But somehow it was only television: West German Narratives of the fall of the Wall in recent novels and their screen adaptations

East Germans have long been criticised for harbouring a feeling of Ostalgie, a nostalgia for their old, Socialist state, but only recently has it become apparent that many west Germans obviously experience a similar sense of loss and longing for a seemingly simpler time before reunification. The texts that express these feelings tend to focus on the fall of the Wall as the pivotal point of change in German post-war history. Typically the characters in these books deny the significance and impact of this major political event and strive to reduce its importance, at best to a minor television moment. This attitude can be observed in the novels liegen lernen and Herr Lehmann and in their film adaptations. Despite having been accused of indulging a feeling of Westalgie, a closer analysis reveals that they are in fact deliberately provocative and challenge eastern and western stereotypes. In addition the films find ways to transport the books’ ironic narrative to the screen, and they also reinforce the authors’ implicitly critical attitude towards their characters’ political apathy by portraying the fall of the Wall in ways different to the books. The films react to the provocation voiced in the novels and function like an intertextual commentary as they integrate the opening of the border into a meaningful context for the protagonists and restore it to its historic importance.

Identification of residues controlling transport through the yeast aquaglyceroporin Fps1 using a genetic screen

Aquaporins and aquaglyceroporins mediate the transport of water and solutes across biological membranes. Saccharomyces cerevisiae Fps1 is an aquaglyceroporin that mediates controlled glycerol export during osmoregulation. The transport function of Fps1 is rapidly regulated by osmotic changes in an apparently unique way and distinct regions within the long N- and C-terminal extensions are needed for this regulation. In order to learn more about the mechanisms that control Fps1 we have set up a genetic screen for hyperactive Fps1 and isolated mutations in 14 distinct residues, all facing the inside of the cell. Five of the residues lie within the previously characterized N-terminal regulatory domain and two mutations are located within the approach to the first transmembrane domain. Three mutations cause truncation of the C-terminus, confirming previous studies on the importance of this region for channel control. Furthermore, the novel mutations identify two conserved residues in the channel-forming B-loop as critical for channel control. Structural modelling-based rationalization of the observed mutations supports the notion that the N-terminal regulatory domain and the B-loop could interact in channel control. Our findings provide a framework for further genetic and structural analysis to better understand the mechanism that controls Fps1 function by osmotic changes.

Perception while watching movies:effects of physical screen size and scene type

Over the last decade, television screens and display monitors have increased in size considerably, but has this improved our televisual experience? Our working hypothesis was that the audiences adopt a general strategy that “bigger is better.” However, as our visual perceptions do not tap directly into basic retinal image properties such as retinal image size (C. A. Burbeck, 1987), we wondered whether object size itself might be an important factor. To test this, we needed a task that would tap into the subjective experiences of participants watching a movie on different-sized displays with the same retinal subtense. Our participants used a line bisection task to self-report their level of “presence” (i.e., their involvement with the movie) at several target locations that were probed in a 45-min section of the movie “The Good, The Bad, and The Ugly.” Measures of pupil dilation and reaction time to the probes were also obtained. In Experiment 1, we found that subjective ratings of presence increased with physical screen size, supporting our hypothesis. Face scenes also produced higher presence scores than landscape scenes for both screen sizes. In Experiment 2, reaction time and pupil dilation results showed the same trends as the presence ratings and pupil dilation correlated with presence ratings, providing some validation of the method. Overall, the results suggest that real-time measures of subjective presence might be a valuable tool for measuring audience experience for different types of (i) display and (ii) audiovisual material.

A loss-of-function screen reveals SNX5 and SNX6 as potential components of the mammalian retromer

