Stimulating Neoblast-Like Cell Proliferation in Juvenile Fasciola hepatica Supports Growth and Progression towards the Adult Phenotype In Vitro

Fascioliasis (or fasciolosis) is a socioeconomically important parasitic disease caused by liver flukes of the genus Fasciola. Flukicide resistance has exposed the need for new drugs and/or a vaccine for liver fluke control. A rapidly improving 'molecular toolbox' for liver fluke encompasses quality genomic/transcriptomic datasets and an RNA interference platform that facilitates functional genomics approaches to drug/vaccine target validation. The exploitation of these resources is undermined by the absence of effective culture/maintenance systems that would support in vitro studies on juvenile fluke development/biology. Here we report markedly improved in vitro maintenance methods for Fasciola hepatica that achieved 65% survival of juvenile fluke after 6 months in standard cell culture medium supplemented with 50% chicken serum. We discovered that this long-term maintenance was dependent upon fluke growth, which was supported by increased proliferation of cells resembling the "neoblast" stem cells described in other flatworms. Growth led to dramatic morphological changes in juveniles, including the development of the digestive tract, reproductive organs and the tegument, towards more adult-like forms. The inhibition of DNA synthesis prevented neoblast-like cell proliferation and inhibited growth/development. Supporting our assertion that we have triggered the development of juveniles towards adult-like fluke, mass spectrometric analyses showed that growing fluke have an excretory/secretory protein profile that is distinct from that of newly-excysted juveniles and more closely resembles that of ex vivo immature and adult fluke. Further, in vitro maintained fluke displayed a transition in their movement from the probing behaviour associated with migrating stage worms to a slower wave-like motility seen in adults. Our ability to stimulate neoblast-like cell proliferation and growth in F. hepatica underpins the first simple platform for their long-term in vitro study, complementing the recent expansion in liver fluke resources and facilitating in vitro target validation studies of the developmental biology of liver fluke.

“Can we walk?” Environmental supports for physical activity in India

India is currently facing a non-communicable disease epidemic. Physical activity (PA) is a preventative factor for non-communicable diseases. Understanding the role of the built environment (BE) to facilitate or constrain PA is essential for public health interventions to increase population PA. The objective of this study was to understand BEs associations with PA occurring in two major life domains or life areas—travel and leisure—in urban India. Between December 2014 and April 2015, in-person surveys were conducted with participants (N = 370; female = 47.2%) in Chennai, India. Perceived BE characteristics regarding residential density, land use mix-diversity, land use mix-access, street connectivity, infrastructure for walking and bicycling, aesthetics, traffic safety, and safety from crime were measured using the adapted Neighborhood Environment Walkability Scale-India (NEWS-India). Self-reported PA was measured the International Physical Activity Questionnaire. High residential density was associated with greater odds of travel PA (aOR = 1.9, 95% CI = 1.2, 3.2). Land use mix-diversity was positively related to travel PA (aOR = 2.1, 95%CI = 1.2, 3.6), but not associated with leisure or total PA. The aggregate NEWS-India score predicted a two-fold increase in odds of travel PA (aOR = 1.9, 95% CI = 1.1, 3.1) and a 40% decrease in odds of leisure PA (aOR = 0.6, 95% CI = 0.4, 1.0). However, the association of the aggregated score with leisure PA was not significant. Results suggest that relationships between BE and PA in low-and-middle income countries may be context-specific, and may differ markedly from higher income countries. Findings have public health implications for India suggesting that caution should be taken when translating evidence across countries.

The Legitimacy Process that Supports the Formation and Development of Cluster Initiatives : The Case of a Tourism Cluster Initiative in Dalarna

Today, large public investments are being made with the aim of creating and developing cooperation between businesses in inter-organizational networks. Such initiatives are commonly denoted cluster initiatives and their underlying purpose are to spur innovation and regional growth. Much research has been conducted in this field, but relatively few studies have examined the process of cluster initiatives. By following the case of a regional cluster project within the tourism industry in the region of Dalarna, Sweden, the objective of this thesis is to deepen the understanding of the formation and development process of cluster initiatives. The investigation has been conducted by examining two main themes; the internal relationships within the cluster initiative and the relationships between the cluster initiative and its external stakeholders, such as funding agencies, regional government and local businesses. The analysis is based on a legitimacy perspective and indicates that the coordinating body of the cluster initiative, the hub, principally deals with a legitimation process. What occurs within the cluster initiative, between the members themselves and between the members and the hub, is legitimation. This also applies to external relationships, between the hub and its external stakeholders. A prerequisite for the realization of its mission is that the hub obtain and sustain legitimacy; legitimacy for itself, for the other members, for the idea, for the different activities and for the industry as such.

