Influence of P53 on the radiotherapy response of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and it has a poor prognosis and few therapeutic options. Radiotherapy is one of the most effective forms of cancer treatment, and P53 protein is one of the key molecules determining how a cell responds to radiotherapy. The aim of this study was to determine the therapeutic efficacy of iodine-131 in three human HCC cell lines.

The Influence of Age, Cardiorespiratory Fitness, Exercise and Sedentary Behaviours on Circulating Angiogenic Cells and Cell Surface Receptor Expression.

Cardiovascular disease (CVD) is the biggest killer of people in western civilisation. Age is a significant risk factor for the development for CVD, and treatments and therapies to address this increased risk are crucial to quality of life and longevity. Exercise is one such intervention which has been shown to reduce CVD risk. Age is also associated with endothelial dysfunction, reduced angiogenic capabilities, and reduced ability to repair the vessel wall. Circulating angiogenic cells (CACs) are a subset of circulating cells which assist in the repair and growth of the vasculature and in the maintenance of endothelial function. Reductions in these cells are observed in those with vascular disease compared to age-matched healthy controls. Exercise may reduce CVD risk by improvements in number and/or function of these CACs. Data was collected from human volunteers of various ages, cardiorespiratory fitness (CRF) levels and latent viral infection history status to investigate the effects of chronological age, CRF, viral serology and other lifestyle factors, such as sedentary behaviours and exercise on CACs. The levels of CACs in these volunteers were measured using four colour flow cytometry using various monoclonal antibodies specific to cell surface markers that are used to identify specific subsets of these CACs. In addition, the response to acute exercise of a specific subset of these CACs, termed ‘angiogenic T-cells’ (TANG) were investigated, in a group of well-trained males aged 20-40 years, using a strenuous submaximal exercise bout. Advancing age was associated with a decline in various subsets of CACs, including bone marrow-derived CD34+ progenitors, putative endothelial progenitor cells (EPCs) and also TANG cells. Individuals with a higher CRF were more likely to have higher circulating numbers of TANG cells, particularly in the CD4+ subset. CRF did not appear to modulate CD34+ progenitors or EPC subsets. Increasing sitting time was associated with reduction in TANG cells, but after correcting for the effects of fitness, sitting time no longer negatively affected the circulating number of these cells. Acute exercise was a powerful stimulus for increasing the number of TANG cells (140% increase), potentially through an SDF-1:CXCR4-dependent mechanism, but more studies are required to investigate this. Latent CMV infection was associated with higher number of TANG cells (CD8+), but only in 18-40 year old individuals, and not in an older age group (41-65 year old). The significance of this has yet to be understood. In conclusion, advancing age may contribute to increased CVD risk partly due to the observed reductions in angiogenic cells circulating in the peripheral compartment. Maintaining a high CRF may attenuate this CVD reduction by modulating TANG cell number, but potentially not CD34+ progenitor or EPC subsets. Acute exercise may offer a short window for vascular adaptation through the mobilisation of TANG cells into the circulation.

Alternative media for public pedagogy: "Chief" concerns and human agency

To demonstrate how the growing influence of alternative media in civil society correlates with the rise of social movements and their influence on contemporary manifestations of resistance, this research uses critical ethnographic methodologies to document the narratives of alternative media producers in the pro-Indigenous and anti-“Chief” campaigns at the University of Illinois at Urbana-Champaign during the 2006-2007 school year. These narratives demonstrate not only the ways alternative media help transmit dissent by distributing information to diverse populations, but also the manner they facilitate contexts that influence identity formations and strengthen counter-cultural communal practices. Particular lineages of critical social theory are used to situate knowledge construction and social relationships within specific socio-historic contexts to approach issues of subjectivity, human agency, and resistance. These include the Frankfurt School for Social Research, the Birmingham Centre for Contemporary Cultural Studies, and the Brazilian education philosopher Paulo Freire, who emphasize criticality based on the engagement of ideological analysis, as well as developing capacities to critique and resist oppressive social and political relationships. Thus, this study argues for expanding traditional notions of literacy to include the ability to decode and produce media as a critical element of meaningful democratic participation.

The growth prerogative: how does an objective of economic growth influence local planning policy?

