Reconstructing the past? Low German and the creating of regional identity in public language display

This article deals with language contact between a dominant standard language -German - and a lesser-used variety - Low German - in a situation in which the minoritised language is threatened by language shift and language loss. It analyses the application of Low German in forms of public language display and the selfpresentation of the community in tourism brochures, focusing on bilingual linguistic practices on the one hand and on underlying discourses on the other. It reveals that top-down and bottom-up approaches to implementing Low German in public language display show a remarkable homogeneity, thus creating a regional 'brand'. The article asks whether a raised level of visibility will in itself guarantee better chances for linguistic maintenance and survival of the threatened language. © 2011 Taylor & Francis.

The other on display: translation in the Ethnographic Museum

The ethnographic museum in the West has a long and troubling history. The display of 'exotic peoples' in travelling exhibitions began as early as the sixteenth century, but it was the mid and late nineteenth century that saw the great expansion of museums as sites to show artefacts collected - under anything but reputable circumstances - from what were considered the 'primitive', 'natural', or 'tribal' peoples of the world. Today the ethnographic museum is still a feature of large European cities, though faced with newly formulated dilemmas in the postcolonial world. For how can the material culture of a non-western people be collected and displayed in the West without its makers being translated into wordless and powerless objects of visual consumption? In national museums the processes of choosing, contextualizing and commentating exhibits help form national identity; in the ethnographic museum, similarly, they shape perceptions of the apparently distant Other. Like written ethnography, the museum is a 'translation of culture', with many of the associated problems traced by Talal Asad (1986). Like the written form, it has to represent the dialogic realities of cultural encounters in a fixed and intelligible form, to propose categories that define and order the material it has gathered. As the public face of academic ethnography, the museum interprets other cultures for the benefit of the general reader, and in that task museum practice, like all ethnography, operates within very specific historical and political parameters. How are museums in western Europe responding to the issues raised by critical ethnographers like James Clifford (1988), with their focus on the politics of representation? Is globalisation increasing the degree of accountability imposed on the ethnographic museum, or merely reinforcing older patterns? What opportunities and problems are raised by the use of more words - more 'translation' in the narrower sense - in ethnographic museums, and how do museums gain from introducing a reflexive and contextualizing concept of "thick translation" (Appiah 1993) into their work of interpretation?

Skin delivery potency and antitumor activities of temozolomide ester prodrugs

Clinical trials have shown temozolomide to be an effective agent for treatment of malignant melanoma. In order to investigate its suitability for delivery via the skin, a series of temozolomide esters was synthesized as prodrugs. In vitro assays demonstrated temozolomide, temozolomide acid and the hexyl ester equi-effective against selected cancer cell lines. The susceptibility of the esters to enzyme hydrolysis and their effectiveness for application to the skin were investigated. The esters effectively diffuse through rat skin and the hexyl ester demonstrated profound potency for penetrating through skin. Topical application of 5% (w/v) hexyl ester in DMSO solution on a mouse model demonstrated a significant inhibition of tumor growth. These results suggest that temozolomide esters could be an effective alternative to temozolomide in the treatment of skin cancer. © 2005 Elsevier Ireland Ltd. All rights reserved.

A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct CD4 T cell-inducing capacity compared to its unsaturated analog

Adjuvants are often composed of different constituents that can be divided into two groups based on their primary activity: the delivery system which carries and presents the vaccine antigen to antigen-presenting cells, and the immunostimulator that activates and modulates the ensuing immune response. Herein, we have investigated the importance of the delivery system and in particular its physical characteristics by comparing the delivery properties of two lipids which differ only in the degree of saturation of the acyl chains, rendering the liposomes either rigid (DDA, dimethyldioctadecylammonium) or highly fluid (DODA, dimethyldioleoylammonium) at physiological temperature. We show that these delivery systems are remarkably different in their ability to prime a Th1-directed immune response with the rigid DDA-based liposomes inducing a response more than 100 times higher compared to that obtained with the fluid DODA-based liposomes. Upon injection with a vaccine antigen, DDA-based liposomes form a vaccine depot that results in a continuous attraction of antigen-presenting cells that engulf a high amount of adjuvant and are subsequently efficiently activated as measured by an elevated expression of the co-stimulatory molecules CD40 and CD86. In contrast, the fluid DODA-based liposomes are more rapidly removed from the site of injection resulting in a lower up-regulation of co-stimulatory CD40 and CD86 molecules on adjuvant-positive antigen-presenting cells. Additionally, the vaccine antigen is readily dissociated from the DODA-based liposomes leading to a population of antigen-presenting cells that are antigen-positive but adjuvant-negative and consequently are not activated. These studies demonstrate the importance of studying in vivo characteristics of the vaccine components and furthermore show that physicochemical properties of the delivery system have a major impact on the vaccine-induced immune response. © 2012 Elsevier B.V. All rights reserved.