The mammalian retromer is a multimeric protein complex involved in mediating endosome-to-trans-Golgi-network retrograde transport of the cation-independent mannose-6-phosphate receptor. The retromer is composed of two subcomplexes, one containing SNX1 and forming a membrane-bound coat, the other comprising VPS26, VPS29 and VPS35 and being cargo-selective. In yeast, an additional sorting nexin--Vps17p--is a component of the membrane bound coat. It remains unclear whether the mammalian retromer requires a functional equivalent of Vps17p. Here, we have used an RNAi loss-of-function screen to examine whether any of the other 30 mammalian sorting nexins are required for retromer-mediated endosome-to-trans-Golgi-network retrieval of the cation-independent mannose-6-phosphate receptor. Using this screen, we identified two proteins, SNX5 and SNX6, that, when suppressed, induced a phenotype similar to that observed upon suppression of known retromer components. Whereas SNX5 and SNX6 colocalised with SNX1 on early endosomes, in immunoprecipitation experiments only SNX6 appeared to exist in a complex with SNX1. Interestingly, suppression of SNX5 and/or SNX6 resulted in a significant loss of SNX1, an effect that seemed to result from post-translational regulation of the SNX1 level. Such data suggest that SNX1 and SNX6 exist in a stable, endosomally associated complex that is required for retromer-mediated retrieval of the cation-independent mannose-6-phosphate receptor. SNX5 and SNX6 may therefore constitute functional equivalents of Vps17p in mammals.

Drug repurposing screen identifies Foxo1-dependent angiopoietin-2 regulation in sepsis

Objective: The recent withdrawal of a targeted sepsis therapy has diminished pharmaceutical enthusiasm for developing novel drugs for the treatment of sepsis. Angiopoietin-2 is an endothelial-derived protein that potentiates vascular inflammation and leakage and may be involved in sepsis pathogenesis. We screened approved compounds for putative inhibitors of angiopoietin-2 production and investigated underlying molecular mechanisms. Design: Laboratory and animal research plus prospective placebo-controlled randomized controlled trial (NCT00529139) and retrospective analysis (NCT00676897). Setting: Research laboratories of Hannover Medical School and Harvard Medical School. Patients: Septic patients/C57Bl/6 mice and human endothelial cells. Interventions: Food and Drug Administration-approved library screening. Measurements and Main Results: In a cell-based screen of more than 650 Food and Drug Administration-approved compounds, we identified multiple members of the 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor drug class (referred to as statins) that suppressed angiopoietin-2. Simvastatin inhibited 3-hydroxy-3-methyl-glutaryl-CoA reductase, which in turn activated PI3K-kinase. Downstream of this signaling, PI3K-dependent phosphorylation of the transcription factor Foxo1 at key amino acids inhibited its ability to shuttle to the nucleus and bind cis-elements in the angiopoietin-2 promoter. In septic mice, transient inhibition of angiopoietin-2 expression by liposomal siRNA in vivo improved absolute survival by 50%. Simvastatin had a similar effect, but the combination of angiopoietin-2 siRNA and simvastatin showed no additive benefit. To verify the link between statins and angiopoietin-2 in humans, we performed a pilot matched case-control study and a small randomized placebo-controlled trial demonstrating beneficial effects on angiopoietin-2. Conclusions: 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors may operate through a novel Foxo1-angiopoietin-2 mechanism to suppress de novo production of angiopoietin-2 and thereby ameliorate manifestations of sepsis. Given angiopoietin-2's dual role as a biomarker and candidate disease mediator, early serum angiopoietin-2 measurement may serve as a stratification tool for future trials of drugs targeting vascular leakage.

Validity and reliability of the Spanish version of Caregiver Abuse Screen (CASE)

Detection of elder abuse risk is a critical issue because a lot of cases remain hidden. Screening tools can be used to detect elder abuse. However, few tools have been developed for use with caregivers. The purpose was to develop a translation and adaptation of a Spanish version of the Caregiver Abuse Screen (CASE) and to assess its validity and reliability. The CASE was then used with 211 primary caregivers. Validity and reliability were evaluated, as well as the factorial structure of the instrument. This version showed good psychometric properties. It was found to have strong internal consistency and split-half reliability as well as allowing for a good replication of the original factorial structure. Additionally, several variables related to elder abuse were linked to the CASE such as depression, burden, frequency, and reactions to problem behaviors. The version developed showed sufficient validity and reliability and could be considered as a suitable instrument to assess risks of elder abuse in a Spanish-speaking context.