This research aimed to explore the privileging of growth and its influence on planning in England. The research examined two contrasting case studies: Middlesbrough Borough Council and Cambridge City Council. The analysis of growth privileging is rooted within a constructionist ontology which argues that planning is about the way in which people construct value relative to the function of land. This perspective enables the research to position growth privileging as a social construction; a particular mental frame for understanding and analyzing place based challenges and an approach which has been increasingly absorbed by the UK planning community. Through interviews with a range of planning actors, the first part of the research examined the state of planning in the current political and economic context and the influence that a privileging of growth has on planning. The second part of the research investigated the merits and feasibility of the capabilities approach as an alternative mental frame for planning, an approach developed through the work of Amartya Sen and Martha Nussbaum. The research results disaggregate the concept of economic growth, based on the responses of interviewees and conclude that it is characterized by homogeneity. Growth is valued, not only because of its economic role, for example, supporting jobs and income but its potential in creating diversity, enriching culture and precipitating transformative change. Pursuing growth as an objective has a range of influences upon planning. In particular, it supports a utilitarian framework for decision-making which values spatial decisions on their ability to support aggregate economic growth. The research demonstrates the feasibility and merits of the capabilities approach as a means with which to better understand the relationship between planning and human flourishing. Based on this analysis, the research proposes that the capabilities approach can provide an alternative ‘mental frame’ for planning which privileges human flourishing as the primary objective or ‘final end’ instead of economic growth.

Comparing the expression of human DNA topoisomerase I in KM71H and X33 strains of Pichia pastoris

Background: Human is an essential cellular enzyme that is found in all human cells. As this enzyme is upregulated in cancer cells exceedingly, it is used as a target for cancer chemotherapeutic drug development. As such, producing the in-house enzyme for the purpose to speed up the search for more cost-effective and target specific hTopoI inhibitors is warranted. This study aims to compare the optimised conditions for the expression of hTopoI in KM71H (MutS) and X33 (Mut+) strains of Pichia pastoris P. pastoris transfected with an hTopoI recombinant vector was used for the optimization of a higher level of hTopoI expression. Results: In the process, fed-batch cultivation parameters that influence the expression of hTopoI, such as culture temperature, methanol induction and feeding strategy, were optimised in the transfected KM71H and X33 P. pastoris strains in a shake flask system. The cell density and total protein concentration (protein level) of transfected P. pastoris were compared to determine the optimum culture conditions for each transfected P. pastoris strain. A higher hTopoI level was observed in the transfected KM71H culture supernatant (2.26 ng/mL) when the culture was incubated in the optimum conditions. Conclusions: This study demonstrated that MutS strain (KM71H) expressed and secreted a higher level of hTopoI heterologous protein in the presence of methanol compared to the Mut+ strain; X33 (0.75 ng/mL). However, other aspects of optimization, such as pH, should also be considered in the future, to obtain the optimum expression level of hTopoI in P. pastoris.

Association of human papillomavirus and Chlamydia trachomatis with intraepithelial alterations in cervix samples

The influence of different infectious agents and their association with human papillomavirus (HPV) in cervical carcinogenesis have not been completely elucidated. This study describes the association between cytological changes in cervical epithelium and the detection of the most relevant aetiological agents of sexually transmitted diseases. Samples collected from 169 patients were evaluated by conventional cytology followed by molecular analysis to detect HPV DNA, Chlamydia trachomatis , herpes simplex virus 1 and 2, Neisseria gonorrhoeae , Mycoplasma genitalium , Trichomonas vaginalis, and Treponema pallidum , besides genotyping for most common high-risk HPV. An association between cytological lesions and different behavioural habits such as smoking and sedentariness was observed. Intraepithelial lesions were also associated with HPV and C. trachomatis detection. An association was also found between both simple and multiple genotype infection and cytological changes. The investigation of HPV and C. trachomatis proved its importance and may be considered in the future for including in screening programs, since these factors are linked to the early diagnosis of patients with precursor lesions of cervical cancer.

Human resource management reform in the Indonesian civil service : towards strategic fit?

