Glass and place: using properties of the one to reflect (on) qualities of the other: an effort of attention

Everything that happens takes place somewhere, in a particular physical or cultural space. The character of a place is constituted, its distinctive timbre generated, by the constellations of events occurring in it and how those blend, interweave and play out over time. Such textural qualities infuse and inform our experience of places, they shape our ‘knowing’ at a visceral level that goes unnoticed in our ordinary lives. Our conscious awareness of the places and spaces we visit and inhabit is filtered by our interests, honed through habit, marshalled and constrained by conventional perceptions of what matters. The contingent qualities of places beyond the purposes they serve for us are rarely considered and harder to attend to. But if we want to appreciate the world in its own right, not just in ours, finding ways to do so seems worthwhile. Artists adopt a variety of strategies to penetrate beyond the more obvious features of place. Some seek estrangement through the systematic application of arbitrary rules, others through strenuous efforts of will. I use ways of looking and thinking that are grounded in my experience of training as a glassmaker and developed using photography and video. My approach employs a broadly defined ‘glass sensibility’ that encompasses both the physical abilities of glass to mediate visual perception and their metaphorical correlates as shapers of ideas. My mode of enquiry is the essay, a flexible and open-­‐ended form of reflexive investigation that is highly attentive and responsive to its subject matter, and follows where that leads. But unlike other essayists who pursue their trains of thought in lines of words, my attempts at understanding are more visual. I explore my chosen places -­‐ a bus, a train, a road junction, a kitchen, a forest, a park, a desert -­‐ by spending periods of time in them doing whatever being there generally involves whilst also noticing how things happen and taking photographs. What I’m looking out for are telling facets, small examples of conjunctions of events which I can somehow ‘cut and polish’ at the critical angle that aids transparency, letting light in on the intrinsic character of the place and making it sparkle. The substantive outcomes of these essays are new awarenesses that bypass language; but each is accompanied and supported in the thesis by a textual account of how it came about. The contributions made by this thesis are three-­‐fold: It expands the repertoire of strategies for appreciating place, develops a novel understanding of how glass-­‐based thinking may inform processes of exploration and offers a new, more literal, version of essayistic reflection

Gleason Grade 4 Prostate Adenocarcinoma Patterns: An Inter-observer Agreement Study among Genitourinary Pathologists

Aims To assess the interobserver reproducibility of individual Gleason grade 4 growth patterns. Methods and results Twenty-three genitourinary pathologists participated in the evaluation of 60 selected high-magnification photographs. The selection included 10 cases of Gleason grade 3, 40 of Gleason grade 4 (10 per growth pattern), and 10 of Gleason grade 5. Participants were asked to select a single predominant Gleason grade per case (3, 4, or 5), and to indicate the predominant Gleason grade 4 growth pattern, if present. ‘Consensus’ was defined as at least 80% agreement, and ‘favoured’ as 60–80% agreement. Consensus on Gleason grading was reached in 47 of 60 (78%) cases, 35 of which were assigned to grade 4. In the 13 non-consensus cases, ill-formed (6/13, 46%) and fused (7/13, 54%) patterns were involved in the disagreement. Among the 20 cases where at least one pathologist assigned the ill-formed growth pattern, none (0%, 0/20) reached consensus. Consensus for fused, cribriform and glomeruloid glands was reached in 2%, 23% and 38% of cases, respectively. In nine of 35 (26%) consensus Gleason grade 4 cases, participants disagreed on the growth pattern. Six of these were characterized by large epithelial proliferations with delicate intervening fibrovascular cores, which were alternatively given the designation fused or cribriform growth pattern (‘complex fused’). Conclusions Consensus on Gleason grade 4 growth pattern was predominantly reached on cribriform and glomeruloid patterns, but rarely on ill-formed and fused glands. The complex fused glands seem to constitute a borderline pattern of unknown prognostic significance on which a consensus could not be reached

