311 research outputs found

    Solidification of melts in the CaO-“Fe2O3”-SiO2 system

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    Ghost hunting in the broken archives:Re-historicizing digital education in an institutional context

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    Digital education is often presented as breaking from tradition. A failure to account for how digital education emerges from historical institutional activity is problematic insofar as this activity continues to circulate through the present and future, appearing and disappearing in often unexpected ways. Using Derrida’s hauntology as a theoretical lens, this paper traces how a digital education initiative at the University of Edinburgh in 2003 carried through to the creation of a course to train teachers to teach online in 2019, which in turn informed the university’s response to the pandemic in 2020. Working in a broadly autoethnographic way alongside archival document analysis, several findings emerged. First, hauntology provides a mechanism for institutions to trace their own histories and to note how these histories, often hidden in archives or carried forward into the present by hosts, inform their present and future trajectories. Second, broken archives, those that have ceased to function as active repositories but are disconnected from institutional domains and ontologies, shut due to absent gatekeepers, or merely forgotten, contribute​ to the sudden and often unexpected emergence of hauntings in present and future trajectories. Third, curation of the archive is an act of reinterpretation, one that troubles historical narratives and introduces new hauntings. All these findings assert a re-historicizing of digital education by emphasising the hauntings from the past that inform its emergent present and contested future, countering many of the ahistorical imaginaries of digital education

    Cool Sex? Hibernation and Reproduction Overlap in the Echidna

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    During hibernation there is a slowing of all metabolic processes, and thus it is normally considered to be incompatible with reproduction. In Tasmania the egg-laying mammal, the echidna (Tachyglossus aculeatus) hibernates for several months before mating in mid-winter, and in previous studies we observed males with females that were still hibernating. We monitored the reproductive activity of radio-tracked echidnas by swabbing the reproductive tract for sperm while external temperature loggers provided information on the timing of hibernation. Additional information was provided by camera traps and ultrasound imaging. More than a third of the females found in mating groups were torpid, and the majority of these had mated. Some females re-entered deep torpor for extended periods after mating. Ultrasound examination showed a developing egg in the uterus of a female that had repeatedly re-entered torpor. The presence of fresh sperm in cloacal swabs taken from this female on three occasions after her presumed date of fertilization indicated she mated several times after being fertilized. The mating of males with torpid females is the result of extreme competition between promiscuous males, while re-entry into hibernation by pregnant females could improve the possibility of mating with a better quality male

    The impact of target frequency on intra-individual variability in euthymic bipolar disorder: a comparison of two sustained attention tasks.

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    Greater intra-individual variability (IIV) in reaction time (RT) on a sustained attention task has been reported in patients with bipolar disorder (BD) compared with healthy controls. However, it is unclear whether IIV is task specific, or whether it represents general crosstask impairment in BD. This study aimed to investigate whether IIV occurs in sustained attention tasks with different parameters. Twenty-two patients with BD (currently euthymic) and 17 controls completed two sustained attention tasks on different occasions: a low target frequency (~20%) Vigil continuous performance test (CPT) and a high target frequency (~70%) CPT version A-X (CPT-AX). Variability measures (individual standard deviation and coefficient of variation) were calculated per participant, and ex-Gaussian modeling was also applied. This was supplemented by Vincentile analysis to characterize RT distributions. Results indicated that participants (patients and controls) were generally slower and more variable when completing the Vigil CPT compared with CPT-AX. Significant group differences were also observed in the Vigil CPT, with euthymic BD patients being more variable than controls. This result suggests that IIV in BD demonstrates some degree of task specificity. Further research should incorporate analysis of additional RT distributional models (drift diffusion and fast Fourier transform) to fully characterize the pattern of IIV in BD, as well as its relationship to cognitive processes

    Use of in vivo phage display to engineer novel adenoviruses for targeted delivery to the cardiac vasculature

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    We performed in vivo phage display in the stroke prone spontaneously hypertensive rat, a cardiovascular disease model, and the normotensive Wistar Kyoto rat to identify cardiac targeting peptides, and then assessed each in the context of viral gene delivery. We identified both common and strain-selective peptides, potentially indicating ubiquitous markers and those found selectively in dysfunctional microvasculature of the heart. We show the utility of the peptide, DDTRHWG, for targeted gene delivery in human cells and rats in vivo when cloned into the fiber protein of subgroup D adenovirus 19p. This study therefore identifies cardiac targeting peptides by in vivo phage display and the potential of a candidate peptide for vector targeting strategies

    An RNA aptamer targets the PDZ-binding motif of the HPV16 E6 oncoprotein.