Studies of strategic HRM have dominated HRM research over the last three decades. Focusing on the HRM-organisation performance relationship, researchers take various themes and perspectives in their approach to strategic HRM. Among these themes, two contrasting approaches of strategic HRM continue to flourish: first, the best practice approach suggests that certain HRM practices will have the same effect irrespective of context and, second, the best fit approach suggests that the choice of HRM practices should be designed in accordance with an organisations’ specific context. While there is little consensus on what constitutes strategic HRM, the most common feature agreed in this field is the notion of the strategic integration; aligning HRM practices with organisations’ overall strategic objectives (vertical fit) and with each other (horizontal fit). Utilising the best fit approach as its theoretical framework, this study examines how vertical and horizontal fit is practised in the Indonesian civil service and what factors likely influence the prevalence of vertical and horizontal fit in the Indonesian civil service context. This study is significant for two important reasons. Firstly, the literature suggests that there are limited studies examining the best fit concept in the civil sector despite its implementation in the private sector positively contributing to organisational performance improvement. Secondly, the study provides enlightenment on how the best fit approach could contribute to performance improvement in the Indonesian civil service. This is in line with the fact that negative images of the Indonesian civil service are continuously highlighted although various HRM reform initiatives have been put in place. To achieve the objectives of the study, the qualitative case study approach accompanied by semi-structured interviews was employed involving 53 senior officials and one focus group discussion from eight Indonesian government agencies, consisting of three central agencies mandated to manage human resources, the National Bureaucratic Reform Team and four line agencies from both central and local governments. Thematic analysis was employed for data analyses and NVIVO software was used to manage the data. The study suggests three main findings. First, various HRM initiatives in relation to the HRM reform have been introduced in the Indonesian civil service differentiating them from the old HRM practices. However, the findings indicate that some HRM policies are still contradicting and hinder vertical and horizontal fit. Second, despite the contradictory policies, vertical and horizontal fit can be seen in the line agencies which have been acknowledged as ‘reformed agencies’. This demonstrates that the line agencies play an important role in aligning HRM practices with the line agencies’ goals and objectives and with one another although they are bounded by HRM policies that are unlikely to support the vertical and horizontal fit concept. Third, factors influencing the prevalence of vertical and horizontal fit include knowledge of contemporary HRM in both central agencies and line agencies, commitment from the line agencies’ leaders, devolvement of HRM to the line agencies and the socio-political and economic environments of the Indonesian civil service. The findings of the study raise policy, practical and theoretical implications. In terms of policy implications, the study highlights the importance of fit in HRM policies to support the achievement of the line agencies’ goals. Therefore, when formulating an HRM policy, the central agencies need to ensure that the HRM policy is linked to line agencies’ goals and to other HRM policies. This is to ensure synchronisation among the policies and thus maximising the achievement of the line agencies’ goals. From the practical perspectives, the study highlights important points which can be learned by the central agencies in carrying out their strategic role with regard to the formulation of HRM policies; by the line agencies in maximising the contribution of HRM to the achievement of the goals and objectives of the agencies through the implementation of the best fit concept, and by the leaders of the agencies in providing continuous support to each of the involved parties in the line agencies and involving the HRM department in all agency’s strategic decision-making. In relation to the theoretical implication, it is clear that the best fit approach is not thoroughly applied due to factors discussed previously. However, this does not mean that the best fit concept cannot be implemented. As argued by McCourt & Ramgutty-Wong (2003), instead of adopting the whole concept of best fit, a modulated approach reflecting the best fit concept, such as selecting individual HRM practices and experimenting with devolution, is possible for civil service organisations which still embrace centralised HRM systems. As demonstrated in the findings, some of the line agencies being studied seem to be ready to adopt the best fit approach given that they have knowledge of the best fit concept, strong support from the top leader, less political intervention and less corruption, collusion, and nepotism practices in their HRM practices.

Global interactions between fire and vegetation, human activities and climate

Doutoramento em Engenharia Florestal - Instituto Superior de Agronomia - UL

Phosphoglucose isomerase variability of Cerastoderma glaucum as a model for testing the influence of environmental conditions and dispersal patterns through quantitative ecology approaches