‘Everything’s from the inside out with PCOS’:exploring women’s experiences of living with Polycystic Ovary Syndrome (PCOS) and co-morbidities through Skype™ interviews

Polycystic ovary syndrome is an endocrine disorder affecting 1 in 10 women. Women with polycystic ovary syndrome can experience co-morbidities, including depressive symptoms. This research explores the experience of living with polycystic ovary syndrome and co-morbidities. Totally, 10 participants with polycystic ovary syndrome took part in Skype™ interviews and analysed using thematic analysis. Four themes emerged from the data: change (to life plans and changing nature of condition); support (healthcare professionals, education and relationships); co-morbidities (living with other conditions and depression, self-harm and suicidal ideation) and identity (feminine identity and us and them). The findings highlight the need for screening of women with polycystic ovary syndrome for depressive disorders.

On-screen pre-deblurring of digital images using the wavefront aberration function of the human eye to improve computer access for the visually impaired

Traditional Optics has provided ways to compensate some common visual limitations (up to second order visual impairments) through spectacles or contact lenses. Recent developments in wavefront science make it possible to obtain an accurate model of the Point Spread Function (PSF) of the human eye. Through what is known as the "Wavefront Aberration Function" of the human eye, exact knowledge of the optical aberration of the human eye is possible, allowing a mathematical model of the PSF to be obtained. This model could be used to pre-compensate (inverse-filter) the images displayed on computer screens in order to counter the distortion in the user's eye. This project takes advantage of the fact that the wavefront aberration function, commonly expressed as a Zernike polynomial, can be generated from the ophthalmic prescription used to fit spectacles to a person. This allows the pre-compensation, or onscreen deblurring, to be done for various visual impairments, up to second order (commonly known as myopia, hyperopia, or astigmatism). The technique proposed towards that goal and results obtained using a lens, for which the PSF is known, that is introduced into the visual path of subjects without visual impairment will be presented. In addition to substituting the effect of spectacles or contact lenses in correcting the loworder visual limitations of the viewer, the significance of this approach is that it has the potential to address higher-order abnormalities in the eye, currently not correctable by simple means.

The first time delivery of the first link learning series using Skype and YouTube

Introduction: This case study documented the experiences of informal and service providers who participated in the first time delivery of the First Link Learning Series from May–August 2013 in Newfoundland and Labrador. The aim of this study was to understand how informal caregivers of people with dementia experience this Internet mediated health resource, and how Skype and YouTube can be used as tools for the Alzheimer Society of Newfoundland and Labrador to effectively deliver the First Link Learning Series. Methods: Sources of data included key informant interviews (n=3), pre- study and post-study interviews with informal dementia caregivers (n=2), institutional documentation, field notes, and YouTube analytics. Framework Analysis was used to make meaning of the qualitative data, and descriptive statistics were used to report on quantitative outcomes. Findings: Between 3% and 17% of registered First Link clients attended the learning series sessions, however only two caregivers participated using Skype or YouTube. Framework Analysis revealed three shared themes: access, connection and privacy. Discussion: The themes helped to begin building theory about barriers and facilitators to Internet mediated health resources for informal dementia caregivers. Experiences of service providers using the Internet to support clients served to begin building a case for the appropriateness of these media. A modified version of Dansky et al.’s (2006) theoretical framework for evaluating E-Health research that situates the person/user in the model, helped guide discussion and propose future directions for the study of Internet based health resources for informal dementia caregivers.

Silent screen: book review.

Book Review. Kevin Rockett, Irish film censorship: a cultural journey from silent cinema to internet pornography (Dublin, 2004) and Mary Corcoran and Mark O'Brien (eds), Political censorship and the democratic state: the Irish broadcasting ban (Dublin, 2005)

Diversity, difference and nation: indigenous peoples on screen in Mexico

This paper draws on constructivist theories of identity that regard the self as, paradoxically, coming into existence through interaction with the other, to investigate the discursive formation of indigenous people in the forging of Mexican national identity. The aim of the essay is to show how difference has been managed and deployed in the establishment of national Mexican identities from independence until the present. This is done with reference to visual culture and film and illustrated with examples from the ‘Golden Age’ as well as ‘the New Mexican Cinema’.

