Landscape Systems and Human Land-Use Interactions in Mediterranean Highlands and Littoral Plains during the Late Holocene: Integrated Analysis from the InterAmbAr Project (North-Eastern Catalonia).

The main goal of the InterAmbAr reseach project is to analyze the relationships between landscape systems and human land-use strategies on mountains and littoral plains from a long-term perspective. The study adopts a high resolution analysis of small-scale study areas located in the Mediterranean region of north-eastern Catalonia. The study areas are distributed along an altitudinal transect from the high mountain (above 2000m a.s.l.) to the littoral plain of Empordà (Fig. 1). High resolution interdisciplinary research has been carried out from 2010, based on the integration of palaeoenvironmental and archaeological data. The micro-scale approach is used to understand human-environmental relationships. It allows better understanding of the local-regional nature of environmental changes and the synergies between catchment-based systems, hydro-sedimentary regimes, human mobility, land-uses, human environments, demography, etc.

Local human capital and productivity: An analysis for Spanish regions

In this paper, we examine the relationship between the stock of human capital and productivity in the Spanish regions (NUTS III), and assess whether the transmission channel involves external economies. The empirical evidence points to a positive relationship between the two variables, although it cannot be explained in terms of the impact of exogenous local human capital external economies, but rather in terms of other demand factors.

Role of human hydroxysteroid (17beta) dehydrogenase type 1 (HSD17B1) in steroid-dependent diseases in females –novel indications for HSD17B1 inhibitors. Phenotypic analysis of transgenic mice overexpressing human HSD17B1.

Hormone-dependent diseases, e.g. cancers, rank high in mortality in the modern world, and thus, there is an urgent need for new drugs to treat these diseases. Although the diseases are clearly hormone-dependent, changes in circulating hormone concentrations do not explain all the pathological processes observed in the diseased tissues. A more inclusive explanation is provided by intracrinology – a regulation of hormone concentrations at the target tissue level. This is mediated by the expression of a pattern of steroid-activating and -inactivating enzymes in steroid target tissues, thus enabling a concentration gradient between the blood circulation and the tissue. Hydroxysteroid (17beta) dehydrogenases (HSD17Bs) form a family of enzymes that catalyze the conversion between low active 17-ketosteroids and highly active 17beta-hydroxysteroids. HSD17B1 converts low active estrogen (E1) to highly active estradiol (E2) with high catalytic efficiency, and altered HSD17B1 expression has been associated with several hormone-dependent diseases, including breast cancer, endometriosis, endometrial hyperplasia and cancer, and ovarian epithelial cancer. Because of its putative role in E2 biosynthesis in ovaries and peripheral target tissues, HSD17B1 is considered to be a promising drug target for estrogen-dependent diseases. A few studies have indicated that the enzyme also has androgenic activity, but they have been ignored. In the present study, transgenic mice overexpressing human HSD17B1 (HSD17B1TG mice) were used to study the effects of the enzyme in vivo. Firstly, the substrate specificity of human HSD17B1 was determined in vivo. The results indicated that human HSD17B1 has significant androgenic activity in female mice in vivo, which resulted in increased fetal testosterone concentration and female disorder of sexual development appearing as masculinized phenotype (increased anogenital distance, lack of nipples, lack of vaginal opening, combination of vagina with urethra, enlarged Wolffian duct remnants in the mesovarium and enlarged female prostate). Fetal androgen exposure has been linked to polycystic ovary syndrome (PCOS) and metabolic syndrome during adulthood in experimental animals and humans, but the genes involved in PCOS are largely unknown. A putative mechanism to accumulate androgens during fetal life by HSD17B1 overexpression was shown in the present study. Furthermore, as a result of prenatal androgen exposure locally in the ovaries, HSD17B1TG females developed ovarian benign serous cystadenomas in adulthood. These benign lesions are precursors of low-grade ovarian serous tumors. Ovarian cancer ranks fifth in mortality of all female cancers in Finland, and most of the ovarian cancers arise from the surface epithelium. The formation of the lesions was prevented by prenatal antiandrogen treatment and by transplanting wild type (WT) ovaries prepubertally into HSD17B1TG females. The results obtained in our non-clinical TG mouse model, together with a literature analysis, suggest that HSD17B1 has a role in ovarian epithelial carcinogenesis, and especially in the development of serous tumors. The role of androgens in ovarian carcinogenesis is considered controversial, but the present study provides further evidence for the androgen hypothesis. Moreover, it directly links HSD17B1-induced prenatal androgen exposure to ovarian epithelial carcinogenesis in mice. As expected, significant estrogenic activity was also detected for human HSD17B1. HSD17B1TG mice had enhanced peripheral conversion of E1 to E2 in a variety of target tissues, including the uterus. Furthermore, this activity was significantly decreased by treatments with specific HSD17B1 inhibitors. As a result, several estrogen-dependent disorders were found in HSD17B1TG females. Here we report that HSD17B1TG mice invariably developed endometrial hyperplasia and failed to ovulate in adulthood. As in humans, endometrial hyperplasia in HSD17B1TG females was reversible upon ovulation induction, triggering a rise in circulating progesterone levels, and in response to exogenous progestins. Remarkably, treatment with a HSD17B1 inhibitor failed to restore ovulation, yet completely reversed the hyperplastic morphology of epithelial cells in the glandular compartment. We also demonstrate that HSD17B1 is expressed in normal human endometrium, hyperplasia, and cancer. Collectively, our non-clinical data and literature analysis suggest that HSD17B1 inhibition could be one of several possible approaches to decrease endometrial estrogen production in endometrial hyperplasia and cancer. HSD17B1 expression has been found in bones of humans and rats. The non-clinical data in the present study suggest that human HSD17B1 is likely to have an important role in the regulation of bone formation, strength and length during reproductive years in female mice. Bone density in HSD17B1TG females was highly increased in femurs, but in lesser amounts also in tibias. Especially the tibia growth plate, but not other regions of bone, was susceptible to respond to HSD17B1 inhibition by increasing bone length, whereas the inhibitors did not affect bone density. Therefore, HSD17B1 inhibitors could be safer than aromatase inhibitors in regard to bone in the treatment of breast cancer and endometriosis. Furthermore, diseases related to improper growth, are a promising new indication for HSD17B1 inhibitors.