Extreme conditions of coastal lagoons could directly modify the genetic patterns of species. The aim of this work was to investigate the influence of environmental conditions and small scale dispersal patterns on the phosphoglucose isomerase (PGI*) genetic variability of Cerastoderma glaucum from the Mar Menor coastal lagoon. For this purpose, 284 cockles were collected around the perimeter of the lagoon. Vertical polyacrylamide gel electrophoresis was used to scan for PGI* polymorphisms, giving a total of seven alleles. The spatial genetic distribution of the PGI* variability, which seems to be marked by the main circulation in the lagoon, discriminates four hydrological basins. In the central basin, a gradient of allelic composition reflects the circulation forced by the dominant winds and the main channel communicated to the open sea. This result is well supported by the salinity GAM model that defines this gradient. The other three basins are defined by the distribution of fine sand in a more complex model that tries to explain the isolation of the three sites localized inside these basins. The southern, western and northern basins show the lowest degree of interconnection and are considered the most confined areas of the Mar Menor lagoon. This situation agrees with the confinement theory for benthic assemblages in the lagoon. The greater degree of differentiation seen in the Isla del Ciervo population is probably due to recent human intervention on the nearby Marchamalo channel, which has been drained in recent years thus altering the influence of the Mediterranean Sea on the southern basin.

Age diversity and firm performance in an emerging economy: Implications for cross-cultural human resource management

This study tests the effect of age diversity on firm performance among international firms. Based on the resource-based view of the firm, it argues that age diversity among employees will influence firm performance. Moreover, it argues that two contextual variables—a firm's level of market diversification and its country of origin—influence the relationship between age diversity and firm performance. By testing relevant hypotheses in a major emerging economy, that is, the People's Republic of China, this study finds a significant and positive effect of age diversity and a significant interactive effect between age diversity and firm strategy on profitability. We also find a significant relationship between age diversity and firm profitability for firms from Western societies, but not for firms from East Asian societies. The paper concludes by discussing the implications of this study's findings. © 2011 Wiley Periodicals, Inc.

Human resources management, citizenship behavior, and turnover intention in the portuguese public administration

Framed by a social exchange perspective, this study address the issue of whether positive employees’ perceptions about human resource management practices influence positive attitudes and behaviour. We hypothesize that human resource management practices (HRMP) have a significant negative effect on intention to voluntary leave the organization and a positive effect on organizational citizenship behaviour (OCB), and that OCB could mediate the relationship between HRMP and turnover intention. A sample of 165 employees from the Portuguese public administration participated in the study. Data was analysed through descriptive statistics, confirmatory factor analysis and hypotheses were tested using single and multiple linear regressions. Results indicate that HRMP is positively associated with OCB, but only internal communication practice is highly valued by Portuguese public employees and successfully predicts OCB. HRMP also show a positive association with turnover intention but only celebration and recognition practices are predictors of turnover intention. Contrary to our hypothesis OCB did not acted as mediator between HRMP and turnover intention. Some suggestions on managerial human resource practices were proposed as well as some main questions raised in the Portuguese public administration context.

EVIDENCE FOR MECHANICAL STRAINS INFLUENCE IN OSTEOPHYTE DEVELOPMENT

Purpose: Osteophytes are osteo-cartilaginous metaplastic tissue outgrowths of bone capped by cartilage usually found in degenerative and inflammatory joint disease. The presence and degree of maturity of osteophytes, along with joint space narrowing, are the main radiographic criteria for diagnosis and grading osteoarthritis (OA). Although osteophytes are known for being anatomic signs of advanced OA, they can occur in non-symptomatic joints, in joints with no other observable alterations, and in early stage OA. It remains unclear if they develop from molecular, physiological and/or mechanical stimuli. We hypothesized that mechanical strains play a role in osteophyte development. The overall objective of this thesis was to find evidence that osteophytes are influenced by mechanical strains. Methods: The first project was to develop a mechanically-induced osteophyte animal model. One single impact load that was reported to induce moderate joint damage was applied to the periosteum of the rat knee. Animals were sacrificed at four time points to characterize the evolution of damaged tissue and the joint by histology. A second study using human mature hip osteophytes was conducted to evaluate if mature osteophyte presented histological signs of proliferating and developmental processes. The histological characterization of mature osteophyte was used to compare findings of the mechanically-induced osteophyte in the animal model to validate the use of this rodent model in studying some aspect of osteophyte development of human. Lastly, a detailed three-dimensional (3D) radiological morphometric analysis was performed on microscopic computed tomography (µCT) scanned femoral heads collected from total hip arthroplasty patients presenting mature hip osteophytes. Quantitative morphometric measures of osteophytes internal structure was compared to three regions of the femoral head of known quality of organisation and mechanical constraint. Results and Conclusion: Osteophyte can be mechanically induced by a single load impact to the joint periosteum, indicating that a moderate trauma to the periosteal layer of the joint may play a role in osteophyte development. Mature osteophytes have proliferation, developing and remodelling zones and have trabecular structures. Mechanically-induced osteophytes and mature osteophytes presented similar histological composition. Mature osteophytes have organized internal structure. These results provide evidence that mechanical strain can influence osteophyte development.

