Feminist Postdigital Inquiry in the Ruins of Pandemic Universities

During Covid-19, higher education made an unprecedented entry into the domestic sphere. However, not all students welcomed the emergency delivery of online courses. Consequently, some learners have been developing resistant practices to technology-driven learning, including being on mute and turning off cameras, but these silences, gaps and evasions are difficult to grasp through normative perspectives. Meanwhile, big tech continues to profit significantly from its encroachment on pedagogy. Conversely, we need alternate conceptions of learners’ varying responses to technologies. To develop a novel perspective, the study considers the Middle East’s traditional mashrabiyya windows, which are carved through an elaborate wooden latticework screen of geometric patterns and designed to deflect rather than let in the light. This mashrabiyya structure is applied as a theoretical metaphor to consider Arab women learners’ technological veiled affordances of filters, avatars and not replying. The mashrabiyya feminist postdigital framework develops unique inquiry into learners’ subtle practices; the authors’ self-reflexivity; and analysis of a (silent) email exchange and a Twitter avatar. Theorising suggests silences, invisibilities and disconnection are not necessarily a deficit but refractive responses enabling students and educators to stay below the radar

Neuroprotective role for RORA in Parkinson’s disease revealed by analysis of post-mortem brain and a dopaminergic cell line

Parkinson's disease (PD) is almost twice as prevalent in men, which has largely been attributed to neuroprotective effect of oestradiol in women. RORA (retinoic acid receptor-related orphan receptor alpha) regulates the transcription of central aromatase, the enzyme responsible for local oestradiol synthesis, simultaneously, RORA expression is regulated by sex hormones. Moreover, RORA protects neurones against oxidative stress, a key mechanism contributing to the loss of dopaminergic neurones in PD. Therefore, we hypothesized that there would be sex differences in RORA expression in the substantia nigra pars compacta (SNpc), which could contribute to sex differences observed in PD prevalence and pathogenesis. In a case control study, qPCR and western blot analyses were used to quantify gene and protein expression in the SNpc of post-mortem brains (n = 14 late-stage PD and 11 age and sex matched controls). The neuroprotective properties of a RORA agonist were then investigated directly using a cell culture toxin-based model of PD coupled with measures of viability, mitochondrial function and apoptosis. RORA was expressed at significantly higher levels in the SNpc from control females' brains compared to males. In PD, we found a significant increase in SNpc RORA expression in male PD compared to female PD. Treatment with a RORA agonist showed a significant neuroprotection in our cell culture model of PD and revealed significant effects on intracellular factors involved in neuronal survival and demise. This study is the first to demonstrate a sex specific pattern of RORA protein and gene expression in the SNpc of controls post-mortem human brains, and to show that this is differentially altered in male and female PD subjects, thus supporting a role for RORA in sex-specific aspects of PD. Furthermore, our in vitro PD model indicates mechanisms whereby a RORA agonist exerts its neuroprotective effect, thereby highlighting the translational potential for RORA ligands in PD

Test-retest reliability of capability measurement in the UK general population

Although philosophically attractive, it may be difficult, in practice, to measure individuals' capabilities (what they are able to do in their lives) as opposed to their functionings (what they actually do). To examine whether capability information could be reliably self-reported, we administered a measure of self-reported capability (the Investigating Choice Experiments Capability Measure for Adults, ICECAP-A) on two occasions, 2 weeks apart, alongside a self-reported health measure (the EuroQol Five Dimensional Questionnaire with 3 levels, EQ-5D-3L). We found that respondents were able to report capabilities with a moderate level of consistency, although somewhat less reliably than their health status. The more socially orientated nature of some of the capability questions may account for the difference. © 2014 The Authors Health Economics Published by John Wiley & Sons Ltd

Inhibition of FGF receptor blocks adaptive resistance to RET inhibition in CCDC6-RET-rearranged thyroid cancer

Genetic alterations in RET lead to activation of ERK and AKT signaling and are associated with hereditary and sporadic thyroid cancer and lung cancer. Highly selective RET inhibitors have recently entered clinical use after demonstrating efficacy in treating patients with diverse tumor types harboring RET gene rearrangements or activating mutations. In order to understand resistance mechanisms arising after treatment with RET inhibitors, we performed a comprehensive molecular and genomic analysis of a patient with RET-rearranged thyroid cancer. Using a combination of drug screening and proteomic and biochemical profiling, we identified an adaptive resistance to RET inhibitors that reactivates ERK signaling within hours of drug exposure. We found that activation of FGFR signaling is a mechanism of adaptive resistance to RET inhibitors that activates ERK signaling. Combined inhibition of FGFR and RET prevented the development of adaptive resistance to RET inhibitors, reduced cell viability, and decreased tumor growth in cellular and animal models of CCDC6-RET-rearranged thyroid cancer