Marketing culture of Finnish research libraries : an analysis of marketing attitude, knowledge and behaviour

The aim of the present dissertation is to investigate the marketing culture of research libraries in Finland and to understand the awareness of the knowledge base of library management concerning modern marketing theories and practices. The study was based onthe notion that a leader in an organisation can have large impact on its culture. Therefore, it was considered important to learn about the market orientation that initiates at the top management and flows throughout the whole organisationthus resulting in a particular kind of library culture. The study attempts to examine the marketing culture of libraries by analysing the marketing attitudes, knowledge (underlying beliefs, values and assumptions), behaviour (market orientation), operational policies and activities, and their service performance (customer satisfaction). The research was based on the assumption that if the top management of libraries has market oriented behaviour, then their marketing attitudes, knowledge, operational policies and activities and service performance should also be in accordance. The dissertation attempts to connect all these theoretical threads of marketing culture. It investigates thirty three academic and special libraries in the south of Finland. The library director and three to ten customers from each library participated as respondents in this study. An integrated methodological approach of qualitative as well as quantitative methods was used to gain knowledge on the pertinent issues lying behind the marketing culture of research libraries. The analysis of the whole dissertation reveals that the concept of marketing has very varied status in the Finnish research libraries. Based on the entire findings, three kinds of marketing cultures were emerged: the strong- the high fliers; the medium- the brisk runners; and the weak- the slow walkers. The high fliers appeared to be modern marketing believers as their marketing approach was customer oriented and found to be closer to the emerging notions of contemporary relational marketing. The brisk runners were found to be traditional marketing advocates as their marketing approach is more `library centred¿than customer defined and thus is in line of `product orientation¿ i.e. traditional marketing. `Let the interested customers come to the library¿ was appeared to be the hallmark of the slow walkers. Application of conscious market orientation is not reflected in the library activities of the slow walkers. Instead their values, ideology and approach to serving the library customers is more in tuneof `usual service oriented Finnish way¿. The implication of the research is that it pays to be market oriented which results in higher customer satisfaction oflibraries. Moreover, it is emphasised that the traditional user based service philosophy of Finnish research libraries should not be abandoned but it needs to be further developed by building a relational based marketing system which will help the libraries to become more efficient and effective from the customers¿ viewpoint. The contribution of the dissertation lies in the framework showing the linkages between the critical components of the marketing culture of a library: antecedents, market orientation, facilitators and consequences. The dissertationdelineates the significant underlying dimensions of market-oriented behaviour of libraries which are namely customer philosophy, inter-functional coordination,strategic orientation, responsiveness, pricing orientation and competition orientation. The dissertation also showed the extent to which marketing attitudes, behaviour, knowledge were related and impact of market orientation on the serviceperformance of libraries. A strong positive association was found to exist between market orientation and marketing attitudes and knowledge. Moreover, it also shows that a higher market orientation is positively connected with the service performance of libraries, the ultimate result being higher customer satisfaction. The analysis shows that a genuine marketing culture represents a synthesis of certain marketing attitudes, knowledge and of selective practices. This finding is particularly significant in the sense that it manifests that marketing culture consists of a certain sets of beliefs and knowledge (which form a specific attitude towards marketing) and implementation of a certain set of activities that actually materialize the attitude of marketing into practice (market orientation) leading to superior service performance of libraries.

