Structural behaviour of glass reinforced plastics

The aim of this research is to promote the use of G.R.P. as a structural material. In the past, the use of G.R.P. has been confined to non-load carrying applications. Such uses are still rapidly increasing but in addition significant changes have been made during the last decade in the development of semi-structural and now even fully structural applications. Glass-reinforced plastic is characterized by a high strength but a relatively low modulus of elasticity. For this reasona G.R.P. structure can expect to show large deformations as a result of which the individual structural members will fail under load due to a loss of stability rather than approaching the ultimate strength of the material. For this reason the selection of the geometrical shapes of G.R.P. structural elements is considered to be an important factor in designing G.R.P. structures. The first chapter of this thesis deals with a general review of the theoretical and experimental methods used to describe the structural properties of G.R.P. The research programme includes five stages dealing with the structural behaviour of G.R.P. The first stage (Chapter 2) begins with selecting and designing an optimum box beam cross-section which gives the maximum flexural and torsional rigidity. The second stage of investigation (Chapter 3) deals with beam to beam connections. A joint was designed and manufactured with different types of fasteners used to connect two beam units. A suitable fastener was selected and the research extended to cover the behaviour of long span beams using multiple joints. The third part of the investigation includes a study of the behaviour of box beams subjected to combined bending, shear and torsion. A special torque rig was developed to perform the tests. Creep deformation of 6 m span G.R.P. was investigated as the fourth stage under a range of loading conditions. As a result of the phenomenon of post buckling behaviour exhibited in the compression flange during testing of box beams during earlier stages of the investigation it was decided to consider this phenomenon in more detail in the final stage of the investigation. G.R.P. plates with different fibre orientation were subjected to uniaxial compression and tested up to failure. In all stages of the investigation theoretical predictions and experimental results were compared and generally good correlation between theory and experimental data was observed.

Hypoxia-inducible factor (HIF) network:insights from mathematical models

Oxygen is a crucial molecule for cellular function. When oxygen demand exceeds supply, the oxygen sensing pathway centred on the hypoxia inducible factor (HIF) is switched on and promotes adaptation to hypoxia by up-regulating genes involved in angiogenesis, erythropoiesis and glycolysis. The regulation of HIF is tightly modulated through intricate regulatory mechanisms. Notably, its protein stability is controlled by the oxygen sensing prolyl hydroxylase domain (PHD) enzymes and its transcriptional activity is controlled by the asparaginyl hydroxylase FIH (factor inhibiting HIF-1).To probe the complexity of hypoxia-induced HIF signalling, efforts in mathematical modelling of the pathway have been underway for around a decade. In this paper, we review the existing mathematical models developed to describe and explain specific behaviours of the HIF pathway and how they have contributed new insights into our understanding of the network. Topics for modelling included the switch-like response to decreased oxygen gradient, the role of micro environmental factors, the regulation by FIH and the temporal dynamics of the HIF response. We will also discuss the technical aspects, extent and limitations of these models. Recently, HIF pathway has been implicated in other disease contexts such as hypoxic inflammation and cancer through crosstalking with pathways like NF?B and mTOR. We will examine how future mathematical modelling and simulation of interlinked networks can aid in understanding HIF behaviour in complex pathophysiological situations. Ultimately this would allow the identification of new pharmacological targets in different disease settings.

Dietary analysis and nutritional behaviour in people with and without age-related macular disease

Background and Aims: Consumption of antioxidant nutrients can reduce the risk of progression of age-related macular degeneration (AMD) - the leading cause of visual impairment in adults over the age of 50 years in the UK. Lutein and zeaxanthin (L&Z) are of particular interest because they are selectively absorbed by the central retina. The objectives of this study were to analyse the dietary intake of a group of AMD patients, assess their ability to prepare and cook healthy food, and to make comparisons with people not affected by AMD. Methods: 158 participants with AMD were recruited via the UK charity The Macular Society, and fifty participants without AMD were recruited from optometric practice. A telephone interview was conducted by trained workers where participants completed a 24 hour food diary, and answered questions about cooking and shopping capabilities. Results: In the AMD group, the average L&Z intake was low in for both males and females. Those able to cook a hot meal consumed significantly more L&Z than those who were not able. Most participants were not consuming the recommended dietary allowance of fibre, calcium, vitamin D and E, and calorific intake was also lower than recommendations for their age-group. The non-AMD group consumed more kilocalories and more nutrients than the AMD group, but the L&Z intake was similar to those with AMD. The main factor that influenced participant’s food choices was personal preference. Conclusion: For an ‘informed’ population, many AMD participants were under-consuming nutrients considered to be useful for their condition. Participants without AMD were more likely to reach recommended daily allowance values for energy and a range of nutrients. It is therefore essential to design more effective dietary education and dissemination methods for people with, and at risk of, AMD.