Discovery of active proteins directly from combinatorial randomized protein libraries without display, purification or sequencing:identification of novel zinc finger proteins.

We have successfully linked protein library screening directly with the identification of active proteins, without the need for individual purification, display technologies or physical linkage between the protein and its encoding sequence. By using 'MAX' randomization we have rapidly constructed 60 overlapping gene libraries that encode zinc finger proteins, randomized variously at the three principal DNA-contacting residues. Expression and screening of the libraries against five possible target DNA sequences generated data points covering a potential 40,000 individual interactions. Comparative analysis of the resulting data enabled direct identification of active proteins. Accuracy of this library analysis methodology was confirmed by both in vitro and in vivo analyses of identified proteins to yield novel zinc finger proteins that bind to their target sequences with high affinity, as indicated by low nanomolar apparent dissociation constants.

The impact of the introduction of visual display terminals on the job characteristics, job satisfaction and well-being of users in government offices

The proliferation of visual display terminals (VDTs) in offices is an international phenomenon. Numerous studies have investigated the health implications which can be categorised into visual problems, symptoms of musculo-skelctal discomfort, or psychosocial effects. The psychosocial effects are broader and there is mixed evidence in this area. The inconsistent results from the studies of VDT work so far undertaken may reflect several methodological shortcomings. In an attempt to overcome these deficiencies and to broaden the model of inter-relationships a model was developed to investigate their interactions and Ihc outputs of job satisfaction, stress and ill health. The study was a two-stage, long-term investigation with measures taken before the VDTs were introduced and the same measures taken 12 months after the 'go-live' date. The research was conducted in four offices of the Department of Social Security. The data were analysed for each individual site and in addition the total data were used in a path analysis model. Significant positive relationships were found at the pre-implementation stage between the musculo-skeletal discomfort, psychosomatic ailments, visual complaints and stress. Job satisfaction was negatively related to visual complaints and musculo-skeletal discomfort. Direct paths were found for age and job level with variety found in the job and age with job satisfaction and a negative relationship with the office environment. The only job characteristic which had a direct path to stress was 'dealing with others'. Similar inter-relationships were found in the post-implementation data. However, in addition attributes of the computer system, such as screen brightness and glare, were related positively with stress and negatively with job satisfaction. The comparison of the data at the two stages found that there had been no significant changes in the users' perceptions of their job characteristics and job satisfaction but there was a small and significant reduction in the stress measure.

Channeled spectrum display using a CCD array for student laboratory demonstrations

The channelled spectrum of an optical beam generated by a laser diode operated below threshold after traversing microscope glass plates is spectrally analysed using a grating and a CCD linear array. The experiment has the following goals: to display the resulting channelled spectrum, to familiarize students with an important topic in metrology and to illustrate some interesting topics from spectroscopy using a CCD array as a spectrometer.

The integration of ProxiMAX randomisation with CIS display for the high-throughput production of novel peptides

Saturation mutagenesis is a powerful tool in modern protein engineering. This can allow the analysis of potential new properties thus allowing key residues within a protein to be targeted and randomised. However, the creation of large libraries using conventional saturation mutagenesis with degenerate codons (NNN or NNK) has inherent redundancy and disparities in residue representation. In this we describe the combination of ProxiMAX randomisation and CIS display for the use of generating novel peptides. Unlike other methods ProxiMAX randomisation does not require any intricate chemistry but simply utilises synthetic DNA and molecular biology techniques. Designed ‘MAX’ oligonucleotides were ligated, amplified and digested in an iterative cycle. Results show that randomised ‘MAX’ codons can be added sequentially to the base sequence creating a series of randomised non-degenerate codons that can subsequently be inserted into a gene. CIS display (Isogencia, UK) is an in vitro DNA based screening method that creates a genotype to phenotype link between a peptide and the nucleic acid that encodes it. The use of straight forward in vitro transcription/translation and other molecular biology techniques permits ease of use along with flexibility making it a potent screening technique. Using ProxiMAX randomisation in combination with CIS display, the aim is to produce randomised anti-nerve growth factor (NGF) and calcitonin gene-related (CGRP) peptides to demonstrate the high-throughput nature of this combination.