Chaotic Behaviour of Active Magnetic Bearing System by Time Series Analysis

Chaotic behaviour is one of the hardest problems that can happen in nonlinear dynamical systems with severe nonlinearities. It makes the system's responses unpredictable. It makes the system's responses to behave similar to noise. In some applications it should be avoided. One of the approaches to detect the chaotic behaviour is nding the Lyapunov exponent through examining the dynamical equation of the system. It needs a model of the system. The goal of this study is the diagnosis of chaotic behaviour by just exploring the data (signal) without using any dynamical model of the system. In this work two methods are tested on the time series data collected from AMB (Active Magnetic Bearing) system sensors. The rst method is used to nd the largest Lyapunov exponent by Rosenstein method. The second method is a 0-1 test for identifying chaotic behaviour. These two methods are used to detect if the data is chaotic. By using Rosenstein method it is needed to nd the minimum embedding dimension. To nd the minimum embedding dimension Cao method is used. Cao method does not give just the minimum embedding dimension, it also gives the order of the nonlinear dynamical equation of the system and also it shows how the system's signals are corrupted with noise. At the end of this research a test called runs test is introduced to show that the data is not excessively noisy.

Clinical and molecular analysis of human reproductive disorders in Brazilian patients

Several genes that influence the development and function of the hypothalamic-pituitary-gonadal-axis (HPG) have been identified. These genes encode an array of transcription factors, matrix proteins, hormones, receptors, and enzymes that are expressed at multiple levels of the HPG. We report the experience of a single Endocrinology Unit in the identification and characterization of naturally occurring mutations in families affected by HPG disorders, including forms of precocious puberty, hypogonadism and abnormal sexual development due to impaired gonadotropin function. Eight distinct genes implicated in HPG function were studied: KAL, SF1, DAX1, GnRH, GnRHR, FSHß, FSHR, and LHR. Most mutations identified in our cohort are described for the first time in literature. New mutations in SF1, DAX1 and GnRHR genes were identified in three Brazilian patients with hypogonadism. Eight boys with luteinizing hormone- (LH) independent precocious puberty due to testotoxicosis were studied, and all have their LH receptor (LHR) defects elucidated. Among the identified LHR molecular defects, three were new activating mutations. In addition, these mutations were frequently associated with new clinical and hormonal aspects, contributing significantly to the knowledge of the molecular basis of reproductive disorders. In conclusion, the naturally occurring genetic mutations described in the Brazilian families studied provide important insights into the regulation of the HPG.