Time–Harmonic Behaviour of a Cracked Piezoelectric Solid by BIEM

ACM Computing Classification System (1998): J.2, G.1.9

Vállalati magatartás és túlélési esélyek a posztszocialista átmenetgazdaságban (Corporate behaviour and chances of survival in a post-socialist transitional economy)

A tanulmányban paneladatokra támaszkodva vizsgáljuk a hazai feldolgozóipari vállalkozások középtávú túlélési esélyeit befolyásoló tényezőket. A kutatás során az 1993-ban mintába került cégekhez tértünk vissza 2000-ben. Az adatok szerint az ágazat, a létszám és a kapacitáskihasználtság mellett a vezetői magatartás és a vállalati stratégia is érdemben befolyásolta a vállalatok fennmaradási esélyeit. Azok a szervezetek, amelyekben a vezetők 1993-ban úgy vélekedtek, hogy a gazdaságban a normaszegő magatartás sikerre számíthat, az átlagosnál kisebb valószínűséggel maradtak életben az évtized végére. Azok a vállalatok, amelyeknek vezetői a vizsgálat elején sikeresnek tartották cégüket, illetve amelyek már 1993-ban is inkább megoldó jellegű válságmenedzselési eszközöket alkalmaztak, nagyobb arányban maradtak fenn, mint azok, amelyek halasztó jellegű eszközökkel próbáltak úrrá lenni a transzformációs visszaesés okozta krízisen. ________ The study uses panel data to examine the factor affected medium-term changes in the chances of survival among Hungarian manufacturing firms. The researchers revisited in 2000 firms surveyed in a 1993 sample. The figures show firms survival chances vary essentially not only by industry, size of labour force and utilization of capacity, but according to managerial behaviour and corporate strategy. Those whose managers be-lieved in 1993 that behaviour breaching accepted norms would succeed in the economy had a lower than average likelihood of surviving until the end of the decade. The survival rate was higher among those whose managers thought they would be successful or were already applying crisis-management techniques of a remedial nature in 1993, than among those using delaying tactics to tackle a crisis caused by the transformational recession.

Behaviour change techniques in home-based cardiac rehabilitation: a systematic review

BACKGROUND: Cardiac rehabilitation (CR) programmes offering secondary prevention for cardiovascular disease (CVD) advise healthy lifestyle behaviours, with the behaviour change techniques (BCTs) of goals and planning, feedback and monitoring, and social support recommended. More information is needed about BCT use in home-based CR to support these programmes in practice.

AIM: To identify and describe the use of BCTs in home-based CR programmes.

DESIGN AND SETTING: Randomised controlled trials of home-based CR between 2005 and 2015 were identified by searching MEDLINE(®), Embase, PsycINFO, Web of Science, and Cochrane Database.

METHOD: Reviewers independently screened titles and abstracts for eligibility. Relevant data, including BCTs, were extracted from included studies. A meta-analysis studied risk factor change in home-based and comparator programmes.

RESULTS: From 2448 studies identified, 11 of good methodological quality (10 on post-myocardial infarction, one on heart failure, 1907 patients) were included. These reported the use of 20 different BCTs. Social support (unspecified) was used in all studies and goal setting (behaviour) in 10. Of the 11 studies, 10 reported effectiveness in reducing CVD risk factors, but one study showed no improvement compared to usual care. This study differed from effective programmes in that it didn't include BCTs that had instructions on how to perform the behaviour and monitoring, or a credible source.

CONCLUSION: Social support and goal setting were frequently used BCTs in home-based CR programmes, with the BCTs related to monitoring, instruction on how to perform the behaviour, and credible source being included in effective programmes. Further robust trials are needed to determine the relative value of different BCTs within CR programmes.

