Highly efficient neural differentiation of human somatic stem cells, isolated by minimally invasive periodontal surgery

Neural stem cells (NSCs) are potential sources for cell therapy of neurodegenerative diseases and for drug screening. Despite their potential benefits, ethical and practical considerations limit the application of NSCs derived from human embryonic stem cells (ES) or adult brain tissue. Thus, alternative sources are required to satisfy the criteria of ready accessibility, rapid expansion in chemically defined media and reliable induction to a neuronal fate. We isolated somatic stem cells from the human periodontium that were collected during minimally invasive periodontal access flap surgery as part of guided tissue regeneration therapy. These cells could be propagated as neurospheres in serum-free medium, which underscores their cranial neural crest cell origin. Culture in the presence of epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2) under serum-free conditions resulted in large numbers of nestin-positive/Sox-2-positive NSCs. These periodontium-derived (pd) NSCs are highly proliferative and migrate in response to chemokines that have been described as inducing NSC migration. We used immunocytochemical techniques and RT-PCR analysis to assess neural differentiation after treatment of the expanded cells with a novel induction medium. Adherence to substrate, growth factor deprivation, and retinoic acid treatment led to the acquisition of neuronal morphology and stable expression of markers of neuronal differentiation by more than 90% of the cells. Thus, our novel method might provide nearly limitless numbers of neuronal precursors from a readily accessible autologous adult human source, which could be used as a platform for further experimental studies and has potential therapeutic implications.

Prolonged cultivation of hippocampal neural precursor cells shifts their differentiation potential and selects for aneuploid cells

Neural precursor cells (NPCs) are lineage-restricted neural stem cells with limited self-renewal, giving rise to a broad range of neural cell types such as neurons, astrocytes, and oligodendrocytes. Despite this developmental potential, the differentiation capacity of NPCs has been controversially discussed concerning the trespassing lineage boundaries, for instance resulting in hematopoietic competence. Assessing their in vitro plasticity, we isolated nestin+/Sox2+, NPCs from the adult murine hippocampus. In vitro-expanded adult NPCs were able to form neurospheres, self-renew, and differentiate into neuronal, astrocytic, and oligodendrocytic cells. Although NPCs cultivated in early passage efficiently gave rise to neuronal cells in a directed differentiation assay, extensively cultivated NPCs revealed reduced potential for ectodermal differentiation. We further observed successful differentiation of long-term cultured NPCs into osteogenic and adipogenic cell types, suggesting that NPCs underwent a fate switch during culture. NPCs cultivated for more than 12 passages were aneuploid (abnormal chromosome numbers such as 70 chromosomes). Furthermore, they showed growth factor-independent proliferation, a hallmark of tumorigenic transformation. In conclusion, our findings substantiate the lineage restriction of NPCs from adult mammalian hippocampus. Prolonged cultivation results, however, in enhanced differentiation potential, which may be attributed to transformation events leading to aneuploid cells.

Interaction of adult human neural crest-derived stem cells with a nanoporous titanium surface is sufficient to induce their osteogenic differentiation

Osteogenic differentiation of various adult stem cell populations such as neural crest-derived stem cells is of great interest in the context of bone regeneration. Ideally, exogenous differentiation should mimic an endogenous differentiation process, which is partly mediated by topological cues. To elucidate the osteoinductive potential of porous substrates with different pore diameters (30 nm, 100 nm), human neural crest-derived stem cells isolated from the inferior nasal turbinate were cultivated on the surface of nanoporous titanium covered membranes without additional chemical or biological osteoinductive cues. As controls, flat titanium without any topological features and osteogenic medium was used. Cultivation of human neural crest-derived stem cells on 30 nm pores resulted in osteogenic differentiation as demonstrated by alkaline phosphatase activity after seven days as well as by calcium deposition after 3 weeks of cultivation. In contrast, cultivation on flat titanium and on membranes equipped with 100 nm pores was not sufficient to induce osteogenic differentiation. Moreover, we demonstrate an increase of osteogenic transcripts including Osterix, Osteocalcin and up-regulation of Integrin β1 and α2 in the 30 nm pore approach only. Thus, transplantation of stem cells pre-cultivated on nanostructured implants might improve the clinical outcome by support of the graft adherence and acceleration of the regeneration process.