Channeled spectrum display using a CCD array for student laboratory demonstrations

The channelled spectrum of an optical beam generated by a laser diode operated below threshold after traversing microscope glass plates is spectrally analysed using a grating and a CCD linear array. The experiment has the following goals: to display the resulting channelled spectrum, to familiarize students with an important topic in metrology and to illustrate some interesting topics from spectroscopy using a CCD array as a spectrometer.

Apoptosis induction in gastric mucous cells in vitro:lesser potency of Helicobacter pylori than Escherichia coli lipopolysaccharide, but positive interaction with ibuprofen

Non-steroidal anti-inflammatory drugs (NSAIDs) cause peptic ulcer disease, but whether they interact with Helicobacter pylori to promote damage is controversial. Moreover, the reported induction of apoptosis in gastric cells by H. pylori lipopolysaccharide (LPS) (10-9 g /ml) contrasts with studies showing low immunological potency of this LPS. Therefore, the effects of LPS from H. pylori NCTC 11637 and Escherichia coli 0111:B4 on apoptosis in a primary culture of guinea-pig gastric mucous cells were investigated in the presence and absence of the NSAID, ibuprofen. Cell loss was estimated by a crystal violet assay, and apoptosis determined from caspase activity and from condensation and fragmentation of nuclei. Exposure to E. coli LPS for 24 h caused cell loss and enhanced apoptotic activity at concentrations ≥ 10-9 g/ml, but similar effects were only obtained with H. pylori LPS at concentrations ≥10-6 g/ml. Although ibuprofen (250 μM) caused cell loss and apoptosis, addition of either E. coli or H. pylori LPSs further enhanced these effects. In conclusion, LPS and ibuprofen interact to enhance gastric cell loss and apoptosis. In such interactions, E. coli LPS is more potent than that of H. pylori. The low potency of H. pylori LPS may contribute to a chronic low-grade gastritis that can be enhanced by the use of NSAIDs. © W. S. Maney & Son Ltd.

The development of a symptom questionnaire for assessing virtual reality viewing using a head-mounted display

ABSTRACT: Purpose. Virtual reality devices, including virtual reality head-mounted displays, are becoming increasingly accessible to the general public as technological advances lead to reduced costs. However, there are numerous reports that adverse effects such as ocular discomfort and headache are associated with these devices. To investigate these adverse effects, questionnaires that have been specifically designed for other purposes such as investigating motion sickness have often been used. The primary purpose of this study was to develop a standard questionnaire for use in investigating symptoms that result from virtual reality viewing. In addition, symptom duration and whether priming subjects elevates symptom ratings were also investigated. Methods. A list of the most frequently reported symptoms following virtual reality viewing was determined from previously published studies and used as the basis for a pilot questionnaire. The pilot questionnaire, which consisted of 12 nonocular and 11 ocular symptoms, was administered to two groups of eight subjects. One group was primed by having them complete the questionnaire before immersion; the other group completed the questionnaire postviewing only. Postviewing testing was carried out immediately after viewing and then at 2-min intervals for a further 10 min. Results. Priming subjects did not elevate symptom ratings; therefore, the data were pooled and 16 symptoms were found to increase significantly. The majority of symptoms dissipated rapidly, within 6 min after viewing. Frequency of endorsement data showed that approximately half of the symptoms on the pilot questionnaire could be discarded because <20% of subjects experienced them. Conclusions. Symptom questionnaires to investigate virtual reality viewing can be administered before viewing, without biasing the findings, allowing calculation of the amount of change from pre- to postviewing. However, symptoms dissipate rapidly and assessment of symptoms needs to occur in the first 5 min postviewing. Thirteen symptom questions, eight nonocular and five ocular, were determined to be useful for a questionnaire specifically related to virtual reality viewing using a head-mounted display.

