Remarks on the Theory of Relativity (1922)

On April 22, 1922, the Societé française de Philosophie hosted Albert Einstein for a discussion of the theory of relativity.  In the course of this discussion, Henri Bergson, who was at that time writing Duration and Simultaneity, which explored some of the philosophical implications of Einstein's theory, was asked to share his thoughts.  The resulting remarks offer a glimpse into Bergson's analysis of the concept of simultaneity, and Einstein's brief reply reveals his insistence that time itself, not just "the physicist's time," is relative

The role of social networks in students’ learning experiences

The aim of this research is to investigate the role of social networks in computer science education. The Internet shows great potential for enhancing collaboration between people and the role of social software has become increasingly relevant in recent years. This research focuses on analyzing the role that social networks play in students’ learning experiences. The construction of students’ social networks, the evolution of these networks, and their effects on the students’ learning experience in a university environment are examined

Relative group size and minority school success: the role of intergroup friendship and discrimination experiences

From an intergroup relations perspective, relative group size is associated with the quantity and quality of intergroup contact: more positive contact (i.e., intergroup friendship) supports, and negative contact (i.e., experienced discrimination) hampers, minority identity, and school success. Accordingly, we examined intergroup contact as the process through which perceived relative proportions of minority and majority students in school affected minority success (i.e., school performance, satisfaction, and self-efficacy). Turkish minorities (N = 1,060) were compared in four Austrian and Belgian cities which differ in their typical school ethnic composition. Across cities, minority experiences of intergroup contact fully mediated the impact of perceived relative group size on school success. As expected, higher minority presence impaired school success through restricting intergroup friendship and increasing experienced discrimination. The association between minority presence and discrimination was curvilinear, however, so that schools where minority students predominated offered some protection from discrimination. To conclude, the comparative findings reveal positive and negative intergroup contact as key processes that jointly explain when and how higher proportions of minority students affect school success

Groundwater dynamics in coastal gravel barriers backed by freshwater lagoons and the potential for saline intrusion: Two cases from the UK

“NOTICE: this is the author’s version of a work that was accepted for publication in Journal of Marine Systems. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Marine Systems, [VOL 123, (01.08.13)] DOI 10.1016/j.jmarsys.2013.04.004". The full text is under embargo until 01.08.15

What are Employers Looking for in New Veterinary Graduates? A Content Analysis of UK Veterinary Job Advertisements

As veterinary educators, we have a responsibility to ensure that our graduates are prepared for working life. Veterinary practices, like any other businesses, rely on good employees, and the implications of a poor match between newly employed veterinarian and employing practice could be extremely costly in terms of personal well-being and enjoyment of work as well as the time, financial, and goodwill costs of high staff turnover for the practice. Contemporary veterinary curricula encompass a range of teaching to complement the clinical content; including communication, teamwork, problem solving, and business skills, to support good practice and increase the employability of new graduates. Previous studies have examined the qualities required of early career veterinarians as viewed by educators, recent graduates, pet owners, and practitioners; however, nobody has previously constructed a picture of the employment market for new veterinary graduates by exploring the nature of its recruitment advertising. Three months of UK veterinary job advertisements were examined. Content analysis yielded 10 distinct characteristics desired by employers of early career veterinarians. The most common by far was “enthusiasm,” followed by an interest in a particular area of practice, being an “all-rounder” (i.e., having a broad range of skills), demonstrating good communication skills, teamwork, client care, and independence, as well as being caring, ambitious, and having high clinical standards. While several of these qualities are expected and are specifically taught in veterinary school, the dominance of “enthusiasm” as a specifically desired trait raises interesting questions about the characteristics of veterinary students who we are supporting, encouraging, or maybe even suppressing, during veterinary training

False recognition in a mouse model of Alzheimer's disease: rescue with sensory restriction and memantine.

Alzheimer's disease is commonly regarded as a loss of memory for past events. However, patients with Alzheimer's disease seem not only to forget events but also to express false confidence in remembering events that have never happened. How and why false recognition occurs in such patients is currently unknown, and treatments targeting this specific mnemonic abnormality have not been attempted. Here, we used a modified object recognition paradigm to show that the tgCRND8 mouse-which overexpresses amyloid β and develops amyloid plaques similar to those in the brains of patients with Alzheimer's disease-exhibits false recognition. Furthermore, we found that false recognition did not occur when tgCRND8 mice were kept in a dark, quiet chamber during the delay, paralleling previous findings in patients with mild cognitive impairment, which is often considered to be prodromal Alzheimer's disease. Additionally, false recognition did not occur when mice were treated with the partial N-methyl-d-aspartic acid receptor antagonist memantine. In a subsequent experiment, we found abnormally enhanced N-methyl-d-aspartic acid receptor-dependent long-term depression in these mice, which could be normalized by treatment with memantine. We suggest that Alzheimer's disease typical amyloid β pathology leads to aberrant synaptic plasticity, thereby making memory representations more susceptible to interfering sensory input, thus increasing the likelihood of false recognition. Parallels between these findings and those from the literature on Alzheimer's disease and mild cognitive impairment suggest a mechanism underlying false recognition in these patients. The false recognition phenomenon may provide a novel paradigm for the discovery of potential therapies to treat the mnemonic dysfunction characteristic of this disease