Identifying the Supports and Challenges of High School Latino English Language Learners

Two out of three English Language Learners (ELLs) graduate from secondary schools nationwide. Of the nearly five million ELLs in public schools, more than 70% of these students’ first language is Spanish. In order to understand and resolve this phenomena and in an effort to increase the number of graduates, this research examined what high school Latino ELLs identified as the major external and internal factors that support or challenge them on the graduation pathway. The study utilized a 32 quantitative and qualitative question student survey, as well as student focus groups. Both the survey and the focus groups were conducted in English and Spanish. The questions considered the following factors: 1) value of education; 2) expectations in achieving their long-term goals; 3) current education levels; 4) expectations before coming to the United States; 5) family obligations; and 6) future aspirations. The survey was administered to 159 Latino ELLs enrolled in grades 9-12. Research took place at three high schools that provide English for Speakers of Other Languages (ESOL) classes in a large school system in the Mid-Atlantic region. The three schools involved in the study have more than 1,500 ELLs. Two of the schools had large ESOL instructional programs, and one school had a comparatively smaller ESOL program. The majority of students surveyed were from El Salvador (72%) and Guatemala (12.6%). Using Qualtrics, an independent facilitator and a bilingual translator administered the online survey tool to the students during their ESOL classes. Two weeks later, the researcher hosted three follow-up focus groups, totaling 37 students from those students who took the survey. Each focus group was conducted at the three schools by the lead researcher and the translator. The purpose of the focus group was to obtain deeper insight on how secondary age Latino ELLs defined success in school, what they identified to be their support factors, and how previous and present experiences helped or hindered their goals. From the research findings, ten recommendations range from suggested policy updates to cross-cultural/equity training for students and staff; they were developed, stemming from the findings and what the students identified.

A social and gender analysis of Northern Province, Zambia: Qualitative evidence that supports the use of a gender transformative approach

A qualitative social and gender analysis was carried out in June 2015 in Luwingu and Mbala Districts in Northern Province, Zambia. The research explored the norms and power relations at various institutional levels that constrain certain social groups from benefiting from programmatic investments aimed at improving livelihoods, health status, and food and nutrition security within the Irish Aid Local Development Programme (IALDP). This technical paper provides a summary of the research findings, lessons learned and suggests options for action the IALDP could consider to help bring about gender transformative change in the lives and livelihoods of poor and vulnerable people.

Perceptions of Social Supports and Services for Intimate Partner Violence Victims

Intimate partner violence (IPV) is a complex issue. The present study explored how media exposure to female and male victims of IPV affected participants’ support for both groups. It was hypothesized that female victims would be supported more than male victims and that presenting stimuli that drew attention to male victims would not decrease support for female victims. Participants were presented with one of three posters, drawing attention to male victims, female victims, or both. A questionnaire was then used to assess perceptions of support for IPV victims, which was completed by 121 participants. Results indicated that females were supported more than males and that drawing attention to male victims did not decrease participants’ support for female victims. An exploratory analysis also revealed that women, overall, have high support for all victims, while men’s level of support changed depending on the type of information to which they were exposed.

Two near-optimal layouts for trusslike bridge structures bearing uniform weight between supports

Although the primary objective on designing a structure is to support the external loads, the achievement of an optimal layout that reduces all costs associated with the structure is an aspect of increasing interest. The problem of finding the optimal layout for bridgelike structures subjected to a uniform load is considered. The problem is formulated following a theory on economy of frame structures, using the stress volume as the objective function and including the selection of appropriate values for statically indeterminate reactions. It is solved in a function space of finite dimension instead of using a general variational approach, obtaining near-optimal solutions. The results obtained with this profitable strategy are very close to the best layouts known to date, with differences of less than 2% for the stress volume, but with a simpler layout that can be recognized in some real bridges. This strategy could be a guide to preliminary design of bridges subject to a wide class of costs.

Tailored mesoporous silica supports for Ni catalysed hydrogen production from ethanol steam reforming

Mesoporous silica supported Ni nanoparticles have been investigated for hydrogen production from ethanol steam reforming. Ethanol reforming is structure-sensitive over Ni, and also dependent on support mesostructure; three-dimensional KIT-6 possessing interconnected mesopores offers superior metal dispersion, steam reforming activity, and on-stream stability against deactivation compared with a two-dimensional SBA-15 support.