Thromboxane A2 receptor (TBXA2R) is a potent survival factor for triple negative breast cancers (TNBCs)

Triple Negative Breast Cancer (TNBC) is defined by the lack of ERα, PR expression and HER2 overexpression and is the breast cancer subtype with the poorest clinical outcomes. Our aim was to identify genes driving TNBC proliferation and/or survival which could represent novel therapeutic targets. We performed microarray profiling of primary TNBCs and generated differential genelists based on clinical outcomes following the chemotherapy regimen FEC (5-Fluorouracil/Epirubicin/Cyclophosphamide -‘good’ outcome no relapse > 3 years; ‘poor’ outcome relapse < 3 years). Elevated expression of thromboxane A2 receptor (TBXA2R) was observed in ‘good’ outcome TNBCs. TBXA2R expression was higher specifically in TNBC cell lines and TBXA2R knockdowns consistently showed dramatic cell killing in TNBC cells. TBXA2R mRNA and promoter activities were up-regulated following BRCA1 knockdown, with c-Myc being required for BRCA1-mediated transcriptional repression. We demonstrated that TBXA2R enhanced TNBC cell migration, invasion and activated Rho signalling, phenotypes which could be reversed using Rho-associated Kinase (ROCK) inhibitors. TBXA2R also protected TNBC cells from DNA damage by negatively regulating reactive oxygen species levels. In summary, TBXA2R is a novel breast cancer-associated gene required for the survival and migratory behaviour of a subset of TNBCs and could provide opportunities to develop novel, more effective treatments.

Gelsolin-mediated activation of PI3K/Akt pathway is crucial for hepatocyte growth factor-induced cell scattering in gastric carcinoma

In gastric cancer (GC), the main subtypes (diffuse and intestinal types) differ in pathological characteristics, with diffuse GC exhibiting early disseminative and invasive behaviour. A distinctive feature of diffuse GC is loss of intercellular adhesion. Although widely attributed to mutations in the CDH1 gene encoding E-cadherin, a significant percentage of diffuse GC do not harbor CDH1 mutations. We found that the expression of the actin-modulating cytoskeletal protein, gelsolin, is significantly higher in diffuse-type compared to intestinal-type GCs, using immunohistochemical and microarray analysis. Furthermore, in GCs with wild-type CDH1, gelsolin expression correlated inversely with CDH1 gene expression. Downregulating gelsolin using siRNA in GC cells enhanced intercellular adhesion and E-cadherin expression, and reduced invasive capacity. Interestingly, hepatocyte growth factor (HGF) induced increased gelsolin expression, and gelsolin was essential for HGF-medicated cell scattering and E-cadherin transcriptional repression through Snail, Twist and Zeb2. The HGF-dependent effect on E-cadherin was found to be mediated by interactions between gelsolin and PI3K-Akt signaling. This study reveals for the first time a function of gelsolin in the HGF/cMet oncogenic pathway, which leads to E-cadherin repression and cell scattering in gastric cancer. Our study highlights gelsolin as an important pro-disseminative factor contributing to the aggressive phenotype of diffuse GC.

Characterisation of polyethylene powders for rotational moulding and effect of powder size and shape on densification behaviour

The particle size, shape and distribution of a range of rotational moulding polyethylenes (PEs) ground to powder was investigated using a novel visual data acquisition and analysis system (TP Picture®), developed by Total Petrochemicals. Differences in the individual particle shape factors of the powder samples were observed and correlations with the grinding conditions were determined. When heated, the bubble dissolution behaviour of the same powders was investigated and the shape factor correlated with densification rate, bubble size and bubble distribution.

Prosocial Behaviour in Palliative Nurses: Psychometric Evaluation of the Prosociality Scale

Aim: The aim of this study was to examine the psychometric properties of a prosociality scale within the palliative nursing context, and then examine the impact of prosocial behaviour in relation to job and educational satisfaction among palliative nurses. Methods: An online cross-sectional survey was conducted in 25 Italian palliative care centres, with a total of 107 nurses completing the prosociality scale by Caprara et al (2005). Exploratory and confirmatory factor analyses were examined to evaluate a multidimensional model of prosociality. Results: A three-factor solution with a second order factor fitted the data well. The three dimensions extracted were labelled as helping, empathy, and sharing. Participants reported high levels of prosociality. In addition, prosociality was positively associated with job and educational satisfaction. Conclusions: The prosociality scale was valid and reliable when tested with palliative nurses. Although prosociality may be embedded in nurses’ personalities, this quality should be actively promoted to expand and improve the culture and the ethics of nursing.