Biallelic Variants in PYROXD2 Cause a Severe Infantile Metabolic Disorder Affecting Mitochondrial Function

Pyridine Nucleotide-Disulfide Oxidoreductase Domain 2 (PYROXD2; previously called YueF) is a mitochondrial inner membrane/matrix-residing protein and is reported to regulate mitochondrial function. The clinical importance of PYROXD2 has been unclear, and little is known of the protein’s precise biological function. In the present paper, we report biallelic variants in PYROXD2 identified by genome sequencing in a patient with suspected mitochondrial disease. The child presented with acute neurological deterioration, unresponsive episodes, and extreme metabolic acidosis, and received rapid genomic testing. He died shortly after. Magnetic resonance imaging (MRI) brain imaging showed changes resembling Leigh syndrome, one of the more common childhood mitochondrial neurological diseases. Functional studies in patient fibroblasts showed a heightened sensitivity to mitochondrial metabolic stress and increased mitochondrial superoxide levels. Quantitative proteomic analysis demonstrated decreased levels of subunits of the mitochondrial respiratory chain complex I, and both the small and large subunits of the mitochondrial ribosome, suggesting a mitoribosomal defect. Our findings support the critical role of PYROXD2 in human cells, and suggest that the biallelic PYROXD2 variants are associated with mitochondrial dysfunction, and can plausibly explain the child’s clinical presentation

Researching Transgression: Ana as a Youth Subculture in the Age of Digital Ethnography

In this paper we explore the contribution of material and digital ethnography to providing a deeper understanding of youth subcultures. We provide the context by reviewing some of the research carried out by the Centre for Contemporary Cultural Studies (CCCS) to provide a historical overview of cultural studies and critically appraise how they have drawn on ethnography as a way of deepening our understanding of young people’s subculture. We then draw on digital ethnographic data to explore the lived experiences of Ana girls, that is young women who advocate anorexic and bulimic behaviours as legitimate lifestyle choices, as they explore and negotiate their identity through online social media platforms with like-minded people. The aim is to demonstrate the potential of longitudinal digital ethnography to provide insights into these girls’ transgressive voices played out through online spaces. In narrating the Ana girls’ through digital storytelling, we argue that digital ethnography is the only way to access and understand their experiences and as such, has a unique role to play in advancing sociological understanding of their complex lived experiences. Thus, we suggest that digital ethnography provides a unique way of capturing longitudinal data and that this knowledge is important to bring about greater understanding of the challenges facing these girls as they grapple with complex problems. This greater understanding could inform changes to practice needed to better support Ana girls in online spaces

The HSP90 Inhibitor NVP-AUY922 Radiosensitizes by Abrogation of Homologous Recombination Resulting in Mitotic Entry with Unresolved DNA Damage

Heat shock protein 90 (HSP90) is a molecular chaperone responsible for the conformational maintenance of a number of client proteins that play key roles in cell cycle arrest, DNA damage repair and apoptosis following radiation. HSP90 inhibitors exhibit antitumor activity by modulating the stabilisation and activation of HSP90 client proteins. We sought to evaluate NVP-AUY922, the most potent HSP90 inhibitor yet reported, in preclinical radiosensitization studies.NVP-AUY922 potently radiosensitized cells in vitro at low nanomolar concentrations with a concurrent depletion of radioresistance-linked client proteins. Radiosensitization by NVP-AUY922 was verified for the first time in vivo in a human head and neck squamous cell carcinoma xenograft model in athymic mice, as measured by delayed tumor growth and increased surrogate end-point survival (p = <0.0001). NVP-AUY922 was shown to ubiquitously inhibit resolution of dsDNA damage repair correlating to delayed Rad51 foci formation in all cell lines tested. Additionally, NVP-AUY922 induced a stalled mitotic phenotype, in a cell line-dependent manner, in HeLa and HN5 cell lines irrespective of radiation exposure. Cell cycle analysis indicated that NVP-AUY922 induced aberrant mitotic entry in all cell lines tested in the presence of radiation-induced DNA damage due to ubiquitous CHK1 depletion, but resultant downstream cell cycle effects were cell line dependent.These results identify NVP-AUY922 as the most potent HSP90-mediated radiosensitizer yet reported in vitro, and for the first time validate it in a clinically relevant in vivo model. Mechanistic analysis at clinically achievable concentrations demonstrated that radiosensitization is mediated by the combinatorial inhibition of cell growth and survival pathways, ubiquitous delay in Rad51-mediated homologous recombination and CHK1-mediated G(2)/M arrest, but that the contribution of cell cycle perturbation to radiosensitization may be cell line specific