Association of Amyloid Pathology With Myelin Alteration in Preclinical Alzheimer Disease

IMPORTANCE: The accumulation of aggregated β-amyloid and tau proteins into plaques and tangles is a central feature of Alzheimer disease (AD). While plaque and tangle accumulation likely contributes to neuron and synapse loss, disease-related changes to oligodendrocytes and myelin are also suspected of playing a role in development of AD dementia. Still, to our knowledge, little is known about AD-related myelin changes, and even when present, they are often regarded as secondary to concomitant arteriosclerosis or related to aging. OBJECTIVE: To assess associations between hallmark AD pathology and novel quantitative neuroimaging markers while being sensitive to white matter myelin content. DESIGN, SETTING AND PARTICIPANTS: Magnetic resonance imaging was performed at an academic research neuroimaging center on a cohort of 71 cognitively asymptomatic adults enriched for AD risk. Lumbar punctures were performed and assayed for cerebrospinal fluid (CSF) biomarkers of AD pathology, including β-amyloid 42, total tau protein, phosphorylated tau 181, and soluble amyloid precursor protein. We measured whole-brain longitudinal and transverse relaxation rates as well as the myelin water fraction from each of these individuals. MAIN OUTCOMES AND MEASURES: Automated brain mapping algorithms and statistical models were used to evaluate the relationships between age, CSF biomarkers of AD pathology, and quantitative magnetic resonance imaging relaxometry measures, including the longitudinal and transverse relaxation rates and the myelin water fraction. RESULTS: The mean (SD) age for the 19 male participants and 52 female participants in the study was 61.6 (6.4) years. Widespread age-related changes to myelin were observed across the brain, particularly in late myelinating brain regions such as frontal white matter and the genu of the corpus callosum. Quantitative relaxometry measures were negatively associated with levels of CSF biomarkers across brain white matter and in areas preferentially affected in AD. Furthermore, significant age-by-biomarker interactions were observed between myelin water fraction and phosphorylated tau 181/β-amyloid 42, suggesting that phosphorylated tau 181/β-amyloid 42 levels modulate age-related changes in myelin water fraction. CONCLUSIONS AND RELEVANCE: These findings suggest amyloid pathologies significantly influence white matter and that these abnormalities may signify an early feature of the disease process. We expect that clarifying the nature of myelin damage in preclinical AD may be informative on the disease’s course and lead to new markers of efficacy for prevention and treatment trials

Laboratory evaluation on the characteristics and pollutant emissions of nanoclay and chemical warm mix asphalt modified binders

This study was conducted to investigate the performance characteristics of nanoclay- and chemical warm-mix asphalt (WMA) additive-modified asphalt binders in terms of their chemical, morphology, rheological and surface energy properties in comparison to conventional asphalt binder. Both the nanoclay modified asphalt binder (NCMB B) and the chemical WMA additive modified asphalt binder (CWAA) were artificially aged under short-term and long-term aging conditions prior to evaluation. The chemical and morphological properties were measured with Fourier Transform Infrared (FTIR) spectroscopy and Field-Emission Scanning Electron Microscopy (FE-SEM) respectively. Rheological eval-uations were conducted to determine binder’s behavior under short-term aging in terms of frequency sweep, temperature sweep, and creep recovery tests by utilizing the dynamic shear rheometer (DSR) machine. Emission test was also conducted on the unmodified and modified WMA mixtures to estimate the gaseous pollutants emitted during their manufacture. FTIR spectroscopy results showed that the addition of WMA modifiers into asphalt binder could delay and weaken the oxidation reaction of the binder which in turn improved the aging process. However, the physical structure did not seem to show any changes after undergoing long term aging. The use of NCMB B 4% (by weight of asphalt binder) seemed to produce better resistance towards rutting when compared to CWAA 1%, 2% and 3% for unaged, and short- and long-term aging test conditions. The modified binders exhibit significantly higher surface energy and hence produced good adhesion between aggregates, which imply increased resistance toward moisture-induced damage. This study also revealed that the manufacture of WMA mixtures reduced up to 50% of the pollutants emitted during mixing in laboratory