AMPK negatively regulates tensin-dependent integrin activity

Tight regulation of integrin activity is paramount for dynamic cellular functions such as cell matrix adhesion and mechanotransduction. Integrin activation is achieved through intracellular interactions at the integrin cytoplasmic tails and through integrin-ligand binding. In this study, we identify the metabolic sensor AMP-activated protein kinase (AMPK) as a beta 1-integrin inhibitor in fibroblasts. Loss of AMPK promotes beta 1-integrin activity, the formation of centrally located active beta 1-integrin- and tensin-rich mature fibrillar adhesions, and cell spreading. Moreover, in the absence of AMPK, cells generate more mechanical stress and increase fibronectin fibrillogenesis. Mechanistically, we show that AMPK negatively regulates the expression of the integrin-binding proteins tensin1 and tensin3. Transient expression of tensins increases beta 1-integrin activity, whereas tensin silencing reduces integrin activity in fibroblasts lacking AMPK. Accordingly, tensin silencing in AMPK-depleted fibroblasts impedes enhanced cell spreading, traction stress, and fibronectin fiber formation. Collectively, we show that the loss of AMPK up-regulates tensins, which bind beta 1-integrins, supporting their activity and promoting fibrillar adhesion formation and integrin-dependent processes.Peer reviewe

Biokinetic processes of extracellular polysaccharide (EPS) stabilization of surface soils against dust generation

Extracellular polysaccharide produced by a copiotrophic and nonpathogenic bacteria, Arthrobacter viscosus, promises to be an effective alternative to the use of chemical substances in dust control on exposed soil surfaces. The feasibility of this biokinetic stabilization approach to dust control depends in part on the capacity of injected microbes to produce EPS that can increase the resistance of soil to drying (desiccation) stresses. Initial laboratory based biokinetic investigations were performed to determine the rate of EPS production by Arthrobacter viscosus in both Haggstrom media (EPS production media) and sterilized samples of silty clay, sandy clay, and sandy silty clay soils and the effects of EPS on dusting resistance indices such as cohesion and retention of intergranular pore liquid. To achieve this objective, both Haggstrom media and the soil samples were inoculated with nutrient broth (20 to 100 ml/mL of Haggstrom media) containing Arthrobacter viscosus and changes in dusting resistance indices (soil cohesion, frictional resistance, and desiccation rate) in response to EPS growth were monitored. It was initially determined through tests that an optimum EPS quantity of 12.5 g/mL of Haggstrom media is produced by microbial broth concentration of 60 ml/mL of Haggstrom media. EPS-CM production rate in soil after initial injection of microbial broth concentrations (5 to 25 mL/g of soil) was tracked using thermogravimetric analysis (TGA), which has been shown to be an effective tool in determining the thermal decomposition of polymeric materials mixed with other composites. TGA results indicate that optimum EPS production in silty clay soil samples occurs at between 48 and 72 hr i after soil injection with the highest EPS quantity determined to be 3.8 mg/mg of soil observed when a microbial broth concentration of 20 mL/g of soil is used. In sandy clay and sandy silty clay soils, EPS quantity of 2.5 mg/mg of soil and 3.3 mg/mg of soil occurred in both soils respectively. To further investigate the effectiveness of EPS-CM in surface soil stabilization against dust generation, a direct application of different concentrations (5 to 25 mL/g of soil) of extracted EPS from the Haggstrom media and an indirect application of extracellular polysaccharide-Culture Media (EPS-CM) to the soil through injection of microbial broth with cells of different concentrations (5 to 25 ml/g of soil) for in situ EPS production with time were compared using deionized water as control. Three soil mixes were used, which include silty clay soil (original sample), sandy clay soil, and sandy silty clay soil were prepared from the sieve analyses of the soil samples collected. As part of the characterization of these soil samples, their specific 22 surface areas were determined to be 8.397 m /g for silty clay soil; 8.121 m /g for sandy 2 clay soil; and 8.193 m /g for sandy silty clay soil. As an indirect measurement of the potential resistance of the stabilized soil to in situ stresses that can be caused by drying, direct shear and unconfined compression tests were performed on replicates of the treated soil samples. The equations developed in chapter 2 to compare the effects of EPS-CM treatment of soil friability indices, deformation resistance indices, coefficient of soil failure, and effective porosity were evaluated in chapter 8. The results of unconfined compression tests show that in EPS-CM amended silty clay soil samples, a strain of 0.34 to 0.20 from day 1 to day 3 occurred at EPS-CM concentration of 5 mL/g of soil but at higher EPS-CM concentrations, soil strain is observed to fluctuate with time. The least strain (0.25) occurs in silty clay soils treated ii with EPS-CM concentration of 25 mL/g of soil compared to sandy clay and sandy silty clay soils. Thus soils with higher specific surface and clay minerals can develop cohesion more effectively than coarser-grained soils following EPS-CM amendment. Desiccation tests performed on treated and control soil samples at 34 % relative o humidity and temperature of 37 C show that soil liquid content decreases with time. At relatively high EPS-CM concentrations of 15 to 25 mL/g of soil, EPS-CM-amended silty clay soils retain 5 % more liquid with time than sandy clay and silty clay soils. Fluorescence microscopic imaging of the treated soil samples clearly show the presence of EPS-CM as intergranular pore material and as smears on soil particles in EPS-CM- amended and microbial broth-amended soil samples whereas they are absent in the control samples. The effects of EPS-CM amendment of the following selected indices of soil resistance to dust generation from exposed ground surfaces were investigated (soil cohesion, frictional resistance, effective porosity, desiccation rate). Data show that effective porosity in EPS-CM amended silty clay soil decreases with time due to continued EPS production by A. viscosus while changes in effective porosity with time in sandy clay and sandy silty clay fluctuated with time and EPS-CM production. After a 21- day monitoring with sampling at three 7-day intervals, unconfined compression and 2 direct shear tests indicate that increase in cohesion from 37 to 45 kN/m occurs in EPS- CM-amended silty clay soil at EPS-CM concentrations ranging 5 to 25 mL/g of soil. In 2 sandy clay and sandy silty clay soils, maximum cohesion levels of 27 kN/m and 24 2 kN/m were observed, respectively, for the same EPS-CM concentrations within this 2 sampling time while control samples show cohesion increments of only 0 to 15 kN/m . Generally, it is observed that despite cyclical fluctuations in EPS-CM content in response to microbial dynamics in soil, frictional resistance decreases with increase in concentration of EPS-CM. Thus EPS-CM increase in intergranular pore space reduces intergranular friction but enhances cohesion within an overall increase in shear strength especially in fine grained soils that are prone to dusting. Liquid retention capacity, which is known to affect dust generation, improves favorably in EPS-CM-amended soils. With respect to practical use of duct control in the field, this research indicates that mixing of EPS-CM with microbial broth and scarified soil surfaces before compaction can be effective

