A novel experimental technique and its application to study the effects of particle density and flow submergence on bed particle saltation

This research was sponsored by EPSRC grant EP/G056404/1 which is greatly appreciated.Peer reviewedPublisher PD

Fractal Dimension and Localization of DNA Knots

The scaling properties of DNA knots of different complexities were studied by atomic force microscope. Following two different protocols DNA knots are adsorbed onto a mica surface in regimes of (i) strong binding, that induces a kinetic trapping of the three-dimensional (3D) configuration, and of (ii) weak binding, that permits (partial) relaxation on the surface. In (i) the gyration radius of the adsorbed DNA knot scales with the 3D Flory exponent $\nu\approx 0.58$ within error. In (ii), we find $\nu\approx 0.66$, a value between the 3D and 2D ($\nu=3/4$) exponents, indicating an incomplete 2D relaxation or a different polymer universality class. Compelling evidence is also presented for the localization of the knot crossings in 2D.Comment: 4 pages, 3 figure

Numerical study of linear and circular model DNA chains confined in a slit: metric and topological properties

Advanced Monte Carlo simulations are used to study the effect of nano-slit confinement on metric and topological properties of model DNA chains. We consider both linear and circularised chains with contour lengths in the 1.2--4.8 $\mu$m range and slits widths spanning continuously the 50--1250nm range. The metric scaling predicted by de Gennes' blob model is shown to hold for both linear and circularised DNA up to the strongest levels of confinement. More notably, the topological properties of the circularised DNA molecules have two major differences compared to three-dimensional confinement. First, the overall knotting probability is non-monotonic for increasing confinement and can be largely enhanced or suppressed compared to the bulk case by simply varying the slit width. Secondly, the knot population consists of knots that are far simpler than for three-dimensional confinement. The results suggest that nano-slits could be used in nano-fluidic setups to produce DNA rings having simple topologies (including the unknot) or to separate heterogeneous ensembles of DNA rings by knot type.Comment: 12 pages, 10 figure

Tourism policy and destination marketing in developing countries: the chain of influence

Tourism marketers including destination marketing organisations (DMOs) and international tour operators play a pivotal role in destination marketing, especially in creating destination images. These images, apparent in tourist brochures, are designed to influence tourist decision-making and behaviour. This paper proposes the concept of a “chain of influence” in destination marketing and image-making, suggesting that the content of marketing materials is influenced by the priorities of those who design these materials, e.g. tour operators and DMOs. A content analysis of 2,000 pictures from DMO and tour operator brochures revealed synergies and divergence between these marketers. The brochure content was then compared to the South African tourism policy, concluding that the dominant factor in the chain of influence in the South African context is in fact its organic image

Principles of Modular Tumor Therapy

Nature is interwoven with communication and is represented and reproduced through communication acts. The central question is how may multimodal modularly acting and less toxic therapy approaches, defined as modular therapies, induce an objective response or even a continuous complete remission, although single stimulatory or inhibitingly acting drugs neither exert mono-activity in the respective metastatic tumor type nor are they directed to potentially ‘tumor-specific’ targets. Modularity in the present context is a formal pragmatic communicative systems concept, describing the degree to which systems objects (cells, pathways etc.) may be communicatively separated in a virtual continuum, and recombined and rededicated to alter validity and denotation of communication processes in the tumor. Intentional knowledge, discharging in reductionist therapies, disregards the risk-absorbing background knowledge of the tumor’s living world including the holistic communication processes, which we rely on in every therapy. At first, this knowledge constitutes the validity of informative intercellular processes, which is the prerequisite for therapeutic success. All communication-relevant steps, such as intentions, understandings, and the appreciation of messages, may be modulated simultaneously, even with a high grade of specificity. Thus, modular therapy approaches including risk-absorbing and validity-modifying background knowledge may overcome reductionist idealizations. Modular therapies show modular events assembled by the tumor’s living world as an additional evolution-constituting dimension. This way, modular knowledge may be acquired from the environment, either incidentally or constitutionally. The new communicatively defined modular coherency of environment, i.e. the tumor-associated microenvironment, and tumor cells open novel ways for the scientific community in ‘translational medicine’

Target Site Recognition by a Diversity-Generating Retroelement

Diversity-generating retroelements (DGRs) are in vivo sequence diversification machines that are widely distributed in bacterial, phage, and plasmid genomes. They function to introduce vast amounts of targeted diversity into protein-encoding DNA sequences via mutagenic homing. Adenine residues are converted to random nucleotides in a retrotransposition process from a donor template repeat (TR) to a recipient variable repeat (VR). Using the Bordetella bacteriophage BPP-1 element as a prototype, we have characterized requirements for DGR target site function. Although sequences upstream of VR are dispensable, a 24 bp sequence immediately downstream of VR, which contains short inverted repeats, is required for efficient retrohoming. The inverted repeats form a hairpin or cruciform structure and mutational analysis demonstrated that, while the structure of the stem is important, its sequence can vary. In contrast, the loop has a sequence-dependent function. Structure-specific nuclease digestion confirmed the existence of a DNA hairpin/cruciform, and marker coconversion assays demonstrated that it influences the efficiency, but not the site of cDNA integration. Comparisons with other phage DGRs suggested that similar structures are a conserved feature of target sequences. Using a kanamycin resistance determinant as a reporter, we found that transplantation of the IMH and hairpin/cruciform-forming region was sufficient to target the DGR diversification machinery to a heterologous gene. In addition to furthering our understanding of DGR retrohoming, our results suggest that DGRs may provide unique tools for directed protein evolution via in vivo DNA diversification