Implementing an agent-based model with a spatial visual display in discrete-event simulation software

There has been an increasing interest in the use of agent-based simulation and some discussion of the relative merits of this approach as compared to discrete-event simulation. There are differing views on whether an agent-based simulation offers capabilities that discrete-event cannot provide or whether all agent-based applications can at least in theory be undertaken using a discrete-event approach. This paper presents a simple agent-based NetLogo model and corresponding discrete-event versions implemented in the widely used ARENA software. The two versions of the discrete-event model presented use a traditional process flow approach normally adopted in discrete-event simulation software and also an agent-based approach to the model build. In addition a real-time spatial visual display facility is provided using a spreadsheet platform controlled by VBA code embedded within the ARENA model. Initial findings from this investigation are that discrete-event simulation can indeed be used to implement agent-based models and with suitable integration elements such as VBA provide the spatial displays associated with agent-based software.

Conformational analysis of the natural iron chelator myo-inositol 1,2,3-trisphosphate using a pyrene-based fluorescent mimic

myo-Inositol phosphates possessing the 1,2,3-trisphosphate motif share the remarkable ability to completely inhibit iron-catalysed hydroxyl radical formation. The simplest derivative, myo-inositol 1,2,3-trisphosphate [Ins(1,2,3)P3], has been proposed as an intracellular iron chelator involved in iron transport. The binding conformation of Ins(1,2,3)P3 is considered to be important to complex Fe3+ in a 'safe' manner. Here, a pyrene-based fluorescent probe, 4,6-bispyrenoyl-myo-inositol 1,2,3,5-tetrakisphosphate [4,6-bispyrenoyl Ins(1,2,3,5)P4], has been synthesised and used to monitor the conformation of the 1,2,3-trisphosphate motif using excimer fluorescence emission. Ring-flip of the cyclohexane chair to the penta-axial conformation occurs upon association with Fe3+, evident from excimer fluorescence induced by π-π stacking of the pyrene reporter groups, accompanied by excimer formation by excitation at 351 nm. This effect is unique amongst biologically relevant metal cations, except for Ca 2+ cations exceeding a 1:1 molar ratio. In addition, the thermodynamic constants for the interaction of the fluorescent probe with Fe3+ have been determined. The complexes formed between Fe 3+ and 4,6-bispyrenoyl Ins(1,2,3,5)P4 display similar stability to those formed with Ins(1,2,3)P3, indicating that the fluorescent probe acts as a good model for the 1,2,3-trisphosphate motif. This is further supported by the antioxidant properties of 4,6-bispyrenoyl Ins(1,2,3,5)P4, which closely resemble those obtained for Ins(1,2,3)P3. The data presented confirms that Fe3+ binds tightly to the unstable penta-axial conformation of myo-inositol phosphates possessing the 1,2,3-trisphosphate motif. © 2010 The Royal Society of Chemistry.

The integration of ProxiMAX randomisation with CIS display for the production of novel peptides

Saturation mutagenesis is a powerful tool in modern protein engineering, which permits key residues within a protein to be targeted in order to potentially enhance specific functionalities. However, the creation of large libraries using conventional saturation mutagenesis with degenerate codons (NNN or NNK/S) has inherent redundancy and consequent disparities in codon representation. Therefore, both chemical (trinucleotide phosphoramidites) and biological methods (sequential, enzymatic single codon additions) of non-degenerate saturation mutagenesis have been developed in order to combat these issues and so improve library quality. Large libraries with multiple saturated positions can be limited by the method used to screen them. Although the traditional screening method of choice, cell-dependent methods, such as phage display, are limited by the need for transformation. A number of cell-free screening methods, such as CIS display, which link the screened phenotype with the encoded genotype, have the capability of screening libraries with up to 1014 members. This thesis describes the further development of ProxiMAX technology to reduce library codon bias and its integration with CIS display to screen the resulting library. Synthetic MAX oligonucleotides are ligated to an acceptor base sequence, amplified, and digested, subsequently adding a randomised codon to the acceptor, which forms an iterative cycle using the digested product of the previous cycle as the base sequence for the next. Initial use of ProxiMAX highlighted areas of the process where changes could be implemented in order to improve the codon representation in the final library. The refined process was used to construct a monomeric anti-NGF peptide library, based on two proprietary dimeric peptides (Isogenica) that bind NGF. The resulting library showed greatly improved codon representation that equated to a theoretical diversity of ~69%. The library was subsequently screened using CIS display and the discovered peptides assessed for NGF-TrkA inhibition by ELISA. Despite binding to TrkA, these peptides showed lower levels of inhibition of the NGF-TrkA interaction than the parental dimeric peptides, highlighting the importance of dimerization for inhibition of NGF-TrkA binding.