A theoretical model of inflammation- and mechanotransduction- driven asthmatic airway remodelling

Inflammation, airway hyper-responsiveness and airway remodelling are well-established hallmarks of asthma, but their inter-relationships remain elusive. In order to obtain a better understanding of their inter-dependence, we develop a mechanochemical morphoelastic model of the airway wall accounting for local volume changes in airway smooth muscle (ASM) and extracellular matrix in response to transient inflammatory or contractile agonist challenges. We use constrained mixture theory, together with a multiplicative decomposition of growth from the elastic deformation, to model the airway wall as a nonlinear fibre-reinforced elastic cylinder. Local contractile agonist drives ASM cell contraction, generating mechanical stresses in the tissue that drive further release of mitogenic mediators and contractile agonists via underlying mechanotransductive signalling pathways. Our model predictions are consistent with previously described inflammation-induced remodelling within an axisymmetric airway geometry. Additionally, our simulations reveal novel mechanotransductive feedback by which hyper-responsive airways exhibit increased remodelling, for example, via stress-induced release of pro-mitogenic and procontractile cytokines. Simulation results also reveal emergence of a persistent contractile tone observed in asthmatics, via either a pathological mechanotransductive feedback loop, a failure to clear agonists from the tissue, or a combination of both. Furthermore, we identify various parameter combinations that may contribute to the existence of different asthma phenotypes, and we illustrate a combination of factors which may predispose severe asthmatics to fatal bronchospasms

Effects of maternal, gestational, and perinatal variables on neonatal line width observed in a modern UK birth cohort

