminosity, we find 100 potential cLBVs, 36 of which fall in the MUSE fields. Five of the latter 36 sources are promising cLBVs which have MV †â7 and a combination of: Hâα with a P-Cygni profile; no [OâI]λ6300 emission; weak or no [OâIII]λ5007 emission; large [NâII]/Hâα relative to HâII regions; and [SâII]λ6716/[SâII]λ6731âŒ1â . It is not clear if these five cLBVs are isolated from O-type stars, which would favour the binary formation scenario of LBVs. Our study, which approximately covers one fourth of the optical disc of NGC 7793, demonstrates how by combining the above HST surveys with multi-object spectroscopy from 8-m class telescopes, one can efficiently find large samples of cLBVs in nearby galaxies
Genetic architecture of epigenetic cortical clock age in brain tissue from older individuals: alterations in <em>CD46</em> and other loci
\ua9 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. The cortical epigenetic clock was developed in brain tissue as a biomarker of brain aging. As one way to identify mechanisms underlying aging, we conducted a GWAS of cortical age. We leveraged postmortem cortex tissue and genotyping array data from 694 participants of the Rush Memory and Aging Project and Religious Orders Study (ROSMAP; 11000,000 SNPs), and meta-analysed ROSMAP with 522 participants of Brains for Dementia Research (5,000,000 overlapping SNPs). We confirmed results using eQTL (cortical bulk and single nucleus gene expression), cortical protein levels (ROSMAP), and phenome-wide association studies (clinical/neuropathologic phenotypes, ROSMAP). In the meta-analysis, the strongest association was rs4244620 (p = 1.29
7 10â7), which also exhibited FDR-significant cis-eQTL effects for CD46 in bulk and single nucleus (microglia, astrocyte, oligodendrocyte, neuron) cortical gene expression. Additionally, rs4244620 was nominally associated with lower cognition, faster slopes of cognitive decline, and greater Parkinsonian signs (n ~ 1700 ROSMAP with SNP/phenotypic data; all p †0.04). In ROSMAP alone, the top SNP was rs4721030 (p = 8.64
7 10â8) annotated to TMEM106B and THSD7A. Further, in ROSMAP (n = 849), TMEM106B and THSD7A protein levels in cortex were related to many phenotypes, including greater AD pathology and lower cognition (all p †0.0007). Overall, we identified converging evidence of CD46 and possibly TMEM106B/THSD7A for potential roles in cortical epigenetic clock age
Azacytidine Enhances Regulatory T-Cells In Vivo and Prevents Experimental Xenogeneic Graft-Versus-Host Disease
Background
The demethylating agent 5-azacytidine (AZA) has proven its efficacy as treatment for myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading to the generation of regulatory T cells (Tregs).
Objective
We investigated the impact of AZA on xenogeneic graft-versus-host disease (xGVHD) in a humanized murine model of transplantation, and described the impact of the drug on human T cells in vivo.
Methods
In order to induce xGVHD, human peripheral blood mononuclear cells (huPBMC) were administered intravenously in NOD-scid IL-2RÎłnull (NSG) mice.
Results
AZA successfully improved both survival (p<0.0001) and xGVHD scores (p<0.0001). Further, AZA significantly decreased human T-cell proliferation as well as INF-γ and TNF-α serum levels, and reduced the expression of GRANZYME B and PERFORIN 1 by cytotoxic T cells. In addition, AZA administration significantly increased the function, proliferation and frequency of Tregs through demethylation of FOXP3i1 and higher secretion of IL-2 by conventional T cells due to IL2 gene promoter site 1 demethylation. Interestingly, among AZA-treated mice surviving the acute phase of xGVHD, there was an inverse correlation between the presence of Tregs and signs of chronic GVHD. Finally, Tregs harvested from the spleen of AZA-treated mice were suppressive and stable over time since they persisted at high frequency in secondary transplant experiments.
Conclusion
These findings emphasize a potential role for AZA as prevention or treatment of GVHD
Gene silencing in tick cell lines using small interfering or long double-stranded RNA
Gene silencing by RNA interference (RNAi) is an important research tool in many areas of biology. To effectively harness the power of this technique in order to explore tick functional genomics and tick-microorganism interactions, optimised parameters for RNAi-mediated gene silencing in tick cells need to be established. Ten cell lines from four economically important ixodid tick genera (Amblyomma, Hyalomma, Ixodes and Rhipicephalus including the sub-species Boophilus) were used to examine key parameters including small interfering RNA (siRNA), double stranded RNA (dsRNA), transfection reagent and incubation time for silencing virus reporter and endogenous tick genes. Transfection reagents were essential for the uptake of siRNA whereas long dsRNA alone was taken up by most tick cell lines. Significant virus reporter protein knockdown was achieved using either siRNA or dsRNA in all the cell lines tested. Optimum conditions varied according to the cell line. Consistency between replicates and duration of incubation with dsRNA were addressed for two Ixodes scapularis cell lines; IDE8 supported more consistent and effective silencing of the endogenous gene subolesin than ISE6, and highly significant knockdown of the endogenous gene 2I1F6 in IDE8 cells was achieved within 48 h incubation with dsRNA. In summary, this study shows that gene silencing by RNAi in tick cell lines is generally more efficient with dsRNA than with siRNA but results vary between cell lines and optimal parameters need to be determined for each experimental system
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