Transduction motif analysis of gastric cancer based on a human signaling network

To investigate signal regulation models of gastric cancer, databases and literature were used to construct the signaling network in humans. Topological characteristics of the network were analyzed by CytoScape. After marking gastric cancer-related genes extracted from the CancerResource, GeneRIF, and COSMIC databases, the FANMOD software was used for the mining of gastric cancer-related motifs in a network with three vertices. The significant motif difference method was adopted to identify significantly different motifs in the normal and cancer states. Finally, we conducted a series of analyses of the significantly different motifs, including gene ontology, function annotation of genes, and model classification. A human signaling network was constructed, with 1643 nodes and 5089 regulating interactions. The network was configured to have the characteristics of other biological networks. There were 57,942 motifs marked with gastric cancer-related genes out of a total of 69,492 motifs, and 264 motifs were selected as significantly different motifs by calculating the significant motif difference (SMD) scores. Genes in significantly different motifs were mainly enriched in functions associated with cancer genesis, such as regulation of cell death, amino acid phosphorylation of proteins, and intracellular signaling cascades. The top five significantly different motifs were mainly cascade and positive feedback types. Almost all genes in the five motifs were cancer related, including EPOR,MAPK14, BCL2L1, KRT18,PTPN6, CASP3, TGFBR2,AR, and CASP7. The development of cancer might be curbed by inhibiting signal transductions upstream and downstream of the selected motifs.

Building climate justice : an analysis of how the nexus between climate change and human rights shapes public policy agendas and alternatives

This thesis provides an analysis of how the nexus between climate change and human rights shapes public policy agendas and alternatives. It draws upon seminal work conducted by John Kingdon, whose landmark publication “Agendas, alternatives, and public policy” described how separate streams of problems, solutions, and politics converge to move an issue onto the public policy agenda toward potential government action. Building on Kingdon’s framework, this research explores how human rights contribute to surfacing the problem of climate change; developing alternative approaches to tackling climate change; and improving the political environment necessary for addressing climate change with sufficient ambition. The study reveals that climate change undermines the realization of human rights and that human rights can be effective tools in building climate resilience. This analysis was developed using a mixed methods approach and drawing upon substantial literature review, the researcher’s own participation in international climate policy design; elite interviews with thought leaders dealing with climate change and human rights; and regular inputs from focus groups comprised of practitioners drawn from the fields of climate change, development and human rights. This is a journal based thesis with a total of six articles submitted for evaluation, published in peer‐reviewed publications, over a five year period. Denna avhandling analyserar hur klimatfrågan och mänskliga rättigheter i samverkan formar den politiska agendan och det politiskt möjliga. Den bygger på banbrytande forskning av John Kingdon, vars publikation “Agendas, alternatives, and public policy” beskriver hur en fråga blir politiskt viktig och lyfts upp på den politiska agendan. Med utgångspunkt i Kingdons ramverk, utforskar avhandlingen hur mänskliga rättigheter bidrar till att blottlägga klimatfrågan som problem; utveckla alternativa metoder för att angripa och hantera klimatfrågan; samt skapa ett politiskt klimat nödvändigt för att på ett ambitiöst sätt kunna angripa klimatfrågan. Studien visar att klimatförändringar undergräver mänskliga rättigheterna men att arbete med mänskliga rättigheter kan vara ett effektivt verktyg för att stå emot och hantera effekterna av klimatförändringar. Analysen har genomförts med hjälp av en rad olika metoder vilka inkluderar litteraturstudier, författarens egna observationer under klimatförhandlingar; intervjuer med ledande tänkare inom klimatfrågan och mänskliga rättigheter; samt data insamlad genom fokusgrupper bestående av yrkesverksamma inom klimat, utveckling och mänskliga rättigheter. Avhandlingen är baserad på totalt sex artiklar som publicerats i fackgranskade tidskrifter under en femårsperiod.

Isolation and characterization of the female sex pheromone of the sugar beet cyst nematode, heterodera schachtii, and an analysis of male precopulatory behaviour /

The sugar beet cyst nematode, Heterodera schachtii, is a major agricultural pest. The disruption of the mating behaviour of this plant parasite in the field may provide a means of biological control, and a subsequent increase in crop yield. The H. schachtii female sex pheromone, which attracts homospecific males, was collected in an aqueous medium and isolated using high performance liquid chromatography. Characterization of the male-attractive material revealed that it was heat stable and water soluble. The aqueous medium conditioned by female H. schachtii was found to be biologically active and stimulated male behaviour in a concentration dependent manner. The activity of the crude pheromone was specific to males of H. schachtii and did not attract second stage juveniles. Results indicated that vanillic acid, a putative nematode pheromone, is not an active component of the H. schachtii sex pheromone. Male H. schachtii exhibited stylet thrusting, a poorly understood behaviour of the male, upon exposure to the female sex pheromone. This behaviour appeared to be associated with mate-finding and was used as a novel indicator of biological activity in bioassays. Serotonin, thought to be involved in the neural control of copulatory behaviour in nematodes, stimulated stylet thrusting. However, the relationship between stylet thrusting induced by the sex pheromone and stylet thrusting induced by serotonin is not clear. Extracellular electrical activity was recorded fi-om the anterior region of H. schachtii males during stylet thrusting, and appeared to be associated with this behaviour. The isolation of the female sex pheromone of H. schachtii may, ultimately, lead to the structural identification and synthesis of the active substance for use in a novel biological control strategy.