The regulation of cancer cell invasive behaviour by Chloride Interacellular Channel 3 (CLIC3) and Transglutaminasae 2

A study into the role of secreted CLIC3 in tumour cell invasion. The initiation and progression of cancers is thought to be linked to their relationship with a population of activated fibroblasts, which are associated with tumours. I have used an organotypic approach, in which plugs of collagen I are preconditioned with fibroblastic cells, to characterise the mechanisms through which carcinoma-associated fibroblasts (CAFs) influence the invasive behaviour of tumour cells. I have found that immortalised cancer-associated fibroblasts (iCAFs) support increased invasiveness of cancer cells, and that this is associated with the ability of CAFs to increase the fibrillar collagen content of the extracellular matrix (ECM). To gain mechanistic insight into this phenomenon, an in-depth SILAC-based mass proteomic analysis was conducted, which allowed quantitative comparison of the proteomes of iCAFs and immortalised normal fibroblast (iNFs) controls. Chloride Intracellular Channel Protein 3 (CLIC3) was one of the most significantly upregulated components of the iCAF proteome. Knockdown of CLIC3 in iCAFs reduced the ability of these cells to remodel the ECM and to support tumour cell invasion through organotypic plugs. A series of experiments, including proteomic analysis of cell culture medium that had been preconditioned by iCAFs, indicated that CLIC3 itself was a component of the iCAF secretome that was responsible for the ability of iCAFs to drive tumour cell invasiveness. Moreover, addition of soluble recombinant CLIC3 (rCLIC3) was sufficient to drive the extension of invasive pseudopods in cancer cell lines, and to promote disruption of the basement membrane in a 3D in vitro model of the ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) transition. My investigation into the mechanism through which extracellular CLIC3 drives tumour cell invasiveness led me to focus on the relationship between CLIC3 and the ECM modifying enzyme, transglutaminase-2 (TG2). Through this, I have found that TG2 physically associates with CLIC3 and that TG2 is necessary for CLIC3 to drive tumour cell invasiveness. These data identifying CLIC3 as a key pro-invasive factor, which is secreted by CAFs, provides an unprecedented mechanism through which the stroma may drive cancer progression.

Marketing channel behaviour and performance

Thesis submitted to University of Manchester for the degree of Doctor of Philosophy in the Faculty of Business Administration.

Motion Cueing Algorithm Development in a 2DOF Driving Simulator: a Driving Behaviour-Centered Approach

I simulatori di guida sono strumenti altamente tecnologici che permettono di svolgere attività di ricerca in vari ambiti quali la psicologia, la medicina e l’ingegneria. Tuttavia, affinché i dati ottenuti mediante le simulazioni siano rapportabili alla loro controparte reale, la fedeltà delle componenti del simulatore di guida deve essere elevata. Questo lavoro tratta del miglioramento del sistema di restituzione del movimento nel simulatore a due gradi di libertà (2DOF) SIMU-LACET Driving Simulator, costruito e sviluppato presso il laboratorio LEPSIS dell’IFSTTAR (Istituto Francese delle Scienze e Tecnologie dei Trasporti, dello Sviluppo e delle Reti), in particolare nella sua sede di Parigi – Marne-la-Vallée. Si è deciso di andare a riprogettare la parte software del sistema di restituzione del movimento (motion cueing), operando su due elementi principali: lo scale factor (fattore di scala) applicato agli impulsi dinamici provenienti dal modello veicolare e i Motion Cueing Algorihms (MCA, algoritmi di restituzione del movimento), questo per entrambi i gradi di libertà. Si è quindi intervenuti sul modello esistente implementato in MATLAB-Simulink nello specifico blocco del motion cueing sul surge (traslazione longitudinale) e sul yaw (imbardata). Riguardo lo scale factor, è stata introdotta una metodologia per creare uno scale factor non lineare in forma esponenziale, tale da migliorare la restituzione degli impulsi meno ampi, pur rispettando i limiti fisici della piattaforma di movimento. Per quanto concerne il MCA, si sono vagliate diverse transfer function dell’algoritmo classico. La scelta finale dei MCA e la validazione del motion cueig in genere è stata effettuata mediante due esperimenti ed il giudizio dei soggetti che vi hanno partecipato. Inoltre, in virtù dei risultati del primo esperimento, si è investigata l’influenza che la strategia in merito al cambio delle marce avesse sulla percezione del movimento da parte del guidatore.