Analysis of metallothionein and vimentin immunoreactivity in pharyngeal squamous cell carcinoma and its microenvironment

Metallothionein (MT) has been shown to have pro-proliferative anti-apoptotic activity and to be involved in microenvironment remodeling. The aim of this study has been to determine whether the changes in MT and vimentin immunoreactivity observed in cancer and its microenvironment are related to the local spread of the disease. The immunoreactivity levels of both MT and vimentin were evaluated together with CD56 and CD57 antigens in 49 tissue samples taken from patients with squamous cell carcinoma originating from the palatine tonsils and in 20 tissue samples derived from patients with chronic tonsillitis (the reference group). MT immunoreactivity levels were statistically significantly higher in the tissue samples from squamous cell carcinoma than in those of the reference group and also higher in the squamous cell carcinoma samples compared with the stromal samples. Moreover, stromal fibroblasts exhibited high vimentin and MT immunoreactivity levels. Statistically significantly higher MT immunoreactivity levels within the tumor cells were identified in patients with the presence of lymph node metastases in contrast to those patients without such metastases. Vimentin was detected in both the tumor and the stromal tissue samples and presented an interesting pattern of staining strongly expressed within the stroma and the septal architecture of the tumor. The number of CD56- and CD57-positive lymphocytes identified in tissue samples both from squamous cell carcinoma and from the stroma was statistically significantly lower than that in the reference group. MT expression by tumor cells is thus associated with an aggressive phenotype of the tumor and the ability to create metastases

Community engagement and professionalization: Emerging tensions

© 2019 by Emerald Publishing Limited. An increase in community engagement by governments across Australia’s three-tiered federal polity conforms to international trends. It represents a multidimensional institutionalization of participatory democracy designed to involve the public in decision-making. Increasingly, it is a practice which displays the markers of professionalization, including (self-described) professionals, professional associations and a code of ethics. The individuals who design, communicate, and facilitate community engagement are placed in a unique position, whereas most professions claim to serve both their client or employer and a greater public good, community engagement practitioners play these roles while also claiming to serve as “guardians” of democratic processes. Yet the claimed professionalization of community engagement is raising some questions: Is community engagement really a profession – and by what criteria ought this be assessed? What tensions do community engagement practitioners face by “serving multiple masters,” and how do they manage these? More pointedly, how can ethics inform our understanding of community engagement and its professionalization? This chapter examines the case for the practice of community engagement as a profession using Noordegraaf’s (2007) pillars of pure professionalism as a guide. It then explores some practical examples of the tensions practitioners may experience. The chapter concludes by reflecting on the future direction of community engagement given its positioning

The Involvement of RCAS1 in Creating a Suppressive Tumor Microenvironment in Patients with Salivary Gland Adenocarcinoma

The tumor microenvironment is the tissue that determines the growth and progression of the tumor as well as its ability to initiate metastases. The aim of the present study has been to evaluate the role of RCAS1 in creating the suppressive tumor microenvironment in cases of parotid adenocarcinoma. The tissue samples of salivary gland adenocarcinomas and their stroma and the palatine tonsils which constituted the reference tissue sample group were obtained during routine surgical procedures. The immunoreactivity of RCAS1, CD3, CD25, CD68, CD69, and Foxp3 antigens was then evaluated by using the immunohistochemistry method. The patient’s consent was obtained in each case. A statistically significantly higher RCAS1 immunoreactivity level was found in the adenocarcinoma tissue samples in comparison to that found in the stromal tissue samples. A statistically significantly higher RCAS1 immunoreactivity was also identified in the adenocarcinoma tissue samples derived from patients who had lymph node metastases in comparison to patients without such metastases. Additionally, we observed the presence of RCAS1-positive macrophages in the stromal tissue samples. The infiltration of CD68-positive cells was significantly stronger in the adenocarcinoma and stromal tissue slides than in the reference group tissue slides; moreover, the infiltration was a good deal more prominent in the stromal tissue than in the adenocarcinoma tissue. The CD68 immunoreactivity levels in both the tumor and stromal tissue samples were found to be significantly higher in those patients who had lymph node metastases than in the patients without such metastases. Additionally, the infiltration of CD3- and CD25-positive cells was more prominent in the reference tissue slides than in the adenocarcinoma and stromal tissue slides, and was stronger in the adenocarcinoma tissue than in the stromal tissue. Furthermore, the infiltration of Foxp3-positive cells was seen exclusively in the stroma whereas it was not even detected in the adenocarcinoma tissue. Lastly, the Foxp3-positive cell infiltration was more prominent in the stromal tissue than in the reference group tissue. The present study demonstrates that RCAS1 expression by both tumor cells and tumor-associated macrophages may participate in creating the immunosuppressive microenvironment in parotid gland adenocarcinoma, thus promoting tumor development as well as metastases