Examination of body image among Canadian adolescents: Relations with physical activity and screen time

Background: Adolescence is a period of life associated with self-perceptions of negative body image. Physical activity levels are low and screen time levels are also high during this stage. These perceptions and behaviours are associated with poor health outcomes, making research on their determinants important. With adolescent populations, certain groups may be at higher risk of body dissatisfaction than others, and body dissatisfaction may influence individual physical activity and screen time levels. Objectives: The objectives of this thesis were to: 1) describe body image among young Canadians, examining possible health inequalities 2) estimate the strength and significance of associations between body satisfaction, physical activity and screen time, and 3) examine the potential etiological role of biological sex. Methods: Objective 1: The 2013/2014 Health Behaviour in School-aged Children study was employed. Sex-stratified Rao-Scott chi-square analyses were conducted to examine associations between socio-demographic factors and body satisfaction. Objective 2: The 2005/2006 and 2013/2014 cross-sectional and 2006 longitudinal HBSC data sets were used. Sex-stratified modified Poisson regressions were conducted and risk estimates and associated confidence intervals obtained. Results: Objective 1: Among males, being older, of East and Southeast Asian ethnicity, and reporting low SES all were associated with body dissatisfaction. Among females, being older, of Arab and West Asian or African ethnicity, being born in Canada, and reporting low SES were all associated with being body dissatisfied. Objective 2: Cross-sectionally, males who reported ‘too fat’ body dissatisfaction were more likely to be physically inactive. Adolescents of both sexes who reported ‘too fat’ body dissatisfaction were more likely to engage in high levels of screen time. Data from the longitudinal component supported the idea that male ‘too fat’ body dissatisfaction temporally leads to physical inactivity, but showed an inverse relationship between body dissatisfaction and screen time. Conclusions: Objective 1: Future prevention efforts in Canada should target subgroups to effectively help those at greatest risk of body dissatisfaction, and ameliorate potential inequalities at the population level. Objective 2: The presence of these relationships may inform future interventions as part of a multi-factorial etiology, in order to increase physical activity and decrease screen time among youth.

Kinome-wide CRISPR-Cas9 screen to identify kinases involved in Taxol resistance in breast cancer

Breast cancer is the most frequently diagnosed cancer in women, accounting for over 25% of cancer diagnoses and 13% of cancer-related deaths in Canadian women. There are many types of therapies for treatment or management of breast cancer, with chemotherapy being one of the most widely used. Taxol (paclitaxel) is one of the most extensively used chemotherapeutic agents for treating cancers of the breast and numerous other sites. Taxol stabilizes microtubules during mitosis, causing the cell cycle to arrest until eventually the cell undergoes apoptosis. Although Taxol has had significant benefits in many patients, response rates range from only 25-69%, and over half of Taxol-treated patients eventually acquire resistance to the drug. Drug resistance remains one of the greatest barriers to effective cancer treatment, yet little has been discerned regarding resistance to Taxol, despite its widespread clinical use. Kinases are known to be heavily involved in cancer development and progression, and several kinases have been linked to resistance of Taxol and other chemotherapeutic agents. However, a systematic screen for kinases regulating Taxol resistance is lacking. Thus, in this study, a set of kinome-wide screens was conducted to interrogate the involvement of kinases in the Taxol response. Positive-selection and negative-selection CRISPR-Cas9 screens were conducted, whereby a pooled library of 5070 sgRNAs targeted 507 kinase-encoding genes in MCF-7 breast cancer cells that were Taxol-sensitive (WT) or Taxol-resistant (TxR) which were then treated with Taxol. Next generation sequencing (NGS) was performed on cells that survived Taxol treatment, allowing identification and quantitation of sgRNAs. STK38, Blk, FASTK and Nek3 stand out as potentially critical kinases for Taxol-induced apoptosis to occur. Furthermore, kinases CDKL1 and FRK may have a role in Taxol resistance. Further validation of these candidate kinases will provide novel pre-clinical data about potential predictive biomarkers or therapeutic targets for breast cancer patients in the future.

International mindedness: kan het positief worden gestimuleerd? Een gestructureerde samenwerkingsopdracht als onderwijskundig middel ter bevordering van de international mindedness met behulp van de computer-mediated communication tool Skype©.

Koops, J. (2016) International mindedness: kan het positief worden gestimuleerd? Een gestructureerde samenwerkingsopdracht als onderwijskundig middel ter bevordering van de international mindedness met behulp van de computer-mediated communication tool Skype©. Augustus, 1, 2016, Heerlen, Nederland: Open Universiteit.