A new post-metallocene-ti catalyst with maltolate bidentade ligand: an investigation in heterogeneous polymerization reactions in different mesoporous supports

A new titanium catalyst easily synthesized from ethylmaltol bidentate chelator ligand was studied in homogeneous and heterogeneous ethylene polymerization. The dichlorobis(3-hydroxy-2-ethyl-4-pyrone)titanium(IV) complex was characterized by 1H and 13C NMR (nuclear magnetic resonance), UV-Vis and elemental analysis. Theoretical study by density functional theory (DFT) showed that the complex chlorines exhibit cis configuration, which is important for the activity in olefin polymerization. The complex was supported by two methods, direct impregnation or methylaluminoxane (MAO) pre-treatment, in five mesoporous supports: MCM-41 (micro and nano), SBA-15 and also the corresponding modified Al species. All the catalytic systems were active in ethylene polymerization and the catalytic activity was strongly influenced by the method of immobilization of the catalyst and the type of support.

Alginate / cellulose beads as supports for slowrelease of nutrient.

2016

Capabilities : describing what services can do

The ability of agents and services to automatically locate and interact with unknown partners is a goal for both the semantic web and web services. This, \serendipitous interoperability", is hindered by the lack of an explicit means of describing what services (or agents) are able to do, that is, their capabilities. At present, informal descriptions of what services can do are found in \documentation" elements; or they are somehow encoded in operation names and signatures. We show, by ref- erence to existing service examples, how ambiguous and imprecise capa- bility descriptions hamper the attainment of automated interoperability goals in the open, global web environment. In this paper we propose a structured, machine readable description of capabilities, which may help to increase the recall and precision of service discovery mechanisms. Our capability description draws on previous work in capability and process modeling and allows the incorporation of external classi¯cation schemes. The capability description is presented as a conceptual meta model. The model supports conceptual queries and can be used as an extension to the DAML-S Service Pro¯le.

Mining in Northern British Columbia

The history of the settlement of the province is tied to patterns of exploration and min development. In Northern British Columbia the Cariboo goldfields provided the impetus for settlement of the region and the beginning for mining to extend into the watern and northern regions in a series of minor gold rushes. The northern half of the province has a geological diverse mineral base that supports a wide variety of mining, and a gradual improvement of exploration and mining methods due to scientific knowledge and technology provided opportunities for lode gold and base metal mines to be developed. The success of mining is based on world ore prices and competitive markets that impact the economic viability of developing a mine. Mining faces increasing pressures in the northern half of the province due to other resource values, such as tourism or protected areas, that claim and compete for a similar land base.

Membrane associated transporter protein gene (SLC45A2) and the genetic basis of normal human pigmentation variation