Toward adaptive management of coastal MPAs: The influence of different conservation targets and costs on the design of no-take areas

There is still much discussion on the most appropriate location, size and shape of marine protected areas (MPAs). These three factors were analyzed for a small coastal MPA, the Luiz Saldanha Marine Park (LSMP), for which a very limited amount of local ecological information was available when implemented in 1998. Marxan was used to provide a number of near-optimal solutions considering different levels of protection for the various conservation features and different costs. These solutions were compared with the existing no-take area of the LSMP. Information on 11 habitat types and distribution models for 3 of the most important species for the local artisanal fisheries was considered. The human activities with the highest economic and ecological impact in the study area (commercial and recreational fishing and scuba diving) were used as costs. The results show that the existing no-take area is actually located in the best area. However, the no-take area offers limited protection to vagile fish and covers a very small proportion of some of the available habitats. An increase in the conservation targets led to an increase in the number of no-take areas. The comparative framework used in this study can be applied elsewhere, providing relevant information to local stakeholders and managers in order to proceed with adaptive management. (C) 2015 Elsevier B.V. All rights reserved.

The influence of nitrogen fertilization on growth, yield, nitrate and oxalic acid concentration in purslane ( Portulaca oleracea )

Purslane (Portulaca oleracea) is widely used for culinary purposes throughout Mediterranean region, and the interest in this plant increased due to it being a source of bio-protective compounds, such as fatty acids and antioxidants. However, the use of purslane could be limited by accumulation of high levels of compounds harmful to human health, such as nitrate and oxalic acid. The main objective of present study was to evaluate the influence of nitrogen fertilization on growth and yield parameters and on nitrate and oxalic acid concentrations in leaves and stems. Plants of golden-leafed purslane of sativa subspecies were grown in styro-foam boxes with substrate and fertilized two times per week during four weeks with ammonium-nitrate solution (16.9% NO3--N and 17.6% NH4+-N), for testing of four nitrogen levels (0, 30, 60 and 90 kg N ha-1). Plant growth, yield, nitrate and oxalic acid concentrations were significantly affected by nitrogen application. The best quantity/quality ratio was achieved at fertilization level of 60 kg N ha-1, which gave a yield of 5.1 kg m-2 FW, while nitrate concentration was 48.98 and 43.90 mg g-1 DW in leaf and stem, respectively, and oxalic acid concentration was 1.27 and 0.55 mg g-1 DW, in leaf and stem, respectively: values which are not harmful for consumer health.

Functional and neural mechanisms of human fear conditioning: studies in healthy and brain-damaged individuals

Fear conditioning represents the learning process by which a stimulus, after repeated pairing with an aversive event, comes to evoke fear and becomes intrinsically aversive. This learning is essential to organisms throughout the animal kingdom and represents one the most successful laboratory paradigm to reveal the psychological processes that govern the expression of emotional memory and explore its neurobiological underpinnings. Although a large amount of research has been conducted on the behavioural or neural correlates of fear conditioning, some key questions remain unanswered. Accordingly, this thesis aims to respond to some unsolved theoretic and methodological issues, thus furthering our understanding of the neurofunctional basis of human fear conditioning both in healthy and brain-damaged individuals. Specifically, in this thesis, behavioural, psychophysiological, lesion and non-invasive brain stimulation studies were reported. Study 1 examined the influence of normal aging on context-dependent recall of extinction of fear conditioned stimulus. Study 2 aimed to determine the causal role of the ventromedial PFC (vmPFC) in the acquisition of fear conditioning by systematically test the effect of bilateral vmPFC brain-lesion. Study 3 aimed to interfere with the reconsolidation process of fear memory by the means of non-invasive brain stimulation (i.e. TMS) disrupting PFC neural activity. Finally, Study 4 aimed to investigate whether the parasympathetic – vagal – modulation of heart rate might reflect the anticipation of fearful, as compared to neutral, events during classical fear conditioning paradigm. Evidence reported in this PhD thesis might therefore provide key insights and deeper understanding of critical issues concerning the neurofunctional mechanisms underlying the acquisition, the extinction and the reconsolidation of fear memories in humans.