OBJECTIVES: The objective of this study was to explore potential relationships between neonatal line (NNL) width and early life history variables such as maternal health, gestation, the birth process, and perinatal health. MATERIALS AND METHODS: Histological thin sections of deciduous canines were studied from 71 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). The width of the NNL was measured in three locations on the tooth crown using spatial mapping techniques (ArcGIS) from digital images from an Olympus VS-120 microscope. Life history variables were collected prospectively through a combination of clinical observations and questionnaires. RESULTS: Infants born late term or post term had narrower neonatal lines than those born prematurely or at full term. Infants born in Autumn (September to November) had narrower NNLs than those born at other times of year. NNLs in infants born to mothers with hypertension were wider than those without. Infants resuscitated at birth or born to obese mothers had narrower NNLs than those that were not. There was no association between NNL width and either the type or duration of delivery. DISCUSSION: The NNL in enamel is an irregular accentuated line, but the factors underlying its formation and width remain unclear. In contrast to some previous studies, we found no association between wider NNLs and long or difficult births. Instead, we found that the width of the neonatal line NNL varied in relation to parameters that reflected the prenatal environment and length of gestation

Differences in Salmonella enterica serovar Typhimurium strain invasiveness are associated with heterogeneity in SPI-1 gene expression

Most studies on Salmonella enterica serovar Typhimurium infection focus on strains ATCC SL1344 or NTCC 12023 (ATCC 14028). We have compared the abilities of these strains to induce membrane ruffles and invade epithelial cells. S. Typhimurium strain 12023 is less invasive and induces smaller membrane ruffles on MDCK cells compared with SL1344. Since the SPI-1 effector SopE is present in SL1344 and absent from 12023, and SL1344 sopE mutants have reduced invasiveness, we investigated whether 12023 is less invasive due to the absence of SopE. However, comparison of SopE+ and SopE− S. Typhimurium strains, sopE deletion mutants and 12023 expressing a sopE plasmid revealed no consistent relationship between SopE status and relative invasiveness. Nevertheless, absence of SopE was closely correlated with reduced size of membrane ruffles. A PprgH–gfp reporter revealed that relatively few of the 12023 population (and that of the equivalent strain ATCC 14028) express SPI-1 compared to other S. Typhimurium strains. Expression of a PhilA–gfp reporter mirrored that of PprgH–gfp in 12023 and SL1344, implicating reduced signalling via the transcription factor HilA in the heterogeneous SPI-1 expression of these strains. The previously unrecognized strain heterogeneity in SPI-1 expression and invasiveness has important implications for studies of Salmonella infection

Autism diagnosis differentiates neurophysiological responses to faces in adults with tuberous sclerosis complex

- Background: Autism spectrum disorder (ASD) is a common and highly heritable neurodevelopmental disorder that is likely to be the outcome of complex aetiological mechanisms. One strategy to provide insight is to study ASD within tuberous sclerosis complex (TSC), a rare disorder with a high incidence of ASD, but for which the genetic cause is determined. Individuals with ASD consistently demonstrate face processing impairments, but these have not been examined in adults with TSC using event-related potentials (ERPs) that are able to capture distinct temporal stages of processing. - Methods: For adults with TSC (n = 14), 6 of which had a diagnosis of ASD, and control adults (n = 13) passively viewed upright and inverted human faces with direct or averted gaze, with concurrent EEG recording. Amplitude and latency of the P1 and N170 ERPs were measured. - Results: Individuals with TSC + ASD exhibited longer N170 latencies to faces compared to typical adults. Typical adults and adults with TSC-only exhibited longer N170 latency to inverted versus upright faces, whereas individuals with TSC + ASD did not show latency differences according to face orientation. In addition, individuals with TSC + ASD showed increased N170 latency to averted compared to direct gaze, which was not demonstrated in typical adults. A reduced lateralization was shown for the TSC + ASD groups on P1 and N170 amplitude. - Conclusions: The findings suggest that individuals with TSC + ASD may have similar electrophysiological abnormalities to idiopathic ASD and are suggestive of developmental delay. Identifying brain-based markers of ASD that are similar in TSC and idiopathic cases is likely to help elucidate the risk pathways to ASD