This work is concerned with the genetic basis of normal human pigmentation variation. Specifically, the role of polymorphisms within the solute carrier family 45 member 2 (SLC45A2 or membrane associated transporter protein; MATP) gene were investigated with respect to variation in hair, skin and eye colour ― both between and within populations. SLC45A2 is an important regulator of melanin production and mutations in the gene underly the most recently identified form of oculocutaneous albinism. There is evidence to suggest that non-synonymous polymorphisms in SLC45A2 are associated with normal pigmentation variation between populations. Therefore, the underlying hypothesis of this thesis is that polymorphisms in SLC45A2 will alter the function or regulation of the protein, thereby altering the important role it plays in melanogenesis and providing a mechanism for normal pigmentation variation. In order to investigate the role that SLC45A2 polymorphisms play in human pigmentation variation, a DNA database was established which collected pigmentation phenotypic information and blood samples of more than 700 individuals. This database was used as the foundation for two association studies outlined in this thesis, the first of which involved genotyping two previously-described non-synonymous polymorphisms, p.Glu272Lys and p.Phe374Leu, in four different population groups. For both polymorphisms, allele frequencies were significantly different between population groups and the 272Lys and 374Leu alleles were strongly associated with black hair, brown eyes and olive skin colour in Caucasians. This was the first report to show that SLC45A2 polymorphisms were associated with normal human intra-population pigmentation variation. The second association study involved genotyping several SLC45A2 promoter polymorphisms to determine if they also played a role in pigmentation variation. Firstly, the transcription start site (TSS), and hence putative proximal promoter region, was identified using 5' RNA ligase mediated rapid amplification of cDNA ends (RLM-RACE). Two alternate TSSs were identified and the putative promoter region was screened for novel polymorphisms using denaturing high performance liquid chromatography (dHPLC). A novel duplication (c.–1176_–1174dupAAT) was identified along with other previously described single nucleotide polymorphisms (c.–1721C>G and c.–1169G>A). Strong linkage disequilibrium ensured that all three polymorphisms were associated with skin colour such that the –1721G, +dup and –1169A alleles were associated with olive skin in Caucasians. No linkage disequilibrium was observed between the promoter and coding region polymorphisms, suggesting independent effects. The association analyses were complemented with functional data, showing that the –1721G, +dup and –1169A alleles significantly decreased SLC45A2 transcriptional activity. Based on in silico bioinformatic analysis that showed these alleles remove a microphthalmia-associated transcription factor (MITF) binding site, and that MITF is a known regulator of SLC45A2 (Baxter and Pavan, 2002; Du and Fisher, 2002), it was postulated that SLC45A2 promoter polymorphisms could contribute to the regulation of pigmentation by altering MITF binding affinity. Further characterisation of the SLC45A2 promoter was carried out using luciferase reporter assays to determine the transcriptional activity of different regions of the promoter. Five constructs were designed of increasing length and their promoter activity evaluated. Constitutive promoter activity was observed within the first ~200 bp and promoter activity increased as the construct size increased. The functional impact of the –1721G, +dup and –1169A alleles, which removed a MITF consensus binding site, were assessed using electrophoretic mobility shift assays (EMSA) and expression analysis of genotyped melanoblast and melanocyte cell lines. EMSA results confirmed that the promoter polymorphisms affected DNA-protein binding. Interestingly, however, the protein/s involved were not MITF, or at least MITF was not the protein directly binding to the DNA. In an effort to more thoroughly characterise the functional consequences of SLC45A2 promoter polymorphisms, the mRNA expression levels of SLC45A2 and MITF were determined in melanocyte/melanoblast cell lines. Based on SLC45A2’s role in processing and trafficking TYRP1 from the trans-Golgi network to stage 2 melanosmes, the mRNA expression of TYRP1 was also investigated. Expression results suggested a coordinated expression of pigmentation genes. This thesis has substantially contributed to the field of pigmentation by showing that SLC45A2 polymorphisms not only show allele frequency differences between population groups, but also contribute to normal pigmentation variation within a Caucasian population. In addition, promoter polymorphisms have been shown to have functional consequences for SLC45A2 transcription and the expression of other pigmentation genes. Combined, the data presented in this work supports the notion that SLC45A2 is an important contributor to normal pigmentation variation and should be the target of further research to elucidate its role in determining pigmentation phenotypes. Understanding SLC45A2’s function may lead to the development of therapeutic interventions for oculocutaneous albinism and other disorders of pigmentation. It may also help in our understanding of skin cancer susceptibility and evolutionary adaptation to different UV environments, and contribute to the forensic application of pigmentation phenotype prediction.

Exchange relationships in building services maintenance activity : a test of transaction cost economics and the resource dependency view

The firm is faced with a decision concerning the nature of intra-organizational exchange relationships with internal human resources and the nature or inter-organizational exchange relationships with market firms. In both situations, the firm can develop an exchange that ranges from a discrete exchange to a relational exchange. Transaction Cost Economics (TCE) and the Resource Dependency View (RDV) represent alternative efficiency-based explanations fo the nature of the exchange relationship. The aim of the paper is to test these two theories in respect of air conditioning maintenance in retail centres. Multiple sources of information are genereated from case studies of Australian retail centres to test these theories in respoect of internalized operations management (concerning strategic aspects of air conditioning maintenance) and externalized planned routine air conditioning maintenance. The analysis of the data centres on pattern matching. It is concluded that the data supports TCE - on the basis of a development in TCE's contractual schema. Further research is suggested towards taking a pluralistic stance and developing a combined efficiency and power hypothesis - upon which Williamson has speculated. For practice, the conclusions also offer a timely cautionary note concerning the adoption of one approach in all exchange relationships.

Market Structures in Air Conditioning Maintenance Activity

It is questionable whether activities like construction, including maintenance and repair, can be considered a single entity or industry - on the basis that different sectors of construction/maintenance use fundamentally distinct resource and skill bases. This creates a number of issues including the development of competition and reform policy. de Valance deployed the Structure-Conduct-Performance model (SCP) to delineate sectors of new/installation construction activity and, in doing so, proposes that there exists multiple market structures in a given project. The purpose of this paper is to apply the SCP model to a different sector of construction activity, that is air conditioning maintenance and test de Valance's proposition concerning the existence of multiple market structures in a supply chain but this time to a built facility. The research method combines secondary data concerning the "Structure" component of the SCP model and primary data with regard to the "Conduct" and "Performance" parts of the SCP model. The results provide further support (beyond de Valance's analysis of new/installation activity) that a sector system approach using the SCP model is a more effective way to analyse market structures in construction activity. This paper also supports de Valance's proposition concerning the existence of multiple market structures in a supply chain to a project/facility.