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    Human papillomavirus 16 (HPV16) is a high-risk DNA tumour virus which is the primary causative agent of cervical cancer. Cell transformation arises from deregulated expression of the E6 and E7 oncogenes. E6 has been shown to bind a number of cellular proteins, including p53 and proteins containing a PDZ domain. This study reports the first RNA aptamers to E6. These have been employed as molecular tools to further investigate E6-p53 and E6-PDZ interactions. This study is focussed on two aptamers (termed F2 and F4) which induced apoptosis in cells derived from an HPV16-transformed cervical carcinoma. The molecules were able to inhibit the interaction between E6 and PDZ1 from Magi1, with F2 being the most effective inhibitor. Neither of the aptamers inhibited E6-p53 interaction or p53 degradation. This study shows the specificity of this approach and highlights the potential benefits of the E6 aptamers as potential therapeutic or diagnostic agents in the future

    The language profile of formal thought disorder

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    Formal thought disorder (FTD) is clinically manifested as disorganized speech, but there have been only few investigations of its linguistic properties. We examined how disturbance of thought may relate to the referential function of language as expressed in the use of noun phrases (NPs) and the complexity of sentence structures. We used a comic strip description task to elicit language samples from 30 participants with schizophrenia (SZ), 15 with moderate or severe FTD (SZ + FTD), and 15 minimal or no FTD (SZ−FTD), as well as 15 first-degree relatives of people with SZ (FDRs) and 15 neurotypical controls (NC). We predicted that anomalies in the normal referential use of NPs, sub-divided into definite and indefinite NPs, would identify FTD; and also that FTD would also be linked to reduced linguistic complexity as specifically measured by the number of embedded clauses and of grammatical dependents. Participants with SZ + FTD produced more referential anomalies than NC and produced the fewest definite NPs, while FDRs produced the most and thus also differed from NC. When referential anomalies were classed according to the NP type in which they occurred, the SZ + FTD group produced more anomalies in definite NPs than NC. Syntactic errors did not distinguish groups, but the SZ + FTD group exhibited significantly less syntactic complexity than non-SZ groups. Exploratory regression analyses suggested that production of definite NPs distinguished the two SZ groups. These results demonstrate that FTD can be identified in specific grammatical patterns which provide new targets for detection, intervention, and neurobiological studies

    Biodistribution and inflammatory profiles of novel penton and hexon double-mutant serotype 5 adenoviruses

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    The use of adenovirus serotype 5 (Ad5) vectors in the clinical setting is severely hampered by the profound liver tropism observed after intravascular delivery coupled with the pronounced inflammatory and innate immune response elicited by these vectors. Liver transduction by circulating Ad5 virions is mediated by a high-affinity interaction between the capsid hexon protein and blood coagulation factor X (FX), whilst penton-α(v)integrin interactions are thought to contribute to the induction of anti-Ad5 inflammatory and innate immune responses. To overcome these limitations, we sought to develop and characterise for the first time novel Ad5 vectors possessing mutations ablating both hexon:FX and penton:integrin interactions. As expected, intravascular administration of the FX binding-ablated Ad5HVR5*HVR7*E451Q vector (AdT*) resulted in significantly reduced liver transduction in vivo compared to Ad5. In macrophage-depleted mice, increased spleen uptake of AdT* was accompanied by an elevation in the levels of several inflammatory mediators. However ablation of the penton RGD motif in the AdT* vector background (AdT*RGE) resulted in a significant 5-fold reduction in spleen uptake and attenuated the antiviral inflammatory response. A reduction in spleen uptake and inflammatory activation was also observed in animals after intravascular administration of Ad5RGE compared to the parental Ad5 vector, with reduced co-localisation of the viral beta-galactosidase transgene with MAdCAM-1+ sinus-lining endothelial cells. Our detailed assessment of these novel adenoviruses indicates that penton base RGE mutation in combination with FX binding-ablation may be a viable strategy to attenuate the undesired liver uptake and pro-inflammatory responses to Ad5 vectors after intravascular deliver
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