Typographic meaning: readers’ impressions of patterns of typographic differentiation

This research explores whether patterns of typographic differentiation influence readers’ impressions of documents. It develops a systematic approach to typographic investigation that considers relationships between different kinds of typographic attributes, rather than testing the influence of isolated variables. An exploratory study using multiple sort tasks and semantic differential scales identifies that readers form a variety of impressions in relation to how typographic elements are differentiated in document design. Building on the findings of the exploratory study and analysis of a sample of magazines, the research describes three patterns of typographic differentiation: high, moderate, and low. Each pattern comprises clusters of typographic attributes and organisational principles that are articulated in relation to a specified level of typographic differentiation (amplified, medium, or subtle). The patterns are applied to two sets of controlled test material. Using this purposely-designed material, the influence of patterns of typographic differentiation on readers’ impressions of documents is explored in a repertory grid analysis and a paired comparison procedure. The results of these studies indicate that patterns of typographic differentiation consistently shape readers’ impressions of documents, influencing judgments of credibility, document address, and intended readership; and suggesting particular kinds of engagement and genre associations. For example, high differentiation documents are likely to be considered casual, sensationalist, and young; moderate differentiation documents are most likely to be seen as formal and serious; and low differentiation examples are considered calm. Typographic meaning is shown to be created through complex, yet systematic, interrelationships rather than reduced to a linear model of increasing or decreasing variation. The research provides a way of describing typographic articulation that has application across a variety of disciplines and design practice. In particular, it illuminates the ways in which typographic presentation is meaningful to readers, providing knowledge that document producers can use to communicate more effectively.

Investigating readers’ impressions of typographic differentiation using repertory grids

Document designers combine a range of stylistic and structural typographic attributes to articulate and differentiate information for readers. This paper explores how the kind of typographic differentiation used in a document influences readers’ impressions of documents. A preliminary study indicated that three patterns of typographic differentiation (high, moderate and low) might underlie participants’ impressions of magazine design. Subsequently, a set of nine magazine layouts with controlled content was purposefully developed to systematically examine the impact of high, moderate and low patterns of typographic differentiation on participants’ impressions of documents. These documents were used in a repertory grid procedure to investigate the kind of impressions readers articulate in relation to typographic presentation and whether readers are likely to formulate similar or differing impressions from high, moderate, and low patterns of typographic differentiation. The results suggest that typographic differentiation influences a range of rhetorical and experiential judgments. For example, participants described high differentiation documents as the most attention-grabbing and easy to skim-read, while they considered moderate and low differentiation documents to require deeper reading strategies. In addition, participants assumed high differentiation documents to be much more sensationalist than moderate or low differentiation documents, which they generally perceived as authoritative and credible.

Parametrizing the horizontal inhomogeneity of ice water content using CloudSat data products

In order to calculate unbiased microphysical and radiative quantities in the presence of a cloud, it is necessary to know not only the mean water content but also the distribution of this water content. This article describes a study of the in-cloud horizontal inhomogeneity of ice water content, based on CloudSat data. In particular, by focusing on the relations with variables that are already available in general circulation models (GCMs), a parametrization of inhomogeneity that is suitable for inclusion in GCM simulations is developed. Inhomogeneity is defined in terms of the fractional standard deviation (FSD), which is given by the standard deviation divided by the mean. The FSD of ice water content is found to increase with the horizontal scale over which it is calculated and also with the thickness of the layer. The connection to cloud fraction is more complicated; for small cloud fractions FSD increases as cloud fraction increases while FSD decreases sharply for overcast scenes. The relations to horizontal scale, layer thickness and cloud fraction are parametrized in a relatively simple equation. The performance of this parametrization is tested on an independent set of CloudSat data. The parametrization is shown to be a significant improvement on the assumption of a single-valued global FSD

Subsurface urban heat island and its effects on horizontal ground-source heat pump potential under climate change

Recent urban air temperature increase is attributable to the climate change and heat island effects due to urbanization. This combined effects of urbanization and global warming can penetrate into the underground and elevate the subsurface temperature. In the present study, over-100 years measurements of subsurface temperature at a remote rural site were analysed, and an increasing rate of 0.17⁰C per decade at soil depth of 30cm due to climate change was identified in the UK, but the subsurface warming in an urban site showed a much higher rate of 0.85⁰C per decade at a 30cm depth and 1.18⁰C per decade at 100cm. The subsurface urban heat island (SUHI) intensity obtained at the paired urban-rural stations in London showed an unique 'U-shape', i.e. lowest in summer and highest during winter. The maximum SUHII is 3.5⁰C at 6:00 AM in December, and the minimum UHII is 0.2⁰C at 18:00PM in July. Finally, the effects of SUHI on the energy efficiency of the horizontal ground source heat pump (GSHP) were determined. Provided the same heat pump used, the installation at an urban site will maintain an overall higher COP compared with that at a rural site in all seasons, but the highest COP improvement can be achieved in winter.