Growth Factor Stimulation Improves The Structure And Properties Of Scaffold-free Engineered Auricular Cartilage Constructs.

The reconstruction of the external ear to correct congenital deformities or repair following trauma remains a significant challenge in reconstructive surgery. Previously, we have developed a novel approach to create scaffold-free, tissue engineering elastic cartilage constructs directly from a small population of donor cells. Although the developed constructs appeared to adopt the structural appearance of native auricular cartilage, the constructs displayed limited expression and poor localization of elastin. In the present study, the effect of growth factor supplementation (insulin, IGF-1, or TGF-β1) was investigated to stimulate elastogenesis as well as to improve overall tissue formation. Using rabbit auricular chondrocytes, bioreactor-cultivated constructs supplemented with either insulin or IGF-1 displayed increased deposition of cartilaginous ECM, improved mechanical properties, and thicknesses comparable to native auricular cartilage after 4 weeks of growth. Similarly, growth factor supplementation resulted in increased expression and improved localization of elastin, primarily restricted within the cartilaginous region of the tissue construct. Additional studies were conducted to determine whether scaffold-free engineered auricular cartilage constructs could be developed in the 3D shape of the external ear. Isolated auricular chondrocytes were grown in rapid-prototyped tissue culture molds with additional insulin or IGF-1 supplementation during bioreactor cultivation. Using this approach, the developed tissue constructs were flexible and had a 3D shape in very good agreement to the culture mold (average error <400 µm). While scaffold-free, engineered auricular cartilage constructs can be created with both the appropriate tissue structure and 3D shape of the external ear, future studies will be aimed assessing potential changes in construct shape and properties after subcutaneous implantation.

Macrophage Cell Activation With Acute Apical Abscess Contents Determined By Interleukin-1 Beta And Tumor Necrosis Factor Alpha Production.

This clinical study has investigated the antigenic activity of bacterial contents from exudates of acute apical abscesses (AAAs) and their paired root canal contents regarding the stimulation capacity by levels of interleukin (IL)-1 beta and tumor necrosis factor alpha (TNF-α) throughout the root canal treatment against macrophage cells. Paired samples of infected root canals and exudates of AAAs were collected from 10 subjects. Endodontic contents were sampled before (root canal sample [RCS] 1) and after chemomechanical preparation (RCS2) and after 30 days of intracanal medication with calcium hydroxide + chlorhexidine gel (Ca[OH]2 + CHX gel) (RCS3). Polymerase chain reaction (16S rDNA) was used for detection of the target bacteria, whereas limulus amebocyte lysate was used to measure endotoxin levels. Raw 264.7 macrophages were stimulated with AAA exudates from endodontic contents sampled in different moments of root canal treatment. Enzyme-linked immunosorbent assays were used to measure the levels of TNF-α and IL-1 beta. Parvimonas micra, Porphyromonas endodontalis, Dialister pneumosintes, and Prevotella nigrescens were the most frequently detected species. Higher levels of endotoxins were found in samples from periapical exudates at RCS1 (P < .005). In fact, samples collected from periapical exudates showed a higher stimulation capacity at RCS1 (P < .05). A positive correlation was found between endotoxins from exudates with IL-1 beta (r = 0.97) and TNF-α (r = 0.88) production (P < .01). The significant reduction of endotoxins and bacterial species achieved by chemomechanical procedures (RCS2) resulted in a lower capacity of root canal contents to stimulate the cells compared with that at RCS1 (P < .05). The use of Ca(OH)2 + CHX gel as an intracanal medication (RCS3) improved the removal of endotoxins and bacteria from infected root canals (P < .05) whose contents induced a lower stimulation capacity against macrophages cells at RCS1, RCS2, and RCS3 (P < .05). AAA exudates showed higher levels of endotoxins and showed a greater capacity of macrophage stimulation than the paired root canal samples. Moreover, the use of intracanal medication improved the removal of bacteria and endotoxins from infected root canals, which may have resulted in the reduction of the inflammatory potential of the root canal content.