Analysis of the feeding behaviour of the mosquito Culex pipiens L. (Diptera: Culicidae) in relation to West Nile virus

The goal ofthis literature review is to inform the reader on several aspects of West Nile Virus (WNV) transmission by its mosquito vector, Culex pipiens and to elucidate how Cx. pipiens and WNV are intertwined. The first few sections of the literature review describe the life cycle and blood feeding behaviours ofmosquitoes so that baseline data ofmosquito biology are established. In addition to explaining how and why a mosquito blood feeds, the section on "Blood Meal Analysis" describes the different methods for determining the vertebrate source of mosquito blood meals and a brief history of these testing methods. Since this thesis looks at the feeding behaviour of Cx. pipiens, it is important to know how to determine what they are feeding upon. Discussion on other mosquito-borne diseases related to WNV gives a broader perspective to the thesis, and examines other diseases that have occurred in Ontario in the past. This is followed by background information on WNV and theories on how this virus came to North America and how it relates to Cx. pipiens. The final sections discuss Cx. pipiens and give background information to how this species of mosquito exists and behaves within North America.

The practical application of a meta-analysis of deinstitutionalization : adaptive behaviour outcomes and the piloting of a transitional questionnaire for adults with intellectual disabilities

This investigation examined the effects of de institutionalization on the adaptive behaviour and adjustment of adults with intellectual disabilities (ID). In study 1, a meta-analysis was conducted with 23 studies on deinstitutionalization adaptive behaviour outcomes. Deinstitutionalization was associated with modest improvements in adaptive behaviour however outcomes varied across adaptive behaviour domains and other substantive variables. Clinical and service implications of these results were explicated. Noting the trends from the meta-analysis, study 2 used this information in refining and piloting an Agency Transition Survey used to evaluate community transitions for persons with ID. Information derived from the survey was found to be valuable and adequate for the effective evaluation of transitional success. Potential applications of the survey and meta-analysis results were illustrated.

Functional analysis and treatment of OCD-related behaviour in a child with Autism Spectrum Disorder

Research indicates that Obsessive-Compulsive Disorder (OCD; DSM-IV-TR, American Psychiatric Association, 2000) is the second most frequent disorder to coincide with Autism Spectrum Disorder (ASD; Leyfer et aI., 2006). Excessive collecting and hoarding are also frequently reported in children with ASD (Berjerot, 2007). Although functional analysis (Iwata, Dorsey, Slifer, Bauman, & Richman, 1982/1994) has successfully identified maintaining variables for repetitive behaviours such as of bizarre vocalizations (e.g., Wilder, Masuda, O'Connor, & Baham, 2001), tics (e.g., Scotti, Schulman, & Hojnacki, 1994), and habit disorders (e.g., Woods & Miltenberger, 1996), extant literature ofOCD and functional analysis methodology is scarce (May et aI., 2008). The current studies utilized functional analysis methodology to identify the types of operant functions associated with the OCD-related hoarding behaviour of a child with ASD and examined the efficacy of function-based intervention. Results supported hypotheses of automatic and socially mediated positive reinforcement. A corresponding function-based treatment plan incorporated antecedent strategies and differential reinforcement (Deitz, 1977; Lindberg, Iwata, Kahng, and DeLeon, 1999; Reynolds, 1961). Reductions in problem behaviour were evidenced through use of a multiple baseline across behaviours design and maintained during two-month follow-up. Decreases in symptom severity were also discerned through subjective measures of treatment effectiveness.