Collusion in a Bertrand duopoly model with decreasing returns and product differentiation

We study cartel stability in a differentiated price-setting duopoly with returns to scale. We show that a cartel may be equally stable in the presence of lower differentiation, provided that the decreasing returns parameter is high. In addition we demonstrate that for a given factor of discount, there are technologies that can have decreasing returns to scale where the cartel always is stable independent of the differentiation degree.

“Action Research into Pre-sessional Students' Differentiation of Assessments: Using Findings to Improve Courses”

Conference proceedings papaer in Whong, M. (Ed.), Proceedings of the 2007 BALEAP conference: English in a globalising world: English as an academic lingua franca,. Bern: Peter Lang.

The horizontal spread of a vertical malady: cosmopolitanism and history in Pernambuco’s recent cinematic sensation

Brazil’s recent cinematic sensation, O som ao redor/Neighboring Sounds (Kleber Mendonça Filho, 2012), displays an effective integration of form and content, as exemplified by its vertical figuration that crystallizes the devastating effects of property development and global capitalism. This chapter will attempt to unravel a two-way drive within this vertical motif: a movement off the ground, resulting in global cosmopolitanism; and another into the ground, in search of the social history and film history at its base. As I hope to demonstrate, despite the characters’ late postmodernist disconnect from local context and history, O som ao redor offers a perspicacious insight into regional and national history that contributes an original and exciting addition to Brazilian and world cinema.

Sahel decadal rainfall variability and the role of model horizontal resolution

Substantial low-frequency rainfall fluctuations occurred in the Sahel throughout the twentieth century, causing devastating drought. Modeling these low-frequency rainfall fluctuations has remained problematic for climate models for many years. Here we show using a combination of state-of-the-art rainfall observations and high-resolution global climate models that changes in organized heavy rainfall events carry most of the rainfall variability in the Sahel at multiannual to decadal time scales. Ability to produce intense, organized convection allows climate models to correctly simulate the magnitude of late-twentieth century rainfall change, underlining the importance of model resolution. Increasing model resolution allows a better coupling between large-scale circulation changes and regional rainfall processes over the Sahel. These results provide a strong basis for developing more reliable and skilful long-term predictions of rainfall (seasons to years) which could benefit many sectors in the region by allowing early adaptation to impending extremes.

Differentiation in populations of the apple scab fungus Venturia inaequalis on cultivars in a mixed orchard remains over time

The ascomycete Venturia inaequalis causes annual epidemics of apple scab worldwide. Scab development is reduced in mixed cultivar orchards compared with monocultures. To use mixtures in commercial production, we need to understand how the population of scab changes in a mixed orchard and how likely a super race, with virulence factors overcoming multiple resistance factors in the mixed orchard, is to emerge and become dominant. We used short sequence repeat (SSR) markers to investigate the temporal change of scab populations in two mixed cultivar orchards in the UK to infer the likelihood of emergence of a scab super race. There were no significant differences between the populations at the two sampling times (six or seven years apart) in either of the two mixed orchards. In one of the orchards apple scab populations on different cultivars were significantly different and the differences did not diminish over time. These results suggest that it is not inevitable that a super race of V. inaequalis will become dominant during the lifetime of a commercial apple orchard.

Differentiation of neotropical ecosystems by modern soil phytolith assemblages and its implications for palaeoenvironmental and archaeological reconstructions II: Southwestern Amazonian forests

Accurate archaeological and palaeoenvironmental reconstructions using phytoliths relies on the study of modern reference material. In eastern Acre, Brazil, we examined whether the five most common forest types present today were able to be differentiated by their soil phytolith assemblages, and thus provide analogues with which to compare palaeoecological assemblages from pre-Columbian earthwork sites in the region. Surface soils and vegetation from dense humid evergreen forest, dense humid evergreen forest with high palm abundance, palm forest, bamboo forest and fluvial forest were sampled and their phytoliths analysed. Relative phytolith frequencies were statistically compared using Principal Components Analyses (PCAs). We found the major differences in species composition to be well-represented by the phytolith assemblages as all forest types, apart from the two sub-types of dense humid evergreen forest, could be differentiated. Larger phytoliths from the sand fraction were found to be more ecologically diagnostic than those from the silt fraction. The surface soil phytolith assemblages we analysed can therefore be used as analogues to improve the accuracy of archaeological and palaeoecological reconstructions in the region.

Investigating typographic differentiation: italics are more subtle than bold for emphasis

Text designers are likely to benefit from guidance on how to use typographic differentiation for emphasis. Three experiments use purposely-designed fonts to explore the size and nature of differences in the stylistic characteristics of fonts (weight, width, contrast, italic) which affect letter identification. Results indicate that words set in bold and expanded fonts, when alternated with words set in a Neutral test font, may impair performance, whereas changing to italic does not. Possible explanations are explored through measuring the physical and perceptual similarities of the test fonts.