HUMAN GENOME VARIATIONS AND EVOLUTION WITH A FOCUS ON THE ANALYSIS OF TRANSPOSABLE ELEMENTS

Genome sequence varies in numerous ways among individuals although the gross architecture is fixed for all humans. Retrotransposons create one of the most abundant structural variants in the human genome and are divided in many families, with certain members in some families, e.g., L1, Alu, SVA, and HERV-K, remaining active for transposition. Along with other types of genomic variants, retrotransponson-derived variants contribute to the whole spectrum of genome variants in humans. With the advancement of sequencing techniques, many human genomes are being sequenced at the individual level, fueling the comparative research on these variants among individuals. In this thesis, the evolution and functional impact of structural variations is examined primarily focusing on retrotransposons in the context of human evolution. The thesis comprises of three different studies on the topics that are presented in three data chapters. First, the recent evolution of all human specific AluYb members, representing the second most active subfamily of Alus, was tracked to identify their source/master copy using a novel approach. All human-specific AluYb elements from the reference genome were extracted, aligned with one another to construct clusters of similar copies and each cluster was analyzed to generate the evolutionary relationship between the members of the cluster. The approach resulted in identification of one major driver copy of all human specific Yb8 and the source copy of the Yb9 lineage. Three new subfamilies within the AluYb family – Yb8a1, Yb10 and Yb11 were also identified, with Yb11 being the youngest and most polymorphic. Second, an attempt to construct a relation between transposable elements (TEs) and tandem repeats (TRs) was made at a genome-wide scale for the first time. Upon sequence comparison, positional cross-checking and other relevant analyses, it was observed that over 20% of all TRs are derived from TEs. This result established the first connection between these two types of repetitive elements, and extends our appreciation for the impact of TEs on genomes. Furthermore, only 6% of these TE-derived TRs follow the already postulated initiation and expansion mechanisms, suggesting that the others are likely to follow a yet-unidentified mechanism. Third, by taking a combination of multiple computational approaches involving all types of genetic variations published so far including transposable elements, the first whole genome sequence of the most recent common ancestor of all modern human populations that diverged into different populations around 125,000-100,000 years ago was constructed. The study shows that the current reference genome sequence is 8.89 million base pairs larger than our common ancestor’s genome, contributed by a whole spectrum of genetic mechanisms. The use of this ancestral reference genome to facilitate the analysis of personal genomes was demonstrated using an example genome and more insightful recent evolutionary analyses involving the Neanderthal genome. The three data chapters presented in this thesis conclude that the tandem repeats and transposable elements are not two entirely distinctly isolated elements as over 20% TRs are actually derived from TEs. Certain subfamilies of TEs themselves are still evolving with the generation of newer subfamilies. The evolutionary analyses of all TEs along with other genomic variants helped to construct the genome sequence of the most recent common ancestor to all modern human populations which provides a better alternative to human reference genome and can be a useful resource for the study of personal genomics, population genetics, human and primate evolution.

A Phenomenologically Sensitized Analysis of Images Depicting Stressed Embodiment in an Adolescent Male with Autism Spectrum Disorder (ASD)

Each person with Autism Spectrum Disorder (ASD) comes with unique characteristics (idiosyncratic) that give clues to the world they know (Connolly, 2008). It is through their body that they (a) know the world they are experiencing, (b) make meaning, and (c) express certain behaviours. I used Laban’s Movement Analysis (LMA) to practice an attuned and appreciative approach to describing and understanding the body movement in one severe manifestation of autism in an adolescent male. LMA observes human movement across many disciplines and can be applied in many contexts providing a body honoring discourse for description (Connolly, 2008). The framework examines movement in body, space, quality, and relation. Each theme provides a detailed description of the individual’s movement, thus, giving us a richer understanding of patterns and possible triggers to self-injurious behaviours (SIB). During the summer of August 2013, I participated in Brock University’s annual Autism Camp and worked with a 15 year old male named “Aaron” who manifests with low functioning autism. The purpose of my research project was to code and analyze a series of photos taken to help gain insight into movement patterns associated with stressed embodiment and self-injury in “Aaron”. As I understood more about these embodied expressions, I uncovered valuable information on how to read patterns and discover what triggers these events, thus providing strategies on how to help people do more refined observations and make meaning of the behaviour. Laban’s movement analysis provided a sensitized discourse appropriate to the embodied expressions depicted in the photos.